30th German Cancer Congress - February 2012, Berlin

A N D 

J O U R N A L O F 

HIJ 

Volume 138 • Supplement 1 • February 2012 

Cancer Research 

Clinical Oncology 

30th German Cancer Congress 

22.–25. February 2012 

ICC and Messe Berlin 

Congress President: Univ.-Prof. Dr. P. Albers 

30. Deutscher Krebskongress 

22.-25. Februar 2012 

Messe und ICC Berlin 

Kongresspräsident: Univ.-Prof. Dr. P. Albers

Inhaltsverzeichnis 

This supplement was not sponsored 

by outside commercial interests . It was 

funded entirely by the publisher . 

Inhaltsverzeichnis 

Best of Poster 

Best of Poster – GI-Tumoren . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 3 

Best of Poster – Hauttumoren . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 4 

Best of Poster – Lungentumoren . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 6 

Best of Poster – Lymphome/Leukämien/kindliche Tumoren . . . . . . . . . . . . . . . . . . . . . . . . . . . 8 

Best of Poster – Mammakarzinom/gynäkologische Tumoren . . . . . . . . . . . . . . . . . . . . . . . . . 10 

Best of Poster – Molekulare Onkologie . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 12 

Best of Poster – Palliativmedizin/Supportivtherapie . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 13 

Best of Poster – Seltene Tumoren . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 15 

Best of Poster – Versorgungsstrukturen/Qualitätssicherung . . . . . . . . . . . . . . . . . . . . . . . . . . 17 

Best of Poster – Urologische Tumoren . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 19 

Discussed Poster 

Discussed Poster – GI-Tumoren . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 20 

Discussed Poster – Mammakarzinom/gynäkologische Tumoren . . . . . . . . . . . . . . . . . . . . . . 23 

Discussed Poster – Molekulare Onkologie . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 26 

Discussed Poster – Seltene Tumoren . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 28 

Discussed Poster – Supportivtherapie/Palliativmedizin . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 30 

Discussed Poster – Versorgungsstrukturen/Qualitätssicherung . . . . . . . . . . . . . . . . . . . . . . . 33 

General Poster 

GI-Tumoren . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 35 

Hauttumoren . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 53 

Lungentumoren . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 55 

Lymphome/Leukämien/pädiatrische Tumoren . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 57 

Mammakarzinom/gynäkologische Tumoren . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 61 

Molekulare Onkologie . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .90 

Seltene Tumoren . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 106 

Supportivmedizin/Palliativtherapie . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 119 

Urologische Tumoren . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 134 

Versorgungsstrukturen/Qualitätssicherung . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 144 

KOK 

KOK . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .151 

Autorenverzeichnis . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 153 

Journal of Cancer Research and Clinical Oncology Suppl 1 · 2011 | 

1

Abstracts 

J Cancer Res Clin Oncol (2012) 

[Suppl 1] · 138:2–162 

10 .1007/s00432-011-1144-4 

© Springer-Verlag 2012 

Programmkomitee DKK 2012 

Adam G (Hamburg), Albers P (Düsseldorf), 

Bartsch HH (Freiburg), Beckmann MW (Erlangen), 

Bokemeyer C (Hamburg), Brümmendorf 

T (Aachen), Bruns J (Berlin), Creutzig 

U (Hannover), Domagk K (Hamburg), 

Ehninger G (Dresden), Engers R (Düsseldorf), 

Enghofer E (Leverkusen), Feyer P (Berlin), 

Gabbert HE (Düsseldorf), Graeven U 

(Mönchengladbach), Gschwend J (München), 

Hallek M (Köln), Hauschild A (Kiel), Hegewisch-Becker 

(Hamburg), Helbig U (Berlin), 

Helou A (Bonn), Hofstädter F (Regensburg), 

Hohenberger W (Erlangen), Hölscher A 

(Köln), Hübner J (Frankfurt/M), Iro H (Erlangen), 

Kastenholz H (Bonn), Kerschgens C 

(Berlin), Kleeberg U (Hamburg), Klingebiel 

T (Frankfurt), Klinkhammer-Schalke M 

(Regensburg), Kohlhuber F (Bonn), Kortmann 

R-D (Leipzig), Kotzerke J (Dresden), 

Lang H (Mainz), Meier K (Soltau), Nettekoven 

G (Bonn), Ortmann, O (Regensburg), 

Paradies K (Hamburg), Propping P (Bonn), 

Riemann JF (Ludwigshafen), Schadendorf 

D (Essen), Schirren J (Wiesbaden), Schmidberger 

H (Mainz), Schmiegel W (Bochum), 

Schmutzler R (Köln), Singer S (Leipzig), 

Stummer W (Münster), Thomas M (Heidelberg), 

Wallwiener D (Tübingen), Weis J (Freiburg), 

Wesselmann S (Berlin), Wiedenmann 

B (Berlin), Wiegel T (Ulm), Wiestler O (Heidelberg), 

Wittekind C (Leipzig), Wolff K-D 

(München), Wylegalla C (Freiburg), Zeeb H 

(Bremen) 

Steering Comitee 

2 | Journal of Cancer Research and Clinical Oncology Suppl 1 · 2011 

30. Deutscher Krebskongress 

22.–25. Februar 2012 

Messe und ICC Berlin 

Kongresspräsident 

Univ.-Prof. Dr. P. Albers 

Albers P (Düsseldorf), Beckmann MW (Erlangen), 

Bokemeyer C (Hamburg), Brümmendorf 

T (Aachen), Bruns J (Berlin), Graeven 

U (Mönchengladbach), Hallek M (Köln), 

Hauschild A (Kiel), Ortmann, O (Regensburg), 

Schmiegel W (Bochum), Zeeb H (Bremen) 

Gutachter 2012 

Al-Batran S (Frankfurt/M.), Albers P (Düsseldorf), 

Alberti W (Wuppertal), Bamberg 

M (Tübingen), Barth J (Gießen), Bartsch H 

(Freiburg), Beckmann M (Erlangen), Belka 

C (München), Berdel W (Münster), Berking 

C (München), Biersack H (Bonn), Bokemeyer 

C (Hamburg), Bosslet K (Penzberg), 

Branscheid D (Bielefeld), Britzen-Laurent 

N (Erlangen), Brossart P (Bonn), Budach 

W (Düsseldorf), Büttner R (Köln), Dartsch 

D (Hamburg), Debatin K (Ulm), Dunst J 

(Lübeck), Ebert M (Mannheim), Einsele H 

(Würzburg), Emons G (Göttingen), Engenhart-Cabillic 

R (Marburg), Engers R (Neuss), 

Engert A (Köln), Fehm T (Tübingen), Feyer 

P (Berlin), Folprecht G (Dresden), Freidank 

A (Fulda), Friedel G (Gerlingen), Gabbert H 

(Düsseldorf), Ganser A (Hannover), Geißler 

M (Esslingen a.N.), Glimm H (Heidelberg), 

Graeven U (Mönchengladbach), Gutzmer R 

(Hannover), Hallek M (Köln), Hartenstein 

R (München), Hartmann J (Kiel), Heike M 

(Dortmund), Henne-Bruns D (Ulm), Hense 

H (Münster), Hertenstein B (Bremen), Hillemanns 

P (Hannover), Hochhaus A (Jena), 

Hofheinz R (Mannheim), Hohenberger W 

(Erlangen), Hölscher A (Köln), Howaldt H 

(Gießen), Hübner J (Frankfurt/M.), Jaehde U 

(Bonn), Jocham D (Lübeck), Jonat W (Kiel), 

Jordan K (Halle/S.), Kaaks R (Heidelberg), 

Keller M (Heidelberg), Kiechle M (München), 

Kimmig R (Essen), Klug S (Dresden), Knüchel-Clarke 

R (Aachen), Koch U (Hamburg), 

Köhne C (Oldenburg), Kortmann R (Leipzig), 

Kreienberg R (Ulm), Krug B (Köln), Kubicka 

S (Reutlingen), Lang H (Mainz), Lehnert T 

(Bremen), Lipp M (Berlin), Loquai C (Mainz), 

Lordick F (Braunschweig), Lorenzen S (München), 

Lutz M (Saarbrücken), Mackensen A 

(Erlangen), Marmé D (Freiburg), Meier K 

(Soltau), Meyer H (Solingen), Meyer T (Ansbach), 

Miller K (Berlin), Möhler M (Mainz), 

Molls M (München), Müller R (Köln), Neuhaus 

P (Berlin), Niederle N (Leverkusen), 

Oettle H (Friedrichshafen), Ortmann O 

(Regensburg), Paradies K (Hamburg), Petersen 

C (Hamburg), Possinger K (Berlin), 

Propping P (Bonn), Reinacher-Schick A (Bochum), 

Riemann J (Ludwigshafen), Rödel C 

(Frankfurt/M.), Schäfer R (Berlin), Schirren 

J (Wiesbaden), Schlag P (Berlin), Schlegel U 

(Bochum), Schmidt E (Bremen), Schmidt- 

Wolf I (Bonn), Schmieder K (Mannheim), 

Schmiegel W (Bochum), Schöning T (Heidelberg), 

Schuler M (Essen), Schütte W Halle/S., 

Schwarz M (Tübingen), Seufferlein T Halle/S., 

Singer S (Leipzig), Stahl M (Essen), Stenzl A 

(Tübingen), Stuschke M (Essen), Tannapfel 

A (Bochum), Thomas M (Heidelberg), Trarbach 

T (Essen), Trefzer U (Berlin), Trepel M 

(Hamburg), Trümper L (Göttingen), Ukena 

D (Bremen), Unger C (Freiburg), Vanhoefer 

U (Hamburg), Wecht D (Marburg), Wiegel 

T (Ulm), Wirth M (Dresden), Wittekind C 

(Leipzig), Wylegalla C (Freiburg)

GI-Tumoren 

Best of Poster – GI-Tumoren 

B1 – 0077 

Protein profiling identifies HDAC2 and TXNL1 as aneuploidy-associated 

markers in colorectal cancer 

*T . Gemoll 1,2,3 , U . Roblick 1,2,3 , S . Szymczak 4 , T . Braunschweig 5 , S . Becker 3 , 

B .-W . Igl 4 , H .-P . Bruch 1 , A . Ziegler 4 , U . Hellman 6 , M . Difilippantonio 7 , T . Ried 7 , 

H . Jörnvall 2 , G . Auer 3 , J . Habermann 1,2,3,7 

1 University of Lübeck, Department of Surgery, Lübeck, Deutschland, 

2 Karolinska Institut, Stockholm, Schweden, 3 Karolinska Biomic Center, 

Stockholm, Schweden, 4 University of Lübeck, Institute for Medical Biometry 

and Statistics, Lübeck, Deutschland, 5 University Clinic RWTH Aachen, 

Institute of Pathology, Aachen, Deutschland, 6 Ludwig Institute for Cancer 

Research, Uppsala, Schweden, 7 NCI/NIH, Genetics Department, Bethesda, 

Deutschland 

Background. DNA aneuploidy has been identified as prognostic factor 

for epithelial malignancies. Further understanding of the translation of 

DNA aneuploidy into protein expression will help to define therapies, 

prognosis and prevention. We therefore aimed at identifying aneuploidy-associated 

protein expression. 

Methods. DNA ploidy assessment by image cytometry identified three 

diploid and four aneuploid colorectal cancer cell lines. All cell lines were 

subjected to protein expression profiling by two-dimensional gel electrophoresis. 

Proteins were identified by mass spectrometry, subjected to 

Ingenuity Pathway Analysis (IPA), and target proteins were validated by 

Western Blot. Validated proteins were clinically evaluated by immunohistochemistry 

using a tissue microarray (TMA). The TMA comprised 

47 aneuploid and 31 diploid primary colorectal carcinomas, as well as 19 

adjacent normal mucosa specimens. 

Results. Two independent statistical analyses revealed 64 proteins that 

were significantly differentially expressed between the diploid and 

aneuploid cell lines. Of these, 26 proteins could be identified by mass 

spectrometry and were subjected to IPA. The majority of these proteins 

interacted in two overlapping high-ranked IPA networks maintaining 

Cellular Assembly and Organization, Cellular Function and Maintenance, 

Infection Mechanism, Cell Cycle, and Cellular Growth and 

Proliferation. Network proteins showed cancer-associated functions of 

Cellular Assembly and Organization, Cell-To-Cell Signalling, and Cell 

Death (p

Abstracts 

their therapeutical role for human gastrointestinal cancers has not yet 

been clarified. 

To define the inhibitory and pro-apoptotic effects of two PI3K inhibitors 

BEZ235 and BKM120, three human colon cancer (HT-29, HCT-116, 

DLD-1) and three gastric cancer cell lines (NCIn87, AGS, MKN-45) with 

different PIK3CA mutation status were analysed. First, viability, apoptosis 

and caspase assays were performed during incubation with these 

inhibitors alone or combined with classical cytotoxic agents. Second, 

molecular consequences for cell cycle and the signalling pathways were 

analysed by defining the protein levels by FACS and Western blot. 

Both, BKM120 and the dual PI3K/mTOR inhibitor BEZ235 induced a 

significant concentration-dependent reduction in cell viability and an 

increase of apoptotic cell death, while mutated cells reacted more sensitive 

to treatment. Here, BKM120 was more effective than BEZ235. It caused 

a G1 arrest in tumor cells. In contrast, BKM120 induced a G2 shift 

in all gastrointestinal cancer cell lines. BKM120 clearly down-regulated 

the AKT pathway and BEZ235 additionally inhibited the mTOR (via 

p70S6K) pathway. In colon cancer cells, BEZ235 caused a synergistic 

induction of apoptosis combined with irinotecan. Combinations with 

5-fluoruracil and both substances induced additive apoptotic effects. 

Human gastric cancer cells were less sensitive to BEZ235 and BKM120. 

In sum, BEZ235 and BKM120 had high pro-apoptotic effects in all human 

cell lines and in special cases a better response in the PIK3CA mutated 

cells. Our in vitro data further support the clinical development of 

these PI3K inhibitors BEZ235 and BKM120 as potential targeting agents 

for patients with different wild type or mutated gastrointestinal cancer 

cells. 

Best of Poster – GI-Tumoren 

B4 – 0499 

STAT3 is a potential molecular target to sensitize colorectal 

cancer cells to chemoradiotherapy 

*M . Grade1 , M . Spitzner1 , G . Emons1 , E . Kendziorra1 , M . Rave-Fränk2 , J . Gaedcke1 

, H . Becker1 , T . Beißbarth3 , M . Ghadimi1 1Universitätsmedizin Göttingen, Klinik für Allgemein- und Viszeralchirurgie, 

Göttingen, Deutschland, 2Universitätsmedizin Göttingen, Klinik für 

Strahlentherapie und Radioonkologie, Göttingen, Deutschland, 3Universi tätsmedizin Göttingen, Medizinische Statistik, Göttingen, Deutschland 

Background. Resistance to preoperative chemoradiotherapy represents 

a major clinical problem in the treatment of patients with locally advanced 

rectal cancer. Therefore, the identification of molecular biomarkers 

that differentiate responsive and resistant tumors is exceedingly important, 

because this may lead to the identification of novel molecular 

targets whose modification could be harnessed to sensitize a priori resistant 

tumors to multimodal treatment. 

Materials and methods. We recently established an in vitro model for 

5-FU based chemoradiotherapy, and correlated differences in treatment 

sensitivity of 12 colorectal cancer cell lines with pretherapeutic gene expression 

profiles. One gene the expression of which correlated positively 

with treatment resistance was the signal transducer and activator of 

transcription 3, STAT3. To test the functional relevance of this observation, 

we first determined STAT3 mRNA and protein expression levels in 

all cell lines. Next, we established doxycycline-inducible stable shRNA 

single-cell clone (SCC) populations. Successful silencing of STAT3 was 

detected by Western blot analysis. The induced SCCs were treated with 

3 µM 5-FU, and subsequently exposed to 0, 1, 2, 4, 6, and 8 Gy of Xrays. 

In addition, STAT3 was inhibited using two different siRNAs, and 

a small-molecular inhibitor (STATTIC). 

Results. STAT3 was significantly overexpressed in resistant cells. In 

SW480 and SW837 cells, both shRNA- and siRNA-mediated silencing 

as well as STATTIC-induced inhibition of STAT3-phosphorylation re- 


sulted in a significantly increased chemoradiosensitivity, with dose-reduction 

factors of 1.8 to 2. 

Conclusion. These results highlight the potential relevance of STAT3 as a 

novel molecular target to sensitize a priori resistant tumor cells to chemoradiotherapy. 

Hauttumoren 

Best of Poster – Hauttumoren 

B5 – 0178 

Efficient induction of apoptosis in melanoma cells and reduced 

melanoma growth in nude mice by a gene therapy approach 

based on oncolytic adenoviral vectors with inducible expression 

of TRAIL 

*L .F . Fecker1 , H . Fechner2 , J . Eberle1 1Charité – Universitätsmedizin Berlin Klinik für Dermatologie, Venerologie 

und Allergologie, Hauttumorzentrum, AG Apoptoseregulation in Hauttumoren, 

Berlin, Deutschland, 2Technische Universität, Institut für Biotechnologie, 

Berlin, Deutschland 

Background. High mortality and therapy resistance of melanoma demands 

the development of new strategies, and overcoming of apoptosis 

deficiency appears as particularly promising. TNF-related apoptosis inducing 

ligand (TRAIL) has been shown previously as highly effective 

for apoptosis induction in melanoma cells and may apply for gene therapy 

due to its selective impact on tumor cells. 

Experimental procedures. Established adenoviral vectors AdV-TRAIL 

and AdV-CD95L encode for the death ligands TRAIL and CD95L, respectively. 

They are characterized by a variant adenoviral E1A protein 

and by deletion of E1B aiming at the restriction of viral replication to 

tumor cells. For melanoma selectivity, the viral replication gene E1A is 

controlled by a tyrosinase promoter. The tetracycline-responsive transactivator 

rtTA and the death ligand are further controlled by a bidirectional 

tetracycline-inducible promoter. Apoptosis was monitored by a 

DNA fragmentation ELISA and cell killing by crystal violet staining. 

For proliferation, real time cell analysis (RTCA) was used. Growth of 

tumors established in nude mice was monitored after intratumoral injections 

of AdV-TRAIL. 

Results. AdV-TRAIL mediated strong expression of E1A and doxycycline 

-dependent induction of TRAIL selectively in melanoma cells, which 

resulted in melanoma cell lysis and induction of apoptosis. In contrast, 

non-melanoma cells and normal human melanocytes appeared as protected. 

Comparison of AdV-TRAIL with AdV-CD95L revealed largely 

similar efficacies of both death ligands in melanoma cells. In melanoma 

xenotransplantation models, AdV-TRAIL demonstrated its efficacy by 

significant growth reduction of established melanomas after intratumoral 

application. Melanoma cell killing by AdV-TRAIL could be further 

improved in vitro by combinations with chemotherapeutics. 

Conclusions. We demonstrate that melanoma cells can be efficiently targeted 

by death ligand-based gene therapy. Possible resistance may be 

overcome by combined chemotherapy. 

The study was supported by the German Cancer Aid (Deutsche Krebshilfe, 

grants 107398 and 108008) .


B6 – 0275 

Cytotoxicity of new Duplex Drugs linking 3’-C-Ethynylcytidine 

and 5-Fluor-2’-deoxyuridine against human Melanoma cells 

*S . Schott1 , H . Niessner2 , T . Sinnberg2 , S . Venturelli3 , A . Berger3 , F . Meier2 , 

C . Garbe2 , C . Busch2 1Universitätsklinikum Heidelberg, Universitätsfrauenklinik, Nationales 

Centrum für Tumorerkrankungen, Heidelberg, Deutschland, 2University of 

Tübingen, Section of Dermato-Oncology, Department of Dermatology and 

Allergology, Tübingen, Deutschland, 3University of Tübingen, Department 

of Internal Medicine I, Tübingen, Deutschland 

Introduction. Melanoma is an increasingly common and potentially fatal 

malignancy of the skin and some mucous membranes. Since no cure 

exists for metastatic disease (stage IV), there is an urgent need for novel 

drugs to overcome melanoma therapy resistance. 2’-Deoxy-5-fluorouridylyl-(3’-5’)-3’-C-ethynylcytidine 

[5-FdU(3’-5’)ECyd] and 3’-C-ethynylcytidinylyl-(5’->1-O)-2-O-octadecyl-sn-glycerylyl-(3-Oà5')-2'-deoxy- 

5-fluorouridine [ECyd-lipid-5-FdU] represent cytostatic active duplex 

drugs, which can be metabolized into various active antimetabolites. 

Methods. The cytotoxicity of these heterodinucleoside phosphate analogues, 

their corresponding monomers ECyd and 5-FdU and combinations 

thereof were evaluated on five metastatic melanoma cell lines and 

six ex-vivo patient-derived melanoma cells in comparison to current 

standard cytostatic agents and the BRAF V600E inhibitor Vemurafenib. 

Further, in vitro studies were performed for cell proliferation and 

cell-cycle analysis. Embyrotoxicity was assessed with the chicken embryo 

assay. In vivo efficacious in the LOX IMVI solid tumor xenograft 

mouse model was tested in the Developmental Therapeutic Program 

(DTP) of the National Cancer Institute (NCI, US). 

Results. In vitro (real-time) proliferation assays demonstrated that 

5-FdU(3’-5’)ECyd and ECyd-lipid-5-FdU had a high cytotoxic efficacy 

causing 75% melanoma cell death at concentrations in the nano- and 

micromolar range. Cytotoxicity was conducted by induction of DNA 

cleavage/apoptosis. Chicken embryotoxicity demonstrated that the duplex 

drugs were less toxic than their parental monomers. In vivo the 

duplex drug 5-FdU(3’-5’)ECyd was efficacious in the murine LOX IMVI 

solid tumor xenograph model upon administration of 11.2 mg/kg/injection 

every fourth day. 

Conclusion. Both duplex drugs are promising novel cytostatic agents for 

the treatment of malignant melanoma meriting clinical evaluation. 


B7 – 0332 

Inhibition of the PI3K-AKT signalling pathway to overcome therapy 

resistance in melanoma-derived brain metastasis 

*H . Niessner1 , A . Adam2 , A . Bornemann3 , J . Honegger4 , L . Quintanilla-Fend2 , 

C . Busch1 , J . Bauer1 , L . Just5 , K . Hoek6 , C . Garbe1 , F . Meier1 1Universität Tübingen, Dermatologische Onkologie, Tübingen, Deutschland, 

2Universität Tübingen, Pathologie, Tübingen, Deutschland, 

3 4 Universität Tübingen, Hirnforschung, Tübingen, Deutschland, Universität 

Tübingen, Neurochirurgie, Tübingen, Deutschland, 5Universität Tübingen, 

Anatomie, Tübingen, Deutschland, 6Universität Zürich, Dermatologie, 

Zürich, Schweiz 

Introduction. Brain metastases occur in over 70% of patients with metastatic 

melanoma and are the most common cause of death. Current 

therapy options are neurosurgery, radiosurgery, whole brain radiation, 

chemotherapy and supportive care. The median survival time for mela- 

noma patients with brain metastasis ranges from 0.7 to 5 months depending 

on age and performance status. Therefore, new therapy strategies 

are mandatory. 

Methods. In melanoma, activation of the RAF-MEK-ERK and PI3K- 

AKT-mTOR signal transduction pathways makes a decisive contribution 

to tumor progression and treatment resistance. Ongoing clinical 

studies suggest a transient effect of BRAF inhibitors in melanoma brain 

metastases. We posed the question as to whether blockade of the RAF- 

MEK-ERK or/and PI3K-AKT-mTOR signalling pathways would be a 

promising strategy for the treatment of melanoma brain metastases. We 

blocked RAF-MEK-ERK or/and PI3K-AKT-mTOR signalling pathways 

at different levels using classical and new pharmacological inhibitors 

and investigated the effects on viability/proliferation and survival/ 

apoptosis of >10 newly isolated cell lines derived from melanoma brain 

metastases. Furthermore, immunohistochemical analyses of brain metastases 

from >10 melanoma patients including matched extracerebral 

metastases from lung and liver in the same patients for p-ERK, ERK, 

AKT, p-AKT and PTEN were performed. 

Results. Growth inhibition was most pronounced with PI3K inhibitors 

achieving growth inhibition rates of up to 80%. Moreover, PI3K inhibition 

potently induced apoptosis in cerebral metastatic melanoma cells. 

Histochemical analysis showed that both cerebral and extracerebral 

metastases were highly positive for ERK and AKT. p-ERK was seen 

exclusively at the tumor periphery of both cerebral and extracerebral 

metastases. Interestingly, most melanoma brain metastases were highly 

positive for activated AKT, whereas matched extracerebral metastases 

from lung and liver in the same patients were weakly positive or negative 

for activated AKT. Moreover, PTEN appeared to be downregulated 

in brain metastases. 

Conclusion. Together, these findings suggest that activation of AKT is 

relevant for the survival and growth of melanoma cells in the brain parenchyma 

and that inhibition of PI3K-AKT signalling may be a suitable 

strategy to enhance and/or prolong the antitumor effect of BRAF inhibitors 

in melanoma brain metastases. 


B8 – 0489 

Validation of a fresh-tissue based prognostic gene signature in 

formalin-fixed, paraffin-embedded melanomas 

*G . Brunner1 , L . Suter1 , H .-J . Schulze2 , C . Berking3 , A . Heinecke4 , J . Atzpodien5 1Hauttumorzentrum Hornheide-Münster, Tumorforschung, Münster, 

Deutschland, 2Hauttumorzentrum Hornheide-Münster, Dermatologie, 

Münster, Deutschland, 3LMU München, Dermatologie und Allergologie, 

München, Deutschland, 4WWU Münster, Medizinische Informatik und Bioinformatik, 

Münster, Deutschland, 5Hauttumorzentrum Hornheide-Münster, 

Onkologie, Münster, Deutschland 

Melanoma incidence is rapidly increasing – with a doubling rate of 10– 

20 years. Precision and reliability of conventional histopathological and 

clinical staging, however, remain limited in predicting clinical outcome. 

On the other hand, complementary molecular prognostic markers 

are not yet available. 

We have recently identified, for the first time, a prognostic gene signature 

expressed in fresh-frozen primary melanomas (n=135), which is 

associated with overall survival (multivariate Cox regression analysis: 

p=0.0004, hazard ratio 3.83). The clinical value of a signature-based risk 

score is its ability to identify patients at low risk, not identified by conventional 

AJCC staging, and to define risk patients in need of adjuvant 

therapies. The purpose of this study was to establish analysis of the signature 

genes in formalin-fixed, paraffin-embedded (FFPE) melanoma 

tissue and to validate prognostic significance. 


5

Abstracts 

We developed a sensitive and robust methodology to analyze and normalize 

gene expression in FFPE tissue samples (some of them more 

than 20 years old): Total RNA was prepared from FFPE sections matching 

the above fresh-frozen primary melanomas (131 out of 135), quality-controlled, 

and transcribed into cDNA. Human reference RNA was 

included as an internal standard. Following pre-amplification of the 

cDNA, expression of the nine signature genes (KRT9, KBTBD10, DCD, 

ECG2/SPINK7, PIP, SCGB1D2, SCGB2A2, COL6A6, HES6) and of four 

house-keeping genes (18S rRNA, GAPDH, GUSB, BPNT1) was quantified 

by real-time PCR using TaqMan assays specific for short amplicons. 

Gene expression data were normalized, in two steps, to correct for interassay 

technical variability (based on the reference RNA data) as well as 

for inter-sample variability of RNA quality (based on the data for the 

house-keeping genes). Significance of correlation of FFPE gene expression 

data (CT values or estimated mRNA copy numbers) with data from 

matched fresh-frozen tissue samples (two-sided t-test) or with patient 

overall survival (univariate Cox regression analysis; clinical follow-up 

data up to 273 months) was evaluated. 

The majority of FFPE primary melanomas (125 out of 131) yielded 

mRNA of sufficient quality. In matched pairs of FFPE and fresh-frozen 

tissue samples, there was significant correlation of expression of all 

nine signature genes. Significance of correlation was higher with CT 

values (r=0.19–0.58; p=0.001–0.05) than with estimated copy numbers. 

Expression of 7 out of the 9 genes in FFPE melanomas (CT values or 

estimated copy numbers) was significantly associated with overall survival 

(p=0.0001–0.07). 

Thus, our prognostic melanoma gene signature was successfully transferred 

from fresh-frozen onto FFPE tissue samples. This greatly increases 

clinical applicability of a gene-signature based prognostic risk score 

and, in addition, allows the retrospective prognostic analysis of primary 

melanomas. 

Lungentumoren 

Best of Poster – Lungentumoren 

B9 – 0198 

Hypofractionated image-guided breath-hold radiotherapy of 

pulmonary tumors and metastases – clinical results 

A . Frauenfeld1 , *J . Boda-Heggemann1 , C . Weiss2 , U . Attenberger3 , 

K . Siebenlist1 , F . Schneider1 , F . Wenz1 , F . Lohr1 1University Medical Center Mannheim, University of Heidelberg, Department 

of Radiation Oncology, Mannheim, Deutschland, 2University Medical 

Center Mannheim, University of Heidelberg, Abteilung für Medizinische 

Statistik, Biomathematik und Informationsverarbeitung, Mannheim, 

Deutschland, 3University Medical Center Mannheim, University of Heidelberg, 

Institute of Clinical Radiology and Nuclear Medicine, Mannheim, 

Deutschland 

Purpose. Stereotactic Ablative RadioTherapy (SABR) of stage I–II tumors 

has been shown to be a highly effective treatment modality with 

low toxicity. It is also a non-invasive therapy option for lung metastases. 

Outcome and toxicity were retrospectively evaluated in a single-institution 

patient cohort who had undergone hypofractionated image-guided 

breath-hold lung SBRT. 

Patients and methods. 50 lesions of 43 patients with NSCLC (n=27, St. I– 

IV including patients with controlled brain metastases or local relapse) 

and lung metastases of various primary tumors (n=16) were consecutively 

treated with image-guided breath-hold SBRT. After an initial dose 

finding phase, patients were irradiated with a regimen of 5×12 Gy. Dose 

calculation was performed with collapsed cone algorithm in 60% of 

the lesions. Breath hold was performed with Active Breathing Control 


(ABC®, Elekta), daily imaging with EPIDs and repeat breath hold cone-beam 

CT. The data were evaluated retrospectively regarding overall 

survival (OS), progression-free-survival (PFS), progression pattern and 

local control (LC). Radiation parameters and follow-up CT images were 

analysed. 

Results. BED2 (Biologically Effective Dose) was 87±20 Gy (median 

83 Gy). 30 lesions were treated with a BED2 of 90 Gy. Median follow-up was 15 months. Median OS 

was 20 months, without significant difference in patients with primary 

lung tumor or metastases. Actuarial 1-year OS-rate was 67%; 2-years OS 

rate 43%, respectively. 27% of the patients died on non-disease related 

reason (cardiovascular events or infections). Actuarial 1-year PFS-rate 

was 42%, 2-years PFS rate 28% without significant difference in patients 

with primary lung tumor or metastases. Site of progression pattern was 

predominantly distant (60% distant metastases and 32% mediastinal 

lymph nodes). Actuarial 1-year LC-rate was 90%, 2-years local control 

rate 85%. 95% of the lesions treated with a BED2 >90 Gy was controlled 

locally after one year. Local progression was observed in only 5 cases, 

mainly in the initial dose finding phase, in one patient with an extremely 

large PTV and in one patient with an only retrospectively recognised 

pleural invasion of the irradiated lesion. Clinically apparent pneumonitis 

(requiring treatment) was present in 23% of the cases. No patient 

experienced fatal toxicity. 

Conclusions. Despite the unfavorable patient selection, high local control 

rates could be achieved. If a reasonably high BED2 can be applied, 

image-guided breath-hold SBRT is an effective non-invasive treatment 

modality with a high local control rate and relatively low toxicity in 

patients with inoperable lung tumors and lung metastases. As disease 

progression was mainly outside the treated area, systemic therapy has 

to be improved. 


B10 – 0290 

First screening round results from the German component LUSI 

of the European trial on the efficacy of multislice CT for the early 

detection of lung cancer, and the perspective of the European 

trial in view of the results of the US NLST trial 

*N . Becker1 , E . Motsch1 , M .-L . Groß1 , C .P . Heussel2 , H . Dienemann3 , P . Schnabel4 

, M . Eichinger5 , D .-E . Optazaite5 , M . Puderbach5 , J . Tremper5 , S . Delorme5 1Deutsches Krebsforschungszentrum, Epidemiologie von Krebserkrankungen, 

Heidelberg, Deutschland, 2Thoraxklinik, Radiologie, Heidelberg, 

Deutschland, 3Thoraxklinik, Chirurgie, Heidelberg, Deutschland, 4Univer sität, Medizin/Pathologie, Heidelberg, Deutschland, 5Deutsches Krebsforschungszentrum, 

Radiologie, Heidelberg, Deutschland 

After closure of the recruitment period of the German Lung Cancer 

Screening Intervention Trial (LUSI) in 2011 the study comprises 4052 

participants, randomised into 2029 subjects in the multislice-CT 

(MSCT) screening arm and 2023 into the „usual care“ control arm. The 

early recall rate for suspicious nodules requiring further examination 

ranges currently around 27%. Nineteen lung cancers have been detected 

(detection rate 0.9%). Related to all early recalls, the positive predictive 

value was about 3%, and related to the immediate recalls about 35%. 

The subsequent screening rounds started in October of the years 2008 

(2nd round) to 2011 (5th and final round) having led so far to the identification 

of eight, two, two and 0 further lung cancers, respectively. 

In overall 41 surgical interventions, 15 were benign and 26 malignant. 

Among the lung cancers detected in the screening arm 22 were adenocarcinoma, 

5 squamous cell carcinoma, two a small-cell carcinoma 

and two a carcinoid. One interval cancer has so far been observed (an 

adenocarcinoma).

The study contributes to the European multicenter study comprising 

studies from the Netherlands and Belgium (NELSON, 15422 participants), 

Denmark (4104 participants), Italy (DANTE, 2472; ITALUNG, 

3206; MILD, 3997) and Germany (LUSI, 4052). The scope is to demonstrate 

an at least 25% reduction of lung cancer mortality by MSCT. However, 

in 2011, the National Lung Screening Trial (NLST) conducted in 

the USA, provided after an average follow-up of 6 years a significantly 

reduced lung cancer mortality by MSCT screening in comparison to 

chest X-ray in the control group. Nevertheless, the European studies decided 

to continue their trials and to conduct a first common evaluation 

in 2012 for several reasons, e.g.: (a) an early visible benefit can disappear 

after prolonged follow-up due to postponement of cause-specific death 

in the screening group, (b) harmful side effects, especially overdiagnosis, 

cannot be properly assessed in comparison to a control group with 

another screening modality (chest X-ray), (c) efficient screening modalities 

are still undefined such as, risk-related selection of the appropriate 

target population, appropriate management of suspicious nodules, 

screening intervals etc, as to be outlined in the presentation. 


B11 – 0436 

The role of sleeve resections in advanced nodal disease of NSCLC 

*J . Schirren1 , M . Eberlein2 , A . Fischer3 , S . Bölükbas1 1Dr . Horst Schmidt Klinik, Thoraxchirurgie, Wiesbaden, Deutschland, 

2Carver College of Medicine, Division of Pulmonary, Critical Care and 

Occupational Medicine, Iowa City, USA, 3Dr . Horst Schmidt Klinik, Anästhesie 

und Intensivmedizin, Wiesbaden, Deutschland 

Objective. The aim of this study was to contrast the short-term and longterm 

results of sleeve resections in centrally located non-small cell lung 

cancer (NSCLC) depending on limited nodal disease (N0/N1, LND) 

and advanced nodal disease (N2/N3, AND). 

Methods. All NSCLC-patients undergoing sleeve resections for centrally 

located NSCLC were reviewed from our prospective database 

between January 1999 and December 2008. Patients’ characteristics, 

morbidity, mortality, locoregional recurrence, distant recurrence and 

survival were analyzed corresponding to LND and AND. 

Results. One-hundred seventy sleeve resections out of 213 consecutive 

sleeve resections were performed for ventrally located NSCLC (LND: 

n=120; AND: n=50). There were no statistically differences between the 

both groups for age (LND: 61.8±12.4 vs. 60.8±9.6 years), gender, co-morbidities, 

type of sleeve resection (bronchial vs. bronchovascular), number 

of dissected lymph nodes (LND: 40.0±12.4 vs. 36.7±14.0), histology 

and completeness of resection (LND: 96.7% vs. 98.0%), respectively. 

More patients had induction chemotherapy in AND group (p=0.049). 

Similar short-term results were monitored with regard to morbidity 

rate (LND: 34.2%, AND: 44.0%), secondary pneumonectomy (LND: 

1.7%, AND: 4.0%) and mortality rate (LND: 5.0%, AND: 6.0%), respectively. 

Better 5-year-survival rate and mean survival were observed in 

LND (LND: 80.8 months; AND: 37.7 months; p=0.014; LND: 67%; AND: 

42%). In the long-term, more distant metastases were identified in AND 

group (26.0% vs. 14.2%, p=0.079) in comparison of identical locoregional 

recurrence (LND: 1.7%; AND: 0%). Mean time to the development of 

distant metastases was similar (LND: 19.1 months; AND: 12.4 months; 

p=0.2) in event of metastazing. 

Conclusions. Lymph node involvement is a negative prognostic factor 

with regard to long-term survival. Sleeve resections in AND are not associated 

with higher morbidity and mortality. Sleeve resections in AND 

are correlated with promising long-term survival and unexpected high 

local control of the disease as a result of high complete resection rates. 

Further investigation for the systemic control of the disease is warranted 

because of high rates of distant failure. 


B12 – 0475 

Prognostic value of estrogen (ESR-1) receptor expression in curatively 

resected non-small cell lung cancer (NSCLC) 

*W . Brückl1 , J . Ficker1 , A . Hartmann2 , R . Wirtz2 1 3 2 Klinikum Nürnberg, Medizinische Klinik , Nürnberg, Deutschland, Universität 

Erlangen, Institut für Pathologie, Erlangen, Deutschland 

Background. Despite undergoing complete resection of NSCLC, 33% and 

77% of patients with stage IA and IIIA, respectively, die within 5 years. 

The benefit of adjuvant chemotherapy (aCTx) is only modest, whereas 

such treatment is associated with adverse effects and predictive factors 

are of utmost importance. We recently could show a better outcome in 

estrogen (ESR-1) receptor expressing tumors in the palliative treatment 

of metastatic NSCLC (Brueckl et al., Proc ASCO 2011). The main objective 

of this study was to test, whether ESR-1 expression is of prognostic/ 

predictive value in the curative setting as well. 

Methods. Affymetrix microarray data from N=138 non-metastatic 

NSCLC patients undergoing curative resection were retrieved from a 

data base (Lee et al., Clin Cancer Res 2008) and used as a test set to 

hypothesize that ESR-1 expression in the tumor is of prognostic value 

in curatively resected NSCLC. Baseline data according to ERS-1 status 

were compared with the use of chi-square tests and in a multivariate 

logistic model including all variables with p values

Abstracts 

Lymphome/Leukämien/kindliche Tumoren 

Best of Poster – Lymphome/ 

Leukämien/kindliche Tumoren 

B13 – 0266 

Safety and efficacy of Nilotinib therapy in CML patients with 

Imatinib failure in routine clinical management – follow-up of 

the non-interventional TARGET study 

*F . Stegelmann1 , J . Dengler2 , P . le Coutre3 , C . Scheid4 , R . Weide5 , T . Illmer6 , 

A . Sauer7 , M . Walter8 , W . Schneider-Kappus9 , M . Kröger10 , A . Distelrath11 , 

G . Stier12 , S . Stern13 , F . Schlegel14 , M . Meincke15 , O . Frank15 , O .G . Ottmann16 1Universitätsklinikum Ulm, Klinik für Innere Medizin III, Ulm, Deutschland, 

2Universitätsklinikum Heidelberg, Medizinische Klink, Innere Medizin V, 

Heidelberg, Deutschland, 3Charité – Universitätsmedizin Berlin, Campus 

Virchow Klinikum (CVK), Medizinische Klinik m . S . Hämatologie, Onkologie 

und Tumorimmunologie, Berlin, Deutschland, 4Uniklinik Köln, Klinik I 

für Innere Medizin, Köln, Deutschland, 5Praxisklinik für Hämatologie 

und Onkologie Koblenz, Koblenz, Deutschland, 6Gemeinschaftspraxis Hämatologie – Onkologie, Dresden, Deutschland, 7Medizinisches Versorgungszentrum 

für Blut- und Krebserkrankungen, Potsdam, Deutschland, 

8Praxis für Innere Medizin, Hämatologie und internistische Onkologie, 

Paderborn, Deutschland, 9Hämato-Onkologische Schwerpunkt-Praxis 

Ulm, Ulm, Deutschland, 10Gemeinschaftspraxis für Ambulante Onkologie, 

Bremerhaven, Deutschland, 11MVZ Osthessen, Fachbereich Innere Medizin, 

Fulda, Deutschland, 12Internistisch-Onkologische Praxis, Zella-Mehlis, 

Deutschland, 13Praxisklinik für integrative Onkologie, Altötting, Deutschland, 

14St .-Antonius-Hospital, Akademisches Lehrkrankenhaus der RWTH 

Aachen, Eschweiler, Deutschland, 15Novartis Pharma GmbH, BU Oncology, 

Nürnberg, Deutschland, 16Klinikum der J .W . Goethe-Universität Frankfurt, 

Med . Klinik II – Hämatologie/Onkologie, Frankfurt, Deutschland 

Introduction. Nilotinib is a potent and highly selective BCR-ABL inhibitor 

with approval for newly diagnosed Ph+ CML patients in CP based 

on superior PFS and faster responses vs Imatinib (IM). Nilotinib is also 

indicated for CP and AP Ph+ CML pts who failed prior therapy including 

IM. 

Methods. Follow-up analysis of an observational study of nilotinib in 

148 pts with Ph+ IM-resistant or -intolerant CML within clinical practice 

in 71 centres in Germany between Jan 2008 and Nov 2010. 

Results. 64.1% of the patients were older than 60 yrs, 7.4% older than 80 

yrs (median age 65.8 yrs). 98.6% (1.4%) presented in CP (AP). 95.9% had 

a good performance status (ECOG index ≤1). All pts were pretreated 

with IM. Further prior drug treatments were chemotherapy (34.5%), 

IFN (26.4%), dasatinib (24.3%) and other unspecified drugs (10.8%). Two 

patients had received SCT in the past. 64.2% of patients were treated 

with nilotinib as 2nd line therapy mostly due to resistance/intolerance 

against IM (50.0%/48.0%) or dasatinib (16.2%/6.1%). At initial visit, a 

dose of 800 mg nilotinib/d was prescribed in 70.3% (400 mg/d in 25%). 

Median duration of nilotinib therapy at the data cut-off for this analysis 

was 235 days. Remission status at study entry was 66.2% in CHR, 

41.9% in MCyR (missing data =17.6%), 20.9%/9.5% in MMR/CMR. These 

responses improved significantly under nilotinib, reaching cumulative 

incidences of CHR, MCyR, MMR and CMR of 89.2%, 33.1%, 41.9% and 

31.1%, respectively. Of note, cytogenetic and molecular examinations 

were frequently not done (e.g. 81.8% and 26.3% after 6 months, respectively). 

Overall, the median time to response was 77 days (5–547 days). 

Dose reduction or therapy interruption at any time occurred in 18.9%. 

In 33.8% nilotinib treatment was stopped prematurely. 73% experienced 

at least one AE during the observation period which was considered serious 

in 14.2%. Hematologic toxicity was observed in 18.9% of pts (12.2% 

with thrombocytopenia), non-hematologic toxicities occurred in 43.2% 


of pts. The most frequently reported AEs were skin reactions including 

pruritus (13.5%) and rash (11.5%), gastrointestinal symptoms such as 

nausea (8.8%), diarrhoea (7.4%) and upper abdominal pain (6.1%) as well 

as headache (11.5%). 

Conclusions. These data from routine clinical management support the 

use of nilotinib as an efficacious and safe drug for treatment of a broad 

population of CML pts with poor response or intolerance to a prior therapy 

including IM. 



B14 – 0294 

Hepatitis B virus infection and risk of lymphoma: results of a 

serological analysis within the European case-control study 

EPILYMPH 

*N . Becker1 , P . Schnitzler2 , P . Boffetta3 , 4 , P . Brennan3 , L . Foretova5 , M . Maynadié6 

, A . Nieters7 , A . Staines8 , Y . Benavente9 , P .L . Cocco10 , S . de Sanjosé9 1Deutsches Krebsforschungszentrum, Epidemiologie von Krebserkrankungen, 

Heidelberg, Deutschland, 2Universität, Medizin, Heidelberg, Deutschland, 

3International Agency for Research on Cancer, Epidemiology, Lyon, 

Frankreich, 4International Prevention Research Institute, Epidemiology, 

Lyon, Frankreich, 5Masaryk Memorial Cancer Institute, Cancer Epidemiology 

and Genetics, Brno, Tschechische Republik, 6University, Registre des 

Hémopathies Malignes, Dijon, Deutschland, 7Universität, Molecular Epidemiology, 

Freiburg, Deutschland, 8University, School of Nursing, Dublin, 

Irland, 9Unitat d’Infeccions i Càncer – Unit of Infections and Cancer (UNIC), 

Institut Català d’Oncologia – Catalan Institute of Oncology, Barcelona, 

Spanien, 10University, Occupational Medicine, Cagliari, Italien 

Introduction. Epilymph is a European multicentric epidemiologic casecontrol 

study on the etiology of lymphoma comprising 2362 cases and 

2458 controls from 6 countries (Czech Republic, France, Germany, Ireland, 

Italy, Spain). After having found a significantly elevated lymphoma 

risk among lymphoma cases with a self-reported medical history of 

HBV infection based on questionnaire data, we used the study material 

to investigate associations between serological indicators of HBV infection 

with risk of HL, NHL and specific lymphoma entities. 

Methods. We tested HBs-antigen (HBsAg), anti-HBc and anti-HBs to 

distinguish between susceptibility, current, past infection and immunity 

by vaccination. Statistical analysis was carried out with unconditional 

logistic regression. 

Results. We found a statistically significant positive association especially 

of a past HBV infection with multiple myeloma (MM, OR=1.97, 

95%-CL=1.16–3.37). Past HBV infection was also associated with B-CLL 

(OR=1.33, 95%-CL=0.82–2.16) and T-NHL (OR=1.59, 95%-CL=0.65–3.90) 

which was, however, not statistically significant. Non-significant association 

occurred also for current HBV infection and NHL (OR=1.49, 

95%-CL=0.65–3.41), B-NHL (OR=1.58, 95%-CL=0.69–3.64) and diffuse 

large B-cell lymphoma (DLBCL, OR=1.50, 95%-CL=0.47–4.82). Subjects 

having HBV infection self-reported were serological positive in 75% of 

cases and 80% of controls. For vaccination, the corresponding figures 

were 49% and 54%, respectively. 

Conclusion. The present results support previous reports of an association 

between a history of HBV infection with an elevated lymphoma 

risk and add multiple myeloma to the list of potentially virus-associated 

lymphoma entities. Chronic antigen stimulation and immune response 

to a past but not fully cleared HBV infection may be an explanation for 

the association.



B15 – 0309 

Retrospective analysis of treatment-related toxicities and outcome 

in high-risk Ewing sarcoma patients receiving Treosulfan or 

Busulfan-based high-dose chemotherapy with autologous stem 

cell transplantation* 

*H . Jürgens1 , U . Dirksen1 , S . Jabar1 , K . Ehlert1 , J . Boos1 , P . Bader2 , R . Ladenstein3 

, A . Ranft1 1University Hospital, Pediatric Hematology and Oncology, Muenster, 

Deutschland, 2Johann Wolfgang Goethe University Medical Center, 

Frankfurt, Deutschland, 3 3Children‘s Cancer Research Institute (CCRI), Wien, 

Österreich 

Objective. Busulfan (BU), in combination with melphalan (MEL), highdose 

chemotherapy (HDC) with autologous stem cell transplantation 

is widely used in consolidation treatment of poor-prognosis Ewing sarcoma 

patients. Treosulfan (TREO) has been newly introduced recently 

into the treatment protocols. We analyzed treatment-related toxicities 

and outcome in patients treated with BU-MEL or TREO-MEL HDC according 

to the EURO-E.W.I.N.G.99 (EE99) protocol of the German Society 

of Pediatric Hematology and Oncology (GPOH) from 1998–2009. 

Methods. 157 patients were identified with full records of BU-based 

HDC, administrated PO in 113 patients and IV in 44 patients, and 44 patients 

with IV TREO-based HDC. BU-MEL was given in 31.8% (n=50) 

according to high-risk localized disease mainly for poor response to 

initial chemotherapy (R2loc), in 25.5% (n=40) for pulmonary metastases 

(R2pulm), and in 42.7% (n=67) for primary mainly skeletal dissemination 

(R3). TREO-MEL patients had a more progressed risk profile 

(R2loc: 6; 13.6%; R2pulm: 5; 11.4%; R3: 33; 75%; p=0.001). HDC toxicity 

was analyzed by descriptive statistics according to modified CTC toxicity 

grade scales of the EE99 protocol. Outcome was analyzed descriptively 

by event-free survival (EFS) and overall survival (OS) controlled 

for risk factors by multivariate regression analysis. 

Results. Grade 3 and 4 ratings occurred in 654 of 2500 toxic episodes 

(26.2%) in BU-MEL HDC (PO: 27.3%; IV: 23.5%), and in 163 of 842 toxic 

episodes (19.4%) in TREO-MEL HDC (vs. BU-MEL PO+IV: p10% in total in single scales were observed in TREO-MEL compared 

to PO+IV BU-MEL and compared to IV BU-MEL: WBC (vs. BU-MEL 

PO+IV: p=.001; IV only: p=.016); granulocytes (p=.016; p=.120); platelets 

(p=.016; p=.114); infection (p=0.020; p=0.075); stomatitis (p12,500 steps/day) 

while 5% had to be considered as sedentary (100 steps/minute), only 8 of 

118 (7%) patients reached the time to be spend on this level of activity as 

recommended for an active lifestyle (i.e., 30 min/day). The TESS score 

(0–100) for tumors located in upper extremity was 90.2 (range 69.6–100; 

SD=11.1), and for lower extremity tumors 88.9 (range 40.8–100; SD=12.1) 

indicating good function following multimodal tumor treatment was 

achieved. 

Conclusions. These preliminary data indicate that patients after Ewing 

sarcoma treatment can reach step activity levels similar to healthy 

adults. However, most patients stay on a rather low intensity of activity. 

SAM can be used to capture activity levels in long-term survivors of 

Ewing sarcoma. It may be advantageous to consider the use of a combination 

of outcome measures, including SAM, for objective functional 

mobility assessment. Parallel recording of physical activity (SAM) and 

TESS provides a better measure reflecting the complex situation of the 

patients by combining objective and subjective parameters. The study 

is being continued to include all long-term Ewing sarcoma survivors 

initially diagnosed between 1980 and 2009. 

*supported by Bundesministerium für Bildung und Forschung (BMBF) 

01ER0807 . 


9

Abstracts 

Mammakarzinom/gynäkologische Tumoren 

Best-of-Poster – Mammakarzinom/ 

gynäkologische Tumoren 

B17 – 0067 

Phase II-study with a targeted cytotoxic LHRH- analog (AEZS- 

108) in patients with LHRH – receptor positive endometrial 

cancer: Protocol AGO-Gyn 5, AGO-Study Group 

*G . Emons1 , S . Tomov2 , J . Sehouli3 , P . Harter4 , P . Wimberger5 , L .C . Hanker6 , 

A . Stähle7 , A . Hristamian8 , F . Hilpert9 , M .W . Beckmann10 , P . Dall11 , H . Sindermann11 

, C . Gründker1 1Georg August Universität, Klinik für Gyn . und Geburtshilfe, Göttingen, 

Deutschland, 2University Hospital, Pleven, Bulgarien, 3Charité, Berlin, 

Deutschland, 4HSK, Wiesbaden, Deutschland, 5University Hospital, Essen, 

Deutschland, 6University Hospital, Frankfurt, Deutschland, 7Karlsruhe, Germany, Deutschland, 8Plovdiv, Bulgarien, Bulgarien, 9University Hospital, 

Kiel, Deutschland, 10University Hospital, Erlangen, Deutschland, 11Aeterna Zentaris, Frankfurt, Deutschland 

Background. Endometrial cancers (EC) commonly express receptors for 

luteinizing homone releasing hormone (LHRH ). AEZS-108 is a targeted 

cytotoxic drug where [ D-Lys(6)]-LHRH is linked to doxorubicin. 

We assessed efficacy and toxicity of AEZS-108 in endometrial cancer. 

Methods. Patients with LHRH-receptor positive advanced (stages FIGO 

III or IV; n=27) or recurrent endometrial cancer (n=16) received AEZS- 

108 (267 mg/m2 3-weekly) for 6 cycles. At least 1 measurable lesion was 

required at baseline. Independent radiologic review was performed. Response 

rate per RECIST was defined as primary endpoint. Secondary 

endpoints were sefaty, time-to-progression (TTP) and overall survival 

(OS). 

Results. 43 patients with median age of 68 years entered the study. Percentages 

of tumor cells staining for LHRH-R ranged 30–90%. 31 patients 

showed endometrioid and 8 serous histological subtype. Prior 

treatment included surgery (n=42), radiotherapy (n=29), chemotherapy 

(n=9) and hormonal therapy (n=11). 62.8% received AEZS-108 for 

6 courses. One patient was retreated at reduced dose. Possibly drug related 

adverse events, except for hematologic toxicity grade 3/4 (rapidly 

reversible neutropenia: 60%, anemia: 5%), was commonly limited to 

CTCAE grade 1/2. There was no evidence of cardiotoxiciy. One patient 

stopped therapy because of recurrent anemia. 12 responses were documented 

(2 CR, 10 PR and 17 SD). After prior chemotherapy, 1 CR, 1 PR 

and 2 SDs were assessed. Median TTP was 30 weeks and median OS 

62 weeks. 

Conclusions. A promising clinical benefit rate of 74% was shown. OS after 

single agent AEZS-108 is similar to that reported for modern triple 

combination chemotherapy, but as achieved with distinctly lower toxicity. 


Best of Poster – Mammakarzinom/ 


B18 – 0117 

Pegylated liposomal doxorubicin and carboplatin (C-PLD) versus 

paclitaxel and carboplatin (C-P) in platinum-sensitive ovarian 

cancer (OC) patients (pts): Treatment at recurrence and overall 

survival (OS) final analysis from CALYPSO phase III GCIG trial 

*C . Kurzeder1 , W . Meier2 , C . Jackisch3 , A . Staehle4 , A . Burges5 , J . Pfisterer6 , 

A . Belau7 , G . Emons8 , U . Canzler9 , W . Schroeder10 , J . Sehouli11 , A . du Bois1,11 , 

P . Wimberger12 , B . Schmalfeldt13 , S . Mahner14 , U . Wagner15 , E . Pujade-Lauraine16 

1Kliniken Essen Mitte, Evang . Huyssens-Stiftung/Knappschaft GmbH, Gynäkologie 

& Gynäkologische Onkologie, Essen, Deutschland, 2Evangelisches Krankenhaus Düsseldorf, Düsseldorf, Deutschland, 3Klinik für Gynäkologie 

und Geburtshilfe Offenbach, Offenbach, Deutschland, 4Frauenarztpraxis, Karlsruhe, Deutschland, 5Klinikum der Universität München, Klinik und 

Poliklinik für Frauenheilkunde und Geburtshilfe, München, Deutschland, 

6Städt . Klinikum Solingen GmbH, Klinik für Frauenheilkunde und 

Geburtshilfe, Solingen, Deutschland, 7Universität Greifswald, Klinik und 

Poliklinik für Frauenheilkunde und Geburtshilfe, Greifswald, Deutschland, 

8 9 Universitätsfrauenklinik Göttingen, Göttingen, Deutschland, Klinik und 

Poliklinik für Frauenheilkunde und Geburtshilfe Universitätsklinikum Carl 

Gustav Carus, Dresden, Deutschland, 10Klinikum Bremen Mitte, Frauenklinik, 

Bremen, Deutschland, 11Charité Campus Virchow-Klinikum, Klinik 

für Gynäkologie, Berlin, Deutschland, 12Universitätsklinikum Essen, Klinik 

für Frauenheilkunde und Geburtshilfe, Essen, Deutschland, 13Frauenklinik und Poliklinik der Technischen Universität München, München, Deutschland, 

14Universitätsklinikum Hamburg-Eppendorf, Klinik und Poliklinik für 

Gynäkologie, Hamburg, Deutschland, 15Universitätsklinikum Gießen u . 

Marburg GmbH, Standort Marburg, Klinik für Gynäkologie, Gynäkologische 

Endokrinologie und Onkologie, Marburg, Deutschland, 16Hopital Hotel-Dieux, 

Paris, Frankreich 

Background. CALYPSO is a large international randomized phase III 

trial comparing CPLD and C-P in pts with OC in late relapse. Results 

of the progression-free survival (PFS), the primary endpoint, suggest 

a benefit in pts treated with C-PLD with a hazard ratio (HR) of 0.82 

(p=0.005). Overall severe non-hematologic toxicity (36.8% vs 28.4%; 

p



B19 – 0279 

Oncofertility; Xenotransplantation of cryopreserved ovarian 

tissue from patients with ovarian tumors into SCID mice – no 

evidence of malignant cell contamination 

*A . Müller1 , L . Lotz1,2 , M . Montag1,2 , H . van der Ven2 , M . von Wollf2,3 , I . Hoffmann1 

, D . Wachter4 , M . Beckmann1 , R . Dittrich1 1 2 Universitätsklinikum Erlangen, Frauenklinik, Erlangen, Deutschland, Universitätsklinikum 

Bonn, Frauenklinik, Bonn, Deutschland, 3Inselspital Bern, 

Frauenklinik, Bern, Schweiz, 4Universitätsklinikum Erlangen, Pathologisches 

Institut, Erlangen, Deutschland 

Background. There are still many unanswered questions regarding the 

safety of ovarian tissue retransplantation in cancer patients, due to the 

potential risk that malignant cells in the frozen tissue may lead to recurrence 

of the primary disease after transplantation. This study examined 

the possible presence of residual malignant cells in ovarian cortex from 

patients with ovarian tumors after xenografting of the ovarian tissue 

into severe combined immunodeficiency (SCID) mice. 

Methods. The ovarian cortex tissue was obtained during surgical laparoscopy 

or unilateral/bilateral oophorectomy. Before cryopreservation, 

the ovarian cortex was examined histologically to ensure that a sufficient 

quantity of primordial follicles had been obtained and to exclude 

involvement of the tissue by malignancy. Freezing of the ovarian tissue 

was undertaken in accordance with three similar slow freezing protocols. 

The ovarian tissue was transplanted into immunodeficient (SCID) 

mice in an intramuscular pocket in the neck muscle. Twenty-four weeks 

after transplantation, the grafts were recovered and hematoxylin-eosin 

stains were performed. In addition, freshly cut sections were stained 

with antibodies against pancytokeratin (monoclonal antibody KL1). 

Results. All of the patients had a normal follicular distribution relative 

to their age, and light microscopy showed no evidence of malignant 

cells in the ovarian tissues prior to transplantation, even in patients with 

bilateral ovarian carcinoma. All of the animals remained in good health 

throughout the study and none of the grafts resulted in recurrences. 

Nor did any of the mice showed macroscopically metastasis. The serial 

sections from human ovarian grafts had a normal histological appearance. 

No carcinoma cells were seen in any of the H&E-stained slides 

examined or in any of the slides with antibodies against cytokeratins. 

Conclusion. Ovarian transplantation appears to be a feasible consideration 

in young female patients with ovarian tumors. The negative 

findings do not rule out malignant cell contamination in the ovarian 

tissue. A larger number of tissue fragments would increase the validity 

of these preliminary results and more sensitive methods may be necessary 

for assessment of possible micrometastases. In order to increase 

the safety of the procedure, ovarian tissue harvesting and re-implantation 

should take place in the setting of clinical trials with clearly defined 

methods, objectives, and end points. 



B20 – 0318 

Prospective comparison of risk assessment tools in early breast 

cancer (Recurrence Score, uPA/PAI-1, central grade, and luminal 

subtypes): final correlation analysis from the phase III WSG-Plan 

B trial 

*O . Gluz1 , H . Kreipe2 , T . Degenhardt1 , R . Kates1 , C . Liedtke1,3 , M . Christgen2 , 

M . Clemens4 , S . Markmann5 , C . Uleer6 , D . Augustin7 , S . Shak8 , C . Thomssen9 , 

U . Nitz1,10 , N . Harbeck1,11 1Westdeutsche Studiengruppe, Mönchengladbach, Deutschland, 

2 3 MHH Hannover, Hannover, Deutschland, Uniklinik Münster, Münster, 

Deutschland, 4Klinikum Mutterhaus der Borromäerinnen, Trier, Deutschland, 

5Uniklinikum Südstadt, Rostock, Deutschland, 6Gynäkologisch onkologische Praxis, Hildesheim, Deutschland, 7Klinikum Deggendorf, 

Degendorf, Deutschland, 8Genomic Health Inc ., Redwood City, Vereinigte 

Staaten von Amerika, 9Uniklinikum Halle/Saale, Halle/Saale, Deutschland, 

10 11 EVK Bethesda, Mönchengladbach, Deutschland, Uniklinik Köln, Köln, 

Deutschland 

Background. Both the Recurrence Score® (RS) multi-gene assay and 

invasion factors uPA/PAI-1 are recommended by guidelines (ASCO, 

AGO) for decision support regarding adjuvant chemotherapy in patients 

with early breast cancer (BC). Here, we present the final WSG- 

Plan B trial correlation analysis of these risk assessment tools. 

Methods. Plan B trial (evaluating anthracyline-free adjuvant chemotherapy, 

6×TC, vs. 4×EC-4×DOC in HER2-negative BC; n=2.448 to 

be randomized for chemotherapy). RS has been used as the selection 

criterion for chemotherapy vs. endocrine therapy alone in HR+ BC (if 

RS25 (21%). In 257 patients 

with 0–3 involved LN, chemotherapy was omitted based on RS results 

(12.3% of patients after amendment). By the last interim analysis in February 

2011, data on central grade are available in 1509 patients and 

Ki-67 in 592 patients. An only moderate positive correlation was observed 

between Ki-67 and RS (Spearman’s coefficient rs =0.336, p

Abstracts 

high-risk according to uPA/PAI-1, Ki-67 or central grade. Further follow-up 

of the WSG-Plan B trial will clarify the clinical significance of 

these findings regarding patient outcomes. 

Molekulare Onkologie 

Best of Poster – Molekulare Onkologie 

B21 – 0208 

Transient telomere dysfunction induces chromosomal instability 

and carcinogenesis in telomerase-proficient mice 

*D . Hartmann1,2 , Y . Begus-Nahrmann2 , P . Eshraghi2 , P . Schirmacher3 , H .- 

W . Lee4 , A . Lechel2 , K .L . Rudolph2 1Chirurgische Klinik und Poliklinik, Klinikum rechts der Isar, München, 

Deutschland, 2Institut für Molekulare Medizin und Max-Planck-Forschungsgruppe 

für Stammzellalterung, Universität Ulm, Ulm, Deutschland, 3Institut für Pathologie, Universitätsklinikum Heidelberg, Heidelberg, Deutschland, 

4Department of Biochemistry, College of Science, Yonsei University, Seoul, 

Korea, Republik 

Introduction. A current concept indicates that telomere dysfunction can 

increase tumor initiation by induction of chromosomal instability, but 

initiated tumor cells need to reactivate telomerase for genome stabilization 

and tumor progression. However, this concept has not been proven 

in vivo since appropriate mouse models were lacking. 

Methods. Here, we analyzed hepatocarcinogenesis (i) in a novel mouse 

model of inducible telomere dysfunction with wildtype telomerase, (ii) 

in telomerase knockout mice with chronic telomere dysfunction (G3 

mTerc-/-), and (iii) in wildtype mice with functional telomeres and telomerase. 

Results. Transient or chronic telomere dysfunction enhanced the rates 

of chromosomal aberrations in developing HCCs, but increases in tumorigenesis 

compared to wild-type mice occurred only in telomeraseproficient 

mice. In contrast to mTerc-/- tumors, telomerase-proficient 

tumors that experienced transient telomere dysfunction retained the 

capacity to minimize DNA damage and exhibited elevated rates of tumor 

cell proliferation compared to wild-type tumors. 

Conclusion. Together, these data provide the first in vivo evidence that 

transient telomere dysfunction promotes chromosomal instability and 

carcinogenesis in a telomerase-proficient background. 


B22 – 0284 

Inhibition of Hsp90 impairs hexokinase (HXK-II) activity by disrupting 

its interactions with voltage dependent anion channels 

(VDAC) 

*M .E . Mycielska1 , C . Moser1 , C . Wagner1 , E . Scheiffert1 , E .K . Geissler1 , 

H .J . Schlitt1 , S .A . Lang1 1Universitätsklinikum Regensburg, Experimentelle Chirurgie, Regensburg, 

Deutschland 

Background. Glycolysis is the predominant metabolic pathway in cancer 

cells (Warburg effect) with hexokinase II (HXK II) as its crucial 

enzyme. Due to ATP requirements, this enzyme has to be attached to 

VDACs in the mitochondrial membrane. In addition, overexpression of 

the molecular chaperone heat-shock protein 90 (Hsp90) in cancer cells 

has been described. Interestingly, TOM complex, responsible for import 

of proteins (e.g. VDACs) into mitochondria, is an Hsp90 client protein. 


Therefore, we hypothesised that targeting Hsp90 would affect localisation 

of HXK II in cancer cells through changes in VDAC import. 

Methods. Human gastric and pancreatic cancer cell lines (TMK1, Mia- 

PaCa2) were used to evaluate the effects of Hsp90 inhibitor 17-DMAG 

(17-(dimethylaminoethylamino)-17-demethoxygeldanamycin) on cancer 

cell metabolism. In vitro, localisation and expression of HXK II and 

VDAC protein were determined using Western blotting and immunocytochemistry. 

Spectrophotometric technique was employed to evaluate 

enzyme activity. In vivo, murine Panc02 pancreatic adenocarcinoma 

cells were used in subcutaneous tumor model. 

Results. Overall hexokinase activity in the mitochondrial fraction was 

decreased by 25±8.1% and 57±9.7% (n=5; p=0.03–0,04) in cells and tissues 

when treated with 17-DMAG compared to control conditions, whilst 

its activity in the cytoplasmic fractions did not differ (p>0.05). Staining 

of HXK II, VDAC and mitochondria in the cells showed large areas of 

colocalisation upon control conditions. Interestingly, colocalisation 

was significantly reduced when cells were treated with the Hsp90 inhibitor. 

Furthermore, treatment with 17-DMAG resulted in a decreased 

expression of HXK II in the mitochondrial fraction in cells and tissues. 

Determination of the expression of HXK I and III in cancer cells and 

tissues showed a slight decrease in HXK III expression in cytoplasmic 

fraction whilst there was no change in mitochondrial fraction in either 

protein. 

Conclusion. Results so far show that targeting Hsp90 affects glucose metabolism 

in cancer cells via inhibition of VDAC incorporation into the 

mitochondrial membrane and in consequence disabling HXK II-VDAC 

binding. Hsp90 inhibitors might, therefore, play a role in treatment 

concepts targeting the Warburg effect in human cancer. 


B23 – 0337 

Genetic analysis for SDH mutations (SDH-B, SDH-C and SDH-D) in 

paraganglioma patients 

*T . Cohnert1 , J . Fruhmann1 , S . Koter1 , A . Baumann1 , J . Geigl2 1Medizinische Universität Graz, Klin . Abt . für Gefäßchiurgie, Graz, 

Österreich, 2Medizinische Universität Graz, Institut für Humangenetik, Graz, 

Österreich 

Introduction. Paraganglioma represent rare tumours of the head and 

neck. They originate from the neural crest cells and can occur from the 

skull base to the pelvic floor. Many cases are sporadic. However, the hereditary 

cases are most often seen in Von Hippel Lindau Disease, MEN 2 

or neurofibromatosis. Recently succinate dehydrogenase mutations 

(SDH) have been described in paraganglioma and phaechromocytoma 

patients. 

Patients and methods. 51 patients (pts.) were operated on 60 Paragangliomas 

(PGL) of the neck (carotid body tumors) between January 1988 

and July 2011. Prospectively collected clinical data were analyzed retrospectively. 

In 2006 genetic analyses were started for succinate dehydrogenase 

mutations (SDH; SDH-B, SDH-C and SDH-D). Follow-up was 

completed. All patients were contacted and genetic testing as well as genetic 

family counselling were offered. Statistical data are given as mean 

values and standard deviation. 

Results. 51 pts. (36 female, 15 male) were operated at a mean age of 

53.9+16.6 years (range 24–80 years). In 9 pts. (4 female, 5 male) there 

were bilateral tumors. After a mean follow-up of 94 months (range 

1–263 months = 21 years 11 months) 6 pts. had died. 45 pts. were alive, 

3 pts. did not agree to genetic testing and one patient was currently not 

available for testing (moved abroad). Of the tested 41 pts. no mutation 

was detected in 20 pts. (17 female, 3 male). In 21 pts. a total of 14 SDH-D 

mutations, 2 SDH-B mutations and 1 SDH-C mutation were found. Additional 

4 pts. showed abnormalities in SDH-C that need further investigation. 

In summary in 17 of 41 pts. (17/41=41.5%) SDH mutations were

confirmed. In all 9 patients with bilateral tumors SDH-D mutations 

were detected. 

Conclusions. Long-term survival after surgical removal of paraganglioma 

of the neck is not limited. Genetic testing is mandatory in patients 

with bilateral tumors or positive family history and strongly recommended 

in all other PGL patients. When a SDH mutation is diagnosed, 

regular clinical and ultrasound investigations, MRI of the head and 

neck, thorax, abdomen and pelvis are recommended for diagnosis or 

exclusion of multiple tumor localizations as well as phaechromocytoma. 

In addition genetic exploration of patients’ families and counselling 

should be offered. 


B24 – 0480 

Two novel splice variants of the transcriptional co-repressor 

Daxx with different p53-regulating properties 

N . Wethkamp1 , S . Funke1 , C .V . Suschek2 , E . Grinstein3 , S . Heikaus1 , H .E . Gabbert1 

, *C . Mahotka1 1Heinrich Heine Universität – Klinikum, Institut für Pathologie, Düsseldorf, 

Deutschland, 2Heinrich Heine Universität – Klinikum, Klinik für Unfallchirurgie, 

Düsseldorf, Deutschland, 3Heinrich Heine Universität – Klinikum, 

Klinik für Kinder-Onkologie, -Hämatologie und -Immunologie, Düsseldorf, 

Deutschland 

Aims. Deregulation of apoptosis is involved in several diseases including 

cancer, characterized by an abnormally prolonged cell survival. 

The ubiquitously expressed protein Daxx is implicated in apoptosis but 

whether its function is pro- or anti-apoptotic is still controversially discussed. 

Daxx is involved in transcriptional control of several genes and 

it comprises domains including a regulatory C-terminus which is responsible 

for the interaction with numerous proteins such as p53, PML, 

or HSP27. 

Methods. RT-PCR, expression cloning, retroviral transfections, confocal 

fluorescence microscopy, western blotting, immunoprecipitations, 

flow cytometry, luciferase reporter gene assays, apoptosis assays, etc. 

Results. Here we describe the identification and characterization of two 

novel variants of Daxx termed Daxx-β and Daxx-γ which are generated 

by alternative splicing. Alternative splicing results in a truncated 

regulatory C-terminus in both proteins. As a consequence, Daxx-β 

and Daxx-γ show a markedly decreased affinity to PML, which in turn 

is associated with a different subnuclear localization of these proteins 

compared to Daxx. While Daxx is mainly localized to PMLoncogenic 

domains (PODs) Daxx-β and Daxx-γ display a distinct distribution pattern. 

Furthermore, Daxx-β and Daxx-γ show a decreased affinity to p53 

also due to the truncated C-terminus. We provide evidence that the p53 

recruitment into PODs is Daxx isoform dependent. The decreased affinity 

of Daxx-β/-γ to p53 and PML results in a diffuse localization of p53 

throughout the nucleus. In contrast to Daxx, Daxx-β and Daxx-γ are 

unable to repress p53-mediated transcription. 

Conclusion. Therefore, alternative splicing of Daxx as a regulator of p53regulated/dependent 

gene expression might indicate an additional level 

in the cellular apoptosis network. 

Palliativmedizin/ Supportivtherapie 

Best of Poster – Palliativmedizin/ Supportivtherapie 

B25 – 0058 

Randomized placebo-controlled double-blind study of modified 

methylphenidate on cancer-related fatigue (CRF) 

*M .E . Heim1 , S . Kuhnt2 , R . Schwarz2 , W . Abenhardt3 , B . Lathan4 , K . Verpoort5 , 

S . Siehl6 , C . Ose7 , A . Engels8 , J .-U . Rüffer9 1 2 Universität Göttingen, Rosdorf, Deutschland, Universität Leipzig, Leipzig, 

Deutschland, 3Onkologische Praxis, München, Deutschland, 4Onkologische Praxis, Dortmund, Deutschland, 5Onkologische Praxis, Hamburg, Deutschland, 

6Onkologische Praxis, Kassel, Deutschland, 7Universitätsklinikum Essen, Inst . f . Med . Informatik, Biometrie u . Epidemiologie, Essen, Deutschland, 

8Medice Pütter GmbH, Iserlohn, Deutschland, 9Deutsche Fatigue 

Gesellschaft, Köln, Deutschland 

Introduction. CRF is the most prevalent symptom of cancer patients 

(pts) following treatment, can persist for months or even years, and significantly 

reduces usual functioning and health related quality of life. 

There is no standard treatment for CRF, initially a comprehensive assessment 

and the treatment of possible causative factors, such as anemia 

or hypothyroidism is recommended. Nonpharmacological treatments, 

such as individualized exercise programs, psychoeducational and cognitive-behavioral 

interventions are the backbone of CRF therapy. Pharmacological 

treatment with the psychostimulant methylphenidate showed 

inconclusive results in several phase II and III studies. 

Patients and methods. Tumor pts without active disease suffering from 

CRF (MFI-score >40) were randomized into a treatment and a placebo 

group. The treatment duration was 3 weeks with modified release methylphenidate 

starting with 20 mg in the 1st week, and dose escalation 

to 40 mg, and 60 mg in the 2nd and 3rd week in case of inadequate 

treatment effect. Treatment results were evaluated by patient reported 

outcome measures with MFI, EORTC-QLQ-C30, HADS, and by the 

clinical global impression (CGI) of the physician at baseline, week 3 and 

6, and for MFI and CGI additionally at week 2 and 3. Primary endpoint 

was the general fatigue in the MFI. A total of 67 pts (46 women, 21 men, 

mean age 48 years) were randomized, 53 could be evaluated, 25 in the 

treatment, 28 in the placebo group. Mean fatigue duration was 4 and 

2.5 years. 

Results. In the intention to treat analysis there was a mean reduction 

of the general fatigue score of the MFI of 22 points (verum) and 13 points 

(placebo), in the per protocol analysis of 25 and 16 (not significant). 

There was a significant difference in the CGI for therapeutic efficacy in 

favor of methylphenidate. Single pts had an impressive advantage of the 

treatment with methylphenidate. No significant differences could be 

observed for anxiety and depression, and the EORTC-subscales, except 

for the cognitive function subscale, which was significantly improved 

in the verum group. 

Conclusion. In accordance with other studies we could not observe 

a significant improvement of CRF in the MFI with methylphenidate. 

However significant better results for the intervention group could be 

observed in the therapeutic efficacy in the CGI and for the cognitive 

function in the EORTC-QLQ-C30. Differences in both groups and subgroup 

analysis will be discussed to explain the results. 


13

Abstracts 


B26 – 0071 

Occupational rehabilitation after partial laryngectomy 

*D . Wollbrück1 , H . Danker1 , E .F . Meister2 , A . Meyer1 1Universität Leipzig, Medizinische Fakultät, Medizinische Psychologie und 

Medizinische Soziologie, Leipzig, Deutschland, 2Klinikum St . Georg, HNO- 

Klinik, Leipzig, Deutschland 

Purpose. Improvements in early detection and treatment of laryngeal 

cancer have let to an increase of numbers of cancer survivors. Against 

this background two questions arise for patients after partial laryngectomy: 

I. How does the work status of patients with partial laryngectomy 

change? II. Which factors are associated with a successful occupational 

rehabilitation? 

Methods. Since 2007, all patients in Middle Germany, who underwent 

a partial laryngectomy due to laryngeal carcinoma, were contacted in 

a multi-centre longitudinal study. Patients were questioned at different 

time points (t1= preoperative; t2=2 weeks after partial laryngectomy; 

t3=12 weeks after operation; t4=1 year postoperative). For this presentation, 

all patients were included, who were interviewed until December 

2010 and were under the age of 65 at t1 (n=38). Instruments used were 

the Quality of Life Questionnaire of the European Organization of Research 

and Treatment of Cancer (EORTC QLQ-C30), single questions 

(importance of having a job) and sociodemographic (age, professional 

career) and medical data (tumour stage; use of rehabilitation). 

Results. I. Employment rate one year postoperatively (40%) has decreased 

in comparison to preoperatively (63%), while the group of patients 

who are no longer available for the job market (due to retirement annuity 

or disability pension) has increased (from 21% at t1 to 36% at t4). All 

patients who worked one year post surgery had already been working 

preoperatively. The perceived extent of limitation in the context of work 

and daily activities has increased (from 26% at t1 to 84% at t4). II. The 

return to work one year postoperatively is correlated with the professional 

career (Rho=0.41*, p=0.04). All other factors show no significant 

correlation. 

Conclusion. Blue-collar workers return to work significantly less often 

than white-collar/self-employed workers. Being able to re-enter the 

workforce and to take an active part in the occupational life should be 

both a matter of the affected patients and of public interest. The introduced 

findings could contribute to further discussion on how to adapt 

the specific work situations of blue-collar workers so that a return, if not 

to the same job, at least to an alternative job may be within the realms of 

possibility for the affected patients. 


B27 – 0145 

Somato-psychosocial caring program to improve symptoms 

in cancer patients with stem cell transplantation (HSCT) – first 

results of a prospective non randomized intervention study 

*H . Schmidt1 , P . Jahn1,2 , S . Böse1 , A . Bauer1 , A . Lau3 , O . Stoll3 , H .-J . Schmoll2 , 

C . Mauz-Körholz2 , O . Kuß4 , M . Landenberger1 1MLU Halle, Institut für Gesundheits- und Pflegewissenschaft, Halle, 

Deutschland, 2Universitätsklinikum Halle, Halle, Deutschland, 3MLU Halle, 

Department Sportwissenschaft, Halle, Deutschland, 4MLU Halle, Institut für 

Medizinische Epidemiologie, Biometrie und Informatik, Halle, Deutschland 

Objective. Patients with hematopoietic stem cell transplantation 

(HSCT) suffer from a range of symptoms including mucositis, fatigue 

and mobility/activity deficits. This single center prospective non randomized 

clinical study examined whether an evidence-based interdisci- 


plinary caring program would improve global health status and reduce 

somatic symptoms in patients with HSCT. 

Method. Patients with HSCT, age >14 years and written informed consent 

were eligible. The intervention group received modified care consisting 

of three modules based on counseling and exercise focusing 

mobility/activity enhancement, prevention of oral mucositis and nutritional 

support. Control group patients received standard care. Primary 

endpoint was global HRQoL measured by EORTC QLQ C30 at 

discharge. Secondary endpoints were symptoms measured by EORTC 

symptom-scales, physical activity (kcal per week) and use of resources 

e.g. duration of hospitalization. 

Results. 82 patients participated (control group n=42, intervention 

group n=37, average age of 52.6±12.7 years, 69.9% male). Baseline characteristics 

were balanced between both groups except ECOG-status which 

was significantly lower for patients of the intervention group (p

patients that were not already (i) in a reduced performance status or (ii) 

experiencing symptoms that are indicators for advanced disease (e.g. 

dyspnoea). 

Results. During the first two years of the project, 862 patients were consulted 

by the PCST. Generally, patients were already in a reduced physical 

state (ECOG 3 & 4: 40%) and experiencing burdening symptoms 

(e.g. dyspnoea 27%) on the initial PCST consultation. After a one-year 

period, the number of burdening symptoms presented at first PC consultation 

decreased significantly from seven to three (p

Abstracts 

Best of Poster – Seltene Tumoren 

B31 – 0218 

Comparison of Cyclophosphamide versus Ifosfamide containing 

adjuvant chemotherapy (CTX) in Ewing sarcoma (ES) patients: 

results of the randomized standard risk (SR) cohort of EURO- 

E.W.I.N.G. 99 Trial 

*U . Dirksen1 , A . Ranft1 , M .-C . Le Deley2 , J . Whelan3 , M . Paulussen4 , O . Oberlin5 

, I . Lewis6 , J . Michon7 , R . Ladenstein8 , B . Brennan9 , P . Marec Bérard10 , 

H . van den Berg11 , L . Hjorth12 , C . Douglas13 , I . Judson14 , M . van Glabekke15 , 

A . Craft16 , H . Jürgens1 , *U . Dirksen1 , A . Ranft1 , M .-C . Le Deley2 , J . Whelan3 , 

M . Paulussen4 , O . Oberlin5 , I . Lewis6 , J . Michon7 , R . Ladenstein8 , B . Brennan9 , 

P . Marec Bérard10 , H . van den Berg11 , L . Hjorth12 , C . Douglas13 , I . Judson14 , 

M . van Glabekke15 , A . Craft16 , H . Jürgens1 1UKM, Pädiatrische Hämatologie und Onkologie, Münster, Deutschland, 

2 3 Institut Gustave Roussy, Biostatisique, Paris, Frankreich, University 

College Hospital, Medical Oncology, London, UK, 4Vestische Kinderklinik, 

Datteln, Deutschland, 5Institut Gustave Roussy, Oncologie Pédiatrique, 

Paris, Frankreich, 6St .James University Hospital, Leeds, UK, 7Institut Curie, 

Paris, Frankreich, 8St . Anna Children’s Hospital and Research Institute, Wien, 

Österreich, 9Royal Manchester Children’s Hospital, Manchester, UK, 10Centre Léon Bérard, Lyon, Frankreich, 11Academic Medical Center, Emma Children’s 

Hospital, Amsterdam, Niederlande, 12Lund University Hospital, Lund, 

Schweden, 13CCLG Data Centre, Leicester, UK, 14University of Birmingham, 

Birmingham, UK, 15European Organisation for Research and Treatment of 

Cancer Headquarters, Brussels, Belgien, 16The Royal Marsden NHS Foundation 

Trust, London, UK 

Background. Anthracyclines and alkylating agents and are the backbone 

of worldwide used chemotherapeutic regimens in ES. Ifosfamide and 

cyclophosphamide have different toxicity profiles and unknown relative 

efficacy. The EURO-E.W.I.N.G.99 R1 trial for SR patients, compared two 

consolidation regimens combining ifosfamide (I) or cyclophosphamide 

(C) with vincristine (V) and actinomycin D (A) (VAI vs VAC). 

Methods. SR patients with localized ES and either good histological response 

to induction chemotherapy or tumor size

Versorgungsstrukturen/Qualitätssicherung 

Best of Poster – Versorgungsstrukturen/ 

Qualitätssicherung 

B33 – 0098 

Comparison of psychosocial outcomes of breast and colorectal 

cancer patients treated in certified cancer centres vs. non-certified 

treatment units 

*G . Weißflog1 , S . Singer1 , G . Klinitzke2 , E . Kleinert1 , C . Wittekind3 , E . Brähler1 , 

J . Ernst1 1Universität Leipzig, Medizinische Psychologie und Medizinische Soziologie, 

Leipzig, Deutschland, 2Universitätsklinikum Leipzig AöR, Klinik und 

Poliklinik für Psychosomatische Medizin und Psychotherapie, Leipzig, 

Deutschland, 3Tumorzentrum am Universitätsklinikum Leipzig e . V ., Leipzig, 

Deutschland 

Purpose. In Germany, breast and colorectal cancer patients are increasingly 

being treated in certified cancer centres. To date, there are no 

research findings investigating potential differences in clinical, sociodemographic 

and psychosocial outcomes (patient satisfaction, quality 

of life, and psychosocial distress) between patients treated in certified 

cancer centres and patients treated in non-certified units. 

Methods. In a cross-sectional study, socio-demographic, disease-related 

(e.g. UICC stage), and psychosocial data of patients with breast or 

colorectal cancer were assessed in a postal survey. The questionnaire 

included the following standardised instruments: for patient satisfaction 

the Hamburger Fragebogen zum Krankenhausaufenthalt (HFK), 

the EORTC Quality of Life Questionnaire – Core instrument (EORTC 

QLQ-C30) and for psychosocial distress the Hospital Anxiety and Depression 

Scale (HADS). 

Results. A total of 1,925 persons were enrolled into the study. 101 persons 

were excluded from this initial sample (48 could not be located, 42 

died in the meantime, 14 were cognitive impaired). Of the remaining 

1,821 patients, a total of 950 cancer patients participated in the survey 

(return-rate: 52%, 666 patients with breast cancer and 284 patients with 

colorectal cancer). The mean age of respondents was 64 years. Patients 

with breast and colorectal cancer treated in certified cancer centres differed 

not to patients treated in non-certified units with respect to clinical 

and socio-demographic data. In both groups, patient satisfaction 

was generally high. There are only few differences in patient satisfaction 

and its subdimensions (e.g. overall judgement was lower in breast cancer 

patients who were treated in a certified breast cancer centre; satisfaction 

with the sub-dimension medical care is higher in colorectal cancer 

patients in certified colorectal cancer centres). There were no differences 

between both groups in psychosocial distress (anxiety and depression), 

but colorectal cancer patients in certified cancer centres experienced 

impaired quality of life. 

Conclusion. With respect to these empirical findings, there is evidence 

of particular (but not general) differences in psychosocial outcomes in 

comparison between certified cancer centres and non-certified units. 

These results must be validated in future studies involving further parameters 

(e.g. guideline-adherence, compliance), and advanced designs 

(longitudinal approach). 



B34 – 0179 

Trends of population-based breast cancer survival in Germany 

and the US: decreasing discrepancies 

*B . Holleczek1 , H . Brenner2 1 2 Saarland Cancer Registry, Saarbrücken, Deutschland, Division of Clinical 

Epidemiology and Aging Research, German Cancer Research Center, 

Heidelberg, Deutschland 

Background. Population-based studies have revealed both higher cancer 

survival in the US than in Germany and substantial improvement of 

cancer prognosis in these two countries in the past. This populationbased 

study aims at comparing most recent 5-year survival of breast 

cancer (BRC) patients and preceding trends in Germany and the US. 

Material and methods. Women with invasive BRC (ICD-10: C50) from 

Germany (Saarland) and the US (SEER 13 registries) diagnosed and 

followed up through 1977 and 2008 were included (in total 21,796 and 

617,882 patients, respectively). Period analysis was used to derive most 

up-to-date 5-year relative survival (RS) for subsequent calendar periods 

of 4 years between 1981 and 2008 according to age (1–69 and 70+ years 

at diagnosis) and stage (localized, local/regional spread, metastasized, 

unknown). 

Results. Between 1981 and 2008, age standardized RS has steadily improved 

in Germany and the US from 65% and 75% to 83% and 89%, respectively. 

In 2005–2008, no differences in age specific RS were observed 

for the US, but RS of elderly patients was only 75% compared to 88% for 

younger patients in Germany. Over time, the gap in RS between Germany 

and the US has almost disappeared for younger patients (from 8 to 

1% unit), but remained unchanged for elderly patients (13% units). Most 

recent age standardized RS of localized BRC was 98% in both countries. 

RS of locally/regionally spread and metastasized BRC was 79% and 24% 

in Germany and 84% and 27% in the US, respectively in 2005–2008. Since 

1993–1996, the differences in RS have decreased by 5 and 7% units for 

localized and locally/regionally spread BRC, but increased by 4% units 

for metastasized BRC. If adjusted for stage mix, the difference in RS has 

almost disappeared over time. 

Conclusion. Differences between 5-year RS of BRC patients in Germany 

and the US have decreased over time. Similar RS is now observed for 

patients below the age of 70 years and localized BRC, but in Germany 

RS is still inferior for elderly patients and advanced disease. Differences 

in the health care systems, implementation and utilization of organized 

screening, delivery of cancer care as well as population characteristics 

may account for the observed differences in survival. Encouraging, the 

survival of BRC patients has improved in Germany to a much greater 

extent than in the US, albeit challenges remain for the care of elderly 

patients and advanced disease in both countries. 


17

Abstracts 



B35 – 0283 

Effects of a longitudinal intervention study on physical activity 

and functional capability in workaday and occupational following 

oncological rehabilitation 

*H . Kähnert1 , A .-K . Exner1 , B . Leibbrand2 , I . Biester3 , D . Gharaei4 , C . Niehues5 , 

M . Trapp6 1Salzetalklinik, IFR, Norderney – Bad Salzuflen, Bad Salzuflen, Deutschland, 

2 3 Salzetalklinik, Onkologie, Bad Salzuflen, Deutschland, MediClin Rose 

Klinik, Onkologie, Horn-Bad Meinberg, Deutschland, 4Klinik Porta-Westfalica, 

Onkologie, Bad Oeynhausen, Deutschland, 5Median Kliniken am 

Burggraben, Onkologie, Bad Salzuflen, Deutschland, 6Median Klinik am 

Park, Onkologie, Bad Oeynhausen, Deutschland 

Introduction. Physical activity (PA) plays a major role in the prevention 

and rehabilitation of breast cancer patients. Although many patients 

may develop an intention to change their PA, they might not act accordingly. 

Based on the Health Action Process Approach, volitional 

factors like action-/coping planning serve to mediate between exercise 

intention and later PA. The study investigates the effectiveness of the 

INOP-intervention (Individuelle Nachsorge onkologischer Patienten) 

focusing on action- and coping planning to change PA and thus functional 

capability in workaday (FCW) as well as occupational (FCO) over 

six months. 

Methods. The sample consisted of 450 breast cancer patients who underwent 

an oncological rehabilitation. They were randomly assigned to 

the control (CG) or intervention group (IG) and were interviewed with 

a questionnaire at the beginning (t1), at the end (t2) and 6 months after 

the rehabilitation (t3). While the CG received the conventional care, the 

IG additionally received the INOP intervention (consisting of a seminar, 

a counseling interview during the clinical setting and/or a phone 

interview 3 months after discharge). Analysis of covariance was applied 

to investigate differences between CG and IG regarding the action-/coping 

planning, the PA, FCW and FCO (IRES-3 questionnaire). 

Results. Compared to the CG the action-/coping planning of the IG 

increased from t1 to t3. The IG patients reported significantly higher 

planning activities to t2 (p

Urologische Tumoren 

Best of Poster – Urologische Tumoren 

B37 – 0005 

A novel stereotactic prostate biopsy system integrating preinterventional 

MRI and live US fusion 

*T .H . Kuru 1 , M . Roethke 2 , H .-P . Schlemmer 2 , M . Hohenfellner 1 , B .A . Hadaschik 

1 

1 Universitätsklinik Heidelberg, Klinik für Urologie und Kinderurologie, 

Heidelberg, Deutschland, 2 DKFZ Heidelberg, Abteilung für Radiologie, 


Purpose. To develop an effective way to precisely diagnose prostate cancer 

employing a novel prostate biopsy system which integrates preinterventional 

MRI with periinterventional ultrasound for perineal navigated 

prostate biopsies. 

Patients and methods. 106 men with suspicion of prostate cancer (median 

age 66 yrs, PSA 8.0 ng/ml, prostate volume 47 ml) underwent multiparametric 

3T-MRI. Suspicious lesions were marked on the MRI and 

the data were transferred to the novel biopsy system. Using a custommade 

biplane TRUS probe mounted on a stepper, 3D-ultrasound data 

were gathered and fused with the MRI. As a result, suspicious MRI-lesions 

were superimposed over the TRUS-data. Next, 3D-biopsy planning 

was performed including systematic biopsies from the peripheral zone 

of the prostate. Perineal biopsies were taken under live US-imaging and 

the precise location of each biopsy was documented in 3D. Feasibility, 

safety, and cancer detection were evaluated. 

Results. Prostate cancer was detected in 63 out of 106 patients (59.4%). 

A positive correlation between MRI findings and histopathology was 

found in 68.9% (71/103). In MRI-lesions marked as highly suspicious, 

the detection rate was 95.8% (23/24). Target registration error of the first 

2461 biopsy cores was 1.7 mm. Regarding adverse effects, two patients 

experienced urinary retention and one patient a perineal hematoma. 

Urinary tract infections did not occur. 

Conclusions. Perineal stereotactic prostate biopsies guided by the combination 

of MRI and ultrasound allow effective examination of suspicious 

MRI-lesions. Each biopsy core taken is documented accurately 

for its location in 3D enabling MRI-validation and tailored treatment 

planning. The morbidity of the procedure was minimal. 


B38 – 0233 

Basal Differentiation Marker KRT14 Identifies High-Risk Bladder 

Cancer Patients 

*J .-P . Volkmer1,2 , D . Sahoo2 , R .K . Chin2 , P .L . Ho3 , C . Tang2 , A .V . Kurtova3 , 

S .B . Willingham2 , S .K . Pazhanisamy3 , H . Contreras-Trujillo 2 , T . Storm2 , 

Y . Lotan4 , A . Beck2 , A . Alizadeh2 , G . Guilherme3 , S . Lerner3 , M . van de Rijn, 2 , 

L . Shortliffe2 , K . Chan3 , I . Weissman2 1 2 Uniklinik Düsseldorf, Urologie, Düsseldorf, Deutschland, Stanford University, 

Institute for Stem Cell Biology & Regenerative Medicine, Stanford, USA, 

3 4 Baylor College of Medicine, Houston, USA, UT Southwestern, Urology, 

Dallas, USA 

Background. Pathological stage and grade are the standard for assessing 

prognosis of bladder cancer (BC). Grade provides a description of 

BC differentiation based on broad histological criteria. We sought to 

determine whether a molecular classification of differentiation could 

improve BC prognostics. 

Methods. We developed a biologically supervised computational approach, 

utilizing pre-existing gene-expression datasets, to predict differentially 

expressed genes during BC differentiation. Tumor cells corresponding 

to each differentiation state were isolated from patient BCs 

by fluorescence-activated cell sorting and their relative tumorigenic and 

differentiation potential were validated by xeno-transplantation. An association 

between the identified molecular markers with patient survival 

was validated in three independent pre-existing BC gene expression 

datasets and two independent patient tissue datasets by immunohistochemistry. 

Results. We identified keratin and corresponding cell-surface marker 

expression patterns that putatively define three differentiation states 

in BCs: basal (KRT14 + KRT5 + KRT20 − /CD90 + CD44 + CD49f + ), intermediate 

(KRT14 − KRT5 + KRT20 − /CD90 - CD44 + CD49f + ), and differentiated 

(KRT14 − KRT5 − KRT20 + /CD90 − CD44 − CD49f + ). These differentiation states 

revealed three subtypes of BC (basal, intermediate, differentiated). 

Only the most primitive cells within each subtype formed xenograft 

tumors and differentiated to all downstream cell compartments. KRT14 

marks the basal differentiation state and is associated with significantly 

worse patient survival in 3 independent gene expression (p

Abstracts 

spectrometry (SELDI-TOF MS) and multiplex-two-dimensional fluorescence 

gel electrophoresis (Multiplex-2DE) provided protein candidates 

separating samples into primary clinical benefit (CB) and primary progressive 

disease (PD). Identification of these candidates was performed 

by peptide mass fingerprinting. Western Blot and ELISA were carried 

out for quantification. 

Results. Protein pattern specific for primary PD could be generated by 

SELDI-TOF MS and biostatistics. Multiplex-2DE revealed i.a. serum 

amyloid A (SAA) as differentially expressed protein. Pre-therapeutic 

SAA-concentrations were significantly different between CB and PD in 

Sunitinib-treated patients but were not for Sorafenib. Comparison of 

therapeutic SAA-concentrations after 3 months resulted in significant 

differences for both drugs. High SAA-levels are representative for primary 

PD. 

Conclusion. Our data show that pre-therapeutic serum is well-suited to 

establish protein signatures for TKI-therapy response prediction based 

on the used techniques. Selection of patients for personalized medicine 

seems possible. In this ongoing study further candidates from the 

detected protein signature have to be identified and validated on an independent 

patient cohort. 


B40 – 0431 

Influence of morbidity on health-related quality of life after 

open retropubic radical prostatectomy 

*B . Löppenberg1 , C . von Bodmann1 , M . Brock1 , T . Eggert1 , J . Palisaar1 , 

J . Noldus1 1Ruhr-Universität Bochum Marienhospital Herne, Klinik für Urologie und 

Neuro-Urologie, Herne, Deutschland 

Introduction and Objectives. Standardized assessment of complications 

following open retropubic prostatectomy (ORRP) results in overall 

complication rates of about 30%.The influence of medical and surgical 

complications on health-related quality of life (HRQOL) has not been 

investigated. Objective was to evaluate the influence of complications, 

continence and erectile dysfunction on HRQOL one year after ORRP. 

Methods. Medical and surgical complications of ORRP were assessed 

prospectively within 30 days postoperative. They were graded according 

to the Clavien-Dindo classification retrospectively. HRQOL was 

assessed preoperatively and one year after ORRP using the EORTC- 

QLQ C30 questionnaire. Pre- and postoperative results were compared 

by using the Wilcoxon rank test. HRQOL of patients without complications 

were compared to patients who had complications using the 

Mann Whitney-U test. A p

de and vice versa. Therefore, blockade of the SDF-1-pathway can only 

become a successful anti-angiogenic approach in tumor therapy with 

respect to I-TAC-mediated signaling. 

Discussed Poster – GI-Tumoren 

D2 – 0223 

Anti-neoplastic activity of Taurolidine in pancreatic cancer – in 

vitro study of different pancreatic cancer cell lines 

*M . Buchholz1 , A . Flier1 , S . Hahn2 , D . Bulut3 , W . Uhl1 , A . Chromik1 1 2 St . Josefs Hospital, Chirurgie, Bochum, Deutschland, Ruhr Universität, 

Bochum, Deutschland, 3St . Josefs Hospital, Bochum, Deutschland 

Introduction. Taurolidine (TRD) – a compound derived from the aminosulfoacid 

Taurine – has been shown to exert anti-neoplastic activity 

in vitro in several malignant cell lines (e.g. glioblastoma, and colorectal 

cancer). However, human pancreatic cancer cells have not been tested 

for susceptibility against TRD induced cell death. The aim of this project 

was therefore to evaluate the anti-neoplastic activity of TRD in different 

pancreatic cancer cell lines in vitro. 

Material and methods. Five pancreatic cancer cell lines (AsPC-1, BxPC- 

3, HPAF II, MiaPaca-2 and Panc1) were incubated with increasing concentrations 

of TRD (10, 100, 250, 500 und 1000 µmol/l) for 6 h, 12 h, 24 h 

and 48 h. Different methods were used to receive a systematic analysis 

of several aspects of anti-neoplastic actions induced by TRD. Cytotoxic 

and anti-proliferative activities were evaluated by colorimetric MTT- 

and ELISA based BrdU-assays, respectively. The TRD related apoptosis 

induction was examined by FACS-analysis (AnnexinV-FITC/Propidiumiodide). 

Dose dependent growth curves during exposure of TRD over 

a certain period of time were rendered using a real-time cell analyzer 

(xCelligence, Roche). To compare the effects of TRD with a standard 

chemotherapeutic agent for pancreatic cancer, gemcitabine was used as 

control treatment (concentrations: 0.01, 0.1, 1, 10, 100 µmol/l). 

Results. TRD showed a strong cytotoxic and anti-proliferative effect 

in all pancreatic cancer cells with maximal reduction of cell viability 

to 10% and proliferation to 15%, as shown in the MTT-and BrdU assay, 

respectively. The FACS analysis resulted in a strong apoptotic response 

upon stimulation by TRD leading to a maximal apoptotic effect of 

40–50%. Among all concentrations, TRD 250 µM caused the strongest 

anti-neoplastic activity. The results of the real-time growth curve experiments 

confirmed the results. Interestingly, gemcitabine was less effective 

compared to TRD in all cell lines. 

Conclusions. In this systematic analysis, it could be demonstrated for 

the first time that TRD exerts anti neoplastic activity in different pancreatic 

cancer cell lines. The results indicate that TRD operates with 

different mechanisms, e.g. inhibition of proliferation, direct cell toxicity 

and induction of apoptosis. As the most effective TRD concentration, 

250 µmol/l was determined, which was also superior to gemcitabine. 

Further studies are necessary to evaluate the in vivo capacity of TRD in 

pancreatic cancer. 


D3 – 0259 

KRAS, BRAF and PI3K mutations in rectal cancer 

*P . Jo1 , K . Jung2 , J . Salendo1 , T . Beissbarth2 , M . Spitzner1 , H .A . Wolff3 , 

L .C . Conradi1 , M . Grade1 , J . Gaedcke1 , H . Becker1 , M . Ghadimi1 1Universitätsmedizin Göttingen, Abteilung für Allgemein- und Viszeralchirurgie, 

Göttingen, Deutschland, 2Universitätsmedizin Göttingen, Abteilung 

für Medizinische Statistik, Göttingen, Deutschland, 3Universitätsmedizin Göttingen, Abteilung für Strahlentherapie und Radioonkologie, Göttingen, 

Deutschland 

Background. The heterogeneous response in locally advanced rectal 

cancer (RC) treated with a 5-FU based radiochemotherapy (RCT) is still 

a considerable clinical dilemma. The pretherapeutic identification of 

responders would allow a patient adjusted therapy. Mutations within 

the MAPK and PI3K pathway were previously shown to activate the pathways. 

However, data on their clinical impact are rare, especially with 

respect to the exchange dependent level of activation. 

Materials and methods. Mutation profile of KRAS, BRAF and PI3K was 

assessed in 192 patients with RC. All patients were treated and followedup 

within the CAO/ARO/AIO-94 and -04 trial of the German Rectal 

Cancer Study Group. Analyses compromised exons 2, 3 and 4 for KRAS, 

exon 15 for BRAF and exons 9 and 20 for PI3K. Mutations were assessed 

using bidirectional Sanger Sequencing. In case of differing results a primer 

extension analyses (SNaPshot Multiplex Kit Applied Biosystems, 

Foster City, CA) was applied for definite decision. 

Results. No typical (V600E) BRAF mutation was identified. 85 (44%) 

tumors revealed a KRAS mutation, 22 (11%) showed a mutation in PI3K. 

In 55% (12 out of 22) of the tumors KRAS and PI3K mutations occurred 

simultaneously. Those patients harboring both mutations revealed 

a significantly worse 3- and 5-year disease free survival (p=0.02). KRAS 

mutation was significantly associated with a lower number of postoperative 

lymph node positivity (ypN+; p=0.05). However, tremendous differences 

occurred between the different type of amino acid exchanges 

(p

Abstracts 


D4 – 0274 

Preoperative chemoradiation for resectable adenocarcinom of 

the pancreas (ISRCTN 78805636): results of a randomized trial 

*H . Golcher1 , H . Witzigmann2 , L . Marti3 , J . Lange3 , W . Bechstein4 , C . Bruns5 , 

H . Jungnickel2 , J . Hauss6 , S . Schreiber7 , T . Brunner8 , G . Grabenbauer9 , S . Merkel1 

, R . Fietkau10 , W . Hohenberger1 1Universitätsklinikum Erlangen, Chirurgie, Erlangen, Deutschland, 

2Krankenhaus Dresden-Friedrichstadt, Allgemein- und Viszeralchirurgie, 

Dresden, Deutschland, 3Kantonsspital St . Gallen, Chirurgie, St . Gallen, 

Schweiz, 4Universitätsklinikum Frankfurt/Main, Allgemein- und Viszeralchirurgie, 

Frankfurt/Main, Deutschland, 5Universitätsklinikum München-Großhadern, 

Chirurgie, München, Deutschland, 6Universitätsklinikum Leipzig, 

Department Operative Medizin, Leipzig, Deutschland, 7Universitätsklini kum Leipzig, Unfall-, Wiederherstellungs- und Plastische Chirurgie, Leipzig, 

Deutschland, 8Gray Institute for Radiation Oncology and Biology, Oxford, 

UK, 9Praxis für Radiologische Diagnostik, Radioonkologie und Nuklearmedizin 

(DiaCura Coburg), Strahlentherapie, Coburg, Deutschland, 10Universi tätsklinikum Erlangen, Strahlentherapie, Erlangen, Deutschland 

Introduction. Standard treatment for resectable pancreatic carcinoma is 

primary surgery, and median overal survival time [mOS] for patients 

[pts] with resected pancreatic cancer is about 20 months. But still most 

pts die from local relapse or metastases. Therefore, we investigated in 

a randomized controlled trial whether preoperative chemoradiation 

[CRT] in resectable pancreatic carcinoma is superior compared to primary 

resection. 

Patients and methods. Pts with histologically proven ductal adenocarcinoma 

of the pancreatic head encircling peripancreatic vessels for 180° 

were randomized into two groups: Group A: primary surgery, Group B: 

preoperative chemoradiation (55.4 Gy; gemcitabine/cisplatin), followed 

by surgery 6 weeks later. In 2005 a protocol amendment suggested adjuvant 

chemotherapy (gemcitabine). The primary endpoint was mOS. 

Results. Between 01.06.2003 and 31.12.2009, 73 pts were randomised in 

8 centres (A: n=37, B: n=36). Due to slow recruitment the trial was closed 

early (planned n=254). By 25.7.11 data of 68 pts (A/B: n=34) could 

be evaluated, 3 pts withdrew consent (A/B: n=2/1), 1 centre did not sent 

data (A/B: n=1). The allocated therapy was received by 33 pts in Group A 

and 30 pts in Group B. 1 pt (A) developed sepsis and died before surgery. 

4 pts refused the allocated CRT and underwent primary surgery. Another 

4 pts (B) did not undergo surgery due to obvious tumor progression 

after CRT. Tumor resection was performed in 24 pts (A) and in 20 pts 

(B) by intention-to-treat-analysis. Explorative laparotomy revealed locally 

unresectable tumor in 6 pts (A/B n=4/2) and distant metastasis 

in 13 pts (A/B n=5/8). The R0-resection rate was 67% (16/24 pts) in A 

and 90% (18/20 pts) in B (p=0.083, fisher exact test). One patient (A) 

died postoperatively due to perioperative myocardial infarction/multiorgan 

failure in hospital. Postoperative complications were comparable 

in both groups. mOS was 14.4 months (A) and 17.4 months (B; p=0.90). 

mOS after tumor resection was 18 months and 25 months respectively 

(p=0,63). For pts whose tumors were not resected mOS was 9.5 months 

(A) and 8.2 months (B; p=0.84; similar figures for per-protocol analysis). 

Conclusion. The results for the primary endpoint mOS of this trial were 

not statistically significant due to low patient numbers. Instead, both 

groups had comparable survival figures for resected as well as for notresected 

disease. There was a trend for a higher rate of clear resection 

margins after CRT and CRT helped to de-mask the biology of the tumor 

sparing pts with rapidly progressive disease from surgery. 



D5 – 0304 

CpG island methylator phenotype infers a poor prognosis in 

locally advanced rectal cancer 

*P . Jo1 , K . Jung2 , M . Grade1 , L .C . Conradi1 , H .A . Wolff3 , J . Kitz4 , J . Rüschoff5 , 

A . Hartmann6 , H . Becker1 , T . Beissbarth2 , A . Müller1 , M . Ghadimi1 , R . Schneider-Stock6 

, J . Gaedcke1 1Universitätsmedizin Göttingen, Abteilung für Allgemein- und Viszeralchirurgie, 

Göttingen, Deutschland, 2Universitätsmedizin Göttingen, Abteilung 

für Medizinische Statistik, Göttingen, Deutschland, 3Universitätsmedizin Göttingen, Abteilung für Strahlentherapie und Radioonkologie, Göttingen, 

Deutschland, 4Universitätsmedizin Göttingen, Abteilung für Pathologie, 

Göttingen, Deutschland, 5Pathologie Nordhessen, Kassel, Deutschland, 

6Universitätsklinikum Erlangen, Abteilung für Pathologie, Erlangen, 

Deutschland 

Introduction. Locally advanced rectal cancers are treated with preoperative 

radiochemotherapy (RCT). However, subsets of patients have no 

benefit from preoperative treatment. Since epigenetic modifications, 

including DNA methylation, may influence response to neoadjuvant 

treatment we studied the CpG island methylator phenotype (CIMP) in 

patients who received a 5-fluoruracil based RCT. 

Material and methods. One-hundred and fifty patients with locally 

advanced rectal cancer, treated within a phase III clinical trial (CAO/ 

ARO/AIO-94 and -04), were included in this analysis. CIMP was assessed 

by methylation specific PCR (MSP) using RUNX3, SOCS1, NEU- 

ROG1, IGF2 and CACNA1G as marker panel. Loss of mismatch repair 

gene (MMR) expression was assessed by immunohistochemistry for a 

subset of patients. KRAS and BRAF mutation status were available from 

previous studies. 

Results. The CIMP status could be established in all (n=150) patients. 

Fifteen (10%) revealed CIMP positivity (≥3 methylated promoters), whereas 

135 patients (90%) where classified as CIMP negative. Analysis for 

MMR status did not reveal any microsatellite instability (MSI). A single 

mutation of the BRAF gene (D594G) was detected. The KRAS gene 

(exon 1, 2, and 3) was mutated in 65 tumors (43%) but was not correlated 

to a specific CIMP status. Three- and 5-year disease-free survival was 

notably worse in CIMP positive patients (56% and 0% vs. 80% and 75%; 

p


D6 – 0382 

Searching for predictive molecular markers for chemoradioimmunotherapy 

with interferon-alpha and 5-fluorouracil of 

pancreatic cancer patients 

*T . Rusch1 , S . Bulashevska2 , J . Werner1 , A .V . Bazhin1 1Universitätsklinikum Heidelberg, Chirurgische Klinik, Heidelberg, Deutschland, 

2Deutsches Krebsforschungszentrum, Division of Theoretical Bioinformatics, 


Background and aims. Nowadays the importance of individualised therapy 

finds its way more and more into the awareness of scientists and 

medical doctors. Pancreatic carcinoma has a particularly poor prognosis 

with a median survival of 6 months. The standard treatment today is 

surgical resection and subsequent adjuvant chemotherapy. This is possible 

in about 20% of all patients, and results in a median survival of over 

20 months. A recent multicenter trial on intensified adjuvant chemoradioimmunotherapy 

with interferon-alpha, the CapRi trial, also could 

not increase survival compared to standard chemotherapy, 5-fluorouracil 

alone. Nevertheless the outcome of over 30 months median survival 

represented the best ever reported outcome for patients with resected 

pancreatic cancer in a randomized trial. The main aim of the work was 

to identify predictive molecular markers for patients’ selection for chemoradioimmunotherapy 

with interferon-alpha. 

Methods. RNA from the frozen tumor tissues of patients with higher 

and lower overall survival (OS) was isolated and used for gene expression 

profiling with Illumina technology. Bioinformatics was applied to 

select differentially expressed genes. The selected gene candidates were 

further validated by real-time PCR. Survival analysis with gene candidates 

as predictors was applied to find predictive markers with respect 

to OS and disease-free survival (DFS). 

Results. 12 gene candidates were selected from the Illumine array data 

as potential candidates for their subsequent evaluation as predictive 

markers. Expression level of these genes was measured with Real-Time 

PCR. Afterwards we applied the Cox Proportional Hazard model on 

the 12 selected genes to identify the significant predictors of the OS and 

disease-free survival (DFS). Highly significant predictors for the OS of 

the patients appeared to be GAGE5 (p =0.0099), as well as MAP3K2 (p 

=0.055) and RTEL1 (p =0.06). 3 genes were detected to be highly significant 

predictors for the DFS: GAGE5 (p =0.0088), MAP3K2 (p =0.02444) 

and TCEA1 (p =0.0304). 

Conclusion. Expression level of GAGE5, MAP3K2 and RTEL1 has been 

found to be predictive for the OS, and GAGE5, MAP3K2 and TCEA1 – 

for the DFS of patients undergoing chemoradioimmunotherapy. These 

markers should be prospectively evaluated in a future clinical trial. 


Discussed Poster – Mammakarzinom/ 


D7 – 0163 

The power of DNA double-strand break repair testing to predict 

breast cancer susceptibility 

M . Keimling1 , M . Deniz1 , D . Varga1 , H . Schrezenmeier2 , R . Kreienberg1 , I . Hoffmann3 

, J . Koenig3 , *L . Wiesmüller1 1 2 Universität Ulm, Universitätsfrauenklinik, Ulm, Deutschland, Universität 

Ulm, Abt . Transfusionsmedizin, Ulm, Deutschland, 3Universität Mainz, 

IMBEI, Mainz, Deutschland 

Purpose. All breast cancer susceptibility genes have been linked to DNA 

double strand break (DSB) repair. However, these genes explain only a 

small fraction of the familial risk. To identify novel markers that may 

serve as indicators for breast cancer risk, we performed DSB repair 

analysis in cohorts of predisposed women, cancer patients, and healthy 

women. 

Methods. We previously developed a GFP-based test system for detection 

of mechanistically distinct DSB repair changes caused by predisposing 

mutations. Here, we analyzed DSB repair using three pathway-specific 

substrates in peripheral blood lymphocytes (PBLs) from 35 female 

members of families with defined history of familial breast and/or ovarian 

cancer, 175 female breast cancer patients, and 245 healthy women 

without previous cancer and without family history of breast cancer. A 

logistic model was fitted for each variable to determine association of 

repair changes with breast cancer/risk. 

Results. We found increases of the error-prone mechanisms non-homologous 

end joining (NHEJ) and single-strand annealing (SSA) in 

women with familial risk and breast cancer patients (risk: p=0.0001– 

0.0022; cancer: p=0.0004–0.0042). Young age (

Abstracts 

Methods. We analyzed the prognostic impact of a B-cell derived gene 

signature, including the most representative marker of this signature, 

immunoglobulin kappa C (IGKC), in gene expression profiles of 1810 

breast carcinomas. Protein and RNA levels of IGKC were examined in 

paraffin embedded tissue of 330 node-negative breast cancer patients. 

Finally, the origin of IGKC expression was determined using immunostaining 

and confocal fluorescence microscopy. Prognosis was analyzed 

with Cox regression, Kaplan-Meier analysis, Brier scores and meta-analyses. 

Results. IGKC as a single gene similarly predicts better prognosis 

in node-negative breast cancer not treated in the adjuvant setting 

(HR=0.81; p

moendocrine therapy (CHT) was changed to endocrine therapy (HT) 

and in10.7% of all, 11.5% of N0 and 9.0% of N+ from HT to CHT. In 25% 

of all, 22% of N0 and 39% of N+ pts initially recommended HT the post- 

RS recommendation changed to CHT; in 38% of all, 39% of N0 and 37% 

of N+ pts initially recommended CHT it changed to HT. Physicians’ 

confidence increased in 45.1% of all (p=0.047), 44.7% of N0 and 45.9% of 

N+ cases. There was a moderate improvement of the decisional conflict 

score which was statistically significant for all pts (p=0.029) and the low 

RS subgroup (p=0.003). Net reduction in adjuvant chemotherapy usage 

was 19.1% in all, 14.0% in N0 and 27.9% in N+ pts. The incremental costeffectiveness 

ratio associated with the use of the test was € 442/life year 

and considering the societal perspective € 155/life year. 

Conclusions. Results of our study suggest an impact of the RS on adjuvant 

treatment decision making in ER+ EBC in German clinical practice 

resulting in a significant net reduction of adjuvant chemotherapy 

usage. The effect was more pronounced for patients with node positive 

disease. 


Gynäkologische Tumoren 

D11 – 0381 

Comparison of the ER, PR and HER/2neu status changes in primary 

and relapsed breast cancer 

*R . Mavrova1 , J . Radosa1 , A . Mayer2 , R .-M . Bohle2 , E .-F . Solomayer1 , I . Juhasz- 

Böss1 1 2 Uniklinik Homburg, Frauenklinik, Homburg /Saar, Deutschland, Uniklinik 

Homburg, Pathologie, Homburg/ Saar, Deutschland 

Question. We analyzed the changes in the estrogene (ER) and progesterone 

(PR) receptor, and HER/2neu status of primary and relapsed breast 

cancer in patients suffering from a relapse and we searched for possible 

causes. 

Methods. We analyzed the data of 68 patients with a relapse detected at 

the Saarland University Hospital during the last 5 years. We compared 

the receptor status of the primary tumor to the receptor status of the 

relapse. 

Results. 44 of 68 (65%) patients analyzed showed a positive ER and PR 

status in the primary tumor. Overall we notices 16 switches in ER status 

(23%) and 23 switches in PR status (34%). The switches occurred from 

negative status to positive status and vice versa. A trend of switch from 

hormone receptor positive status towards negative status could be observed. 

In contrast the Her2/neu status changed from negative to positive 

in each case. 

Conclusion. The hormone and Her2/neu receptor status can vary strongly 

between primary tumor and relapse in breast cancer in the same patient. 

It is to be noted that there are more switches in PR than in ER status. 

In our patients collective the occurrence of receptor status switches 

were independent of hormone therapy after the initial diagnosis. 


Gynäkologische Tumoren 

D12 – 0407 

Multivariate analysis of obesity and survival in patients with 

node-positive primary breast cancer: The ADEBAR trial 

*C . Hagenbeck1 , W . Janni1 , B . Rack2 , P . Hepp1 , U . Andergassen2 , N . Harbeck3 , 

J . Neugebauer2 , K . Annecke4 , A . Wischnik5 , W . Simon6 , M . Rezai7 , T . Fehm8 , 

A . Schneeweiss9 , P .A . Fasching10 , B . Gerber11 , T . Zwingers12 , H . Sommer2 , 

K . Friese2 , M . Kiechle4 1Universitätsklinik Düsseldorf, Frauenklinik, Düsseldorf, Deutschland, 

2Ludwig-Maximilians-Universität, Frauenklinik, München, Deutschland, 

3 4 Universitätsklinik, Frauenklinik, Köln, Deutschland, Technische Universität 

München, Frauenklinik, München, Deutschland, 5Klinikum Augsburg, Frauenklinik, 

Augsburg, Deutschland, 6Robert-Bosch-Krankenhaus, Frauenklinik, 

Stuttgart, Deutschland, 7Luisenkrankenhaus, Düsseldorf, Deutschland, 

8Universitätsklinikum Tübingen, Frauenklinik, Tübingen, Deutschland, 

9Universitätsklinikum Heidelberg, Nationales Centrum für Tumorerkrankungen, 

Heidelberg, Deutschland, 10Universitätsklinik Erlangen, Frauenklinik, 

Erlangen, Deutschland, 11Universitätsklinik Rostock, Frauenklinik, 

Rostock, Deutschland, 12Estimate, Augsburg, Deutschland 

Background. The prevalence of obesity increases throughout most industrialized 

countries. Epidemiological studies have shown not only an 

increase in breast cancer (BC) among obese women but also an adverse 

impact of obesity on BC survivors. This analysis focuses on the impact 

of obesity on high risk BC patients (pts) treated within the ADEBAR 

study protocol. 

Methods. The ADEBAR Trial compared 4 cycles of EC followed by 

4 cycles of Doc vs. 6 cycles of FEC (120) in pts with primary BC (≥4LN). 

1500 pts have been accrued from Sep/01 through May/05. For this analysis 

data of 1361 pts have been analyzed about the impact of obesity 

on disease free survival. Therefore pts have been grouped to be either 

underweight (BMI

Abstracts 

Molekulare Onkologie 

Discussed Poster – Molekulare Onkologie 

D13 – 0125 

Expression of p53D133 isoforms in novel papillary urothelial 

cancer cell lines 

*A . Koch1 , J . Hatina2 , H . Rieder3 , R . Stoer4 , W .A . Schulz1 1Heinrich Heine Universität, Forschungslabor Urologische Klinik, Düsseldorf, 

Deutschland, 2Charles University, Department of Biology, Pilzen, 

Tschechische Republik, 3Heinrich Heine Universität, Inst . f . Humangenetik 

und Anthropologie, Düsseldorf, Deutschland, 4Universitätsklinikum Erlangen, 

Pathologie, Erlangen, Deutschland 

Commonly used urothelial cell lines are mostly derived from invasive 

urothelial tumors, whereas cell lines derived from papillary tumors are 

rare. To expand the repertoire of papillary derived cell lines, we have 

established two novel lines BC61 (pTaG2) and BC44 (papillary part of a 

pT4G3 carcinoma) using a specifically adapted culture technique. Both 

cell lines presented karyotypes typical of progressive papillary urothelial 

cancers including monozygosity of chromosome 9. Accordingly, 

CDKN2A at 9p21 was homozygously deleted as in many papillary 

and invasive urothelial carcinomas. An oncogenic mutation of FGFR3 

(S249C) characteristic of low grade papillary urothelial tumors was detected 

in BC61 but not BC44. Likewise typical of such tumors BC61 had 

wild-type (wt) TA-p53, whereas p53 was initially undetectable in BC44. 

The TP53 gene contains alternative promoters from which several isoforms 

are transcribed. In particular, p53D133 isoforms expressed from 

promoter p2 were shown to inhibit wt p53 function in several tumors. 

We therefore studied p53 expression with Do-6 antibody detecting 

TA-p53 and others (PAB240, Do-12) detecting several isoforms. BC61 

had a normal level of nuclear wt p53 and weak expression of other p53 

isoforms, whereas exclusively p53D isoforms were detectable in BC44. 

Western blot and PCR identified these isoforms as p53D40 and D133. 

In an extended set of urothelial cancer cells and tissues, D133 was expressed 

mostly in additional papillary urothelial tumor cell cultures, 

but also individual invasive cancer tissues. Methylation and sequencing 

analysis of the TP53 gene p1 promoter and gene in BC44 revealed neither 

mutations nor hypermethylation as potential causes of the promoter 

shift. 

In invasive urothelial carcinomas p53 is typically inactivated by missense 

or nonsense mutations in one allele with loss of the second wild-type 

allele, whereas mutations are much rarer in papillary tumors. We show 

that some urothelial carcinomas predominantly or exclusively express 

p53 isoforms from the p2 promoter that do not exhibit the full spectrum 

of p53 functions. Alternative promoter usage may therefore constitute 

a further mode of p53 inactivation in urothelial carcinomas and might 

compromise p53 function particularly in papillary tumors, where point 

mutations in the gene are rare. 



D14 – 0168 

The role of TGF-b1 dependent L1CAM expression in malignant 

transformation of intestinal epithelial cells 

B . Struck1 , E .-M . Feldmann1 , F . Bergmann2 , E . Grage-Griebenow1 , C . Geismann3 

, P . Altevogt4 , H . Schäfer3 , *S . Sebens1 1Department of Internal Medicine I, Institute for Experimental Medicine, 

Kiel, Deutschland, 2University of Heidelberg, Institut of Pathology, Heidelberg, 

Deutschland, 3Department of Internal Medicine I, Laboratory for Molecular 

Gastroenterology & Hepatology, Kiel, Deutschland, 4German Cancer 

Research Center, Translational Immunology D015 , Heidelberg, Deutschland 

Background. Inflammatory bowel disease (IBD) patients have an increased 

risk to develop colorectal cancer (CRC), particularly after longduration 

of the disease. Chronic inflammation of the intestinal mucosa 

is characterized by a marked enrichment of immune cells such as macrophages 

and a plethora of cytokines and growth factors e.g. Transforming 

growth factor-beta 1 (TGF-b1). In colorectal cancer tissues, the 

adhesion molecule L1CAM has been detected associating with metastatic 

spread and poor prognosis of CRC patients. Moreover, L1CAM 

induces apoptosis protection and chemoresistance as well as motility 

of tumor cells. 

Aim. The present study investigates the role of TGF-b1 and macrophages 

in the upregulation of L1CAM in intestinal epithelial cells and its functional 

consequences. 

Methods and results. We demonstrate by immunohistochemistry that 

colonic tissues from IBD patients are already characterized by considerable 

L1CAM expression in intestinal epithelial cells particularly in 

the presence of macrophages compared to normal non-inflammatory 

colon tissues. When cocultured with in vitro generated macrophages 

the transcription factor Slug and L1CAM are upregulated in the human 

colonic cell line NCM460 along with a Slug- and L1CAM-dependent 

increase of cell motility and apoptosis resistance against Irinotecan and 

Trail. Pharmacological interference with TGF-b1 signaling abolished 

the elevated expression of Slug and L1CAM in cocultured NCM460 

cells and decreased cell migration and apoptosis protection. Chromatin 

immunoprecipitation (ChIP) and luciferase assays revealed that direct 

binding of Slug to the L1CAM promoter is essential for gene activation 

and upregulation of L1CAM expression in NCM460 cells. 

Conclusion. These data provide new insights into the mechanisms by 

which IBD promotes malignant transformation of intestinal epithelial 

cells and underscore the role of L1CAM in this scenario. 


D15 – 0211 

Targeting fibroblast growth factor receptor (FGFR) system impairs 

angiogenic signaling in gastric cancer, endothelial cell and 

periycytes 

*C . Moser1 , C . Hackl1 , H .J . Schlitt1 , E .K . Geissler1 , S .A . Lang1 1Universitätsklinik Regensburg, Klinik und Poliklinik für Chirurgie, Regensburg, 

Deutschland 

Background. Expression of FGFRs has been associated with poor prognosis 

in gastric cancer patients at least in part via activation of MAPK/ 

Erk and PI3K/Akt signaling. In addition, activation of FGFRs is a crucial 

event in induction of tumor angiogenesis through regulation of 

endothelial cell/pericyte motility and survival. Therefore, we sought to 

evaluate the effects of targeting FGFR on gastric cancer cells as well as 

endothelial cells and pericytes.

Methods. Human gastric cancer cells (TMK-1, KKLS), endothelial 

cells (ECs), pericytes (vascular smooth muscle cells, VSMCs) and the 

FGFR inhibitor BGJ398 (Novartis Oncology, Basel) were used for the 

experiments. Effects of BGJ398 on tumor growth and chemoresistance 

were determined by MTT assays. For evaluation of cancer cell motility, 

modified Boyden chambers were used. Signaling pathways affected by 

BGJ398 treatment were assessed by Western blot analyses. Conditioned 

media from gastric cancer cells was used to determine effects of FGFR 

blockade by BGJ398 on ECs and VSMCs. 

Results. Targeting FGFR with BGJ398 impaired in vitro growth of gastric 

cancer cells in a dose-dependent manner. Furthermore, activation 

of Akt and Erk in cancer cells was effectively blocked while expression 

of HIF-1α and c-Myc was reduced. In addition, treatment with BGJ398 

led to marked inhibition of constitutive tumor cell migration and invasion 

(p

Abstracts 


D18 – 0498 

The Wnt transcription factor TCF4 mediates resistance of colorectal 

cancer cells to (chemo-)radiotherapy 

*M . Grade 1 , E . Kendziorra 1 , K . Ahlborn 1 , M . Spitzner 1 , C . Eimer 1 , M . Rave- 

Fränk 2 , J . Gaedcke 1 , G . Emons 1 , H . Becker 1 , T . Ried 3 , T . Pukrop 4 , M . Ghadimi 1 

1 Universitätsmedizin Göttingen, Klinik für Allgemein- und Viszeralchirurgie, 

Göttingen, Deutschland, 2 Universitätsmedizin Göttingen, Klinik für 

Strahlentherapie und Radioonkologie, Göttingen, Deutschland, 3 National 

Cancer Institute, Genetics Branch, Bethesda, Deutschland, 4 Universitätsmedizin 

Göttingen, Klinik für Hämatologie und Onkologie, Göttingen, 

Deutschland 

Background. The clinical response of locally advanced rectal cancers 

to preoperative chemoradiotherapy is very heterogeneous. We recently 

profiled a series of responsive and resistant rectal carcinomas using 

gene expression microarrays and identified TCF4, a key effector of the 

Wnt/β-catenin pathway, as over-expressed in resistant tumors. The aim 

of this study was to explore the functional relevance of TCF4 for mediating 

treatment resistance. 

Methods. Three colorectal cancer cell lines (SW837, SW480, and HT-29) 

were transfected with two different shRNA-vectors targeting TCF4. 

After establishing stable single-cell clone (SCC) populations, selected 

clones were irradiated at 0, 1, 2, 4, 6 and 8 Gy. γH2AX staining was used 

to evaluate DNA double strand repair after irradiation, and changes 

in cell cycle distribution were analyzed before and after radiation. βcatenin/TCF 

signaling activity was assessed using the TOP-FLASH/ 

FOP-FLASH reporter assay. 

Results. RNAi-mediated silencing of TCF4 led to a significant radiosensitization 

in SW837 and SW480, whereas no effect was observed in 

HT-29. Well-fitting, we observed significantly more γH2AX foci 24 h 

after radiation in SW837 SCCs compared to HT-29 SCCs, pointing to an 

impaired DNA damage repair in SW837 SCCs. Furthermore, in SW837 

SCCs, but not in HT-29 SCCs, we noticed a change in the cell cycle distribution 

towards radiosensitive cell cycle phases before radiation, and 

compromised cell cycle control after radiation. Analysis of the reporter 

assay revealed that SW837 cells shower high β-catenin/TCF signaling 

activity compared to HT-29 cells. 

Conclusion. TCF4 was found to be over-expressed in resistant rectal carcinomas, 

and its RNAi-mediated silencing caused a significant radiosensitization, 

mediated by DNA damage repair deficiencies and impaired 

cell cycle control. Thus, we have uncovered a novel role of the Wnt 

transcription factor TCF4 for mediating radioresistance. Moreover, 

these data suggest that TCF4 is a potential therapeutic target to sensitize 

resistant tumor cells to radiation. 


Seltene Tumoren 

Discussed Poster – Seltene Tumoren 

D19 – 0276 

Histologic diagnoses in persistently swollen cervical lymph 

nodes 

*W . Laffers1 , K . Eggert1 , H .-U . Schildhaus2 , F . Bootz1 , A .O . Gerstner1 1Universität Bonn, Klinik für HNO-Heilkunde/Chirurgie, Bonn, Deutschland, 

2Universität Köln, Institut für Pathologie, Köln, Deutschland 

Background. Biopsy and histological examination of persistently enlarged 

cervical lymph nodes represent a major health care issue and have 

high impact on further clinical therapy. Tertiary health centers are 

faced with an increased demand for diagnostic work-up of persistently 

swollen cervical lymph nodes in order to rule out malignancy. We 

performed a retrospective study from I/2000 to VI/2008 to identify 

patients referred to us for diagnostic biopsy and to document the histopathological 

result. 

Methods. Patients with a diagnostic biopsy but neither clinical signs of 

head and neck cancer nor other malignancies were identified within the 

records. Patient characteristics and histopathological diagnosis were 

retrieved from the system. 

Results. Within that period 326 patients were identified (146 female, 

180 male). 123 patients (38%; 44 female, 79 male) had a malignancy: 61 

with metastatic disease and 62 with malignant lymphoma, the youngest 

15 years and the oldest 92 years old. 

Conclusions. Persistently swollen cervical lymph nodes should trigger a 

thorough clinical examination and prompt biopsy for histopathological 

work-up. 


D20 – 0281 

The endogenous nicotinamide adenine dinucleotide precursor 

quinolinic acid confers resistance of glioma to oxidative stress 

*F . Sahm1 , A . von Deimling1 , W . Wick2 , M . Platten2 1Institut für Pathologie, Abt . Neuropathologie, Heidelberg, Deutschland, 

2Abt . Neuroonkologie, Heidelberg, Deutschland 

Background. Quinolinic acid (QA) is a product of tryptophan degradation 

and may serve as a precursor for nicotinamide adenine dinucleotide 

(NAD) synthesis, an enzymatic step catabolized by quinolinic acid 

phosphoribosyltransferase (QPRT) as a source for energy. Pathologic 

accumulation of QA has been found in Alzheimer’s and Huntington’s 

disease. In these conditions QA is thought to be toxic for neurons by 

activating the N-methyl-D-aspartate (NMDA) receptor and inducing 

oxidative stress. The role of QA in glioma biology is unclear till date. 

Methods. QA accumulation and expression patterns of the QA producing 

enzyme 3-hydroxyanthranilate oxygenase (HAAO) and QA metabolizing 

QPRT were analyzed in diffusely infiltrating glioma of the 

World Health Organization (WHO) grades II, III and IV by immunohistochemistry. 

Immunofluorescent double-labelling with CD68 and 

glial fibrillary acid protein (GFAP) was applied to assess HAAO and 

QPRT expression in different cell populations within the tumor. Real 

time-quantitative polymerase chain reaction and western blot analysis 

were performed to analyze HAAO and QPRT expression levels in 

the human glioma cell lines U251, A172 and the human astrocyte cell 

line CRL-8621. Effects of QA on oxidative stress conditions induced 

by 100 µM hydrogen peroxide and NAD synthesis inhibition by 10 nM

FK866 were determined by crystal violet viability assay and western blot 

for markers of apoptosis. 

Results. There was QA accumulation in human gliomas, which is associated 

with a malignant phenotype. Expression of the QA producing 

enzyme HAAO was confined to microglial cells in glioma tissue. QPRT 

expression correlates with glioma malignancy, determined by WHO 

grade and is upregulated in recurrent tumors after radio-chemotherapy 

compared to specimens of untreated primary lesions. Human malignant 

glioma cells but not non-neoplastic astrocytes express QPRT 

and utilize QA for NAD synthesis when de novo NAD synthesis was 

blocked. QA protects malignant glioma cells but not non-neoplastic astrocytes 

from apoptosis induced by NAD depletion or oxidative stress. 

Conclusion. There is QA expression in neoplastic astrocytes and a WHO 

grade-dependent expression of QPRT as well as induction in treated, 

recurrent tumors. Our data indicate that neoplastic transformation in 

astrocytes is associated with a switch in NAD metabolism by exploiting 

microglia-derived QA as a source of energy and thereby increasing 

the resistance to oxidative stress. These findings have implications for 

therapeutic approaches inducing intracellular NAD depletion such as 

alkylating agents or direct NAD synthesis inhibitors. 


D21 – 0371 

The role of relative lymphocyte count as a new biomarker for 

the effect of catumaxomab on overall survival in patients with 

malignant ascites: follow-up results from a phase ll/lll study 

*M .M . Heiss1 , M . Ströhlein1 , C . Bokemeyer2 , D . Arnold3 , S .L . Parsons4 , M . Ott5 , 

E . Schulze6 , H . Lindhofer7 , D . Seimetz5 , M . Hennig5 1 2 Cologne-Merheim Medical Center, Cologne, Deutschland, University 

Hamburg-Eppendorf, Clinic for Oncology/Haematology and Stemcell 

Transplantation, Hamburg, Deutschland, 3Martin Luther University Halle, 

Clinic for Internal Medicine IV, Halle, Deutschland, 4Nottingham University 

Hospitals NHS Trust, Nottingham, UK, 5Fresenius Biotech GmbH, Munich, 

Deutschland, 6Fresenius Biotech GmbH, Medical Affairs, Munich, Deutschland, 

7TRION Pharma GmbH, Munich, Deutschland 

Background. Catumaxomab (anti-EpCAM x anti-CD3) is approved in 

the EU for the intraperitoneal treatment of malignant ascites in patients 

with EpCAM-positive carcinomas. Here we report the follow-up overall 

survival (OS) results including long-term survival for the pivotal phase 

II/III randomized study in patients with malignant ascites due to different 

epithelial cancers. In addition, the impact of relative lymphocyte 

count in peripheral blood before treatment (RLC) as a new biomarker 

for the efficacy of catumaxomab therapy was tested on the basis of a 

separate small hypothesis-generating study. 

Methods. Survival analyses were performed for the safety set of the pivotal 

trial (paracentesis + catumaxomab [catumaxomab]: n=157; paracentesis 

alone [control]: n=88) including only patients who received at 

least one dose of catumaxomab. In order to identify patients with pronounced 

OS benefit, the impact of treatment and RLC was evaluated 

using the Cox model. For group comparisons, the Kaplan-Meier method 

and log-rank test were applied. 

Results. Follow-up results showed a statistically significant benefit in OS 

for catumaxomab-treated patients compared with controls (p=0.0219, 

HR=0.649). The 6-month OS rate in these patients was 28.9% compared 

with 6.7% for the control group. In addition, higher RLC had a positive 

impact on OS (p13% (n=159: 100 

catumaxomab; 59 control), catumaxomab treatment was associated 

with a more pronounced beneficial effect on OS vs controls (p=0.0072, 

HR=0.518), with a median/mean OS benefit of 31/131 days and an increased 

6-month survival rate of 37.0% vs 5.2% in the control group. Regarding 

the time to first paracentesis patients with a RLC ≤13% (p13% (p13% at start of treatment was a significant biomarker 

for a prolonged OS outcome with catumaxomab therapy and should 

lead to further investigation into the immunology of this clinical observation. 


D22 – 0379 

Podoplaninexpression in oralen Plattenepithelkarzinomen 

*M . Kreppel1,2 , M . Scheer1,2 , U . Drebber3,2 , I . Wedemeyer3,2 , H .-T . Eich4 , 

J .E . Zöller1,2 1Universitätsklinik Köln, Klinik für Mund-, Kiefer- und plastische Gesichtschirurgie, 

Köln, Deutschland, 2Centrum für Integrierte Onkologie, 

Köln, Deutschland, 3Universitätsklinik Köln, Institut für Pathologie, Köln, 

Deutschland, 4Universitätsklinik Münster, Klinik für Strahlentherapie, 

Münster, Deutschland 

Fragestellung. Trotz verbesserter therapeutischer Möglichkeiten hat 

sich die Überlebenswahrscheinlichkeit von Patienten mit fortgeschrittenen 

oralen Plattenepithelkarzinomen in den letzten 30 Jahren nicht 

wesentlich verbessert. Die Ursache hierfür ist überwiegend ein lokoregionäres 

Therapieversagen. Aktuelle Studien weisen auf die Bedeutung 

molekularer Faktoren für die Prädiktion und Prognose bei oralen Plattenepithelkarzinomen 

hin. Dem muzinähnlichen Glykoprotein Podoplanin, 

das maßgeblich an der Lymphangiogenese beteiligt ist, scheint 

dabei eine besondere Bedeutung zuzukommen. Ziel unserer Untersuchungen 

war es, zum einen den Einfluss von Podoplanin auf die Prognose 

und das Metastasierungsverhalten und von oralen Plattenepithelkarzinomen 

und andererseits den Wert als Marker für das Ansprechen 

des Tumors auf eine präoperative Radiochemotherapie zu untersuchen. 

Methoden. Gegenstand der Untersuchungen waren 150 Patienten mit 

oralen Plattenepithelkarzinomen, von denen 63 mit einer präoperativen 

(neoadjuvant) Radiochemotherapie und 87 mit einer primären 

Operation gefolgt von einer adjuvanten Radiochemotherapie behandelt 

wurden. Die Podoplaninexpression wurde semiquantitativ immunhistochemisch 

bestimmt. Die Podoplaninexpression wurde mit verschiedenen 

klinisch-pathologischen Parametern korreliert, zudem wurde 

der Einfluss auf das Gesamtüberleben und die lokoregionäre Kontrolle 

untersucht. 

Ergebnisse. Sowohl bei den neoadjuvant behandelten als auch bei den 

primär operativ behandelten Patienten konnte sowohl univariat als 

auch multivariat ein starker Einfluss der Podoplaninexpression auf 

das Gesamtüberleben nachgewiesen werden (p

Abstracts 


D23 – 0447 

Prognostic impact of Survivin in oral squamous cell carcinomas 

*C .B . Keschke 1 , M . Kappler 1 , U . Bilkenroth 2 , J . Schubert 1 , H . Taubert 1 , 

A .W . Eckert 1 

1 Martin-Luther-Universität Halle-Wittenberg, MKG-Chirurgie, Halle(Saale), 

Deutschland, 2 Institut für Pathologie, Eisleben, Deutschland 

Introduction. Oral Squamous cell carcinomas (OSCC) are one of the ten 

most common human tumors. However, the 5-year survival rate stagnates 

at almost 50% since 40 years. For a better prognostic calculation 

of patients with OSCC as well as for stratification to an individualized 

therapy more promising prognostic markers are necessary. The aim of 

the present investigation was to analyze the prognostic impact of Survivin 

in OSCC, an inhibitor of apoptosis. 

Materials and methods. 72 patients with oral squamous cell carcinomas 

were enrolled for the study. Tumor specimens were stained for Survivin 

using a standard immunohistochemical technique. Expression of Survivin 

was determined by assessing semi-quantitatively the percentage 

of decorated tumor cells and the staining intensity. All stained tumor 

specimens were viewed at magnifications of 100× and 200× by three independent 

investigators and correlated with clinicopathological data. 

Statistical analyses were performed using χ2-test, KAPLAN-MEIERanalysis, 

the log-rank-test and multivariate Cox’s proportional-hazards 

regression analysis. 

Results. The patient’s median age was 59 years (ranging from 23 to 83 years). 

There were 45 T1/T2-tumors and 27 patients suffered from advanced 

T3/T4-forms. Twenty-four were well, 33 moderately and 15 poorly 

differentiated. Forty-five patients were only surgically treated the other 

27 had a combination of surgery and radiotherapy. Survivin had an impact 

on prognosis in OSCC of all patients (RR=2.5, p=0.0026). The Cox’s 

regression analysis (adjusted to tumor size and tumor grade) revealed 

that patients, whose tumors highly expressed Survivin had a 6.83-fold 

increased risk of tumor related death in the operated group (p=0.0015). 

Conclusion. Survivin is a member of the IAP-family (inhibitor of apoptosis) 

and can be considered as an independent prognostic marker in 

OSCC. In summary, increased levels of Survivin are significantly correlated 

with poor prognosis of OSCC patients. We therefore suggest that 

expression of this protein can be used for an early diagnosis. Immunohistochemical 

stainings for Survivin should complete the diagnostic 

concept (TNM system, grading) at the beginning. 


D24 – 0482 

Moguntinones – new selective inhibitors for treating solide 

tumours 

*A . Müller1 , S . Plutizki2 , K . Khillimberger1 , G . Dannhardt2 , M . Moehler1 1 2 Universitätsmedizin Mainz, I . Med . Klinik, Mainz, Deutschland, Johannes 

Gutenberg Universität, Pharmazie, Mainz, Deutschland 

Introduction. Moguntinones are new innovative, synthetic designed 

small molecules, which are a combination of three natural products. 

These patent-protected kinase inhibitors were invented by the Institute 

of Pharmacy and our Department of Internal Medicine, Mainz. The 

substances displayed a new generation of targeted inhibitors for tumour 

progression, angiogenesis suppression and resistance blockage. 

Methods. The substances were analysed by kinase assays and HET-CAM 

as well as in vitro in four human colon cancer (HT-29, HCT-116, DLD- 

1, SW480) and two gastric cancer cell lines (MKN-45, AGS) for RNA 

and protein expression levels (RT-PCR, Western blot, ELISA, FACS). 


Different viability and apoptosis assays were performed in the tumour 

cells, which were incubated with Moguntinones and different cytostatic 

drugs. Additionally, intracellular signalling pathways were analysed. 

In vitro data were further verified in a human xenograft NOD/SCID 

mouse model. 

Results. Moguntinones showed clear anti-angiogenic effects in HET- 

CAM assays and inhibitory activities in IC50 kinase assays. After generating 

additional substances with little structural changes and better 

biological effects, these Moguntinones alone induced apoptosis only in 

higher concentrations (>10 µM). Furthermore, stronger synergistic effects 

for induction of apoptosis were observed in lower concentrations 

(

nificant difference between the two groups in the later request for these 

offers. 

Additionally, a remarkable relation between education and knowledge 

of psychosocial-help offers was found. Patients with a higher level of 

education also showed a better knowledge about the offers, independent 

of their group membership. Concerning the request for help it could 

be shown that patients with higher degree of education profited more 

from the information given, therefore requesting professional help offers 

more often. 

In summary the findings demonstrate that systematically providing information 

about psychosocial-help offers can influence the knowledge 

of and the request for these offers. This seems to be especially the case 

for patients with higher levels of education. 

Discussed Poster – Supportivtherapie/ 

Palliativmedizin 

D26 – 0079 

Decision making at the end of life: Cancer patients’ treatment 

preferences and prevalence of advance directives 

*J . Hilbig1,2 , *S . Sahm3,1 1Goethe-Universität, Institut für Geschichte und Ethik der Medizin, Frankfurt, 

Deutschland, 2Capio Mathilden Hospital, Klinik für Innere Medizin, 

Büdingen, Deutschland, 3Ketteler Krankenhaus, Medizinische Klinik I, 

Offenbach, Deutschland 

Introduction. Advanced directives (AD) are promoted as a means to ensure 

patient’s autonomy in case they are no longer able to decide themselves. 

Little is known about cancer patients’ capacity to express their 

treatment preferences in advance and the prevalence of ADs. As part 

of a project to evaluate attitudes with respect to ADs we examined treatment 

preferences and presence of ADs in cohort of cancer patients. 

Method. Cancer patients (CP) were interviewed using a structured 

questionnaire that had been established before (Sahm et al 2006). All 

CPs had proven diagnosis of neoplastic disease of various stages. The 

questionnaire included items inquring CPs treatment preferences (in 

case of severe non-curable disease), presence of an AD, as well as demographic 

data and information about CPs’ current state of health. Association 

with demographic and health data were calculated using χ2-test. 

Results. 100 CPs inlcuded, 51 male, mean age 68 yrs. Site of disease: 51 

colorectal, 8 pancreas, 1 CUP syndrome, 3 breast cancer, 3 ovary, 9 esophagus, 

8 stomach, 1 thyroid, 2 renal cell, 5 prostrate, 10 lung, 3 other 

(double specification possible). 11 (11%) CPs had an AD fulfilled. Treatment 

preferences with respect to particular options are given in table 1. 

The presence of AD was not associated to sex, general health state or 

frequency of pain (p>0.05). 

Tab. 1 D26-0079 

n Wish to 

be treated 

Refusal Not 

known 

i .v . fluid 100 73 2 25 

Artificial nutrition 100 16 35 49 

Antibiotic treatment 

for pneumonia 

100 36 28 36 

Analgesia if 

consciousness will 

be affected 

100 82 6 12 

Chemotherapy/ 

dialysis 

100 31 19 50 

Artificial ventilation 100 3 70 27 

Conclusion. Prevalence of ADs amongst CPs is low. Many CPs are not 

able to make decisions in advance as they are unsure about their preferences. 

In case pain management will affect consciousness a considerable 

amount of responders refuse that treatment signifying retaining 

autonomy as the more important value. Artificial ventilation is rejected 

overwhelmingly while i.v. fluid is favoured by a majority. The high proportion 

of answer not known proves a lack of information amongst CPs 

which treatment may be comforting (or too burdensome) at the end of 

life. To have CPs fulfilling an AD may be not be of value if they have not 

been informed appropriately about the respective goals of various treatment 

options. Other strategies such as advanced care planning should 

be adopted to manage care and sustain CPs’ autonomy at the end of life. 



D27 – 0269 

Optimism and habitual coping as predictors of group psychotherapy 

effectiveness for women after treatment for breast cancer 

*K . Teich1 , C . Hamm2 , A . Hamm1 , H . Freyberger2 1Institut für Psychologie, Physiologische und Klinische Psychologie/Psychotherapie, 

Greifswald, Deutschland, 2Universitätsklinikum, Klinik für 

Psychiatrie und Psychotherapie, Greifswald, Deutschland 

Purpose. After treatment for breast cancer psychotherapy helps enhancing 

the well-being and quality of life of the patients. Several programs 

have been conducted for this purpose but the effectiveness of psychological 

intervention on cancer patients’ outcomes varies considerably. 

The aim of the present study is to contribute to the improvement of psychological 

intervention programs by identifying individual differences 

that help understand who benefits from such programs and who does 

not. The study focused on differences in optimism, habitual coping, and 

social support (SS) and examined effects on health-related quality of life 

(HRQL), states of mood, anxiety, and depressive symptoms. 

Methods. Data were collected from twenty-four Western Pomeranian 

women (mean age: 50 years) receiving an adapted 10-week version of 

the cognitive behavioral therapy (CBT) based intervention program B- 

SMART by Antoni in a group setting. Participants filled in questionnaires 

assessing optimism, habitual use of coping strategies, and SS and 

completed pre- and post-assessments on HRQL, states of mood, anxiety, 

and depressive symptoms. 

Results. The intervention improved reports of vigour, physical, emotional, 

and functional well-being and reduced reports of anxiety, depressive 

symptoms, numbness, fatigue, and irritability. The effects remain 

stable after three months. Furthermore, amount of improvement depended 

on two personality variables. Correlation analysis showed that 

reduction in depressive symptoms was higher in the less optimistic patients 

(r=0.51), and in participants with a less avoidance (r=0.44) and a 

more emotion-oriented coping style (r=−0.43). Vigour increased more 

in participants with a less avoidance (r=−0.49) and a more emotionoriented 

coping style (r=0.42). Emotional well-being increased (r=0.49) 

and anxiety decreased (r=−0.45) more in patients with a emotion-oriented 

coping style. No such effects emerged for SS. 

Conclusions. The adapted CBT group intervention helped Western Pomeranian 

women in coping with the diagnosis breast cancer. The intervention 

was especially effective for less optimistic patients and participants 

with a less avoidance-oriented and a more emotion-oriented 

coping style. The results suggest that the effectiveness of psychological 

programs could be enhanced by accounting for differences in personality 

traits that eventually lead to tailored interventions for breast cancer 

patients. 


31

Abstracts 



D28 – 0457 

Changes in quality of life, anxiety, and depression of women 

with and without breast-reconstruction undergoing oncological 

rehabilitation: A prospective multi-center study 

*J . Giesler1 , H .H . Bartsch1 , J . Weis1 1Klinik für Tumorbiologie, Institut für Reha-Forschung und Prävention, 

Freiburg, Deutschland 

Objectives. Research on quality of life and subjective well-being of women 

with breast cancer undergoing oncological rehabilitation after 

breast reconstruction is sparse. Similarly, not much is known about the 

specific needs and expectations these patients might have regarding rehabilitation. 

Therefore, we surveyed breast cancer patients with (n=129) 

and without (n=155) post-mastectomy breast reconstruction with respect 

to quality of life, anxiety, depression, and satisfaction with the 

outcome of surgery at the beginning, the end, and 6 months after the 

end of rehabilitation in 7 rehabilitation clinics. 

Method. Quality of life was measured by the QLQ C-30 and the BR- 

23 of the EORTC, anxiety and depression were assessed by the HADS. 

Quality of life facets specifically related to breast reconstruction were 

measured through items addressing sequelae of reconstruction as well 

as patients’ satisfaction. In addition, information on selected medical 

and demographic variables was obtained. Data were analyzed by 2 (with 

vs. without breast reconstruction) ×2 (time of assessment) repeated 

measures ANOVAs. Since patient groups differed by age (M=50.9 vs. 

M=56.4 years, p


Discussed Poster – Versorgungsstrukturen/ 


Abstract withdrawn 

D30 – 0073 

Disclosing information about randomized clinical trials: A difficult 

and time consuming tasks for oncologists – results of a time 

efficient communication skills training evaluated in randomized 

controlled design 

*A . Wünsch1 , T . Gölz1 , G . Ihorst2 , H . Bertz3 , K . Fritzsche4 1Universitätsklinikum Freiburg, Psychoonkologischer Dienst der Abt . 

Psychosomatische Medizin und Psychotherapie sowie Innere Medizin 1 , 

Freiburg, Deutschland, 2Universitätsklinikum Freiburg, Studienzentrum, 

Freiburg, Deutschland, 3Universitätsklinikum Freiburg, Innere Medizin I 

(Hämatologie und Onkologie), Freiburg, Deutschland, 4Universitätsklini kum Freiburg, Psychosomatische Medizin und Psychotherapie, Freiburg, 

Deutschland 

Background and Objectives. Disclosing information about randomized 

clinical trials (RCT) is one of the hardest communication tasks for physicians 

and it is time consuming. Physicians have to address complex 

information, e.g. explaining randomization, and they have to respect 

patients’ rights to come to a free and uncoerced decision concerning 

participation. A Communication Skills Training (CST) was developed 

to train physicians to convey key information about RCT adequately, to 

respect patients’ rights and to be time efficient. (1) Can a CST improve 

communication skills about conveying key information about clinical 

trials? (2) Does this CST change the amount of time needed for consultations 

about RCTs? 

Methods. We developed a time efficient CST, based on the experience of 

Jenkins (2005) and Brown (2004, 2007). First, individual learning goals 

of participating physicians were derived from a video assessment. Then, 

these learning goals were used in role play with actor-patients in a CST 

to train each physician. For evaluation, 40 physicians were randomly 

assigned to training or waiting control group. Training success was evaluated 

by blinded rater using a specific checklist to evaluate video-recorded 

standardized consultations with actor-patients. Duration of the 

consultation was assessed before and after the training. 

Results. (1) Results show significant improvements in content specific 

communication skills of trained physicians. (2) By the time of the 

conference final data about time changes of these consultations will be 

presented. 

Conclusions. The developed CST is the first CST, which can show improvements 

in communication skills conveying key information about 

clinical trials evaluated in a randomized controlled design. It addresses 

ethical and legal standards, patient needs in understanding complex 

information and especially physicians’ needs in having a time efficient 

training for this difficult matter. This CST should be integrated as a 

standard training for physicians who disclose information about RCT. 



D31 – 0173 

Quality assurance of oral Xeloda® chemotherapy by a mobile 

phone application 

*M . Welslau1 , S . Haase2 , A . Jakob3 , N . Marschner4 1 2 Praxis Dr . Klausmann, Dr . Welslau, Aschaffenburg, Deutschland, IFETH Ltd . 

& Co GbR, Hamburg, Deutschland, 3Gemeinschaftspraxis für Hämatologie 

& Onkologie Offenburg, Offenburg, Deutschland, 4Praxis für Interdisziplinäre 

Hämatologie & Onkologie, Freiburg, Deutschland 

Oral chemotherapy needs active cooperation of patient, physician and 

health personnel concomitant with time-consuming elucidation and 

supervision to assure effective therapy. The mobile phone-based project 

P-com-X was started to support patients suffering from colon-CA, gastric-CA, 

and mamma-CA to provide therapeutic safety during Capecitabine 

(Xeloda®) oral chemotherapy. Real-time monitoring by a mobile 

phone may improve compliance and sense of therapy safety along with 

less personnel deployment. 

From 03/2008 to 03/2009 n=17 patients (3m/14f, age range 23–87 years) 

treated by Xeloda® of its approved indication in 4 oncologic centres in 

Germany (Berlin, Duisburg, Freiburg, Aschaffenburg) were evaluated 

in this study. Two patients were in adjuvant therapy, 7 patients in 

first-line (metastasized), 6 patients in second-line (metastasized) and 

2 patients were in third-line treatment or more. Ten patients received 

monotherapy, 7 patients combination therapy (CAPOX, CAPIRI, Bevacizumab, 

Xeloda®/Herceptin®, Xeloda®/Lapatinib). 

Customary mobile phones were programmed with specially developed 

Xeloda® documentation software. Within this software patients recorded 

general condition, side effects and their feeling of mentoring by the 

mobile phone application twice daily. Real-time data submission to the 

supervising medical centre allowed direct call-back by the physician if 

intervention was required. The project was approved by the Bavarian 

Chamber of Physicians Ethical Committee. All patients gave written 

informed consent. 

2546 treatment days from 17 patients were evaluable. This corresponds 

to 119 cycles of Xeloda® treatment (3–14 cycles) while the documentation 

time varied between 49–267 days. For general condition data evaluation 

revealed no difference between treatment days and treatment-free interval. 

Due to adverse effects intervention was necessary only in 7.7% of 

treatment days and hospitalisation could be avoided during the surveillance. 

Compliance amounted to 100%. The mobile phone application 

allowed quick and realistic record of patients’ quality of life. 

Patients felt safe and well assisted on 98% of all reviewed days during 

Xeloda® therapy by the mobile phone application. None of the elderly 

patients reported about handling problems. Evaluation of the therapy 

monitoring by the mobile phone application demonstrated considerably 

improvement of compliance and allowed rapid intervention at arising 

toxicities. Furthermore, it showed multicentre applicability. 


33

Abstracts 



D32 – 0193 

Quality of life in patients with thyroid cancer during rehabilitation 

compared to the German general population 

*S . Singer1 , T . Lincke2 , E . Gamper3 , K . Bhaskaran4 , S . Schreiber5 , A . Hinz5 , 

T . Schulte6 1Bergische Universität Wuppertal, Gesundheitspsychologie, Wuppertal, 

Deutschland, 2Universität Leipzig, Nuklearmedizin, Leipzig, Deutschland, 

3 4 Medizinische Universität, Innsbruck, Österreich, London School of Hygiene 

and Tropical Medicine, Epidemiology, London, UK, 5Universität Leipzig, 

Medizinische Psychologie, Leipzig, Deutschland, 6Rehabilitation Clinic, Bad 

Oexen, Deutschland 

Background. Since patients with thyroid cancer have a very good prognosis 

overall, clinicians may often assume that their quality of life is 

comparable to the general population. We hypothesized that quality of 

life of thyroid cancer patients is lower compare to the general population 

while controlling the effect of age and gender. 

Methods. At the beginning of their stay at an inpatient rehabilitation clinic, 

a cohort of n=121 patients with thyroid cancer were assessed using 

the quality of life core questionnaire of the European Organisation for 

Research and Treatment of Cancer (EORTC QLQ-C30). Data for comparison 

were derived from a representative German community sample 

with n=2037. 

Results. The patients reported significantly more problems than the 

community sample participants independently of gender and age effects 

in all but two domains, namely constipation and diarrhoea. The 

strongest effects of the group (patients vs. general population) were 

found in the following domains: insomnia (B=−43.7, p

elevant, up-to-date, comprehensible, free of charge, with the opportunity 

to speak to somebody. Few have used independent counselling 

and information services, but 37–45% would do so if they needed information 

again. 

Conclusions. The internet is already a major source of health information, 

but does not provide tailored information and has not widely reached 

the older age groups. Overall person to person settings, first of all 

with a doctor, are preferred. Counselling services can come up to that 

preference, too. They have to stress independence and to cover a broad 

range of topics, including complementary medicine, to reach the potential 

target groups. People of younger age and lower education, especially 

if not affected in any way, seem to have no considerable interest in cancer 

related information and don’t seek it. 



D35 – 0468 

Proxy assessment of quality of life (QoL) before and after radiotherapy 

for brain metastases: results of a prospective study 

using the DEGRO brain module 

*D . Steinmann1 , D . Vordermark2 , H . Geinitz3 , G . Ernst4 , M . Hipp5 , M . Theodorou3 

, A . Bayerl6 , U . Eichenseder-Seiss6 , H .-J . Wypior7 , R . Aschoff8 , C . Schäfer5 1 2 MHH, Strahlentherapie, Hannover, Deutschland, M .-Luther-Universität, 

Strahlentherapie, Halle/Saale, Deutschland, 3TU, Strahlentherapie, München, 

Deutschland, 4MHH, Medizinische Psychologie, Hannover, Deutschland, 

5Universität, Strahlentherapie, Regensburg, Deutschland, 6Hospital, Strahlentherapie, Krems, Österreich, 7Hospital, Strahlentherapie, Landshut, 

Deutschland, 8St .-Josef-Hospital, Strahlentherapie, Gelsenkirchen-Horst, 

Deutschland 

Purpose. Quality of life (QoL) studies in patients undergoing palliative 

cancer treatment are difficult to perform due to poor performance status 

of patients and their limited ability to complete questionnaires. Proxies 

of such patients could give useful informations about patients’ QoL. 

We applied a newly developed questionnaire, the DEGRO brain module 

(DBM), in a prospective QoL study of patients undergoing radiotherapy 

for brain metastases and compared results to scores obtained with validated 

patient-completed instruments. 

Materials and methods. From 01/2007 to 06/2010 n=166 patients with 

previously untreated brain metastases were recruited at 14 centers in 

Germany and Austria. The EORTC-QLQ-C15-PAL and the brain module 

BN20 were used to assess QoL in patients at the start of treatment 

(T0) and at 3 months (T3mo). At the same timepoints 141 of their proxies 

estimated the QoL with the new DEGRO brain module (DBM), a tenitem 

questionnaire rating the general condition as well as functions and 

impairment by symptoms in areas relevant to patients with brain metastases. 

QoL scores were compared between patients and their proxies as 

well as between the two timepoints by calculation of the Spearman-Rho 

correlation coefficient and by comparison of group means. 

Results. At T3mo, 85 of 141 patients (60%) with initial response by a 

proxy were alive. 67 of these patients (79% of 3-month survivors) and 

65 proxies completed the second set of questionnaires. After 3 months, 

QoL significantly deteriorated in all items of proxy-assessed QoL except 

headache. Correlations between self-assessed and proxy-assessed QoL 

were high in single items like nausea, headache and fatigue and in total 

scores of the whole questionnaires at both points in time (r=0.57–0.78). 

Conclusions. The high correlation between self assessment and proxy 

ratings for the total questionnaire and for single items of physical symptoms 

as well as a similar change over time for both approaches suggest 

that in patients with brain metastases, proxy assessment using the DBM 

questionnaire can be an alternative approach to obtain QoL data when 

patients are unable to complete questionnaires themselves. 

General Poster 

GI-Tumoren 

0017 

The Janus face of neoadjuvant therapy: the pelvic-perineal 

morbidity 

*J . Bunse1 , H . Hollerbuhl1 , F . Fritze1 , K . Gellert1 1Sana Klinikum Lichtenberg, Klinik für Allgemein- und Viszeralchirurgie, 


Introduction. In elevating neoadjuvant radiochemotherapy to being the 

standard therapy for localized advanced rectal cancer (S3-guidelines), 

the risks and side effects of biologically highly-active therapy inevitably 

accumulate and pose a significant challenge to both surgeon and 

wound therapist. Both the immunosuppression caused by the cancer 

and increasingly the localized radiation treatment effects of aggressive 

neoadjuvant therapy regimens play a part in the general postoperative 

risks. Other relevant risk factors are catabolism, which is present 

in almost all cases, hypoproteinemia and age-related multi-morbidity 

(such as atherosclerosis, diabetes and hypertonus). With regard to modern 

wound management, it seems necessary to adjust the therapeutic 

strategy – based on good documentation – to the individual needs of 

the patient, taking into consideration the methods available for wound 

therapy such as VAC therapy, biological surgery and novel wound dressings. 

It is equally important, however, to balance out the catabolic state 

and achieve prompt patient mobilization. A positive physician-patient 

relationship is required during long periods of hospitalization in order 

to maintain good adherence. 

Method. 120 patients (2004–2008) with rectal cancer were retrospectively 

divided into two groups: patients (n=60) with neoadjuvant therapy 

[short-term radiotherapy (RT) and long-term radiochemotherapy 

(RCHT) respectively] vs. patients who had undergone surgery without 

neoadjuvant therapy. From the period between 2008 and 2010, four patients 

with particularly complicated sacral wound healing were retrospectively 

extracted. 

Results. The evaluation of the two groups (neoadjuvant vs. non-adjuvant) 

shows an increase of almost double the rate of disorders of wound 

healing in the group of patients with rectum amputation and pre-treatments. 

A particularly vulnerable group in terms of complicated healing 

processes is women, as the anatomical boundary between the vagina 

and the rectum (the rectovaginal fascia) may fall victim to the oncological 

resection or debridement subsequent to a sacral cavity infection, 

resulting in the formation of a cloaca. 

Discussion. The irradiated infected sacral cavity poses a big challenge to 

surgeons and patients and requires courses of therapy adjusted to the 

individual which include surgical debridement as well as all available 

wound therapy options. Success is usually achieved only very slowly and 

often requires changes in strategy at a very early stage. The psycho-social 

guidance of the patients makes very high demands of the attending 

team of doctors. This can only be ensured by an interdisciplinary team. 


35

Abstracts 

0051 

Trastuzumab in combination with standard chemotherapy as 

first-line treatment for patients with HER2-positive metastatic 

gastric cancer: safety findings from the German non-interventional 

observation study HerMES 

*S .-E . Al-Batran1 , C .V . Hannig2 , D . Pott2 , C . Tirier2 , C . Lerchenmüller3 , E . Moorahrend4 

, H . Kröning5 , S . Hegewisch-Becker6 , V . Petersen7 , M . Königsmann8 , 

E . Böcher9 , T . Hamm9 , K .-U . Däßler10 , M . Groschek11 , C . Maintz11 , C . Hinske11 , 

W . Schneider-Kappus12 , V . Kächele12 1Krankenhaus Nordwest, Klinik für Onkologie und Hämatologie, Frankfurt, 

Deutschland, 2Schwerpunktpraxis für Hämatologie und Onkologie, Bottrop, 

Deutschland, 3Gemeinschaftspraxis für Hämatologie und Onkologie, 

Münster, Deutschland, 4Onkologische Praxis, Porta Westfalica, Deutschland, 

5Schwerpunktpraxis für Hämatologie und Onkologie, Magdeburg, 

Deutschland, 6Internistische Praxisgemeinschaft Eppendorf, Hamburg, 

Deutschland, 7Onkologische Schwerpunktpraxis, Heidenheim, Deutschland, 

8Onkologische Schwerpunktpraxis und Tagesklinik am Diakoniekrankenhaus 

Henriettenstiftung, Hannover, Deutschland, 9Gemein schaftspraxis, Soest, Deutschland, 10Onkologische Schwerpunktpraxis, 

Freital, Deutschland, 11Hämatologisch-Onkologische Praxis, Würselen, 

Deutschland, 12Praxis für Hämatologie und interdisziplinäre Onkologie, 

Ulm, Deutschland 

Background. The ToGA trial, an international multicenter phase III clinical 

study involving 24 countries globally, has recently shown that the 

anti-HER2 humanized monoclonal antibody trastuzumab is effective 

in prolonging survival in HER2-positive carcinoma of the stomach and 

the gastroesophageal junction (GEJ). However, few data are available on 

trastuzumab when used as part of routine clinical practice in Germany. 

Methods. This non-interventional observation study was conducted to 

evaluate the efficacy, safety and feasibility of trastuzumab in previously 

untreated patients with HER2-positive metastatic gastric cancer (MGC) 

in Germany. Data from all patients with MGC who received trastuzumab 

were recorded in detail on standardized forms (eCRF) until they 

had developed disease progression or for a maximum of 12 months of 

trastuzumab therapy. 

Results. Between April 2010 and June 2011, data from 50 patients were 

collected. All patients were evaluable for safety. Baseline patient characteristics 

were as follows: median age 59.5 years (range 29–88); gender 

(male 66%; female 34%); ECOG PS (0: 28%; 1: 46%; 2: 16%; 3: 6%); distant 

metastases (92%); liver metastases (48%), lymph node metastases (38%); 

peritoneum metastases (24%); lung metastases (12%); bone metastases 

(12%). The median duration of trastuzumab treatment was 3.3 months 

(range 0–10.6). The median trastuzumab dose per patient and cycle was 

6.2 mg/kg BW. Only 27% of patients received trastuzumab according to 

the label in combination with cisplatin and fluoropyrimidine (5-FU or 

capecitabine), the remainder received trastuzumab either as monotherapy 

(8%) or in other combinations: cisplatin, 5-FU and leukovorin (12%); 

5-FU, leukovorin, oxaliplatin and docetaxel (10%); 5-FU, leukovorin and 

oxaliplatin (8%); capecitabine (6%); 5-FU, cisplatin and docetaxel (4%). 

The most common adverse events (AEs, all grades) were as follows: 

nausea (8%), diarrhoea (8%), vomiting (8%), and fatigue (6%). The most 

common grade 3/4 AEs were nausea (4%), vomiting (4%), fatigue (4%), 

diarrhoea (2%), and urinary tract infection (2%). 

Conclusions. Trastuzumab, administered either as monotherapy or in 

combination with standard chemotherapy, is well tolerated in the routine 

treatment of MGC. These findings support those from the ToGA 

trial and suggest that treatment with trastuzumab should be regarded 

as standard of care for patients with HER2-positive MGC. 


0059 

Tumor response and clinical outcome in advanced gastrointestinal 

stromal tumors under sunitinib therapy: comparison of 

RECIST, Choi and volumetric criteria 

*N . Schramm1 , M . Schlemmer2 , E . Englhart1 , C . Becker1 , M . Reiser1 , F . Berger1 1Klinikum der Universität München, Institut für Klinische Radiologie, München, 

Deutschland, 2Klinikum der Universität München, Medizinische Klinik 

und Poliklinik III, München, Deutschland 

Purpose. For patients with metastatic gastrointestinal stromal tumor 

(GIST) under imatinib it has been demonstrated that radiological response 

according to Choi criteria also taking into account CT density 

changes correlates better than RECIST with early therapy response and 

disease-specific survival (DSS). Purpose of the study was the comparison 

of RECIST, Choi and volumetric radiological response in GIST-patients 

under 2nd-line-sunitinib-therapy with correlation to DSS. 

Methods. 20 patients with baseline-CT of the abdomen under imatinib 

obtained follow-up-CTs 3 months and 1 year after change to sunitinib. 

Therapy response was evaluated according to RECIST, Choi and volumetric 

criteria (PR: decrease ≥40%, PD: increase ≥33%). The response 

categories respectively were: partial response (PR), stable disease (SD) 

and progressive disease (PD). Response according to the different assessment 

systems was correlated to the DSS of the patients. 

Results. The mean DSS (in months) of the response groups 3 months 

after therapy change was: RECIST: PR (0/20); SD (17/20): 29.2 (months); 

PD (3/20) 11.6/Choi: PR (10/20) 27.9; SD (8/20) 26.4; PD (2/20) 13.5 / 

Volumetry: PR (4/20) 29.7; SD (11/20) 28.4; PD (5/20) 17.2. Reponse 

groups after 1 year of sunitinib showed the following mean DSS: RE- 

CIST: PR (3/20) 33; SD (9/20) 28.2; PD (8/20) 20.3 /Choi: PR (10/20) 21.3; 

SD (4/20) 39.6; PD (6/20) 23.9 /Volumetry: PR (6/20) 27.0; SD (5/20) 35.9; 

PD (9/20) 19.3. Patients classified as PR after 1 year according to Choi 

and volumetry had a shorter DSS than patients classified as SD. 

Conclusion. In our GIST-patient collective Choi and volumetric criteria 

could detect responders with prolonged survival time under sunitinib 

only in the early follow-up but not in the later course of disease. These 

results have to be verified in larger patient cohorts. Our data provide 

support for the assumption that Choi criteria might not be appropriate 

to select GIST-patients with prolonged survival in later follow-up examinations. 

0072 

Gene markers of progression of Barrett’s metaplasia to carcinoma 

*Q . Wang1 , M . Fehlker1 , M . Vieth2 , P .-M . Schlag3 , T . Wex4 , P . Malfertheiner4 , 

W . Kemmner1 1 2 MDC-Berlin Buch, Surgical Oncology, Berlin, Deutschland, Klinikum 

Bayreuth, Pathology, Bayreuth, Deutschland, 3Charité – Universitätsmedizin, 

Comprehensive Cancer Center, Berlin, Deutschland, 4Magdeburg University, Gastroenterology, Magdeburg, Deutschland 

Background. The incidence of esophageal adenocarcinoma has increased 

strongly during the past 30 years and 5-year survival remained poor 

at approximately 20%. Esophageal adenocarcinoma develops through 

a multistage process. Barrett’s esophagus metaplasia is considered to 

be the key precursor lesion of esophageal adenocarcinoma. The aim of 

this study is to generate and validate biomarkers to stratify patients with 

Barrett’s esophagus in terms of their risk for developing cancer. 

Patients and methods. We studied gene expression profiling of 59 frozen 

specimens, consisting of esophageal squamous epithelium from 18 

healthy subjects, 20 specimens from patients with Barrett’s epithelium 

and 21 cases of esophageal Barrett’s adenocarcinoma, by whole genome 

microarray analysis. Laser capture microdissection technique was applied 

to procure cells from defined regions of Barrett’s metaplasia and 

esophageal Barrett’s adenocarcinoma. Microarray results were validated 

by quantitative real-time polymerase chain reaction (qRT-PCR) in

a second and independent cohort consisting of 12 healthy cases, 20 Barrett’s 

epithelium, 8 intermediate dysplastic BE closed to esophageal adenocarcinoma 

and 10 esophageal Barrett’s adenocarcinomas. Furthermore, 

immunohistochemistry was performed on a third independent 

cohort consisting of 12 normal squamous esophagus samples, 12 esophageal 

adenocarcinoma cases and 12 Barrett’s esophagus samples, five 

of which were close to esophageal Barrett’s adenocarcinoma, representing 

Barrett’s esophagus at high risk for developing adenocarcinoma. 

Results. Microarray analysis showed that 1176 genes were significantly 

differentially expressed in esophageal Barrett’s adenocarcinoma compared 

to squamous esophagus epithelium. In a second step, the expression 

profile of Barrett’s esophagus metaplasia was compared to esophageal 

Barrett’s adenocarcinoma and squamous epithelium resulting in a 

short list of 16 genes which were differentially expressed among all three 

groups. Hierarchical clustering of the samples based on the expression 

of these 16 genes allowed a clear discrimination of NE, BE and EAC. 

Validation of the microarray results in an independent patient cohort 

by qPCR confirmed these results. This analysis showed that in particular 

the genes CTHRC1, INHBA, PROCR and ADH7 were significantly 

differently expressed between NE, BE and EAC. Furthermore, immunohistochemistry 

showed that CTHRC1 and INHBA were only high in 

EAC and BE located close to EAC on protein level. 

Conclusions. This study identified novel biomarkers to predict esophageal 

Barrett’s adenocarcinoma at its Barrett’s esophagus precursor 

stage, not only in original cohort, but also in validation cohorts. These 

biomarkers can be determined by quantitative expression analysis, 

which will complement conventional semi-quantitative immunohistochemical 

analysis in the future. However, further efforts are needed to 

understand the contribution of these genes to Barrett’s carcinogenesis. 

0089 

Resection vs. transplantation as curative treatment options for 

hepatocellular carcinoma in cirrhosis – Systematic review and 

metaanalysis 

*A . Proneth1 , F . Zeman2 , S . Bhoorie3 , V . Mazzaferro3 , E .K . Geissler1 , 

H .J . Schlitt1 , A .A . Schnitzbauer1 1Uniklinikum Regensburg, Klinik und Poliklinik für Chirurgie, Regensburg, 

Deutschland, 2Uniklinikum Regensburg, Zentrum für Klinische Studien, 

Regensburg, Deutschland, 3National Cancer Institute, Istituto Nazionale 

Tumori Fondazione IRCCS, Gastrointestinal Surgery and Liver Transplantation 

Unit, Milano, Italien 

Objective. To systematically review the literature on resection (Rx) and 

liver transplantation (LT) for hepatocellular carcinoma (HCC) in patients 

with Child A cirrhosis. 

Background. Hepatocellular Carcinoma is the fifth most neoplasm 

worldwide. Current standard curative therapeutic strategies include 

resection and liver transplantation with or without prior bridging with 

ablative procedures. Organ shortage leads to discussion whether HCC 

should be transplanted or whether resection can achieve similar results. 

Methods and aims. A systematic review of various databases (Pubmed, 

PICO, MEDLINE, Cochrane and Library for RCT) was performed. Studies 

investigating Rx vs. LT, and Rx or LT only, and in which patients 

were regarded to be both resectable and transplantable between 1998 

and 2011 were included in the analysis. The primary endpoint was overall 

survival (OS). Secondary endpoints were disease free survival (DFS) 

as well as prognostic factors (AFP, tumor size and number, micro- and 

macrovascular invasion, stadium of cirrhosis, MELD-score, bridging 

therapies etc.). The results should serve as a decision-making basis to 

either transplant or resect the patient primarily in case of HCC-diagnosis. 

Results. Database research revealed a total 843 hits. To date there is no 

existing randomized controlled trial (RCT) investigating Rx vs. Tx for 

HCC. A total of 71 publications were eligible for statistical evaluation. 

OS and DFS data for LT and Rx differ significantly between groups fa- 

voring LT. However, surrogate predictive markers for outcome reveal a 

lower microvascular invasion, a better differentiation, less microsatellites, 

smaller tumors and lower pre-treatment AFP values in patients 

being transplanted. 

Conclusion. Current evidence in literature does not allow a meaningful 

comparison between patient collectives undergoing Rx or LT for HCC. 

There are no data from randomized controlled trials. Analyses do not 

compare patients in a comparable tumor stadium. A RCT in patients 

without contraindications for transplantation or resection and comparable 

surrogate characteristics should be initiated investigating the 

hypothesis that resection of HCC achieves similar results than transplantation. 

0122 

Implementation of adjuvant treatment in routine care of colorectal 

cancer – data of a population-based sample 

*A . Schlesinger-Raab1 , S . Schrodi1 , R . Emeny1 , R . Eckel1 , G . Schubert-Fritschle1 

, J . Engel1 1Tumorzentrum München (TZM), Tumorregister München (TRM), München, 

Deutschland 

Introduction. In 2004, the first national S3 guideline for the diagnosis, 

therapy and aftercare of colorectal patients was implemented in Germany, 

and the first update was released in 2008. Adjuvant chemotherapy is 

recommended in colon cancer with UICC stage III. Neoadjuvant radiation 

therapy is recommended in rectal cancer with UICC II/III. 

Objective. The study aim was to evaluate guideline compliance for adjuvant 

treatment of patients with colorectal cancer and to determine 

possible influences on survival in a population-based sample. 

Methods. The Munich Cancer Registry (MCR) records all cancer patients 

treated in the registration area that covers upper Bavaria, with 

4.5 million inhabitants, since 2007. Data from almost 45,000 cases of 

patients with colorectal cancer, diagnosed between 1988 and 2008 were 

analysed. The distribution of adjuvant therapies was analysed in regard 

to associations with time, age and tumour-related factors. Survival as 

outcome parameter was examined by the Kaplan-Meier method and 

Cox proportional hazard modelling. 

Results. Stratification into two decades (1988–1997, 1998–2002) showed 

the demographic ageing, the proportion of patients 80 years and older 

increases from 15 to 20% over these two time periods. The proportion of 

male patients increased as well from 53 to 56%. UICC stage distribution 

was quite stable. Documentation improved continuously; missing values 

in tumour-related variables were less than 10%. The realisation of 

adjuvant chemotherapy in colon cancer stage III improved from 30% 

in the years before 1998 to almost 50% after 1998 and is still improving 

year by year. Only 16% of stage II rectal cancer patients were treated with 

neoadjuvant radiation before 1998 and about 70% after 1998. In stage III 

patients, the proportions improved from 53% to about 80%. A slight 

improvement in relative survival can be seen in rectal cancer patients: 

about 3% points in 10-year relative survival. Thus, since 1998 colon and 

rectal cancer have the same prognosis with 65% and 57% probability for 

5- and 10-year relative survival, respectively. 

Conclusion. The guideline recommendations concerning adjuvant and 

neoadjuvant therapies continue to be brought into practice, especially 

in UICC III in rectal cancer patients. Their increasing implementation 

may be a reason for improvement in survival in rectal cancer patients. 


37

Abstracts 

0131 

The impact of multimodal treatment on long-term quality of life 

in patients with rectal carcinoma. Results of the CAO/ARO/AIO-94 

study 

*S . Merkel1 , M .-T . Villanueva1 , W . Hohenberger1 , T . Liersch2 , H . Becker2 , 

R . Raab3 , C . Rödel4 , R . Sauer5 1Universitätsklinikum Erlangen, Chirurgische Klinik, Erlangen, Deutschland, 

2Universitätsmedizin Göttingen, Klinik für Allgemein- und Viszeralchirurgie, 

Göttingen, Deutschland, 3Klinikum Oldenburg, Klinik für Allgemeinund 

Visceralchirurgie, Oldenburg, Deutschland, 4Universitätsklinikum Frankfurt am Main, Klinik für Strahlentherapie und Onkologie, Frankfurt 

am Main, Deutschland, 5Universitätsklinikum Erlangen, Strahlenklinik, 

Erlangen, Deutschland 

Introduction. The German multicenter study CAO/ARO/AIO-94 compared 

preoperative chemoradiotherapy with postoperative chemoradiotherapy 

(CRT) in locally advanced rectal cancer. Preoperative CRT 

was found to improve local control and was associated with reduced 

acute toxicity but did not improve survival. The aim of our study was 

to compare quality of life in the long-term survivors after a median of 

11 years (range: 8–15 years). 

Patients and methods. Until 2010 of 799 participating patients, 340 patients 

(42.6%) had died and 8 patients (1.0) were lost to follow-up. 359 

(79.6%) of the 451 long-term survivors (8–15 years) completed the quality 

of life questionnaires of the EORTC, the QLQ-C30 and its new colorectal 

module, the QLQ-CR29: 190 patients who had preoperative CRT, 

109 patients who received postoperative CRT and 60 patients of the 

postoperative treatment arm without receiving CRT due to overstaging, 

understaging, postoperative complications or denial. The QLQ-CR29 

permits a combined analysis of patients with and without a stoma even 

in bowel function. Median age of the 237 men and 122 women was 71 years 

(range: 43–88 years). For comparisons the Mann-Whitney U test and 

the Kruskal-Wallis one-way of variance were used. 

Results. Significant differences between the three groups were found in 

social functioning, diarrhea, stool frequency, faecal incontinence, flatulence, 

bloated feeling, embarrassing bowel movements, abdominal 

pain, urinary frequency and dysuria. Patients without CRT indicated 

more favourable statements in most measures, followed by patients with 

preoperative CRT, while patients with postoperative CRT stated the 

most unfavourable results. Impotence was rated highest of all symptom 

scales but without differences between the primary treatment groups. 

Age, sex, tumour site and stoma were found to be additional factors influencing 

significantly quality of life in several aspects. 

Conclusion. Multimodal treatment, especially preoperative CRT reduces 

the rate of locoregional recurrences. The indication for multimodal 

treatment has to be based on evidence based criteria, because long-term 

survivors complain about reduced quality of life, especially with respect 

to bowel function and defecation. However, long-term quality of life was 

found to be superior after preoperative CRT when compared to postoperative 

CRT. 


0133 

Locoregional recurrence in rectal carcinoma: Long-term results 

of the German multicenter study CAO/ARO/AIO-94 

*S . Merkel1 , M .-T . Villanueva1 , W . Hohenberger1 , T . Liersch2 , H . Becker2 , 

R . Raab3 , C . Rödel4 , R . Sauer5 1Universitätsklinikum Erlangen, Chirurgische Klinik, Erlangen, Deutschland, 

2Universitätsmedizin Göttingen, Klinik für Allgemein- und Viszeralchirurgie, 

Göttingen, Deutschland, 3Klinikum Oldenburg, Klinik für Allgemeinund 

Visceralchirurgie, Oldenburg, Deutschland, 4Universitätsklinikum Frankfurt am Main, Klinik für Strahlentherapie und Onkologie, Frankfurt 

am Main, Deutschland, 5Universitätsklinikum Erlangen, Strahlenklinik, 


Introduction. The German multicenter study CAO/ARO/AIO-94 of locally 

advanced rectal cancer showed in 2004 after a median follow-up of 

46 months in the intention-to-treat-analysis, that preoperative chemoradiotherapy 

(CRT) compared with postoperative CRT improved local 

control (6% vs 13% locoregional recurrences) and reduced acute toxicity, 

but did not improve survival (74% vs 76%). Now we report long-term 

results after a median follow-up of 11 years (8–15 years). 

Methods. Until 2010 of 799 participating patients, 340 patients (42.6%) 

had died and 8 patients (1.0) were lost to follow-up. 764 patients treated 

with curative intent (M0/M1, R0/R1) were selected for analysis: 386 patients 

after preoperative CRT, and 378 in the postoperative CRT arm 

(132 of these did not receive any postoperative treatment due to overstaging, 

understaging, complications or denial. An as-treated analysis was 

performed to estimate 10-year rate of locoregional recurrences and to 

evaluate treatment and prognosis of those patients. 

Results. The 5- and 10-year rates of locoregional recurrences of all patients 

were 7.2% and 8.5%. These rates differed significantly (p=0.008) 

between the preoperative CRT (4.2% and 6.3%) and the postoperative 

CRT arm (10.4% and 10.7%) after the long-term follow-up. In multivariate 

analysis, R1-resection was the most adverse factor for locoregional 

recurrences. Late locoregional recurrences (≥60 months after primary 

treatment) were seldom in our study with 7 out of 58 recurrences: five in 

the preoperative arm and two in the postoperative CRT arm. In general, 

the treatment choice for locoregional recurrences depended on primary 

treatment. Radiotherapy or CRT was administered in 7/41 patients (17%) 

who had former CRT and in 12/17 patients (71%) with primary surgery 

alone (p

0134 

Hyperthermia induced by nanotherapy for oesophageal and 

pancreatic cancer 

*B . Rau1 , M . Steinbach2 , M . Hünerbein2 , J .-T . Ollek3 , A . Jordan3 1Charité Campus Mitte, Klinik für Allgemein-, Thorax- und Gefäßchirurgie, 

Berlin, Deutschland, 2Helios Klinken Buch, Berlin, Deutschland, 3Magforce, Berlin, Deutschland 

Background. In the literature is postulated, that hyperthermia enhances 

the effect of radio- and chemotherapy. Intra-tumorally instilled superparamagnetic 

ironoxide nanoparticles (NanoThermR) inducing localized 

hyperthermia are a potential option to further improve cancer 

treatment. Oesophageal (OC) and pancreatic cancer (PC) have a poor 

outcome regarding overall and progression free survival. The objective 

of this study was to show that NanoThermR can be applied safely in 

incurable OC and PC and effectively induce interstitial hyperthermia. 

Methods. The method comprised direct injection of the nanoparticles 

into the tumor. Instillation was controlled by CT scan prior to exposure 

to the magnetic field. Hyperthermia was applied synchronously or 

directly before chemotherapy. Patients were subsequently exposed to 

an alternating magnetic field which stimulates the nanoparticles causing 

interstitial heat needed for effective thermotherapy. Altogether 

17 patients with OC (11) and PC (6) were treated with nanoparticles in 

combination with chemo- or chemoradiotherapy. Temperature was 

monitored via thermometry catheter placed at the tumor. Treatment 

emergent toxicities were records according to the common Toxicity 

Criteria (CTC). 

Results. Mean tumor volume was 27.3 and 42.3 cm3 in OC and PC, respectively. 

Placement of the nanoparticles was feasible in all tumors. 

Temperature at the tumor could not be measured in OC. Instead mean 

simulated temperatures based on the distribution of the nanoparticles 

determines by post-instillation CT was 42.8°C. In PC temperatures 

were successfully measured at the tumor yielding 40.0°C on average. 

Occurrence of the treatment emergent CTC grade 3 and 4 toxicity was 

low. Hot spots during treatment were observed in every patient. 

Conclusion. NanoThermR therapy in combination with chemo- or chemoradiotherpy 

was feasible and reasonably well tolerated even in this 

late-stage patient population. To optimize the NanoThermR application 

procedure and to improve the quality of temperature measurement as 

well as to show efficacy of the therapy in combination with current therapy 

options in OC and PC further investigations are planned. 

0141 

Identification of predictive molecular markers for chemoradiation 

by ICPL proteom amalysis in rectal carcinomas 

*R . Croner1 , M . Sevim2 , P . Jo3 , V . Schellerer1 , E . Naschberger4 , M . Stürzl4 , 

W . Hohenberger1 , F . Lottspeich2 , J . Kellermann2 1Universitätsklinikum Erlangen, Chirurgische Klinik, Erlangen, Deutschland, 

2Max-Planck Institut Martinsried, Proteinanalytik, Martinsried, Deutschland, 

3Universitästklinkum Göttingen, Chirurgische Klinik, Göttingen, 

Deutschland, 4Universitästklinkum Erlangen, Abteilung für Molekulare und 

Experimentelle Chirurgie, Erlangen, Deutschland 

Background. Neodajuvant chemoradiation (CRT) is an established procedure 

in rectal carcinomas to increase sphincter preservation and to 

decrease local tumor recurrence (9.6%). But only 53% of the carcinomas 

respond with tumor regression, while 8–15% show complete response. 

Molecular markers may be an option to identify responder from nonresponder 

prior to CRT. 

Material and methods. Tumor biopsies from 20 rectal carcinomas were 

harvested prior to CRT (CAO/ARO/AIO-04). After laser microdissektion 

(LCM) of the specimens, proteins were isolated. The samples of CRT 

responders (rCRT; n=10) and CRT non reponders (nCRT; n=10) were 

pooled regarding their postoperative histopathological tumor regression 

rate (Dworak). Isotope Coded Protein Label (ICPLTM) was perfor- 

med of the LCM specimen’s proteom to identify differential proteins 

between rCRT and nCRT. 

Results. From all tumor biopsies a sufficient amount of material could be 

harvested during LCM to perform ICPLTM. The isolated protein lysate 

was of good quality and ICPLTM worked well. We identified 43 differentially 

expressed proteins between the rCRT and nCRT group. These 

proteins belonged to the tumor stroma, immune system and gluthation 

metabolism. 

Conclusions. ICPLTM is a sufficient technology to identify differentially 

expressed proteins in rectal carcinoma biopsies. The identified markers 

may be potential candidates for CRT prediction, but their clinical value 

has to be validated during further analysis. 

0151 

Evaluation of sorafenib in combination with local microtherapy 

guided by gadolinium-EOB-DTPA enhanced MRI in patients with 

inoperable hepatocellular carcinoma 

*J . Ricke1 , K . Schütte2 , O . Rosmorduc3 , A .L . Jacob4 , J . Lammer5 , C . Verslype6 , 

B . Sangro7 , J . Walecki8 , H .-J . Klumpen9 , B . Peynircioglu10 , S . Yalcin11 , C . Bartolozzi12 

, H . Amthauer1 , P . Malfertheiner2 1Universität Magdeburg/ Medizinische Fakultät, Radiologie und Nuklearmedizin, 

Magdeburg, Deutschland, 2Universität Magdeburg, Klinik für 

Gastroenterologie, Hepatologie und Infektiologie, Magdeburg, Deutschland, 

3Hôpital Saint Antoine, Service d’Hepatologie, Paris, Frankreich, 4Uni versitätsspital, Klinik für Radiologie und Nuklearmedizin, Basel, Schweiz, 

5Medizinische Universität, Interventional Radiology, Wien, Österreich, 

6 7 Medizinische Universität, Digestive Oncology, Wien, Österreich, Clinica 

Universitaria and CIBEREHD, Liver Unit, Pamplona, Spanien, 8Centralny Szpital Kliniczny, MSWiA, Department of Radiology, Warszawa, Polen, 

9 10 Academic Medical Center, Oncology, Amsterdam, Niederlande, Haceteppe 

University of Medicine, Department of Radiology, Ankara, Türkei, 

11Haceteppe University of Medicine, Medical Oncology, Ankara, Türkei, 

12University of Pisa, Department of Radiology, Pisa, Italien 

Background. Hepatocellular carcinoma (HCC) is the fifth most common 

cancer worldwide with an increasing incidence rate. Tumour stage 

at diagnosis, liver function and general health status are the most important 

prognostic factors for the individual patient. Treatment strategy 

in early HCC aims at the local removal of the tumor and represents a 

potentially curative treatment option [resection, liver transplantation 

or local ablation using percutaneous ethanol injection (PEI) or radiofrequency 

ablation (RFA)]. In intermediate and advanced stages of 

HCC patients receive treatment with palliative intent [transarterial 

chemoembolisation (TACE), Yttrium-90-radioembolisation (SIRT) 

or systemic therapy with sorafenib]. Studies with the combined use of 

locoregional and systemic therapy with their potential of a beneficial 

synergism are few and conducted in a small number of patients. 

Methods. This phase II study (SORAMIC) is composed of three sub-studies 

with the following primary objectives: (1) In patients in whom local 

ablation is appropriate to determine if sorafenib in combination with 

radiofrequency ablation (RFA) prolongs the time-to-recurrence in comparison 

with RFA + placebo. Primary endpoint (PEP): time to recurrence, 

n=290 pts. (2) In patients in whom RFA is not appropriate (palliative 

treatment group) to determine if the combination of yttrium-90-microspheres 

(SIRT) + sorafenib improves the overall survival in comparison 

to sorafenib alone. PEP: overall survival, n=375 pts. (3) To test the 

diagnostic and staging accuracy of Gd-EOB-DTPA enhanced MRI with 

contrast-enhanced multisclice CT. PEP: correct stratification of patients 

to a palliative versus local ablation treatment strategy; n=830 pts. 

Results. This trial has already started with 34 out of 830 patients enrolled 

until July, 18th 2011 and will recruit in 41 European centers in 14 

countries. Preliminary results regarding the feasibility of these treatments 

within such a complex trial design under academic sponsorship 

will be presented. Safety data after at least 2 months of treatment with 


39

Abstracts 

sorafenib /placebo for the first 20 patients did not indicate an increased 

toxicity for the combination of local microtherapy and sorafenib. 

Conclusion. Findings will provide insight in the synergism of local microtherapy 

and systemic treatment in patients with HCC. The complex 

trial design with three separate study sections with own PEP will additionally 

define the optimal imaging staging modality. 

0152 

Progression free survival and overall survival in patients with 

metastastic gastrointestinal stromal tumor (GIST) treated with 

sorafenib as 3rd- or 4th-line therapy 

*U . Bitz1 , D . Pink1 , J . Rahm1 , A . Koepke1 , P . Reichardt1 1HELIOS Klinikum Bad Saarow, Klinik für Hämatologie und Onkologie, 

Sarkomzentrum Berlin-Brandenburg, Bad Saarow, Deutschland 

Background. There is no approved treatment option for patients with 

unresectable or metastastic GIST with resistance to imatinib and sunitinib. 

Results of phase II trials indicate an efficacy of the multi-tyrosinkinase-inhibitor 

sorafenib in this population. 

Methods. We performed a retrospective analysis of all patients with metastastic 

GIST treated with sorafenib in our institution regarding their 

progression free survival and overall survival. All of these patients had 

suffered disease progression to imatinib and sunitinib, some of them 

had also been treated with everolimus and/or nilotinib. Response to 

treament was assesed using CT-Scans and RECIST-criteria every three 

months. 

Results. 37 patients (median age 53 years [33–75 years]) treated with 

sorafenib 800 mg daily were included in our analysis. Primary sites 

of GIST were small intestine (42%), stomach (30%), duodenum (15%), 

unknown (10%) and rectum (3%). 35 patients were eligible for response 

evaluation. 3 patients (9%) had a partial remission, 19 patients (54%) 

showed stable disease, resulting in a disease control rate (PR + SD) of 

63%. 13 (37%) patients showed no response to treatment. Median progression 

free survival (mPFS) was 5 months (0–38 months). mPFS in patients 

with at least stable disease was 8,5 months (4–38 months). Median 

overall survival since start of treatment was 10 months (1–38 months), 

82 months (21–158 months) since first diagnose of GIST and 76 months 

(10–126 months) since first diagnose of metastasis. Main toxicities during 

treatment were skin reactions (rash, hand and foot-syndrome), hypertension, 

diarrhea and fatigue. In 24% of the patients a dose reduction 

due to toxicity was necessary. 

Conclusion. To our knowledge this is the largest collection of patients 

with metastastic GIST treated with sorafenib by a single institution, 

that has been reported so far. In the majority of patients with intensively 

pretreated metastatic GIST, treatment with sorafenib can at least lead to 

stabilisation of disease. Our results are comparable to those of phase II 

trials from South Korea und the USA. The conduction of randomised 

prospective trails is necessary for further evaluation. 


0180 

Investigating the relationship between quality of life (QoL) and 

tumour response in patients (pts) with metastatic colorectal 

cancer (mCRC) receiving FOLFIRI plus panitumumab (pmab) as 

first-line therapy: an exploratory analysis of study 314 

*M . Karthaus1 , J . Thaler2 , R . Hofheinz3 , L . Mineur4 , H . Letocha5 , R . Greil6 , E . 

Fernebro7 , E . Gamelin8 , A . Baños9 , C .-H . Köhne10 1 Department of Hematology, Oncology and Palliative Medicine, Klinikum 

Neuperlach/ Klinikum Harlaching, München, 2 Department of Hematology 

and Medical Oncology, Klinikum Wels-Grieskirchen, Wels, 3 Day treatment 

centre at the Interdisciplinary Tumour Centre Mannheim, Universitätsmedizin, 

Mannheim, 4 Radiology and Oncology Centre, Institut Sainte- 

Catherine, Avignon, 5 Department of Oncology, County Hospital, Västerås, 

6 3 7 rd Medical Department, University Hospital, Salzburg, Department of 

Oncology, University Hospital, Lund, 8 Department of Medical Oncology 

and Oncopharmacology, Centre Paul Papin, Angers, 9 Department of Biostatistics, 

Amgen, Uxbridge, 10 Department of Hematology and Oncology, 

Onkologie Klinikum, Oldenburg 

Introduction. Study 314 was a phase II, single-arm, multicentre study 

assessing the efficacy/safety of first-line FOLFIRI plus pmab in pts with 

mCRC, stratifying by KRAS tumour status. Here, we explored the relationship 

between QoL and tumour response. 

Methods. FOLFIRI and pmab (6 mg/kg) were administered every 14 

days until disease progression, unacceptable toxicity or consent withdrawal. 

EUROQOL EQ-5D Index scores were recorded at screening, 

then every 8 wks until wk 32, every 3 months thereafter until disease 

progression, and 56 days after stopping study treatment (referred to as 

the safety follow up visit). EQ-5D scores range from −0.594 to 1 (1 being 

equal to perfect health). A change of ≥0.08 was considered to be clinically 

meaningful. Data were analyzed descriptively by best overall response 

and by tumour KRAS status (wild type [WT] or mutant [MT]). 

Results. In those pts with higher baseline EQ-5D scores, a trend for better 

tumour response was observed. In those pts who achieved complete 

or partial response, the difference in EQ-5D score between the WT 

group and the MT group surpassed the clinically meaningful threshold 

at wk 8 and wk 24. 

Tab. 2 Mean (SE) change in EQ-5D score from baseline 

Mean (SE) 

baseline 

score 

PD 

WT 

PD 

MT 

SD 

WT 

SD 

MT 

CR or PR 

WT 

n 4 3 25 26 45 22 

0 .720 

(0 .178) 

0 .588 

(0 .205) 

0 .833 

(0 .039) 

0 .790 

(0 .034) 

0 .812 

(0 .034) 

Wk 8 n 3 2 23 23 43 21 

+0 .047 

(0 .047) 

−0 .087 

(0 .122) 

−0 .023 

(0 .044) 

+0 .015 

(0 .030) 

+0 .049 

(0 .032) 

Wk 16 n 1 1 20 19 39 22 

−0 .240 

(–) 

−0 .327 

(–) 

+0 .024 

(0 .039) 

−0 .007 

(0 .073) 

+0 .067 

(0 .031) 

Wk 24 n 0 10 9 33 19 

0 .000 – +0 .014 

(0 .073) 

+0 .111 

(0 .046) 

+0 .053 

(0 .028) 

Wk 32 n 1 0 3 5 15 8 

Safety 

follow up 

visit 

−0 .311 

(–) 

– +0 .195 

(0 .195) 

+0 .172 

(0 .081) 

+0 .019 

(0 .037) 

n 2 1 13 15 19 14 

−0 .087 

(0 .343) 

+0 .000 

(–) 

−0 .040 

(0 .060) 

−0 .034 

(0 .085) 

+0 .048 

(0 .042) 

CR or PR 

MT 

0 .817 

(0 .052) 

−0 .036 

(0 .052) 

+0 .018 

(0 .045) 

−0 .027 

(0 .033) 

−0 .015 

(0 .080) 

−0 .019 

(0 .038)

CR complete response, PD disease progression, PR partial response, SD 

stable disease, SE standard error. 

Conclusions. Those pts with WT KRAS mCRC who responded to pmab 

appeared to maintain their EQ-5D score over time. These results suggest 

that the relationship between QoL and tumour response in this 

treatment setting should be further investigated, perhaps in a larger 

patient population. 

0183 

Inhibition of portal branch ligation-induced extrahepatic tumor 

growth by rapamycin 

*S . Dold1 , S . Senger1,2 , B . Huber2 , J . Sperling1 , M .D . Menger2 , M .K . Schilling1 , 

O . Kollmar1 1Universität des Saarlandes, Klinik für Allgemeine Chirurgie, Viszeral-, 

Gefäß- und Kinderchirurgie, Homburg/Saar, Deutschland, 2Universität des 

Saarlandes, Institut für Klinische & Experimentelle Chirurgie, Homburg/ 

Saar, Deutschland 

Background. Portal branch ligation (PBL) is a frequently used procedure 

to achive curative resection of initially unresectable tumors by inducing 

liver regeneration in the unligated liver lobe. However, PBL induces 

tumor growth within the ligate part of the liver. The mTOR inhibitor 

rapamycin (RAPA) has been shown to exhibit potent anti-tumor activities. 

Therefore, we analyzed the effect of RAPA on tumor growth and 

angiogenesis under the conditions of PBL-associated liver regeneration. 

Materials and methods. Tumor growth was studied using GFP-transfected 

CT26.WT colorectal cancer cells implanted into the dorsal skinfold 

chamber of BALB/c-mice. Directly after tumor cell implantation, PBL 

of the left liver lobe was performed. The animals were treated daily with 

PBS as control and with RAPA (1.5 mg/kg) starting at day 0 or day 5 

after PBL (n=8 each group). Tumors were analyzed for angiogenesis and 

tumor growth via intravital fluorescence microscopy at defined time 

points until day 14 after PBL. 

Results. Extrahepatic tumor growth was markedly reduced by PBL 

compared non-PBL controls. Interestingly, RAPA treatment starting 

at day 0 significantly inhibited tumor growth compared to PBL-controls 

(1.35±0.56 mm2 vs. 3.86±1.28 mm2). RAPA treatment starting at 

day 5 did not influenced tumor growth within the observation period 

(2.98±0.35 mm2 vs. 3.86±1.28 mm2). The inhibition of tumor growth was 

associated with a significantly decreased macro and microvascular density 

within the tumor border (6.5±2.7 cm/cm2 vs. 63.0±19.4 cm/cm2) as 

well as tumor center (6.3±2.9 cm/cm2 vs. 72.4±29.8 cm/cm2) compared 

with controls. This inhibitory effect on the angiogenesis of the tumors 

was seen in both RAPA treatment groups. 

Conclusion. RAPA treatment is capable of inhibiting angiogenesis and 

tumor growth of colorectal metastasis during PBL-associated liver regeneration. 

Moreover, our experimental data indicate that an early onset 

of RAPA-therapy after PBL has a more potent anti-tumoral effect. 

0185 

After major liver resection cilostazol stimulates liver regeneration 

but not growth of residual colorectal liver metastases 

*M . Strowitzki1 , M .R . Moussavian2 , S . Dold2 , M . von Heesen2 , M .K . Schilling2 , 

M .D . Menger1 , O . Kollmar2 1Universität des Saarlandes, Institut für Klinische & Experimentelle Chirurgie, 

Homburg/Saar, Deutschland, 2Universität des Saarlandes, Klinik für 

Allgemeine Chirurgie, Viszeral-, Gefäß- und Kinderchirurgie, Homburg/ 


Background. Liver resection is still the accepted gold standard of treatment 

for liver tumours. The resectability rate for liver tumors is about 

20–30% in normal livers, but reduced in patients with impaired liver 

function caused by neoadjuvant chemotherapy, steatosis or cirrhosis. In 

spite of improvements in adjuvant chemotherapy and increasing surgical 

confidence and expertise, the parameters determining how much 

liver can be resected have remained largely unchanged. Major liver resection 

for primary or secondary liver tumors can lead to postoperative 

liver dysfunction or even liver failure. Therefore, this study analyzed 

whether cilostazol, a selective phosphodiesterase-III inhibitor, is capable 

to improve hepatic perfusion and liver regeneration after 70% hepatectomy 

and influences tumor growth of colorectal metastases within 

the remnant liver. 

Methods. Sprague-Dawley-rats were pre-treated with cilostazol (5 mg/ 

kg bw) or glucose solution. After 5 days animals underwent either 70% 

hepatectomy or sham operation. Additional animals (WAG-rats) received 

placebo- or cilostazol-treatment followed by 70% hepatectomy or 

sham operation and subcapsular implantation of 5×105 CC531-colorectal 

cancer cells. 

Results. In sham-operated animals cilostazol-treatment resulted in an 

improved hepatic blood flow and an elevated hepatic microcirculation 

(692±17 vs. 431±24aU). After hepatectomy cilostazol-treated animals 

showed improved portal venous flow and hepatic microcirculation 

(893±33 vs. 651±54aU). Liver regeneration was found enhanced by cilostazol-treatment 

over the whole observation period, as indicated by 

significantly increased number of PCNA-expressing hepatocytes (day 

3: 21±2 vs. 12±1 cells/HPF) and augmentation of recovered liver mass at 

day 6. Tumor volume in cilostazol-treated animals was not different to 

controls after 7 respectively after 14 days. 

Conclusion. We could demonstrate that cilostazol-treatment efficiently 

improves hepatic perfusion and stimulates liver regeneration after 

70% hepatectomy. No coincidental stimulation of tumor growth could 

be observed. Thus, cilostazol may represent an appropriate therapy to 

improve liver function after extended hepatectomy for colorectal liver 

metastases. 

0187 

Comparison of three putative methylation markers for the early 

detection of colon cancer 

*C . Gerecke1 , Y . Löwenstein1 , I . Fait1 , B . Scholtka1 1Universität Potsdam/IEW, Ernährungstoxikologie, Nuthetal, Deutschland 

Background. Colon Cancer is one of the most frequent occurring cancers 

in the western civilization. Thus it is one of leading causes of cancer 

related deaths. Colorectal cancer mortality can be reduced significantly 

by early detection of premalignant adenomas and early staged cancers. 

Therefore it is necessary to develop sensitive non-invasive screening 

tests. In the past few years it has become clear that abnormal hypermethylation 

of tumorsuppressor linked gene promoters, resulting in loss of 

gene expression, is one of the early events in colonic carcinogenesis. To 

evaluate a marker panel including methylated marker genes for an early 

detection of colon cancer we analyzed the methylation status of the gene 

promoters of integrin alpha subunit 4 (ITGA4), tissue factor pathway 

inhibitor II (TFPI2) and vimentin (VIM) in paired patient tissue and 

stool samples as well as in stool samples from healthy individuals. 

Methods. In this present study we analyzed samples of 4 inflamed tissue 

(IT), 13 hyperplastic polyps (HP), 50 adenomas (Ad) and 9 colorectal 

carcinomas (CRC). Additionally, stool samples derived from 5 healthy 

individuals and from 5 CRC patients were studied. The isolated genomic 

DNA was converted by sodium bisulphite treatment and subsequently 

analyzed by nested methylation-specific PCR (nMSP) encompassing 

the respective promoter regions of ITGA4, TFPI2 and vimentin. 

Results. The nMSP revealed a methylated promoter of the ITGA4-gene 

in 3/4 IT, 13/13 HP, 44/50 Ad and 8/9 CRC. In 4/5 CRC patient stool samples 

a methylated ITGA4 promoter was detected. None of the healthy 

stool samples were methylated in the ITGA4-promoter. A methylated 

TFPI2-promoter was found in 1/4 IT, 4/13 HP, 32/50 Ad and 8/9 CRC. In 

4/5 CRC patient stool samples we detected a methylated TFPI2 promoter 

as well. However, no healthy stool sample contained a methylated 


41

Abstracts 

TFPI2-promoter. A methylated VIM-promoter was detected in 3/4 IT, 

8/13 HP, 36/50 Ad and in 4/9 CRC. In stool samples from CRC patients 

we discovered in 2/5 individuals a methylated VIM-promoter whereas 

no healthy sample was methylated. 

Conclusion. Because of the high methylation frequency of inflamed tissue 

it is concluded that the methylation analysis of VIM and ITGA4 is 

no suitable biomarker for early detection of colon cancer and premalignant 

adenomas. However, our findings suggest that the TFPI2 methylation 

is a proper biomarker with a good specificity and sensitivity. 

0188 

Quality of life and intestinal symptoms and after multimodal 

therapy of rectal cancer 

*H . Geinitz1 , A . Seidl1 , R . Thamm1 , R . Rosenberg2 , F . Lordick3 , M . Fuchs4 , 

W . Heitland5 , F . Zimmermann1 , M . Molls1 1Technische Universität München, Klinik für Strahlentherapie, München, 

Deutschland, 2Technische Universität München, Chirurgische Klinik, 

München, Deutschland, 3Technische Universität München, III . Medizinische 

Klinik, München, Deutschland, 4Klinikum München Bogenhausen, Klinik für 

Gastroenterologie, München, Deutschland, 5Klinikum München Bogenhausen, 

Klinik für Chirurgie, München, Deutschland 

Purpose and objective. This cross sectional study was carried out in order 

to assess quality of life (QOL) and intestinal symptoms and after 

multimodal therapy of locally advanced rectal cancer. 

Materials and methods. 216 patients with neoadjuvant or adjuvant radiochemotherapy 

and surgery for stage III rectal cancer were assessed at a 

median of 62 months (16–137 m.) after the end of radiochemotherapy. 

Intestinal symptoms and fecal continence were evaluated with standardized 

instruments. Quality of life assessment was carried out with 

the EORTC QLQ-C30 and the colorectal module CR38. 

Results. 164 patients had received preoperative RChT (45 Gy with continous 

5-FU) and 52 patients postoperative RChT (50.4 Gy with 5-FU 

continously or bolus). As compared to the age and gender adjusted German 

general population (Schwarz and Hinz; Eur J Cancer 2001) quality 

of life was significantly compromised in younger patients (50–60 years 

old) affecting in particular role functioning, emotional functioning, 

cognitive functioning, social functioning and fatigue, while in older 

patients (>60 y.) QOL-reduction was less pronounced and involved 

mainly social functioning. The most prevalent fecal symptoms were: 

diarrhoea (80%), flatulence (75%) and tenesmus (15%). In patients without 

a colostomy (n=152) only 18% reported a perfect fecal continence. 

Incontinence involved mainly gas (73%) and liquid stool (66%) with 

16% reporting incontinence for solid stool. 46% of the non-colostomy 

patients reported to wear pads because of fecal incontinence and 49% 

were unable to delay defecation for more than 15 minutes. Patients with 

low lying tumors (p=0.006) and those with reoperation because of 

anastomotic leakage (p=0.041) experienced more incontinence. Global 

QOL (p=0.041), physical functioning (p

and NAF were detectable by ICAM-1 staining. In 15 of 16 TAF cultures 

ICAM-1 was higher expressed compared to corresponding NAF cultures. 

After stimulation of cultures with interleucin-1β also 14 of 16 TAF 

cultures presented with higher ICAM-1 levels than corresponding NAF 

cultures. Performing an U937 adhesion assay also unstimulated and 

with tumor necrosis factor stimulated TAF cultures showed a higher 

adherence than corresponding stimulated and unstimulated NAF cultures. 

Conclusions. The isolation of TAF and NAF is possible and fibroblasts 

present with differences although in vitro cultivation. Isolated fibroblast 

present as a useful tool for further functional investigations of the desmoplastic 

tissue of CRC. 

0222 

cDNA-microarray gene expression analysis in different malignant 

pancreatic cancer cell lines after induction of apoptosis 

induced by Taurolidine (TRD) 

*M . Buchholz1 , A . Flier1 , S . Hahn2 , D . Bulut3 , W . Uhl1 , A . Chromik1 1 2 St . Josefs Hospital, Chirurgie, Bochum, Deutschland, Ruhr Universität, 

Bochum, Deutschland, 3St . Josefs Hospital, Bochum, Deutschland 

Introduction. The originally anti-infective agent Taurolidine (TRD) has 

been shown to have cell death inducing properties, but the mechanism 

of its action is largely unknown. The aim of this study was to identify 

potential common target genes modulated at the transcriptional level 

following TRD treatment in different malignant pancreatic cancer cell 

lines 

Material and methods. Five different malignant human pancreatic cancer 

cell lines (AsPC-1, BxPC-3, HPAF II, MiaPaca-2 and Panc1) were 

incubated with TRD (250 µmol/l) and Povidon 5%, which served as 

control. After 2 h incubation, gene expression analysis was carried out 

using the Agilent -microarray platform to indentify early genes which 

displayed conjoint regulation following the addition of TRD in all pancreatic 

cancer cell lines. Agilant’Feature Extraction Software was used 

to analyze acquired array images. Further data processing was performed 

using the GeneSpring GX11.01 software package. Following the 

data sets were reduced by filtering the raw signal intensity value ≥50 

and a quantile normalization of raw data. (T-test was used to examine 

the hypothesis that there was no difference in expression between the 

TRD treatment group and the Povidon control group). Candidate genes 

were analyzed by Ingenuity Pathways Analysis and selected genes were 

validated by qRT-PCR and Western Blot. 

Results. Among cell death associated genes with the strongest regulation 

in gene expression (factor x5–x60), we identified a broad range of 

pro-apoptotic proteins, e.g. pro-apoptotic transcription factors (EGR1, 

EGR2, EGR4, ATF3) as well as genes involved in proliferation (c-FOS, 

DUSP1). Furthermore, inhibitors of the JAK/STAT signaling pathway 

(SOCS1), genes involved in oxidative stress response (ADM) as well 

as pro-apoptotic proteins of GADD family (GADD45B, GADD45A, 

GADD34) were identified. The results of the validation by qRT-PCR and 

Western Blot confirmed the prior results. 

Conclusions. This is the first conjoint analysis of potential early target 

genes of TRD which was performed simultaneously in different malignant 

pancreatic cancer cell lines. The increased expression of several 

pro-apoptotic proteins of various origins indicates that TRD might be 

involved in different signal transduction pathways leading to apoptosis 

in pancreatic cancer cell lines. However, further functional studies are 

necessary to elucidate the exact mechanism and relative contribution of 

death inducing pathways of TRD. 

0230 

Molecular repair mechanisms and chemoresistance in hyperthermic 

intraperitoneal chemotherapy in patients with peritoneal 

carcinosis 

*M . Vetterlein1 , M . Lazariotou1 , T . Grimmig1 , N . Matthes1 , M . Faber1 , C .-T . Germer2 

, J . Pelz2 , A .M . Waaga-Gasser1 , M . Gasser2 1Universitätsklinikum Würzburg, Chirurgische Klinik I, Molekulare Onkoimmunologie, 

Würzburg, Deutschland, 2Universitätsklinikum Würzburg, 

Chirurgische Klinik I, Würzburg, Deutschland 

Background. In patients with isolated peritoneal carcinosis (PC) of 

gastric, colorectal and ovarian cancer hyperthermic intraperitoneal 

chemotherapy (HIPEC) represents a promising treatment option integrated 

into multimodal concepts. We analyzed relevant heat shock proteins 

(HSPs) that confer resistance to physical stress like hyperthermia 

as well as specific multidrug resistence (MDR) genes in patients with 

PC. 

Methods. Patients with different adenocarcinomas and additional PC 

that underwent HIPEC therapy between 09/09 and 03/11 in our department 

(gastric, colorectal and ovarian cancer) were included in the study. 

HIPEC therapy was performed under specific conditions (1hr permanent 

chemotherapeutical flux via external pump into the abdominal cavity 

after resection of relevant tumor masses with elevated temperature 

up to 43°C). Tumors before and after HIPEC therapy were analyzed for 

HSPs, ABC transporter and CD133 expression by immunohistochemistry, 

Western Blot, and RT-qPCR. Additionally, HT29 tumor cells were 

exposed in vitro to different conditions of hyperthermia up to 43°C for 

60 minutes and comparably analyzed. Tumor cells were counted and 

studied for apoptosis. 

Results. HSP70/72, HSP90 and CD133 expression was upregulated in the 

investigated tumors, in particular post HIPEC therapy. Upregulated 

protein and gene expression was also shown for MDR genes ABCB5, 

ABCG2 and ABCC5. Hyperthermia induced upregulated protein and 

gene expression in HT29 tumor cells dependent on incubation temperature, 

mainly for HSPs observed in western blot, immunohistochemistry 

and RT-qPCR. Furthermore, cell viability decreased with increasing 

incubation temperature. 

Conclusions. Therapeutic approaches like HIPEC to achieve antiproliferative 

and apoptosis inducing cellular effects in patients with PC seem 

to be negatively influenced by highly conserved HSP mechanisms as 

well as multidrug resistance genes. Studying HSP and MDR expression 

profiles both in patient tumors and in vitro are valuable tools to further 

clarify the effects of hyperthermia and chemotherapeutical agents in 

context with the treatment of HIPEC therapy in the affected patients. 

0232 

PDGF stimulates proliferation in colorectal cancer 

*M . Faber1 , N . Matthes1 , M . Kim2 , T . Grimmig1 , C .-T . Germer2 , M . Gasser2 , 

A .M . Waaga-Gasser1 1Universitätsklinikum Würzburg, Chirurgische Klinik I, Molekulare Onkoimmunologie, 



Background. Platelet derived growth factor (PDGF) plays an important 

role in angiogenesis of several cancer types. It induces cell migration 

and proliferation in stromal cancer tissue and is a key target in cancer 

metastasis therapy. Aim of our study was to analyze the Mitogen-activated 

protein kinase (MAPK)-pathway in colon cancer cells stimulated 

by PDGF for putative future therapeutic interventions in colorectal cancer 

(CRC). 

Methods. The human colorectal cancer cell line HT-29 was cultured 

and stimulated with PDGF-BB over the time periods of 5, 10, 15, 

30 and 60 minutes. Cell protein and RNA extracts were analyzed by 

Western Blot and RT-PCR for PDGF-receptor-β and for proteins of the 

MAPK-pathway. To determine effects on proliferation HT-29 cells were 


43

Abstracts 

cultured on a Matrigel layer and stimulated with PDGF over two weeks 

and cell count and colony formation were analyzed. 

Results. Western blot analysis and RT-PCR revealed no relevant PDGFreceptor-β 

in HT-29 cells. Nevertheless, stimulation of PDGF-BB resulted 

in an upregulation of downstream MAPK-pathway events in 

Western Blot analysis and in an increased proliferation in the matrigel 

assay. After two weeks of stimulation with PDGF cell count as well as 

colony forming significantly increased compared to unstimulated cell 

populations. 

Conclusions. PDGF-receptor-β expression has been described in cancer 

stromal tissues. We could show for the first time that in the absence 

of its receptor, stimulation with PDGF-BB results in activation of the 

MAPK-pathway and consecutive proliferation in colon cancer cells. 

Our results suggest that PDGF activates MAPK and cancer cell proliferation 

by an alternative signaling route. 

0245 

CAES/ CAMIC- Zentralregister: “Okkultes Gallenblasenkarzinom”. 

Analyse der Prognosefaktoren nach Auswertung von mehr als 

700 Fällen 

*T . Goetze1 , V . Paolucci1 1Ketteler-Krankenhaus, Chirurgische Klinik, Offenbach, Deutschland 

Background. The incidental gallbladder carcinoma (IGBC) is a cancer 

first discovered by the pathologist after cholecystectomy. The indication 

for the operation was a benign disease. The indication for early radical 

re-resection (ERR) is debated in the recent literature and the S3 guidelines. 

According to the S3 guidelines a ERR is recommended in T2 and 

more advanced carcinomas. Recent data of the literature, the German 

Registry, and even international guidelines, e.g. National Comprehensive 

Cancer Networks show that patients with T1b carcinomas do profit 

from an ERR. Another important prognostic factor that has to be discussed 

in context with ERR is the lymph node status. 

Methods. For data analysis we used „The German Registry“ ( CAES/ 

CAMIC- Zentralregister: „Okkultes Gallenblasenkarzinom“, der deutschen 

Gesellschaft für Chirurgie) . For getting the data a questionnaire 

was sent to all German surgical clinics. The data are actualised in a period 

of 3 months. All patients of the registry have been treated according 

to the S3 guidelines. 

Results. To date more than 700 patients have been registered and 684 

cases of IGBC are calculated by the statistics. In 29 patients with T1a 

carcinomas there was no ERR. In 6 cases of T1a carcinomas there was 

an ERR. In 28 of 84 patients with T1b tumors there was a ERR. The 5 

year- survival rate shows a significant prognostic survival benefit for 

T1b- tumors with ERR, but there is no prognostic benefit for T1a carcinomas 

after ERR. All of the liver resections have been combined with a 

lymph node dissection of hepatoduodenale ligament. The liver resection 

in cases of T1b tumors was 16× a wedge resection, 6× a IVb/V resection 

and 5× another kind liver resection technique was used. The wedge resection 

shows a 5 year survival of 84%, the IVb/V resection 75%. Patients 

with positive lymph nodes show a worse prognosis compared with nodal 

negative IGBC’s in all stages. 

Discussion. The analysis of more than 700 cases of IGBC of the German 

registry shows, a significant benefit for T1b patients with ERR. For 

patients with T1a carcinomas a simple cholecystectomy is enough. The 

positive nodal status is a significant negative prognostic factor in T1–3 

tumors. Patients with radical re-resection show always a better survival 

than without. Liver resection and lymph node dissection of the hepatoduodenal 

ligament has to be highly recommended up to T1b. 


0256 

Analysis of tumor cell dissemination gives evidence for peripheral 

tumor initiating cells in colorectal cancer 

*M . Kim1 , M . Frank2 , N . Frank2 , T . Grimmig3 , C .-T . Germer1 , A .M . Waaga-Gasser3 

, M . Gasser1 1Universitätsklinikum Würzburg, Chirurgische Klinik I, Würzburg, Deutschland, 

2Children‘s Hospital, Harvard Medical School, Boston, USA, 3Universi tätsklinikum Würzburg, Chirurgische Klinik I, Molekulare Onkoimmunologie, 

Würzburg, Deutschland 

Background. Recent findings suggest that tumor initiating cells beside 

differentiated tumor cells are responsible for disseminated tumor disease. 

This study evaluates CD133, a marker described for tumor initiating 

cells, together with ABCB5 and ALDH1 as putative additional markers 

in peripheral blood and bone marrow of patients with colorectal cancer 

(CRC). 

Methods. Expression of CD133, ABCB5, a chemoresistance mediator, 

ALDH1, and Lgr5 were analyzed in cells from peripheral blood of patients 

with CRC (n=105, UICC stages I–III) and completed 5-year followup 

by RT-qPCR. A cohort of 26 healthy individuals served as controls. 

Bone marrow aspirates (n=24) were analyzed for further evidence of 

cancer cell migration in this compartment. 

Results. CD133 and ABCB5 expression in peripheral blood cells was 

upregulated in patients with CRC even at early tumor stages (p

clinical tumors less present. Further in vitro analysis of a specifically 

induced expression seems to be relevant to develop clinical strategies 

for increased tumor cell apoptosis in pancreatic cancer with detected 

increased TLR expression patterns. 

0288 

Outcome of surgical and interventional therapy of patients with 

hepatocellular carcinoma 

*T . Förtsch1 , W . Hohenberger1 , S . Merkel1 , V . Mueller1 , R . Croner1 1Universität Erlangen, Chirurgische Klinik, Erlangen, Deutschland 

Introduction. Hepatocellular carcinoma (HCC) represents the fifth most 

common malignant tumor worldwide with a rising incidence especially 

in the western countries. Our retrospective analysis compares outcome 

and survival of patients with HCC, who were treated at the department 

of surgery of University of Erlangen from 1998–2008, by the means of 

different possibilities of treatment. In addition risk factors like pT classification, 

tumor size and lymph node dissection are tested for their prognostic 

influence on survival. 

Material and methods. At our department 260 patients (231 male, 29 

female) with HCC were treated from 1998–2008. Thereof 96 patients 

received a removal of the tumor by liver resection; on 23 patients with 

small HCC a liver transplantation (LTx) was performed. 71 patients were 

treated by an interventional therapy (radiofrequency ablation, chemoembolization). 

Because of advanced liver cirrhosis or advanced tumor 

stage only a supportive palliative therapy was done in 70 patients. 

Results. The 1-, 3- and 5-year survival rates for all patients who underwent 

surgery amounted to 75%, 50% and 37%. Comparing the group of 

liver resected patients with patients who underwent LTx, the survival 

rates resulted in 70%, 46% and 32% vs. 85%, 64% and 59% (log-rank test 

p=0.007). In patients who have received interventional therapy without 

surgical resection, the 1-, 3-, and 5-year survival rates were 58%, 25% and 

17% (log-rank test compared to all operated patients p

Abstracts 

Median disease free survival (DFS) was 23.2 months revealing 3700 differentially 

regulated probes (q≤0.005). 

Conclusion. Whole genome expression analyses enable a correct prediction 

of lymph node negativity after preoperative RCT in 81%. Although 

validated by LOOCV these data still need an independent validation 

that is currently ongoing. The high number of differentially regulated 

probes for DFS is promising to find a predictive profile. 

0311 

Influence of multimodality treatment on the immune system of 

patients with esophageal cancer 

*T . Herbold1 , E . Bollschweiler1 , A . Worring1 , H . Alakus1 , W . Schröder1 , A . Hölscher1 

, R . Metzger1 1Universität zu Köln, Allgemein-, Viszeral- und Tumorchirurgie, Köln, 

Deutschland 

Introduction. Neoadjuvant radiochemotherapy (RTx/CTx) is an important 

part of the multimodality treatment in locally advanced esophageal 

cancer. Analyzed were the effects of neoadjuvant radiochemotherapy 

on the immune status of patients with esophageal cancer. 

Patients and methods. In this prospective study 86 patients (m: 71, w: 15) 

with locally advanced esophageal cancer (uT3/4) were included. Median 

age was 59 years (min: 31, max: 78). 27 patients had a squamous cell carcinoma 

(SCC), 59 patients an adenocarcinoma (AC) of the esophagus. 

All patients underwent induction therapy with 5-FU, CDDP and 40 Gy. 

Analysis of the cellular immune system (leucocytes, lymphocytes, CD3- 

, CD4-, CD8-, CD16-, CD19-, CD25-, CD56-, HLA-DR-bearing cells) 

was performed before and 3 weeks after induction therapy. 

Results. The neoadjuvant radiochemotherapy resulted in a significant 

decrease of leucocytes, lymphocytes and subgroups. Pathologic low values 

after induction therapy were detected in 19% of the patients for leucocytes, 

in 20% for thrombocytes, in 61% for lymphocytes, in 76% for B 

cells, in 37% for T cells, in 31% for T helper cells, in 33% for T suppressor 

cells, in 30% for NK cells. The posttherapeutic results reflect the preoperative 

status of the cellular immune system. 

Conclusion. In our cohort of patients with locally advanced esophageal 

cancer (uT3/4) neoadjuvant radiochemotherapy results in a significant 

decrease of immune competent cells particularly in lymphocytes. However, 

we didn’t observe any case of aplasia caused by induction therapy. 

In consideration of a demanding surgical procedure this would be 

unfavorable. 

0323 

GPI-anchored tissue inhibitor of matrix metalloproteinase-1 

(TIMP-1) inhibits tumor growth in fibrosarcoma and pancreatic 

cancer 

*Q . Bao1 , H . Niess1 , R . Djafarzadeh2 , Y . Zhao1 , B . Schwarz1 , K .-W . Jauch1 , 

P .J . Nelson2 , C .J . Bruns1 1Campus Großhadern, LMU, Department of Surgery, Munich, Deutschland, 

2LMU, Medical Policlinic, Clinical Biochemistry Group, Munich, Deutschland 

Background. The family of tissue inhibitors of metalloproteinases 

(TIMPs) exhibit diverse physiological/biological functions including 

the moderation of tumor growth, metastasis, and apoptosis. TIMP-1 

is a secreted protein that can be detected on the cell surface through 

its interaction with surface proteins. The diverse biological functions 

of TIMP-1 are based, in part, on the kinetics of TIMP-1/MMP/surface 

protein interactions. Proteins anchored by glycosylphosphatidylinositol 

(GPI), when purified and added to cells in vitro, are incorporated into 

their surface membranes. A GPI anchor was fused to TIMP-1 to generate 

a reagent that could be added directly to cell membranes and thus 

deliver defined concentrations of TIMP-1 protein on any cell surface independent 

of protein-protein interaction. 


Methods. We produced and purified a fusion protein based on the tissue 

inhibitor of matrix metalloproteinase-1 linked to a glycosylphosphatidylinositol 

anchor (TIMP-1-GPI). TIMP-1-GPI was exogenously added 

to the human fibrosarcoma cell (HT1080) and murine pancreatic cancer 

cells (Panc02) culture medium. Fluorescent staining assays, proliferation 

assays, clonogenic assays, migration assays, and apoptosis assays 

were performed comparably with rhTIMP-1 and vehicle treatment. In 

a homogenetic subcutaneous pancreatic cancer mouse model, TIMP- 

1-GPI, rhTIMP-1, and vehicle were applied locally, and their effects on 

tumor growth were investigated. 

Results. TIMP-1-GPI showed better incorporation with cell membranes 

compared to TIMP-1. As the concentration of TIMP-1-GPI increased 

(2–14 ng/ml), the proliferation rates of both cancer cell lines were significantly 

inhibited. The inhibition effects were enhanced by incubation 

time prolongation. While control rhTIMP-1 protein did not significantly 

affect proliferation of HT1080 and Panc02 cells at the concentration 

(14 ng/ml) tested, the GPI-anchored TIMP-1 protein showed a pronounced 

suppression of cancer cell clone formation and migration. Furthermore, 

TIMP-1-GPI induced significant higher percentage of apoptotic 

cells than rhTIMP-1 and control group, the sequentially combination of 

TIMP-1-GPI and chemotherapy (Doxorubicin) had synergetic effects of 

inducing apoptosis. In addition, TIMP-1-GPI can inhibit HT1080 sidepopulation 

cells with Hoechst staining. Treatment of Panc02 tumors 

implanted in C57BL/6 mice with local applied TIMP-1-GPI, control 

rhTIMP-1 protein, or vehicle showed a significant inhibition of tumor 

growth following treatment with TIMP-1-GPI. 

Conclusion. Compared with rhTIMP-1, exogenous administration of 

TIMP-1-GPI result in transient morphological changes of tumor cells 

including better incorporation of TIMP-1 in the cell membrane, pronounced 

inhibition of proliferation, clone formation, migration, and 

enhancement of side-population cells, inducing more apoptotic cells 

either as single reagent or combined with chemotherapy. In vivo, TIMP- 

1-GPI significantly inhibited tumor growth. GPI-anchored TIMP-1 may 

represent a more effective version of the protein for cancer therapy. 

0344 

Ulcerative colitis-associated carcinogenesis depends on alternatively 

activated “M2 macrophages” – from mice to men 

R . Kesselring1 , M . Martin1 , P . Ruemmele2 , H .J . Schlitt1 , *S . Fichtner-Feigl1 1Universität Regensburg, Klinik und Poliklinik für Chirurgie, Regensburg, 

Deutschland, 2Universität Regensburg, Institut für Pathologie, Regensburg, 

Deutschland 

The pathogenesis of human ulcerative colitis (UC) is characterized by 

the presence of IL-13-producing Natural Killer T cells (NKT cells). One 

major complication of UC is the development of colitis-associated colorectal 

cancer. In these studies we determined the role of alternatively 

activated „M2 macrophages“ in a new mouse model of colitis-associated 

carcinogenesis based on chronic Oxazolone-colitis in combination with 

an initial i.p. azoxymethane (AOM) injection. Further, we verified these 

results through the immunological analysis of surgical specimens obtained 

from 6 patients with UC-associated colon cancer. 

We could show that chronic Oxazolone-colitis was mediated by colonic 

alpha-galactosyl-ceramide+CD1+ NKT-cells producing IL-13 and therefore 

resembles the immunological characteristics of human UC. Colon 

cancer development in this model was dependent on the presence of 

F4/80+CD11bhighGr1low macrophages producing IL-6 and EGF. Those 

cells inherited phenotypic characteristics of IL-13-stimulated alternatively-activated 

“M2 macrophages”. To elucidate the importance of these 

“M2 macrophages”, we conducted bone marrow chimera studies and 

demonstrated that innate immune signaling through MyD88 in “M2 

macrophages” is the key event for the production of tumor supporting 

factors like IL-6 and EGF. In surgical specimens obtained from patients 

with UC-associated colon cancer we verified those experimental findings. 

We consistently found a dense accumulation of IL-13-producing

NKT cells inside the tumors. In addition, in this IL-13-dominated tumor 

micromilieu CD14+ and CD68+ antigen-presenting cells accumulated 

intensively and those antigen-presenting cells demonstrated an alternatively 

activated “M2 phenotype” by the expression of CD163 and CD205. 

In conclusion, we could demonstrate that in an experimental UC model, 

as well as in human UC, pathogenic IL-13-producing NKT cells 

accumulate in the tumor micromilieu of UC-associated colon cancers. 

This immunologic situation inside the tumor microenvironment of 

mice and men induces tumor promoting M2 macrophages. Therefore 

M2 macrophages represent a potential target for future therapeutic strategies. 

0353 

Pancreatic cancer cells expressing stem cell markers survive 

Gemcitabine treatment in vitro 

*K . Quint1 , P . Di Fazio1 , R . Montalbano1 , M . Ocker1 1Philipps Universität Marburg, Institut für Chirurgische Forschung, Marburg, 

Deutschland 

Introduction and objectives. The prognosis of pancreatic carcinoma patients 

remains among the worst of all solid tumors. Response rates to 

the standard chemotherapeutic regimens remain low and tumors recur 

frequently. In recent years, subpopulations of cells have been identified 

in various solid tumors, which express stem cell associated markers and 

are associated with increased resistance against radiochemotherapy. In 

this study, we address the question whether chemotherapy leads to a 

selection of resistant cancer stem cells and whether the epithelial-tomesenchymal 

transition (EMT) is associated with chemoresistance. 

Materials and methods. Panc-1 and Capan-1 cells were continuously incubated 

with 10 µM Gemcitabine for up to 6 days. Vital cells were counted 

after one, 3 and 6 days after trypan blue staining. Gene expression of 

the early developmental markers and stem cell associated genes PDX-1, 

SHH, CD24, CD44, CD133, EpCAM, CBX7 and OCT4, EMT markers 

Slug, Snail and Twist were quantified using qPCR. PDX-1, SHH, CBX7, 

Oct-4, CD133, Ki-67, E-Cadherin and β-catenin were stained by immunocytochemistry. 

Results. After 3 days, Gemcitabine treatment reduced viable cell numbers 

to less than 10% of the untreated controls. mRNA levels of all investigated 

genes showed a time-dependent increase in both cell lines 

compared to the untreated controls (normalized n-fold gene expression 

for Panc-1/Capan-1, respectively): PDX1: 13.3/4.1; SHH: 24.1/2.0; CD24: 

1.7/47.3; CD44: 17.4/3.2; CD133: 20.2/7.8; EpCAM: 3.1/15.9; CBX7: 3.1/3.5; 

OCT4: 4.2/13.4, Snail: 6.4/6.4, Slug: 15.2/3.5. Immunocytochemistry confirmed 

gene expression for Oct-4, SHH, PDX-1, CD133, E-Cadherin and 

β-catenin. The majority of surviving cells stained positive for Ki-67. 

Conclusion. Cells surviving six days of high-dose Gemcitabine treatment 

express increased levels of stem cell and EMT markers and retain their 

proliferative capacity. These data suggest a selection of cancer stem cells 

which could be responsible for tumor recurrence in the clinical setting. 

0355 

Mutation analysis of the metastasis-inducing gene MACC1 and 

association with colon cancer metastasis 

*F . Schmid1 , K . Klockmeier2 , S . Burock3 , P .M . Schlag3 , U .S . Stein4 1 2 Max-Delbrück-Center for Molecular Medicine, Berlin, Deutschland, Freie 

Universität Berlin, Berlin, Deutschland, 3Charité Comprehensive Cancer 

Center, Berlin, Deutschland, 4Experimental and Clinical Research Center, a 

joint cooperation between the Charité Medical Faculty and the Max-Delbrück-Center 

for Molecular Medicine, Berlin, Deutschland 

Colorectal cancer is one of the most common cancer diseases in the 

Western world. About 90% of cancer deaths arise from the formation 

of metastases. Recently, the new gene MACC1 (metastasis-associated 

in colorectal cancer 1) was identified as a prognostic marker for colon 

cancer metastasis. Tumors, which developed later metastases, showed a 

significantly higher MACC1 expression compared to non-metastasizing 

tumors. The 5-year survival rate for patients with a high MACC1 expression 

was only 15% compared to 80% for subjects with a low MACC1 

expression. It was shown that MACC1 is a key-regulator of Met (met 

proto-oncogene) expression that plays a decisive role in epithelial-mesenchymal 

transition, cell motility, invasiveness and metastasis. In this 

study, we analyzed the mutation status of the genes MACC1 and Met in 

human colorectal tumors. We wanted to evaluate if mutations in these 

genes are associated with expression modulation of MACC1 and Met, 

as well as with clinicopathological data, particularly with the metastasis 

formation. We sequenced the genomic coding exons of MACC1 and the 

exons of the juxtamembrane and the tyrosine kinase domain of Met. We 

detected in a test set of 60 tumors the Met variants T1010I and R988C 

in only two tumors. We identified in the same test set three MACC1 

single nucleotide polymorphisms (SNPs): L31V, S515L and R804T. Additionally, 

we screened them in a validation set of further 94 tumors. We 

found them almost as frequent as in the test set. L31V occurs in 13%, SNP 

S515L in 48% and SNP R804T in 84% of all 154 tumors. We correlated 

the MACC1 SNPs to sex, age, tumor grade, tumor stage, lymph node 

metastasis and metachronous metastases and did not find a significant 

correlation. In order to evaluate the biological abilities of the SNPs we generated 

plasmids containing MACC1 SNPs by site-directed mutagenesis. 

Colon cancer cells were transfected with these constructs. MACC1 SNPs 

had no impact on the migratory, proliferative or wound healing abilities 

of the cells. So far, MACC1 mutation analysis even when combined with 

MACC1 expression data does not improve the prediction of colon cancer 

metastasis. 

0365 

Capecitabine-induced cardiotoxicity associated with complete 

remission in a rectal cancer patient treated with neoadjuvant 

radio-chemotherapy 

*N . Henze1 , J . Kuhfahl1 , S . Wagner1 1Klinikum Deggendorf, Med . Klinik II, Deggendorf, Deutschland 

Background. Neoadjuvant radiochemotherapy is the therapeutic standard 

in patients with locally advanced rectal cancer. Infusional or oral 

5-FU-derivatives form the basis of chemotherapy. Cardiotoxicity is a 

rare but clinically important side effect of 5-FU. Here we report a case 

with complete histomorphologic remission despite dose reduction caused 

by severe capecitabine-induced cardiotoxicity. 

Case report. A 63-year-old male patient (80 kg, 168 cm) with rectal 

cancer (uT3, G3, uN+, cM(HEP); UICC IV) and six hepatic metastatic 

cancer lesions (maximum diameter 32 mm) was presented to the local 

tumour board. A curatively-intented neoadjuvant radiochemotherapy 

with capecitabine and oxaliplatin combined with 50.4 Gy pelvine radiation 

was recommended as consensus decision. Five days after initiation 

of capecitabine (3000 mg/d) rapidly increasing cardiostenotic 

pain and dyspnoea developed. Coronary artery disease was excluded by 

percutaneous coronary arterial angiography. Stenocardiac symptoms 

dissolved after stopping of cabecitabine. Thus the diagnosis of cabecitabine 

induced coronary spasms was established. Re-treatment with 

cabecitabine in a 50% reduced dose was started using prophylaxis with 

nitrate. Oxaliplatin was given in unchanged dosage. Neoadjunvant radiochemotherapy 

then could be applied as planned without any further 

complaints. Total mesorectal excision (TME) and simultaneous hepatic 

resection of all intraoperatively detectable lesions was performed [ypT0, 

yV0, yL0, yN0 (0/15)]. Histopathologic examinations revealed no vital 

cancer cells in colonic and hepatic resection material. 

Conclusion. Capecitabine may rarely induce coronary spasms. After 

exclusion of coronary artery disease, therapy can be restarted at individually 

adapted dose. Despite dose reduction complete remission may 

be induced which could suggest a special tumour response to 5-FU in 

such patients. 


47

Abstracts 

0385 

Immune status in patients with esophageal squamous cell carcinoma 

and adenocarcinoma 

*R . Metzger 1 , E . Bollschweiler 1 , T . Herbold 1 , W . Schöder 1 , A . Worring 1 , 

H . Alakus 1 , A .H . Hölscher 1 

1 Uniklinik Köln, Allgemein-, Viszeral- und Tumorchirurgie, Köln, 

Deutschland 

Introduction. Esophageal cancer comprises the tumor entities squamous 

cell carcinoma (SCC) and adenocarcinoma (AC) of the esophagus. 

Epidemiology, etiology and tumorbiology are different in both SCC 

and AC. Consequently the two histological subtypes are considered to 

be different tumors. Patients with AC usually are overweight and report 

on a long history of reflux. Contrary, patients with SCC usually are smokers 

and have an abuse of alcohol leading to cirrhosis and malnutrition. 

The immune status was analyzed and compared in patients with SCC 

and AC; the influence of alcohol and malnutrition was evaluated. 

Patients and methods. In this prospective cohort study 86 patients 

(m: 71, w: 15) with locally advanced esophageal cancer (uT3/4) were included 

so far. Median age was 59 years (min: 31, max: 78). 27 patients 

had SCC, 59 patients had AC. As part of the initial staging comparative 

analysis of the cellular immune status (leucocytes, lymphocytes, CD3-, 

CD4-,CD8-, CD16-, CD19-, CD25-, CD56-, HLA-DR-bearing cells) was 

performed in all patients. 

Results. Pretherapeutic values were detected in a pathological range in 

3.5% oft he patients for leukocytes, in 3.5% for thrombocytes, in 7% for 

lymphocytes, in 7% for B cells, in 5.8% for T cells, in 3.5% for T helper 

cells, in 11.6% for T suppressor cells, in 5.9% for NK-cells. 

Conclusions. Despite a locally advanced oncological disease and different 

risk factors the immune system in patients with esophageal cancer 

was not significantly compromised. Comparing the different tumor 

subtypes SCC and AC no significant difference was detectable regarding 

the immune system. 

0395 

Cancer stem cells and chemoresistance in oesophageal cancer 

*Y . Zhao1 , B . Schwarz1 , S . Gros2 , A . Renner1 , J . Mysliwietz3 , J . Ellwart3 , P . Camaj1 

, Q . Bao1 , E . Yecebas2 , J . Izbicki2 , C . Bruns1 1 2 Klinikum Großhadern, LMU Munich, Munich, Deutschland, Department of 

Surgery, University Hamburg-Eppendorf, Hamburg, Deutschland, 3Institute of Molecular Immunology, Helmholtz Center for Environment and Health, 

Munich, Deutschland 

Introduction. Side population (SP) cells – potential cancer stem cells 

(CSC) – are known to be resistant to chemotherapy and more likely to 

cause epithelial-to-mesenchymal transition (EMT). We examined the 

existence of the SP subpopulation in 5 human oesophageal cancer cell 

lines. In addition, corresponding 5-FU, Cisplatin and Sorafenib resistant 

cell lines were developed in order to evaluate the potential contribution 

of SP-CSC to chemotherapy resistance of oesophageal cancer. 

Methods. OE19, OE21, OE33 and PT1590 (derived from a primary tumor) 

as well as LN1590 (derived from a corresponding lymph node with 

micro-metastasis) were analyzed in this study. Cells resistant to 5-FU, 

Cisplatin, and Sorafenib were identified via IC-50 determination after 

long-term in vitro exposure. The SP subpopulation was detected and 

sorted by Hoechst 33342 staining as previously described. ABCG2 and 

CD133 expression was detected by FACS, immunofluresence staining, 

and RT-PCR in both SP and Non-SP populations and EMT markers (E- 

Cadherin, ZEB1 and Vimentin) were evaluated at the protein level. 

Results. Five esophageal cell lines showed different chemo-sensitivity 

and processed different metastatic potential in vitro. Neither LN1590 

nor PT1590 had detectable SP cells, while the percentage of SP cells in 

OE19, OE21, and OE33 cells was 17.07%, 0.83% and 8.82%, respectively. 

Sorted OE19 SP cells were more resistant to 5-FU and Cisplatin than 

OE19 non-SP cells. Colony formation assay showed significant higher 


clonogenic capabilities of the SP population in OE19, OE21, and OE33. 

All chemotherapy-resistant oesophageal cell lines contained an enriched 

SP subpopulation with enhanced efflux capacity. 

Conclusions. Further in vivo studies are necessary to elucidate SP stemlike 

characteristics. SP cells purified from oesophageal cancer cell lines 

harbor cancer stem-like properties and may be related to metastasis, 

therapeutic-resistance, and EMT stimulation in oesophageal carcinoma. 

Identifying new molecular targets against chemotherapy resistant 

CSCs might potentially result in more effective anti-cancer strategies. 

0398 

Measurements of 5-FU level in serum of patients with gastrointestinal 

cancer: 5-FU levels in blood reflect 5-FU dose applied 

(24 h CIV) Response to 5-FU therapy reflects AUC values and 5-FU 

dosage 

*M . Blaschke1 , M . Nischwitz1 , G . Ramadori1 , S . Cameron1 1UM Göttingen, Gastroenterologie und Endokrinologie, Göttingen, 

Deutschland 

Introduction. 5-Fluorouracil (5-FU) is the base of most combination chemotherapies 

for gastrointestinal tumors. It is generally well tolerated, 

but side-effects might require dose-adjustment. As chemotherapy-induced 

adverse events might not be specific for the 5-FU component of 

the chemotherapy-combination, the knowledge of 5-FU serum levels 

might help to attribute these side effects to the 5-FU compound. 

Methods. 5-FU serum levels (n=230) in 30 patients with gastrointestinal 

cancer treated with 5-FU containing infusional therapy were monitored 

using the Saladax 5-FU PCMTM- Immunoassay. Patients received 

different 5-FU regimens based on a 24 or 48-hour AIO treatment-schedule 

using a Baxter pump. Blood was taken before and towards the end 

of the infusion (21-23h), when 5-FU concentrations are at a steady-state 

level. In 14 patients long term measurements of 5-FU levels over up to 

50 weeks and up to 18 measurements per patient were obtained. 

Results. Care has to be taken with blood sample collection before the 

pump is empty, placement on ice and prompt centrifugation of the samples. 

5-FU concentrations did increase with elevated 5-FU doses. Intraindividual 

variation in 5-FU plasma concentration was negligible. One 

third of our patients reached AUC-values within the proposed range of 

20–25 mgh/l (Gamelin 2008): 3 patients achieved AUC-levels 25 mgh/l. There was a tendency to better response in 

patients receiving higher 5-FU doses and therefore obtaining higher 

AUC-levels (>20 mgh/l). Side effects could not necessarily be attributed 

to 5-FU concentrations, as they did not correlate with the measured 

5-FU concentrations. 

Conclusions. The measurement of 5-FU plasma concentrations leads to 

reproducible results in our test system. Our preliminary data show that 

5-FU concentrations are dose-dependent with low intraindividual variability. 

The measurement of 5-FU plasma concentrations may in the 

future allow to optimize the 5-FU dose and to identify the cause of toxicity. 

0402 

Prognosis in colon cancer 

*K . Oeckl1 , W . Hohenberger1 , S . Merkel1 , M . Langheinrich1 1Chirurgische Universitätsklinik, Allgemeinchirurgie, Erlangen, Deutschland 

From 1978 to 2004 1453 patients from our ERCRC with solitary colon 

carcinoma were selected and the data analysed for local recurrence, distant 

metastasis and 5-year survival-rate. 

The 5-year rate of local recurrence was 4.8 % (95% CI 3.6–6.0). Local recurrence 

occurred in median 20 months after primary therapy. In univariate 

analysis it was significantly elevated at tumors with advanced pT 

and pN category, high tumor stadium, high grade tumors, tumors with

extramural venous invasion and emergency presentation with emergency 

operation. In multivariate analysis we analysed three risc factors: 

pN-category (relative risk 8.6 in pN2-tumors), grading of tumor tissue 

(relative risk: 8.6 in high grade tumors) and emergency presentation (relative 

risk: 1.6 in emergency operation). 

The 5-year rate of distant metastases was 19.2 % (95% CI 17.0–21.4). In 

univariate analysis we found significantly factors in advanced pT and 

pN category, tumor stadium, grading, extramural venous invasion and 

emergency presentation as well as lymphatic invasion and in patients 

without adjuvant chemotherapy. Independent factors in multivariate 

analysis were pT and pN category, tumor stadium, extramural venous 

invasion and emergency presentation. 

The 5-year survival rate of all patients was 84.4 %. Similar to local recurrence 

significant factors in univariate analysis were an advanced pT and 

pN category, tumor stadium and grading, extramural venous invasion 

and emergency presentation. In multivariate analysis we found advanced 

pT and pN category and emergency presentation as independent 

factors. 

At contemplating the independent risk factors advance pT and pN category 

and emergency presentation are the most important factors. Using 

better prevention and early diagnosis the tumor can be diagnosed and 

treated in an earlier tumor stage. A sophisticated operation technique 

and performing the operation by a specialized surgeon with high experience 

can improve prognosis. In our data we can see, that prognosis is 

considerably better since introduction the method of CME (complete 

mesocolic exczsion) in 1995. (Exemplary 10,4% of local recurrence in 

stadium III tumors in 1978–1984, 4.9 % local recurrence in 2000–2004.) 

0416 

Therapy resistance in HCC is modulated by IL-29 and Rapamycin 

*E .B . Schwarz1 , Y . Zhao1 , F . Beigel2 , J . Mysliwietz3 , J .W . Ellwart3 , S . Brand2 , 

K .-W . Jauch1 , C .J . Bruns1 1Universitätsklinikum der LMU München Campus Großhadern, Chirurgie, 

München, Deutschland, 2Universitätsklinikum der LMU München Campus 

Großhadern, Med II, München, Deutschland, 3Helmholtz Center for Environment 

and Health, Institute of Molecular Immunology, München, 

Deutschland 

Background. HCC is the fifth leading cause of cancer-related death 

worldwide. Patients with advanced HCC rarely benefit from the available 

first-line therapies. Second line therapies are often associated with 

development of resistance. Thus, it is essential to gain deeper knowledge 

of HCC tumor biology, in particular the significance of cancer stem 

cells and their impact on therapy resistance, to develop novel therapeutic 

strategies. Therefore, we investigated in vitro and in vivo the 

effects of interleukin-29 (IL-29) and the mTOR-inhibitor Rapamycin 

on different cancer stem cell subpopulations in HCC. Our aim was to 

characterize CSC markers on sensitive and Sorafenib-resistant human 

HCC cells (Huh7) and to demonstrate the therapeutic effects of IL-29 

and Rapamycin. 

Methods. For in vitro experiments sensitive and Sorafenib-resistant 

(Huh7-SoR) Huh7 cells were used. To characterize CSC surface markers 

FACS and immunofluorescence staining for SP (side population), 

CD133, CD44, ABCG2 were performed. Cell viability, migration, colony 

formation and apoptosis of sensitive and Sorafenib-resistant Huh7 cells 

were analyzed under treatment of IL-29 and Rapamycin. 

Results. We could demonstrate a significant dose-dependent inhibition 

of cell proliferation in both Huh7 and Huh7-SoR cells under IL-29 treatment. 

The Huh7 SP subpopulation increased after 72 h of therapy with 

Sorafenib at IC50-concentrations and enriched with long term therapy 

after 3 months (5,19% vs. 12,9%). The CD133+ and CD44+ double positive 

subpopulation significantly increased in Huh7-SoR compared to sensitive 

Huh7 cells over the same treatment period. Interestingly, Rapamycin 

reduced the SP subpopulation in sensitive Huh7 and Huh7-SoR 

cells more effectively than IL-29. Inhibition of colony formation in both 

sensitive Huh7 and Huh7-SoR cells was more pronounced following 

treatment with Rapamycin compared to IL-29. Immunofluorescence 

stainings showed similar results. 

Conclusions. There is an obvious effect of IL-29 treatment on sensitive 

and Sorafenib-resistant Huh7 cells. However, with respect to different 

cancer stem cell subpopulations Rapamycin was a more effective inhibitor 

in vitro. Therefore, mTOR inhibition seems to open new possibilities 

for second line therapy in HCCs. 

0427 

microRNA signature for the chemoradiosensitivity in colorectal 

cancer cell lines 

*J . Salendo1 , M . Spitzner1 , P . Jo1 , F . Kramer2 , T . Beissbarth2 , H .A . Wolff3 , 

M . Grade1 , H . Becker1 , B .M . Ghadimi1 , J . Gaedcke1 1Universitätsmedizin Göttingen, Allgemein- und Viszeralchirurgie, Göttingen, 

Deutschland, 2Universitätsmedizin Göttingen, Medizinische Statistik, 

Göttingen, Deutschland, 3Universitätsmedizin Göttingen, Strahlentherapie 

& Radioonkologie, Göttingen, Deutschland 

Background. Preoperative 5-fluorouracil-based chemoradiotherapy is 

the standard treatment for locally advanced rectal carcinomas. However, 

the individual tumor response is very heterogeneous, ranging from 

complete resistance to regression. Recently, it has been shown that microRNAs 

(miRNAs) play a key role in the initiation, progression and 

therapy response of cancer. Therefore, the identification of miRNAs as 

predictive markers for response remains very crucial. 

Materials and methods. Previously, we established in vitro models for 

studying the molecular basis of this heterogeneous tumor response. 12 

colorectal cancer cell lines were exposed to 3 µM of 5-fluorouracil and 

2 Gy of radiation. The pretherapeutic miRNA expression profiles of these 

cell lines were assessed using 60 K Agilent Human miRNA Microarray. 

Differences in treatment sensitivity of the cell lines and miRNAs 

expression were then correlated. 

Results. Using a linear model analysis, we identified 36 miRNAs whose 

expression levels correlated significantly with the heterogeneous sensitivity 

of the cell lines to chemoradiotherapy (p

Abstracts 

infiltrating lymphocytes (TIL). Additionally, immunogenic factors of 

the gastric tumors at hand were to be investigated. 

Methods. Tumor samples of 52 patients with gastric adenocarcinoma of 

the intestinal subtype located at the cardia were assessed using tissue 

microarrays. The relationship between subtypes of tumor infiltrating 

immune cells (CD3+, CD8+, CD20+, CD68+, GranzymeB+, FoxP3+ 

and CXCR3+) in different histologic compartments and no evidence of 

disease (NED) – survival was investigated. To further understand the 

specific immunogenic tumoral environment human epidermal growth 

factor receptor 2 (Her2) overexpression and Ebstein-Barr virus (EBV) – 

status of the carcinomas were determined and set into relation to TIL 

infiltration. 

Results. A strong compartmentalization with high TIL counts in the tumoral 

stroma as compared to low intratumoral infiltration was noted. 

In the stromal compartment, an association of high FoxP3+ regulatory 

T cells with long NED-survival was observed, while high stromal 

CD68+/FoxP3+ ratios were linked to shorter NED-survival times. Her2 

overexpression/amplification had no correlation to TIL infiltration, 

whereas EBV infection showed an association with both intratumoral 

and stromal CD8+ cell accumulation. Stromal CXCR3+ T cell infiltration 

equalling Th1 cell infiltration showed an inverse correlation to T 

category. 

Conclusion. The association of Treg with improved outcome might be 

due to an inhibition of carcinogenic inflammatory processes. CD68+ 

macrophages on the other hand are possible promoters of carcinogenesis. 

The diminishing CXCR3+ T cell infiltration with increasing T 

category suggests a subversion of Th1 immunoresponse in cancer progression. 

This underlines the important role of inflammation for early 

carcinogenesis. 

0435 

Circulating microRNAs in rectal cancer 

*J . Salendo1 , P . Jo1 , T . Beissbarth2 , M . Spitzner1 , H .A . Wolff3 , L .C . Conradi1 , 

M . Grade1 , H . Becker1 , B .M . Ghadimi1 , J . Gaedcke1 1Universitätsmedizin Göttingen, Allgemein- und Viszeralchirurgie, Göttingen, 

Deutschland, 2Universitätsmedizin Göttingen, Medizinische Statistik, 

Göttingen, Deutschland, 3Universitätsmedizin Göttingen, Strahlentherapie 

& Radioonkologie, Göttingen, Deutschland 

Background. The identification of response in locally advanced rectal 

cancer (RC) to a 5-FU based chemoradiotherapy is a crucial step towards 

an individualization of the therapy. The impact of microRNAs 

(miRNAs) on progression or resistance in cancer has recently been described. 

Although their impact in patients’ blood has recently been described 

in different cancer types data in rectal cancer are scarce. 

Materials and methods. miRNAs were extracted from patient and healthy 

control plasma including C. elegans miRNA mimics for the normalisation 

process. Each miRNA was detected using SYBR-Green based 

miScript PCR system from Qiagen. 15 differentially regulated miRNAs 

that were retrieved from the comparison of rectal cancer and normal 

tissue based on miRNA microarray analyses were analysed in a first set 

of 17 patients. All patients were treated within the CAO/ARO/AIO-94 

and -04 trial of the German Rectal Cancer Study Group. Additionally, 

14 age and gender matched healthy controls were analysed. In a second 

set of 46 controls and 122 patients a subset of miRNAs was validated and 

analysed on postsurgical blood specimens. 

Results. 5 of the 15 analyzed miRNAs turned out to be significantly 

down regulated in plasma compared to healthy controls (miR-17, miR- 

18b, miR-20a, miR-31 and miR-193a-3p). Subsequently, a second set of 

patients was analysed and two of the previously identified miRNAs 

could be validated in this independent cohort. Interestingly, all miR- 

NAs were downregulated in the RC patients. Comparing pretherapeutical 

and postsurgical expression 4 out of 5 miRNAs were significantly 

differentially expressed. 


Conclusion. This study demonstrates for the first time the differential 

expression of plasma miRNAs in RC patients compared to healthy controls. 

To assess the impact of miRNAs on response or prognosis prediction 

these results will be correlated to the clinical data and a more 

comprehensive approach will be undertaken. 

0440 

Isolation and characterisation of different stem cell-like subpopulations 

in an esophagus ascites 

*S . Stoelting1 , H . Ungefroren1 , H . Lehnert1 , F . Gieseler1 1UK S-H, Campus Lübeck, Med . Klinik I, Onkologie, Lübeck, Deutschland 

Background. First indication for the existence of cancer stem cells 

(CSCs) was made by J. Dick et al in 1994. They identified the presence 

of CSCs in acute lymphatic leukaemia. CSCs represent only 1% of the 

tumor but appear to be the only cells that are able to generate a new 

tumor. CSCs were discussed as the origin of tumor resistance and metastases. 

So far CSCs would be isolated and characterized only from solid 

tumors. Basack et al. (2009) detected cells similar to stem cells with specific 

markers in a NSCLC pleura effusion for the first time. Until know 

it is not clear whether only one population of stem cell like cells exist in 

maligne effusions or different subpopulations with stem cell characters. 

For the time being no data about the behaviour of those cells have been 

determined. 

Material and methods. We detected CSCs from an esophagus ascites 

with stemgent alkaline phosphatase staining kit II and characterised 

different subpopulations with stem cell markers by separating CD133+, 

CD133+/Lin- and TRA-1-60+ cells with the miltenyi separating kits. 

These cells had been cultured with the esophagus CSC medium from 

cell system and analysed by determined surface marker (e.g. CD133) 

with FACS, quantitative gene expression of stem cell transcription 

factors (Oct3/4, Sox2, Nanog, cMyc), expression of microRNA (system 

bioscience) and their behaviour of migration under TGFβ stimulation. 

Results. After separation of different cell subpopulations with stemness 

from an esophagus ascites we cultured the cells under specific conditions 

for CSCs. We obtained differences in gene expression of stem cell 

markers (e.g. Oct3/4, Nanog) and also for microRNA. We also obtained 

differences in migration behaviour. Under TGFβ stimulation TRA-1- 

60+ cells showed migration, in contrast the migration of CD133+ and 

CD133+/Lin− cells have been inhibited. 

Discussion. We demonstrated that cells with stemness not only exist 

within solid tumors but also in ascites. These cells exhibit markers like 

CD133 which describe for CSCs and TRA-1-60 which describes for pluripotent 

stem cells. The quantitative analysis of specific transcription 

factors and microRNA indicates that only the subpopulation of TRA- 

1-60+ cells feature a stem cell potential and maybe play an important 

role in metastases. This hypothesis is supported by the observance that 

only the TRA-1-60+ cells showed migration under TGFβ stimulation. 

The presented data clarify the importance of understanding CSCs and 

to generate a treatment. 

0444 

Generating scFv antibodies against pancreatic carcinoma from 

naïve human Phage Display Libraries for clinical application 

*E .-M . Siepert1 1Helmholtz Institute for Applied Biomedical Engineering, Experimental 

Medicine and Immunotherapy, Aachen, Deutschland 

Pancreatic carcinoma (PC) is an aggressive form of cancer characterized 

by its high potential for metastasis and thus resulting in a low survival 

rate. As the initial stages of this disease are almost asymptomatic, early 

detection, before metastasis occurs, is challenging because no reliable 

detection tools for early diagnosis and treatment of PC are available. In 

patients with metastasis the average survival rate of 5 years is less than

5%. Therefore, the need to develop tumour-specific therapies and tools 

for early diagnosis is significant. The aim of this study was to develop an 

immunotherapeutic approach for targeted diagnosis and treatment of 

pancreatic cancer by using highly specific human antibody fragments 

(scFv). Using the Phage Display Technology highly specific scFv were 

generated from the naïve human Tomlinson phage library in a two-step 

panning strategy with depletion on human peripheral blood lymphocytes 

(PBL) followed by a positive selection on the metastatic pancreatic 

cancer cell line (L3.6pl). Monoclonal phage ELISA identified 16 unique 

positive binders which were subsequently expressed in eukaryotic cells 

(HEK293T) as scFv-SNAP-tag fusion proteins. The SNAP-tag® is a novel 

tool for site specific conjugation of any benzylguanine-labeled molecule 

to a given protein, providing the imaging of tumor cells in vitro and in 

vivo. IMAC-purified fusion proteins were analyzed by protein ELISA 

and flow cytometry for their binding specificity on several pancreatic 

cancer cell lines. Eight clones were identified as recognizing L3.6pl cells 

with cross-reactivity to other pancreatic cancer-derived cell lines. To 

validate the selective binding of these clones to human pancreatic cancer 

cells, frozen primary tissue sections from patients with pancreatic 

carcinoma were used and selective binding of at least one individual clone 

to tumor cells over normal cells was shown. All clones are currently 

being tested for their ability for internalization in order to identify candidate 

clones for development of immunotoxins eliminating pancreatic 

cancer cells. 

0454 

The systematic assessment of health information on colorectal 

cancer screening in Germany 

*M . Dreier1 , B . Borutta1 , G . Seidel1 , S . Kramer1 , I . Kreusel1 , J . Töppich2 , 

E .M . Bitzer3 , M .-L . Dierks1 , U . Walter1 1Medizinische Hochschule Hannover, Institut für Epidemiologie, Sozialmedizin 

und Gesundheitssystemforschung, Hannover, Deutschland, 

2Bundeszentrale für gesundheitliche Aufklärung (BZgA), Köln, Deutschland, 

3Pädagogische Hochschule, Freiburg, Deutschland 

Objective. The informed choice to attend or not attend colorectal cancer 

screening tests (fecal occult blood test FOBT, screening colonoscopy) 

may be supported by evidence-based health information. The aim was 

to assess whether written health information on colorectal cancer screening 

meet the criteria of evidence-based health information. 

Methods. The development of a criteria list included the following steps: 

systematic literature review in 8/2010 in relevant electronic databases 

(including Medline, Embase, search period from 2000) and Internet, 

identification of recommendations and assessment tools for health information, 

extraction of the criteria, summary of the criteria by topics, 

review by external experts, modification. In 8/2010 major players in 

Germany were asked for leaflets via email. 

Results. The criteria list was based on 16 documents with recommendations 

and 17 tools for health information and contains a total of 235 

criteria in the following categories: formal issues, information on the 

target disease, information on screening-colonoscopy/FOBT, readability 

and comprehensibility, layout, neutrality, correctness of the information. 

Input of free text ensures the transparency. An accompanying 

manual supports the assessment by giving the correct answers, based 

on systematic reviews, HTA reports, and guidelines. Eighteen flyers and 

13 brochures on colorectal cancer screening were identified and assessed. 

It turned out that information was often not given (including risks, 

quantification of the benefits), false information were given (“screening 

results in a gain in life years in any case”), benefits and risks of the procedure 

were not be represented in a balanced way, and information was 

partly misleading, e.g. the accuracy of colonoscopy was circumscribed 

as the safest kind of prevention, which could be misunderstood as a low 

risk of the procedure. 

Discussion. An evaluation concept was developed and applied, which 

goes beyond previous tools by considering not only the presence but 

also the correctness of information. It also allowed the detailed detection 

of missing information, distorted presented benefits and risks as well 

as of false and misleading information. The requirements for evidencebased 

patient information were currently not met by most of the offered 

leaflets in Germany. The results may be used to revise existing leaflets 

or to develop new health information on colorectal cancer screening. 

0465 

Solid pseudopapillary tumor of the pancreas: a new name for an 

old enigmatic, but universally recognized entity 

*N . Vassos1 , A . Agaimy2 , P . Klein1 , W . Hohenberger1 , R . Croner1 1Universitätsklinikum Erlangen, Chirurgische Klinik, Erlangen, Deutschland, 

2Universitaetsklinikum Erlangen, Pathologisches Institut, Erlangen, 

Deutschland 

Background. Solid pseudopapillary tumor (SPT) of the pancreas is an 

infrequently-encountered tumor, typically affects young women without 

significant symptoms. Its behavior is relatively indolent and largely 

benign. 

Material and methods. We report a case series of four patients with SPT 

of pancreas, who were treated at our hospital between 2008 and 2011. 

The clinical, pathological and immunohistochemical parameters as 

well as the therapy and follow-up were investigated retrospectively. 

Results. All four patients were female whose ages ranged between 15 and 

42 years. Two patients were presented with abdominal pain, one patient 

with abdominal mass and one with acute abdominal signs following 

blunt trauma. The tumor’s size ranged between 1 and 16 cm. Two of them 

were diagnosed preoperatively through a percutaneous needle biopsy 

and the other two underwent surgery because of the high clinical and 

radiological suspicion of SPT. By immunohistochemistry, all four cases 

were stained strongly for vimentin, progesterone-receptor and beta-catenin 

and variably with pankeratin and neuroendocrine markers. The 

proliferation index (Ki-67) was less than 2%. The patients underwent 

surgical resection of the tumor and after a follow-up period between 3 

and 36 months, all of them were alive with no evidence of disease. 

Conclusion. SPT of pancreas should be considered in the differential diagnosis 

of any solid or partly cystic pancreatic or upper abdominal mass, 

particularly in young females. The tumor has a low malignant potential 

and the treatment of choice consists of surgical resection. Adequate surgical 

intervention is associated with an excellent prognosis. 

0466 

Management of liver metastases of gastrointestinal stromal 

tumors (GISTs) 

*N . Vassos1 , A . Agaimy2 , W . Hohenberger1 , R . Croner1 1Universitätsklinikum Erlangen, Chirurgische Klinik, Erlangen, Deutschland, 

2Universitätsklinikum Erlangen, Pathologisches Institut, Erlangen, 

Deutschland 

Introduction. Liver metastases and/or peritoneal dissemination are the 

main clinical manifestations of advanced GISTs. With the advent of tyrosine 

kinase inhibitors (TKI), the role of surgery in management of 

advanced GISTs has radically changed. The effectiveness of TKI-therapy 

has provided an increasing proportion of GIST-patients with liver 

metastases who are candidates for potentially curative therapy. 

Material and methods. We herein present our experience about management 

of liver metastases of GISTs, investigating in retrospective analysis 

clinical, macro-/microscopic and immunohistochemical criteria, surgical 

or TKI therapy and follow-up in these cases. 

Results. Within a 10-year period (2000–2009), 85 patients with GISTs 

were referred to our institution. In 24 patients (28.2%) metastatic disease 

was disclosed. Of these, 10 patients (11.7%; M:F=1:1) were rendered 

to have liver metastases. The mean age was 59 (range: 35–75) years. The 

primary GISTs were located in stomach (40%) and in small intestine 


51

Abstracts 

(60%), expressed CD117 and/or CD34. Liver metastases were commonly 

multiple, distributed in both lobes (70%) and detected synchronously 

with primary tumor (n=4) or metachronously (n=6). The period of time 

between diagnosis of GIST and metachronous liver metastases ranged 

from 23 to 76 (mean period: 36.3) months. All patients with liver involvement 

were considered to treatment with imatinib. The liver metastases 

were estimated as resectable in 4 cases (R0). In recurrent (2/4, 50%) or 

resistant cases, other treatments were carried out, including radiofrequency 

ablation (RFA) and sunitinib or nilotinib therapy. During a 

mean follow-up of 52.6 months (range: 7–111 months), death for progressive 

disease occurred in 2 cases (20%). Eight patients (80%) were alive; 

five of them remained free of disease and the other three have maintained 

disease with partial response or stabilization. 

Conclusion. The liver is a common metastatic site for GISTs. Appropriate 

initial evaluation remains of paramount importance for selecting the 

correct treatment strategy. Combining surgery with TKI treatment is 

the most effective management for GIST patients with liver metastases. 

For unresectable disease, RFA, hepatic artery chemoembolization 

(TACE), TKI therapy, or any combination of these treatments can be 

considered. Multidisciplinary management of this disease is important 

for both curative and palliative treatment in these patients. 

0483 

Tumorinfiltrierende regulatorische T-Lymphozyten als prognostische 

Marker mit therapeutischer Relevanz beim Rektumkarzinom 

*T . Borschitz1 , D . Wohland1 , E . von Stebut2 1Deutsche Klinik für Diagnostik, Chirurgie und Koloproktologie, Wiesbaden, 

Deutschland, 2Universitätsmedizin Mainz, Core Facility-Histologie, 

Dermatologie, Mainz, Deutschland 

Fragestellung. Die Behandlung von Rektumkarzinomen erfordert eine 

stadiengerechte, optimierte Therapie. Dabei entscheiden Histologie/ 

Eindringtiefe/Lymphknotenmetastasen sowohl über das Operationsverfahren 

(lokale vs. radikale Exzision), als auch (neo-)adjuvante Therapien. 

Ziel dieser Untersuchung war es, zu evaluieren, inwiefern die 

Infiltration des Tumors mit immunmodulierenden T-Lymphozyten 

prognostisch relevant und in Therapieentscheidungen einzubeziehen 

ist. 

Methode. Getrennt nach Lymphknotenmetastasen (n=40 N+/n=40 N0) 

wurden Tumorschnitte von 80 Patienten (8% T1, 44% T2, 46% T3, 3% T4) 

mit einem Follow-up von ≥5 Jahren untersucht, die nicht neoadjuvant 

behandelt wurden. Sechs Patienten (8%) wiesen im Verlauf Lokalrezidive 

(LR) auf, 14 (18%) synchrone und 10 (13%) metachrone Fernmetastasen 

(M). Es wurden tumorinfiltrierende CD4+/CD8+ Lymphozyten, 

CD57+ NK-Zellen sowie FoxP3+ bzw. CD25+ regulatorische T-Zellen 

(Treg) immunhistochemisch dargestellt. Durch Auszählen aller positiven 

Zellen und Mittlung von 5 repräsentativen Gesichtsfeldern/Tumor 

wurde die jeweilige Infiltrationsdichte quantifiziert und statistisch 

mittels Mann-Whitney-U-Test auf Unterschiede hinsichtlich T-Kategorie, 

Lymphknotenstatus (N0/N+), Grading (G) und LR-/M-Auftritt 

untersucht. Unterschiede im Gesamtüberleben (GSÜ) wurden mit Log- 

Rank-Test und Cox-Regression ausgewertet. 

Ergebnisse. Färbungen gegen CD4, CD8, CD57 und CD25 wiesen keine 

Unterschiede in den jeweiligen Verteilungen auf. Die FoxP3+ Treg- 

Dichte war bei T1 Karzinomen am höchsten und nahm mit zunehmender 

T-Kategorie signifikant ab (T1/2 vs. T3/4 p=0,002). Gleiches ergab 

sich für N+ und M1 gegenüber N0 (p=0,033) bzw. M0 Karzinomen (synchrone 

p=0,006/metachrone p=0,04/kombiniert p=0,004). Außerdem 

fanden sich bei „high-grade“- (G3–4) signifikant weniger FoxP3+ Tregs 

als bei „low-grade“- (G1–2) Karzinomen (p=0,012) und schließlich für 

hohe Treg-Infiltrationsdichten ein signifikant längeres GSÜ (p

Hauttumoren 

0022 

R1-Status bei fazialen Basalzellkarzinomen – Realität oder 

Mythos 

*L . Tischendorf1 1Praxis MKG-Chirurgie, Praxis, Halle, Deutschland 

Fragestellung. Aktuelle Leitlinien für die Behandlung von Basalzellkarzinomen 

(BCC) fordern den Einsatz der mikroskopisch kontrollierten 

Chirurgie und der sekundären Defektabdeckung speziell im Gesichtsbereich. 

Diese Ansicht ist wissenschaftlich nicht ausreichend belegt, vor 

allem nicht durch randomisierte kontrollierte Studien. Wir analysierten 

2 Fragen: 1.) Ist der R1-Status realistisch beurteilbar? 2.) Was ist der 

prognostische Wert des R1-Status? 

Material und Methodik. Ergebnisse der operativen Behandlung fazialer 

BCC (649 stationär 1948–1982 retrospektive R1-Bewertung, 847 ambulant 

1993–2007 prospektive R1-Bewertung). Berechnungen der Rezidivwahrscheinlichkeit 

(Kaplan-Meier) in Abhängigkeit von R1-Status. 

Ergebnisse. 1.) R1-Status beträgt bei unvorbehandelten BCC: 9% bzw. 

3%, bei rezidivierten: 8% bzw. 19%. 2.) Rezidivwahrscheinlichkeit ist 26fach 

(unvorbehandelte BCC) bzw. 3-fach (rezidivierte BCC) höher bei 

R1-Status. Nachgewiesen werden Tumorreste in 30–85%. 3. R1-Status 

beeinflusst Überleben nicht. Allerdings treten in 30% Zweitgeschwülste 

auf und die Lebenserwartung verkürzt sich im Vergleich zur Normalpopulation 

um 5 Jahre. 

Schlussfolgerungen. 1.) R1-Status beeinflusst Prognose nur begrenzt auf 

das Rezidivverhalten. 2.) Mikroskopisch kontrollierte Chirurgie bildet 

(auch in vereinfachten Modifikationen) R1-Status im lateralen Bereich 

sicher ab und kann die onkologische Sicherheit erhöhen. 3.) Verzögerte 

Defektabdeckungen bleiben seltenen Ausnahmefällen vorbehalten. 

0027 

Sensitization of melanoma cells for TRAIL-induced apoptosis by 

the kinase inhibitor indirubin is mediated through upregulation 

of p53 and death receptors 

*A . Berger1 , S .-A . Quast1 , M . Kunz2 , P . Langer3,4 1Charité – Universitätsmedizin Berlin, Klinik für Dermatologie und Allergologie, 

Berlin, Deutschland, 2University Hospital of Leipzig, Department of 

Dermatology and Allergy, Leipzig, Deutschland, 3University of Rostock, Institute 

of Organic Chemistry, Rostock, Deutschland, 4University of Rostock, 

Leibniz Institute of Catalysis e .V ., Rostock, Deutschland 

Background. No effective therapy is available for metastatic melanoma 

so far. An anti-tumour activity of indirubin is known from traditional 

Chinese medicine, and its derivative 8-Rha-beta has been described as 

a cyclin-dependent kinase inhibitor. However, the molecular basis underlying 

8-Rha-beta-induced apoptosis remained elusive. TNF-related 

apoptosis-inducing ligand (TRAIL) is known to trigger apoptosis in a 

variety of human cancer cells, while normal cells are largely spared. 

However, prevalent or inducible resistance prevented its efficient use in 

cancer therapy so far. TRAIL resistance in melanoma cell lines is frequently 

associated with downregulation of its agonistic receptors DR4 

and DR5. 

Methods. TRAIL-sensitive melanoma cell lines A-375 and Mel-HO 

were compared to permanently resistant MeWo and Mel-2a as well as 

to cell lines selected for death ligand resistance A-375-TS, Mel-HO-TS 

(TRAIL-selected) and A-375-CS, Mel-HO-CS (selected with an agonistic 

CD95 antibody, CH-11, for resistance to the death ligand CD95L). 

Results. Both death ligand-sensitive cell lines (A-375 and Mel-HO) responded 

with enhanced apoptosis to combinations of death ligands 

(TRAIL, CH-11) with 8-Rha-beta. The indirubin was further able to 

sensitize resistant Mel-2a and A-375-TS (DR4+, DR5+) for death ligand- 

induced apoptosis. In contrast, MeWo and Mel-HO-TS (DR4−, DR5+) 

remained without effect. The unraveling of proapoptotic signaling 

pathways in A-375-TS revealed strong enhancement of the effector caspase-3 

in the combination. Significant loss of the mitochondrial membrane 

potential, release of cytochrome c and apoptosis-inducing factor 

(AIF) as well as processing of caspase-9 was evident for activation of 

intrinsic apoptosis pathways. On the other hand, enhanced surface expression 

of DR4 and DR5 as well as processing of initiator caspase-8 was 

indicative for activation of extrinsic apoptosis pathways. Remarkably, 

this combination was able to overcome an apoptosis block due to ectopic 

Bcl-2 overexpression. The effects may be explained by downregulation 

of antiapoptotic proteins Mcl-1 and XIAP as well as by activation of 

the master regulator p53 seen in course of 8-Rha-beta treatment. 

Conclusions. Apoptosis resistance to TRAIL may be overcome by kinase 

inhibitors, and the indirubin 8-Rha-beta appears as a promising therapeutic 

strategy for melanoma cells, dependent on their expression of 

TRAIL receptors. 

0032 

Sensitization of melanoma cells for death ligand-induced apoptosis 

by the potassium channel inhibitor TRAM-34 correlates 

with the intrinsic pathway and SMAC release 

*S .-A . Quast1 , A . Berger1 , N . Buttstädt2 , K . Friebel2 , R . Schönherr2 , *J . Eberle1 1Charité – Universitätsmedizin Berlin, Klinik für Dermatologie und Allergologie, 

Berlin, Deutschland, 2Universität Jena, Zentrum für molekulare 

Biomedizin, Jena, Deutschland 

Introduction. Melanoma only poorly responds to chemotherapy, and the 

death ligand TRAIL, which mediates apoptosis via TRAIL-R1/DR4 and 

TRAIL-R2/DR5, appears as a promising therapeutic strategy. However, 

prevalent and inducible TRAIL resistance may limit its clinical use in 

melanoma cells. Potassium channels as KCa3.1 are involved in tumor 

progression and may serve as additional targets. 

Material and methods. Functional expression of KCa3.1 in melanoma 

cells is demonstrated by quantitative RT-PCR analysis and patch-clamp 

recordings. We prove that TRAM-34, a selective KCa3.1 inhibitor, 

strongly enhanced TRAIL sensitivity of melanoma cells and overcomes 

prevalent and inducible TRAIL resistance. Unraveling the signaling 

pathways revealed that TRAM-34 was able to overrule the lack of caspase-3 

processing in selected TRAIL-resistant cells. Disruption of the 

mitochondrial membrane potential and the release of proapoptotic mitochondrial 

factors such as SMAC clearly indicate the involvement of 

the mitochondrial apoptosis pathway. Importantly, TRAM-34 mediated 

enhancement of the TRAIL-induced apoptosis was critically dependent 

on the expression of either Bax or Bak, as shown in genetic models, 

and apoptosis was abrogated in Bax/Bak double knockout cells as well 

as by overexpression of the antiapoptotic Bcl-2 protein Bcl-2. 

Conclusion. Taking into account the physiological role of death ligands 

in immune surveillance, sensitization of melanoma cells for death ligands 

may be supportive for an anti-tumor immune response. The data 

prove the critical role of the mitochondria in TRAIL resistance and present 

a new strategy for TRAIL sensitization based on the targeting of 

potassium channels. Furthermore, combinations with the potassium 

channel inhibitor TRAM-34 may help for a breakthrough of TRAILmediated 

strategies in melanoma. 


53

Abstracts 

0251 

Mechanism analysis of melanoma chemosensitization by 

MIDGE-mediated hTNF-alpha gene transfer in combination with 

vindesine 

*D . Kobelt1 , J . Aumann2 , M . Schmidt3 , M . Schroff3 , I . Fichtner4 , P .M . Schlag5 , 

W . Walther2 1MDC Berlin Buch, Chirurgie/chirurgische Onkologie, Berlin, Deutschland, 

2Experimental and Clinical Research Center, a joint cooperation 

between the Charité Medical Faculty and the MDC for Molecular Medicine, 

Chirurgie/chirurgische Onkologie, Berlin, Deutschland, 3MOLOGEN AG, 

Berlin, Deutschland, 4MDC Berlin Buch, Experimental Pharmacology, Berlin, 

Deutschland, 5Charité University Medicine, Charité Comprehensive Cancer 

Center, Berlin, Deutschland 

Non-viral vectors are frequently used for clinical gene therapy trials. 

Compared to viral vectors they offer a better safety profile due to their 

limited ability to integrate or to provoke immune reactions. Besides 

long known plasmids as gene transfer vectors there are novel non-viral 

vectors available. Among those, the MIDGE vector technology (Mologen, 

Berlin, Germany) offers the smallest vectors for transient gene 

transfer. They are linear double stranded DNA molecules with end-sealing 

loops at their ends. Using those vectors it is possible to avoid the 

transfer of any unnecessary genetic material like ORIs, CpG islands or 

resistance genes besides the expression cassette. 

In our in vitro experiments using luciferase reporter gene we showed, 

that the MIDGE vector is superior compared to plasmid vectors. In 

different human melanoma (A375, MeWo, SKMEL-5, SK-MEL-28) and 

colon carcinoma (HCT116, SW480) cell lines, reporter gene expression 

increased up to 10-fold after equimolar transfection and >100-fold after 

equimolar electroporation compared to the parental plasmid harboring 

the identical expression cassette. This increase was due to an enhanced 

transgene expression when using MIDGE vectors as shown by expression 

studies at the mRNA level by qRT-PCR. For a therapeutic approach 

we were combining the MIDGE based gene transfer of human tumor 

necrosis factor alpha (hTNF-alpha) with vindesine in vitro and in vivo. 

The equimolar gene transfer by transfection/electroporation in vitro or 

in vivo jet-injection gene transfer in melanoma xenotransplants showed 

improved MIDGE-mediated transgene expression. The hTNF-alpha 

gene transfer led to an up to 10-fold reduction of the vindesine IC50 in 

vitro. Analyzing the mechanism of enhanced cell killing using lactate 

dehydrogenase (LDH) release assay and caspase 8, 9, 3/7 activation assays 

we showed in vitro, that particularly an accelerated activation of 

caspases leads also to accelerated apoptosis. 

The in vivo tumor growth was significantly reduced by MIDGE-based 

hTNF-alpha gene transfer in combination with i.v. vindesine treatment. 

Additionally, the MIDGE vector showed a good safety profile with low 

systemic leakiness and fast clearance of the vector after intratumoral 

jet-injection. The MIDGE vector demonstrated its great potential for 

future clinical application in tumor gene therapy. 

0321 

Bone morphogenetic protein and nodal induce epithelial-mesenchymal 

transition in melanoma cells and confer a neural crest 

phenotype to melanocytes in vitro and in vivo 

*C . Busch1 , C . Garbe1 1Universitäts-Hautklinik, Dermatologische Onkologie, Tübingen, Deutschland 

During embryonic development, TGF-β family members nodal and 

bone morphogenetic protein-2 (BMP-2) induce an epithelial-mesenchymal 

transition (EMT) in the neural crest. Here we demonstrate numerous 

effects of BMP-2, BMP-7 and nodal, their antagonists noggin and 

lefty, and the nodal receptor (Alk4/5/7) antagonist SB431542 on melanoma 

cells and melanocytes. 


There was no effect on cell cycle or cell proliferation. In melanoma cells 

aggregate formation was reduced by agonist treatment and increased 

by antagonists. Migration and invasion were increased by agonists and 

blocked by antagonists. Western Blot analyses showed a down-regulation 

of neural crest proteins Slug and SOX9 upon antagonist treatment. 

mTOR signalling was also inhibited by antagonists. In epidermal skin 

reconstructs invasion of melanoma cells was reduced by antagonists. 

BMP-2 and nodal induced invasiveness in radial growth phase melanoma 

cells in epidermal reconstructs. In vivo, the SB431542 entirely 

abrogated neural crest migration of SKMel28 cells upon transplantation 

into the chick embryonic neural tube. Cytoplasmatic expression of 

nodal was confined to melanoma cells performing EMT. Noggin and 

SB431542 significantly inhibited invasion of BLM melanoma cells in a 

newly established in vivo model of brain metastasis in the chick embryo. 

Agonists (BMP-2, BMP-7, nodal) conferred a neural crest phenotype 

to primary human melanocytes: They reduced adhesiveness, induced 

migration and invasion in vitro, induced neural crest-specific proteins 

Slug and SOX9, and mTOR signalling. In vivo BMP-2 and nodal induced 

EMT in melanocytes transplanted into the chick embyonic neural 

crest, thus behaving like melanoma cells in the same experimental setup. 

Expression of nodal and its receptors were determined in a newly-generated 

melanoma tissue microarray. Expression of nodal receptors significantly 

increased from nevi to primary melanoma. Further, BMP-2 

levels were determined in plasma of 40 melanoma patients and healthy 

controls. BMP-2 levels were significantly higher in plasma of patients 

with a short survival time when compared to long-term survivors. 

In summary, we highlight that BMP and nodal are crucial for melanoma 

cell invasiveness in vitro and in vivo. Plasma level of BMP-2 turned 

out to be a novel biomarker for rapid disease progression in melanoma 

patients. Together, we are able to demonstrate that BMP and nodal represent 

highly crucial therapeutic targets to prevent melanoma progression. 

0357 

The BRAFV600E kinase inhibitor vemurafenib induces endoplasmic 

reticulum stress-mediated apoptosis in BRAFV600E mutated 

melanoma cells 

*D . Beck1 , H . Niessner1 , D . Kulms2 , C . Garbe1 , F . Meier1 1Universität Tübingen, Dermatologische Onkologie, Tübingen, Deutschland, 

2Universität Stuttgart, Institute of Cell Biology and Immunology, 

Stuttgart, Deutschland 

Background. In a previous study, we observed that the pan-RAF inhibitor 

sorafenib induces upregulation of endoplasmic reticulum (ER) 

stress-related genes and apoptosis in melanoma cells in vitro. In this 

study, we investigated whether vemurafenib, which selectively inhibits 

the BRAFV600E kinase and demonstrates potent antitumor activity in 

melanoma patients with the BRAFV600E mutation, induces ER stressmediated 

apoptosis. 

Methods and results. The BRAFV600E kinase inhibitor vemurafenib inhibited 

growth, induced caspase-dependent apoptosis and upregulated 

the ER stress-related genes p8, CHOP, ATF4, ATF3 and TRB3 mRNA 

levels exclusively in BRAFV600E mutated melanoma cell lines. Apoptosis 

was correlated with the induction of the proapoptotic BH3-only protein 

Bim-particularly Bim short, which is linked to ER stress-mediated 

apoptosis. Western blot analysis showed that vemurafenib increases the 

protein levels of the ER stress marker CHOP in BRAF mutated but not 

in NRAS mutated melanoma cells. Furthermore, electron microscopy 

showed typical morphological signs of ER stress, in particular significant 

swelling of the endoplasmic reticulum lumen of BRAFV600E 

mutated melanoma cells treated with vemurafenib. siRNA inhibition 

of ATF4 diminished melanoma cell apoptosis induced by vemurafenib. 

Furthermore, classical ER stress inducers such as thapsigargin and tunicamycin 

potently inhibited growth, induced apoptosis and suppressed

invasive tumor growth of melanoma cells. Moreover, both thapsigargin 

and tunicamycin upregulated p8 and CHOP and induced apoptosis in 

vemurafenib-resistant melanoma cells. 

Conclusions. These data suggest that the BRAFV600E kinase inhibitor 

vemurafenib induces apoptosis in BRAFV600E mutated melanoma 

cells through upregulation of ER stress-related genes. 

Lungentumoren 

0097 

A multi-centric, open-label, phase II study investigating the combination 

of RAD001 (everolimus) with paclitaxel and carboplatin 

in first line treatment of patients with advanced (stage IV) Large 

Cell Lung Cancer with neuroendocrine differentiation (LCNEC) 

*C . Grohé1 , O . Zaba1 , N . Reinmuth2 , I . Nimmrich3 , J . Stieglmaier4 , C . May4 , 

M . Serke5 , M . Thomas2 1Evangelische Lungenklinik Berlin, Pneumologische Klinik, Berlin, Deutschland, 

2Thoraxklinik am Universitätsklinikum Heidelberg, Onkologie der 

Thoraxtumoren, Heidelberg, Deutschland, 3i .A . Novartis Pharma GmbH, 

Berlin, Deutschland, 4Novartis Pharma GmbH, Nürnberg, Deutschland, 

5Lungenklinik Hemer, Abt .Pneumologie III, Hemer, Deutschland 

Neuroendocrine tumors (NET) of the lung can be divided into typical 

carcinoid (TC), atypical carcinoid (AC), large cell neuroendocrine carcinoma 

(LCNEC) and small cell lung carcinoma (SCLC). LCNEC, which 

accounts for approximately 3% of all lung cancers, progresses rapidly, is 

aggressively metastatic, and exhibits a poor prognosis, with currently 

no curative treatment option. Upcoming targeted therapies such as angiogenesis 

inhibitors, tyrosine kinase inhibitors, and mTOR inhibitors 

are discussed as promising approaches to improve outcome of LCNEC. 

RAD001 (everolimus) is an inhibitor of mTOR, a component of the PI3/ 

AKT/mTOR pathway known to be dysregulated in numerous human 

cancers. RAD001 is approved for treatment of metastatic renal cell cancer 

and known to be effective in pancreatic neuroendocrine tumors. 

In the presented trial for advanced (stage IV) LCNEC patients, RAD001 

is combined with carboplatin and paclitaxel, a standard chemotherapy 

routinely used in both non-small cell lung cancer (NSCLC) and smallcell 

lung cancer (SCLC) patients. The primary objective of this study 

is to evaluate the efficacy of this treatment in patients with advanced 

LCNEC. The primary endpoint is the proportion of patients progression-free 

after three months. Main inclusion criteria are histologically 

confirmed stage IV LCNEC (at least positive for one of the neuroendocrine 

markers CD56, Synaptophysine, Chromogranine A), measurable 

disease according to RECIST, adequate bone marrow, renal, and liver 

function. Main exclusion criteria are symptomatic CNS metastases, prior 

treatment for advanced LCNEC, and any severe other medical condition. 

Patients receive four cycles of combined treatment and are allowed 

to continue with RAD001 treatment as long as they benefit from treatment. 

The trial is open for recruitment and seeking 85 patients at 10 sites 

in Germany. The study design will be presented in detail. 

In summary, a combined therapy of carboplatin and paclitaxel with the 

mTOR inhibitor RAD001 might be a promising approach for more efficient 

treatment of LCNEC patients. 

0123 

Active participation in a sports club has a protective effect on the 

development of lung cancer in smokers 

*A . Schmidt1 , J . Jung1 , N . Ernstmann1 , E . Driller1 , M . Neumann2 , A . Staratschek-Jox3 

, C . Schneider4 , J . Wolf5 , H . Pfaff1 1Universität Köln, Institut für Medizinsoziologie, Versorgungsforschung 

und Rehabilitationswissenschaft der Humanwissenschaftlichen Fakultät 

und Medizinischen Fakultät der Universität zu Köln, Köln, Deutschland, 

2Medical Department of the Private University of Witten/Herdecke, 

Gerhard Kienle Institute for Medical Theory, Integrative and Anthroposophic 

Medicine, Integrated Curriculum for Anthroposophic Medicine 

(ICURAM), Witten, Deutschland, 3University Bonn, LIMES (Life and Medical 

Sciences Bonn), Genomics and Immunoregulation, Bonn, Deutschland, 

4University Hospital of Cologne, Department III for Internal Medicine, Köln, 

Deutschland, 5University Hospital of Cologne, First Department of Internal 

Medicine, Molecular Tumour Biology and Tumour Immunology & Centre 

for Integrated Oncology (CIO), Köln, Deutschland 

Background. This study analyzes the effect of social networks and participation 

in a sports club on the development of lung cancer in patients 

who smoke. Our hypothesis is that study participants lacking social 

support are at a greater risk for lung cancer than those who have social 

support. 

Methods. Data for the study were taken from the Cologne Smoking 

Study (CoSmoS), a retrospective case-control study examining potential 

psychosocial risk factors for the development of lung cancer. Our 

sample consisted of n=158 participants who had suffered lung cancer 

and n=144 control group participants. Both groups had a history of 

smoking. Data on social support were collected by asking participants 

whether they participate in a sports club and about the number of 

friends and relatives in their social environment. In addition, sociodemographic 

data and data on pack years were collected to control for 

potential confounders. Logistic regression was used for the statistical 

analysis. 

Results. The results revealed that participants who participate in a 

sports club are at a lower risk for lung cancer than those who do not 

(n=302; adjusted OR=0.435; CI=0.222–0.853). Number of friends and 

relatives had no statistically significant influence on the development 

of the disease. 

Conclusions. The results of the study suggest that there is an association 

between smokers who have suffered lung cancer and participation in a 

sports club. In the study sample, participation in a sports club seemed 

to have a greater protective effect than a social network of friends and 

relatives. 

0149 

Pulmonary neuroendocrine tumours: prevalence in 1244 resected 

patients and analysis of patient characteristics, smoking 

habits and tumour stage 

*E .-R . Walburga1 1Kliniken der Stadt Köln, Lungenklinik, Köln, Deutschland 

Objective. Neuroendocrine tumours of the lung can be divided in typicalcarcinoid 

(TC), atypical carcinoid (AT), large cell neuroendocrine 

carcinoma (LCNEC) and small cell lung carcinoma (SCLC). Apart from 

SCLC which accounts for 20–25% of pulmonary tumors, carcinoids and 

LCNEC are rare tumors with a reported prevalence of approximately 

3% among surgically resected lung cancers. Generally speaking there 

is only little information on the prevalence of neuroendocrine tumors 

in resected patients so that we would like to present the data collected 

our institution. 

Patients and method. Retrospective analysis of 1244 surgically resected 

lung cancer patients in our institution between January 2007 and 


55

Abstracts 

December 2010. For patients with a diagnosis of TC, AT and LCNEC we 

compared the data in terms of age, sex, smoking habits and tumor stage. 

Results. Among the resected patients 17 (1.7%) were diagnosed with TC, 

6 with AT (0.6%) and 25 patients with LCNEC (2.5%). A mixed histology 

of LCNEC and SCLC was found in 8 out the 25 patients with a LCNEC. 

LCNEC highly correlated with smoking (all were smokers) and the patients 

were diagnosed at a later stage compared to those with carcinoids. 

Patients with TC and AT happened more likely to be women, neversmokers 

and were mainly diagnosed in stage I. There was no significant 

difference in age between these groups. 

Conclusions. Neuroendocrine tumours of the lung are rare. Retrospective 

analysis of this data allows us to differentiate between these patients 

in terms of prognosis. The importance of clinical trials is underlined 

especially for patients with LCNEC as they have a poor prognosis. Two 

new clinical Trials are initiated to examine the efficacy and safety of 

Pasireotid LAR (SOM230) and Everolimus (RAD 001) in the treatment 

of LCNEC. 

0367 

Expression profiling of serum microRNAs in non-small cell lung 

cancer 

S . Kaduthanam1,2 , T . Muley2 , M . Meister2 , J .C . Brase1 , M . Johannes1 , S . Gade1 , 

F .F . Herth3 , H . Dienemann4 , H . Sültmann1 , *R . Kuner1 1 2 DKFZ/NCT, AG Krebsgenomforschung, Heidelberg, Deutschland, Thoraxklinik, 

University of Heidelberg, Translational Research Unit, Heidelberg, 

Deutschland, 3Thoraxklinik, University of Heidelberg, Department of Pneumology 

and Critical Care Medicine, Heidelberg, Deutschland, 4Thoraxklinik, University of Heidelberg, Department of Thoracic Surgery, Heidelberg, 

Deutschland 

Introduction. Lung cancer is the leading cause of cancer related death 

worldwide. At the time of diagnosis, about 40% of non-small cell lung 

cancer (NSCLC) patients already have metastases, which lead to a worse 

prognosis. Detection of NSCLC at early stage and the subsequent surgical 

resection strongly increase the 5-year survival rate. However, even 

for early-stage tumor diagnosis, the outcome is critically determined by 

metastatic spread: About 30–50 % of patients encounter a recurrence 

after surgery for lung cancer. At the time of diagnosis, those patients 

might benefit from additional treatment like chemotherapy and radiation. 

The aim of the study was to identify serum microRNAs associated 

with early relapse of NSCLC patients. 

Methods. The study included serum from 231 patients with NSCLC 

diagnosis, chronic obstructive pulmonary disease (COPD) or healthy 

controls. Upon RNA extraction, qRT-PCR based microRNA screening 

using low-density arrays (667 microRNAs) was performed from a subset 

of 40 patients. Several microRNA candidates were further validated in 

an independent patient cohort. Moreover, microRNA expression was 

compared between serum and tissues of the same NSCLC patients including 

matched tumor and normal specimens. 

Results. The screening experiment suggested six circulating microR- 

NAs to be associated with NSCLC relapse. Two serum microRNAs 

could be validated in an independent cohort to be differentially abundant 

between patients with early and late relapse. The abundance of 

microRNAs was also found to be influenced by the non-malignant lung 

disease COPD, which represent a risk factor for lung cancer. Moreover, 

microRNAs were found to be similarly abundant in serum and tissues 

of NSCLC patients. 

Conclusion. In this study, we have found promising circulating microR- 

NAs associated with early relapse of NSCLC. The abundance of microR- 

NA biomarkers can be influenced by other lung diseases like COPD. 


0432 

Debulking surgery followed by adjuvant chemoradiation in 

malignant pleural mesothelioma 

*S . Bölükbas1 , M . Eberlein2 , A . Fisseler-Eckhoff3 , D . Ghezel-Ahmadi1 , J . Schirren1 

1Dr . Horst Schmidt Klinik, Thoraxchirurgie, Wiesbaden, Deutschland, 

2Carver College of Medicine, Division of Pulmonary, Critical Care and Occupational 

Medicine, Iowa City, USA, 3Dr . Horst Schmidt Klinik, Institut für 

Pathologie und Zytologie, Wiesbaden, Deutschland 

Objective. To investigate the effectiveness of extended debulking surgery 

in terms of lung-sparing radical pleurectomy (RP) within a standardized 

multimodality treatment of malignant pleural mesothelioma 

(MPM). 

Methods. All patients with histologically proven MPM and without 

prior treatment for MPM were assessed for trimodality therapy in a 

prospective, non-randomized study from November 2002 to December 

2008: RP (visceral and parietal pleurectomy) followed by 4 cycles 

of chemotherapy (Cisplatin/Pemetrexed) and radiation of the intervention 

sites (21 Gy in 3 fractions). Primary end-point was overall survival. 

Secondary end-points were progression-free survival (PFS), patterns of 

recurrence, morbidity and mortality. 

Results. Fifty-two out of 135 consecutive patients were included in the 

study. Forty-nine patients (94%) completed the trimodality therapy. 

Surgical morbidity and mortality were 23.1% (12/52) and 1.9% (1/52), 

respectively. Primary histology was epithelial (80.8%). Macroscopic 

complete resection (MCR) could be achieved in 65.4%. Thirty patients 

(57.7%) had advanced disease at International Mesothelioma Interest 

Group (IMIG) stages III/IV. Mean follow-up was 26.9 months. Median 

survival was 26.3 months. One- and 5-year-survival rates were 76% and 

33%, respectively. Mean PFS was 21.5 months. The sites of failure were 

locoregional (28/51, 54.9%), distant (10/51, 19.1%) and both (2/51, 3.9%). 

Significant survival differences were seen for MCR vs. incomplete resections 

(p

were inoperable at the time of diagnosis. Twenty patients underwent 

resection with en bloc hemivertebrectomy (n=16) or total vertebrectomy 

(n=4). Induction chemotherapy was given to 6 patients (30%). Complete 

resection rate (R0) was achieved in 16 patients (80%). Morbidity 

and mortality rates were 40% and 0%, respectively. Adjuvant radiation 

(n=14) or chemoradiation (n=6) were administered with 66 Gy. The 

mean survival was 46.0 months. Five-year survival for patients who 

underwent surgery (n=20) was 47%. Inoperability was associated with 

poorer survival (14.0 months; p=0.004). Sublobar resections (p=0.002) 

and incomplete resections (p=0.02) were negative prognostificator. A 

trend towards prolonged survival were observed in patients with adjuvant 

chemoradiation (p=0.088), hemivertebrectomy (p=0.062) and 

age

Abstracts 

Discussion. Patients undergoing cancer treatment experienced severe 

reductions in their level of PA. Inpatient stays especially affected PA due 

to being restricted on the ward. Patients with a bone tumor showed the 

greatest limitations which is attributable to the consequences of surgery. 

Patients were at an increased risk for sustained inactivity. Consequently 

patients being restricted to the ward and especially patients with a 

bone tumor should receive special attention to prevent inactivity related 

negative health effects. This baseline data emphasizes the need for interventions 

individually tailored to the patients’ well-being. While wellestablished 

in adult cancer treatment, this has not yet been sufficiently 

taken into account in children. The method used in the study could be 

an appropriate tool to compare different cancer entities, points in time 

and the effects of intervention. 

0207 

Costs of Posaconazole compared to standard prophylaxis in patients 

with a high-risk of invasive fungal diseases: an economic 

analysis from the Cologne Cohort of Neutropenic Patients 

*S . Heimann1 , O .A . Cornely1 , H . Wisplinghoff2 , M .J .G . Vehreschild1 , B . Franke1 , 

J .-P . Glossmann1 , J . Vehreschild1 1 2 Uniklinik Köln, Klinik I für Innere Medizin, Köln, Deutschland, Uniklinik 

Köln, Institut für Medizinische Mikrobiologie, Immunologie und Hygiene, 

Köln, Deutschland 

Background. Prior trials have demonstrated efficacy and effectiveness 

of posaconazole in the prophylaxis of invasive fungal diseases (IFD) 

in high-risk patients. Controversy exists about the cost effectiveness of 

posaconazole prophylaxis in neutropenic patients with a high risk of 

invasive fungal diseases. We performed an analysis comparing the direct 

costs of posaconazole prophylaxis against topical polyene (thrush) 

prophylaxis in patients with acute myelogenous leukemia (AML) and 

myelodysplastic syndrome (MDS). 

Methods. Data of AML/MDS patients receiving remission-induction 

chemotherapy were extracted from the Cologne Cohort of Neutropenic 

Patients to compare hospital costs of patients before (2003–2005) and 

after (2006–2008) introduction of posaconazole prophylaxis. All cases 

were part of an earlier analysis demonstrating effectiveness of posaconazole 

over topical prophylaxis [Vehreschild et al., J Antimicrob Chemother. 

2010 Jul;65(7):1466–71]. Duration on general ward, intensive 

care unit, mechanical ventilation, diagnostic procedures and all antiinfective 

drugs were included into the cost analysis. 

Results. Patient groups were well matched according to age, gender, 

underlying disease, and duration of neutropenia. The average costs per 

patient in the posaconazole group (n=76) and the topical polyene group 

(n=81) were 23,235 € (95% CI: 19,722–26,749 €) and 26,531 € (95% CI: 

21,887–31,175 €) per patient, respectively. Average daily treatment costs 

were 495 € (95% CI: 434–555 €) and 508 € (95% CI: 433–582 €). Antifungal 

treatment costs were nominally lower in the posaconazole group 

(6,773 € [95% CI: 5,187–8,360 €] vs. 7,419 € [95% CI: 5,062–9,775 €]). The 

costs for other anti-infectives were also numerically decreased in the 

posaconazole group (4,845 € [95% CI: 4,019–5,671 €] vs. 5,402 € [95% 

CI: 4,507–6,297 €]). Average duration of ICU stays were 1.79 (95% CI: 

0.68–2.90) days per patient for the posaconazole group compared to 3.83 

(95% CI: 1.53–6.13) days per patient in the topical polyene group. Costs 

for diagnostic procedures were 611 € (95% CI: 478–744 €) and 653 € (95% 

CI: 552–754 €) per patient, respectively. 

Conclusions. In our hospital, there was a trend towards cost-saving by 

posaconazole prophylaxis in patients receiving remission-induction 

chemotherapy. These cost savings were demonstrated in all aspects taken 

into consideration, including overall treatment costs as well as cost 

of anti-infective and antifungal medication. 


0234 

Bedeutung von CT-Größe und -Dichte (“size and attenuation 

CT-SACT”) von residuellen Raumforderungen nach spezifischer 

Therapie follikulärer Non-Hodgkin-Lymphome 

*M . Horger1 , D . Spira1 1Eberhard-Karls-Universität Tübingen, Radiologie, Tübingen, Deutschland 

Ziel. Evaluation der CT-Dichte-Ratio von residuellen Tumormanifestationen 

bei Patienten mit follikullären Non-Hodgkin-Lymphome (FL) 

am Ende der Therapie verglichen mit den Ausgangsbefunden und Ermittlung 

deren prognostischer Bedeutung. 

Material und Methodik. Es konnten retrospektiv über das hauseigene 

digitale Datenarchiv im Zeitraum 2002–2010, 52 konsekutive Patienten 

mit FL welche am Ende der Therapie noch residuelle Lymphommanifestationen 

beibehalten hatten und sich sowohl in der Primärdiagnostik 

als auch zum Therapieabschluss einer kontrastmittelangehobener 

Ganzkörper-CT unterzogen hatten, identifiziert werden. Eine Schwächungsratio, 

definiert als Quotient von CT-Dichte zwischen Tumor und 

umliegender Muskulatur (HU) wurde anschließend für beide Zeitpunkte 

berechnet. Die Größe der analysierten Lymphommassen wurde 

als Produkt von Länge und Breite dieser Befunde registriert. 28 von 52 

Patienten wurden dann im weiteren Verlauf über ≥2 Jahre nach Therapieabschluss 

kontrolliert und die Ergebnisse mit dem rezidivfreien 

Intervall korreliert. 

Ergebnisse. AR und Tumorgröße nahm signifikant ab im Vergleich Ausgang- 

zu Endtreatment-Untersuchung bei Respondern (n=51; p

Discussion. In the surveys part of this study, children and adults as well 

stated they had an enormous interest in finding further information on 

the disease they were confronted with. Furthermore, data from various 

other studies of the past indicates the existence of two facts about patient 

orientated health education to keep in mind: First of all, the internet 

as a source of growing importance as provider of health-related information. 

Second, the difficulties of lay people, especially children, to 

comprehend texts including high quality medical information. “KONI” 

and its design can be an online-presence solving the difficulties resulting 

from these two facts. 

Conclusion. For the benefit of children of the enormous potential of the 

internet as a source of information it is of tremendous importance to 

enable them to understand the content. Therefore, it is very important 

to design web pages eligible for youth. KONI can be a website meeting 

this expectation. 

0302 

Durable complete remissions in a pivotal phase 2 study of SGN- 

35 (brentuximab vedotin) in patients with relapsed or refractory 

Hodgkin lymphoma (HL) 

*A . Younes1 , A .K . Gopal2 , S .E . Smith3 , S .M . Ansell4 , J .D . Rosenblatt5 , K .J . Savage6 

, J .M . Connors6 , A . Engert7 , E .K . Larsen8 , D .A . Kennedy8 , E .L . Sievers8 , 

R . Chen9 1 2 University of Texas, MD Anderson Cancer Center, Houston, USA, University 

of Washington, Cancer Research Center, Seattle, USA, 3Loyola University, 

Medical Center, Maywood, USA, 4Mayo Clinic, Rochester, USA, 5University, Miami, USA, 6BC Cancer Agency, Center for Lymphoid Cancer, Vancouver, 

Kanada, 7University Hospital, Cologne, Deutschland, 8Seattle Genetics, Inc ., 

Bothell, USA, 9City of Hope National Medical Center, Duarte, USA 

Introduction. CD30 expression by Reed-Sternberg cells is a defining feature 

of HL. SGN-35 comprises an anti-CD30 antibody conjugated by a 

plasma-stable linker to the potent antimicrotubule agent, monomethyl 

auristatin E (MMAE). SGN-35 selectively induces apoptotic death of 

CD30+ cells by binding, internalizing, and releasing MMAE. 

Methods. A pivotal, phase 2, single-arm, multicenter study evaluated 

the efficacy and safety of SGN-35 in patients (pts) with relapsed 

or refractory HL after autologous stem cell transplant (auto-SCT). Pts 

received SGN-35, 1.8 mg/kg q3 weeks (wks) as a 30-min. outpatient IV 

infusion for up to 16 cycles. The primary endpoint was the objective response 

rate (ORR) per an independent review facility (IRF) according 

to Cheson 2007. 

Results. 102 pts were enrolled; 53% female, median age was 31 yrs (range 

15–77). Pts had received a median of 3.5 (range 1–13) prior systemic therapies 

excluding auto-SCT. 71% of pts had primary refractory disease and 

42% had not responded to their most recent prior therapy. ORR per IRF 

was 75% (76 of 102 pts) with complete remissions (CRs) in 34% of pts 

(n=35). At the time of database lock (August 2010), median duration of 

follow up from first dose was approx. 9 months (for responders). Median 

duration of response for pts with CR per IRF has not yet been reached 

(range 0.3+ to 61.4+ wks); follow up continues and 6+ months of additional 

data will be available for presentation. Treatment-related AEs of any 

grade in ≥15% pts were peripheral sensory neuropathy, nausea, fatigue, 

neutropenia, and diarrhea. AEs ≥ grade 3 in ≥5% of pts were neutropenia, 

peripheral sensory neuropathy, thrombocytopenia, and anemia. 

Conclusions. With manageable AEs, single-agent SGN-35 induced objective 

responses in 75% of pts with relapsed or refractory HL. In this 

heavily pretreated population, 35 of 102 pts (34%) achieved a durable CR, 

with more than 65% of pts remaining in CR. 

0312 

Molecular monitoring, response and adherence to treatment 

in outpatients with chronic myeloid leukemia in chronic phase 

(CML-CP) treated with imatinib: 42-month follow-up results of a 

non-interventional study 

*H . Tesch1 , M . Welslau2 , C . Spohn3 , K . Blumenstengel4 , U . von Verschuer5 1Onkologische Gemeinschaftspraxis am Bethanien Krankenhaus, Frankfurt/M, 

Deutschland, 2Onkologische/Diabetologische Gemeinschaftspraxis 

Klausmann/Welslau, Aschaffenburg, Deutschland, 3Onkologische Gemeinschaftspraxis, Halle, Deutschland, 4Onkologische Gemeinschaftspraxis, 

Eisenach, Deutschland, 5Onkologische Gemeinschaftspraxis, Essen, 

Deutschland 

The availability of imatinib has changed the treatment paradigm in 

CML. Long-term benefits from imatinib in terms of overall survival, 

increasing response and decreasing disease progression have been confirmed 

by data from the 7-year update of the phase III IRIS (International 

Randomized Study of Interferon vs STI571). However, good patient 

adherence is mandatory to achieve maximal treatment benefit and to 

avoid imatinib resistance. Estimation of BCR-ABL transcript levels by 

quantitative polymerase chain reaction (qPCR) is the method of choice 

for monitoring therapeutic efficacy and prognosis. The aim of this 

non-interventional study was to evaluate molecular response of patients 

with CML-CP by qPCR with respect to adherence during treatment 

with imatinib. A total of 514 outpatients from 56 centers, mainly hematology/oncology 

practices and outpatient clinics were included. Patients 

received imatinib according to the prescription information and physician‘s 

decision. 4.1% of the patients belonged to the high risk, 42.7% to 

the intermediate risk and 41.8% to the low risk group (Hasford prognostic 

score). Molecular monitoring was performed in 91.3% of the patients. 

Major molecular response (BCR-ABL transcript reduction >3 log), was 

observed in 34.5% of the patients, no BCR-ABL transcripts at all were 

detected in 50.1%, and a minor molecular response

Abstracts 

in MDS patients with transfusion-dependent iron overload. The study 

is currently being conducted in approx. 100 hematology/oncology institutions 

in Germany. Patients are being treated with deferasirox according 

to established guidelines and the prescribing information. 

Iron overload is assessed by serum ferritin measurement as well as by 

MRI-LIC determination if routinely performed. Moreover, the number 

of blood transfusions, co-medication, safety and efficacy of deferasirox 

as well as adherence to treatment are assessed. For patients, in whom 

no bone marrow biopsy is performed, cytogenetic analysis of CD34+ 

cells from peripheral blood can be requested at a reference institution. 

Patients are evaluated before starting therapy and after about 3, 6, 9, 

12, 18, and 24 months of treatment. Between March 2010 and the first 

interim analysis with data cut-off in May 2011 82 of 250 planned patients 

were prospectively enrolled. Mean patient age was 73.9±10.0 years. Median 

serum ferritin levels before treatment were 1751±1483 ng/ml. Most 

patients were classified as IPSS low (15%) or intermediate 1 (29%). Median 

deferasirox dose was 135±590 mg/day. Further data from the first 

interim analysis will be presented. These data will reflect medical care 

of MDS patients in Germany with respect to the monitoring of iron 

chelation therapy and may provide evidence for a potential role of LIC 

determination by MRI. 

0334 

Physical performance status as independent predictor for cancer-related 

fatigue and physical functioning in allogeneic stem 

cell-transplanted patients 

*D . Vandenbergh1 , M . Bohus2 , P . Dreger3 , R . Schwerdtfeger4 , D . Jäger5 , 

C . Ulrich1 , N . Rea1 , J . Wiskemann5,1 1National Center for Tumor Diseases (NCT) and German Cancer Research 

Center (DKFZ), Heidelberg, Preventive Oncology, Heidelberg, Deutschland, 

2 3 Central Institute of Mental Health, Mannheim, Deutschland, University 

Clinic Heidelberg, Department of Hematology, Oncology, and Rheumatology, 

Heidelberg, Deutschland, 4German Clinic for Diagnostic, BMT Unit, 

Wiesbaden, Deutschland, 5National Center for Tumor Diseases (NCT) and 

University Clinic Heidelberg, Medical Oncology, Heidelberg, Deutschland 

Introduction. Allogeneic hematopoietic stem cell transplantation (allo- 

HSCT) is a medical treatment with many and severe side effects. Nevertheless, 

for many patients with hematologic malignancies it is the last 

and only chance for cure. Due to the malignancy itself and prior treatment 

many patients have already impairments in physical functioning 

when the transplantation process starts [Morishita et al. 2011 (1)]. Moreover 

patients suffer from Cancer-Related Fatigue (CRF) and an even 

further reduced physical functioning after being transplanted [Hacker 

et al. 2006(2)]. We hypothesized that reduced physical performance before 

allo-HSCT is an independent predictor for patients’ physical functioning 

(PF) and their CRF status 6–8 weeks after transplantation. 

Methods. We evaluated the physical performance status of n=60 patients. 

We used the 6 min walk distance (6 MWD) as a marker for the 

patients’ cardiovascular fitness. Arm strength (elbow flexors and extensors, 

shoulder abductors) and leg strength (hip abductors and flexors, 

knee flexors and extensors) were measured using a Hand-Held-Dynamometer 

and were jointly used to calculate a general Force Index (FI). 

CRF and physical functioning were evaluated using subscales of the 

EORTC-QLQ-C30 quality of life questionnaire. For regression analyses 

we defined 6 MWT and FI as independent variables and CRF and PF as 

dependent variables. p-values

1 . Al-Majid S, Gray D (2009) A biobehavioral model for the study of exercise 

interventions in cancer-related fatigue . Biol Res Nurs 10:381–91 

2 . Wiskemann J et al (2011) Effects of a partly self-administered exercise 

program before, during and after allogeneic stem cell transplantation . Blood 

117:2604–13 

0417 

High serum-free light chain levels correlate with the poor prognostic 

cytogenetic aberration del(17)(p13) in multiple myeloma 

patients 

*S . Janjetovic1 , E .M . Murga Penas1 , P . Behrmann1 , C . Bokemeyer1 , G . Schilling1 

1Universitätsklinikum Eppendorf, Hämatologie-Onkologie, Hamburg, 

Deutschland 

Multiple myeloma (MM) is a monoclonal B-cell malignancy characterized 

by terminally differentiated plasma cells and monoclonal 

immunoglobulin secretion in the majority of cases. Cytogenetics is 

an important tool to estimate prognosis in this disease. Recently developed 

serum-free light chain (SFLC) assay has proved invaluable in 

case of light-chain-secreting MM and in a proportion of patients with 

non-secretory disease. It has been previously demonstrated that high 

serum-free light chain levels define an aggressive MM subtype with 

poor prognosis and are associated with higher levels of LDH and β2 microglobulin, 

as well as higher plasma cell bone marrow infiltration (van 

Rhee et al. 2007). 

In order to investigate whether cytogenetic changes correlate with SFLC 

levels in patients with newly diagnosed MM, we compared the SFLC 

levels of 35 patients with their cytogenetic findings done by fluorescence 

in situ hybridization (FISH). 

The cut off value for “high” SFLC levels was fixed at 75 mg/dL, as previously 

described (van Rhee et al. 2007). We identified a SFLC baseline 

level higher than 75 mg/dL in 12 out of 35 patients (34%), with the highest 

level being 2741,7 mg/dL. The remaining 23 patients showed SFLC levels 

between 60 and 0.1 mg/dl and, therefore, constituted our control group 

with low SFLC. 

The most common cytogenetic aberration in both groups was 13q14 deletion, 

found in 17 out of 35 analyzed patients (49%). Six deletions were 

found in group with high SFLC (50%) and 11 deletions in lower SFLC 

group (48%). Interestingly, we detected deletion 17p13 (TP53) in 2 patients 

both of them showing SFLC level higher than 75 mg/dL (2741.7 

and 402.2 mg/dL respectively), but none in patients in “low level” group. 

TP53 deletion is known to be an adverse prognostic factor in MM associated 

with a poor prognosis and refractoriness to conventional 

chemotherapy, allogenic stem cell transplantation, and, so called, new 

substances. 

In this study we found that only patients with SFLC levels higher than 

75 mg/dL exhibit the negative prognostic deletion of 17p13, whereas the 

neutral deletion 13q14 was detected in both groups with the same frequency. 

Our results point to a correlation between the negative prognostic deletion 

of the tumour suppressor gene TP53 and high SFLC levels. Further 

investigations on larger patient cohorts are needed to confirm our interesting 

findings. 

0476 

Survival of Non-Hodgkin’s lymphoma patients in Germany 

D . Pulte1,2 , *L . Jansen1 , A . Gondos1 , B . Holleczek3 , A . Katalinic4 , H . Brenner1,5 1Deutsches Krebsforschungszentrum (dkfz), Klinische Epidemiologie und 

Alternsforschung, Heidelberg, Deutschland, 2Thomas Jefferson University, 

Division of Hematology, Philadelphia, Deutschland, 3Krebsregister Saarland, Saarbrücken, Deutschland, 4Krebsregister Schleswig-Holstein, 

Lübeck, Deutschland, 5GEKID Cancer Survival Working Group, Deutschland 

Background. Non-Hodgkin’s lymphoma (NHL) is the most common hematologic 

cancer in adults. Recent advances in treatment of NHL have 

led to improved survival both in clinical trials and on the population 

level. Previously, in Germany data on population-level changes in survival 

was restricted to data from the Saarland cancer registry. Our study is 

based on survival data provided by 11 population-based German cancer 

registries covering 33 million people (40% of the population). This data 

set allowed a detailed analysis of survival of German NHL patients by 

major age groups and sex. 

Methods. Patients diagnosed with NHL (ICD-10: C82–C85) in 1997– 

2006 were included in the analysis. Period analysis was used to calculate 

5-year relative survival estimates overall and by sex and age at diagnosis 

(15–49, 50–54, 55–59, 60–64, 65–69, 70–74, 75+ years) for the time period 

2002–2006. Trends in relative survival between 2002 and 2006 were 

estimated by model-based period analysis. Relative survival estimates 

for Germany and the United States (US) were compared using the Surveillance, 

Epidemiology, and End Results (SEER13) database. 

Results. Overall age-standardized 5-year relative survival for NHL patients 

in Germany in 2002–2006 was 62.8%. Survival decreased strongly 

with age from 81.7% at age 15–49 to 46.5% at age 75+. Women had a better 

prognosis overall and in each age group. Survival significantly increased 

between 2002 and 2006 by 5.3 percent units (% units). This increase 

can mainly be attributed to improvements in survival for patients aged 

60–74 years. No increase was observed for the age groups 15–49 and 75+. 

In the US, overall age-standardized 5-year relative survival was slightly 

higher (65.1%) as a result of better survival of patients aged 65+ in the US 

(+4.4 to +6.1% units). Patients aged 50–64 had comparable prognosis in 

the US and in Germany, whereas patients aged 15–49 had a 6.6 % units 

higher 5-year relative survival in Germany. 

Conclusion. Our results show that age-standardized 5-year relative survival 

of NHL patients in Germany and in the US is comparable. However, 

patients aged 65+ had lower survival rates in Germany than in the 

US. While the difference for patients aged 65–74 may decrease over time 

as the prognosis of patients in this age group improved strongly between 

2002 and 2006, no improvement was observed for patients aged 

75+. These results suggest that greater focus on treatment of NHL in the 

oldest patient group in Germany may be needed. 


0015 

Breast self-examination (BSE) in post treatment surveillance 

after breast cancer: a prospective study 

*J . Johannsen-Wrana1 , H .J . Hamm1,2 1 2 Allg . med . Praxis Bachmann, Sylt OT Westerland, Deutschland, UK-SH, 

Campus Kiel, medizinische Fakultät, Kiel, Deutschland 

Introduction. Breast cancer is the most frequent tumor among women 

in Germany, accounting for about 28% of all female cancer cases. Breast 

self-examination (BSE) is an important part of breast cancer detection. 

Many patients after surgery are reluctant to practice BSE because of 

personal, cognitive, emotional and health-care provider factors. This 

prospective consecutive two-arm study was conducted to investigate 


61

Abstracts 

the performance of BSE in rehab patients with or without a targeted 

education program. 

Methods. 1521 patients between the age of 30 and 75 were included in 

the study. From September 2009 to September 2010, they were asked to 

fill out a standardized self-report questionnaire about their use of BSE 

before diagnosis, at the beginning of rehabilitation, after rehabilitation 

and six month after rehabilitation. The last questionnaire asked for any 

profit of the BSE-training and if they practice BSE or not. Patients were 

divided into three groups. Group I (n=487) performed a classical S3-guideline-breast 

cancer-rehab, group II (n=534) was additionally educated 

in BSE in theory and was offered the possibility to practice BSE with 

educated physiotherapists. Group III (n=500) received the normal rehab 

program and served as a wash-out-group between study groups. 

Results. At the end of rehab in group I 61.3% reported to perform BSE regularly, 

24.7% sometimes and 13.9% never. In group II 69.9% reported to 

perform BSE regularly, 21.5% sometimes and 8.6% never. A questionnaire 

six month after rehab was answered by 789 patients (77.30% response 

rate, 789/1021). Group I reported to perform BSE 55.8% regularly, 29.7% 

sometimes and 14.5% never. Group II reported to perform BSE 53.8% 

regularly, 35.5% sometimes and 10.8% never. 84.4% of group II reported 

a profit regarding BSE while 41.1% did so in group I. 

Conclusion. In this study, patients after breast cancer therapy reported a 

significant profit after an education-program for BSE during rehabilitation 

in comparison to a control group undergoing a standard rehab program. 

However, the program promoted the performance of BSE only to 

a small extent. We speculate that the questionnaire itself may have had 

a positive impact on BSE performance. Further research is needed to 

evaluate the quality of BSE after our program and the long-term adherence 

of the women to the procedure. Additionally, it would be of interest 

to show if such a program would have an impact on morbidity and/or 

mortality of breast cancer patients. 

0024 

The ProBone study: influence of zoledronic acid on bone mineral 

density in premenopausal women with breast cancer and neoadjuvant 

or adjuvant chemotherapy and/or endocrine treatment 

*P . Hadji1 , A . Kauka1 , T . Bauer1 , M . Kalder1 , U .-S . Albert1 , K . Birkholz2 , M . Baier2 , 

M . Muth2 , M . Ziller1 1Philipps-University of Marburg, Department of Gynecology, Endocrinology 

and Oncology, Marburg, Deutschland, 2Novartis Pharma GmbH, BU 

Oncology, Nürnberg, Deutschland 

Background. Based on baseline bone mineral density (BMD), adjuvant 

chemotherapy (CT) or endocrine therapy (ET) for early breast cancer 

(BC) patients (pts) can lead to substantially increased osteoporotic 

fracture risk. After 2 years of CT and/or ET, a significant decrease of 

BMD has been reported. In recent studies (e. g. ABCSG-12, Z-FAST, 

ZO-FAST), the treatment of pts with zoledronic acid (ZOL) led to an 

increase in BMD in premenopausal and postmenopausal pts with BC. 

In addition, a significant increase in disease-free survival (DFS) with 

ZOL versus no ZOL was observed in most of these studies. 

Methods. The aim of 2 single-center, placebo-controlled, randomized 

studies – Probone I and II – was to investigate the effect of adjuvant 

treatment with ZOL on BMD in premenopausal women with early BC 

treated with CT and/or ET. Pts with hormone-receptor-negative (HR-) 

BC (ProBone I) were treated with (neo)adjuvant CT; pts with hormonereceptor-positive 

(HR+) BC (ProBone II) were treated with adjuvant ET 

alone or in combination with (neo) adjuvant CT. Pts received ZOL 4 mg 

or placebo IV every 3 months for 24 months. The primary objective was 

the change in BMD at the lumbar spine between baseline and month 

24 (measured by DXA). Secondary objectives included metastasis-free 

survival; BMD at total hip; QUS at os calcis and phalanges; markers of 

bone turnover (e.g. CTX and P1NP); endocrine hormones (e.g. FSH, estradiol, 

testosterone, SHBG, PTH, vitamin D, AMH, inhibin A/B, etc.); 

pathologic fractures; safety and tolerability. 


Results. 71 HR+ and 11 HR-BC pts have been enrolled into the studies at 

1 site. The last patient will have been treated for 24 months by the end of 

June 2011. The results of the primary and secondary endpoints will be 

presented at the meeting. 

Conclusion. The results of the ProBONE studies will provide information 

regarding the efficacy of ZOL in the prevention of bone loss in premenopausal 

women under CT or ET. Furthermore, the analysis of bone 

markers will provide insights in bone metabolism and the evaluation 

of several endocrine hormones could contribute important findings on 

the relationship between the hormone status and the course of bone 

markers with or without ZOL. Therefore, important findings could be 

obtained for the growing number of young BC survivors who will enter 

menopause early and experience a prolonged period of estrogen deficiency 

and an increased long-term fracture risk due to cancer treatment. 

0026 

Reduced HFSR incidence observed in a randomized phase II study 

in advanced breast cancer patients treated with sorafenib and 

paclitaxel by initial ramp-up dose escalation (PASO) 

*F . Overkamp1 , C .-C . Steffens2 , W . Abenhardt3 , C . Lerchenmüller4 , A . Nusch5 , 

T . Göhler6 , M . Groschek7 , S . Hegewisch-Becker8 , N . Marschner9 , S .B . Rösel10 , 

C . Salat11 , T . Decker12 1 2 Oncologianova GmbH, Recklinghausen, Deutschland, Schwerpunktpraxis 

Hämatologie/Onkologie, Stade, Deutschland, 3Münchner Onkologische 

Praxis, München, Deutschland, 4Hämatologisch-Onkologische Gemeinschaftspraxis, 

Münster, Deutschland, 5Praxis für Hämatologie und internistische 

Onkologie, Velbert, Deutschland, 6Onkologische Gemeinschaftspraxis, 

Dresden, Deutschland, 7Onkologische Gemeinschaftspraxis, Würselen, 

Deutschland, 8Onkologische Schwerpunktpraxis, Hamburg, Deutschland, 

9Praxis für interdisziplinäre Onkologie & Hämatologie, Freiburg i . Br ., 

Deutschland, 10Onkodok, Gütersloh, Deutschland, 11Gemeinschaftspraxis f . 

Innere Medizin, Hämatologie und Int . Onkologie, München, Deutschland, 

12Onkologie Ravensburg, Ravensburg, Deutschland 

Introduction. Breast cancer is the most common malignancy among 

women in Germany and despite some therapeutic progress still challenging 

in the metastatic stage. The importance of the VEGF pathway 

was recently discovered and clinically verified in terms of prognosis. 

Sorafenib (Sor) is a multi-targeted inhibitor for several tyrosine and serine/threonine 

protein kinases including VEGF, PDGF, cKIT and Raf. 

Sor showed a considerable efficacy in three phase II trials in advanced 

breast cancer (aBC) in combination with paclitaxel (pac), capecitabine 

(cap) and gemcitabine (gem). The side effect profile seems manageable 

and clinically safe but an improvement in terms of hand foot skin reaction 

(HFSR) remains desirable. A phase II trial was planned by the 

AIO study group sponsored by GMIHO to investigate a combination 

of sor with pac vs. pac monotherapy including an initial ramp-up dose 

escalation in patients with aBC. 

Patients and methods. The study will recruit 140 pts with aBC due for 

second or third line cytostatic treatment in 30 AIO centers. The pts 

are randomized to weekly 80 mg/m2 pac in combination with 400 mg 

sor bid in treatment cycles of 4 weeks or applied as monotherapy until 

progression or intolerable side effects. Dose modifications or temporary 

discontinuation are carried out in case of severe side effects for sor 

and pac according to protocol. A ramp-up dose escalation scheme is 

implemented starting with 400 mg/day for the first, 600 mg/day for the 

second cycle and 800 mg/day as a continuous treatment starting with 

the third cycle. 

Results. The first safety analysis after 20 pts treated for at least two cycles 

in June 2011 showed a side effect profile comparable with known data 

from pac and sor. The overall incidence of HFSR in the sor+pac group 

was found as previously published with 5/10 pts showing a HFSR of any 

CTCAE grade but the incidence of grade 3 HFSR was surprisingly low 

with only 2/10 pts (20%).

Conclusions. The incidence of grade 3 HFSR seems to be remarkably low 

despite the early stage of our trial comparing our results with data for 

sor + cap (Baselga et al., ESMO 2009; 89% all grade and 45% grade 3), for 

sor + pac (Gradishar et al., SABCS 2009; 55% all grade and 30% grade 3) 

and for sor + gem (Hurdis et al., ASCO 2011, 39% grade 3). The used 

ramp-up dose escalation for sor seems promising. The study will be 

continued as planned to confirm the reduction in HFSR using the new 

dose scheme and determine the efficacy for the sor + pac combination 

in pts with aBC. 

0039 

Fibroblast growth factor receptor 4 gene (FGFR4) 388Arg allele 

predicts prolonged survival and platinum sensitivity in advanced 

ovarian cancer 

*F . Marmé1 , T . Hielscher2 , S . Hug1 , S . Bondong3 , R . Zeilinger4 , D . Castillo- 

Tong4 , J . Sehouli5 , I . Braicu5 , I . Vergote6 , I . Cadron6 , S . Mahner7 , C . Sohn1 , 

A . Schneeweiss1 , P . Altevogt3 1Universitätsklinikum Heidelberg, Frauenklinik, Heidelberg, Deutschland, 

2Deutsches Krebsforschungszentrum (DKFZ), Biostatistik, Heidelberg, 

Deutschland, 3Deutsches Krebsforschungszentrum (DKFZ), Translationale 

Immunologie, Heidelberg, Deutschland, 4General Hospital of Vienna, 

Ludwig Boltzmann Cluster Translational Oncology, Wien, Österreich, 5Uni versitätsmedizin Berlin, Charité Campus Virchow Klinikum, Department 

of Gynecology, European Competence Center for Ovarian Cancer, Berlin, 

Deutschland, 6Universitaire Ziekenhuizen Leuven, Katholieke Universiteit 

Leuven, Division of Gynaecological Oncology, Department of Obstetrics 

and Gynaecology, Belgium, Belgien, 7Universitätsklinik Hamburg Eppendorf, 

Gynäkologie und Geburtshilfe, Hamburg, Deutschland 

Background. FGFR4 has been shown to play an important role in the 

etiology and progression of solid tumors. A single nucleotide polymorphism 

(SNP) within the FGFR4 gene has previously been linked 

to prognosis and response to chemotherapy in breast cancer and other 

malignancies. This study evaluates the relevance of this SNP in advanced 

ovarian cancer. 

Patients and methods. FGFR4-genotype was analyzed in 236 patients 

recruited as part of the OVCAD project. Genotyping was performed on 

germ-line DNA using a TaqMan based genotyping assay. Results were 

correlated with clinicopathological variables and survival. 

Results. The FGFR4 388Arg genotype was significantly associated with 

prolonged progression-free and overall survival (univariate: HR 0.68, 

p=0.017; HR 0.49, p=0.005; multivariate: HR 0.69, p=0.025; HR 0.49, 

p=0.006) though the positive prognostic value was restricted to patients 

without post-operative residual tumor. Indeed, there was a significant 

interaction between FGFR4 genotype and tumor rest for overall survival. 

Furthermore, the FGFR4 388Arg genotype significantly correlated 

with platinum sensitivity in the same subgroup (multivariate OR 3.81, 

p=0.004). 

Conclusion. FGFR4 Arg388Gly genotype is an independent and strong 

context specific prognostic factor in patients with advanced ovarian 

cancer and could be used to predict platinum-sensitivity. 

0045 

An epidemiological prospective cohort study with Fulvestrant 

and Exemestane in postmenopausal patients with advanced 

HR+ breast cancer under real-life conditions in Germany: The 

ACT-FASTER study 

*H . Tesch1 , B . Bruno2 , W . Greiner3 , H . Ostermann4 , K . Possinger5 , S . Zaun6 , 

N . Maass2 1 2 Onkologische Gemeinschaftspraxis, Frankfurt, Deutschland, Universitäts-Frauenklinik, 

Aachen, Deutschland, 3Universität Bielefeld, Fakultät für 

Gesundheitswissenschaften, Bielefeld, Deutschland, 4Klinikum Großhadern 

der Ludwig-Maximilians-Universität, Medizinische Klinik und Poliklinik III, 

München, Deutschland, 5Charité, Medizinische Klinik mit Schwerpunkt 

Onkologie und Hämatologie, Berlin, Deutschland, 6AstraZeneca, Medizin, 

Wedel, Deutschland 

Introduction. With the introduction of aromatase inhibitors followed 

by fulvestrant as endocrine treatments for ER+ postmenopausal (PMP) 

women with advanced breast cancer (ABC), sequential endocrine treatment 

has become the clinical standard of care in this setting (unless 

disease is acutely life threatening; see AGO guidelines). Fulvestrant 

500 mg (2×250 mg i.m. days 0, 14, 28, then monthly) was approved in 

March 2010 for ER+ ABC in PMP patients, and both fulvestrant and 

exemestane are approved post antiestrogen treatment in this setting. 

ACT-FASTER aims to generate data on the use of fulvestrant 500 mg 

and exemestane under real-life conditions with a focus on the use of 

fulvestrant in different treatment lines. 

Methods. ACT-FASTER is a prospective non-interventional cohort study 

sponsored by AstraZeneca Germany (ClinTrials ID: NCT01171417). 

It is planned to enrole 660 PMP women with ER+ ABC at approx. 

40 breast clinics and 100 office-based gynaecologists/oncologists. Data 

on clinical characteristics, clinical outcome, epidemiological and pharmacoeconomic 

parameters of treatment with fulvestrant 500 mg or exemestane 

under real-life conditions in Germany will be collected. The 

two co-primary objectives are, firstly, for patients receiving fulvestrant, 

to compare the time to progression (TTP) as a function of the line of 

treatment (i.e. 1st- vs. 2nd- vs. 3rd-line), and secondly, for all patients, to 

collect and explore real-life data on the epidemiology and management 

of patients receiving fulvestrant or exemestane for ER+ ABC, including 

tumour characteristics, data on co-morbidities and treatments received. 

Secondary endpoints are effectiveness endpoints, pharmacoeconomic 

data (resource use, etc.) and data on health related quality of life. 

Results. Recruitment started in August 2010. By July 2011, approx. 

230 patients have been recruited. Study rationale, design and an update 

on the recruitment will be presented. 

Conclusion. ACT-FASTER aims to generate real-life information on the 

endocrine treatment of PMP patients with ER+ ABC with a focus on the 

effectiveness of fulvestrant 500 mg in different treatment lines. Patient 

management in clinical practice, quality of life and pharmacoeconomics 

will also be explored. As such, ACT-FASTER constitutes an important 

project of outcomes research in this patient setting. 


63

Abstracts 

0046 

Final results from PACT (Patient’s Anastrozole Compliance to 

Therapy Programme), a non-interventional study evaluating the 

influence of a standardized information service on compliance in 

postmenopausal women with early breast cancer 

*M . Blettner1 , P . Hadji2 , N . Harbeck3 , C . Jackisch4 , H .-J . Lück5 , S . Zaun6 , 

C . Windemuth-Kieselbach7 , R . Haidinger8 , A . Rexrodt von Fircks9 , R . Kreienberg10 

1Gutenberg-Universität Mainz, Institut für medizinische Biometrie, Epidemiologie 

und Informatik, Mainz, Deutschland, 2Klinikum der Philipps- 

Universität, Klinik für Gynäkologie, gyn . Endokrinologie und Onkologie, 

Marburg, Deutschland, 3Klinik und Poliklinik für Frauenheilkunde und 

Geburtshilfe, Brustzentrum Köln/Frechen, Köln, Deutschland, 4Städtisches Klinikum, Frauenklinik, Offenbach, Deutschland, 5Gyn . Onkologische Praxis, 

Hannover, Deutschland, 6AstraZeneca, Medizin, Wedel, Deutschland, 7Alce dis GmbH, Giessen, Deutschland, 8Brustkrebs Deutschland e .V ., München, 

Deutschland, 9Selbstständig, Autorin, Ratingen, Deutschland, 10Frauenuni versitätsklinik, Ulm, Deutschland 

Introduction. In clinical trials, compliance to adjuvant endocrine therapy 

for hormone-receptor positive (HR+) early breast cancer (EBC) is 

generally high (>80%), yet, retrospective data from non-study settings 

shows that compliance may drop below 70% after one year and to only 

50% by year 4. PACT aimed to generate data from routine clinical practice 

on treatment compliance in postmenopausal women taking an adjuvant 

aromatase inhibitor and to increase treatment adherence via a 

standardized information service (educational arm). 

Methods. PACT was a prospective, randomised, two-arm parallel-group 

study in Germany (sponsor AstraZeneca; NCT00555867). Postmenopausal 

women on anastrozole for HR+ EBC were randomized to routine 

clinical care alone or to receive additional standardized information 

(educational arm) over the first year of adjuvant therapy. Primary endpoints 

were compliance and persistence rates in the educational versus 

routine arm after 12 months. Secondary endpoints included longer follow-up, 

reasons for non-compliance, influence of baseline characteristics, 

and clinical outcome parameters. Compliance was evaluated via 

patient questionnaires, prescription data and physician recall. Per protocol 

compliance was analysed only for patients with full baseline documentation 

both by patients and physicians. Persistence was defined as 

the duration of time from initiation to discontinuation of therapy and 

measured by prescription data. Regression analysis was performed to 

investigate variables influencing compliance or persistence rate. 

Results. 4923 patients were enrolled at 109 breast centres and 1361 specialist 

practices. 4397 patients were evaluable for baseline characteristics, 

and 2707 patients for the primary endpoint. No difference in compliance 

was shown between the standard (88.2%) and the educational arm 

(88.3%) at 12 months (p=0.92, Fisher’s exact test). Persistence rates were 

40.3% for the standard and 43.0% for the educational arm, respectively 

(p=0.17, Fisher’s exact test). At 24 months, data from 1539 patients was 

available for compliance per protocol. Compliance rates were 88.7% 

(educational arm) and 87% (standard arm; p=0.29), persistence 41.1% 

and 42.1% (p=0.68). Variables influencing compliance were regular 

attendance to follow-up visits, participation in a cancer rehabilitation 

program, number of co-morbidities and current employment status. 

Persistence was influenced by factors such as tumour stage, joint pain 

and cancer rehab program participation. 

Conclusion. The addition of standardized information materials to standard 

clinical care did not increase the compliance or persistence rates. 

This result led to closing the study after the 24 months follow-up (planned 

60 months). However, PACT represents the largest prospective study 

to evaluate compliance and persistence to adjuvant endocrine therapy 

in postmenopausal patients with HR+ EBC and provides valuable 

data on clinical practice and treatment adherence in Germany. 


0060 

COMPliance and Arthralgias in Clinical Therapy (COMPACT): 

Assessment of the incidence of arthralgia, therapy costs and 

compliance within the first year of adjuvant anastrozole therapy 

*H .-J . Hindenburg1 , M . Blettner2 , W .W . Bolten3 , P . Hadji4 , N . Harbeck5 , 

C . Jackisch6 , R . Kreienberg7 , W . Rief8 , D . Wallwiener9 , S . Zaun10 , P . Klein11 , 

K . König12 1 2 BNGO e .V ., Berlin, Deutschland, Universität Mainz, Institut für medizinische 

Biometrie, Epidemiologie und Informatik, Mainz, Deutschland, 

3 4 Klaus-Miehlke-Klinik für Rheumatologie, Wiesbaden, Deutschland, Phillips-Universität 

Marburg, Schwerpunkt für Gynäkologische Endokrinologie, 

Reproduktionsmedizin und Osteologie, Marburg, Deutschland, 5Unifrauen klinik, Brustzentrum, Köln, Deutschland, 6Klinikum Offenbach, Klinik für Gynäkologie 

und Geburtshilfe, Offenbach, Deutschland, 7Universitätsfrauen klinik, Ulm, Deutschland, 8Philipps-Universität, Psychotherapie-Ambulanz, 

Marburg, Deutschland, 9Universitätsfrauenklinik, Tübingen, Deutschland, 

10 11 AstraZeneca, Medizin, Wedel, Deutschland, d .s .h . statistical services 

GmbH, Rohrbach, Deutschland, 12Berufsverband der Frauenärzte e .V ., 

Steinbach/Ts, Deutschland 

Objective. Aromatase inhibitors (AI) are well established as adjuvant 

endocrine treatment for postmenopausal women with hormone receptor-positive 

(HR+) early breast cancer (EBC). However, clinical trials 

have shown for AI to be significantly more frequently associated with 

arthralgia than tamoxifen. As arthralgia may be a determining factor 

in influencing compliance to adjuvant endocrine therapy, we designed a 

prospective trial to collect real world data on the effects of AI-associated 

arthralgia on patient compliance, patient outcomes as well as treatment 

costs of arthralgia. 

Materials and methods. COMPACT is an open, prospective, non-interventional 

study assessing the incidence of arthralgia, therapy costs, 

and compliance within the first year of adjuvant anastrozole therapy 

in postmenopausal patients with HR+ EBC. The study is sponsored 

by AstraZeneca and supported by German health insurance funds 

(GWQ ServicePlus AG, DAK, TK). Patients on adjuvant anastrozole for 

3–6 months were enrolled and stratified by initial adjuvant anastrozole 

or switch from tamoxifen. All patients receive regular standardized 

information about breast cancer from baseline to week 20 after study 

start to support treatment compliance. Data on demographics, arthralgias, 

therapy of arthralgia and quality of life are collected at baseline, 3, 

6 and 9 months. Primary endpoints are scaled data on arthralgia and 

compliance within the first year of anastrozole therapy. Secondary endpoints 

include the incidence of arthralgias, therapy costs, reasons for 

non-compliance, and influence of arthralgias on clinical outcome. For a 

subgroup of patients data on arthralgia therapy and compliance will be 

validated with corresponding accounting data of participating health 

insurance funds. 

Results. From April 2009 to March 2011, 2313 patients were recruited, 

2007 receiving upfront anastrozole and 306 patients on switch therapy. 

The mean age was 64.5 years, mean BMI 27.7. Only 16.8% of patients 

had received HRT prior to their EBC. 41.5% of patients had concomitant 

symptoms relating to skeleton or musculature, and 11.9% stated arthralgias 

existing prior to anastrozole treatment. 13.1% reported a worsening 

of pre-existing arthralgias or new arthralgia after starting anastrozole. 

All patients will be followed for arthralgia, treatment thereof, and compliance 

to therapy. 

Conclusion. COMPACT aims to provide valid data on AI-associated arthralgias, 

treatment, therapy compliance and treatment costs. This may 

help to better inform patients and health care providers about these clinically 

important issues with the aim to improve adherence to anastrozole 

treatment, breast cancer outcomes, and therapy costs.

0061 

Vandetanib and Pegylated Liposomal Doxorubicin (PLD) in recurrent 

ovarian cancer: a phase I trail of the AGO Study Group 

*F . Hilpert1 , A . du Bois2 , J . Sehouli3 , P . Wimberger4 , J . Rau5 , C . Kurzeder2 , 

G . Elser6 , S . Zaun7 , P . Harter2 1Universitätsklinikum Schleswig-Holstein Campus Kiel, Klinik für Gynäkologie 

und Geburtshilfe, Kiel, Deutschland, 2Kliniken Essen-Mitte, Gynäkologie 

und Gynäkologische Onkologie, Essen, Deutschland, 3Charité Campus Virchow, 

Klinik für Gynäkologie, Berlin, Deutschland, 4Unirversitätsklinikum, Klinik für Frauenheilkunde und Geburtshilfe, Essen, Deutschland, 5Philipps Universität, Koordinierungszentrums für Klinische Studien, Marburg, 

Deutschland, 6AGO Studiengruppe, Wiesbaden, Deutschland, 7Astra Zeneca, 

Wedel, Deutschland 

Background. PLD is a standard treatment in patients with recurrent 

platinum-resistant or refractory ovarian cancer. Vandetanib is an oral 

once daily inhibitor of VEGFR-, EGFR- and RET-signalling with activity 

in combination with chemotherapy in some other solid tumours. 

Therefore, we aimed to establish a feasible combination therapy of PLD 

and vandetanib. 

Methods. Eligible patients were treated with PLD 50 mg/m2 q28 and 

vandetanib 100 mg/d po. It was planned to recruit at least 10 patients 

evaluable for toxicity over 2 treatment cycles. Primary endpoints were 

tolerability and safety; secondary endpoint was efficacy. 

Results. Fourteen of 15 registered patients started treatment and were 

evaluable for toxicity. Three patients (21%) stopped after first cycle (PD, 

withdrawal of consent, nausea/vomiting). The remaining 11 patients 

were treated for at least 2 cycles. Dose reductions of PLD and vandetanib 

were indicated in 4 (29%) and 5 patients (36%), respectively. The 

following G3/4 toxicities occurred per patient: 3 (21%) elevated liver enzymes 

G3, 2 (14%) neutropenia G3/4, 5 (36%) PPE G3/4, 2 (14%) mucositis 

G3. Tyrosine kinase inhibitor attributed side effects like hypertension or 

bowel perforations were not reported. Toxicity led to end of treatment 

in 4 patients (29%). Ten patients were evaluable for response: PR 1, SD 4. 

The median PFS was 6.7 months and median OS was 11.1 months. 

Conclusions. The combination of PLD and vandetanib is feasible, but 

shows considerable toxicity. Efficacy has to be proven in subsequent 

phase II trials. 

This study was sponsored by AstraZeneca GmbH . 

0074 

Survival of metastatic breast cancer (MBC): Is there a survival 

benefit over time? 

*M .-P . Ufen1 , B . Rosien1 , T . Hammer1 , U . Schubert1 , E . Malik2 , *C .-H . Köhne1 1Klinikum Oldenburg, Hämatologie Onkologie, Oldenburg, Deutschland, 

2Klinikum Oldenburg, Gynäkologie, Oldenburg, Deutschland 

Background. Whether survival of patients with MBC is improved over 

time remains controversial. Randomised clinical trials demonstrated 

if at all a small benefit between different therapies and a meaningful 

translation into clinical practice is doubtful. 

Methods. Excluding patients with local recurrence only, we analysed 

839 patients, treated at our institution from 1985–2009, according to 

date of primary diagnosis or date of first metastasis. The influence of 

hormonal receptor status (HR+, HR−), metastasis free intervall (MFI) 

(60 months) and diagnosis before or after 1996 (introduction 

of taxanes and aromatase inhibitors) was examined. 

Results. Improvement of survival was observed, when the primary tumor 

was diagnosed later (intervals of 1985–1990, 1990–1994, 1995–1999, 

2000–2004, 2005–2009; p=0.006) however, no survival effect was observed 

according to date of metastasis (p=0.11). Median survival of patients 

with HR+ was 32.1 vs. 17.0 months for in HR− (p

Abstracts 

0080 

Comparison of the HER2, estrogen and progesterone receptor 

expression profile of metastases and circulating tumor cells in 

metastatic breast cancer patients 

*B . Aktas1 , M . Tewes2 , V . Müller3 , S . Kasimir-Bauer1 , T . Fehm4 1Universitätsklinik, Gynäkologie und Geburtshilfe, Essen, Deutschland, 

2 3 Universitätsklinik, Innere Tumorklinik, Essen, Deutschland, Universitätsklinik, 

Klinik und Poliklinik für Gynäkologie, Hamburg, Deutschland, 4Universi tätsklinik, Gynäkologie und Geburtshilfe, Tübingen, Deutschland 

Background. Several studies have indicated that the expression of predictive 

markers including HER2, the estrogen (ER) und progesterone 

(PR) receptor can change during course of disease. Therefore, reassessment 

of the predictive markers at the time of disease progression might 

help to optimize treatment decisions. In this context, characterization 

of circulating tumor cells (CTCs) could be of relevance in the future, 

since metastatic tissue may be difficult to obtain for repeated analysis. 

Therefore, the purpose of the present study was to compare the hormone 

receptor status as well as HER2 expression profile of metastases with 

the expression profile on CTCs. 

Materials and methods. A total of 82 patients with metastatic breast cancer 

from eight German University Breast Cancer Centers were enrolled 

in this study. Blood was obtained at the time of first diagnosis of metastatic 

disease or disease progression. HER2 status of CTCs was assessed 

using the FDA-approved CellSearch® assay and the hormonal receptors 

were analyzed by immunomagnetic enrichment using the AdnaTest 

BreastCancerSelect (AdnaGen AG, Germany) followed by RNA isolation 

and subsequent gene expression analysis by reverse transcription 

and Multiplex-PCR in separated tumor cells using the AdnaTest BreastCancerDetect. 

Expression of the ER and PR receptor was assessed in 

an additional RT-PCR. The analysis of PCR products was performed by 

capillary electrophoresis on the Agilent Bioanalyzer 2100. 

Results. The overall detection rate for CTCs was 27 of 82 (33%) with the 

expression rates of 33% for HER2, 10% for ER and 6% for PR, respectively. 

Comparisons of expression profiles on CTCs with those on metastases 

were only performed in CTC-positive patients. In 15 patients with 

ER-positive metastases, only one patient had ER-positive CTCs. 11 patients 

with PR-positive metastases expressed PR on CTCs in also only one 

case. The rate of breast cancer patients with HER2-positive metastases 

and HER2-positive CTCs was 27%. Metastases and CTCs displayed a 

concordant ER, PR and HER2 status in 21% (not significant), 42% (not 

significant) and 52% (not significant) of cases, respectively. 

Conclusion. The concordance between expression profile of CTCs and 

corresponding metastatic disease is low. The consequences for palliative 

treatment have to be determined by monitoring therapy response based 

on each expression profile. 

0082 

Pertuzumab is superior to Trastuzumab in rescuing the HRGcaused 

reversion of Lapatinib’s inhibitory effect on breast cancer 

cells 

*S . Diermeier-Daucher1 , S . Breindl1 , S . Buchholz1 , O . Ortmann1 , G . Brockhoff1 1Caritas Hospital St . Josef, Department of Gynecology and Obstetrics, 

Regensburg, Deutschland 

Background. Monoclonal antibodies and small molecule inhibitors 

emerged as potent therapeutic agents in the treatment of HER2 overexpressing 

breast cancer. However, many patients do not adequately 

respond to anti-EGFR/HER2 receptor targeting. In this study we investigated 

receptor- and growth-stimulating effects, which potentially 

hamper anti-proliferative cell treatment. 

Methods. BT474 and SK-BR-3 breast cancer cell lines were treated with 

therapeutic monoclonal antibodies Trastuzumab and Pertuzumab and 

with tyrosine kinase inhibitor Lapatinib alone and in different combinations. 

EGF or HRG were added to reveal potential growth factor-me- 


diated compensatory effects. The treatment-specific activation status of 

EGFR and HER2 receptors and intracellular signaling cascades were 

correlated to cell cycle kinetics and apoptosis. 

Results. The presence of EGF or HRG strongly impaired Lapatinib-caused 

growth inhibition. This compensatory effect caused by EGF, however, 

was reversed by additional cell treatment with either Trastuzumab 

or Pertuzumab. In contrast, the compensatory effect caused by HRG 

treatment was only reversed by Pertuzumab, but not by Trastuzumab. 

These data suggest that Pertuzumab might be superior to Trastuzumab 

in affecting a HRG-caused HER receptor interaction (activation) involved 

in compensation of Lapatinib-caused cell cycle exit. 

Conclusions. Modular HER/ErbB receptor targeting with Lapatinib, 

Trastuzumab and Pertuzumab more efficiently affects receptor function 

than single treatment. Growth inhibition by anti-cancer drugs targeted 

to HER/ErbB receptors, however, can be significantly undermined 

in the presence of EGF and in particular by HRG treatment. This observation 

suggests that specific therapeutic growth factor sequestration 

might further enhance anti-EGFR/HER2 targeting. 

0083 

Hyperthermia triggers down-regulation of Estrogen receptor 

α isoforms and its co-activators DEAD-box5 and DEAD-box17 in 

breast cancer cells 

*M . Hirschfeld1 , M . Jäger1 , V . Neumann1 , G . Gitsch1 , E . Stickeler1 1Gynecological Hospital of Freiburg University Medical Center, Molecular 

Oncology, Freiburg, Deutschland 

Background and aims. Recently, the clinical application of hyperthermal 

therapy becomes more and more reintroduced and is used concomitant 

to chemotherapy or radiotherapy, that might improves the effect of 

those classical anti-cancer treatments. RNA helicases p68 (DEAD-box5, 

DDX5) and p72 (DEAD-box17, DDX17) act as transcriptional co-activators 

of several tumor-relevant genes, e.g. estrogen receptor α (ERα). 

DDX17 is significantly associated to an increase in relapse-free and 

overall survival in ERα-positive breast cancer, however inversely associated 

to Her2/neu expression. In contrast, DDX5 expression correlates 

with elevated levels of Her2/neu and higher stages of tumor grading. 

Both factors regulate ERα-activity in breast cancer. We investigated 

potential regulatory effects of hyperthermia on the expression of these 

breast cancer-related factors. 

Methods. Various ERα-positive breast cancer cell lines (MCF-7, ZR-75-1, 

T47D, BT-474) were cultured under hyperthermia (42°C, 2 h) followed 

by maintenance under regular culture conditions (37°C, 4 h). As a negative 

control the same cell lines were cultivated under regular temperature 

conditions permanently. mRNA and protein expression levels of 

ESRα isoforms, DDX5 and DDX17 were analyzed by RT-PCR, Western 

blot and immunocytochemistry technique. 

Results. The analyses revealed markedly decreased mRNA and protein 

levels of ERα isoforms, as well as of DDX5 and DDX17 in cells exposed 

to hyperthermia compared to cells cultured under regular conditions. 

Our results clearly indicate a regulatory effect of hyperthermal treatment 

on both, the mRNA and protein expression of the breast cancerrelevant 

gene ERα and its co-activators DDX5 and DDX17. 

Conclusion. According to our findings, hyperthermal treatment seems 

to represent a method that may improve classical anti-cancer therapies 

by down-regulating the activity of important factors in breast cancer 

biology. We hypothesize that hyperthermia inhibits the expression of 

ERα isoforms and its co-activators, thus probably leading to a suppression 

of tumor progression. However, the molecular background of signaling 

pathways that undergo hyperthermia-dependent alterations and 

its concomitant effects on tumor biology still need to be investigated in 

more detail.

0085 

Quality of life (QoL) in patients with metastatic breast cancer 

(MBC) treated with capecitabine – second interim analysis of the 

German non-interventional study (NIS) 

*C .-C . Steffens1 1MVZ Hämatologie/Onkologie, Onkologie, Stade, Deutschland 

Background. Capecitabine (CAPE) is a commonly used treatment option 

for MBC with proven efficacy. The aim of this study was to analyse 

QoL. 

Patients and methods. Patients with MBC, irrespective of HER2-status 

are included in this NIS. To evaluate QoL the EORTC Quality of Life 

questionnaire QLQ-C30 (v 3.0) was used. The presented data are part of 

a pre-planned interim analysis with up to 12 documented cycles. 

Results. Until 12/2010, 594 of 750 planned patients had been registered 

and 447 of these were documented to have received at least one cycle 

of CAPE. The average age of the patients was 61.4 (±11) years. 45% 

of patients received CAPE monotherapy (MT) and 55% combination 

therapy (CT). 41% of patients were treated 1st line, 28% 2nd line and 

the remaining in 3rd or higher lines. The most common combination 

partners were bevacizumab (16%), lapatinib (13%), vinorelbine (10%) or 

trastuzumab (9%). Clinical responses were displayed by 27.9% patients 

for MT and 39.9% for CT, while clinical benefit was noted in 61% of patients 

irrespective of treatment modality. Data from up to 482 patients 

were available for analyses of QoL. Patients with CT showed significantly 

better scores at baseline than MT patients for physical, role and 

cognitive functioning as well as fatigue, pain and financial problems. 

During the course of treatment global health, emotional and role functioning 

increased for CT patients, but only the rise in global health was 

statistically significant. Irrespective of treatment, physical functioning 

remained stable over the course of up to 12 treatment cycles. Social 

functioning showed a decrease in the group treated with MT, but an 

increase for the group treated with CT. Compliance rates were between 

68% (cycle 12, n=31) and 87% (cycle 1, n=209) during the 12 cycles. Patient 

satisfaction regarding the information given on the overall cancer 

treatment and side effects was high (mean ≥4 out of 5). At least half of 

the patients evaluated their treatment, the treatment outcome and the 

side-effects as or better than expected. 

Conclusions. CAPE was most commonly used as 1st line treatment and 

displayed better treatment outcome when given in combination. Overall, 

QoL did not decrease and was better for the combination therapy 

group. However, further data, especially for the later cycles, need to be 

acquired to verify these assumptions. 

0090 

Survival analysis of patients with primary breast cancer initially 

treated at a certified academic breast unit 

* J . Heil1,2 , A . Gondos3 ; F . Marmé2,4 , H . Brenner3 , G . Rauch5 , C . Sohn1,2 , A . 

Schneeweis1,2 1 2 Frauenklinik, Brustzentrum, Heidelberg, Deutschland, Nationales 

Centrum für Tumorerkrankungen, Gynäkologische Onkologie, Heidelberg, 

Deutschland, 3DKFZ, Division of Clinical Epidemiology and Aging Research, 

Heidelberg, Deutschland, 4Frauenklinik, Brustzentrum, Heidelberg, 

Deutschland, 5Institut für medizinische Biometrie, Heidelberg, Deutschland 

Aim. Outcome evaluation of patients with primary breast cancer treated 

at a certified academic breast unit. 

Methods. We prospectively collected data of 3338 patients, diagnosed 

with primary breast cancer between 01.01.2003 and 31.12.2010 and treated 

at the Breast Unit Heidelberg in order to analyze outcome in clinical 

practice. We evaluated local control rate (LCR), disease-free survival 

(DFS), distant disease-free survival (DDFS), observed overall survival 

(OOS) and age adjusted relative overall survival (ROS). In addition, the 

impact of known prognostic factors on these outcome variables was examined 

in univariate and multivariate analyses. 

Results. Of all patients, 368 (11.0%) had carcinoma in situ (CIS) and 197 

(5.9%) had bilateral cancers., For the 2970 patients with invasive cancer, 

of which 49 patients (1.7%) had metastastic disease at time of diagnosis, 

DFS, LCR, DDFS, OOS and ROS at 5 years were 79.8%, 84.7%, 81.2%, 

86.3%, and 89.8%, respectively. In multivariate analysis age, pT category, 

nodal status, hormone receptor status and grading were identified as 

independent prognostic factors for OS. 

Conclusion. Compared with recent population based reports from Germany, 

more favourable patient characteristics and nominally higher 

survival was found among this large cohort of patients with primary 

breast cancer treated at a single certified breast unit. 

0094 

Sequential treatment with Epirubicin/Cyclophosphamide, followed 

by Docetaxel vs. FEC120 in the adjuvant treatment of breast 

cancer patients with extensive lymph node involvement: final 

survival analysis of the German ADEBAR phase III study 

*W . Janni1 , N . Harbeck2 , H . Sommer3 , B . Rack3 , D . Augustin4 , W . Simon5 , 

J . Jueckstock3 , A . Wischnik6 , K . Anneke7 , K . Friese3 , M . Kiechle7 1 2 HHU, Frauenklinik, Düsseldorf, Deutschland, Universitätsklinik Köln, 

Brustzentrum Köln Frechen, Köln, Deutschland, 3LMU, Frauenklinik, 

München, Deutschland, 4Klinikum, Brustzentrum Ostbayern, Deggendorf, 

Deutschland, 5Robert-Bosch-Krankenhaus, Frauenklinik, Stuttgart, 

Deutschland, 6Zentralklinikum, Frauenklinik, Augsburg, Deutschland, 

7Technische Universität, Frauenklinik, München, Deutschland 

Background. Based on meta-analytic evidence, taxane containing adjuvant 

chemotherapy has been established as standard treatment in 

node-positive breast cancer. However, in the MA-21 study, adriamycincyclophosphamide, 

followed by paclitaxel (AC-P) was significantly inferior 

to the gold standard of anthracycline treatment, FEC120 (Burnell, 

SABCS 2006). We prospectively compared a sequential epirubicin-docetaxel 

chemotherapy regimen to FEC120. 

Patients and methods. The ADEBAR study was a multicenter phase III 

trial (n=1502) to evaluate whether breast cancer (BC) pts with >3 axillary 

lymph node metastases benefit from a sequential anthracycline-docetaxel 

regimen (E90C–D: 4 cycles epirubicin [E] 90 mg/m2 plus cyclophosphamide 

[C] 600 mg/m2 q21 days followed by 4 cycles docetaxel [D] 

100 mg/m2 q21 days) compared to dose-intensive anthracycline-containing 

polychemotherapy (FE120C: 6 cycles E 60 mg/m2 d 1+8, 5-FU 

500 mg/m2 d 1+8 and C 75 mg/m2 d 1–14, q4 weeks). The median followup 

time will be 60 months. 

Results. Treatment was stopped prematurely in 3.7% of the pts in the 

E90C–D arm and in 8.0% in the FE120C arm due to toxicity (p=0.0009). 

Antibiotic treatment was given in 10.4% (E90C–D) vs. 19.7% (FE120C), 

G-CSF support in 39.2% vs 61.4 % and erythropoietin stimulation in 

8.7% vs. 20.0%, respectively. Mature final 5-year-survival data will be 

presented at the SABCS meeting 2011. 

Conclusion. Different toxicity profiles given, hematological toxicity in 

the FE120C group was more severe than in the E90C–D. Mature survival 

data will be discussed in this context. 


67

Abstracts 

0108 

Trastuzumab treatment of early breast cancer patients receiving 

no adjuvant chemotherapy 

*P . Dall1 , K . Friedrichs2 , H . Timmer³, V . Petersen4 , A . Hinke5 , C . Brucker6 , 

A . Nacke7 , P . Schmidt8 , A . von der Assen9 1 Städt . Klinikum, Frauenklinik, Lüneburg, Deutschland, 2 Krankenhaus 

Jerusalem, Mammazentrum, Hamburg, Deutschland, ³Onkologische Gemeinschaftspraxis, 

Münster, Deutschland, 4 Praxis, Heidenheim, Deutschland, 

5 WiSP, Biostatistik, Langenfeld, Deutschland, 6 Klinikum Nürnberg, 

Brustzentrum, Nürnberg, Deutschland, 7 Praxis, Remagen, Deutschland, 

8 Praxis, Neunkirchen, Deutschland, 9 Franziskus-Hospital Harderberg, 

Georgsmarienhütte, Deutschland 

Background. Trastuzumab (T) is approved for the treatment of early, 

HER2+ breast cancer (BC) in parallel or sequentially to adjuvant chemotherapy 

(CT). However, as in advanced disease, the antibody is obviously 

used without chemotherapy in a selected group of HER2+ patients 

(pts). The analysis characterizes this subgroup and describes safety and 

efficacy outcome parameters based on data from a large prospective observation 

trial. 

Methods. 2870 pts have currently been enrolled and documented in 

this ongoing non-interventional study from 270 German institutions. 

At data lock for this evaluation, adequate documentation was available 

from 2422 eligible pts. 

Results. T was given to 180/2422 pts (7.4 %) without preceding or concomitant 

CT (noCT). In this subgroup pts typically were older (median 

58 vs. 56 in the CT group, p=0.0026; ≥70 years: 18%/10%), had smaller 

tumors (pT1 49%/43%, p=0.11), more favorable histology (G3 45%/53%, 

p=0.045), a higher percentage of positive hormone receptor (67%/61%, 

p=0.096) and less radiotherapy (64%/79%, p

EMT and ALDH1 expression was not correlated to any of the prognostic 

clinical markers. 

Conclusion. Our data indicate that (1) a subset of primary breast cancer 

patients shows EMT and stem cell characteristics and (2) the currently 

used detection methods for CTC are not efficient to identify a subtype 

of CTC which underwent EMT. (3) The clinical relevance on prognosis 

and therapy response has to be further evaluated in a prospective trial. 

0114 

The PACOVAR-trial: A phase I/II study of pazopanib (GW786034) 

and metronomic cyclophosphamide in patients with platinumresistant 

recurrent, pre-treated ovarian cancer 

*C . Mayer1 , R . Eickhoff2 , E . Bischofs1 , G . Gebauer3 , T . Fehm4 , F . Lenz5 , 

H .-C . Fricke6 , E .-F . Solomayer7 , N . Fersis8 , M . Schmidt9 , M . Wallwiener1 , 

A . Schneeweiss1,10 , C . Sohn1 , M . Eichbaum1 1 2 Universitäts-Frauenklinik Heidelberg, Heidelberg, Deutschland, Alcedis 

GmbH, Gießen, Deutschland, 3Marienkrankenhaus, Frauenklinik, Hamburg, 

Deutschland, 4Universitäts-Frauenklinik Tübingen, Tübingen, Deutschland, 

5Krankenhaus Hetzelstift, Frauenklinik, Neustadt/Weinstraße, Deutschland, 

6 7 Klinikum Konstanz Frauenklinik, Konstanz, Deutschland, Universitätsklinikum 

des Saarlandes, Frauenklinik, Homburg, Deutschland, 8Klinikum Chemnitz gGmbH, Frauenklinik, Chemnitz, Deutschland, 9Universitäts- Frauenklinik Mainz, Mainz, Deutschland, 10Nationales Centrum für Tumorerkrankungen, 

Gynäkologische Onkologie, Heidelberg, Deutschland 

Background. The prognosis of patients with recurrent, platinum-resistant 

epithelial ovarian cancer (EOC) is poor. There is no standard 

treatment available. Emerging evidence suggests a major role for antiangiogenic 

treatment modalities in EOC, in particular in combination 

with the metronomic application of low dose chemotherapy. The novel, 

investigational oral antiangiogenic agent pazopanib targeting vascular 

endothelial growth factor receptor (VEGFR), platelet-derived growth 

factor receptor (PDGFR) and c-kit is currently being studied in different 

tumour types and is already used as first line therapy in recurrent renal 

cell carcinoma. A combined therapy consisting of pazopanib and metronomic 

oral cyclophosphamide may offer a well-tolerable treatment 

option to patients with recurrent, pretreated EOC. 

Methods and design. This study is designed as a multicenter phase I/ 

II trial evaluating the optimal dose for pazopanib (phase I) as well as 

activity and tolerability of a combination regimen consisting of pazopanib 

and metronomic cyclophosphamide in the palliative treatment of 

patients with recurrent, platinum-resistant, pre-treated ovarian cancer 

(phase II). The patient population includes patients with histologically 

or cytologically confirmed diagnosis of EOC which is platinum resistant 

or refractory, cancer of the fallopian tube or peritoneal cancer. Patients 

must have measurable disease according to RECIST criteria and 

must have failed available standard chemotherapy. 

Primary objectives are determination of the optimal doses for pazopanib 

(phase I) and the overall response rate according to RECIST criteria 

(phase II). Secondary objectives are time to progression, overall survival, 

safety and tolerability. The treatment duration is until disease progression 

or intolerability of study drug regimen (with a maximum of 13 

cycles up to 52 weeks per subject). Enrollment has started in November 

2010 in 5 sites experienced in the conducture of clinical trials. Three patients 

have completed first eight weeks of treatment without DLT so far. 

Discussion. The current phase I/II trial shall clarify the potential of the 

multitargeting antiangiogenic tyrosinkinaseinhibitor GW 786034 (pazopanib) 

in combination with oral cyclophosphamide as salvage treatment 

in patients with recurrent, pretreated ovarian cancer. Preliminary 

safety results will be presented. 

0115 

Bevacizumab (rhuMAB VEGF) in combination with metronomic 

cyclophosphamide in advanced gynecological cancers resistant 

to standard treatment 

*K . Smetanay, J . Aigner1 , F . Marmé1 , M . Eichbaum1 , C . Sohn1 , A . Schneeweis1 1Universitätsklinikum Heidelberg, Frauenklinik/NCT Gynäkologische Onkologie, 


Introduction. Patients with heavily pretreated gynecological cancers 

(ovarian cancer, adenocarcinoma of the cervix uteri and endometrial 

cancer) have limited treatment options. Vascular endothelial growth 

factor (VEGF) is the best characterized angiogenic factor and is regarded 

as a promising therapeutic target at least in patients with ovarian 

cancer. In addition to bevacizumab, the monoclonal antibody against 

VEGF, low dose metronomic cyclophosphamide has shown some antiangiogenic 

properties. Here we report results of a retrospective analysis 

of our patients with heavily pretreated gynecological cancers who received 

bevacizumab in combination with low dose cyclophosphamide 

at our institution since 2008. In addition we present an overview of the 

recent literature published in PubMed-, MEDLINE and EMBASE-database. 

Patients and methods. Five patients with heavily pretreated (at least four 

lines of chemotherapy) platin-resistent gynecological carcinomas received 

intravenous bevacizumab 10 m/kg every two weeks in combination 

with oral cyclophosphamide 50 mg per day. Endpoints were time to progression 

and toxicity according to Common Terminology Criteria of 

Adverse Events Version 3.0 (CTCAEv3.0). 

Results. All patients showed a rapid improvement of tumour symptoms. 

Median time to progression was 10 months (range: 6–33). One patient 

with an adenocarcinoma of the cervix is still in remission for 7 months. 

Bevacizumab related toxicities comprised deep vein thrombosis grade 

III in one patient and arterial hypertension grade II in 3 patients, 

which were well manageable by standard treatment. We experienced no 

proteinuria >grade 1 as assessed by urine dipsticks before each administration 

of bevacizumab. Although data to endometrial and cervical 

cancers are very rare a comprehensive literature review supports our 

experience and will be presented at the meeting. 

Conclusion. Bevacizumab in combination with oral metronomic cyclophosphamide 

is well tolerated and has significant activity as palliative 

therapy of heavily pretreated patients with platin-resistent gynecological 

cancers. Translational research to define predictors of response e.g. 

anti-angiogenesis gene polymorphisms and severe side effects e.g. gastro-intestinal 

perforation to further improve the therapeutic index are 

eagerly needed. 

0124 

LOH at chromosomal band 6q and 10q in fractionated circulating 

DNA of ovarian cancer patients is predictive for tumor cell spread 

and reduced disease-free and overall survival 

*P . Wimberger1 , J .D . Kuhlmann1 , H . Schwarzenbach2 , M . Heubner1 , M . Poetsch3 

, R . Kimmig1 , S . Kasimir-Bauer1 1Universität Duisburg-Essen, Klinik für Gynäkologie und Geburtshilfe, 

Essen, Deutschland, 2Universität Hamburg-Eppendorf, Institut für Tumorbiologie, 

Hamburg, Deutschland, 3Universität Duisburg-Essen, Institut für 

Forensische Medizin, Essen, Deutschland 

Background. We recently showed that LOH proximal to M6P/IGF2R locus 

(D6S1581) in ovarian tumors is predictive for tumor cell spread to 

the bone marrow (BM). For therapy-monitoring, it would be desirable 

to establish a blood-based biomarker. Therefore, we quantified circulating 

DNA (cirDNA) in sera of 63 ovarian cancer patients before surgery 

and after chemotherapy, measured incidence of LOH at four cancer-relevant 

chromosomal loci, correlated LOH with tumor cell spread to the 

BM and evaluated prognostic significance of LOH. 


69

Abstracts 

Methods. cirDNA was fractionated into high- and low molecularweight 

fraction (HMWF, LMWF) for LOH-profiling, utilizing PCRbased 

fluorescence microsatellite analysis. BM aspirates were analyzed 

for DTC by immunocytochemistry using the pan-cytokeratin antibody 

A45-B/B3. 

Results. cirDNA levels in the HMWF before surgery were predictive for 

residual tumor load (p=0.017). After chemotherapy, we observed a decline 

of cirDNA in the LMWF (p=0.0001) but not in the HMWF. LOH 

was prevalently detected in the LMWF with an overall frequency of 67 

%, only moderately ablating after chemotherapy (45%). Before surgery, 

LOH in the LMWF at marker D10S1765, D13S218 and D6S1581 significantly 

correlated with tumor grading, FIGO stage and disease-free 

survival (p=0.004, p=0.033, p=0.032, respectively). In both combined 

fractions, LOH at D6S1581 additionally associated with overall survival 

(p=0.030). Moreover, solely LOH at D10S1765 in LMWF after therapy 

correlated with DTC in BM after therapy (p=0.017). 

Conclusion. We demonstrate the necessity of DNA-fractionation for 

LOH analysis on cirDNA and identified LOH at D10S1765 and D6S1581 

as blood-based biomarkers for ovarian cancer, being relevant for treatment-monitoring. 

0127 

Implementation of the national S3 guideline recommendations 

for primary surgery of breast cancer patients in different regions 

of Germany: a population-based evaluation 

*S . Schrodi1 , A . Tillack2 , A . Naas2 , A . Niedostatek3 , C . Werner3 , B . Holleczek4 , 

C . Stegmaier4 , G . Schubert-Fritschle1 , J . Engel1 1Tumorzentrum München (TZM), Tumorregister München (TRM), München, 

Deutschland, 2Tumorzentrum Land Brandenburg, Frankfurt (Oder), 

Deutschland, 3Regionales Klinisches Krebsregister Dresden, Dresden, 

Deutschland, 4Epidemiologisches Krebsregister Saarland, Saarbrücken, 

Deutschland 

Purpose. In 2004, the first national S3 guideline for the diagnosis, therapy 

and aftercare of breast cancer patients was implemented in Germany, 

and the first update was released in 2008. One aim of the study was to 

evaluate guideline adherence for primary surgery of breast cancer and 

possible influences on survival in four different regions of Germany. 

Methods. Data from 69,587 cases of operated breast cancer patients, 

diagnosed between 1999 and 2010 was obtained from cancer registries 

in the regions of Brandenburg (n=18,928), Dresden (n=9607), Munich 

(n=33,496) and Saarland (n=7556). Guideline adherence was examined 

first by means of annual percentages of the quality indicators breast 

conserving surgery (BCS) and sentinel lymph node biopsy (SLNB), and 

subsequently with multiple logistic models for three time periods. For 

the interpretation of outcome quality (survival), cox regression models 

were additionally calculated. 

Results. Although regional differences in the frequency and speed of 

realization of the quality care procedures BCS and SLNB were observed, 

both procedures were already conducted in all four regions before 

the implementation of the S3 guidelines. Regarding the different distribution 

of prognostic factors, patients with small (pT1/2) tumours had 

a 2.6-fold higher chance for BCS in the western regions compared to 

the eastern regions during the period from 1999 to 2003. This difference 

declined to an odds ratio (OR) of 1.2 in the period 2008 to 2010. While 

SLNB has been known to be effective for the definition of nodal status 

since 2003, it was not recommended in German guidelines for clinical 

routine until 2008. Nevertheless, SLNB rates rose rapidly in all regions 

starting in 2003, although faster rates were observed in the western regions 

than in the eastern regions. Between 2003 and 2007, the chance 

of receiving SLNB was 3.2-fold higher in the west than in the east, but 

these rates converged in 2008–2010 (OR 1.3). Such regional differences 

in procedural quality could not be observed in the quality of outcome. 

The better 10-year overall survival in Munich can largely be described 

by different distributions of prognostic factors. 


Conclusion. Concerning BCS and SLNB, guideline recommendations 

were already practiced in all four German regions before their implementation. 

The East-West differences in the proportions of these procedures 

declined over the years and the speed of realisation seems not to 

have had any impact on survival. 

0128 

Population-based consequences of mammography screening for 

therapy of breast cancer patients. An analysis of Bavarian cancer 

registry data 

*S . Schrodi1 , U . Braisch2 , G . Schenkirsch3 , T . Maisel4 , S . Petsch5 , M . Klinkhammer-Schalke6 

, D . Hölzel1 , U . Mäder7 , S .H . Heywang-Köbrunner8 , M . Meyer2 , 

J . Engel1 1Tumorzentrum München (TZM), Tumorregister München (TRM), München, 

Deutschland, 2Bevölkerungsbezogenes Krebsregister Bayern, Registerstelle, 

Erlangen, Deutschland, 3Tumorzentrum Augsburg, Augsburg, Deutschland, 

4Klinikregister Bayreuth, Bayreuth, Deutschland, 5Tumorzentrum der 

Universität Erlangen-Nürnberg, Erlangen, Deutschland, 6Tumorzentrum Regensburg, Regensburg, Deutschland, 7Tumorzentrum Würzburg, 

Würzburg, Deutschland, 8Referenzzentrum Mammographie München, 

München, Deutschland 

Purpose. A quality controlled mammography screening program was 

initiated at the end of 2003 in Bavaria, a region with 12.5 million inhabitants, 

and transferred over to the national screening program at 

the end of 2006. The purpose of this study was to evaluate immediate 

population-based consequences of mammography screening on breast 

cancer therapy. 

Methods. Data from 75,475 breast cancer cases, diagnosed between 2000 

and 2008 and registered in one of the six Bavarian clinical cancer registries 

were analysed. 51.4% of these patients were between 50 and 69 years 

of age and therefore the target population for screening. Trends of 

prognostic factors and standard therapies were calculated for three age 

groups (≤49 years, 50–69 years, ≥70 years) by means of annual percentages 

as well as 95%-confidence intervals for the percent difference between 

2000 and 2008 (year of diagnosis). For interpretation of therapy 

trends, logistic regression models were calculated. 

Results. Therapy trends showed that the increasingly favourable stage 

distribution may have resulted in the reduction of more radical surgical 

methods such as mastectomy (2000: 32.6%; 2008: 19.6%) or axillary 

dissection (89.0% vs. 37.0%). An increase of radiation therapies (59.7% 

vs. 66.6%) can be explained to some extent by the increase in breast conserving 

surgeries. The shift to more favourable prognostic factors led, 

in accordance with the guidelines, to an increase of the proportion of 

singular endocrine therapies (28.5% vs. 40.7%), a decrease of chemotherapies 

(20.4% vs. 13.1%) and therefore to more gentle systemic therapies 

overall. These trends strengthened in the years following the introduction 

of screening, with a simultaneous rise of screening participants in 

the target population. 

Conclusion. The introduction of mammography screening in Bavaria 

already shows the expected trend towards more favourable prognostic 

factors. Among other things, this could be a reason for the increasing 

use of more gentle therapies. Whether the screening in Bavaria leads 

to a mortality reduction, has to be analysed on the basis of an initial 

comparison of participation status followed by the trends in mortality 

thereafter.

0139 

Pegylated liposomal doxorubicin (PLD) and carboplatin in 

malignant mixed epithelial mesenchymal and mesenchymal 

gynecologic tumors. A meta-analysis of three prospective AGO 

Study Group trials 

*P . Harter1 , A . Reuss2 , L . C . Hanker3 , J . Sehouli4 , K . Baumann5 , W . Meier6 , P . 

Wimberger7 , W . Schröder8 , A . Burges9 , A . du Bois1 1Kliniken Essen Mitte, Gynäkologie & Gynäkologische Onkologie, Essen, 

Deutschland, 2Universitätsklinikum Gießen und Marburg, KKS, Marburg, 

Deutschland, 3Johann Wolfgang Goethe Universität, Frauenklinik, 

Frankfurt, Deutschland, 4Charite Campus Virchow, Frauenklinik, Berlin, 

Deutschland, 5Universitätsklinikum Gießen und Marburg, Frauenklinik, 

Marburg, Deutschland, 6Evangelisches Krankenhaus, Frauenklinik, Düsseldorf, 

Deutschland, 7Universitätsklinik, Frauenklinik, Essen, Deutschland, 

8 9 GYNAEKOLOGICUM, Bremen, Deutschland, Uniklinikum Großhadern, 

Frauenklinik, München, Deutschland 

Background. After conduction of a pure gynecologic sarcoma trial 

(AGO-GYN7), showing promising activity of PLD and carboplatin, we 

decided to perform a meta-analysis including two other trials in whom 

patients with gynecologic sarcoma treated with the same regimen were 

included. 

Methods. Patients of the AGO-GYN 2, AGO-GYN 3, and AGO-GYN 7 

trial with advanced or recurrent gynecologic sarcoma or carcinosarcoma 

were included. AGO-GYN 2 was a dose finding phase I/II trial (PLD 

20 to 50 mg and carboplatin AUC 6). The 2 other trials investigated PLD 

40 mg/m2 and carboplatin AUC 6, q28. 

Results. 59 patients were included in this analysis: 30 pts with carcinosarcoma, 

20 pts with leiomyosarcoma, and 9 pts with endometrial stromal 

sarcoma. 93% of the patients had first diagnosis. 91.5% of the pts 

were treated with PLD 40 mg/m2 and carboplatin AUC 6, q28d. The 

incidence of grade 3/4 hematologic toxicities was: anemia 17.0%, neutropenia 

52.6%, and thrombocytopenia 23.8%. There was one febrile 

neutropenia. Main grade 3/4 non-hematologic toxicities were: PPE 5.1%, 

and constipation 3.4%. The rate of CR/PR was 31.6%, CR/PR/SD 68.4% 

(58.8% in carcinosarcoma, 80% in leiomyosarcoma, 66.7% in endometrial 

stromal sarcoma). 12 months PFS and OS was 38.1% and 74.6%, 

respectively. 12 months PFS and OS in carcinosarcoma was 37.6% and 

71.3%, and in leiomyosarcoma and endometrial stromal sarcoma 37.9% 

and 78.6%. 

Conclusions. The combination of PLD and carboplatin is active in this 

indication. The safety profile seems to be favourable compared to other 

widely used combination therapies for these diseases. 

0144 

Review of screening mammograms from interval cancers – First 

results of the pilot study of mammography screening in Lower 

Saxony 

*I . Urbschat1 , G . Hecht2 , J . Kieschke1 1Epidemiologisches Krebsregister Niedersachsen (EKN), Registerstelle, 

Oldenburg, Deutschland, 2Referenzzentrum Mammographie Nord, Oldenburg, 

Deutschland 

Aim. Interval cancers (IV-Ca) are breast cancers which appear between 

two screening examinations. The detection of IV-Ca is of crucial importance 

for the quality of any screening program and is a key parameter 

defined in the EU Guidelines. The goal of the quality assurance of 

IV-Ca is to categorize them into five categories (“true interval cancer”, 

“minimal sign”, “false-negatives”, “radiological occult”, “unclassifiable”) 

and to guarantee an optimisation of the quality of the screening 

(§ 23 Abs. 10 Krebsfrüherkennungs-Richtlinie vom 15.10.09). The pilot 

study in Lower Saxony will provide the opportunity to gain experiences 

with the different review processes of IV-Ca in Germany. 

Methods. In June 2010, IV-Ca were identified by record linkage of data 

from the population-based epidemiological cancer registry in Lower 

Saxony (EKN) with the data of 25,000 women, who attended the 2006 

mammography screening in one screening unit of Lower Saxony. The 

classification of “false-negative” cases initially had to take place only 

with the retrospective reviewing of the screening mammograms of the 

IV-Ca without diagnostic mammograms (provisional classification). 

Afterwards, the review will be repeated with medical tumour data 

from EKN (ICD-10 code, side, localisation, tumour size). Lastly and 

according to the EU Guidelines, radiologists should compare the screening 

mammograms with diagnostic mammograms to categorize them 

into five categories (definitive classification). 

Results. 65 IV-Ca were identified in the EKN; 22 of them were diagnosed 

in the first year after screening, 43 in the second year. First results 

of the “provisional classification” will be shown. 

Discussion: For optimisation of the quality of the mammography screening 

program, the results of the first review process (provisional classification) 

would be reported to the radiologists of the screening unit. 

Actually, there are no possibilities to make a “definitive classification” 

of all IV-Ca, because diagnostic mammograms are not available for 

all patients. Without “definitive classification” there are no comparable 

results of IV-Ca-rates and frequencies of false-negative diagnoses. 

In contrast to the Scandinavian and some other European countries, 

in Germany the diagnostic records and mammograms can only be 

accessed with the consent of the patient; this will be difficult for the 

screening program. Alternatively, the government can enact laws to 

facilitate the transfer of the diagnostic mammograms. 

0146 

Mammakarzinom und Adipositas – was zeigen die deutschen 

BRENDA-Daten? 

*L . Schwentner1 , R . Wolters2 , M . Wischnewsky2 , C . Kurzeder3 , R . Kreienberg1 

, A . Wöckel1 1 2 Universität Ulm, Gynäkologie und Geburtshilfe, Ulm, Deutschland, Universität 

Bremen, E-science, Bremen, Deutschland, 3Klinikum Essen Mitte, 

Gynäkologische Onkologie, Essen, Deutschland 

Einleitung. BRENDA („Breast Cancer Care under evidence-based-guidelines“) 

ist eine multizentrische Versorgungsforschungsstudie von 

Patientinnen mit primärem Mammakarzinom. Ziel dieser Kohorten- 

Studie war die Untersuchung einer Korrelation zwischen Body-Mass- 

Index (BMI) und dem Endpunkt RFS unter Berücksichtigung der adjuvanten 

Therapie. 

Methoden. In einer Subgruppenanalyse des BRENDA-Kollektives 

wurden retrospektiv die Daten von 4912 Patientinnen in multivariaten 

Analysen untersucht. 

Ergebnisse. Insgesamt lag bei 3992 (81,3%) Patientinnen ein BMI 30 vor. In der Gruppe der östrogenrezeptorpositiven 

Mammakarzinome zeigte sich ein signifikanter Überlebensvorteil 

für Patientinnen mit einem BMI

Abstracts 

makarzinom. Weitere prospektive Studien müssen bestätigen, welche 

Therapieformen bei hohem BMI das Outcome im adjuvanten Setting 

günstig beeinflussen. 

0160 

Abagovomab maintenance therapy in patients with ovarian cancer 

after complete response (CR) post-first-line chemotherapy: 

Results of the randomized, double-blind, placebo-controlled, 

multicenter AGO-OVAR 10 (MIMOSA) trial 

*S . Mahner1 , P . Harter2,3 , J . Sehouli4 , W . Meier5 , P . Wimberger6 , N . de 

Gregorio7 , A . Hasenburg8 , K . Baumann9 , B . Schmalfeldt10 , L . Hanker11 , 

E . Solomayer12,13 , A . Staehle14 , M . Beckmann15 , U . Canzler16 , A . Burges17 , 

K . Wollschlaeger18 , P . Hillemanns19 , C . Jackisch20 , F . Hilpert21 , G . Emons22 , 

W . Schröder23 , A . Belau24 , B . Richter25 , J . Pfisterer26 , AGO Study Group and 

Mimosa Investigators27 1Universitätsklinikum Hamburg-Eppendorf, Gynäkologie, Hamburg, 

Deutschland, 2Kliniken Essen-Mitte, Klinik für Gynäkologie und Gynäkologische 

Onkologie, Essen, Deutschland, 3HSK, Klinik für Gynäkologie und 

Gynäkologische Onkologie, Wiesbaden, Deutschland, 4Charite Campus 

Virchow Klinikum, Frauenklinik, Berlin, Deutschland, 5Evangelisches Krankenhaus Düsseldorf, Klinik für Gynäkologie, Düsseldorf, Deutschland, 

6 7 Universitätsklinik Essen, Frauenklinik, Essen, Deutschland, Universitätsklinik 

Ulm, Frauenklinik, Ulm, Deutschland, 8Universität Freiburg, 

Frauenklinik, Freiburg, Deutschland, 9Universität Marburg, Frauenklinik, 

Marburg, Deutschland, 10Klinikum Rechts der Isar, Frauenklinik, München, 

Deutschland, 11Universität Frankfurt, Frauenklinik, Frankfurt, Deutschland, 

12 13 Universität Tübingen, Frauenklinik, Tübingen, Deutschland, Universität 

des Saarlandes, Frauenklinik, Homburg, Deutschland, 14Klinikum Karlsruhe, 

Frauenklinik, Karlsruhe, Deutschland, 15Universität Erlangen, Frauenklinik, 

Erlangen, Deutschland, 16Universität Dresden, Frauenklinik, Dresden, 

Deutschland, 17Klinikum Großhadern, Frauenklinik, München, Deutschland, 

18 19 Universität Magdeburg, Frauenklinik, Magdeburg, Deutschland, Medizinische 

Hochschule Hannover, Frauenklinik, Hannover, Deutschland, 

20 21 Klinikum Offenbach, Frauenklinik, Offenbach, Deutschland, Universität 

Kiel, Frauenklinik, Kiel, Deutschland, 22Universität Göttingen, Frauenklinik, 

Göttingen, Deutschland, 23Klinikum Bremen-Mitte, Frauenklinik, Bremen, 

Deutschland, 24Universität Greifswald, Frauenklinik, Greifswald, Deutschland, 

25Klinikum Radebeul, Frauenklinik, Radebeul, Deutschland, 26Klinikum Solingen, Frauenklinik, Solingen, Deutschland, 27AGO Study Group, Mimosa 

Investigators, Deutschland 

Background. Abagovomab (A), a murine monoclonal anti-idiotypic 

antibody directed against CA125, has been shown to induce an active 

immune response against CA125 tumor-associated antigen in advanced 

ovarian cancer patients. 

Methods. A has been tested in a randomized (2:1) double-blind, placebo 

(P) controlled, multicenter phase III trial in patients with FIGO stage 

III/IV ovarian cancer after complete response to platinum-taxane firstline 

chemotherapy. A (2 mg/1 ml) or P was given subcutaneously every 

2 weeks for 6 weeks (induction phase); then every 4 weeks (maintenance 

phase) until recurrence, or up to 21 months after the last patient had 

been randomized. Primary endpoint is progression-free survival (PFS); 

secondary endpoints are OS and immunological response. An estimated 

870 patients, with a mean follow-up of 18 months, were needed to 

observe at least 535 recurrences, which provides a power >90% in rejecting 

the null hypothesis of equality between A and P on PFS according 

to an HR (hazard ratio) of 1.33. Primary analysis was run on PFS in the 

ITT population. 

Results. 888 patients were enrolled by December 2008, 593 in A arm 

and 295 in P arm. The median follow-up was 28.1 months and the mean 

number treatment administrations was 18. Baseline characteristics 

were balanced between arms. Overall tolerability profile was consistent 

with previous A studies. Median (95% CI) PFS was 13.24 (10.612–13.602) 


months for A arm and 13.21 (10.612–16.000) months for P arm; HR=1.099 

(0.919–1.315); p=0.301. 

Conclusion. Treatment with A did not translate into a prolonged PFS. 

0169 

The adhesion molecule L1CAM as novel therapeutic target for 

highly malignant pancreatic and ovarian carcinoma 

C . Dieckmann1 , O . Korniienko2 , G . Moldenhauer3 , A . Krüger4 , P . Altevogt3 , 

H . Schäfer1 , *S . Sebens5 1Department of Internal Medicine I, Laboratory for Molecular Gastroenterology 

& Hepatology, Kiel, Deutschland, 2Institute for Experimental 

Cancer Research, Molecular Oncology, Kiel, Deutschland, 3German Cancer 

Research Center, Translational Immunology D015 , Heidelberg, Deutschland, 

4Technische Universität München, Institute of Experimental Oncology and 

Therapy Research, München, Deutschland, 5Department of Internal Medicine 

I, Institute for Experimental Medicine, Kiel, Deutschland 

Background. The adhesion molecule L1CAM (CD171) accounts for enhanced 

motility, invasiveness and chemoresistance of tumor cells and 

thus represents a promising therapeutic target structure for various tumor 

entities. In pancreatic ductal adenocarcinoma (PDAC) and ovarian 

carcinoma elevated L1CAM expression has been detected being associated 

with an advanced tumor stage and poor prognosis. 

Aim. The present study intended to evaluate the therapeutic potential 

of combined treatment with L1CAM antibodies and chemotherapeutic 

drugs in PDAC and ovarian carcinoma model systems in vivo. 

Methods and results. Two L1CAM-specific antibodies showing strong 

binding to the L1CAM expressing PDAC cell line Colo357 and the ovarian 

carcinoma cell line SKOV3ip were used for treatment regimens. 

Combined therapy of SCID mice with either L1CAM antibody and gemcitabine 

and paclitaxel, respectively, reduced the growth of Colo357 or 

SKOV3ip tumors more efficiently than the treatment with the cytostatic 

drug alone or in combination with control IgG. The improved therapeutic 

response was accompanied by an increased number of apoptotic 

tumor cells, whereas proliferation of the tumor cells was not affected by 

combined treatment. Furthermore, a lowered activation of NF-kB along 

with a reduced expression of VEGF and a diminished number of CD31positive 

blood vessels were observed in tumors after combined therapy 

compared to control treatments, while the infiltration of macrophages 

was enhanced. 

Conclusion. Overall, these data support the suitability of L1CAM as therapeutic 

target and of L1CAM-interfering antibodies as an appropriate 

tool for an improved therapy of PDAC and ovarian carcinoma. 

0181 

Patient’s Perception and possibilities of optimization of clinical 

trials in gynaecological oncology 

*S .-M . Knetzger1 , T . Hildebrandt1 , M . Bani1 , C . Bayer1 , A . Hein1 , L . Kahmann1 , 

C . Löhberg1 , S . Jud1 , M . Schauder1 , F . C . Thiel1 , P . Fasching1 , M . Beckmann1 , 

M . P . Lux1 1Frauenklinik, Universitätsklinikum Erlangen, Universitäts-Brustzentrum 

Franken, Erlangen, Deutschland 

Introduction. Clinical trials are becoming more and more important to 

optimize prevention, diagnosis and therapy. They contribute towards 

transferring the latest knowledge to daily clinical life. Moreover, the option 

of participating in trials is a criterion of quality – certified centres 

are obliged to offer trials as well as to fulfil trial-quotes. On the other 

hand, trials are highly dependent on the cooperation of patients. Therefore 

the perception of clinical studies and the possibilities to optimize 

the offers from the patient’s point of view is very important. 

Material and methods. 2500 women are surveyed on the topics of perception 

and optimization of clinical trials by 24 specific questions. The

esults are compared relating to disease entity and other anamnestic 

factors. 

Results. 1029 patients could be evaluated (24.0% senological, 8.1% gynaecologic-oncological, 

29.3% obstetrical, 7.5% with endometriosis, 2.0% 

with desire of children, 21.9% others and 6.6% with missing categorization). 

Knowledge about clinical trials turned out to be very heterogeneous; 

e.g. only 18.5% of the participants know the term “randomisation”. 

91.9% consider clinical trials as useful (0.7% not useful, 7.4% do not 

know). In contrast, only 54.2% would participate in a clinical trial, 18.0% 

reject this and 27.8% are undecided. 69.9% support the participation in 

surveys and 64.4% would take part in trials to improve diagnosis. Only 

13.0% agree with drug testing trials. Regarding the treatment in clinical 

trials, 24.2% judge the quality of care better and 20.6% worse than treatment 

outside of trials (55.2% do not know). But 49.6% of the patients believe 

that they will get the best possible treatment within clinical trials. 

While financial compensation would only influence the willingness to 

participate of 11.8%, 33.4% of the patients think that a recommendation 

of the German Cancer Society would be a positive factor for participation. 

82.7% mention the medical specialist as the most important source 

of information about clinical trials. Significant differences were found 

in the sub-groups, which will be presented in detail. 

Summary. Generally a high percentage of patients consider clinical trials 

as important, though trials for drug testing are still seen most critically. 

Knowledge about trails is very heterogeneous. More educational work 

seems to be necessary, whereby patients have clear wishes and suggestions. 

0182 

Implementierung genexpressionsanalytischer Verfahren zur 

Bestimmung des individuellen Mammakarzinomrückfallrisikos 

in die klinische Praxis – Implementation of gene array methods 

to determine the risk of recurrence in breast cancer in clinical 

routine 

*S . Paepke1 , P . Völkel1 , H . Bronger1 , J . Ettl1 , M . Kiechle1 1Technische Universität München, Klinikum rechts der Isar, Frauenklinik, 


Introduction. The biomarkers used so far to asses prediction and prognosis 

of early breast cancer are unreliable to a certain extent; grading 

shows a high intraobserver variability, Ki67 is not validated enough to 

differentiate between intermediate and highly proliferative disease, and 

lymph node status is subordinated to tumor biology. Genomic arrays 

(70- and 21-gene array) are available and partly used internationally in 

clinical decision making, in Germany, however, only in clinical trials or 

in individual cases. 

Material and methods. At the IBZ (interdisciplinary breast center) of the 

Technische Universität München an algorithm was developed for the 

use of the 21-gene array in routine diagnostics, which leads to a therapy 

decision change in 60% of the cases tested. The MammaPrint® test is a 

DNA-micro array based diagnostic, multivariate in-vitro-Index-Assay 

(IVDMIA) and measures the activity of 70 genes to determine the probability 

of recurrent disease (as low or high risk group). MammaPrint® 

is used in both ER positive and ER negative stage I and II breast cancer 

with up to three positive lymph nodes. 

Concept. In a cohort study 15 cases in which the MammaPrint® assay 

was used were compared to the standard collective. We expect that between 

30% and 50% less cases will include chemotherapy in their therapy 

recommendations. The actual therapy changes and the cost-benefit ratio 

are analysed as these will be relevant for an implementation of the 

test in clinical routine. 

Outlook. The feasibility of MammaPrint® in clinical routine has been 

confirmed in several trials; an implementation in routine diagnostics 

must be critically discussed on the basis of prospectively collected data 

relevant to the German health care system. The results from the IBZ of 

the TU München are be presented. 

0191 

BKM120 in advanced endometrial cancer: an update on clinical 

trials 

*J . Sehouli1 , B . Gerber2 , L . Trandafir3 , C . Massacesi3 , N . Fretault3 , J . Stieglmaier4 

, M . Potzner4 , W . Lichtenegger5 1Charité Berlin, Europäisches Kompetenzzentrum für Eierstockkrebs, Berlin, 

Deutschland, 2Klinikum Südstadt, Universitätsfrauenklinik und Poliklinik, 

Rostock, Deutschland, 3Novartis Pharma, S .A .S ., Rueil-Malmaison, Frankreich, 

4Novartis Pharma, OCF, Nürnberg, Deutschland, 5Charité Berlin, Klinik 

für Frauenheilkunde und Geburtshilfe, Berlin, Deutschland 

Background. BKM120 is an oral pan-class I PI3K inhibitor targeting the 

PI3K/AKT/mTOR pathway which is commonly deregulated in cancer. 

The PI3K pathway is a key signal transduction system linking multiple 

oncogenes, tumor suppressors and receptor classes to essential cellular 

functions e.g. cell growth. Alterations of key components, like activating 

mutations of PIK3CA (the gene encoding the PI3K catalytic subunit) 

and loss of PTEN (phosphatase and the tensin homolog), trigger 

aberrant activation of the pathway signaling, leading to a modulation 

of different cell processes. BKM120 is an oral agent that showed potent 

antitumor activity in preclinical research and has demonstrated antiproliferative 

effects in endometrial carcinoma (EC) cell-lines and xenograft 

models. 

Current development. Most ECs showed dependency on PI3K pathway 

activation. Both PIK3CA and PTEN alterations are observed. Mutations 

in both genes lead to an activation of the PI3K pathway signaling 

in 26–36% and 26–59% of endometrioid EC, respectively, and in 5–21% 

and 0–11% of non-endometrioid EC. Thus, efficacy of BKM120 is currently 

investigated in a prospective multi-center, open-label, single arm, 

phase II study in patients with advanced, metastatic endometrial cancer. 

Adult patients with ECs whose disease progressed while on or after 

first-line antineoplastic treatment for advanced EC who have not been 

treated with any PI3K inhibitor are enrolled. After enrollment, PI3Kpathway 

activation status will be assessed, and defined as: PIK3CA mutation 

and/or PTEN mutation and/or PTEN-negative expression (

Abstracts 

our breast unit since 2003. For each patient an ITB gave two treatment 

recommendations: The first recommendation based on the results available 

from the sentinel node biopsy (ITB I). The second recommendation 

based on the results of the secondary axillary dissection (ITB II). 

We evaluated differences regarding the indication of chemotherapy (yes 

versus no), the type of adjuvant chemotherapy (conventional scheduled 

versus dose dense regimes) and the type of radiotherapy (whole breast 

irradiation with or without irradiation of regional lymph nodes). 

Results. 170 patients were enrolled. 133 had one and 28 had two tumor 

involved sentinel nodes. Comparing the two ITB recommendations for 

each patient we could demonstrate an overall difference in 33 (20%) patients. 

In 29 (17%) patients ITB II recommended a more intensive treatment 

i.e. dose dense chemotherapy and/or additional irradiation of the 

lymph nodes. In 4 patients (2.4%) a chemotherapy was recommended by 

ITB I but not by ITB II. 

Conclusion. Our results showed that a secondary ALND might have 

a strong impact on treatment recommendations of an ITB favouring 

more intensive adjuvant chemotherapy and/or irradiation. 

0200 

Carboplatin plus weekly Paclitaxel as an effective, non-anthracyclin-containing 

preoperative chemotherapy in triple negative 

breast cancer (TNBC) 

*L . Kahmann1 , C .R . Löhberg1 , M .G . Schrauder1 , M .R . Bani1 , C .M . Bayer1 , 

O . Strahl1 , A . Hartmann2 , R . Schulz-Wendtlandt3 , E . Wenkel3 , P .A . Fasching1 , 

M .W . Beckmann1 , M .P . Lux1 1 21 23 Frauenklinik des Universitätsklinikums Erlangen, Universitätsstraße - , 

Deutschland, 2Pathologisches Institut des Universitätsklinikums Erlangen, 

Erlangen, Deutschland, 3Institut für diagnostische Radiologie des Universitätsklinikums 

Erlangen, Erlangen, Deutschland 

Objective. Despite substantial progresses in breast cancer therapy, patients 

with TNBC still remain a challenge. Pathological complete response 

(pCR) is one of the most important prognostic markers in preoperative 

setting of breast cancer treatment. Platinum-containing regimens 

have been included as a possible preoperative option for patients with 

TNBC into the recommendations of the AGO in 2011, due to increasing 

data showing a high degree of effectiveness. The aim of this retrospective 

analysis is to evaluate the pCR rate after preoperative chemotherapy 

with Carboplatin and Paclitaxel in the treatment patients with TNBC. 

Methods. 20 patients with TNBC received preoperative chemotherapy 

with six cycles of carboplatin (AUC 5), d1, in combination with paclitaxel 

(80 mg/m2), d1, 8, 15, q21d. Evaluation of clinical response was done 

after cycle three and six by palpation and mammography/ ultrasound. 

pCR was defined as no invasive cancer in the breast and axillary specimen 

after breast-conserving therapy/ breast ablation plus axillary dissection 

(pT0/pTis and pN0). 

Results. 15 of 20 patients received surgery (breast-conserving therapy/ 

breast ablation plus axillary dissection). Clinical (cCR) and pCR were 

seen in 46% (n=7/15) and 60% (n=9/15), respectively. Histological assessment 

showed a general response of minimum SINN grade 2.The 

combination of carboplatin and paclitaxel was well tolerated except one 

peripheral polyneuropathy grade 3 (NCI-CTC). 

Conclusion. The combination of carboplatin (AUC 5), d1, and paclitaxel 

(80 mg/m2), d1, 8, 15, q21d, in the preoperative setting is a highly effective 

and well tolerated option for patients with TNBC. Final results are 

expected for December 2011 and will be demonstrated. Results of this 

retrospective analysis should be proofed in major prospective, randomised 

trials. 


0201 

Whole gene expression profiling in patients with primary breast 

cancer 

*J . Aigner1 , K . Smetanay1 , M . Zapatka2 , B . Burwinkel1 , H . Junkermann1 , 

F . Marme1 , H .P . Sinn1 , P . Lichter2 , C . Sohn1 , A . Schneeweiss1 1Universitätsklinik Heidelberg, Frauenklinik/NCT Gyn Onko, Heidelberg, 

Deutschland, 2Universität Heidelberg DKFZ, Biologie, Heidelberg, Deutschland 

Objective. Breast cancer is a heterogeneous disease in terms of therapeutic 

response and patients’ outcome. Gene expression analysis provides 

new classification systems on the molecular level which might be used 

to determine prognosis of outcome and prediction of response to specific 

therapies leading to a more individualized treatment for each patient. 

The aim of our program is to validate prospectively four gene expression 

signatures on our own platform which were either already commercially 

available or have been extensively tested within clinical trials. 

Material and methods. Since 11/2010 patients with primary invasive breast 

cancer received one additional core biopsy at diagnosis to perform 

a whole gene expression profiling and read out the expression of genes 

belonging to the signatures Intrinsic Signature (IS), Genomic Grade Index 

(GGI), Recurrence Score (RS) and Amsterdam Signature (AS). In a 

second step subtypes according to IS (luminal A, luminal B, HER2-enriched, 

basal-like), GGI (low, high), RS (low risk, intermediate risk, high 

risk) and AS (low risk, high risk) were correlated with the immunohistochemical 

determined subtypes according to the expression of estrogen 

receptor (ER), progesterone receptor (PgR), HER2 and Ki-67 (luminal 

A-like: ER and PgR positive (+), HER2 negative (−), Ki-67 14%; HER2like: 

ER and PgR−, HER2+; triple negative: ER and PgR and HER-) and 

the histological grade (G1–2, G3). 

Results. Until June 2011, 94 patients have been enrolled. 18 patients had 

to be excluded. 23 (30%) had tumor involved lymph nodes. Histological 

grade I, II and III was reported in 8 (11%), 41 (54%) and 27 (36%) patients. 

63 (83%) patients had a ER/PgR positive and 69 (91%) patients a 

HER2 negative breast cancer. 51 patients showed a Ki-67>14%. The concordance 

between subgroups according to immunohistochemistry and 

IS or GGI was 16% and 70%. Most G2 patients showed a low risk GGI. 

A validation of RS and AS with the commercial available tests is still in 

process. 

Conclusion. In our cohort of primary breast cancer, thus far, there is 

only partial overlap of subtypes according to immunohistochemistry 

and gene expression analyses. Gene expression signatures as prognostic 

or predictive markers have to be validated prospectively before they are 

used outside of clinical trials. Updated results will be presented at the 

meeting. 

0203 

A consecutive series of 12 heavily obese endometrial cancer 

patients treated by robotic laparoscopic surgery 

*Z . Maden1 , P . Kannisto1 , P . Harter1 , A . du Bois1 1Kliniken-Essen-Mitte, Gynäkologische Onkologie, Essen, Deutschland 

Objective. The robotic technique was introduced in February 2011 in 

our centre. We report here the first 12 consecutive cases of endometrial 

cancer. 

Methods. Surgery was performed by the SE da Vinci system without 

uterine manipulator but with four robot arms. All patients got perioperative 

antibiotics as well as low molecular heparin. 

Results. The mean BMI value was 40.6 and 33% of the patients had at 

least one former abdominal surgery. Mean blood loss for the robot procedures 

was 140 ml. The average skin-to-skin time was 222 minutes. 

The pressure controlled ventilation was used during anesthesia and the 

PEEP values were kept 5–7 mmHg. There was a preparedness for early 

intervention with cathecholamines. Ventilation was controlled by tran-

cutaneous CO2 monitoring, which has previously been shown to reduce 

the risk of respiratory acidosis significantly. The conversion rate to laparatomy 

was 8.3% (1/12 pts) due to multiple adhesions and intestinal injury. 

The only severe complication was observed in a patient with BMI 70. 

She had double dose heparine and experienced a heavy bleeding from 

vaginal cuff 16 days after da Vinci surgery. A laparatomy was performed 

and she suffered thereafter from a wound infection. 

Conclusion. Robotic assisted hysterectomy is a safe procedure and showed 

a considerably low rate of major complications in this morbidly 

obese group of endometrial cancer patients. 

0205 

Quality of life and therapy expectations of patients with recurrent 

platinum-sensitive ovarian cancer – a German substudy of 

the Calypso/AGO-Ovar 2.9 trial 

*K .H . Baumann1 , J . Sehouli2 , A . du Bois3 , D . Lubbe4 , P . Wimberger5 , 

M .W . Beckmann6 , F . Hilpert7 , L .C . Hanker8 , A . Hasenburg9 , B . Richter10 , 

S . Mahner11 , A . Burges11,12 , E . Pujade-Lauraine13 , U . Wagner1 1Universitätsklinikum Gießen und Marburg, Standort Marburg, Gynäkologie, 

Gyn . Endokrinologie und Onkologie, Marburg, Deutschland, 2Charite – University Medicine of Berlin, Gynecology, Berlin, Deutschland, 3Hospital Essen Mitte, Gynecology, Essen, Deutschland, 4University of Marburg, 4Co ordinating Centre for Clinical Trials Marburg, Marburg, Deutschland, 5Uni versity of Duisburg-Essen, Gynecology and Obstetrics, Essen, Deutschland, 

6University of Erlangen, Gynecology and Obstetrics, Erlangen, Deutschland, 

7University Hospital of Kiel, Gynecology and Obstetrics, Kiel, Deutschland, 

8University of Frankfurt, Gynecology and Obstetrics, Frankfurt am 

Main, Deutschland, 9University of Freiburg, Gynecology and Obstetrics, 

Freiburg, Deutschland, 10Elblandklinikum, Gynecology and Obstetrics, 

Radebeul, Deutschland, 11University Medical Center Hamburg-Eppendorf, 

Gynecology, Hamburg, Deutschland, 12Ludwig-Maximilians-University, Gynecology and Obstetrics, München, Deutschland, 13Hopital Hotel Dieu, 

Paris, Frankreich 

Background. In patients receiving radiotherapy, correlations between 

patients’ expectation regarding healing at start of therapy and quality 

of life (QoL) have been reported. So far, in recurrent platinum-sensitive 

ovarian cancer little is known about patients’ expectation undergoing 

reinduction chemotherapy. 

Objective. In this German substudy of the international CALYPSO/ 

AGO-Ovar 2.9 trial (JCO 28, 3323-9) patients’ subjective assessments of 

success of therapy, and the relationship to QoL were evaluated. In the 

CALYPSO/AGO-Ovar 2.9 trial patients with recurrent platinum sensitive 

ovarian cancer were randomized to receive carboplatin-paclitaxel 

or carboplatin-pegylated liposomal doxorubicin chemotherapy. Systemic 

treatment consisted of 6–9 cycles carboplatin and paclitaxel (TC) 

or carboplatin and pegylated liposomal doxorubicin (CD). At baseline 

registration before randomization and at the end of therapy patients 

completed the QoL questionaires (FACT-O, EORTC QLQ C-30 and 

OV-28) and an expectations checklist (J Royal Soc Med 93, 621–8) with 

the scores: “healing expectation”; “tumor and symptom control”; “pain 

and emotional control”. 

Results. Of 299 patients enrolled in Germany, 97 patients completed the 

expectation checklist (50 in the TC arm; 47 in the CD arm). At baseline, 

44 (TC) and 45 (CD) patients stated a positive “healing expectation”. 

The subjective assessment of the patients at the end of therapy showed, 

that 29 (CD) and 37 (TC) patients found their healing expectations fulfilled. 

Only one of the scales of the expectations checklist (“pain and 

emotional control”) revealed a significant correlation with the QoL 

questionnaires. Results of the QoL questionnaires and the expectations 

checklist did not differ significantly between the treatment groups. 

Conclusion. “Healing” was stated most frequently as expectation and assessment 

of success in patients with recurrent ovarian cancer, followed 

by the other categories. QoL did not differ significantly between treat- 

ment groups and patients with or without healing expectations, only 

the expectation category “pain and emotional control” revealed some 

correlation with the QoL questionnaires. 

0224 

Superparamagnetic nanoparticles for magnetic particle imaging 

in breast cancer sentinel lymph node detection 

*D . Finas1 , K . Baumann1 , B . Ruhland1 , K . Heinrich1 , K . Lüdtke-Buzug1 , K . Diedrich1 

, T . Buzug1 1Universität zu Lübeck, Klinik für Frauenheilkunde und Geburtshilfe, 

Lübeck, Deutschland 

Introduction. Radical axillary lymphonodectomy is associated with 

high morbidity and significant loss of QoL. But, the exploration of the 

axillary lymph nodes is part of the surgical staging in breast cancer. 

The adverse effects decreased since the introduction of the sentinel lymphonodectomy 

(SNLB), were dyes and radio nuclides are injected. Super 

paramagnetic iron oxide nano particles (SPIOs) could replace these 

marker substances. Through the magnetic particle imaging (MPI), a 

3D-imaging and distinct localization of SPIOs can be achieved in SNLB. 

Qualitative and quantitative enrichment of SPIOs in the axillary lymphatic 

tissue is unexplored until now. 

Methods. Within a healthy mouse model and than in a tumor bearing 

mouse model with metastatic axillary lymph nodes we prove the principle 

of SNLB by MPI. Axillary and environmental tissues are analyzed 

with different techniques: histology, Prussian blue staining, electron 

microscopy, atomic absorption spectrometry and MPI spectrometry. 

Nanoparticles are widely discussed as environmental toxins. Therefore, 

we will extract the inoculated SPIOs from all organs and explore them 

whether there are any SPIOs. 

Results. We aim to show that SPIOs and the MPI technique are effective 

to be used as SNLB tracer and finder as a new SNLB technique. This will 

be less complex and incriminating for the patient and the staff. A new 

MPI hand probe with unilateral solenoid arrangement designed for use 

in the operating theater is under construction. Therewith the sentinel 

lymph node detection can be easily performed after intra operative tracer 

application. 

Conclusion. Intra operative 3D-imaging with the MPI hand probe facilitates 

the axillary SNL detection and moreover makes it more precise. 

Through the avoidance of intensive surgical exploration of the axilla the 

morbidity will be dramatically reduced. The tracer for MPI is easy to 

obtain. This makes the method accessible to all patients. The concept of 

SNLB by MPI can be applied in principle in all solid tumors. 

Supported by the German Federal Ministry of Education and Research 

(BMBF Grant number 01EZ0912). Part of the University Research Program 

Imaging of Disease Processes, University of Lübeck. 

Abstract withdrawn 

0228 

Staging accuracy of gynaecological cancers with endorectal coil 

MRI 

*K . Brocker1 , C . Alt1 , C . Sohn1 , M . Eichbaum1 , P . Hallscheidt1 1Universität Heidelberg, Frauenklinik, Heidelberg, Deutschland 

Objective. Endometrial, cervical and vulvar cancer are frequent gynaecological 

cancers. The aim was to evaluate staging accuracy of MRI in 

patients with primary endometrial, cervical or vulvar cancer using MRI 

with an endorectal coil. 

Material and methods. Patients with histologically proven cancers received 

1.5T MRI with endorectal surface coil (eMRI) before surgery. 

Performed sequences: sagittal, axial and coronal T2w turbo spin echo 

(TSE), axial T1 incoherent gradient echo (gradient spoiled) 2D fat saturated 

(fs), sagittal T1 incoherent gradient echo (gradient spoiled) 3D 


75

Abstracts 

with/without contrast enhancement (CE), axial T1 TSE fs CE. eMRI staging 

was compared to histopathological results. 

Results. 19 patients with vulvar cancer, 15/19 had primary surgery. 10 of 

15 patients (pts) underwent eMRI, 5 underwent MRI without (w/o) endorectal 

surface coil due to eMRI contraindications. Histopathological 

result was: 2 pts with stage T1a, 8 pts T1b, 4 pts T2 and one patient with 

stage T3. Overall MRI accuracy was 53% (8/15), eMRI was 60% (6/10) and 

MRI w/o endorectal coil was 40% (2/5). The urethra was histologically 

affected in 5 cases, vagina in 3 cases, perineum and anus in 2 cases each. 

Overall agreement of invasion of surrounding structures was 75% (9/12). 

Histological proven lymph node (LN) affection in 7 of 15 pts, correctly 

diagnosed with eMRI in 71% (5/7). If LNs were not affected, MRI staged 

correctly N0. 33 pts with endometrial cancer, 21/33 with primary surgery. 

8 pts had histological stage T1a, 10 pts T1b, 2 pts T2b, one patient T3a. 

Overall eMRI staging accuracy of local tumor spread was 71% (15/21). In 

lower tumor stage eMRI correctly diagnosed stage T1a in 6 of 8 pts and 

T1b in 8 of 10 pts. In 2 cases eMRI overstaged, in 2 cases eMRI understaged. 

In only one patient LN were positive; correctly diagnosed by eMRI. 

44 patients with cervical cancer received primary surgery of which 2 

were inoperable. Histological results were 8/44 Cis, 3/44 T1a1, 2/44 T1a2, 

15/44 T1b1, 1/44 T1b2, 0/44 T2a, 12/44 T2b, 0/44 T3 and 1/44 with T4 stage. 

In 43% eMRI staged correctly, clinical examination staged correct in 

47.6%. eMRI sensitivity of deciding between tumours up to T2a or a size 

beyond was 92.3%, in clinical examination 38.5%. Uterine infiltration 

was detected in 100% by eMRI. 

Conclusion. eMRI presented high staging accuracy in lower endometrial 

tumour stage. In cervical cancer eMRI proved a reliable tool for tumours 

greater FIGO IIa improving the assessment of surround tumour 

infiltration. In lower staged cases more practice and technical development 

is needed. In vulvar cancer eMRI is helpful for pretherapeutic 

planning, especially for urethral involvement and lymph node affection. 

eMRI is a useful supplement in clinical gynaecological oncology 

treatment planning. 

0236 

Targeting triple negative breast cancer through the luteinizing 

hormone-releasing hormone receptor 

*S . Seitz1,2 , A .V . Schally2 , A . Treszl2 , F . Weber3 , M . Mögele1 , A . Machleidt1 , 

O . Ortmann1 , S . Buchholz1,2 1Universität Regensburg, Frauenheilkunde, Regensburg, Deutschland, 

2University of Miami, endocrine, polypeptide and cancer institute, Miami, 

Deutschland, 3Universität, Pathologie, Regensburg, Deutschland 

Introduction. Receptors for luteinizing hormone-releasing hormone receptor 

(LHRH-R) are expressed in >50% of human breast cancers. For 

our knowledge to date the expression of LHRH-R in the distinct subtype 

of triple negative breast cancer (TNBC) was not evaluated. Systemic 

treatment options for TNBC are limited to chemotherapy. New structures 

for targeted therapy would be very favourable. AN-152 [AEZS-108] is 

a LHRH-analog conjugated to doxorubicin. AN-152 is targeted through 

the peptide moiety to the LHRH-R. In this study we investigated the 

expression of the LHRH-R on TNBC samples and the effect of AN-152 

on tumor growth inhibition of AN-152 in an in vivo model. 

Material and method. For the in vivo model we used the TNBC cell lines 

MDA-MB-231 and HCC 1806. The cell lines were checked for LHRHreceptor 

expression by RT-PCR. Tumors grown from these cell lines 

were xenotransplanted into nude mice subcutaneously. Animals were 

randomised into three groups receiving solvent only (control), AN-152 

(2.5 µmol/kg d 1, 7, 14 i.v.) or Doxorubicin (2.5 µmol/kg d 1, 7, 14 i.v.). 

The experiment ended on day 28. The expression of LHRH-R on tumor 

samples form patients with TNBC (n=69) was evaluated by immunhistochemistry. 

Results. The LHRH-R was expressed in both cell lines on mRNA level. 

In the animal experiment with the cell line MDA-MB-231 animals treated 

with AN-152 showed a significant (p

matic and nuclear compartmentalization of the oncogene Akt and the 

tumor suppressor mTOR are integrated in negative regulatory feedback 

loops. The macrolide derivative of rapamycin RAD001 (everolimus) is 

an inhibitor of the serine-threonine kinase mTOR, and was developed 

as an anti-proliferative and anticancer agent. However, inhibition of 

mTOR signaling by RAD001 leads to increased Akt activation through 

phosphorylation. Akt activation abrogates RAD001-induced antiproliferative 

effects and results in RAD001 resistance. 

Chloroquine is a 4-alkylamino substituted quinoline, an effective chemosensitizer 

when used in combination with PI3K/Akt inhibitors and 

mediated breast cancer protective effects. Using MCF7 breast cancer 

cells our aim was to test if Chloroquine could inhibit tumor growth 

through PI3K signaling and overcome RAD001-induced Akt activation. 

Chloroquine and RAD001 inhibited phospho-mTOR and its 

downstream target gene S6K1, especially in the nucleus. Importantly, 

Chloroquine blocked the RAD001-induced phosphorylation of nuclear 

phospho-Akt. Additionally, Chloroquine and RAD001 induced G1 cell 

cycle arrest, reduced MCF7 breast cancer cell proliferation on a collagen 

matrix and disturbed formation of mammospheres. Furthermore, 

Chloroquine and RAD001 together significantly reduced mammary 

tumor growth in a murine xenograft model. 

Our data show that Chloroquine exerts its anti-cancer effects through 

modifications of the PI3K/Akt/mTOR pathway involving the nucleus 

where cellular compartmentalization of Akt and mTOR might play a 

crucial role. Treatment of breast cancer patients with Chloroquine in 

combination with RAD001 may be important for overcoming RAD001 

resistance. 

0243 

Prognostic role of lymph-node metastases in vulvar cancer and 

implications for adjuvant radiotherapy 

*L . Woelber1 , C . Eulenburg2 , M . Choschzick3 , D . Rohsbach1 , F . Gieseking1 , 

A . Kruell4 , C . Petersen4 , F . Jaenicke1 , S . Mahner1 1University Medical Center Hamburg-Eppendorf, Department of Gynecology, 

Hamburg, Deutschland, 2University Medical Center Hamburg-Eppendorf, 

Department of Medical Biometry and Epidemiology, Hamburg, 

Deutschland, 3University Medical Center Hamburg-Eppendorf, Institute of 

Pathology, Hamburg, Deutschland, 4University Medical Center Hamburg- 

Eppendorf, Department of Radiotherapy and Radio-Oncology, Hamburg, 

Deutschland 

Background. Lymph-node metastases are the most important prognostic 

factor for recurrence and survival in vulvar cancer. However, conclusions 

regarding the impact of the number of positive nodes on survival 

are inconsistent and so are recommendations when to apply adjuvant 

radiotherapy to the groins/pelvis. 

Methods. One-hundred-and-fifty-seven consecutive patients with primary 

squamous cell cancer of the vulva treated at our center were analyzed. 

All patients underwent primary surgery by triple incision resulting 

in complete tumor resection. 

Results. Median age was 61 years; 49 patients (31%) had lymph-node metastases; 

21 patients had 1, 13 had 2 and 15 had >2 positive lymph-nodes. 

The risk of lymph-node metastases increased with age, greater tumor 

size, deeper invasion and higher tumor grade. 32% of the patients received 

adjuvant radiotherapy. Median follow-up was 36 months; 23 patients 

(14.6%) developed disease-recurrence (61% vulva, 35% groins and 

4% both). Compared to node-negative patients, survival in all nodepositive 

patients was significantly impaired with no evidence of disease 

after 2 years in 88% of node negative patients and 60%, 43% and 29% in 

patients with one, 2 and >2 affected nodes, respectively, p

Abstracts 

0247 

Prognostic impact of circulating tumor cells and their HER2 

status assessed with two detection methods in patients with 

metastatic breast cancer 

*T . Fehm1 , B . Rack2 , S . Riethdorf3 , W . Janni4 , P . Fasching5 , E . Solomayer6 , 

B . Aktas7 , S . Kasimir-Bauer7 , K . Pantel3 , V . Müller8 1 2 Universitätsklinikum, Frauenklinik, Tübingen, Deutschland, Ludwig-Maximilians-Universität, 

Frauenklinik, München, Deutschland, 3Universitäts klinikum Eppendorf, Institut für Tumorbiologie, Hamburg, Deutschland, 

4Heinrich-Heine-Universität, Frauenklinik, Düsseldorf, Deutschland, 

5 6 Universitätsklinikum, Frauenklinik, Erlangen, Deutschland, Universitätsklinikum, 

Frauenklinik, Homburg/Saar, Deutschland, 7Universitätsklinikum, Frauenklinik, Essen, Deutschland, 8Universitätsklinikum Hamburg-Eppendorf, 

Klinik für Gynäkologie, Hamburg, Deutschland 

Purpose. Circulating tumor cells (CTC) can be detected in the peripheral 

blood of 30–60% of metastatic breast cancer patients. However, the 

optimal method for CTC detection is not clear so far. Therefore, we examined 

the prognostic impact of two methods for CTC detection in a 

prospective multicenter study. 

Methods. A total of 254 patients with metastatic breast cancer from nine 

German breast centers were enrolled in this study. CTC detection and 

HER2 status on CTC was examined at the time of tumor progression 

using both the FDA-approved CellSearch® assay based on immunocytochemistry 

and the RNA-based AdnaTest Breast CancerTM. 

Results. Using the CellSearch assay, 122 of 245 (50%) patients had ≥5 

CTC, and HER2-positive CTC were observed in 50 (41%) of these patients. 

Ninety of 229 (39%) patients were CTC positive using AdnaTest, 

and HER2 positivity rate was 47% (42 of 90). The rate of breast cancer 

patients with HER2-negative primary tumors but HER2-positive 

CTC was 32% (25 of 78) and 49% (28 of 57) using the CellSearch assay 

and AdnaTest, respectively. Detection of CTC was not correlated with 

progression free survival for both methods. Patients with positive CTC 

detected by Cell Search Assay showed shorter overall survival (14.6 mo. 

versus 20.1 mo.; p

0273 

Resection of hepatic metastases from breast cancer imbedded 

in a multimodal treatment concept – can it improve prognosis? A 

systematic review of the literature 

*K . Smetanay1 , J . Bodem1 , P . Schemmer2 , K . Jensen3 , J . Rom1 , A . Schneeweiss1 , 

C . Sohn1 , M . Eichbaum1 1Universitätsklinikum Heidelberg, Frauenklinik/NCT Gynäkologische Onkologie, 

Heidelberg, Deutschland, 2Universitätsklinikum Heidelberg, Klinik für 

Allgemein-, Viszeral- und Transplantationschirurgie, Heidelberg, Deutschland, 

3Universitätsklinikum Heidelberg, Institut für Medizinische Biometrie 

und Informatik, Heidelberg, Deutschland 

Introduction. For many patients suffering from metastatic breast cancer 

(MBC), surgical treatment of liver metastases is limited or not beneficial 

due to the systemic, multitopic character of the disease. Instead, for 

patients with isolated hepatic metastases from colorectal cancer, liver 

resection is a common procedure with a 5-year-survival of around 40%. 

Previous retrospective studies, however, demonstrated that liver resection 

for selected patients with MBC limited to the liver could prolong the 

survival rate to a greater extent than only systemic treatment. A 5-yearsurvival 

for resectable patients ranged from 18 to 59 %. The aim of this 

systematic overview is to clarify the survival and morbidity of patients 

with an additional surgical treatment within a multimodal concept. 

Methods. We performed a systematic overview of all peer-reviewed published 

trials and studies documented in the PubMed-, MEDLINE and 

EMBASE-database. Furthermore, a detailed search within published 

trials in the Cochrane Library was undertaken. Included were all retrospective 

and prospective clinical trials published on patients with MBC 

treated with surgery due to liver metastases. Primary endpoint of this 

systematic review was overall survival (OS). Secondary endpoint was 

peri- and postoperative morbidity. 

Results. We analyzed 36 studies which were published between 1991 and 

2010. From all included trials n=1428 patients had liver metastases from 

breast cancer and n=803 patients were treated by surgery. In most of the 

cases a major resection of the liver (3 or more than 3 segments) was performed. 

The mean disease-free interval comprised 44 months (range: 

34–70 months). After surgery, patients with a R0-resection showed a median 

survival of 44 months (range: 27–73 month). The median OS after 

5 years was described by n=393 patients with 40%. Complications were 

reported on 95 patients. The most common local complications included 

infected edema (n=12) and biliary leckage (n=12), while pleural effusion 

(n=8) was the main systemic complication. The mean hospitalization 

time was 9 days. 

Conclusion. This systematic overview should help to advise patients with 

hepatic MBC. Considering selected patients, the surgical treatment is an 

additional option within a multimodal concept as it can prolong survival 

with a relatively low morbidity. The aim of further studies should be to 

identify prognostic factors for a more individual risk-benefit-profile of 

each patient. 

0280 

Survial analyses in triple negative breast cancer patients: a 

comparison between neoadjuvant and adjuvant chemotherapy 

strategies 

*G . Pfeiler1 , C . Staudigl1 , A . Brunner2 , C . Singer1 , R . Königsberg3 1Medical University of Vienna, Department of Gynecology and Gynecologic 

Oncology, Vienna, Österreich, 2Landesklinikum Thermenregion Mödling, 

Department of Obstetrics and Gynaecology, Mödling, Österreich, 3Applied Cancer Research – Institution for Translational Research Vienna (ACR-ITR 

VIEnna)/CEADDP, Vienna, Österreich 

Background. The primary goal of neoadjuvant treatment in breast cancer 

is to downstage breast cancer tumor size thereby increasing the breast 

conserving operation rate. Regarding triple negative breast cancer 

(TNBC), there is a lack of evidence describing and comparing survival 

parameters of neoadjuvant and adjuvant treated TNBC patients. 

Methods. Between 1998 and 2006 pathologic and clinical data of 220 

TNBC patients were retrospectively analysed of whom Eighty-two 

were matched regarding neoadjuvant and adjuvant treatment. Baseline 

demographic and tumor characteristics were compared between the 

two matched TNBC patient cohorts using a Students-t test for means 

and χ2-test for frequencies.Kaplan-Meier plots for disease free survival 

(DFS), distant disease free survival (DDFS), loco-regional disease free 

(LDFS) and overall survival (OS) were used for each comparison. All 

p values are two sided and a value of

Abstracts 

rioration. In conclusion, the monoclonal rat antibody directed against 

BSPII is a powerful tool in treating experimental skeletal metastasis 

and warrants further development. 

0287 

Efficacy of platinum/taxane-based chemotherapy in elderly with 

advanced ovarian cancer: explorative analysis of three phase III 

trials from the AGO Study Group 

*A .M . Hempel1 , P . Harter2 , A . Strauss1 , J . Hedderich3 , E . Pujade-Lauraine4 , 

A . du Bois2 , J . Pfisterer5 , F . Hilpert1 1Universitätsklinikum Schleswig-Holstein Campus Kiel, Klinik für Gynäkologie 

und Geburtshilfe, Kiel, Deutschland, 2Kliniken Essen-Mitte, Gynäkologie 

und Gynäkologische Onkologie, Essen, Deutschland, 3Universitätsklinikum Schleswig-Holstein Campus Kiel, Institut für Medizinische Informatik und 

Statistik, Kiel, Deutschland, 4Hôpital Hôtel-Dieu, Oncology, Paris, Frankreich, 

5Städtisches Klinikum Solingen, Gynäkologie und Gynäkologische 

Onkologie, Solingen, Deutschland 

Background. Age is a negative prognostic factor for survival in ovarian 

cancer (OC). We analysed efficacy and prognostic factors in patients 

≥70 years of age treated with platinum-based 1st-line chemotherapy. 

Methods. Exploratory analysis of 3 prospective randomized trials 

(AGO-OVAR 3, 5, 7) investigating platinum/taxane-based chemotherapy 

in OC FIGO IIb–IV conducted between 1995 and 2002. Datasets 

from each trial were merged into a combined meta-dataset. Patients 

≥70 years of age at randomization who had received at least one cycle 

of the assigned treatment were analysed for progression-free (PFS) and 

overall survival (OAS) by Kaplan Meier method and prognostic factors 

by cox regression analysis. 

Results. Out of 3333 patients 359 (10.8%) were ≥70 years of age and eligible. 

Age was an independent prognostic factor for survival: Median PFS 

was 23.8 and 18.4 months (p

0329 

PRÄFERENZ STUDY – Patients’ individual choice for oral vs. 

intravenous Treosulfan in elderly patients with ovarian cancer: 

analysis of tolerability – for the North-Eastern German Society of 

Gynecological Oncology (NOGGO) study group 

*S . Mahner1 , P . Harter2 , S . Fuxius3 , L .C . Hanker4 , L . Müller4,5 , P . Klare6 , E . Heidrich-Lorsbach7 

, J . Sehouli8 1Universitätsklinikum HH-Eppendorf, Gynäkologie, Hamburg, Deutschland, 

2 3 Kliniken Essen-Mitte, Essen, Deutschland, Onkologische Schwerpunktpraxis 

Heidelberg, Heidelberg, Deutschland, 4University Cancer Center Frankfurt, 

Frankfurt, Deutschland, 5Onkologische Schwerpunktpraxis Leer, Leer, 

Deutschland, 6Praxisklinik Krebsheilkunde für Frauen, Berlin, Deutschland, 

7 8 Alcedis GmbH, Gießen, Deutschland, Charite University Medicine Campus 

Virchow, Gynecology and Gynecologic Oncology, Berlin, Deutschland 

Background and aims. There is an increasing interest in oral drug administration 

in oncology. Treosulfan is effective as oral (p.o.) and intravenous 

(i.v.) formulation for recurrent ovarian carcinoma. Primary 

aim of this study was to explore individual preference and compliance 

of elderly patients (≥65 years) for p.o. or i.v.-treosulfan. Secondary aims 

were to evaluate toxicity, response and survival. We present an interim 

analysis of patient’s characteristics and treatment choice, compliance of 

the treatment and toxicities for 102 included patients. 

Methods. Patients with platinum resistant or refractory ovarian cancer 

had free choice of treosulfan i.v. (7000 mg/m2 d1, qd29) or p.o. (600 mg/ 

m2 d1-28, qd56) for a maximum of 12 cycles (i.v.) or 12 months (p.o.). 

Indecisive patients were randomized. Toxicity was evaluated according 

to the NCI-CTC version 2.0. 

Results. 102 recruited patients completed therapy at the time of this analysis 

(median age 72 years, range 65–87). 84 patients chose i.v. and 14 

p.o., 3 were randomized to i.v and 1 to p.o. Median ECOG was 1 (n=0–2), 

and median number of prior chemotherapy-regimens was 3 (n=1–6). In 

total, 351 cycles of chemotherapy (n=1–12, median: 3) were administered. 

Most common hematological toxicites (grade 3/4) were thrombopenia 

(12.7%), leukopenia (11.8%) and anemia (3.9%). Most frequent non-hematological 

toxicities (grade 3/4) were fatigue (4.9%) and constipation 

(6.9%). 

Conclusions. Treosulfan therapy was generally well tolerated despite 

heavy pretreatment in most patients. As nearly 82% of patients at this 

interim analysis chose i.v.-treosulfan there seems to be an individual 

preference for i.v.-administrations in elderly patients with recurrent 

ovarian cancer. 

0330 

Quality of life and sexuality in patients with borderline tumors of 

the ovary (a substudy of the ROBOT-Study of the AGO-Ovar) 

*A . Hasenburg1 , J . Farthmann1 , M . Weil1 , C . Fotopoulou2 , N . Ewald-Riegler3 , 

O . du Bois3 , F . Trillsch4 , S . Mahner4 , H .-G . Strauß5 , P . Wimberger6 , A . du Bois7 1 2 Universitätsklinik, Frauenklinik, Freiburg, Deutschland, Charité, Frauenklinik, 

Berlin, Deutschland, 3Horst-Schmidt-Kliniken, Frauenklinik, Wiesbaden, 

Deutschland, 4Universitätsklinik, Frauenklinik, Hamburg, Deutschland, 

5 6 Universitätsklinik, Frauenklinik, Halle/ Saale, Deutschland, Universitätsklinik, 

Frauenklinik, Essen, Deutschland, 7Kliniken Essen Mitte, Frauenklinik, 

Essen, Deutschland 

Background and aims. Being sexually active may be an important aspect 

of quality of life (QoL). Both diagnosis itself and therapy of borderline 

tumors of the ovary (BOT) including surgical bilateral salpingo-oophorectomy 

could have an impact on quality of life (QoL) and sexual 

function. Therefore, we evaluated the influence of disease and surgical 

treatment on QoL including sexuality. Treatment impact on QoL and 

sexuality of patients with borderline tumors were evaluated with questionnaires. 

Methods. The presented study is a substudy of the ROBOT-study of the 

AGO Study Group. ROBOT is a pattern of care study, in which 1237 patients 

diagnosed with BOT between 1998 and 2008 in 27 institutions were 

included. 111 patients from 7 gyneco-oncological centres in Germany 

were evaluated with three different questionnaires (EORTC QoL-C30 

and SAQ, as well as a self-made questionnaire designed for this purpose). 

With these tools the impact of the different therapeutic strategies on 

QoL and sexual function and pleasure was evaluated. 

Results. Of the 111 patients (mean age 53 years) 55 were sexually active 

(mean age 44 years), whereas 51 were not (mean age 62 years). 5 patients 

did not answer this question. The mean value of the overall quality of 

life was 5.42 (0 meaning low quality, 7 high QoL). Asked about the subjective 

state of health, the mean score was 5.19 (0 meaning impaired status 

of health, 7 high status of health). Those patients (n=55) who were 

sexually active had a mean score of pleasure of 7.34 (ranging from 0 to 

18, a low score representing low pleasure). 28 patients were able to have 

an orgasm always with every intercourse or almost always without greater 

difficulty, 24 patients had small or moderate problems to obtain an 

orgasm, 5 patients almost never or never reached an orgasm. 

Conclusions. Overall sexual function and QoL were quite high, but only 

about half of the patients were sexually active at the time of our survey. 

Those patients who were sexually active were younger than those who 

were not. As patients with BOT have a very good overall survival, the 

long-term impact on QoL and sexual function needs special attention. 

0343 

Therapeutic genes delivered by targeted AAV9-vectors inhibit 

tumor growth in breast cancer in vivo 

*S . Michelfelder1 , A . Hunger1 , E . Koziolek2 , M . Kaul2 , J . Kleinschmidt3 , 

M . Trepel1 1Universitätsklinikum Hamburg Eppendorf, Hubertus Wald Tumorzentrum 

und Abteilung für Hämatologie und Onkologie, Hamburg, Djibouti, 2Uni versitätsklinikum Hamburg Eppendorf, Klinik und Poliklinik für Diagnostische 

und Interventionelle Radiologie, Hamburg, Deutschland, 3Deutsches Krebsforschungszentrum, Heidelberg, Deutschland 

Introduction. Targeted gene therapy is a potential means to systemically 

treat cancer. Vectors derived from adeno-associated virus serotype-9 

(AAV9) are particularly attractive due to their high transduction efficiency 

and their excellent safety profile, but their tropism is unspecific. 

Here, we report a combined approach to target therapeutic genes to 

disseminated tumors by incorporation of tumor specific peptides into 

the viral capsid and microRNA (miR)-regulated gene expression in a 

mouse model for multifocal breast cancer. 

Methods. Targeted AAV9 vectors harbouring a mir1-d binding domain 

and luciferase or an HSV-tk gene (SR39) displaying a breast cancer-targeted 

peptide selected from random AAV display libraries were 

established. Vectors were applied intravenously to PymT mice bearing 

palpable breast tumors. In vivo transduction of rAAV-luciferase was 

determined by bioluminescence imaging (BLI) and single organ transduction 

was analyzed by luminometry. Gancyclovir (GCV) treatment 

was initiated four days after application of SR39 vectors. Therapeutic efficiency 

and possible side effects of suicide gene therapy was assessed by 

tumor growth, histology and magnetic resonance tomography (MRT) 

analysis. 

Results. After systemic vector injection, AAV-ESG-mir1-d luciferase 

vectors mediated strong gene expression in tumor tissue while, compared 

to wild type vectors, expression decreased in almost all control 

tissues including heart and liver. Suicide gene treatment significantly 

inhibited tumor growth after one single vector administration and eight 

cycles of GCV treatment [tumor volume 0.51±0.12 ×1000 mm3 treated 

(n=8) vs. 3.4±0.81 ×1000 mm3 control group (n=10)]. Treatment response 

was further validated by MRT. 

Conclusions. Tumor-specific gene delivery can be realized by insertion 

of targeting peptides into putative receptor-binding capsid regions of 


81

Abstracts 

AAV9 and microRNA-regulated transgene expression. Systemic HSVtk 

suicide gene transfer inhibits progression of growth of multifocal 

tumors in vivo, while apparent side effects do not occur. This demonstrates 

the feasibility of targeted AAV vectors as promising candidate 

for therapeutic application in disseminated cancer. 

0358 

Radiation-related quality of life parameters after targeted 

intraoperative radiotherapy versus whole breast radiotherapy 

in patients with breast cancer: Results from the randomized 

phase III trial TARGIT-A 

*G . Welzel1 , A . Boch1 , E . Blank1 , U . Kraus-Tiefenbacher1 , A . Keller1 , B . Hermann2 

, M . Sütterlin3 , F . Wenz1 1Universitätsmedizin Mannheim, Universität Heidelberg, Klinik für 

Strahlentherapie und Radioonkologie, Mannheim, Deutschland, 2Klinikum Hanau GmbH, Klinik für Radioonkologie und Strahlentherapie, Hanau, 

Deutschland, 3Universitätsmedizin Mannheim, Universität Heidelberg, Universitäts-Frauenklinik, 

Mannheim, Deutschland 

Purpose. In the multicenter phase III trial TARGIT-A women with early 

breast cancer were randomly treated either with targeted intraoperative 

radiotherapy (IORT, 20 Gy) during breast-conserving surgery or whole 

breast radiotherapy (WBRT, 56 Gy). In presence of risk factors, postoperative 

WBRT (46–50/2 Gy) was added after IORT. Initial results show 

non-inferiority of IORT and WBRT in terms of local recurrence and 

toxicity (Vaidya et al. Lancet 2010; 376: 91–102). Here, we assess radiation-related 

quality of life parameters from 123 women of a single centre 

from the phase III trial TARGIT-A. 

Patients and methods. Radiation-related quality of life was collected 

using two validated questionnaires of the EORTC (QLQ-C30, QLQ- 

BR23). In addition, fatigue, anxiety, depression, self-esteem and body 

image parameters were controlled. The response rate was 72% (n=88). 

Forty-six patients were randomized to IORT. Of them, 16 patients were 

postoperatively treated with additional WBRT, 5 patients did not receive 

IORT due to technical problems: 4 patients were treated with WBRT, 1 

patient refused WBRT. The median age at the time of TARGIT-A entry 

was 65 years (range: 47–84). With a median follow-up time of 25 months 

(range: 9–94), all patients were disease-free at the time of the survey. 

Results. IORT patients reported less pain, breast and arm symptoms and 

better role functioning as compared to WBRT patients (mean ± standard 

deviation: 21.3±33.2 versus 40.9±32.3 points, p=0.007; 7.0±14.0 versus 

19.0±20.0 points, p=0.001; 15.1±22.2 versus 32.8±28.6 points, p=0.009; 

and 78.7±35.2 versus 61.8±28.3 points, p=0.007). IORT + WBRT patients 

reported significantly more pain (mean ± standard deviation: 43.8±32.1 

points), breast (mean ± standard deviation: 29.7±22.8 points) and arm 

symptoms (mean ± standard deviation: 32.6±25.8 points) compared to 

patients with IORT alone (p-values: 0.018 for pain,

0387 

ID4 and WISP-2: potential role as tumorsuppressor in ovarian 

cancer? 

*K . Bräutigam1 , Y .-N . Maché1 , D .O . Bauerschlag1 , I . Meinhold-Heerlein1 , 

N . Maass1 1Uniklinikum Aachen, Klinik für Gynäkologie und Geburtshilfe, Aachen, 

Deutschland 

Objective. Ovarian cancer stands for the most fatal disease among gynecological 

malignancies. Late stage-diagnosis and high recurrence rate 

as reason for poor prognosis stimulate the detection of new prognostic 

marker and the development of targeted therapies. Thus, the aim of this 

study was to characterize the role of ID4 and WISP-2 in ovarian cancer 

by expression analyses in ovarian cancer cell lines, in primary cultured 

cells derived from tumor-tissue and ascites and in tissues of malignant, 

benign and normal origin. 

Methods. To characterize the role of ID4 and WISP-2 oligonucleotide 

and methylation array analyses, qRT-PCR experiments, immunoblotting 

and immunhistochemistry analyses were performed. 

Results. The microarray analyses showed higher expression of ID4 

in low malignant potential (LMP) tumors versus high grade (G2/G3) 

tumors. Expression analyses of mRNA and protein level displayed a 

downregulation of ID4 in malignant tumors compared to normal and 

benign cases. Interestingly, strong ID4 expression could be examined 

in primary culture originated from metastasis or ascites. WISP-2 was 

shown to be hypermethylated while mRNA and protein expression was 

strongly repressed in malignant ovarian cancer compared to normal 

ovarian tissue samples. In benign cases the expression of WISP-2 was 

diverse. 

Conclusion. While ID4 seems to have a dual role in ovarian cancer progression 

and may be used as prognostic marker, the protective effect of 

WISP-2 in ovarian cancer progression may have important therapeutic 

implications. 

0394 

Radical vaginal trachelectomy with laparoscopic pelvic lymphonodectomy 

in a pregnant patient with cervical cancer 

*K . Abel1 , E .-F . Solomayer1 , I . Juhasz-Böss1 1Universitätsklinik Homburg, Frauenklinik, Homburg, Deutschland 

Malignancies occurring during pregnancy are always a challenge both 

from the oncologic and the obstetric point of view. Despite a generally 

declining incidence in western countries cervical cancer is still one of 

the most frequent malignant diseases in pregnant patients. So far different 

therapeutic strategies have been described depending on the stage 

of the disease, gestational age at diagnosis as on whether the patient wishes 

to continue her pregnancy: Postponing surgery after delivery, neoadjuvant 

chemotherapy, fertility-sparing operation during pregnancy 

or determination of pregnancy by radical hysterectomy. 

We report on a 30 years old primigravida who presented with a FIGO 

Ib1 cervical cancer and a tumor size of 25 mm at 11 weeks gestation. 

Radical vaginal trachelectomy combined with laparoscopic pelvic lymphonodectomy 

was performed without any complications. After close 

monitoring during pregnancy a planned caesarean section followed by 

a radical hysterectomy was performed at 35 weeks gestation. After one 

year of follow-up both mother and child are doing well without any evidence 

of recurrent disease. 

0396 

Kisspeptin-10 reduces tumor growth and metastasis in a breast 

cancer model in vivo 

*E . Ziegler1 , G . Emons1 , C . Gründker1 1Universitätsmedizin Göttingen, Frauenklinik, Göttingen, Deutschland 

Kisspeptin-10 (KP-10) belongs to a group of peptides derived from 

KISS1, a gene identified as metastasis suppressor. The antimetastatic effect 

of the kisspeptins was shown in mice having less metastasis after injection 

of melanoma and breast cancer cells transfected with KISS1. Peripherally 

administered kisspeptins also inhibited metastasis in mouse 

models with melanoma and prostate cancer cells. In vitro, kisspeptins 

showed an inhibitory effect on cell migration and invasion in addition. 

The aim of this study was to show the effect of KP-10 on breast cancer 

growth and metastasis in vivo. 

As xenograft CD-1 nude female mice were chosen. Tumor cells of two 

human breast cancer cell lines HCC 1806 and MDA-MB-435 were injected 

orthotopically. Mice were treated daily with KP-10 by intraperitoneal 

injection and tumor growth was measured. Metastasis was quantified 

after the end of the study as amount of human DNA in murine 

organs by real-time PCR. 

An increasing tumor growth could be detected. The treated groups 

bore smaller tumors compared to the untreated groups. Metastasis 

was measured in lung showing a decreased amount of human DNA in 

the groups treated with KP-10. To verify the inhibitory effect on tumor 

growth, KP-10 was tested for antiproliferative capacities in a viability 

assay. No difference between treated and untreated samples could be 

detected in vitro. 

The results in vivo demonstrate an inhibitory effect of KP-10 on breast 

cancer growth and metastasis. An antiproliferative effect of KP-10 could 

not be confirmed in cell culture assays. This may be based on the used 

experimental conditions. Furthermore, reduced proliferation caused 

by kisspeptins is controversially described in literature. The observed 

inhibition of tumor growth may also be mediated by an antiangiogenic 

effect of KP-10. 

According to the decreased amount of metastasis found in the treated 

group of mice, this effect could be caused by the lower tumor growth. 

But on the opposite, KP-10 also showed antiinvasive properties in vitro. 

Thus, KP-10 can be described having antimetastatic properties within 

the treatment of breast cancer in vivo. 


83

Abstracts 

0397 

Treatment of ovarian cancer by combining rapamycin and cytostatic 

drugs under hypoxic conditions 

*K . Bräutigam1 , L . Schacht1 , D .O . Bauerschlag1 , I . Meinhold-Heerlein1 , 

N . Maass1 1Uniklinikum Aachen, Klinik für Gynäkologie und Geburtshilfe, Aachen, 

Deutschland 

Objective. Malignant tumors usually involve a relatively hypoxic state, 

which induces overexpression of hypoxia-inducible factor-1alpha (HIF- 

1alpha) to satisfactorily enable the tumor to survive. And inhibition 

of the mammalian target of rapamycin (mTOR) pathway including 

HIF-1alpha is expected to play a major role in suppression of tumor cell 

growth. Thus the aim of this study was to assess the potential to use 

rapamycin and currently applied anticancer agents in combination in 

ovarian cancer under normoxic and hypoxic conditions. 

Methods. The chemosensitive ovarian cancer cell line HEY was utilized 

to induce resistance against cisplatin, etoposide, doce- and paclitaxel. 

Besides these four chemoresistant subclones and the parental HEY cell 

line, IGROV-1 and SKOV-3, two resistant ovarian cancer cell lines were 

treated with either rapamycin or one of the four cytostatic drugs alone 

and also with the combination of rapamycin with each of the drugs. 

Cell viability and the expression of proteins in apoptotic pathways and 

molecules downstream of the mTOR signaling pathways were assessed 

by chrystal violet assay and immunoblotting. 

Results. Synergistic effects could be observed in all cell lines from the 

combination of rapamycin with either cisplatin or etoposide. Rapamycin 

enhanced induction of apoptosis and inhibition of proliferation by 

influencing the AKT pathway. Comparison of incubation under hypoxic 

or normoxic conditions led to no significant difference. 

Conclusion. The combination of the chemotherapeutic drugs cisplatin 

and etoposide with rapamycin could be worth exploring as a treatment 

modality for epithelial ovarian cancer. 

0403 

Reverse phase protein microarrays for protein profiling in breast 

cancer tumor samples 

*J . Sonntag1 , S . von der Heyde2 , T . Beissbarth2 , S . Wiemann1 , H .-P . Sinn3 , 

A . Schneeweiss4 , U . Korf1 1DKFZ, Division of Molecular Genome Analysis, Heidelberg, Deutschland, 

2University Medical Center Göttingen, Department of Medical Statistics, 

Göttingen, Deutschland, 3University Hospital of Heidelberg, Department of 

Pathology, Heidelberg, Deutschland, 4National Center for Tumor Diseases, 

Department of Gynecology and Obstetrics, Heidelberg, Deutschland 

Introduction. Breast cancer is nowadays recognized as a heterogeneous 

disease. With the knowledge of the histopathological as well as molecular 

heterogeneity in mind and following the hypotheses that intrinsic 

biologic features of breast tumors affect the response to different therapies, 

we want to further elucidate the underlying molecular mechanisms 

on the proteome level using reverse phase protein microarrays 

(RPPA, [1]). 

Method. RPPA allow the quantitative analysis of target protein expression 

and posttranslational modifications in large sample sets. The method, 

in principle, is a miniaturized dot blot immunoassay. Tissue lysates 

of 140 fresh-frozen breast cancer tumor samples (80% ERa positive, 5% 

HER2 positive, 13% triple negative) were spotted with a highly accurate 

contact printer on numerous nitrocellulose coated glass slides. Each replicate 

array of tumor samples was probed with one of over 100 targetspecific 

antibodies. A secondary antibody coupled to a near-infrared 

dye was used for detection of the primary antibody. Data analysis was 

done with the RPPanalyzer [2]. 

Results. As proof of principle, RPPA data for ERa and HER2 were compared 

with the routine classification of the respective targets as obtained 

by immunohistochemical (IHC) staining. RPPA data significantly 


separated the IHC ERa positive from the ERa negative as well as the 

IHC HER2 positive from the HER2 negative group of patients (p

0428 

HPV16-L1-specific antibody rapidtest improves the prognostic 

significance of Cytoactiv® 

G . Mehlhorn1 , *S . Hautmann1 , M .W . Beckmann1 , R . Hilfrich2 1 2 Fraunklinik/Universität, Onkologie, Erlangen, Deutschland, Labor, Cytoimmun 

Diagnostics, Pirmasens, Deutschland 

Background. Immunochemical detection of the HPV-L1 capsid-protein 

with Cytoactiv is used as a prognostic marker to predict remission and 

progression of HPV High risk (HR) associated LSIL/HSIL. In the presence 

of the HPV-L1 capsid-protein an activation of the immune system 

is expected and a spontaneous remission is observed. In a minor proportion 

of cases (20%) the immune system fails to clear the dysplasia, 

and a progression of HPV-L1 capsid-protein positive cells occur. 

Objective. The aims of this study were 1.) to validate the use of an HPV16 

L1-specific antibody rapidtest as a marker for the L1-specific activation 

of the immune system and 2.) to validate if this test could improve the 

prognostic significance of Cytoactiv for HPV HR+ LSIL/HSIL. 

Material and methods. 84 patients showing HPV HR+ LSIL/HSIL were 

recruted for this study. Immunochemical detection of the HPV-L1 capsid-protein 

was carried out with Cytoactiv®. All serum samples were 

tested with an HPV16 L1-specific antibody rapidtest (HPVix-Cytoimmun 

diagnostics). HCII was used to confirm HPV HR positivity. Serum 

samples of 50 Pap-negative, HCII positive women served as control. 

Results and Conclusion. 22 (26%) patients of the study groupe but only 2 

(4%) women of the control groupe showed an HPV16 L1-specific antibody 

response. A combined analysis of Cytoactiv and HPVix showed 

no progression for 11, L1 capsid-protein and L1-antibody, double positive 

women. Seven women showed a progression to CIN3 within the L1 single 

positive or double negative women. The observed 6.5-fold increase of 

the antibody response for women showing an HPV HR+ LSIL/HSIL is 

indicative for an L1-specific activation of the immune response. Since 

no progression was observed for L1 double positive women, the rapidtest 

could be a promissing tool to improve risk assesement of HPV HR+ 

LSIL/HSIL. 

0429 

miRNAs as a prognostic marker/marker for circulating tumour 

cells in metastatic breast cancer 

*D . Madhavan, M . Wallwiener, K . Cuk, C . Modugno, I . Baccelli, M . Zucknick, 

A . Trumpp, S . Riethdorf, P . Sinn, C . Sohn, K . Pantel, A . Schneeweiss, 

B . Burwinkel 

Circulating tumour cells (CTCs) have been shown to be an independent 

prognostic factor in metastatic breast, prostate and colorectal cancer. 

Based on these evidences, the FDA has approved the use of CTCs counted 

by the Veridex Cell Search system, as an index to monitor therapy 

and assess outcome. However, there are few logistical challenges, technical 

difficulties and discrepancies in the detection of CTCs. Therefore, 

an easier and more robust method committed to an equal or even better 

prognostic value is strongly appreciated. We exploited the potential of 

circulating miRNAs in plasma to distinguish CTC positive from CTC 

negative patients. By array based analysis of 667 miRNAs in plasma of 

11 CTC positive and 9 CTC negative patient samples and further verification 

via TaqMan realtime PCR of the identified hits in 60 CTC 

positive and 60 CTC negative samples, we identified a set of miRNAs 

capable of reliably distinguishing CTC positive from CTC negative patients 

as well as from normal control individuals. These data show that 

circulating miRNAs are suitable prognostic marker in metastatic breast 

cancer. 

0434 

Quality of care for premenopausal patients with early-onset 

breast cancer in Germany 

*D . Fischer1 , M . Hedderich1 , A . Heinrichs1 , M . Thill1 , C . Dittmer1 , B . Wedel1 , 

C . Banz1 1Unversitätsklinikum SH, Campus Lübeck, Frauenklinik, Lübeck, Deutschland 

Background and objective. The objective of the study is to evaluate how 

young breast cancer patients are treated adjuvantly and whether treatment 

adheres to the guidelines. The distinction between this cohort and 

a normally distributed cohort was verified. 

Materials and methods. The study evaluates the data from a total of 

1100 patients who were treated adjuvantly in the period from 2006 until 

now and participated in a resident mother-child program. To date, the 

data of 535 patients have been analyzed. The data includes TNM-stage, 

the biology of tumor, therapies and their guideline-adherence. In addition 

the amount of participation in studies was evaluated. All data was 

compared to an age-heterogeneous cohort from the state of Schleswig- 

Holstein and the DMP report of the state of North Rhine-Westphalia. 

Results. Of the patients that have been evaluated so far, 46% were diagnosed 

with stage pT1, 38% pT2, 7% pT3 and 2% pT4. 5% had merely 

DCIS. 49% of the patients were pN0, 31% pN1 and 20% had a more intense 

infestation of lymph nodes. 44% of the tumors showed G3, 34% were 

ER negative, 36% PR negative and 73% HER2 negative. 21% of the examined 

probands showed a triple negative carcinoma. 58% of the patients 

with stage pT1 underwent breast-conserving surgery, 54% with stage T2 

and 25% with stage pT3. Overall 15% of the women received mastectomy 

with subsequent reconstruction. 73% of the patients received axillary 

dissection, 90% received chemotherapy. Overall 21% were treated 

within studies. 61% of the patients with antihormonal therapy received 

GnRH-analoga. An additional analysis of data, the examination with 

regard to the conformity with guidelines and the comparison with a 

normally distributed age group has not been completed yet. 

Conclusion. Young breast cancer patients provide a special challenge for 

the therapists because their prognosis is often worse, frequently the tumor 

has developed to a worse stage, and carcinomas are more aggressive. 

Furthermore we have to view the kind of surgery in this age group in 

a more differentiated way. It remains unclear to what extent guidelines 

adherence improves overall survival and disease free survival. 

0437 

Prognostic value of CA 27.29 trend during adjuvant chemotherapy 

and two years thereafter in patients with primary breast 

cancer 

*J . Neugebauer1 , B . Rack1 , P . Hepp2 , U . Andergassen1 , J . Salmen2 , G . Heinrich3 

, J . Schreier4 , A . Hönig5 , D . Finas6 , T . Zwingers7 , R . Kreienberg8 , 

M .W . Beckmann9 , W . Lichtenegger10 , K . Friese1 , W . Janni2 1Klinikum der LMU München – Innenstadt, Frauenklinik, München, 

Deutschland, 2Universitätsfrauenklinik, Düsseldorf, Deutschland, 3Praxis Dr . Heinrich, Fürstenwalde, Deutschland, 4DRK-Kliniken, Berlin Köpenick, 

Deutschland, 5Universitätsfrauenklinik, Würzburg, Deutschland, 6Frauen klinik, Universität zu Lübeck, Deutschland, 7estimate GmbH, Augsburg, 

Deutschland, 8Universitätsfrauenklinik, Ulm, Deutschland, 9Universitäts frauenklinik, Erlangen, Deutschland, 10Charité, Berlin, Deutschland 

Background. Emerging data show that the use of tumor markers (TM) 

can lead to an early diagnosis of tumor recurrence in breast cancer. TM 

are therefore frequently used in routine clinical patient care. But it is 

still under investigation whether early treatment induction can improve 

the prognosis of breast cancer patients with recurrence of their disease. 

Methods. The SUCCESS Trial compares adjuvant FEC-Docetaxel (Doc) 

vs. FEC-Doc-Gemcitabine (Doc-G) regime and two vs. five year treatment 

with Zoledronate in nodal positive or high risk nodal negative pa- 


85

Abstracts 

tients with primary breast cancer. CA27.29 was measured prior to and 

immediately after chemotherapy (CHT), as well as 2 years thereafter 

with the ST AIA-PACK Ca27.29 reagent using MUC-1 for AIA-600II 

(Tosoh Bioscience, Tessenderlo, Belgium). For this analysis, the change 

of Ca27.29 from pre-chemotherapy baseline to 2 years was evaluated. 

Results. CA27.29 data was available of 3202 patients before and 2015 patients 

2 years after chemotherapy. 20.2% of patients showed increasing 

(≥1 U/ml) CA27.29 levels from before CHT to 2 years thereafter. 59.7% 

of patients had decreasing and 20.1% had stable CA27.29 levels from baseline 

to 2 years. Patients with increasing CA27.29 levels from before 

CHT to 2 years after CHT had a significant worse disease-free survival 

(DFS) (HR 1.016; [95% CI 1.011–1.021] p=5 U/ml had a 81% increased risk 

for recurrence (HR 1.81; [CI: 1.111–2.948]). Between those patients with 

stable and decreasing levels there was no significant difference in terms 

of prognosis. In the multivariate analysis taking into account tumor 

size, nodal status, grading, age, hormonal and Her2/neu receptor status 

increasing CA27.29 levels were an independent prognostic marker with 

respect to poor DFS and OS. 

Conclusion. A small increase of the tumor marker Ca27.29 compared to 

pre-chemotherapy level was associated with a worse prognosis. Therefore, 

individual changes in tumor marker values compared the patient’s 

baseline could lead to a more accurate and clinically relevant interpretation 

of tumor markers. 

0442 

Primary colorectal adenocarcinoma metastatic to the breast: 

case Report and review of the literature 

*J . Radosa1, , R . Mayroya1 , A . Leingartner1 , I . Juhasz-Böss1 , E .-F . Solomayer1 , 

S . Baum1 1Universitätsklinikum des Saarlandes, Frauenklinik, Homburg/Saar, 

Deutschland 

Introduction. Metastases to the breast from extramammarian carcinomas 

are extremely rare and account for 1–6% of all breast malgnancies. 

Mostly gastric and lung carcinomas, lymphoma and malignant melanoma 

are the most freuquently nonmammary metastases. Colorectal 

carcinoma as a metasis in the breast are very uncommon. We presented 

a case of poorly differentiated colon cancer metastatic to the breast. 

Case presentation. A 79-year-old caucasian woman who was diagnosed 

with primary colon adenocarcinoma stage Duke C in 2010 and treated 

with right hemycolectomy and chemotherapy (Folfox 10 cycles). Six 

month after chemotherapy a tumor in the right upper quadrant of the 

breast was discovered incidentally during re-staging. Patients received 

segment resection of the right breast, sentinel node biopsy and intraoperative 

radiation. Postoperative pathology results showed an undifferentiated 

adenocarcinoma which could be identified as a metastasis 

from the primary colorectal carcinoma. 

Conclusion. Colorectal metastases in the breast are extremely seldom 

and there is no general therapy standard. Very important in the management 

of this occurrence is a multidisciplinary approach to provide 

best treatment for the patient. 


0448 

Clinical value of circulating tumour cells (CTC) in metastatic breast 

cancer (MBC) as prognostic and predictive factors 

*M . Wallwiener1,2 , C . Modugno2 , I . Baccelli3 , M . Sprick3 , B . Schoenfisch4 , 

S . Riethdorf5 , S . Schott1,2 , C . Domschke1,2 , C . Pantel5 , F . Marmé1,2 , C . Sohn1 , 

A . Trumpp3 , A . Schneeweiss2 1 2 Universitäts-Frauenklinik, Onkologie, Heidelberg, Deutschland, NCT, 

National Center for Tumor Diseases, Heidelberg, Deutschland, 3HI-STEM, DKFZ, German Cancer Research Center, Heidelberg, Deutschland, 4Universi ty of Tübingen, Department of Obstetrics and Gynaecology, Tübingen, 

Deutschland, 5University Medical Center Hamburg-Eppendorf, Institute of 

Tumour Biology, Hamburg, Deutschland 

Background. CTC (≥5/7.5 ml blood) are prognostic of worse progressionfree 

survival (PFS) and overall survival (OS) in MBC. We aimed to correlate 

CTC kinetics during first cycle of treatment and CTC phenotype 

to response. 

Methods. Patients (pts) with progressive MBC had 7.5 ml blood samples 

taken at baseline and after completing the first cycle of a new line 

of systemic therapy. CTC changes from baseline (BL) to first cycle (C1) 

+ − + + (CTC → CTCC1 / CTCBL → CTCC1 ) were correlated with Radiologi- 

BL 

cal Response Evaluation Criteria in Solid Tumors (RECIST). Changes 

from CTCBL → CTCC1 were grouped as increasing (>25%), decreasing 

(>25%),) or constant (

0451 

Epithelial cell adhesion molecule (EpCAM) is associated with a 

favorable prognosis in epithelial ovarian cancer patients 

*H . Woopen1 , K . Pietzner1 , R . Richter1 , C . Fotopoulou1 , T . Joens1 , E . Braicu1 , 

J . Shetje2 , H . Mellstedt2 , S . Darb-Esfahani3 , C . Denkert3 , J . Sehouli1 1Charité – Universitätsmedizin Berlin, Department of Gynecology, Berlin, 

Deutschland, 2Cancer Center Karolinska, Department of Oncology, Karolinska, 

Schweden, 3Charité – Universitätsmedizin Berlin, Department of 

Pathology, Berlin, Deutschland 

Background. EpCAM, a well known cancer antigene is currently experiencing 

a renaissance in its use as a binding site for targeted oncologic 

therapy and prognostic marker in various epithelial carcinomas such as 

breast cancer or carcinomas of the oral cavity. Goal of this retrospective 

study was to identify EpCAM as a potential prognostic marker for patients 

with primary epithelial ovarian cancer (EOC). 

Methods. EpCAM Expression was assessed in tumor tissue by immunohistochemistry 

using the Avidin-Biotin-Complex method on paraffinembedded 

ovarian cancer tissue samples. EpCAM overexpression was 

defined as an expression of EpCAM as high as 76–100%. Clinical data 

as well as tumor tissue samples were collected within the “Tumorbank 

Ovarian Cancer” network. 

Results. Seventy-four patients with the primary diagnosis of EOC between 

01/1994 and 12/2009 were included in this study. Median age at 

diagnosis was 56 years. The vast majority of the patients (75.4%) presented 

an advanced stage disease (FIGO III/IV). Forty-one (55.4%) patients 

were diagnosed with a serous, 19 (25.6%) a endometrioid and 14 (19%) a 

mucinous histology. EpCAM was overexpressed in 87.7% of the patients. 

Serous tumors expressed EpCAM significantly higher than mucinous 

tumors (p=0.045). There was no significant difference in the expression 

of EpCAM between the other histological subgroups. EpCam overexpression 

correlated in univariate analysis with a significantly better 

overall survival. When classifying EpCAM expression into two groups, 

namely ≤50% and 76–100%, in a Log Rank (Mantel Cox), it was proved 

that EpCAM overexpression of higher than 76% was found to be associated 

with a significantly better survival compared to a lower EpCAM 

expression of ≤50% (p=0.008). 

Discussion. EpCam overexpression in EOC appears to be significantly 

associated with significantly higher overall survival rates. Larger, 

prospective multicenter studies are warranted to further evaluate and 

confirm these novel findings and possibly establish EpCAM as a potent 

therapeutic target in EOC. 

0452 

Breast density and breast cancer characteristics 

*K . Heusinger1 , S .M . Jud1 , C .R . Loehberg1 , C . Hack1 , M . Bani1 , M .P . Lux1 , 

M .G . Schrauder1 , R . Schulz-Wendtland2 , B . Adamietz2 , M . Meier-Meitinger2 , 

M .W . Beckmann1 , P .A . Fasching1 1University Hospital Erlangen, Dept . of OB/Gyn, Erlangen, Deutschland, 

2University Hospital Erlangen, Dept . of Radiology, Erlangen, Deutschland 

Background. Breast cancer risk factors are increasingly linked with breast 

cancer molecular subtypes. For example family history might be linked 

to triple negative breast cancer and hormone replacement therapy 

is supposed to increase the risk for hormone receptor positive breast 

cancer. Aim of our study was to associate mammographic density with 

the tumor characteristics of invasive breast cancers. 

Methods. In a case only design 1974 invasive breast cancers with available 

information about age at diagnosis, BMI and parity on the one 

hand and tumor characteristics like quantitative ER and PR status, were 

analyzed concerning their association with mammographic density. 

Mammographic density was obtained with the MADENA. For the association 

of the continuous variable mammographic density with the 

other factors an unconditional linear regression model was built. 

Results. Mammographic density was strongly associated with age, BMI 

and parity. Concerning tumor characteristics mammographic density 

was negatively correlated with tumor stage and progesterone receptor 

status and negatively correlated with estrogen receptors status. After adjusting 

for the influence of BMI, age and parity, the negative association 

with the estrogen receptor status and the positive association with the 

progesterone receptor status remained statistically significant. 

Conclusions. There seems to be a positive correlation between mammographic 

density and the progesterone receptor status, and a negative 

correlation of the estrogen receptor status of the breast tumor with 

the mammographic density of the breast, implying a possible balanced 

interaction between both sex hormones in the pathogenesis of breast 

tumors. 

0455 

Prognostic relevance of circulating tumor cells in the peripheral 

blood of primary breast cancer patients 

*B . Rack1 , C . Schindlbeck2 , U . Andergassen1 , R . Lorenz1,3 , T . Zwingers1,3,4 , 

A . Schneeweiss1,3,4,5 , W . Lichtenegger1,3,4,5,6 , M .W . Beckmann1,3,4,5,6,7 , H . Sommer1 

, K . Pantel1,8 , K . Friese1,8 , W . Janni1,8,9 1 2 LMU, Gynäkologie, München, Deutschland, Klinikum Traunstein, Traunstein, 

Deutschland, 3Gemeinschaftspraxis Dr . Lorenz/Hecker/Wesche, 

Braunschweig, Deutschland, 4estimate GmbH, Augsburg, Deutschland, 

5 6 Universität Heidelberg, Heidelberg, Deutschland, Charite Universitätsmedizin, 

Berlin, Deutschland, 7Universitätsfrauenklinik, Erlangen, Deutschland, 

8Institut für Tumorbiologie, Hamburg, Deutschland, 9Heinrich-Heine- Universität, Düsseldorf, Deutschland 

Background. Circulating tumor cells (CTC) in blood have been shown 

as predictor of shortened survival in metastatic disease. We evaluated 

whether the presence of CTC before the start of systemic adjuvant treatment 

increases the risk of subsequent relapse and death. 

Patients and methods. The SUCCESS A -Study compares disease-free 

survival in patients treated with 3 cycles of FEC (100/500/100), followed 

by 3 cycles of Docetaxel (100) versus 3 cycles of FEC, followed by 3 cycles 

of Gemcitabine (1000 mg/m2 d1,8)-Docetaxel (75). In 2026 patients 

CTC were analyzed using the CellSearchSystem (Veridex, USA). 23 ml 

of peripheral blood were drawn before the start of adjuvant systemic 

treatment. After immunomagnetic enrichment with an anti-Epcamantibody, 

cells were labelled with anti-Ck8/18/19 and anti-CD45 antibodies. 

Patients were followed for a median of 35 months. Patients with 

evidence of at least 1 CTC were counted as positive. 

Results. In 21.5% of patients (n=435) CTC were detected before the start 

of systemic treatment (median 1.3, range 1–827). Patients with CTC before 

treatment were more frequently node-positive (p

Abstracts 

0459 

Impact of the ratio of positive to resected nodes on prognosis of 

advanced epithelial ovarian cancer 

*C . Bachmann1 , *S . Bachmann1 , E . Grischke1 , E . Solomayer2 , T . Fehm1 , 

D . Wallwiener1 1Universitätsfrauenklinik, Gynäkologie/Geburtshilfe, Tübingen, Deutschland, 

2Universitätsfrauenklinik, Gynäkologie/Geburtshilfe, Homburg/ Saar, 

Deutschland 

Introduction. The objective of this study was to assess the value of metastatic 

lymph node ratio (positive to resected nodes) in predicting 

prognosis of patients with stage IIIc ovarian cancer. 5-year survival 

rate is about 25% for advanced ovarian cancer with worst prognosis in 

FIGO IIIc. The most important prognostic factor is radical surgery without 

residual tumour. Additionally according to the FIGO classification 

IIIc can present abdominal tumour lesions >2 cm and/ or positive 

retroperitoneal or inguinal nodes. Known is the increasing node positivity 

in advanced ovarian cancer; with about 40% of node positivity 

in patients with advanced ovarian cancer. Prognostic impact of node 

status or node ratio in advanced ovarian cancer is still unknown and is 

examined in studies. In other tumor entities a node ratio (e.g. colon cancer) 

already showed a unique significant prognostic value. So far there 

is very little data about node ratio in ovarian cancer. Possibly the node 

ratio is a way to assess the prognosis for initial diagnosis in stage IIIc 

ovarian cancer patients. 

Methods. Therefore, 261 consecutive patients with primary ovarian cancer 

underwent surgery between 2000 and 2007 at the Department of 

Gynecology at the University Hospital, Tübingen, Germany. Every patient 

underwent surgical staging or tumour debulking as clinically indicated 

and adjuvant standard platinum- based chemotherapy. Patients 

with residual tumour mass>2cm or reduced general health got no lymphadenectomy. 

Tumour stage was classified according to FIGO classification. 

Data of all patients with primary advanced ovarian cancer and 

FIGO IIIc were evaluated (133 patients). The ratio of positive to resected 

lymph nodes was stratified into the following groups: 1 (LNR=0); 2 (>0– 

0.5) had similar OS 

(34.7 vs. 32.6 months). No significant impact on PFS was seen with the 

node ration in the three groups. In other tumor entities a node ratio (e.g. 

colon cancer) already showed a unique significant prognostic value. So 

far there is very little data about node ratio in ovarian cancer. 

Conclusion. So far there are very few studies on the importance of the 

node ratio in ovarian cancer. Our results show that node ratio can estimate 

prognosis in FIGO IIIc ovarian cancer for OS, but had no significant 

impact on PFS. Best OS have patients with node ratio >0–

0485 

Variations in VEGF- and TIMP2-expression during therapy seem 

to predict the response to platinum-based chemotherapy in 

patients with primary cervical-cancer (CC) 

*E .I . Braicu1 , C . Fotopoulou1 , R . Chekerov1 , R . Richter1 , J .-U . Blohmer2 , C . Pop1 , 

M . Mentze1 , S . Kümmel3 , W . Lichtenegger1 , J . Sehouli1 1 2 Charité, Virchow Klinikum, Frauenklinik, Berlin, Deutschland, Sankt Gertrauden-Krankenhaus, 

Frauenheilkunde und Geburtshilfe, Berlin, Deutschland, 

3Kliniken Essen Mitte, Brustzentrum, Essen, Deutschland 

Objective. The aim of this study was to analyze the type of variations 

in expression-profile of MMP2, MMP9, TIMP2, and VEGF before and 

after chemotherapy in patients with advanced FIGO stage Ib–IIb CC. 

Therefore we analysed the impact of changes in expression on platinum 

response. 

Methods. Serum from 72 CC patients treated within a phase-III trial 

with either simultaneous radiochemotherapy with cisplatin S-RC or 

systemic paclitaxel and carboplatin followed by percutaneous radiation 

PC-R was analyzed by ELISA. Sera were obtained during surgery and 

after end of the adjuvant treatment. Statistical analysis was performed 

using SPSS and following standard procedures. 

Results. The median age at time of diagnosis was 46 years (range 30– 

71 years). Most of the patients presented a squamous cell- (73.6%) followed 

by adenocarcinomas (25%). 35 (48.6%) patients received surgery 

followed by S-RC and 37 (51.4%) patients were treated with PC-R. Five 

patients developed recurrence within 6 months after end of chemotherapy. 

VEGF levels were increased in platinum non-responders (mean 

difference: 150 pg/ml) and decreased in platinum-responder patients 

(mean difference: −233 pg/ml). This difference reached no statistical significance 

(p=0.144). The TIMP2 expression was not significantly increased 

in platinum-sensitive patients compared to platinum-resistant ones 

(p=0.112). An increase of more than 500 pg/ml VEGF and a decrease 

of more than 9% of the pre-therapeutically value of TIMP2 were significantly 

associated with a higher risk of platinum resistance (RR=8.5, 

95% CI=1.8–39.8 and RR=11.0, 95% CI=2.5–48.2, respectively). 

Conclusions. Our results indicate that VEGF and TIMP2 might predict 

the platinum-response in patients with advanced primary CC. 

0491 

Zoledronic acid has antitumor activity in primary breast cancer 

cells as determined by the ATP tumor chemosensitivity assay 

*T . Fehm1 , H . Seeger1 , M . Zwirner1 , D . Wallwiener1 , H . Neubauer1 1Eberhard-Karls-University Tübingen, Department of Obstetrics and Gynecology, 

Tübingen, Deutschland 

Introduction. The NeoAzure study has demonstrated that the use of the 

bisphosphonate zole-dronate increases the rate of complete response in 

primary breast cancer and therefore indicates direct antitumor activity. 

The aim of this study was to compare the antitumor effect of zolendronic 

acid with standard chemotherapy in primary breast cancer cells 

using ATP-tumor chemosensitivity assay (ATP-TCA). 

Material and methods. Tumor specimens were obtained from patients 

with breast cancer who underwent primary breast cancer surgery at the 

Department of Obstetrics and Gynecology, Tübingen, Germany, between 

2006 through 2009. Antitumor effects of zoledronic acid (Zol), 

TAC (Docetaxel, Adriamycin, Cyclophosphamide) and FEC (5-Fluorouracil, 

Epirubicin, Cyclophosphamide) were tested in 116 fresh human 

primary breast cancer specimens using ATP-TCA. ATP-TCA results 

were analyzed with different cut-off levels for the half maximal inhibitory 

concentration (IC50) and for IC90 or a defined sensitivity index 

(IndexSUM). Each single agent or combination was tested at six doubling 

dilutions from 6.25, 12.5, 25, 50, 100, and 200% of test drug concentrations 

(TDC) derived from the plasma peak concentrations determined 

by pharmacokinetic and clinical information. The assay was carried 

out in duplicate wells with positive and negative controls. 

Results. For Zol the median IndexSUM value was 36.8% and 12.9% lower 

than for FEC and TAC, respectively, indicating increased antitumor 

activity in primary breast cancer cells. The difference between Zol 

and FEC was significant (p

Abstracts 

0496 

Expression of embryonic stem cell factor Sox2 in serous ovarian 

carcinomas 

*T . Fehm1 , D . Pham2 , V . Scheible2 , C . Lengerke3 , S . Perner2 , H . Neubauer1 , 

A . Staebler2 1Eberhard-Karls-University Tübingen, Department of Obstetrics and 

Gynecology, Tübingen, Deutschland, 2Eberhard-Karls-University Tübingen, 

Department of Pathology, Tübingen, Deutschland, 3Eberhard-Karls-Univer sity Tübingen, Department of Internal Medicine, Tübingen, Deutschland 

Background. The transcription factor Sox2 is involved in the maintenance 

of embryonic stem cell pluripotency and is expressed in several 

carcinoma types such as adenocacinoma of the lung and squamous cell 

carcinomas (SCC) of various origins. The gene SOX2 is located at chromosome 

3q26, a region that is a frequently amplified in serous ovarian 

carcinoma. Therefore, the aim of this study was to explore the potential 

role of Sox2 in ovarian carcinogenesis by correlating Sox2 protein expression 

in 167 serous ovarian carcinomas with clinical outcome. 

Methods. 167 consecutive cases of serous ovarian carcinoma were analyzed 

by immunohistochemistry and in a tissue microarray for nuclear 

expression of Sox2. The cut-off level for Sox2 positity was>0% stained 

cells (Lengerke et al. BMC 2010). Correlation with clinicopathological 

factors were determined by chi-squared test. Recurrence-free and overall 

survival was compared by the logrank-test. 

Results. 57% of all 167 serous ovarian carcinomas showed detectable 

Sox2 positive cells. Sox2 expression was associated with grade 3 tumors 

(p

subgroup of patients with B-Raf mutation will likely benefit, and that 

due to the robustness of the healthy cells that have no B-Raf mutation 

side effects might be minimal. We believe that analysing robustness of 

other signalling pathways in a similar way will be the key to devise efficient 

targeted interventions for these, and will unveil which mutations 

in the pathway will break robustness and thereby open the door for efficient 

intervention. 

0034 

Mutual regulation of Bcl-2 proteins independent of the BH3 

domain as shown by the BH3-lacking protein Bcl-xAK 

*M . Plötz1 , A . M . Hossini1 , B . Gillissen2 , P . T . Daniel2 , E . Stockfleth1 , J . Eberle1 1Charité, Department of Dermatology and Allergy, Skin Cancer Center, 

Berlin, Deutschland, 2Charité, Department of Hematology, Oncology and 

Tumor Immunology, Berlin, Deutschland 

Introduction. The BH3 domain of Bcl-2 proteins was regarded as indispensable 

for mutual regulation of pro- and antiapoptotic family 

members as well as for apoptosis induction. We have recently described 

Bcl-xAK, a proapoptotic splice product of the bcl-x gene, which lacks 

BH3 but encloses BH2, BH4 and a transmembrane domain. It remained 

however unclear, how Bcl-xAK may trigger apoptosis. 

Materials and methods. For its efficient overexpression, Bcl-xAK was 

subcloned in an adenoviral vector under Tet-OFF control. 

Results. Strong induction of apoptosis was seen in melanoma and nonmelanoma 

cell lines in a time-dependent manner, reaching up to 50% 

of apoptotic cells at 72 h. Interestingly, Bcl-xAK shared typical characteristics 

with other proapoptotic Bcl-2 proteins, namely mitochondrial 

translocation, disruption of mitochondrial membrane potential and 

cytochrome c release, clearly indicating its regulation of the mitochondrial 

apoptosis pathway. Importantly, Bcl-xAK activity was critically 

dependent on the expression of either Bax or Bak, as shown in genetic 

models, and apoptosis was abrogated in Bax/Bak double knockout cells 

as well by overexpression of antiapoptotic Bcl-2 proteins as Bcl-2 or BclxL. 

A direct interaction with Bcl-2 or Bax was however ruled out by 

immunoprecipitation. 

Conclusion. Bcl-xAK proves the existence of an additional level of mutual 

regulation of Bcl-2 proteins that is independent of the described BH3mediated 

interaction between family members. Therein, mitochondrial 

translocation appears as a critical step, and this type of regulation may 

also play a role for other proapoptotic family members. New pathways 

may be used for overcoming therapy resistance frequently determined 

by Bcl-2 protein of cancer cells. 

0035 

SEC62: A new oncogene bridging the gap from 3q amplification 

to molecular cell biology in non-small cell lung cancer 

*J . Linxweiler1 , M . Linxweiler1 , M . Greiner1 , M . Barth1 , V . Jung2 , R . Grobholz3 , 

Y .-J . Kim4 , R .M . Bohle4 , R . Zimmermann1 1Universität des Saarlandes, medizinische Fakultät, Institut für medizinische 

Biochemie und Molekularbiologie, AG Zimmermann, Homburg/ Saar, 

Deutschland, 2Universitätsklinikum des Saarlandes, Klinik für Urologie 

und Kinderurologie, Homburg/Saar, Deutschland, 3Kantonsspital Aarau, 

Institut für Pathologie, Aarau/Schweiz, Schweiz, 4Universitätsklinikum des 

Saarlandes, Institut für allgemeine und spezielle Pathologie, Homburg/ 


We previously reported a markedly increased Sec62-protein level in 

lung and thyroid cancer tissue samples compared to respective tumor 

free tissue using a multi-tumor-tissue-microarray. Keeping in mind the 

SEC62-gene locus at 3q26.2 and with respect to 3q-amplification having 

repeatedly been reported as the most common genetic alteration in 

non-small cell lung cancer (NSCLC) with emphasis on squamous-cell 

carcinoma (SCC) we wanted to elucidate a possible oncogenic function 

of SEC62 in lung cancer. 

Therefore, we analyzed the SEC62-mRNA and protein level in freshfrozen 

tissue samples from 70 lung cancer patients (35 SCC, 35 adenocarcinoma 

(AC)) by quantitative real time PCR (qPCR), Western Blot 

(WB) as well as immunhistochemistry (IHC) and found a significantly 

increased SEC62-mRNA (p

Abstracts 

0040 

Impact of polymorphisms in genes regulating apoptosis on further 

course of disease in patients with prostate cancer 

*A . Meyer1 , S . Janssen1 , N . Bogdanova1,2 , F . Imkamp3 , C . von Klot3 , J .H . Karstens1 

, J . Serth3 , T . Dörk-Bousset2 1Medizinische Hochschule Hannover, Klinik für Strahlentherapie und 

spezielle Onkologie, Hannover, Deutschland, 2Medizinische Hochschule 

Hannover, Klinik für Frauenheilkunde und Geburtshilfe, Hannover, 

Deutschland, 3Medizinische Hochschule Hannover, Klinik für Urologie und 

Urologische Onkologie, Hannover, Deutschland 

Purpose. Ionising irradiation leads to changes of the DNA with activation 

of cellular mechanisms responsible for the detection and repair of 

DNA double strand breaks or induction of apoptosis. Aim of this evaluation 

is the possible impact of polymorphisms in genes responsible for 

apoptosis on further course of disease in patients with low-risk prostate 

cancer for individualization of the therapy. 

Methods. 139 patients with low-risk prostate cancer treated with LDR 

brachytherapy between 11/2000 and 10/2004 at Hannover Medical 

School were included. The minimum follow-up was >12 months in all 

these patients. After extraction of the genomic DNA a screening for 

certain polymorphisms in 10 candidate genes with a key function in 

apoptosis was carried out: ATM (Ser49Cys), BID (Ser56Cys), CASP8 

(Asp302His), CASP10 (Val410Ile), LGALS3 (Pro64His), RASSF1 

(Ser133Ala), TP53 (Arg72Pro), TP53AIP1 (Ala7Val), BCL2 (-938C/A) and 

HDM2 (SNP309). 

Results. The median age of the patients at the implantation was 66.8 years, 

the mean Gleason score was 6, the mean PSA level before implantation 

was 7.2 ng/dl, the mean follow-up was 62,4 months. The overall 

survival after 2 and 5 years was 100% and 99%, the biochemical disease-free 

survival according to the ASTRO definition 90% and 84% and 

according to the Phoenix definition 97% and 91%. After correlation with 

the underlying polymorphisms only for BID (Ser56Cys) a statistical significant 

impact for biochemical disease-free survival according to the 

ASTRO definition could be detected (p=0.010). A biochemical recurrence 

could be seen in 2 of 4 carrier (50%) vs. 20 of 135 non-carrier (15%) 

though the small number of events and carrier has to be considered. 

Conclusions. In our analysis no clear correlation between polymorphisms 

in genes regulating the apoptosis and further course of disease 

could be detected that could lead to an individualization of the therapeutic 

options. 

0042 

Heat-shock protein 27 (HSP27) levels define the efficacy of HSP90 

inhibitors in cancer therapy 

H . Nagata1 , T .Y . Tsui1 , *O . Stöltzing2,1 1Universitätsklinikum Hamburg-Eppendorf, Hepatobiliäre Chirurgie, Hamburg, 

Deutschland, 2HELIOS Klinikum Berlin-Buch, Allgemein-, Viszeralund 

Onkologische Chirurgie, Berlin, Deutschland 

Heat-shock protein 90 (Hsp90) inhibitors have gained great interest for 

therapy of gastrointestinal cancers. Although Hsp90 inhibitors harbor 

the potential to impair multiple oncogenic signaling pathways in cancer 

cells, they also lead to induction of certain transcription factors and 

heat-shock proteins, such as Hsp27. Initially we sought to improve the 

anti-neoplastic efficacy of mTOR inhibitors in therapy of cholangiocarcinomas 

by combining them with Hsp90 antagonists in order to overcome 

the mTOR-inhibitor induced oncogenic Akt/Erk feed-back loop 

activation. However, we observed that dual-targeting mTOR/Hsp90 

displayed variable efficacy on cancer cells, which was paralleled by differences 

in an Hsp90-inhibitor-mediated Hsp27 induction. We therefore 

hypothesized that Hsp27 levels may modulate the efficacy of Hsp90 

inhibitors. 

Human cholangiocarcinoma and colon cancer cell lines were used for 

experiments. Hsp27 expression levels were additionally investigated on 


human colon cancer liver metastases. The results showed that low Hsp27 

expressing cancer cells were substantially less sensitive to Hsp90 inhibitors 

(17DMAG), as determined in proliferation assays and by Western 

blotting. Knock-down of Hsp27 (shRNA) in high-Hsp27-expressing 

cancer cells significantly reduced their response to Hsp90 inhibition 

(p

0064 

Fatty acid synthase (FAS-272) expression increases with rise of 

WHO-grade of human gliomas and can be blocked by specific 

inhibitors 

*P . Dünisch1 , J . Walter1 , S . Grube1 , R . Kalff1 , A . Waschke1 , R . Bauer2 , C . Ewald1 1 2 Universitätsklinikum Jena, Neurochirurgie, Jena, Deutschland, Friedrich- 

Schiller-Universität, Molekulare Zellbiologie, Jena, Deutschland 

Purpose. Fatty acid synthase is a multifunctional polypeptid which 

plays an essential role in cell metabolism. High expression levels of fatty 

acid synthase (FAS) have been reported in hormone receptor-positive 

tumors. In our current study we investigate the expression of FAS in 

gliomas of different WHO-Grades as a possible new target for anti tumor 

therapy. 

Material and methods. First 80 tumor samples of human brain tumors, 

were immunohistochemically evaluated via densitometric analysis. 

The FAS-mRNA concentration in fresh glioma tissue, removed during 

surgery, was analysed using Real-time PCR. We measured the effect 

of known FAS Inhibitors like Cerulenin, Orlistat, and C75 on glioma 

cell viability, cell proliferation and cell migration in the glioma cell line 

A-172 with the MTT assay and the xCELLigenceTM System. Cell apoptosis 

was visualizes via a nuclear fragmentation assay with the fluorescence 

dye Hoechst 33258 (Invitrogen). 

Results. Densitometric measurement revealed a significant increase of 

FAS expression in high grade gliomas. The incubation of the glioma cell 

line A172 with the FAS inhibitors Cerulenin, C75 and Orlistat leads to 

a time and dose dependent proliferations stop and induced cell death. 

This apoptotic cell death was confirmed by the nuclear fragmentation 

assay and Western blotting. 

Conclusion. With our study we could underline the essential role of 

FAS in the biology of human gliomas on protein and mRNA level. And 

our findings suggest that FAS might be a possible target for antiglioma 

therapy. Further studys in animal models are nessecary to confirm our 

findings in vivo. 

0081 

New molecular and imaging tools to detect and follow up extraadrenal 

phaeochromocytoma 

*D . Barski1 , V . Müller-Mattheis1 , S . Ezziddin2 , S . Heikaus3 , H . Neumann4 , 

P . Albers1 1 2 Universitätsklinik Düsseldorf, Urologie, Düsseldorf, Deutschland, Universität, 

Nuklearmedizin, Bonn, Deutschland, 3Universitätsklinik Düsseldorf, 

Pathologie, Düsseldorf, Deutschland, 4Universität, Nephrologie, Freiburg, 

Deutschland 

Background. The prevalence of phaeochromocytoma in patients with 

hypertonia is 0.1–0.6% and about 15% of phaeochromocytoma are detected 

in extraadrenal tissue. The diagnosis and therapy of this rare disease 

detected as a retroperitoneal tumor mass can be difficult for clinicians. 

Objective. The publication aims to highlight the importance of standardised 

management and new genetic tools for the outcome and prognosis. 

Evidence acquisition. A literature review of the recent peer-reviewed 

articles was performed. Additionally we report on a 50-yr-old man presenting 

in our clinic with unclear retroperitoneal tumor mass, detected 

as extraadrenal phaeochromocytoma with SDHB mutation. 

Evidence synthesis. MRI is a first choice imaging for phaeochromocytoma, 

showing a hyperintense mass in T2-phase. Alternatively a CT 

scan can be done with nearly the same sensitivity (90–100%). For the 

validation of the diagnosis or follow up the functional imaging with 

radioactive tracers as 131I, 123I-metaiodobenzylguanidine (MIBG) or 

Fluorine-18-L-dihydroxyphenylalanine (18F-DOPA) positron emission 

tomography (excellent specificity and sensitivity of 90–100% in detection 

of small tumors >1–2cm) are used. Laparoscopic surgery with 

complete resection is safe and a first choice approach. The conversion 

(about 5%) or direct open operation was needed for large lesions (>8 cm) 

with the suspicion of malignancy. Currently there are no histological 

criteria for distinguishing benign and malignant tumors. The genetic 

testing (PCR, DNA sequencing) for hereditary syndromes (MEN, von 

Hippel-Lindau, neurofibromatosis, etc.) is a new crucial tool for prediction 

of malignancy and recurrence. All patients should get genetic 

analysis and consultation including family members. First, the rate of 

malignancy in phaeochromocytoma is about 5% but the prevalence of 

malignant disease is about 33% for extraadrenal phaeochromocytomas 

and even higher in patients with specific familial mutations (e.g. SDHB, 

NF1, VHL, MEN2). In patients with proven germline mutations, multiple 

phaeochromocytomas and recurrences are likely. A stringent lifelong 

clinical follow-up is recommended in these cases. Second, the patients 

with syndromic hereditary forms should be screened for the often associated 

other neoplasms. 

Conclusion. Genetic analysis provides an important and good tool for 

the prognosis of phaechromocytoma. 

0105 

The influence of combined treatment with 13-cis retinoic acid 

and Thalidomide on the growth of U251 glioblastoma xenografts 

*D . Milanovic1 , A .L . Grosu1 , G . Niedermann1 1Universitätsklinikum Freiburg, Strahlenheilkunde, Freiburg, Deutschland 

Objective. 13-cis retinoic acid (RA) and Thalidomide (THAL) show 

some clinical effects in Glioblastoma (GBM) patients as sole agents or 

in combination with other chemotherapeuticals. RA is a differentiation 

agent acting on cell cycle regulation and on EGFR-mediated growth 

stimulation. However, RA may induce expression of homeobox (HOX) 

genes, i.e., of developmental regulators during embryogenesis that are 

normally inactive in adults but may become active during carcinogenesis. 

RA-induced HOXB7 may in turn induce bFGF, which is a potent 

angiogenic and mitogenic factor, and this might limit the usefulness of 

RA in the treatment of GBM. THAL has immunomodulatory and antiangiogenic 

effects and can downregulate bFGF. In our previous work 

we showed that in vitro THAL inhibits RA stimulation of homeobox B7 

gene expression in human GBM cells. The purpose of the present study 

was to test the influence of RA and THAL, as sole agents and in combination, 

on the growth of U251 glioblastoma xenografts. 

Materials and methods. 1.5×106 U251 cells were inoculated s.c. into the 

right hind limb of NMRI-Foxn1nu athymic female nude mice. Animals 

were randomly assigned in 4 groups (7–11 animals/group) for treatment: 

control, RA, THAL and RA + THAL. The animals were treated daily 

(Monday-Friday) via intragastric tube with RA (30 mg/kg), THAL 

(30 mg/kg), or RA (30 mg/kg) plus THAL (30 mg/kg). Xenografts from 

sacrifed animals were used for hematoxylin and eosin staining. 

Results. The treatment was tolerated excellently; no side effects were observed. 

RA and THAL as sole agents did not affect the tumor growth in 

comparison to untreated controls. However, combined treatment caused 

a significant decrease in tumor volume. The final tumor volumes 

were: control = 1.37±0.2 cm3, RA = 1.38±0.23 cm3, THAL = 1.43±0.5 cm3, 

RA + THAL =0.69±0.075 cm3. Hematoxylin and eosin staining of xenografts 

showed marked hypocellularity in the case of combined treatment. 

Conclusions. Additive growth inhibition by RA and THAL can be achieved 

in U251 glioblastoma xenografts. These results support our prevoious 

findings from in vitro experiments. Because RA and THAL are well 

tolerated in patients, these data encourage further clinical studies on 

combinations of these compounds. Molecular-biological analysis of xenografts 

is underway and will be presented at the meeting. 


93

Abstracts 

0136 

The membrane transport protein Na+K+ATPase and intracellular 

ATP are involved in the selective inhibition of tumor stem cells by 

salinomycin 

*H . Bühler1 , A . Kochanneck1 , B . Priesch1 , K . Polz2 , R . Galalae2 , I . Adamietz2 1Marienhospital, Klinikum der Ruhr-Universität Bochum, Institut für Molekulare 

Onkologie, Strahlenbiologie und Experimentelle Strahlentherapie, 

Herne, Deutschland, 2Marienhospital, Klinikum der Ruhr-Universität, Klinik 

für Strahlentherapie und Radio-Onkologie, Herne, Deutschland 

Background. In 2009 Gupta et al. did show that some ionophores for 

monovalent kations could inhibit cancer stem cells (CSCs) at significantly 

lower doses than epithelial cancer cells, however the mechanism 

remained unclear. The antibiotic salinomycin was identified as the 

most effective substance. We checked this compound as to its inhibitory 

potency in CSCs isolated from a breast cancer cell line and tried to 

clarify the underlying mechanism. An obvious candidate is the membrane 

transporter Na+K+ATPase since this enzyme is responsible for 

the maintenance of the important Na+/K+ gradient over the cellular 

membrane. 

Methods. CSCs were isolated from MDA-MB 231 breast cancer cells via 

spheroids. An epithelial counterpart was obtained by transfection of keratin 

18 into MDA 231 wt cells. Salinomycin was added in concentrations 

from 10−7 to 5×10−5 M. Cellular viability with and without inhibitor 

was measured by a MTS-test. In addition, Na+K+ATPase was partially 

inhibited by 2.5×10−8 M hellebrin. Intracellular ATP was measured by 

chemiluminescence. Na+K+ATPase was quantified by qRT-PCR. 

Results. In our model system we could show a selective reduction of 

tumor stem cells viability in response to salinomycin, comparable to 

the published data. The isolated stem cell fraction was compromised 

at significantly lower doses than the epithelial subclone (IC50 10−6 vs. 

2×10−5 M). First approaches revealed that the Na+K+ATPase might play 

a role in this selective effect: the dose dependent inhibition of stem cells 

by salinomycin was approximated in epithelial cells, if additionally the 

Na+K+ATPase inhibitor hellebrin was added in low doses. However, 

qRT-PCR did not reveal any difference in the expression of the enzyme 

on the transcriptional level but a significantly lower content of free ATP 

was observed in stem cells. 

Conclusion. The selective inhibition of cancer stem cells by salinomycin 

might be caused by a disturbed Na+/K+ gradient originating more 

likely from energy deficiency than from a less active Na+K+ATPase in 

these cells. 

0143 

Radiotherapy combined with immune therapeutic approaches is 

capable to induce immunogenic tumor cells leading to anti-tumor 

immunity 

B . Frey1 , Y . Rubner1 , E .-M . Weiss1 , R . Fietkau1 , *U . Gaipl1 1Strahlenklinik Erlangen, Strahlen-Immunbiologie, Erlangen, Deutschland 

Combination of classical tumor therapies like radiotherapy with immune 

therapy has been considered, for a long time, to be counterproductive. 

Nowadays it is well accepted that specific immune responses contribute 

to the eradication of smaller tumor masses, recurrent tumors and metastases. 

To find the optimal combination and chronological sequence of 

radiotherapy, chemotherapy and immune therapy will be a great future 

challenge of scientists and clinicians. We present how tumor cells can 

be rendered immunogenic by ionising radiation (X-ray) alone and most 

importantly by combination with further immune stimuli like quality 

controlled hyperthermia (41.5°C for 1 h) or the naturally occurring 

adjuvant AnnexinA5. The latter is a ligand for phosphatidylserine that 

gets exposed on tumor cells after irradiation. X-ray plus heat led to the 

release of the immune activating danger signals high-mobility group 

box 1 protein (HMGB1) and heat shock protein 70 by tumor cells and 

subsequent activation of dendritic cells (DC). In addition, AnnexinA5 


shifted the uptake of tumor cells from macrophages to DC. The latter 

are key players in starting a tumor specific adaptive immune response. 

In vivo syngeneic mice experiments with radiation procedures closely 

resembling the human situation give first hints that AnnexinA5 further 

retards tumor growth when combined with X-ray. We conclude that radiotherapy 

alone or especially in combination with additional immune 

activatory stimuli like heat or AnnexinA5 is capable to induce an immune 

activatory tumour microenvironment that triggers anti-tumour 

immunity via activation of DC. 

This work is supported by the German Research Foundation (GA 1507/1-1 and 

GK1660) and by the Bundesministerium fuer Bildung und Forschung (BMBF; 

01EX1021R) . 

0148 

Hyperthermia induces increased Estrogen Sulfotransferase 

SULT1E1 gene expression in vitro 

*M . Jäger1 , M . Hirschfeld1 , G . Gitsch1 , E . Stickeler1 1Universitäts-Frauenklinik, Molekulare Onkologie, Freiburg, Deutschland 

Background and aims. The clinical application of hyperthermal therapy 

is gaining more importance, by its beneficial co-application in combination 

with chemotherapy or radiotherapy in malignant disease management. 

This approach might improve the therapeutical effect of these 

classical anti-cancer treatment strategies in certain circumstances. The 

SULT1E1 is a member of the Sulfotransferase family. Sulfotransferases 

are responsible for the sulfate conjugation of various hormones, drugs 

and xenobiotics. SULT1E1 is capable to inactivate estrogen by adding a 

sulfate group to the estrogen molecule. 

Methods. We investigated the potential regulatory effects of hyperthermia 

on the expression of SULT1E1. Several gynecological and breast 

cancer cell lines were cultured under hyperthermia (42°C, 2 h) followed 

by maintenance under regular culture conditions (37°C, 4 h). As a negative 

control, these cell lines were also permanently cultivated under 

regular temperature conditions. Transcript and protein expression levels 

of SULT1E1 were investigated by RT-PCR and Western Blot, respectively. 

Results. The analyses revealed an increase in mRNA and protein level 

of SULT1E1 under hyperthermia. Our results demonstrate a regulatory 

effect of hyperthermal treatment on the Estrogen Sulfotransferase 

SULT1E1 

Conclusion. We therefore hypothesize that hyperthermia can induce the 

expression of SULT1E1, thereby creating suppressive effects on tumorigenesis. 

The regulatory effect of hyperthermia on Estrogen receptor 

expression was described by our group previously. Our findings support 

the theory that hyperthermal treatment might represent a method that 

may improve classical anti-cancer therapies by a direct influence on the 

regulation of gene expression of important factors in cancer biology. 

0165 

Differential regulation of p53 isoforms in clear cell renal cell 

carcinomas 

*S . Heikaus1 , L . van den Berg1 , H .E . Gabbert1 , C . Mahotka1 1Universitätsklinikum Düsseldorf, Institut für Pathologie, Düsseldorf, 

Deutschland 

Aims. Renal cell carcinomas (RCCs) exhibit a marked resistance towards 

conventional chemotherapy, which is – at least in part – due to 

functional suppression of p53. In contrast to many other tumours, however, 

this p53 suppression in RCCs is mediated by mechanisms other 

than inactivating mutations. One of these mechanisms might be differential 

expression of p53 isoforms, which can influence the transcriptional 

activity of p53. Therefore, the aim of our study was to elucidate 

the relevance of differential p53 isoform expression for carcinogenesis, 

progression and therapy-resistance of RCCs.

Methods. Semiquantitative “Realtime PCR”, Western Blot and Caspaseassays. 

Results. RCCs revealed a shift towards a more p53 activating isoform expression 

pattern during tumour initiation and progression, in vivo. In 

vitro, two cell lines exhibiting a similar sensitivity towards Topotecaninduced 

cell death revealed a similar induction of p53 target genes by 

Topotecan but differed in the extend of Topotecan-induced apoptosis. 

Furthermore, they strongly differed in their basal expression patterns of 

the p53 isoforms as well as in the differential regulation of p53 isoform 

expression upon Topotecan-treatment. 

Conclusions. p53 isoforms are strongly differentially regulated by chemotherapy 

in RCCs. However, p53 isoform expression and regulation 

seems to be neither responsible for induction and progression of RCCs 

in vivo, nor for regulation of p53 gene expression, sensitivity towards 

chemotherapy and induction of apoptosis in vitro. 

0167 

Investigation of the postulated EGFR-pAkt- HIF1 alpha-survivin 

pathway in tumor cell lines and the role of HIF1 alpha under 

normoxic conditions 

*M . Kappler1 , S . Rot2 , H . Taubert3 , M . Bache2 , D . Vordermark4 , J . Schubert5 , 

A .W . Eckert5 1Universitätsklinik und Poliklinik für Mund-, Kiefer- und Plastische Gesichtschirurgie, 

Molekulare Tumorbiologie, Halle(S), Deutschland, 2Universitäts klinik und Poliklinik für Strahlentherapie, Molekulare Strahlenbiologie, 

Halle(S), Deutschland, 3Universitätsklinik und Poliklinik für Urologie, 

Nikolaus-Fiebiger-Zentrum für Molekulare Biologie, Erlangen, Deutschland, 

4Universitätsklinik und Poliklinik für Strahlentherapie, Halle(S), Deutschland, 

5Universitätsklinik und Poliklinik für Mund-, Kiefer- und Plastische 

Gesichtschirurgie, Halle(S), Deutschland 

Background. The tumorbiological importances of tyrosine kinases receptors 

(e.g., insulin and EGF receptor) for proliferation, apoptosis and 

metabolism of tumor cells have already been shown. Both receptors 

(insulin receptor and EGFR) activate the tumor-relevant PI3K/AKT 

pathway. Recently, an EGFR- pAkt- HIF1α-survivin pathway was described, 

which activates the prognostic relevant inhibitor of apoptosis 

protein survivin in breast cancer cell lines under normoxic conditions 

(Peng et al. 2006). 

Methods. Accordingly to the study published by Peng et al. we treated 

two breast cancer cell lines (MDA-MB-231, MCF-7) with 100 ng/ml EGF, 

0.65 µg /ml insulin or with 50 nM of a PI3-K-Inhibitor Ly294006 under 

serum free conditions. The protein expression of pAkt, survivin and 

HIF1α was analyzed by western blot analysis. Furthermore, a cell cycle 

analysis was performed. 

Results. In accordance to the results of Peng et al, the cell line MCF-7 

showed an increase in survivin expression using EGF/insulin-stimulation 

in vitro. However, that pathway is detectable only under none 

physiological conditions (without serum). The cell cycle analysis demonstrated 

a G1-cell cycle arrest caused by serum deprivation, which 

is associated with a low protein expression of the IAP survivin. Insulin 

or EGF application induced an increase of G2/M-cell cycle cells and an 

increase of the expression of the G2/M marker protein survivin. In opposite 

to the MCF-7 cell line in the cell line MDA-MB231 the G1-cell 

cycle arrest caused by the serum deprivation is not influenced by EGF/ 

insulin-stimulation. The IAP survivin is slightly induced by insulin 

application. Moreover, the HIF1α expression is not directly induced by 

signal transduction caused by an insulin or EGF induction, but by metabolic 

processes under normoxia. 

Conclusion. We found that the postulated EGFR- pAkt- HIF1 alpha-survivin 

pathway is unverifiable in the same cell lines used by Peng et al. 

We propose that the postulated activation of the protein survivin by 

EGF or insulin application is caused by a simple change in the distribution 

of cells in different cell cycle phases. Moreover, and in accordance 

to our results, the cell line MDA-MB231 was described by other aut- 

hor as insensible to an EGF-like stimulus (Takabatake et al. 2007). The 

accumulation of HIF1 alpha under normoxia seems to be induced by 

metabolic processes. We assume that the pathway postulated by Peng et 

al. is an artificial pathway. 

0172 

Decreased cell proliferation and induced apoptosis in CTCL cells 

lines by non-steroidal anti-inflammatory drugs (NSAIDs) 

*F . Braun1 , M . Plötz1 , N . Al-Yacoub1 , M . Möbs1 , W . Sterry1 , J . Eberle1 1Charité – Universitätsmedizin Berlin, Klinik für Dermatologie, Venerologie 

und Allergologie, Berlin, Deutschland 

Cutaneous T cell lymphomas (CTCL) form a heterogeneous group of 

non-Hodgkin lymphomas with primary involvement of the skin. Even 

though early stages of CTCL are often indolent over long periods of 

time, advanced stages are refractory and difficult to treat. Death ligands 

(CD95L and TRAIL) critically contribute to lymphocyte homeostasis 

due to induction of apoptosis and may further represent safeguard mechanisms 

to prevent lymphoma development. In previous studies, we 

characterized CTCL cell lines as resistant to TRAIL-mediated apoptosis 

which was correlated to high c-FLIP expression. In the present study, 

we investigated the effects of non-steroidal anti-inflammatory drugs 

(NSAIDs) as acetylsalicylic acid, sodium salicylate and diclofenac in 

CTCL cell lines (HH and MyLa) as well as in tumor T cells from SzS patients. 

NSAIDs decreased cell proliferation and induced apoptosis, associated 

by caspase-3 processing. Decreased mitochondrial membrane 

potential and cytochrome c release were indicative for an involvement 

of intrinsic pathways. Furthermore, downregulation of c-FLIP and caspase-8 

processing clearly indicated an activation of extrinsic pathways. 

Finally, NSAIDs sensitized CTCL cells for TRAIL-induced apoptosis. 

In conclusion, the study provides a rational for the use of NSAIDs as 

a potentially new therapeutic option for cutaneous T cell lymphomas. 

0197 

Conditional RNAi-mediated knockdown of osteopontin in 

MDA-MB-231 breast cancer subclones in vitro 

*M . Kovacheva1 , S . Berger2 , M . Berger1 1DKFZ, Toxikologie and Chemotherapie, Heidelberg, Deutschland, 

2Zentralinstitut für Seelische Gesundheit, Molekularbiologie, Mannheim, 

Deutschland 

Breast cancer is the second most common cause of cancer-related death 

in women. This is due to metastasis which renders breast cancer virtually 

incurable. In breast cancer progression, high levels of osteopontin 

(OPN) correlate with poor prognosis. As a member of the SIBLING 

(small integrin-binding ligand N-linked glycoprotein) family of glycoproteins, 

OPN has a pivotal role in the processes of migration and 

invasion, which are essential for metastasis formation. 

The combination of RNA interference (RNAi) with the tetracyclinecontrolled 

transcription activation (tet) system is a powerful method 

for conditional gene inactivation in cultured cells. Here, we aimed to 

investigate, whether the conditional RNAi-mediated knockdown of 

OPN would impair the metastatic properties of invasive breast cancer 

cells. Therefore, two MDA-MB-231 subclones (OPN clones 1 and 2) were 

generated, in which the tetracycline-dependent transactivator tTA controls 

the simultaneous expression of the red fluorescent protein mCherry, 

firefly luciferase and a highly efficient and specific miRNA targeting 

OPN mRNA. 

Knockdown efficiency was determined by quantifying OPN mRNA 

and protein concentrations after cultivating respective cell clones for 

either 3 or 6 days with or without doxycycline in the medium. Here, 

OPN mRNA concentration was reduced by 62–96% after 3 days and 

85–98% after 6 days respectively. However, a decrease in OPN protein 

was only observed after 6 days. The decrease in OPN expression led to 


95

Abstracts 

a reduction in colony formation by 55–60 % and to a similar inhibition 

of spontaneous migration, determined 9 days after initiation of OPN 

miRNA expression. However, there was no significant influence on proliferation 

as assessed by MTT assay after cultivating the respective cell 

clones for 3 and 6 days in the same media. 

In conclusion, the conditional knockdown of OPN in breast cancer subclones 

resulted in a distinct reduction of OPN mRNA and protein concentrations. 

This effect was associated with significantly reduced migration 

and colony formation, but there was no effect on cell proliferation. 

0202 

TPX2 as potential target in breast cancer treatment 

*C . Wilde1 , S . Berger2 , M . Berger1 1 2 DKFZ, Chemotherapie und Toxikologie, Heidelberg, Deutschland, ZI- 

Mannheim, Mannheim, Deutschland 

The microtubule-associated protein TPX2, a key component in mitotic 

cell division and cell cycle progression, is discussed as a potential 

therapeutic target in different types of human cancer. Several studies 

implicated that there is a TPX2 over-expression in tumor cells, which 

is considered to be important for the maintenance of the tumorigenic 

state. Our intention was to evaluate the expression and role of TPX2 as 

a target for new anti-mitotic therapies in breast cancer. 

TPX2 expression was compared in cell lines including the non-tumorigenic 

cell line MCF-10A and in various breast cancer cell lines as well 

as in primary patient samples. The expression was determined at the 

protein (Western Blot) and mRNA (real-time PCT) levels. There was 

only a marginal TPX2 expression in MCF-10A cells, whereas the various 

breast cancer cell lines showed a significant up-regulation of TPX2 expression 

both at RNA and protein levels. In contrast, Western blot and 

real-time PCR analysis from fresh frozen tissue samples of breast cancer 

patients showed low TPX2 levels. 

To investigate the functional role of TPX2 in breast cancer cells, two 

MDA-MB-231 cell lines with a conditional TPX-knockdown were generated. 

In these cell lines TPX2 production can be inhibited by a TPX2specific 

miRNA under the transcriptional control of the TetOff system. 

The efficiency of the knockdown was also determined by real-time PCR 

and Western Blot. 

In the absence of doxycycline an almost complete knockdown could be 

seen both at RNA and protein levels. TPX2 expression was suppressed 

up to 97% in MDA-MB-231-TPX-54-1.1 and up to 99% in MDA-MB-231- 

TPX-23-25. This effective inhibition of TPX2 production led to an increased 

number of apoptotic cells as identified by life cell imaging. In 

addition, MTT assay showed a significantly reduced cell proliferation of 

34% (MDA-MB-231-TPX-54-1.1) and 19% (MDA-MB-231-TPX-23-25) at 

three days after induction of the knockdown. 

In conclusion TPX2 knockdown causes apoptosis and has an anti-proliferative 

effect. TPX2 expression was more pronounced in breast cancer 

cell lines than in primary tissues from breast cancer patients. The value 

of TPX2 as potential target for breast cancer treatment needs further 

consideration. 

0204 

Estrogen receptor β agonists reduce invasiveness of triple-negative 

human breast cancer cell lines 

*C . Lattrich1 , J . Häring1 , R . Meier1 , S . Schüler1 , A . Stegerer1 , O . Treeck1 , O . Ortmann1 

1University Medical Center Regensburg, Department of Obstetrics and 

Gynecology, Regensburg, Deutschland 

Objective. Estrogen receptor β (ERβ) is expressed in the majority of triple-negative 

breast cancer cases. In this study, we tested to what extent 

treatment of triple-negative breast cancer cell lines with two highly specific 

ERβ agonists would affect their invasiveness and motility. 


Methods. Cellular invasion was assessed by means of a modified Boyden 

chamber with a membrane pore size of 8 µm coated with a soluble basement 

membrane extract. Migration was measured using the same model 

system without ECM. Relative cell numbers were assessed by means 

of the fluorimetric Cell Titer Blue Assay (Promega). Gene expression 

was examined by RT-qPCR using a Light Cycler 2.0 device (Roche) and 

by Western Blot analysis. 

Results. Selective ERβ agonist ERB-041 significantly reduced invasiveness 

of the triple negative breast cancer cell lines MDA-MB-231 and 

HS578T in vitro in a dose-dependent manner. ERB-041 inhibited invasion 

of MDA-MB-231 cells down to 70.7% (p

iment demonstrated that overexpression of Sox9 gene supports tumor 

growth and metastasing. 

Conclusions. Proangiogenic genes such as VEGF are upregulated in 

the more aggressive cell line L3.6pl, compared to FG. We identified a 

gene cluster that is constitutively upregulated in L3.6pl, independent 

of hypoxia. These genes are controlled by the transcription factor Sox9 

physically binding on their promoters. A Sox9 promoter differential 

methylation may be the reason for the escape from hypoxic regulation 

in L3.6pl cells and thus may contribute to the higher angiogenic and 

metastatic potential. 

0231 

Cancer initiating cells in colon and pancreatic cancer are resistant 

to nutrient stress – a characteristic for tumor growth? 

*T . Grimmig1 , J . Schmitt1 , N . Matthes1 , M . Faber1 , C .-T . Germer2 , M . Gasser2 , 

A .M . Waaga-Gasser1 1Universitätsklinikum Würzburg, Chirurgische Klinik I, Molekulare Onkoimmunologie, 



Background. Recent findings suggest that conditions of ischemia and 

low nutrient tumor microenvironment stimulate tumor growth and 

involve survival advantage of pluripotent and resistant tumor cells. The 

aim of this study was to determine the presence of different Toll-like 

receptors (TLR), heat shock proteins (Hsp), and markers for putative 

tumor initiating cells (CD133 and multidrug resistance proteins ABCB1 

and ABCB5) in colon and pancreatic cancer cells suffering from nutrient 

stress. 

Methods. To mimic pathophysiological nutrient stress in the tumor microenvironment 

human colon and pancreatic cancer cell lines (HT-29 

and PANC1, MIA PaCa-2) were cultured using different media providing 

varying conditions of nutrient stress (basic culture medium containing 

10% FCS or 10% FCS and 2.5% HS basic culture medium without 

serum and PFHM-II protein-free hybridoma medium). Cells were kept 

in each medium for 24, 48, and 72 hours before harvesting and protein 

(Western Blot) and gene analysis (RT-qPCR) were performed for their 

TLR 1-10, Hsp70, Hsp90, ABCB1 and ABCB5, and CD133 profiles. 

Results. Compared to normal nutrient cell conditions TLRs were found 

at higher protein and gene expression levels in cells exposed to starvation. 

Upregulated CD133, ABCB1 and ABCB5 levels were observed as well 

as rising levels of Hsp70 and Hsp90. Expression levels varied between 

both cell lines and were dependant on the duration of nutrient stress. 

Conclusions. TLR, Hsp70 and Hsp90, as well as CD133, ABCB1 and 

ABCB5 expression characterizes surviving cells that are relatively unsusceptible 

to starvation. This indicates that a minor population of cells 

within a tumor is comparably resistant to nutrient stress through specific 

repair mechanisms compared to the bulk of differentiated tumor 

cells. Thus through this survival advantage this cell population may 

contribute to further metastatic growth in vivo. 

0249 

Estrogen receptor targeting by raloxifene potently inhibits 

human pancreatic adenocarcinoma growth 

*H . Seeliger1 , N . Seel1 , P . Camaj1 , I . Ischenko1 , K .-W . Jauch1 , C .J . Bruns1 1Klinikum der Universität München, Chirurgische Klinik und Poliklinik, 


Background. The role of estrogen receptor (ER) signaling in pancreatic 

cancer is unknown. Recently, we demonstrated that expression of 

the isoform ER beta correlates with an adverse prognosis in patients 

with pancreatic cancer. Here, we show that raloxifene, a specific estrogen 

receptor modulator (SERM), suppresses in vitro and in vivo tumor 

growth by interfering with ER beta signaling in human pancreatic adenocarcinoma. 

Methods. The human pancreatic adenocarcinoma cell line L3.6pl was 

cultured and exposed to raloxifene in vitro, and cell proliferation was 

determined by the BrdU assay. To analyze the specificity of raloxifene 

induced effects, ER knockdown was performed using siRNA specific 

for ER alpha and ER beta. In an in vivo model of orthotopic tumor xenografts 

in nude mice, raloxifene was administered daily, and tumor 

growth was monitored. Expression of ER beta and the proliferation 

marker Ki-67 were determined by immunohistochemistry. 

Results. Raloxifene treatment resulted in a potent, dose dependent reduction 

of proliferation in vitro over a nanomolar dose range. This effect 

was completely reversed by siRNA knockdown of ER beta, but not 

ER alpha, indicating an ER isotype specific signaling. In vivo, orthotopic 

tumor growth, as well as lymph node and liver metastases, was 

significantly suppressed in raloxifene treated mice. Analogous to the in 

vitro data, Ki-67 expression in vivo was significantly reduced in raloxifene 

treated mice, while ER beta expression was not changed in vivo. 

Conclusions. Inhibition of ER beta signaling by raloxifene results in a 

potent reduction of human pancreatic adenocarcinoma growth in vitro 

and in vivo. Treatment with SERMs may be an attractive therapeutic 

option in subjects expressing the ER beta isotype. 

0261 

shRNA mediated knock down of S100A4 in colorectal carcinoma 

reduces metastasis formation in vivo 

*M . Dahlmann1 , U . Sack2 , P . Herrmann1 , M . Lemm3 , I . Fichtner3 , P .M . Schlag4 , 

U . Stein2,1 1Charité Universitätsklinikum, Chirurgische Onkologie, Berlin, Deutschland, 

2 3 MDC-Berlin, Chirurgische Onkologie, Berlin, Deutschland, MDC-Berlin, 

Experimentelle Pharmakologie, Berlin, Deutschland, 4Charité Universitätsklinikum, 

Comprehensive Cancer Center, Berlin, Deutschland 

Colon carcinoma, due to its metastases, is still a major cause of death 

even after the excision of the primary tumor. The small calcium binding 

protein S100A4 was found to be an indicator for metachronous metastasis 

formation. Its expression level positively correlates to the metastatic 

potential of human colon cancer, where it promotes cell motility and 

invasion, and negatively affects the survival of colon cancer patients. A 

therapeutic decrease of S100A4 expression in patients could therefore 

result in less metastasis formation and increased survival rates. In the 

present study, we used shRNA expressing plasmids to inhibit S100A4 

expression in the colorectal carcinoma cell line HCT116 and observed 

a clear reduction of cellular migration and invasion in vitro to about 

45% and 55%, respectively, while proliferation of the cell lines was not 

affected. Intrasplenical transplantation of either S100A4 knock down or 

control cells in mice reduced the formation of liver metastases in correlation 

with reduced S100A4 expression. 

We also evaluated the therapeutic potential of systemically applied 

shRNA expressing plasmids via repeated hydrodynamics-based tail 

vein injection of plasmid DNA, expressing either specific S100A4shRNA 

or unspecific control shRNA. Mice with intrasplenically transplanted 

HCT116-LUC cells showed a 3-fold decrease in metastasis formation 

in the liver, when treated with S100A4-shRNA plasmids. The 

average tumor size of treatment and control group was comparable, 

but showed a decrease of S100A4 and MMP-9 expression levels to 60% 

and 20%, respectively, when treated with S100A4-shRNA plasmids. The 

developed liver metastases showed a similar reduction in S100A4 expression, 

while the decrease in MMP-9 expression was less pronounced 

(50% and 60%, respectively). In summary, the knockdown of S100A4 via 

systemic application of plasmid DNA, expressing gene specific shRNA, 

resulted in a decrease of metastasis formation in a xenograft mouse model 

of colon cancer. 


97

Abstracts 

0286 

Cancer-retina antigens in pancreatic adenocarcionoma: impact 

of guanylyl cyclase 1 

S . Karakhanova1 , J . Werner1 , *A . Bazhin1 1Uniklinikum Heidelberg, Chirurgische Klinik, Heidelberg, Deutschland 

Background and aims. Recently, we have shown that the key photoreceptor 

proteins, that are normally restricted to retinal cells, function in 

cancer cells as cancer-retina antigens (CRA). The aim of the work was 

to investigate the phenomenon of CRA in pancreatic carcinoma cells 

with a focus on function of guanylyl cyclase 1 (GC1) in the tumor cells. 

Methods. shRNA plasmids were used to knock-down the GC1 expression. 

RT-PCR, Western blotting, cyto/histoimmunochemistry, Ca2+ 

and cGMP measurement and FACS analysis were applied for in vitro 

experiments. An orthotopic mouse model of pancreatic carcinoma was 

used for in vivo experiments. 

Results. We showed that CRA are expressed in pancreatic carcinoma 

cell lines and tumors. Moreover, GC1, phosphodiesterase 6 and transducin 

are expressed in pancreatic cancer at a high frequency. Expression 

of these antigens leads to autoantibody production in the pancreatic 

cancer patients. Besides, we found that GC 1 is functional in pancreatic 

carcinoma cells, and this enzyme is involved in cGMP metabolism and 

Ca2+ accumulation in the tumor cell lines. Knocking-down of the enzyme 

affect viability, proliferation, radiosensitivity, migration and invasion 

of pancreatic carcinoma cell in vitro. The GC 1 knocking-down 

reduces the tumor volume, appearance of peritoneal carcinosis and metastases, 

and has a tendency to prolong a survival of the tumor-bearing 

mice in an orthotopic model of pancreatic cancer. Moreover, inhibition 

of GC1 leads to better activation of CD4+ T cells by tumor cells. 

Conclusions. We suggest that the aberrant expression of GC1 in pancreatic 

carcinoma cells is important for the tumor biology. Establishing of 

new methods for an in vivo knocking-down of GC1 and searching a 

down-stream molecular partner of GC1 could be important for the pancreatic 

carcinoma treatment. 

0296 

Cell-in-cell structures in tumours 

*L . Distel1 , M . Büttner2 , M . Schwegler1 , F . Putz1 1 2 Strahlenklinik, Strahlenbiologie, Erlangen, Deutschland, Universität Erlangen, 

Pathologie, Erlangen, Deutschland 

Objective. Cell-in-cell structure means the entire internalisation of a 

cell by another cell. This phenomenon is mainly found in tumour cells, 

especially in malignant exudate cells and sporadic in tumour tissue 

specimen. Entosis was recently identified to be a mechanism for the 

generation of cell-in-cell structures. This process is regarded as a nonapoptotic 

cell death. Some studies exist, describing cell-in-cell structures 

generated by in vitro experiments. Additionally, there are several 

case reports on cell-in-cell structures in tumour tissues. To study the 

appearance of cell-in-cell structures we have scanned tumour tissue 

sections. Cell-in-cell positive tumours were stained for apoptosis and 

cell adhesion molecules. 

Methods. Tumour tissue sections (2 µm thickness) of three individuals 

were stained immunohistochemical for cleaved caspase-3, β-Catenin 

and E-Cadherin. The total tissue sections were scanned with high resolution 

(Mirax Scan, Zeiss, Germany) and the corresponding tumour 

regions with different stainings were analysed and compared to each 

other. 

Results. Two renal carcinoma and one metastasis of an unknown primary 

cancer were identified harbouring numerous cell-in-cell structures. 

Cell-in-cell structures were clustered in special regions of the tissue 

specimens with a frequency of up to one cell-in-cell per ten cells. Some 

cell-in-cells were very complex with more than one cell internalised in 

another cell and cells with an internalised cell having internalised another 

cell. The apoptotic rates in the three tumours were 5%, 4% and 1%, 


however only very small numbers of cell-in-cells were involved in apoptotic 

events. Regularly the internalised cells were non apoptotic. The regional 

distribution of cell-in-cell structures hints on special alterations 

of the cells in these regions. Therefore the tissue specimen were stained 

for adhesion molecules. In all three tumour types cells were positive for 

β-Catenin and E-Cadherin. Cells with cell-in-cell had no different staining 

for β-Catenin and E-Cadherin compared to non cell-in-cell cells. 

Conclusion. Entosis or cell-in-cell may be a cell death modality occurring 

in tumour cells as frequently, or even more frequently than apoptosis. 

A simultaneous apoptotic event in the internalised cell seems to 

be a very rare event. 

0303 

Retinoid receptors in pancreatic cancer: Differential expression 

in malignant and healthy pancreatic cells and link to the epithelial-mesenchymal 

transition 

*T . Bleul1 , J . Werner1 , A . Bazhin1 1Universitätsklinikum Heidelberg, Chirurgie, Heidelberg, Deutschland 

Background and aims. Pancreatic adenocarcinoma is a cancer with 

extremely poor prognosis and limited therapeutic options. Although 

preclinical experiments with retinoids showed beneficial effects of retinoid 

treatment, clinical studies had disappointing results. However, 

little quantitative data is available concerning retinoid receptor expression 

in healthy pancreas compared to pancreatic carcinoma. The main 

aim of this work was to study comprehensively the retinoid receptor 

expression in order to evaluate their role in pancreatic cancer and try to 

find reasons for the negative clinical results. 

Methods. Nine human pancreatic carcinoma cell lines and one healthy 

cell line were used. Expression of the retinoic acid receptor (RAR) 

and retinoic X receptor (RXR) subtypes (α, β, γ) was quantified on RNA 

level in all cell lines as well as in the murine pancreatic carcinoma samples 

using quantitative real-time PCR. On protein level the expression 

of RAR and RXR subtypes was studied with immunocytochemistry in 

all cell lines. As differentiation markers cytoceratin 7 and carbonic anhydrase 

II were analyzed by immunocytochemistry. To determine epithelial-mesenchymal 

transition vimentin expression was assessed with 

immunocytochemistry. Cytotoxicity of retinoic acid was tested with the 

MTT assay and the effects on proliferation with the BRDU assay. 

Results. On protein level RAR α and β is significantly lower expressed in 

seven out of nine pancreatic tumor cell lines compared to healthy cells. 

No difference in the expression occurred between primary tumor and 

metastatic cell lines on RNA and protein level. Retinoic acid treatment 

of pancreatic cancer cell lines with high and low expression of RAR showed 

neither cytotoxic, nor antiproliferative, nor differentiating effects. 

A negative correlation between vimentin expression and RAR α and β 

expression was found. In the orthologous system of murine pancreatic 

cancer RAR α and β as well as RXR α and β is significantly lower expressed 

in tumor samples compared to healthy pancreas at RNA level. 

Conclusions. Our results show that malignant transformed pancreatic 

cells express less retinoid receptors than their healthy counterparts. 

Mesenchymal transition leads to decreased RAR α and β expression. It 

is tempting to speculate that the decreased retinoid receptor expression 

could play an important role in pancreatic cancer and it would be a reason 

for the negative clinical results of pancreatic carcinoma treatment 

with retinoids.

0328 

Differential Daxx isoform expression in renal cell and colorectal 

carcinoma 

*S . Funke1 , N . Wethkamp1 , S . Heikaus1 , K .-L . Schäfer1 , H .E . Gabbert1 , 

C . Mahotka1 1Universitätsklinikum Düsseldorf, Institut für Pathologie, Düsseldorf, 

Deutschland 

Aims. Death associated protein (Daxx) is an important transcriptional 

co-repressor for a large number of genes, mostly related to apoptosis. 

Daxx interacts with p53 and represses its transcriptional activity. Alternative 

splicing of the Daxx results in the generation of a c-terminally 

truncated and modified isoform termed Daxx-β. According to the new 

C-terminus, Daxx-β shows a markedly reduced affinity to PML and p53. 

Consequently, in contrast to Daxx, Daxx-β is unable to repress transcriptional 

activity of p53. As deregulation of p53 is closely related to 

carcinogenesis, alternative splicing of Daxx may also participate in tumour 

development and progression. 

Methods. Here, we examined the in vivo splicing pattern of Daxx and 

Daxx-β during renal cell and colon carcinoma progression using kinetic 

RT-PCR. 

Results. Both Daxx transcripts are expressed in epithelia from kidney 

and colon, in non-neoplastic as well as in tumour tissue. Interestingly, 

in renal cell carcinoma a significant reduction of both isoforms was notable 

whereas in colorectal carcinoma a different Daxx splicing pattern 

was evident with only Daxx-β being transcriptionally reduced. In both 

tumour types, these alterations could be found already at early stages 

(pT1/2) and did not further change in late stages (pT3/4). 

Conclusion. Therefore, our results indicate for the first time that differential 

Daxx isoform expression is associated with tumourigenesis of 

renal cell and colorectal carcinoma and may serve as a novel biomarker 

on mRNA level. 

0336 

Inhibition of FGFR impairs angiogenic signaling in human HCC 

cell lines and stromal cells 

*T .P . Scheller1 , C . Moser1 , M . Mycielska1 , C . Hellerbrand2 , A .A . Schnitzbauer1 , 

E .K . Geissler1 , H .-J . Schlitt1 , S .A . Lang1 1 2 Universität Regensburg, Chirurgie, Regensburg, Deutschland, Universität 

Regensburg, Innere Medizin I, Regensburg, Deutschland 

Background. Expression of receptors for fibroblast growth factors 

(FGFR) and their corresponding ligands have been associated with tumor 

growth in human hepatocellular carcinoma (HCC). Furthermore, 

hypervascularisation is a typical characteristic of HCC and activation 

of the FGF/FGFR system is a crucial event in tumor angiogenesis via 

effects on both, tumor cells and stromal cells. Therefore, we sought to 

evaluate the effects FGFR inhibition on cancer cells and stromal cells in 

a model of HCC. 

Methods. For the experiments HCC cell lines (Huh-7, HepG2), stromal 

cells (endothelial cells (EC), vascular smooth muscle cells (VSMC), hepatic 

stellate cells (HSC)) and the FGFR inhibitor BGJ398 (Novartis Oncology, 

Basel) were used. Effects of targeting FGFR on growth of cells 

were determined by MTT assays. Inhibition of constitutive and growth 

factor induced cell motility was investigated using modified Boyden 

Chamber assays. Activation of signaling pathways and expression of 

trasncription factors upon FGFR inhibition was assessed by Western 

Blot analyses. Effects on expression of vascular endothelial growth factor-A 

(VEGF-A) and FGFs were determined by RT-RCP and ELISA, 

respectively. 

Results. Targeting FGFR system with BGJ398 impaired growth of tumor 

cells and ECs in dose-dependent manner, whereas only minor effects 

were observed on VSMC and HSCs as determined by MTT assays. In 

addition, motility of tumor cells and stromal cells was significantly reduced 

(p

Abstracts 

0351 

The pandeacetylase inhibitor panobinostat induces autophagy 

related factors in liver cancer cells 

*P . Di Fazio1 , R . Montalbano1 , S . Jabari2 , K . Quint1,2 , M . Ocker1 1Philipps University of Marburg, Institute for Surgical Research, Marburg, 

Deutschland, 2Universität Erlangen-Nürnberg, Institut für Anatomie, Erlangen, 

Deutschland 

Background. Liver cancer, placed as the 5th common malignant tumor 

entity, has rising incidence rates also in Western countries. Panobinostat 

(LBH589, Novartis Oncology), a pandeacetylase inhibitor, represents 

a new agent with a promising future in liver cancer therapy. We have 

previously demonstrated that panobinostat is able to induce cell death 

through activation of ER stress related apoptotic pathways. Panobinostat 

also significantly reduced the growth of HepG2 xenografts in nude 

mice (Cell Oncol 2010, 32:285–300). We, here, clarify the implication of 

autophagy mechanisms into cell demise mediated by panobinostat. 

Materials and methods. HepG2 (p53 wt) and Hep3B (p53 null) were 

treated for 72 hours with panobinostat and cell death was quantified 

through FACS with propidium iodide staining and CK18 fragmentation 

staining. Impedance based real-time cell analysis (Xcelligence Roche) 

was performed to monitor cell viability after panobinostat treatment. 

The expression of autophagy related factors was analyzed through RTqPCR, 

western blot and immunofluorescence based cytochemistry; 

transmission electron microscopy (T.E.M.) was performed to monitor 

autophagosome formation. 

Results. Panobinostat induced cell death in a dose and time dependent 

manner. Autophagy related factors Atg5, Beclin and its activators Ambra, 

p62 and UVRAG were upregulated after 48 hours of treatment. 

We also observed significant increase of p73 expression in Hep3B cells 

after 24 hours of treatment. Immunofluorescence based cytochemistry 

showed a modification of the ubiquitous cytosolic distribution of Beclin 

and LC3B in both cell lines to a defined spot formation after treatment 

with panobinostat, indicating a probable autophagosome formation. 

Western blot analysis also demonstrated an increase of Beclin 

and LC3-I and LC3-II; no variations in the level of Apg12 were detected. 

T.E.M. showed double-membrane cellular vescicles, after treatment 

with panobinostat, which represent autophagosomes. 

Conclusion. Panobinostat treatment determines the involvement of autophagy 

related mechanisms in an ER stress related apoptosis scenario. 

The wide spectrum of mechanisms of action of panobinostat needs to 

be further investigated. 

0356 

The pandeacetylase inhibitor panobinostat determines downregulation 

of oncogenic miRNAs in HCC cells 

A . Henrici1 , M . Ocker1 , *P . Di Fazio1,2 1Philipps University of Marburg, Institute for Surgical Research, Marburg, 

Deutschland, 2Universität Erlangen-Nürnberg, Institut für Anatomie, Erlangen, 

Deutschland 

Background. miRNAs represent new targets for future cancer therapy. 

It has been shown that they possess tumorigenic and tumorsuppressor 

activity. In particular, miR-19a, miR-19b and miR-30a promote tumor 

progression by blocking the translation of proteins related to apoptotic 

and autophagic cell death like APAF1, PAK6 and Beclin1 in many solid 

tumors. We have previously shown that panobinostat, a potent pandeacetylase 

inhibitor, was able to promote the modulation of hsa-let7b and 

its related target HMGA2 favouring the block of cellular proliferation 

in liver cancer cells (HCC). Here we clarify, for the first time, that panobinostat 

is responsible for downregulating the above mentioned oncogenic 

miRNAs with subsequent modulation of their targets in HCC 

cell lines. 

Material and methods. HepG2 (TP53 wt) and Hep3B (TP53 null) liver 

cancer cells were treated with 0.1 mM panobinostat for 6–48 hours. 


Quantitative RT-PCR was used to determine the expression of miR-19a, 

miR-19b, miR-30a, and their precursor transcripts; moreover their targets 

were also quantified. 

Results. We demonstrate that panobinostat treatment causes a downregulation 

of miR-19a, miR-19b and their precursors. Panobinostat treatment 

determines also a downregulation of miR-30a while its precursor 

is detectable neither in nuclear nor in cytosolic compartment. miRNAs 

targets expression was differently affected in the two cell lines. 

Conclusion. Panobinostat negatively regulate oncogenic miRNAs by favouring 

the expression of their targets. The modulation of these miR- 

NAs has been shown for the first time in liver cancer cells and it needs to 

be further investigated. Panobinostat represents a promising modulator 

of miRNAs in a cancer related scenario. 

0362 

Overexpression of Hepatitis B virus envelope proteins induce 

endoplasmic reticulum-mediated stress pathways in liver cancer 

cell lines 

*R . Montalbano1 , P . Di Fazio1 , D . Glebe2 , M . Ocker1 1University of Marburg, Institute for Surgical Research, Marburg, Deutschland, 

2University of Gießen, Institute of Medical Virology, Gießen, Deutschland 

Background. Hepatocellular carcinoma (HCC) is the 5th most common 

malignancy worldwide. More than 90% of HCCs develop in cirrhotic 

livers on a background of chronic liver disease, esp. infection with the 

Hepatitis B virus (HBV). HBV represents the most common chronic 

viral infection with about 370 million people being affected worldwide. 

Although HBV has been documented to cause HCC, the exact role of 

HBV in the development of HCC remains enigmatic. HBV is a hepatotropic 

virus with an outer lipoprotein envelope and an inner core bearing 

the viral genome. HBV envelope consists of 3 co-carboxyterminal 

proteins, the small (SHBs), the middle (MHBs) and the large surface 

protein (LHBs) that are cotranslationally inserted into the endoplasmic 

reticulum (ER) as transmembrane (glycol-)proteins. When overexpressed, 

all three viral proteins are secreted as non-infectious subviral particles 

via the secretory pathway, while only virions containing the viral 

core are secreted by multivesicular bodies (MVB). The LHBs cannot build 

viral particles by itself, but needs SHBs or MHBs for proper propagation. 

A massive storage of HBV envelope proteins was reported to lead 

to cell stress causing cell death and sustained inflammatory responses. 

Here we investigate if overexpression of L and S proteins in liver cancer 

cells can induce ER-stress and trigger the expression of genes involved 

in this pathway. 

Methods. Human HCC cells HuH-7 was cultured under standard conditions 

and transfected with pSVL and pSVBX24H plasmids, overexpressing 

only LHBs and SHBs, respectively. Impedance based real-time 

cell analysis was performed to continuously monitor cell viability. ERstress 

factors were evaluated by RT-PCR, FACS and IF analysis. ER-staining 

was performed by IF analysis. 

Results. Cell based impedance analysis of HuH-7 cells showed that the 

transfection with the plasmid encoding LHBs caused a reduction of cell 

growth comparable with the effect of 10 nM thapsigargin, an ER-stress 

inducer. Interestingly, the SHBs expression was cytostatic. The expression 

of both viral proteins induced an increase of BiP and CHOP mRNA 

levels after 24–96 h of transfection, while the protein level was stable. ER 

detection by IF revealed an increase of the selective fluorescent dye in 

cells transfected with LHBs. 

Conclusions. Overexpression of HBV envelope proteins LHBs and SHBs 

activate ER-stress markers in HuH-7 cells. Further investigations are 

needed to better clarify their mechanism of action.

0364 

Formation and incidence of cell-in-cell structures in tumor and 

normal tissue cells in vitro 

*M . Schwegler1 , B . Abendroth2 , F . Putz2 , L . Distel1 1Universitätsklinikum Erlangen, Strahlenklinik, Erlangen, Deutschland, 

2Friedrich-Alexander Universität Erlangen-Nürnberg, Erlangen, Deutschland 

Objective. Internalisation of cells is a phenomenon called cell cannibalism 

or entosis that has been recently described. These cell-in-cell structures 

(CIC) have been detected in tumor tissue sections and studied by 

in vitro experiments. CIC structure has a characteristic appearance. 

The cell is filled with a cell inside a vacuole that pushes the nucleus crescent 

shaped to one side. CIC is regarded to be one type of cell death 

modality. Our question was whether CIC formation is common among 

tumor cells and whether cells from normal tissue are able to form CIC. 

Methods. The precondition for cell uptake is cell adhesion. For quantification 

of adhesion two samples of tumor cells were stained either with 

the life cell dye CellTrace Oregon Green or CellTrace Far Red, mixed 

and analyzed by flow cytometry before and after 90 minutes of coincubation. 

One of the so dyed samples was heat-treated (56°C, 45 min) to 

stimulate incorporation. Microscopic analysis followed 4 hours of coincubation. 

This experiment was repeated 3 times with 5 tumor cell lines, 

one primary tumor cell line, one lymphoblastoid cell line and 3 primary 

skin fibroblasts cell lines. Additionally the process of incorporation was 

imaged via life-cell microscopy. 

Results. Flow cytometry analysis showed a significant increase of adhesion 

between untreated and heat-treated samples of all cell lines. All 

cell lines were able to form CIC structures. Using an image, analysis 

software CIC rates of 1000–2500 cells were quantified. Highest rates 

were among the tumor cell lines (e.g. pancreatic carcinoma cell line 

BxPC-3: 2.71%), lower rates in the fibroblasts (e.g. cell line GP: 2.17%) and 

lowest in the lymphoblastoid cell line (0.66%). The number of cell-incell 

structures found via microscopy correlated with the degree of adhesion 

quantified via FACscan. We observed that 41.7% of viable green 

cells adhered to necrotic red cells of the pancreatic carcinoma cell line 

BxPC-3, 37.3% of the primary skin fibroblast cell line GP and only 9.4% 

of the lymlphoblastoid cell line SBL-1. Engulfment of early necrotic cells 

seems to be a membrane-dependent process whereas damaged cells 

which had lost completely their shape and membrane integrity could 

not be taken up. 

Conclusion. Not only tumor cells but even normal tissue cells and lymphoblastoid 

cells are able to form CIC. CIC seems to be more frequent 

in tumor cell lines but common to a variety of cell types and may be an 

underestimated type of cell death. 

0372 

Activation of the human immune system via Toll-like receptors 

by the oncolytic parvovirus H-1 and its combination with chemotherapeutic 

or targeted agents 

*M . Sieben1 , S . Roth1 , F . Springsguth1 , C . Dinsart2 , P .R . Galle1 , J . Rommelaere3 , 

M . Möhler1 1Universitätsmedizin Mainz, I . Medizinische Klinik und Poliklinik, Mainz, 

Deutschland, 2German Cancer Research Center, Infection and Cancer 

Program, Department F010 , Heidelberg, Deutschland, 3German Cancer 

Research Center, Institut National de la Santé et de la Recherche Médicale 

Unité 701 , Heidelberg, Deutschland 

Background. Promising new approaches to tumor-directed therapy include 

oncolytic parvoviruses since they also increase the host immune 

response by priming effector immune cells against the tumors. During 

the activation of dendritic cells (DC) by H-1PV-induced tumor cell lysates 

(TCL) the functional role of Toll-like receptors (TLR) and their 

signaling pathways is yet unknown. Since H-1PV kills human cancer 

cells using different pathways than other anticancer therapies, we eva- 

luated the immunologic effects of H-1PV induced TCL for efficient human 

antitumor immune responses. Thus, we explored the molecular 

interactions and synergistic effects between H-1PV, chemotherapeutic 

agents and the targeted agent sunitinib as a typical molecule of the new 

multi-tyrosine kinase inhibitors (TKI) for targeted therapy. 

Methods. In view of the stimulatory capacity for DCs by H-1PV-infected 

SK29Mel cell lysates, we stably transfected human HEK293 cells expressing 

single TLRs, analysed the expression and function of TLRs during 

H-1PV infection and determine whether the parvovirus-induced immune 

stimulation is correlated with the Toll-like receptor (TLR) signaling 

pathways. In addition our human melanoma model enables to study 

immune responses in the context of corresponding HLA-restricted 

human DCs. In this human tumor model, activation of tumor-specific 

autologous CTL clones can also be analysed. 

Results. In TLR-transfected HEK293 cells we identified TLR3 and 9 

which were clearly activated by H-1PV. Furthermore, NFkB-expression 

was increased after H-1PV infection. In addition, TLR expression profiles 

of DCs coincubated with H-1PV-infected SK29Mel cells was studied 

and showed an increased TLR3 and 9 expression. DC co-cultures with 

TCL incubated with H-1PV combined with chemotherapeutic agents or 

sunitinib induced effective immune stimulation via a pronounced DC 

maturation, significant better cytokine release and cytotoxic T-cell activation. 

Again, cytokine levels increased after coculture of autologous 

CTLs with DCs stimulated by H-1PV-induced TCLs. 

Conclusions. H-1PV induced tumor cell lysates stimulate human immature 

DCs and cytotoxic T-cells, at least in major parts by the TLR signaling 

pathway. Even more, combined treatment with chemotherapeutic 

or targeted agents did not interfere with the pronounced immunomodulatory 

properties of H-1PV, but reinforced drug-induced tumor cell 

killing. Thus, this very promising approach has also high immunotherapeutic 

potentials for tumor patients. 

0374 

Akt/mTORC1-signalling in human sarcoma cells under heatshock. 

*E . Strozyk1 , V . Sujeva1 , E . Kampmann2 , R . Issels2,1 1Helmholtz Zentrum München, KKG Hyperthermie, München, Deutschland, 

2Universitätsklinikum Großhadern, Medizinische Klinik und Poliklinik III, 


Introduction. The completed randomized phase III EORTC/ESHO 

intergroup trial (NCT 0003052) showed that regional hyperthermia 

(RHT) combined with neo-adjuvant chemotherapy (NAC) improves 

response, tumor control and survival of patients with high-risk soft 

tissue sarcomas (STS; Lancet Oncol 2010). Recently, the notion is that 

grade 2 STS, which are thought to be less chemosensitive than grade 3, 

predominantly benefit from the addition of RHT to NAC (ASCO 2011). 

Because grading is mainly scored on mitotic index, we investigated the 

Akt/mTORC1 pathway, which is involved in proliferation, survival and 

protein synthesis, under heat-shock conditions. 

Methods. Human sarcoma cell lines were exposed to heat-shock (41.8 or 

43°C for 90 or 150 min) and treated with perifosine (0–15 µM) as inhibitor 

of Akt-phosphorylation or RAD001 (0.1–10,000 nM) as inhibitor of 

mTORC1 kinase-activity. Induction of HSP70 and phosphorylation of 

Akt and downstream proteins mTOR, p70S6K and S6 were detected by 

immunoblotting. Cytotoxic effects were estimated by using the WST-1 

assay, measuring clonogenic survival and recording colony diameters. 

Results. Increased HSP70 expression and enhanced phosphorylation 

of Akt, mTOR, p70S6K and S6 were immediately detected after heatshock. 

Both, inhibition of Akt-phosphorylation by perifosine and inhibition 

of mTORC1 kinase-activity by RAD001 led to reduced HSP70-induction. 

Perifosine reduced cellular viability dose-depently and yielded 

enhanced cytotoxicity when combined with heat-shock. Combining 

RAD001 and heat-shock did not enhance cytotoxicity. Chosen concen- 


101

Abstracts 

trations of RAD001 had only marginal effects on clonogenic survival 

but reduced colony growth. 

Conclusion. Activation of Akt/mTORC1 is important for HSP70-induction 

in response to heat-shock. Inhibition of Akt-phosphorylation but 

unexpectedly not of mTORC1 kinase-activity reduced survival when 

combined with heat-shock. Other targets of Akt besides mTOR might 

be essential for surviving cellular stress and are investigated in ongoing 

experiments. 

0383 

CTLA-4 antibodies Tremelimumab and Ipilimumab overcome 

tumor-mediated immunsuppressive effects of CTLA-4 on human 

dendritic cells 

*K . Goepfert1 , P . Schäfer1 , B . Heinrich1 , P . Galle1 , M . Moehler1 1Universitätsmedizin Mainz, I . Medizinische Klinik, Mainz, Deutschland 

Introduction. Tumors have distinct mechanisms to circumvent the human 

immune system. Expression of CTLA-4 (cytotoxic T-lymphocyte-associated 

antigen 4) on tumors and regulatory T cells (Tregs) can 

lead to suppression of immune defence mechanisms. However CTLA-4 

mediated blockage of human dendritic cells (DCs) by CTLA-4 expressing 

tumors have not been analysed so far. As CTLA-4 receptors can be 

blocked by new CTLA-4 antibodies tremelimumab or ipilimumab, we 

analysed these antibodies in our ex vivo human melanoma model for 

their effects on maturation of DCs and their role on Tregs. 

Methods. Tregs and monocytes were isolated from human Buffy coats 

from HLA-A2 restricted donors with magnetic beads. For differentiation 

of monocytes into DCs, monocytes were stimulated with IL-4 and 

GM-CSF and maturation of iDCs was induced by a cytokine cocktail 

(CC), containing 0.01 µg/ml TNFα, IL-6, IL-1β and 1 µg/ml PGE2 [Jonuleit 

et al. (1997), Eur J Immunolo 27(12):3135–42]. Parvovirus H1-infected 

and uninfected Sk29Mel melanoma cells were cocultured with iDCs 

with or without tremelimumab (10 µg/ml) and with or without ipilimumab 

(10 µg/ml) in a ratio of 1:3 for 3 days. 

Results. Sk29Mel cells and some colon carcinoma cells (CaCo2) clearly 

expressed CTLA-4 on the surface, measured by extra- and intracellular 

FACScan analyses. Furthermore, tremelimumab and ipilimumab did 

not disturb maturation of iDCs. In coculture, the oncolytic parvovirus 

H1-infected (H1-PV) SK29Mel cell lysates induced maturation of iDCs 

which was increased by the addition of tremelimumab and ipilimumab. 

Using ELISA, a clear increase in IFNgamma and IL-6 was detected in 

the supernatants of H-1PV infected SK29Mel cocultured with iDCs in 

the presence of tremelimumab and ipilimumab. In further coculture 

experiments the negative effect of Tregs on mDCs was partially restored 

in the presence of tremelimumab and a decrease of IL-10 was detected in 

the supernatant via ELISA. The further analysis of CTL activation and 

DC cross presentation will be presented at the meeting. 

Conclusion. To our knowledge this is the first direct analysis that tremelimumab 

and ipilimumab can overcome the negative feedback of 

tumor cells expressed CTLA-4 on human DCs. These results clarify the 

importance of CTLA-4 as therapeutical goal for treatment of human 

tumours to overcome tumor-induced immune suppression. 


0393 

Radiation-induced damage of the rat intestine after external 

beam irradiation of the liver 

*S . Cameron1 , A . Schwartz1 , S . Sultan1 , I .-M . Schaefer1 , M . Rave-Fraenk1 , 

C .F . Hess1 , H . Christiansen1 , G . Ramadori1 1UM Göttingen, Gastroenterologie und Endokrinologie, Göttingen, 

Deutschland 

Introduction. Ionizing radiation is routinely used in the treatment of 

malign tumors. To date, no experimental setting exists for investigating 

out-of-field effects of the intestine, with a parenchymatous organ 

as target. 

Methods. A single dose of 25 Gray was administered percutaneously to 

the liver of randomly paired male Wistar rats after a planning CT-scan. 

Sham-irradiated animals served as controls. At 1, 6, 24, 96 hours (h), 

and 1.5 and 3 months the duodenum, jejunum, ileum and distal colon 

were removed, washed and frozen in liquid nitrogen or prepared for 

paraffin staining. 

Results. All animals survived the treatment. In the duodenum and jejunum, 

acute changes at 1 h resulted in epithelial cell damage. At 6 h, the 

villus architecture was disrupted. In the submucosa, vessel congestion 

was observed. Radiation mucositis with granulocyte (MP0+) infiltration 

was seen from 1 to 24 h in the duodenum and jejunum, when ED1+ 

macrophages, CD3+ T-lymphocytes, and CD34+ hematopoietic precursor 

cells were recruited. Duodenum and jejunum showed regeneration 

of the crypt-villus axis at 1.5 and 3 months. In the ileum at 1 h after irradiation, 

only edema was observed. At 6 h, the ilial mucosa showed complete 

denudation of the villi and destruction of the crypt lining. In the 

lamina propria, vessels were scarce with increased collagen deposition. 

Early granulocyte infiltration was delayed but continued throughout 

the observation time. Recruitment of macrophages and lymphocytes 

was missing with a lack of induction of chemokines such as CCL2. Tissue 

regeneration in the ileum was deficient during the observation time. 

In the colon, changes were minor and transient. 

Conclusion. The ileum, even though it received only scattered irradiation, 

was most sensitive to radiation. This needs to be taken into account 

to prevent the clinically observed irradiation complications to the 

ileum. 

0404 

Effect of Sox9 induced IFIT3 expression in pancreatic cancer 

*R . Mair1 , P . Camaj1 , I . Ischenko1 , A . Renner1 , Q . Bao1 , Y . Zhao1 , K .-W . Jauch1 , 

C .J . Bruns1 1Klinikum Großhadern, Experimentelle Forschung Chirurgie – AG Bruns, 


Introduction. Pancreatic cancer is associated with a very poor overall 

prognosis. To analyze the aggressive tumor biology of human pancreatic 

cancer, we genomically compared high-metastatic and non-metastatic 

human pancreatic cancer cell lines and analyzed the relevance of 

differentially expressed IFIT3 gene in vivo and in vitro. 

Methods. The transcriptomes of the non-metastatic FG and the highmetastatic 

L3.6pl human pancreatic cancer cell lines were compared 

via Affymetrix analysis. The interferon-induced protein with tetratricopeptide 

repeats 3 (IFIT3) gene was significantly over-expressed 

in L3.6pl cells. The results were validated with RT-PCR and Westernblotting. 

Promoter sequence analysis was used to determine transcription 

factor binding sites. L3.6pl, FG, their IFIT3-transfectants and the 

L3.6pl-Sox9shRNA-transfectant were examined in vitro with regard 

to proliferation, apoptosis, angiogenesis, chemotherapy-resistance and 

cytokine-production and orthotopically injected into nude mice. One- 

STrEP-tag identified interacting proteins. Regulation of gene expression 

was studied after treatment with IFN-alpha and/or inhibitors NFκB 

(BAY-11-7082) and STAT1 (S-19).

Results. IFIT3 was significantly over-expressed in high metastatic L3.6pl 

cells and inducible by IFN-alpha. The IFIT3-promoter presented a binding 

site for the transcription factor Sox9 which is constitutively upregulated 

in L3.6pl cells. Overexpression of the IFIT3 gene increased 

tumor growth, angiogenesis and metastasis. In addition, it led to an 

increased VEGF production, higher proliferation rate and decreased 

apoptosis as well as resistance to chemotherapy. Furthermore, a significant 

increase in IL-6 production was detected, whereas IFIT3-downregulation 

via downregulation of its transcription factor Sox9 led to 

a decreased IL-6 production. STAT1 and JNK were shown to be interacting 

partners. Inhibition of NFκB and STAT1 led to diminished IFIT3 

expression, respectively. 

Conclusion. Previous studies have shown an up-regulation of IFIT3 in 

the context of inflammation. In our experiments IFIT3 led to an aggressive 

phenotype in pancreatic cancer. It is inducible by IFN-alpha. Sox9triggered 

over-expression of IFIT3 led to an increased IL-6 production 

in tumor cells. Therefore, our results suggest that Sox9 triggered IFIT3 

over-expression induces a pseudo-inflammatory environment, supporting 

tumor cell proliferation and metastasis, which is represented in the 

phenotype of L3.6pl cells. 

0421 

A new in vitro model for cell-in-cell structure formation using the 

pancreatic carcinoma cell line Bxpc-3 

*F . Putz1 , M . Schwegler1 , R . Fietkau1 , *L . Distel1 1Strahlenklinik der Universität Erlangen-Nürnberg, Strahlenbiologie, 


Objective. Pathologists have described cell-in-cell structures in malignant 

tumor samples for many years. This cell-in-cell phenomenon, also 

referred to as “cell cannibalism”, consists of a tumor cell that has completely 

engulfed another tumor cell leading to a characteristic bird´s eye 

appearance. Recently, a new mechanism, called entosis, was described, 

which can partially explain cell-in-cell structure formation. Nevertheless, 

the mechanisms underlying the cell-in-cell phenomenon in tumors 

still remain largely unknown. We have discovered a new in vitro model 

using a mechanism different from entosis that allows the generation 

of numerous cell-in-cell structures. As the uptake of apoptotic cells in 

neighboring cells is well recognized in the literature, we investigated 

whether the observed cell-in-cell structure formation was induced by 

apoptosis. 

Methods. Bxpc-3 cells were stained red and green with CellTrace Oregon 

Green and CellTrace Far Red, respectively. Red Bxpc-3 were heattreated 

(56°C, 45 min) with or without the caspase inhibitor ZVAD- 

FMK (0.5 h pretreated, 100 µM). Alternatively, red Bxpc-3 were treated 

with 25% ethanol or 1 M sodium azide for 1 hour. After coincubation of 

red and green cells in suspension for 3 hours, cells were fixed and examined 

under the fluorescence microscope. Red cells that were completely 

internalized into green cells were counted as cell-in-cell structures. 

Furthermore, cells were immunostained for cleaved caspase-3. 

Results. Bxpc-3 cells were present in small clusters. Numerous characteristic 

cell-in-cell structures were noted, irrespective of treatment. 

Cell-in-cell structures consisted of a red Bxpc-3 cell that was completely 

engulfed by a green cell with typical crescent-shaped nucleus. Treated 

cells were negative for cleaved caspase-3. Using heat-treated cells we 

observed 1.25% (39/3108) and 1.36% (41/3010) cell-in-cell structures with 

and without caspase inhibition, respectively. 

Conclusions. Engulfment of early necrotic cells by viable Bxpc-3 cells 

can lead to characteristic cell-in-cell structures in vitro strongly resembling 

those frequently described in histological and cytological tumor 

specimens. In conclusion, we present a new mechanism for cell-in-cell 

structure formation between malignant cells that is different from entosis 

and apoptotic cell uptake. 

0426 

Conditional RNAi-mediated knockdown of TPX2 synergizes with 

docetaxel cytotoxicity against HeLa cell sub-clones in vitro and 

in vivo 

*A .J . Allmendinger1 , K . Schönig2 , O . Gruss3 , S . Berger2 , M .R . Berger1 1Deutsches Krebsforschungszentrum, AG Toxikologie und Chemotherapie, 

Heidelberg, Deutschland, 2Zentralinstitut für Seelische Gesundheit, 

Mannheim, Deutschland, 3Zentrum für Molekulare Biologie, Heidelberg, 

Deutschland 

The microtubule-associated protein TPX2 could be a potent novel target 

for anti-cancer therapy. Knockdown of TPX2 is highly effective in inhibiting 

tumor cell growth, both in vitro and in vivo. The combination 

of TPX2-knockdown with docetaxel could further augment therapeutic 

efficacy. To test this hypothesis, respective experiments were performed 

with a HeLa cell line in which the reverse tetracycline-dependent 

transactivator rtTA2S-M2 drives the expression of eGFP and a miRNA, 

inducing RNAi-dependent inhibition of TPX2 expression, from the bidirectional 

tet-regulated promoter (Hela EM2-11-TPX2). A similar cell 

line (Hela EM2-11), in which the presence of the inducer doxycycline 

(dox) activates expression of the genes mCherry and firefly luciferase, 

served as a negative control. 

First, the combined effect of TPX2-knockdown and docetaxel (DCX) 

on in vitro proliferation was determined by MTT assay. Here, the respective 

cells were treated with either DCX (0.2–4.0 nmol/l) or dox 

(0.5 μg/ml) or a combination of both and cell viability was assessed after 

72 h. Treatment with DCX caused a concentration-dependent decrease 

in proliferation in vitro, whereas dosages of dox, which were sufficient 

to knock down TPX2 expression but not yet anti-proliferative, reduced 

cell growth by 42%. The proliferation of HeLa EM2-11-TPX2 was synergistically 

reduced by the combination treatment compared to the single 

agent exposures. 

Next, the therapeutic potential of TPX2-knockdown alone or in combination 

with DCX was tested in a nude mouse xenograft model. Here, 

the size of tumors growing in nude mice following s.c. implantation was 

monitored over a period of 4-5 weeks. A control group received no treatment; 

a TPX2-knockdown group received treatment with dox (0.2 mg/ 

ml in drinking water), starting on day 14 after cell injection and being 

continued for 18 days; a DCX group was given 22.3 mg/kg (applied twice, 

on days 14 and 25); a fourth group received a combination treatment. In 

nude mice, TPX2-knockdown alone caused a 52% reduction in tumor 

growth and DCX a reduction by 25%. The combination of both treatments 

inhibited tumor growth synergistically by 87%. 

In our experiments, knockdown of TPX2 alone was highly effective 

against HeLa cell growth. The combination of TPX2-knockdown with 

docetaxel showed a synergistic therapeutic effect, both in vitro and in 

vivo. It is concluded that TPX2 is a valuable treatment target, which can 

be successfully combined with other anti-mitotic agents. 

0477 

Preclinical evidence that CD47 is a common therapeutic antibody 

target on human solid tumors 

*S .B . Willingham1 , J .-P . Volkmer2,1 , H . Contreras-Trujillo 1 , R . Martin1 , J .D . Cohen1 

, K . Weiskopf1 , A .K . Volkmer1 , P . Dalerba1 , F .A . Scheeren1 , I .L . Weissman1 1Stanford University, Institute for Stem Cell Biology & Regenerative Medicine, 

Stanford, USA, 2Uniklinik Düsseldorf, Urologie, Düsseldorf, Deutschland 

Background. CD47 is a ligand for SIRP-alpha, a protein expressed on 

macrophages and dendritic cells. CD47 binding to SIRP-alpha transmits 

a “don’t eat me” signal that results in the inhibition of phagocytosis. 

Blocking anti-CD47 monoclonal antibodies neutralize the CD47- SIRPalpha 

interaction, enabling macrophages to phagocytose leukemia and 

lymphoma cells. We hypothesized that patient solid tumor cells express 

CD47 to circumvent macrophage surveillance and that blocking anti- 


103

Abstracts 

CD47 antibodies would inhibit the growth and metastasis of solid tumors. 

Methods. All experiments were performed with either primary or lowgeneration 

xenograft human tumors, including bladder, breast, colorectal, 

glioblastoma, hepatocellular carcinoma ovarian, prostate, and 

head and neck squamous cell carcinoma samples. CD47 expression was 

analyzed on solid tumor cells by flow cytometry or immunofluorescence. 

Patient gene expression and survival data were analyzed to evaluate 

CD47 as a prognostic factor. CD47 was evaluated as a therapeutic antibody 

target using in vitro assays and orthotopic xenotransplantation 

models established with patient solid tumor cells. 

Results. Nearly all solid tumor cells express CD47. CD47 mRNA expression 

levels correlated with a decreased probability of survival. Blocking 

anti-CD47 monoclonal antibodies enabled macrophages to phagocytose 

patient tumor cells in vitro, and in vivo inhibited tumor growth, 

prevented metastases, and increased survival. 

Conclusions. These results suggest that CD47 expression is a common 

mechanism exploited by human solid tumor cells to evade phagocytosis 

and establish CD47 as a potential therapeutic antibody target for solid 

tumors. 

0487 

MMP11 expression increases during progression of breast cancer 

*S . Schultz1 , H . Bartsch2 , B . Kootz1 , K . Sotlar2 , K . Petat-Dutter2 , M . Bonin3 , 

S . Poths3 , M . Walter3 , O . Riess3 , D . Wallwiener1 , T . Fehm1 , *H . Neubauer1 1Eberhard-Karls-University Tübingen, Department of Obstetrics and Gynecology, 

Tübingen, Deutschland, 2Ludwig-Maximilians-University Munich, 

Institute for Pathology, Munich, Deutschland, 3Eberhard-Karls-University Tübingen, Microarray Facility Tübingen, Tübingen, Deutschland 

Aims. The ductal carcinoma in situ (DCIS) of the breast is considered 

to be the pre-invasive form of the invasive duct carcinoma (IDC). The 

aim of this project is (1) the identification and validation of potential 

progression markers and (2) to identify markers for high risk DCIS with 

aggressive potential. MMP11 (matrix-metalloproteinase 11) is a marker 

for the transition from DCIS to IDC. It is associated with tumour cell 

invasion and a poor clinical outcome. 

Material and methods. 14 formalin fixed and in paraffin embedded 

(FFPE) tissue samples with a pure DCIS without IDC component 

(patients were at least five years free of cancer), and 15 paraffin tissue 

samples with DCIS/IDC tumours were selected. Tissue sections were 

prepared, stained with hematoxylin-eosin and the epithelial cells were 

isolated by laser capture microdissection (LCM). 200 ng RNA were extracted, 

hybridized to the Whole Genome DASL Array (Illumina) and 

bioinformatically evaluated. The RNA was linear amplified using the 

Ribo-SPIA® technology (WT-Ovation TM FFPE System, NuGenTM) 

and the validation was done by qRT-PCR using the LightCycler® 480 

System (Roche). 

Results. We were able to identify 993 transcripts that are differentially 

expressed between DCIS and IDC of the same tumor and 1138 transcripts 

which are differentially expressed between pure DCIS and DCIS/ 

IDC tumors. Differential expression was validated for 9 transcripts 

using two sample sets, the technical validation sample set (15 DCIS/IDC 

tumors, 14 pure DCIS) and an independent validation sample set (26 

DCIS/IDC tumors, 17 pure DCIS). MMP11 is highly expressed in IDC 

and moderately expressed in DCIS with IDC component. In pure DCIS 

less or no expression of MMP11 was determined. 

Conclusion. We identified progression-specific candidate transcripts 

using LCM and microarray analysis from FFPE breast cancer tissues. 

MMP11 is a progression marker which differentiates between high- and 

low-risk DCIS. 


0488 

Analysis of single tumor cells by a one-step Multiplex-RT-PCR 

*H . Schneck1 , A . Tögl2 , P . Hartmann2 , C . Grimmel3 , T . Biedermann3 , T . Fehm1 , 

H . Neubauer1 1Eberhard-Karls-University Tübingen, Department of Obstetrics and 

Gynecology, Tübingen, Deutschland, 2Beckman Coulter Biomedical GmbH, 

Munich, Deutschland, 3Eberhard-Karls-University Tübingen, Institute for 

Dermatology, Tübingen, Deutschland 

Objectives. Circulating tumor cells (CTC) are essential for establishing 

metastasis and therefore their detection and molecular characterization 

might help to optimize treatment decisions. By dint of a one-step Multiplex-RT-PCR 

approach on the breast cancer cell line MCF-7 the parallel 

analysis of tumor-related expression markers (e.g. CK19, EpCAM, 

Muc1) was established and served as proof of principle for the molecular 

characterization of CTC. 

Material and methods. For analysis of single cells MCF-7 cells were spiked 

into blood of healthy donors or 7.5 ml of blood obtained by metastatic 

breast cancer patients was used. Patients’ blood was collected in 

EDTA tubes (Monovette, Sarstedt) and CTC were either enriched using 

a Percoll density gradient method or processing the blood samples with 

the CellSearch® Profile Kit (Veridex, LLC). Single cell deposition happened 

in 1×PBS after staining against epithelial cell-specific markers 

(EpCAM, MUC1; Beckman Coulter) by cell sorting (FACSAria, BD) or 

micromanipulation onto the reaction sites of an AmpliGrid slide (Beckman 

Coulter). Multiplex-RT-PCR was performed using the Single Cell 

One-Step RT-PCR Kit and primers for β2-microglobulin, calmodulin, 

GAPDH, EpCAM, CK19 and Muc1 on the AmpliSpeed cycler (Beckman 

Coulter). Products were analysed with the Agilent DNA 1000 Kit 

and the Agilent 2100 Analyzer. 

Results. Single epithelial cells were successfully deposited on the reaction 

sites of AmpliGrid slides with both cell sorting and micromanipulation. 

For confirmation and in order to correlate RT-PCR results with template 

presence or absence, a visual quality control using a microscope 

was performed. Furthermore, single-plex one-step RT-PCRs for three 

housekeeping genes (β2-microglobulin, calmodulin and GAPDH) and 

three epithelial markers (EpCAM, Muc1 and cytokeratin-19), as well as 

the combination of all markers in a 6-Plex-RT-PCR could be achieved 

on single cells. 

Conclusion. A One-Step Multiplex-RT-PCR using the AmpliGrid system 

can be applied for parallel analysis of multiple transcripts from single 

epithelial cells isolated from peripheral blood of breast cancer patients. 

0495 

Combined transcriptome and methylation analyses to identify 

new targets of cisplatin resistance in ovarian cancer patients 

*T . Fehm1 , J . Hoffmann2 , M . Walter2 , A . Staebler3 , S . Poths2 , O . Riess2 , D . Wallwiener1 

, M . Bonin2 , *H . Neubauer1 1Eberhard-Karls-University Tübingen, Department of Obstetrics and 

Gynecology, Tübingen, Deutschland, 2Eberhard-Karls-University Tübingen, 

Microarray Facility, Tübingen, Deutschland, 3Eberhard-Karls-University Tübingen, Institute for Pathology, Tübingen, Deutschland 

Objectives. The standard therapy for Ovarian cancer consists of aggressive 

cytoreductive surgery followed by platinum-based chemotherapy. 

However, intrinsic or acquired platinum resistance in the majority of 

patients leads to high mortality rate. To gain new insights in resistance 

mechanisms and modified pathways, we performed combined wholegenome 

expression and methylation studies using Illumina BeadArrays. 

Material and methods. Eleven cryopreserved tissue samples from each 

platinum resistant and platinum sensitive ovarian carcinomas were selected. 

From consecutive tissue sections RNA and DNA was extracted 

and analysed for differences in gene expression and methylation pat-

terns by using Illumina BeadArray platforms. Results obtained were 

confirmed using qRT-PCR and pyrosequencing. 

Results. We assessed the DNA methylation profile of approx. 

27,000 CpG sites (associated with approx. 14,000 transcripts) and found 

613 differentially methylated promoter sites using M-value statistics. To 

investigate the relationship between DNA methylation status and gene 

expression, we measured levels of transcripts from the same set of genes 

in the same samples. After normalization and biostatistical analysis we 

detected 115 significantly differentially expressed transcripts with a fold 

change >1.6 and a p-value

Abstracts 

insufficient bioavailability when injected intraperitoneally or subcutaneously 

as a suspension in high concentration in in vivo tests. 

1 . O’Dwyer P, Stevenson J ., Johnson SW (1999) . In: Lippert B . (ed .), Cisplatin . Chemistry 

and Biochemistry of a Leading Anticancer Drug, WILEY-VCH, Weinheim, 

pp 31 Fluorinated [1,2-diarylethylenediamine]platinum(II) complexes 72 

2 . Reedijk J (1999) Chem Rev 99:2499–2510 

3 . Boulikas T, Vougiouka M (2003) Oncol Rep 10:1663 

4 . Spruß T, Bernhardt G, Schickaneder E, Schönenberger HJ (1991) Cancer Res 

Clin Oncol 117:435–443 

Seltene Tumoren 

0016 

The oral cancer knowledge of dentists and physicians in Schleswig-Holstein 

*K . Hertrampf1 , H .-J . Wenz2 , M . Koller3 , N . Arpe4 , J . Wiltfang1 1Universitätsklinikum Schleswig-Holstein, Campus Kiel, Klinik für MKG- 

Chirurgie, Kiel, Deutschland, 2Universtitätsklinikum Schleswig-Holstein, 

Campus Kiel, Klinik für Zahnärztliche Prothetik, Propädeutik und Werkstoffkunde, 

Kiel, Deutschland, 3Universitätsklinikum Regensburg, Zentrum 

für Klinische Studien, Regensburg, Deutschland, 4Universtitätsklinikum Schleswig-Holstein, Campus Kiel, Klinik für Strahlentherapie, Kiel, Deutschland 

Objectives. Oral cancer is a considerable health problem with more than 

10,000 new diagnosed cases each year in Germany. Comparable little is 

known about the knowledge of dentists and physicians on oral cancer 

with focus on diagnostic items. It was the aim of the project to evaluate 

the level and determinants of knowledge about diagnostic factors of oral 

cancer by means of a standardised questionnaire in the State of Schleswig-Holstein, 

Germany. 

Material and methods. A self-administered survey was mailed together 

with a business reply envelope to all dentists (n=2233) and the medical 

disciplines involved in oral cancer diagnostics (Otolaryngology, dermatology, 

internal Medicine, general medicine; n=2575) in Schleswig- 

Holstein. Three and six weeks after the initial mailing, a reminder was 

sent to all possible participants. The survey was composed of 41 items. 

Descriptive statistics of the sample and responses to the questionnaire 

were reported by means of counts and percentages. 

Results. 306 questionnaires of the dentists (14%) and 408 questionnaires 

of the physicians (17%) were returned and analysed. Around 90% 

and more of the respondents knew that early detection improves the 

5-year survival rate. Almost two-thirds of all respondents correctly recognized 

that the floor of the mouth is one of two most commonly affected 

sites. The knowledge that the tongue is the second of the two most 

commonly affected sites was recognized 45–70%. Twenty-one percent to 

60% of the respondents knew that early cancer lesions usually appear 

as small, painless red areas. However, only 27–57% (except dermatology 

with 82%) correctly recognized that patients in early stage of oral cancer 

are asymptomatic. The oral cancer knowledge with regard to signs and 

symptoms showed interesting differences among the different responder 

groups. 

Conclusions. Appropriate knowledge about signs and symptoms of oral 

cancer is not only essential for dentists but also for several medical disciplines. 

Although the knowledge of different diagnostic items was almost 

sufficient, the responders were surprisingly unaware about the fact 

that the early stage of oral cancer is almost symptom-free and discrete 

in appearance. These results underline the development and implementation 

of specific advanced educational programmes for dentists and 

the several medical disciplines. 


0019 

Die Rhinobasisrekonstruktion durch vital-autologen lokalen 

sowie distalen Gewebetransfer 

*T . Hoffmann1 , P . Schuler1 , O . Müller2 , R . Hierner1 , M . Wagenmann3 , G . Lehnerdt1 

, U . Sure2 , S . Lang1 , D . Hänggi4 , I .E . Sandalcioglu2 1Universitätsklinik Essen, Hals-Nasen-Ohrenklinik, Essen, Deutschland, 

2 3 Universitätsklinik Essen, Neurochirurgie, Essen, Deutschland, Universitätsklinik 

Düsseldorf, HNO, Düsseldorf, Deutschland, 4Universitätsklinik Düsseldorf, Neurochirurgie, Düsseldorf, Deutschland 

Die nach Tumorchirurgie oder Trauma eröffnete Rhinobasis bedarf 

eines suffizienten Abschlusses um Rhinoliquorrhoe u./o. Hirngewebeprolaps 

zu verhindern. Das alleinige Einbringen von avitalem autologen, 

allogenem sowie xenogenem Material ist oft unzureichend und 

verlangt unter Umständen nach einer zuverlässigen Versorgung mit 

Hilfe eines vaskularisierten lokalen oder distalen Gewebetransfers. 

Rhinobasisdefekte von insgesamt 41 Patienten wurden interdisziplinär 

mit Hilfe von autologem Gewebetransfer gedeckt. Kleinere, nach endoskopisch 

endonasaler Chirurgie entstandene Defekte (n=23, hierunter 

Meningeome, spontane Liquorfisteln, Chordom, Chondroblastom, Metastase, 

nasale Fistel) wurden durch lokale gefäßgestielte (A. sphenopalatina) 

Schleimhautlappen aus der unteren Muschel (3) oder dem Septum 

(20) gedeckt. Bei größeren Defekten [n=14, hierunter Malignome 

(10), Meningoencephalozelen (2), Aneurysmatische Knochenzyste (1)] 

wurde die Rhinobasis mit Hilfe eines Calvarian-Split und eines Galea- 

Periost-Lappens in einer „Sandwich-Technik“ verschlossen. In einem 

Fall wurde der Defekt mit Hilfe eines M. temporalis Lappens gedeckt. 

In 4 Fällen (Trauma, Adenokarzinom) wurden nach mehrfachen, auswärts 

durchgeführten und frustran verlaufenen Deckungsversuchen 

die Rhinobasis mit einem freien, gefäßanastomisierten und desepithelisierten 

Unterarmlappen revidiert. Alle 41 Fälle wurden in Hinblick auf 

die Prävention/Behandlung einer Rhinoliquorrhoe und/oder Hirngewebeprolaps 

erfolgreich abgeschlossen. Die suffiziente Revision komplexer 

Rhinobasisdefekte gelingt unter Verwendung eines autologen 

lokalen und im Extremfall auch distalen Gewebetransfers und bedarf 

einer engen Kooperation zwischen den in der Kopf-Hals-Chirurgie tätigen 

Fachdisziplinen. 

0023 

Vollhauttransplantate für die temporäre und definitive Defektabdeckung 

im Rahmen der mikroskopisch kontrollierten Chirurgie 

bei bösartigen Geschwülsten der Gesichtshaut 

*L . Tischendorf1 1Praxis MKG-Chirurgie, Praxis, Halle, Deutschland 

Einleitung. Die tumorfreie Absetzungsgrenze (R0-Resektion) ist der 

prognostisch bedeutsamste Faktor für den Behandlungserfolg bei bösartigen 

Geschwülsten de Gesichtshaut. Ihre Bewertung ist mit hoher 

Präzision mit den Methoden der mikroskopisch kontrollierten Chirurgie 

möglich- allerdings nur mittels definitiver formalinfixierter 

histologischer Schnitte vor allem im basalen Bereich. In den aktuellen 

Leitlinien wird folglich eine verzögerte Defektabdeckung empfohlen – 

nämlich dann, wenn Gewissheit darüber besteht, dass alle Schnittränder 

tumorfrei sind. Eine verzögerte also zweizeitige Defektabdeckung 

ist eine langwierige und für den Patienten belastende Prozedur. Um 

diesem aus dem Weg zu gehen rekonstruieren wir bis zu mittelgroße 

Defekte sofort mit freien Vollhauttransplantaten. Dies erlaubt eine einfache 

Revision im Fall einer nachgewiesenen R1-Resektion. Wenn das 

ästhetische Ergebnis befriedigt, handelt es sich dabei um die definitive 

Rekonstruktion. Andernfalls kann eine Korrektur zum Zeitpunkt der 

Wahl erfolgen. 

Material und Methode. Von September 1993 bis zum April 2010 wurden 

nach mikroskopisch kontrollierter Exzision von 265 bösartigen Tumoren 

der Gesichtshaut die Defekte durch infraklavikuläre Vollhauttransplantate 

versorgt.

Resultate. Die ursprünglich temporäre Defektabdeckung mit den infraklavikulären 

Vollhauttransplantaten nach Resektionen der bösartigen 

Tumoren der Gesichthaut führt in 262 von 265 (99%) Fällen zu derart 

guten ästhetischen Ergebnissen, dass die Patienten eine mögliche 

sekundäre Korrektur durch Nahlappen nicht mehr wünschten. Nur in 

wenigen Fällen war eine sekundäre Korrektur notwendig. In den sehr 

seltenen Fällen einer primären R1-Resektion (4 Fälle = 1,5%) konnten wir 

problemlos eine dreidimensional orientierte Nachexzision ohne Notwendigkeit 

einer aufwendigen sekundären plastischen Rekonstruktion 

ausführen. Alle Operationen erfolgten unter ambulanten Bedingungen. 

Schlussfolgerung. Die Anwendung von infraklavikulären Vollhautransplantaten 

zum sofortigen Defektverschluss nach Entfernung bösartigen 

Geschwülste der Gesichtshaut erlaubt bei mittlerer Ausdehnung eine 

onkologisch sichere, in ästhetischer Hinsicht in der überwiegenden 

Anzahl der Fälle befriedigende und zeitsparende operative Behandlung 

unter ambulanten Bedingungen ohne die Nachteile einer verzögerten 

chirurgischen Rekonstruktion. 

0025 

Expression of activated EGF-receptor and k-ras mutations in 

carcinomas of the salivary glands 

T . Schneider1 , A . Strehl2 , A . Rosenwald2 , A . Kübler1 , *U . Müller-Richter1 1Universitätsklinikum Würzburg, Mund-, Kiefer- und Plastische Gesichtschirurgie, 

Würzburg, Deutschland, 2Universität Würzburg, Institut für 

Pathologie, Würzburg, Deutschland 

Background. The activated EGF-receptor has been proved as a prognostic 

as a prognostic aid and therapeutic target in many different tumours. 

In this context k-ras plays a crucial role. Autonomous activation of the 

EGFR pathway by a mutated k-ras would preclude treatments with 

EGFR-antibodies. Aim of this study is to analyze EGF-receptor and kras 

status in salivary gland carcinomas. 

Methods. 43 patients with carcinomas of the salivary glands were selected 

(24 males, 19 females). The chosen tumours included 23 adenoidcystic 

carcinomas, 17 mucoepidermoid carcinomas and 3 adenocarcinomas 

not otherwise specified (NOS). First, a molecular examination 

of mutations by PCR and sequencing of the codons 12 and 13 of the k-ras 

gene were performed. Second, the activated EGF-receptor was detected 

by immunohistochemistry. The results were statistically correlated with 

clinical parameters. 

Results. None of the tested carcinomas showed mutations in codon 12 or 

13 of the k-ras gene. The activated EGF-receptor was present in 79% of 

the tumours. Statistically significant correlations (p>0.05) were found 

for age and lymph node metastasis. A correlation of tumour stage and 

EGFR-status was not found. 

Conclusions. As we did not find any k-ras mutation in the tested tumours 

we can rule out an important role of it in salivary gland tumours. 

The percentage of activated EGF-receptor was high. Unfortunately this 

finding did not correspond to many clinical parameters. Additionally, 

the high percentage of activated EGF-receptor seemingly facilitates a 

treatment with EGFR-antibodies. This is in contradiction with clinical 

results that did not yield any good results in patients treated with such 

target drugs. Therefore, the role of the activated EGF-receptor in salivary 

gland tumours remains unclear. 

0029 

An open-label multicenter phase II study of Imatinib mesylate 

(Glivecâ) treatment of patients with malignant peripheral nerve 

sheath tumors 

*J . Panse1 , V .-F . von Mautner2 , P . Reichardt3 , T . Brümmendorf1 , M . de Wit4 1 2 Universitätsklinukum Aachen, Aachen, Deutschland, Universitätsklinikum, 

Hamburg Eppendorf, Deutschland, 3Helios Klinikum, Bad Saarow, 

Deutschland, 4Vivantes Klinikum Neukölln, Berlin, Deutschland 

Introduction. Malignant peripheral nerve sheath tumors (MPNSTs) are 

malignancies with poor prognosis, arising sporadically or in patients 

with neurofibromatosis type 1 (NF1). In adult NF1 patients MPNSTs are 

the main cause for mortality and therapeutic options are unsatisfying. 

The only curative treatment is complete surgical resection with a wide 

tumor free margin. MPNSTs exhibit individual variability in chemotherapeutic 

sensitivity. Radiotherapy and chemotherapy rarely result in 

local control of the MPNST; they do not have major impact on survival. 

Immunohistochemistry showed that PDGFRalpha is highly expressed 

in the majority of MPNSTs, while few cases showed focal c-Kit expression. 

Interestingly, MPNSTs with PDGFRA amplification generally 

also showed KIT amplification. In-vitro Imatinib treatment (10 µM) of 

a PDGFRalpha expressing MPNST cell cultures resulted in more than 

50% reduced cell proliferation after 48 hours, indicating that MPNST 

treatment with Imatinib warrants further investigation. 

Methods. A multicenter, single-stage, open label phase II trial was conducted 

to determine the efficacy and safety of Imatinib in patients with 

local recurrent or metastatic MPNST who already had undergone surgery 

and had no further surgical treatment options. Patients (pts.) were 

included in two subgroups based on the assumption that pts. with NF1 

associated or sporadic MPNST might respond differently to treatment. 

Each subgroup was planned to include 16 patients. The primary objective 

was the number of patients showing response defined as at least once 

stable disease (SD) within 36 weeks according to RECIST after treatment 

with 400 mg Imatinib daily. 

Results. The STI571BDE57 trial was started in 2006. While 32 patients in 

total were planned to be included only 10 patients have been recruited (4 

male and 6 female; median age 34; range 20–51) until April2009; based 

on the slow recruitment rate the study was terminate d in 2009. Six of 

the ten patients enrolled in the study showed at least once stable disease 

during the course of the study, with a 95% confidence interval of (29.6– 

90.4). Only one patient showed stable disease after 24 weeks. All patients 

discontinued treatment due to unsatisfactory results. Imatinib was safe 

and well tolerated; however, one patient experienced a facial paresis. 

Conclusion. While protein expression in MPNST suggested a potential 

treatment benefit in selected MPNST patients, our results did not show 

a significant clinical impact. However, given the low toxicity profile of 

STI571BDE57 and the fact that 6/10 patients showed disease stabilization, 

imatinib therapy may still be considered in selected patients in addition 

to other treatment modalities or in combination with therapies 

targeting other over expressed proteins such as somatostatin. 

0038 

The role of imaging in modern cancer research 

*B . Walter1 1LMU München, Institut für klinische Radiologie in der Chirurgischen Klinik, 


Background. The modern pharmaceutical research mainly bases on the 

development of substrates triggering special tissue structures by causing 

certain effects. The evaluation of efficacy and innocuousness occur 

in several phases. Only a few active ingredients are finally suitable for 

the marketing approval. Highest priority therefore has the establishment 

of new procedures to improve risk assessment and predictability. 

Material. The integration of functional imaging in the early phases of 

pharmaceutical development enables the application of radio-labelled 


107

Abstracts 

agents to show localization and distribution pattern of pharmaceutical 

effects by computer-assisted analyses as well as the assessment of the 

saturation levels of the target receptors 

Results. The calculation of distribution and concentration of the substances 

used in correlation with measured metabolites and proper clinical 

parameters results into a standardized profile of dose and efficacy. 

Risks and benefits can be more objectively evaluated so that the number 

of probands and costs can be reduced significantly. 

Conclusions. Until now preferentially nuclear medicine diagnostics 

have been applied. Other radiologic procedures with tracer technique 

are necessary to be established. The future way of pharmaceutical research 

continues to rest upon antibody applications and on concepts 

named “personalized medicine”. The latter comprises recent therapeutic 

approaches by which individual cells are extracorporally treated and 

reinfused. Illustrations in vivo of efficacy by imaging technique would 

support these developments in marketing approval, and therapy-monitoring. 

0056 

Specific activity of substanceP radiolabeled with bismuth-213 

plays a critical role in targeted alpha-therapy in the treatment of 

glioblastoma 

*C . Friesen1 , I . Hormann1 , M . Roscher1 , O . Leib2 , S . Marx2 , J . Moreno2 , E . Miltner1 

1 2 Institute of Legal Medicine, University Ulm, Ulm, Deutschland, Isotope 

Technologies Garching GmbH (ITG), Garching, Deutschland 

Aim. Targeted alpha-therapy using substanceP radiolabeled with the 

alpha-particle bismuth-213 ([Bi-213]SubP) is a promising treatment approach 

for glioblastoma. Different specific activities are used during 

radioimmunotherapy of high risk leukemia and lymphoma. However, 

the effect on cell killing using different specific activities at radiopeptidetherapy 

was not examined. In the present study we analyzed the effect 

of different specific activities (MBq/µg substanceP) on cell death induction 

and activation of apoptosis pathways in glioblastoma cells using 

[Bi-213]SubP. 

Methods. The glioblastoma cell line T98G was treated with 2000, 1000 

and 500 kBq/mL of [Bi-213]SubP using different specific activities (40, 

20 and 5 MBq/µg substanceP). 24, 48, 72 and 96 h after treatment induction 

of cell death, induction of apoptosis, cell cycle, caspase activation 

and activation of apoptosis pathways were determined using flowcytometry 

and Western Blot analyses. 

Results. Our results demonstrate that specific activities of substanceP 

radiolabeled with Bi-213 play a critical role in induction of cell death, 

apoptosis and in activation of deficient apoptosis pathways in glioblastoma 

cells. The efficacy of cell death induction depends on both dose 

and specific activity. At a specific activity of 40 MBq/µg substanceP, it 

was possible to induce high rates of apoptotic cell death in glioblastoma 

cells also at a very low activity concentration (500 kBq/mL) of [Bi-213] 

SubP after 96 h. In addition, decreasing the specific activity of [Bi-213] 

SubP to 5 MBq/µg substanceP only a low percentage of glioblastoma 

cells could be killed. Similar results were also found after examination 

of the effect of different specific activities of [Bi-213]SubP in activation 

of apoptosis pathway at comparable concentrations. Only at a specific 

activity of 40 MBq/µg and a specific activity of 20 MBq/µg substanceP 

a strong activation of caspases and PARP cleavage were found. Reactivation 

of deficient apoptosis pathway was strongly decreased at lower 

specific activities. 

Conclusions. Our findings suggest that not only the activity concentrations 

of substanceP radiolabeled with Bi-213 play an important role in killing 

glioblastoma cells and in activation of apoptosis pathways but also 

the specific activities meaning the amount of radionuclides per peptide 

are crucial. These findings have important implications for glioblastoma 

therapies using radiolabeled substanceP with Bi-213 during targeted 

alpha-therapy. 


0057 

Deficient apoptosis induction and caspases activation can be 

reversed in glioblastoma-initiating stem cells as well as primary 

human glioblastoma cells by targeted alpha-therapy using [Bi- 

213]SubstanceP 

*C . Friesen1 , I . Hormann1 , M . Roscher1 , J . Moreno2 , S . Marx2 , O . Leib2 , L . Nonnenmacher3 

, K .-M . Debatin3 , E . Miltner1 1 2 Institute of Legal Medicine, University Ulm, Ulm, Deutschland, Isotope 

Technologies Garching GmbH (ITG), Garching, Deutschland, 3Children‘s Hospital, University Ulm, Ulm, Deutschland 

Aim. Glioblastomas are the most malignant type of brain tumors. Because 

glioblastoma and in particular the high tumorigenic glioblastoma-initiating-stem 

cells are resistant to conventional therapies, 

glioblastomas are untreatable. Novel strategies are needed to improve 

therapeutic success. Targeted alpha-therapy using the alpha-emitter Bi- 

213 seems to be a promising approach for killing tumor cells. Glioblastomas 

and glioblastoma-initiating-stem cells overexpress neurokinin-1receptors, 

the binding site for Bi-213 labelled substanceP ([Bi-213]SubP). 

In our studies, we tested the cell death inducing potential of [Bi-213] 

SubP and clarified the molecular pathways of apoptosis induction by 

[Bi-213]SubP in primary glioblastoma cells and glioblastoma-initiating 

stem cells. 

Materials and methods. Primary human glioblastoma cells and glioblastoma-initiating-stem 

cells were treated with a range of activities (3000– 

500 kBq/mL) [Bi-213]SubP. At different time points after irradiation cell 

death induction was measured by flowcytometry. Involvement of apoptotic 

pathways was assessed by Western-Blot-analyses. 

Results. We found that [Bi-213]SubP induced a strong apoptotic cell 

death in primary glioblastoma cells as well as in the highly resistant 

glioblastoma-initiating-stem cells overexpressing neurokinin-1-receptors. 

In the highly resistant glioblastoma-initiating-stem cells, [Bi-213] 

SubP reversed deficient activation of caspases, cleavage of PARP and 

restored activation of the apoptotic mitochondrial pathway. In addition, 

downregulation of the death inhibitory protein Bcl-xL and the strong 

caspase inhibitor XIAP, both contributing to glioblastomas’ resistance, 

was provoked by [Bi-213]SubP in the highly resistant glioblastoma-initiating-stem 

cells comparable to primary glioblastoma cells. 

Conclusions. Our findings demonstrate that [Bi-213]SubP is a promising 

strategy to break radio-and chemoresistance in primary glioblastoma 

cells and to kill the extremely resistant glioblastoma-initiating-stem 

cells efficiently by reversing deficient activation of caspases and downregulation 

of XIAP and Bcl-xL. [Bi-213]SubP seems to improve therapeutic 

success in glioblastoma by targeting and killing glioblastomainitiating 

stem cells. 

Supported by Deutsche Forschungsgemeinschaft (DFG) . 

0062 

The prognostic value of molecules of the HIF 1 alpha – and 

TGF beta 1 pathway crosstalk in patients with oral squamous cell 

carcinoma 

*C .K . Müller1 , M . Mtsariashvilli1 , S . Schultze-Mosgau1 1Universitätsklinikum Jena, Klinik und Poliklinik für Mund-, Kiefer- und Gesichtschirurgie/Plastische 

Chirurgie, Jena, Deutschland 

Background and aim. Despite improvements in diagnosis and treatment 

of patients with oral squamous cell carcinoma survival rates have not 

changed significantly over the past years. Molecular markers might 

provide an additional tool for evaluation of the patients’ prognosis. Hypoxia 

Inducible Factor (HIF) 1 alpha as well as Transforming Growth 

Factor (TGF) beta 1 were investigated extensively as prognostic markers 

with conflicting results. Taking this into account the present study was 

conducted to investigate a correlation between the activity of markers 

at the HIF 1 alpha/ TGF beta 1 pathway crosstalk and tumor prognosis.

Materials and methods. Biopsies from the tumor margin were harvested 

in 50 patients with histologically confirmed squamous cell carcinoma 

of the oral cavity at the time of tumor resection. Biopsies were subjected 

to immunohistochemical staining for TGF beta 1, HIF 1 alpha as well as 

the transcription factor Sp1. Staining intensity was evaluated histomorphometrically. 

A multivariate statistical approach was chosen to verify 

the correlation between marker expression and disease free survival. 

Results. Median disease free survival was found to be 31 months. HIF1 

alpha + (p=0.023), TGFbeta1 + (p=0,019) as well as Sp1 + (p=0.022) tumor 

patients showed significantly reduced disease free survival in the 

bivariate testing. Using the multivariate approach only combined HIF1 

alpha+, TGF beta 1+ and Sp1+ tumor patients showed significantly reduced 

disease free survival (p=0.043). 

Conclusion. Patients with combined HIF 1 alpha+, TGF beta 1+ as well 

as Sp1+ tumors showed significantly reduced disease free survival in 

the investigated patients collective. Investigation of prognostic markers 

located at molecular pathway crosstalks might improve sensitivity and 

specifity of prognostic markers. 

0063 

D,L-Methadone sensitizes glioblastoma-initiating stem cells and 

primary glioblastoma cells for doxorubicin treatment ex vivo 

*C . Friesen1 , I . Hormann1 , M . Roscher1 , L . Nonnenmacher2 , K .-M . Debatin2 , 

E . Miltner1 1 2 Institute of Legal Medicine, University Ulm, Ulm, Deutschland, Childrens’ 

Hospital, University Ulm, Ulm, Deutschland 

Aim. Glioblastomas are highly malignant primary brain tumors with one 

of the worst survival rates among all human cancers, because glioblastoma 

cells are extremely resistant to conventional therapies. After surgery 

or radiotherapy glioblastomas recur in focal masses. This recurrence is 

linked to glioblastoma-initiating stem cells, a high tumorigenic subpopulation, 

which could not be killed. Thus, novel therapeutic strategies 

are needed to break resistance by targeting glioblastoma cells as well as 

glioblastoma-initiating stem. The synthetic opioid D,L-methadone is effectively 

used in substitution and pain therapy and it can kill leukemia 

cells. In our studies, we analyzed the effect of D,L-methadone alone and 

D,L-methadone in addition to doxorubicin on glioblastoma-initiating 

stem cells in comparison to primary human glioblastoma cells. 

Materials and methods. Primary glioblastoma cells isolated from human 

specimen and glioblastoma-initiating-stem cells were treated with 

different therapeutic concentrations of D,L-methadone alone or in addition 

to therapeutic concentrations of doxorubicin using as Caelyx® 

in glioblastoma treatment. After different time points, cell death was 

measured by flowcytometry and activation of apoptosis pathways was 

analyzed by Western Blot analyses. 

Results. We found that D,L-methadone sensitizes primary glioblastoma 

cells as well as the highly resistant glioblastoma-initiating stem cells 

for doxorubicin-induced cell death and reverses deficient activation of 

apoptosis pathways. Therapeutic concentrations of D,L-methadone in 

addition to doxorubicin induced a strong apoptotic cell death in primary 

glioblastoma cells as well as in the extremely resistant glioblastoma-initiating 

stem cells. In addition, D,L-methadone reversed deficient 

caspases activation and cleavage of PARP by doxorubicin. The strong 

inhibitor of apoptosis XIAP, playing a crucial role in glioblastomas’ resistance 

was inactivated by cotreatment with D,L-methadone and doxorubicin. 

Futhermore, D,L-methadone provoked downregulation of the 

antiapoptotic protein Bcl-xL by doxorubicin in primary glioblastoma 

cells and glioblastoma-initiating stem cells. 

Conclusions. Our findings suggest that D,L-methadone in addition to 

doxorubicin kills the highly resistant glioblastoma-initiating stem cells 

similar to the primary glioblastoma cell. D,L-methadone seems to be a 

promising strategy to enhance doxorubicin-sensitivity in glioblastoma 

therapy. 

Supported by Deutsche Krebshilfe . 

0068 

Group-specific therapy comparison of the quality of life in patients 

with head and neck cancer 

*C . Zaldivar Wither1 , K . Bikowski2 , K . Freier1 , C . Hofele1 , J . Hoffmann1 1Universitätsklinik Heidelberg, MKG-Chirurgie, Heidelberg, Deutschland, 

2Nationales Centrum für Tumorerkrankungen Heidelberg, Medizinische 

Onkologie, Heidelberg, Deutschland 

Background. Head and neck cancer treatment is associated with loss of 

quality of life independent from treatment modality. We investigated 

the influence of treatment surgical vs. conservative treatment (RC/Neoadjuvant/Adjuvant) 

in regard to quality of life of patients during different 

stages of therapy. 

Method. In an observational study, 57 patients of the Clinic of Oral and 

Maxillofacial Surgery Heidelberg of all stages were enrolled (2007– 

2010). We evaluated the quality of life before treatment, immediately 

after the primary therapy, after three, six and twelve months. The survey 

of quality of life was established by the EORTC QLQ-C30 and EORTC 

H&N35. 

Results. “Global Health Status improved in both treatment arms 

(p=0.038) from 3th month to one year after treatment. Physical functioning” 

was 3 months after primary treatment lower in the conservative 

treatment group, but this changed completely after 12 months, the value 

has deteriorated significantly in the surgical arm. Regarding the Pain, 

surgical patients suffer significantly more after 3 months (34.4–28.07) 

but from the 3rd month on they suffer less than other forms of therapy 

(p=0.011). After 12 months we evaluated better quality of life in Swallowing, 

Speech and Felt ill in patients after surgery (p=0.011, p=0.021, 

p=0.003 respectively). We found a pronounced deterioration in mouth 

opening and dry mouth after conservative therapy, after 6 (p=0.007) 

and 3 months (p=0.04). 

Conclusions. The aspect of quality of life gains increasing attention in 

addition to the quantity of life in the discussion about the treatment 

of tumors in the head and neck region. Patients undergoing a primary 

surgery suffer considerably loss-of-function after 6 months, but have 

superior coping in the study period than other forms of therapy. In order 

to measure long-term results and to exclude acute adverse effects, 

a study in the course of time points after 12 or 18 months is reasonable. 

0069 

TGFbeta activates NF-kappaB signaling through a TAK1-dependent 

mechanism in head and neck cancer 

*C . Freudlsperger1,2 , Y . Bian2 , J . Hoffmann1 , Z . Chen2 , C . Van Waes2 1Universitätsklinikum Heidelberg, Mund- . Kiefer- und Gesichtschirurgie, 

Heidelberg, Deutschland, 2NIH, NIDCD, Bethesda, USA 

TGFbeta signaling in epithelial malignancies, including head and 

neck squamous cell carcinoma (HNSCC), is complex. Inactivation of 

TGFbeta signaling promotes the de novo development of epithelial 

cancer, while the activation of attenuated but residual TGFbeta signaling 

in established cancer clearly favors the progression to a more invasive 

and metastatic phenotype. The mechanism responsible for these 

double-edged effects of TGFbeta signaling in oncogenesis is less well 

characterized. Since aberrant activation of transcription factor Nuclear 

Factor-kappaB (NF-kappaB) promotes the malignant phenotype 

similar to TGFbeta mediated effects in late staged tumors, we hypothesized 

that TGFbeta signaling in tumor promotion could be mediated 

through the cross-activation of NF-kappaB pathway. Here, we show 

that TGFbeta-1 treatment induced phosphorylation and activation 

of IKK, leading to phosphorylation of IkappaBalpha, the inhibitor of 

NF-kappaB, and subsequential NF-kappaB activation in HNSCC lines. 

TGFbeta-1 and TNFalpha induced NF-kappaB activation was 

mediated through TGFbeta-activated kinase 1 (TAK1), since knocking 

down of TAK1 using siRNA decreased both TGFbeta-1 and TNFalpha 

induced NF-kappaB-dependent reporter gene activity. Furthermore, 


109

Abstracts 

TAK1 knockdown decreased degradation of IkappaBalpha and promoted 

nuclear translocation and binding activity of the transactivating 

NF-kappaB subunit p65 (RELA). Consequently, transcription of 

NF-kappaB downstream genes was attenuated. Conversely, transient 

overexpression of TAK1 increased basal, TGFbeta-1 and TNFalpha 

induced NF-kappaB reporter gene activity. Futhermore, Celastrol, an 

herb extract from Tripterygium wilfordii used in the traditional Chinese 

medicine for decades because of its immunosuppressive properties, 

decreased TGFbeta-1 induced phosphorylation of TAK1 and p65, and 

suppressed basal, TGFbeta-1 and TNFalpha induced NF-kappaB reporter 

gene activity. In addition, Celastrol reduced cell growth as measured 

by XTT assay (IC50=1.2–1.3 µM) and increased sub-G0 DNA fragmentation 

indicating induction of apoptosis. 

In conclusion, we identified a cross-talk between TGFbeta and NF-kappaB 

pathways, where TGFb signaling leads to NF-kappaB activation 

through a sequential activation of TAK1 and IKK activities, and promotes 

malignant phenotype of HNSCC. With Celastrol being a potent suppressor 

of TAK1 mediated NF-kappaB activation; we present a potential 

therapeutic strategy targeting this alternative TGFbeta pathway. 

0087 

The versatility of the antero-lateral thigh flap (ALT) in the reconstruction 

of oral and maxillofacial defects after ablative tumor 

surgery 

*K . Freier1 , J . Bodem1 , M . Engel1 , J . Hoffmann1 1Universitätsklinikum Heidelberg, Klinik und Poliklinik für Mund-, Kieferund 

Gesichtschirurgie, Heidelberg, Deutschland 

The anterolateral thigh flap (ALT) is pedicled on septocutaneous or musculocutaneous 

perforators of the descending branch of the lateral circumflex 

femoral artery. Due to its extraordinary versatility and low donor 

site morbidity it has gained increasing popularity in the treatment 

of oral and maxillo-facial defects after ablative tumor surgery in the last 

decade. The anterolateral thigh flap allows the generation of subcutaneous, 

fasciocutaneous, myocutaneous, or adipofascial flap, which has 

made it to a work-horse in reconstructive maxillo-facial surgery. The 

aim of the present retrospective analyses of a collection of n=135 cases, 

which were treated in two highly specialized institutions for craniomaxillo-facial 

surgery, was to illustrate the intriguing applications of 

the ALT flap as well as the clinical robustness and excellent functional 

outcome of this approach. The overall flap failure rate was low in this 

patient series (13/135) and comparable to other free flaps utilized in the 

head and neck area like the radial forearm flap. It was successfully used 

for reconstruction in case of oral cavity, oropharynx, external skin and 

maxilla defects after ablative tumor surgery. For more bulky reconstructions 

after total parotidectomy or skull base surgery, a muscle component 

was frequently harvested and transferred additionally. When 

a thinner, more pliable flap was required for the reconstruction of the 

floor of the mouth, suprafascial anterolateral thigh flaps were raised or 

the flaps were thinned after harvesting. In conclusion, the anterolateral 

thigh flap is a highly versatile and reliable flap for use in the reconstruction 

of various soft tissue defects of the head and neck area. This flap 

has gained great popularity given its versatility, ability for a two-team 

approach, and minimal donor site morbidity. 


0112 

The determination of urokinase plasminogen activator (uPA) and 

plasminogen activator inhibitor 1 (PAI-1) based on immunohistochemistry 

and semiquantitative image analysis represent a 

potential alternative to the quantitative ELISA method 

*D .S . Lang1 , U . Heilenkötter2 , W . Schumm3 , B . Lie4 , O . Behrens5 , R . Simon6 , 

E . Vollmer1 , T . Goldmann1 1Forschungszentrum Borstel, Klin . & Exp . Pathologie, Borstel, Deutschland, 

2Klinikum Itzehoe, Frauenklinik, Itzehoe, Deutschland, 3Krankenhaus Rendsburg, Pathologie, Rendsburg, Deutschland, 4Paracelsus Klinik Henstedt-Ulzburg, 

Frauenklinik, Henstedt-Ulzburg, Deutschland, 5Krankenhaus Rendsburg, Frauenklinik, Rendsburg, Deutschland, 6UKE HH-Eppendorf, 

Pathologie, Hamburg, Deutschland 

Aim. During the last few years, the tumor associated proteolytic factors 

urokinase Plasminogen-Activator (uPA) und plasminogen activator inhibitor 

1 (PAI-1) have gained clinical significance as invasion markers 

with both predictive and prognostic potential for individual treatment 

regimens of patients with breast cancer. A commercially available ELI- 

SA test as the only validated method for routine determination is laborious 

with the need of considerable amounts of fresh, shock frozen material. 

Therefore, this study was aimed at the establishment of a reliable 

alternative method suitable for routine procedures based on immunohistochemistry 

(IHC) and image analysis to overcome these drawbacks. 

Materials and methods. Tissue samples of primary ductal invasive breast 

cancer were treated with the alternative HOPE (Hepes-glutamic acid 

buffer mediated Organic solvent Protection Effect) fixation and paraffin-embedding 

method that does not require antigen retrieval. For enhanced 

comparability, the specimens were arranged on tissue microarrays 

(TMA) and stained with the respective specific primary antibodies 

(mouse anti-human uPA, DCS, Hamburg; goat anti-human PAI-1, Morphosys, 

Düsseldorf). The intensity of the cytoplasmic staining patterns 

of both proteins was measured at the tumor front by adapted semiquantitative 

image analyzing. 

Results. There was a statistically significant correlation between the semiquantitative 

data based on IHC for uPA and PAI-1 (uPA n=67; PAI-1 

n=27) and the corresponding quantitative ELISA results with p=0.011 

and p=0.029, respectively. Analogous to the ELISA method, a cut off 

value of >115 was obtained for the semiquantitative uPA results (χ2-test, 

two-tailed p=0.032). 

Conclusion. These first results strongly suggest that an optimized IHC 

protocol combined with a matched image analysis can provide a reliable 

alternative method for the commercial ELISA test. The validation 

of these experimental results will be achieved by incorporating the relevant 

clinical data of the corresponding patients examined in this ongoing 

study conducted in collaboration with the Holsteinisches Brustzentrum. 

0116 

Classification of human mucosa by in-vivo hyperspectral imaging 

*A . Gerstner1 , W . Laffers1 , R . Martin2 , B . Thies2 1Universitätsklinikum Bonn, Klinik für HNO-Heilkunde/Chirurgie, Bonn, 

Deutschland, 2Universität Marburg, Geographische Fakultät, Marburg, 

Deutschland 

Aim. To give proof of principle for the applicability of hyperspectral 

imaging for the analysis and classification of human mucosal surfaces 

in vivo. 

Material and methods. The larynx as a well-defined anatomical region 

was chosen as a prototypical surgical test area. The standard intra-operative 

setting for microlaryngoscopies was modified by using a polychromatic 

light source and a synchronous triggered monochromatic 

CCD-camera. Image stacks were analyzed by established software tools

for principal component analysis and unsupervised hyperspectral classification. 

Results. Sequential illumination of the same field of view by stepwise 

increasing wavelengths (390–680 nm, with 10 nm steps) yielded a hyperspectral 

image datacube of the mucosa. These lambda-image stacks 

could be analyzed and classified by commercially available software. In 

principal component analysis, images at 590–680 nm loaded most onto 

the first principal component. Typically, the first principal component 

contained 95% of the total information. Unsupervised hyperspectral 

classification clustered the data thus highlighting areas of altered mucosa. 

Conclusion. The technology of hyperspectral imaging can be applied to 

mucosal surfaces. This approach opens the way to analyze spectral characteristics 

of histologically different lesions in order to build up a spectral 

library and to allow non-touch classification of mucosal changes. 

0135 

Paraoxonase-2 (PON-2) expression in four head and neck 

carcinoma cell lines as potential predictor of resistance against 

radiotherapy – a pilot study 

*M . Krüger1 , M . Moergel1 , B . Al-Nawas1 , S . Horke2 1Universitätsmedizin Mainz, Klinik und Poliklinik für Mund- Kiefer- und 

Gesichtschirurgie, Mainz, Deutschland, 2Universitätsmedizin Mainz, Institut 

für Pharmakologie, Mainz, Deutschland 

Background. Apoptosis induction is a key mechanism of radio- and 

chemotherapy. Unfortunately, carcinomas often present altered protein 

expression which leads to upregulation of antiapoptotic proteins. 

It is known, that changes in redox-potential of tumors have critical 

influence on the intrinsic apoptotic pathway. Recent studies showed a 

protective effect against ROS (reactive oxygen species) for cells of the 

vascular system by Paraoxonase-2 (PON-2). In vascular cells PON-2 is 

mainly localized to nuclear lamina, endoplasmatic reticulum (ER) and 

mitochondria, with potential to prevent endothelial cells to undergo 

mitochondrial induced apoptosis. Since irradiation typically induces 

elevated levels of ROS and subsequent oxidative damage in nucleus, 

mitochondria and ER, elevated expression of PON-2 could also protect 

squamous cell carcinoma against oxidative stress. The present study is 

the first to examine expression pattern and potential functional influence 

of PON-2 in squamous cell carcinoma of the head and neck. 

Methods. Therefore, the basal PON-2 expression was determined in vitro 

in four squamous cell carcinoma cell lines by western blot analysis. 

Further visualisation of PON-2 utilized immunfluorescence staining. 

We also examined induction of PON-2 protein expression after singular 

radiation with 7 Gray 24, 48 and 72 hours after irradiation. Simultaneously, 

activity of caspase 3/7 was examined for apoptosis detection. 

Finally expression of PON-2 was tested in 5 patients with oral carcinoma 

within tumor tissue compared to normal mucosa. 

Results. The present study revealed regular expression of PON-2 in 

carcinoma of the head and neck region for the first time. Furthermore, 

the basal PON-2 expression pattern varies in different individuals. We 

found that irradiation leads to a general upregulation of PON-2 expression. 

Intriguingly, higher basal levels of PON-2 seem to protect cells 

against radiation-induced apoptosis. 

Discussion. The pilot study showed regular but variable expression of 

PON-2 in head and neck carcinoma. Furthermore, the in vitro model 

revealed elevated levels of PON-2 in head and neck carcinoma possibly 

protect the tumor against radiation-induced apoptosis. Thus, characterization 

of PON-2 expression might serve as clinical prediction marker 

for irradiation response and patient outcome. Since the distinct molecular 

mechanism remains still unclear, further experiments are needed 

to unveil the biological role of PON-2 in squamous cell carcinoma of the 

head and neck region. 

0137 

The migration of cultured glioblastoma cells is enhanced in 

response to radio therapy 

*T . Abeln1 , A . Kochanneck1 , K . Polz2 , C . Demirel2 , H . Bühler1 , I . Adamietz2 1Marienhospital, Klinikum der Ruhr-Universität Bochum, Institut für 

Molekulare Onkologie, Strahlenbiologie und Experimentelle Strahlentherapie, 

Herne, Deutschland, 2Marienhospital, Klinikum der Ruhr-Universität 

Bochum, Klinik für Strahlentherapie und Radio-Onkologie, Herne, 

Deutschland 

Background. Glioblastoma multiforme is a very aggressive tumor with 

an unfavorable prognosis for the patient. It is characterized by early recurrences 

frequently adjacent to the primary tumor. One reason, widely 

overlooked so far, might be based on the motility and migratory 

potential of the tumor cells. Low dose radiation in the penumbra of an 

irradiated volume might enhance the motility of the cells enabling them 

to escape the ionizing radiation. We, therefore, have analyzed whether 

or not low dose irradiation enhances the migration of cultivated glioblastoma 

cells. 

Methods. U343 or U87 cells were irradiated with 1.7 MeV electrons or 

with photons from a 15 MeV linear accelerator. For beta irradiation cells 

were placed as central spot in a culture dish on a 32P-activated foil and 

irradiated with 10×2 Gy. Subsequently the cells were stained with crystal 

violet to evaluate number and distance of satellite colonies. Cells irradiated 

with 4×2 Gy photons were placed in an environmental chamber 

and observed by time laps videography over a period of 5 days. The 

image stacks were analyzed with ImageJ as to distance and velocity of 

the cells. 

Results. In response to beta irradiation, the number of colonies increased 

from 33 (control) to 102 (irradiated). In addition the mean distance 

of the colonies to the central spot was significantly higher for the 

irradiated cells. The videographic analysis of the cells irradiated with 

photons revealed an increase in velocity that peaked at +80% 2 days after 

irradiation. 

Conclusion. The hypothesis of induced cellular migration in response 

to therapeutic irradiation is supported by our data. This effect might 

contribute to the poor prognosis of glioblastoma patients and has to be 

elucidated in further studies. There might be promising implications for 

new radio-chemotherapies e.g. with inhibitors of the focal adhesion kinase, 

a central point of cellular migration. 

0156 

A monocenter evaluation of the frequency of malignant tumours 

in the head and neck area 

*O . Thiele1 , R . Seeberger1 , J . Hoffmann1 , K . Freier1 1Universitätsklinik Heidelberg, Mund-, Kiefer-, Gesichtschirurgie, Heidelberg, 

Deutschland 

Introduction. In this study, we analysed how many patients were diagnosed 

with a malignant tumour in the head and neck area in our 

department of oral and maxillofacial surgery over a 20-year period 

(1989–2008). The aim of this study was to evaluate the distribution and 

frequency of different malignant diseases in our field. 

Results. 2277 patients with a malignant tumour were included. We found 

49 different histological diagnoses in this group. Overall, we found the 

squamous cell carcinoma to be the most frequent histological diagnosis 

(n=1903). Salivary gland tumours were the second entity (n=121), 

followed by basal cell carcinoma (n=117), sarcomas (n=62) and distant 

metastases to the head and neck (n=55), respectively. These subgroups 

consist of a broad variety of different histological entities. They must 

be very well defined by the pathologist because treatment strategies are 

different and depend upon the histological diagnosis. For example, the 

subgroup of the distant metastases consisted of 10 different histologies, 

the sarcoma subgroup consisted of 12 different histological entities. A 

“top 10 list” of the histological diagnoses would include squamous cell 


111

Abstracts 

carcinoma, basal cell carcinoma, adenoid cystic carcinoma, malignant 

lymphoma, malignant melanoma, mucoepidermoid carcinoma, adeno 

carcinoma, osteosarcoma, rhabdomyosarcoma, cup- syndrome and 

plasmocytoma (in descending order of frequency). 

Conclusion. These results could be the basis for a standardised oncological 

training of young doctors and surgeons. Especially for the rare tumours, 

an interdisciplinary treatment is often necessary. 

0162 

Functional characterization connects individual patients’ mutations 

in ataxia telangiectasia mutated (ATM) with dysfunction of 

specific DNA double-strand break repair signalling pathways 

M . Keimling1 , M . Volcic1 , A . Csernok1 , B . Wieland2 , T . Dörk2 , *L . Wiesmüller1 1 2 Universität Ulm, Universitätsfrauenklinik, Ulm, Deutschland, Medizinische 

Hochschule Hannover, Frauenklinik im Forschungszentrum, Hannover, 

Deutschland 

ATM has multiple functions in homologous recombination (HR) and 

non-homologous end-joining (NHEJ), which lead to conflicting data 

regarding its DNA-double-strand-break-repair (DSBR) functions in 

previous studies. To explore the effect of clinically relevant ATM mutations, 

we characterized DSBR between mutated EGFP genes and ATM 

kinase signalling in 9 lymphoblastoid cell lines (LCLs) derived from 

Ataxia telangiectasia (AT) patients with defined versus 3 control LCLs 

without ATM mutations. Our study revealed that the DSBR phenotype 

in AT cells is not uniform, but appears to depend on the mutation 

causing up to 32-fold increased or up to 3-fold decreased activities in 

particular pathways. Comparison with a further 10 LCLs mutated in 

downstream factors (BRCA1, BRCA2, Nibrin, Rad50, Chk2) showed 

that the most diametrically opposed DSBR patterns in AT cells phenocopied 

NBN/RAD50 or BRCA1 mutations. Importantly, re-expressing 

wild-type ATM reversed these defects by 2.3- to 3.5-fold. Our data suggest 

that ATM stimulates repair proteins like Nibrin, which execute HR, 

single-strand annealing (SSA), and NHEJ. Concomitantly ATM minimizes 

error-prone repair (SSA, NHEJ) through activation of surveillance 

factors like BRCA1. Since the outcome of the individual defect can be 

diametrically opposed, distinguishing repair patterns in patients with 

ATM mutations may also be relevant regarding therapeutic responses. 

0210 

Targeting of cancer-associated fibroblasts for integrative tumor 

therapy 

*C . Monasterio1 , D . Jäger1 , C . Renner2 , S . Bauer1 , V . Teichgräber1 1Nationales Centrum für Tumorerkrankungen, Medizinische Onkologie, 

Heidelberg, Deutschland, 2Universitätsspital Zürich, Klinik und Poliklinik für 

Onkologie, Zürich, Schweiz 

Solid tumors modulate their environment to keep non-malignant stromal 

cells in a tumor-promoting state. Recent studies have revealed that 

the extrinsic cues provided by these stromal cells are essential for tumor 

cells to even manifest a fully transformed phenotype, angiogenesis 

and metastasis. Delineation of these cues and their underlying cellular 

and molecular pathways offers the opportunity of a new era of integrative 

cancer therapy based on combinatorial drug regiments that act 

synergistically to destroy the tumors by targeting both, the intrinsic 

and extrinsic oncogenic pathways. The main cells in the stroma of epithelial 

derived tumors are cancer-associated fibroblasts (CAF) that are 

critical to tumorigenesis and angiogenesis. CAFs also supply the tumor 

cells with growth factors and extracellular matrix (ECM) degrading 

enzymes. They are thus essential for tumor initiation as well as tumor 

progression and metastasis, suggesting that they represent an ideal 

cellular target of an integrative tumor therapy. Fibroblast activation 

Protein (FAP) is a well defined marker, expressed at high levels at the 

cell surface of CAFs. FAP, a constitutively active serine peptidase with 


both dipeptidyl peptidase IV (DPIV) and collagenase activity, promotes 

malignant and invasive behaviour of epithelial cancers and stromal 

expression levels correlate with worse prognosis. Normal adult tissue 

lacks FAP expression. In our experiments, we aimed for a reduction of 

the pro-tumorigenic activities of CAFs by downregulating FAP expression. 

The decrease of FAP at the CAF surface is achieved by two different 

ways: FAP internalisation using a specific antibody or FAP gene silencing 

by transfecting CAFs with small interfering RNA (siRNA). The 

anti-FAP IgG antibody ESC11 is cross-reactive for mouse and human 

FAP and binds to FAP at low nanomolar affinities. Regarding migration 

and invasion, the antibody converted a FAP-positive cellular phenotype 

into a negative one. Hence, the antibody is capable of reversing the FAP 

mediated migratory and invasive capacity. FAP RNA interference was 

equally effective when compared to the antibody. Thus, targeting FAP 

on CAF suppresses pro-tumorigenic activities and may result in a reduction 

of tumor progression and dissemination. 

0213 

Non-thermal irreversible electroporation (NTIRE): a novel cancer 

therapy 

*J .J . Wendler1 , M . Porsch1 , M . Pech2 , M . Schostak1 , J . Ricke2 , U .-B . Liehr1 1University of Magdeburg, Department of Urology and Paediatric Urology, 

Magdeburg, Deutschland, 2University of Magdeburg, Department of 

Radiology and Nuclear Medicine, Magdeburg, Deutschland 

Purpose. Typical features, current experimental knowledge and first clinical 

results of non-thermal irreversible electroporation (NTIRE) as a 

novel cancer therapy are presented. Future aspects of using NTIRE in 

oncology are discussed. 

Methods. NTIRE is a new localized soft-tissue ablation technology that 

applies high-voltage and high-current electrical pulses on a microsecond 

timescale with inserted needle-like electrodes. NTIRE just alters 

in vivo cells on a molecular level via induced high-electric field transmembrane 

voltage that causes an electrical breakdown of the dielectric 

lipid bilayer. This leads to a generation of nanometer sized pores with 

irreversible permeabilization of the cell membrane that ends in the loss 

of cell homeostasis and a delayed apoptosis within approximately 4 (±3) 

days. This new electrical, non-thermal technique does not alter the extracellular 

matrix and does not cause protein denaturation that is usually 

associated with other current ablation methods. Hence, anatomical 

borders as well as the organ integrity in the NTIRE ablation zone are 

safe. Since the 60s, NTIRE is used commercially as a bactericidal method 

in the food industry. Its use as an ablative method in the context of 

medical applications was not studied until the early 2000s. 

Results. Recent studies have shown the multidisciplinary potential in 

oncologic therapy. Previous experimental studies in animal models 

investigated the effect of NTIRE in liver, kidney, lung, prostate, heart, 

pancreas, brain, dermis, breast and muscle. Hereby, it could be demonstrated 

that NTIRE leads to a localized complete decellularization whereby 

the tissue matrix stays unaltered. Moreover, in the ablation zone located 

structures such as blood vessels, nerves, exocrine glandular ducts, 

urethra, ureter, renal calyxes and pelvis were spared out and showed 

regeneration. Thus, the organ function can be preserved. The first clinical 

results of human phase-I studies showed the safety and the potential 

of NTIRE in the ablation of renal cell cancer, hepatocellular cancer and 

metastases from different entities. 

Conclusions. NTIRE is a new soft-tissue ablation technology that offers 

minimal-invasive, locally targeted cancer therapy. It seems to be superior 

to current thermal ablation techniques and is a therapeutic alternative 

in inoperable cases with curative treatment intention. Further 

human studies are warranted to determine NTIRE ablation efficacy of 

this novel technology in different cancers.

0235 

Evaluation und Quantifizierung der Tumorperfusion von hyperarterialisierten 

Tumoren unter Nutzung der neuen computertomographischen 

4D-Volumenperfusion(VPCT)-Technik 

*M . Horger 1 , M . Schulze 1 

1 Eberhard-Karls-Universität Tübingen, Radiologie, Tübingen, Deutschland 

Ziel. Vergleich von Perfusionsparametern folgender maligner Tumoren: 

Sarkome, gastrointestinale Stroma-Tumoren (GIST), neuroendokrine 

Tumoren (NET) und Nierenzellkarzinome (RCC) mithilfe der VPCT 

zwecks Differenzierung und Charakterisierung (angiogenetische Signatur). 

Material und Methodik. Alle Tumoren wurden histologisch gesichert und 

keiner war bereits anbehandelt. Mittleres Patientenalter war 60 Jahre. 

Es wurden 18 Sarkome, 6 NETs, 5 RCCs und 5 GISTs untersucht. Folgende 

Parameter wurden gemessen: Blutfluss (BF in ml/100 ml/min), 

Blutvolumen (BV in ml/100 ml) und k-trans oder Gefäßwandpermeablitätskonstante 

(ml/100 ml/min) im Gesamttumor (avg) und in der 

am stärksten vaskularisierten Tumorregion (max). Für die statistische 

Analyse Mean-Werte wurden berechnet und die Ergebnisse als Means 

± SD angegeben. Die Differenz zwischen den jeweiligen Gruppen 

wurde mittels eines exakten „Wilcoxon signed-rank“-Test berechnet. 

Statistische Analysen wurden durchgeführt mittels JMP 9.0 (Biostatistische 

Software -SAS Institute); p

Abstracts 

0277 

The Sarcoma Treatment and Burden of Illness in North America 

and Europe (SABINE) Study – Results from Germany 

*P . Reichardt1 , S . Bauer2 , A . Reichardt1 , M . Hoiczyk2 , M . Brunner3 , P . Kaskel4 , 

L . Jönsson5 , A . Musayev5 , E . Landfeldt5 , T . Burke6 , C .-M . Wendtner3,7 1HELIOS Klinikum Bad Saarow, Hämatologie, Onkologie und Palliativmedizin, 

Sarkomzentrum Berlin-Brandenburg, Bad Saarow, Deutschland, 2Uni versitätsklinikum Essen, Innere Klinik (Tumorforschung), Westdeutsches 

Tumorzentrum, Essen, Deutschland, 3Universitätsklinikum Köln, Klinik I für 

Innere Medizin, Centrum für Integrierte Onkologie Köln-Bonn, Köln am 

Rhein, Deutschland, 4MSD SHARP & DOHME GMBH, Outcomes Research, 

Haar, Deutschland, 5Optum Insight, Stockholm, Schweden, 6MERCK & CO ., 

INC ., Global Health Outcomes, Whitehouse Station, NJ, USA, 7Städtisches Klinikum München GmbH, Klinikum Schwabing, Klinik für Hämatologie 

und Onkologie, München, Deutschland 

Background. Data on treatment patterns in patients (pts) with metastatic 

soft tissue sarcoma (mSTS) in general, and Germany in particular, 

are limited. The objective of this study was to describe chemotherapy 

(CTX) treatment patterns after 1st attainment of favorable response 

(FR) to CTX in pts with mSTS in 7 European and 2 North American 

countries. 

Methods. Data from medical records were collected from initiation of 

1st line CTX to end of follow-up (EOFU) or death. Inclusion criteria 

were: 1) Confirmed mSTS diagnosis; 2) FR (complete, partial, or stable 

disease) after ≥4 cycles within any line of CTX; 3) Age ≥13 years. First 

line CTX was to be initiated between Jan 2004 and Dec 2009. 

Results. A total of 240 pts were enrolled at 25 sites, with 214 comprising 

the evaluable patient set (n=14 from 3 German sites). In contrast to other 

countries, German sites were allowed to recruit only non-deceased pts. 

The mean age at diagnosis of mSTS pts was 54.8 years and 41.6% were 

male (52.7 years and 28.6% male for German pts). The most common 

pathologies were leiomyosarcoma (46.3%) and liposarcoma (26.2%). The 

mean time from CTX initiation to EOFU or death was 27.2 months, 

with 62.6% of pts dying during follow-up. A total of 585 lines of CTX 

were used by 213 pts (mean = 2.7 lines). The most commonly used 1st 

line CTX regimens were doxorubicin (36.6%), doxorubicin/ifosfamide 

(19.2%), and gemcitabine/docetaxel (8.9%). FR to CTX was first observed 

in 1st line (81.8%) or 2nd line plus (18.2%) CTX. The main reason for 

CTX discontinuation in lines where FR was observed was a pre-defined 

number of CTX cycles given for 1st and 2nd lines of therapy (64.0% 

and 34.3%, respectively), and disease progression for 3rd line (52.4%). 

The median overall survival from first FR to CTX was 26.3 months (95% 

CI: 21.8, 31.9). For German pts, undifferentiated pleomorphic sarcoma/ 

malignant fibrous histiocytoma and synovial sarcoma were the most 

common STS pathologies. A total of 43 lines of CTX were used by 14 pts 

(mean =3.1 lines) over 36.7 months of follow-up. FR was observed in 1st 

line CTX for 71% of German patients. Ifosfamide/epirubicin was the 

most commonly used 1st line CTX regimen (43%), while gemcitabine 

(29%) and trofosfamide (29%) were the most commonly used regimens 

in 2nd line. 

Conclusions. Multiple lines of CTX are used to treat mSTS pts with FR 

to CTX. The data will assist in service planning and evaluation of new 

therapies for mSTS pts with FR to CTX in Germany. 


0320 

CD90-positive perivascular cells as mediators of immunosuppression 

in human malignant glioma 

*K . Ochs1,2 , F . Sahm3,4 , C . Opitz1,2 , U . Litzenburger1,2 , A . von Deimling3,4 , 

W . Wick1,5 , M . Platten1,2 1 2 Neurologische Klinik, Neuroonkologie, Heidelberg, Deutschland, Deutsches 

Krebsforschungszentrum, Experimentelle Neuroimmunologie, 

Heidelberg, Deutschland, 3Pathologisches Institut, Neuropathologie, Heidelberg, 

Deutschland, 4Deutsches Krebsforschungszentrum, Klinische Kooperationseinheit 

Neuropathologie, Heidelberg, Deutschland, 5Deutsches Krebsforschungszentrum, Klinische Kooperationseinheit Neuroonkologie, 


Background. Malignant gliomas are primary brain tumors characterized 

by an extensive neoangiogenesis including the recruitment of endothelial 

cells and pericytes. Besides their role in vascular development, 

perivascular cells have been discussed as a source of undifferentiated 

mesenchymal stem cell-like cells. CD90-positive (CD90+) bone marrow-derived 

mesenchymal stem cells (MSC) exert immunosuppressive 

properties. In the present study, we analyzed the immunomodulatory 

effect of cerebral perivascular cells in human malignant glioma. 

Methods. The influence of human cerebral CD90+ pericytes (HBVP) 

on allogeneic or mitogen-activated T cell responses was assessed and 

compared to the inhibitory capability of MSC. Using immunohistochemical 

stainings, the presence of CD90+ cells and blood vessel associated 

leukocyte common antigen (LCA) expressing cells in human healthy 

brain and glioma tissue was analyzed. 

Results. Proliferation of peripheral blood mononuclear cells (PBMC) 

was equally effective inhibited by HBVP than by MSC. HBVP-caused 

immunosuppression was mediated by prostaglandin E2, nitric oxide, 

soluble human leukocyte antigen-G, hepatocyte growth factor and 

transforming growth factor-β. While in human healthy brain only neurons 

showed CD90 expression, in human glioblastoma tissue CD90+ 

cells were associated with tumor blood vessels. These CD90+ cells were 

identified as platelet derived growth factor receptor-β expressing perivascular 

cells distinct from CD31 expressing endothelial cells. Analysis 

of CD90 expression levels in glioma WHO grade II-IV demonstrated a 

positive correlation between perivascular CD90 expression and glioma 

malignancy and a negative correlation between perivascular CD90 expression 

and the presence of blood vessel associated leukocytes. 

Summary. Human cerebral CD90+ perivascular cells possess a T cell 

inhibitory capability comparable to the immunosuppressive phenotype 

of human bone marrow-derived MSC. Presence of CD90+ perivascular 

cells in malignant glioma is associated with a decreased perivascular 

leukocyte infiltration. Thus, besides their critical role in tumor vascularization, 

perivascular cells may also promote glioma immunevasion. 

0326 

Prognosis and treatment variables in primary and secondary 

angiosarcomas 

*J . Hartmann1 , V . Hanf2 , D . Drücke3 , E . Dehnke1 , H . Kross1 1Universitätsklinikum Schleswig-Holstein Kiel, Klinik für Innere Med . II, Hämatologie 

und Internische Onkologie, Kiel, Deutschland, 2Klinikum Fürth, 

Frauenklinik, Fürth, Deutschland, 3Universitätsklinikum Schleswig-Holstein 

Kiel, Plastische, Hand- und Mikrochirurgie, Kiel, Deutschland 

Background. Angiosarcoma (AS) can be divided into primary (PAS) and 

secondary angiosarcoma (SAS) the latter occurring after prior radiation 

therapy. The objective was to compare clinicopathologic factors for both 

groups. 

Methods. AS cases of the Sarcoma Center North were identified. In a 

retrospective analysis, patient characteristics, treatment modality, and 

survival were determined and compared for both types of AS, PAS and 

SAS.

Results. Fourty patients (pts) with PAS and 24 pts with SAS were identified, 

overall representing 5.7% of pts in the database. Patients with PAS 

were younger at time of diagnosis than pts with SAS (median age: 52 years 

vs 65 years, respectively). The proportion of female patients was 57.5 

% for PA, but 95.8 % for SA. The distribution of cancer types was uneven, 

with AS of the breast accounting for 17.5% of PAS, but 87.5% of SAS. For 

the majority of PAS (63.2%), tumor size was ≥5 cm, as opposed to only 

8.3% of SAS with tumor size ≥5 cm. At the time of diagnosis of the angiosarcoma, 

42.5% of PAS had metastasized, but only 8.3% of SAS. All 

pts with SAS had previously received radiation therapy with a median 

time from radiation to diagnosis of SAS of 6.9 years (range: 0.7–24.8). 

The proportion of pts treated with surgery was the same for both groups 

with 79%, however, more pts with PAS received chemotherapy. 35.5% of 

PAS were treated with radiotherapy and 13.3% received radiochemotherapy. 

23.5% of SAS pts received a second course of radiation as part of 

their SAS treatment. While only half of the PAS relapses (53.6%) were 

local, 88.9% of SAS developed a local relapse. Median PFS was 11 months 

for PAS and 17 months for SAS (OR: 1.45; CI 95%, 0.71–2.96; p=0.31). Median 

overall survival (OS) was 18 months for PAS and 36 months for 

SAS (OR: 1.74; CI 95%, 0.85–3.59; p=0.13). Both PFS and OS (n.s.) were 

higher in pts with R0 compared to R1/2 resection, particularly for breast-AS 

(p=0.01). Metastases at time of diagnosis lowered PFS (n.s.) and 

OS (p=0.02). Non-breast AS had a lower PFS (p=0.01) and trend for inferior 

OS (p=0.09). 

Conclusions. As expected, PAS and SAS were heterogeneous in their clinical 

behaviour. PAS consisted mostly of non-breast AS in both males 

and females, while SAS were primarily located in the breast of younger 

female pts. SAS were detected at an earlier stage than PAS. Overall the 

prognosis is limited and early detection in a localized stage is warranted. 

0340 

Overview of the development of catumaxomab in malignant 

ascites 

*C . Schmidt-Rimpler1 , A . Burges2 , P . Ruf3 , E . Schulze1 , M .M . Heiss4 , S .L . Parsons5 

1 2 Fresenius Biotech GmbH, Medical Affairs, Munich, Deutschland, Clinic and 

Policlinic, LMU Munich, Gynecology and Obstetrics, Munich, Deutschland, 

3TRION Research GmbH, Antibody Development, Munich, Deutschland, 

4 5 Cologne-Merheim Medical Center, Cologne, Deutschland, Nottingham 

University Hospitals NHS Trust, Nottingham, UK 

Background. Malignant ascites (MA) is a manifestation of advanced 

malignancies, associated with a poor prognosis and poor survival. 

The trifunctional antibody catumaxomab (Removab®) is the first drug 

worldwide with an approval (EU) for intraperitoneal (i.p.) treatment of 

malignant ascites due to EpCAM-positive carcinomas. Catumaxomab 

targets EpCAM (epithelial cell-adhesion molecule) on tumor cells and 

CD3 on T cells in parallel. In addition, its Fc region binds to accessory 

cells like macrophages and natural killer cells. These bindings induce 

a simultaneous activation of immune cells resulting in an effective destruction 

of tumour cells. 

Methods. The clinical development of catumaxomab in MA is based 

on three key studies: a phase I/II dose finding study in patients with 

MA due to ovarian cancer, a pharmacokinetic study and a pivotal II/III 

study, the latter in patients with MA due to epithelial cancer. Further 

studies are currently ongoing. 

Results. In the dose-finding study a MTD of 10, 20, 50, 200 and 200 µg 

i.p. was determined, resulting in the recommended dose of 10, 20, 50, 

150 µg. In addition, first signs of efficacy could be shown in this phase I/ 

II study: Reduction of ascites flow, no puncture in 22 patients until end 

of study, reduction of tumor cells in the ascites flow, which are regarded 

as the main cause of ascites. The phase II pharmacokinetic study 

revealed that i.p. catumaxomab becomes detectable in plasma. In the 

pivotal study a statistically significant and clinically relevant superio- 

rity of catumaxomab over paracentesis has been shown in treatment of 

MA. Moreover, the data indicate a positive influence of catumaxomab 

on overall survival. The safety profile of catumaxomab is predictable 

as it reflects its mode of action, i.e. the main adverse effects are typical 

signs of an immunological reaction. 

Conclusion. Catumaxomab administered as a sequence of four i.p. infusions 

resulted in a clear clinical benefit in the treatment of patients with 

malignant ascites. The predictable and manageable safety profile underlines 

the positive benefit/risk ratio. Catumaxomab in malignant ascites 

is further being investigated in several studies (CASIMAS, SECIMAS, 

CARMA, ACT). Other indications, e.g. peritoneal carcinomatosis 

and gastric cancer and other administration routes, e.g. intravenously 

are under investigation. All carcinomas expressing EpCAM could be 

potential targets for catumaxomab in the future. 

0346 

Interim analysis of a cooperative registry to optimize neoadjuvant 

treatment for large size, high grade non-rhabdomyo soft 

tissue sarcoma (NRSTS; IAWS-2) 

*J . Hartmann1 , V . Grünwald2 , F . Mayer3 , A . Wolff4 , H .-G . Mergenthaler5 , 

W . Blau6 , I . Sturm7 , V . Budach8 1Universitätsklinikum Schleswig-Holstein Kiel, Klinik für Innere Med . II, 

Hämatologie und Internische Onkologie, Kiel, Deutschland, 2Medizinische Hochschule Hannover, Internistische Onkologie, Hannover, Deutschland, 

3 4 Universität Tübingen, CCC Tübingen, Tübingen, Deutschland, Universität 

Würzburg, Hämatologie/Onkologie, Würzburg, Deutschland, 5Klinikum Stuttgart, Hämatologie und Internistische Onkologie, Stuttgart, Deutschland, 

6Universitätsklinikum Gießen und Marburg, Internistische Onkologie, 

Gießen, Deutschland, 7Charité – Universitätsmedizin Berlin, Hämatologie/ 

Onkologie, Berlin, Deutschland, 8Charité – Universitätsmedizin Berlin, Klinik 

für Strahlentherapie, Berlin, Deutschland 

Introduction. The role of adjunctive anthracycline and ifosfamide based 

combination chemotherapy prior to or after resection in the treatment 

of adult and childhood “so-called” NRSTS continues to be controversial. 

In order to examine whether concomitant chemotherapy with doxorubicin 

(DOXO) and ifosfamide (IFO) and radiation (RTX) improves 

disease-free survival for patients with resectable, large (>5 cm), high 

grade (G2/3) adult-type NRSTS compared to surgery alone (and RTX if 

indicated/applicable) a multicenter register was launched. 

Methods. Patients (pts) with locally advanced (stage III) or locally recurrent 

NRSTS were treated with IFO (3 g/sqm for 3 days)-DOXO 

(60 mg/sqm, day 1) ×3 cycles – IFO (3 g/sqm for 2 days) ×2 cycles + RTX 

50.4 Gy* – IFO-DOXO ×1 (*if indicated/applicable, otherwise IFO-DO- 

XO ×5 cycles) prior to surgery. Key inclusion criteria were age ≤65 years 

at date of biopsy, histopathologically confirmed high grade NRSTS 

according FNCLCC, size >5 cm, no evidence of metastatic disease, no 

previous cytotoxic or radiation treatment. This interim analysis evaluates 

the pCR rate. 

Results. 63 pts with locally advanced NRSTS were included, but 5 were 

not eligible. Histologies were pleomorphic sarcoma, NOS (n=20), liposarcoma 

(11), synovial sarcoma (7), leiomyosarcoma (5), myxofribrosarcoma 

(6), MPNST (2), other (5). Median age was 50 yrs (range: 19–65). 

Other pts characteristics: male/female ratio was 1.2; grade 2 (21), grade 3 

(34), median size 10 cm (range: 4–23); localisation: extremity 36, central 

10, head and neck 5, retroperitoneal 3, girdle 2. Fourty-two pts are currently 

evaluable: 35 completed treatment and surgery. Six pts stopped 

treatment due to toxicity and 1 pt due to progressive disease. Pathological 

assessment according to Salzer-Kuntschik was performed in 38 pts: 

14 pts achieved complete regression (grade 1) and 10 pts grades 2 and 3 

(

Abstracts 

Conclusions. 63% of all patients responded well to concomitant IFO-DO- 

XO + RTX (regression grades 1–3, Salzer-Kuntschik). These preliminary 

results in terms of pathologic response suggest that the combination of 

neoadjuvant chemo- and radiotherapy may have a role in selected pts 

with high risk NRSTS. Accrual is ongoing. 

0360 

Catumaxomab observational study to investigate efficacy and 

safety profile in clinical practice – the CARMA study 

*V . Kunzmann1 , J . Sehouli2 , B . Schmalfeldt3 , P . Wimberger4 , C .M . Kurbacher5 , 

G .-F . Tempelhoff6 , F . Breuer7 , H . Schulz7 , M . Welslau8 , D . Finas9 , J . Sagasser10 , 

M . Kiehl11 , S . Fruehauf11,12 , M .M . Essing13 1 2 Medical Clinic and Policlinic II Würzburg, Würzburg, Deutschland, Charité 

Campus Virchow, Clinic for Gynaecology and Obstetrics, Berlin, Deutschland, 

3Technical University Munich, Clinic for Gynaecology, Munich, 

Deutschland, 4University Essen, Clinic for Gynaecology, Essen, Deutschland, 

5 6 Medical Centre Bonn Friedensplatz, Bonn, Deutschland, Clinic Aschaffenburg, 

Clinic for Gynaecology, Aschaffenburg, Deutschland, 7Private Practice Pioh, Frechen, Deutschland, 8Private Practice Klausmann, Welslau, 

Aschaffenburg, Deutschland, 9University Schleswig-Holstein, Clinic for 

Gynaecology and Obstetrics, Lübeck, Deutschland, 10Clinic Augsburg, Clinic 

for Gynaecology, Augsburg, Deutschland, 11Clinic Frankfurt/Oder, Medical 

Clinic I, Frankfurt/Oder, Deutschland, 12Paracelsus-Clinic, Haematology and 

Oncology, Osnabrueck, Deutschland, 13Fresenius Biotech GmbH, Medical 

Affairs, Munich, Deutschland 

Background. The trifunctional anti-EpCAM/anti-CD3 antibody catumaxomab 

is approved in the EU for intraperitoneal (i.p.) treatment of 

malignant ascites in patients with EpCAM-positive carcinomas. Clinical 

data for catumaxomab are based on the randomized, pivotal trial 

and several phase I/II trials. So far, the routine use of catumaxomab 

in clinical practice has not been evaluated systematically. Therefore, a 

large prospective observational study was started in 2010, investigating 

the administration of catumaxomab in patients with malignant ascites 

under routine conditions in daily clinical practice. 

Methods. In this study, a total of 160 patients with malignant ascites due 

to EpCAM-positive carcinomas (e.g. ovarian, breast, gastrointestinal 

cancer) treated with i.p. catumaxomab under routine conditions in clinical 

practice will be evaluated. Participating centres are hospitals and 

practices of oncologists in Germany and Austria. The following data are 

being collected (amongst others): demographic factors, cancer disease, 

distant metastasis, chemotherapeutic regimen, surgery, laboratory parameters, 

ascites signs and symptoms, management of catumaxomab 

therapy, number of punctures, tumor response, survival, quality of life, 

safety results. The data will be analyzed by descriptive statistical methods. 

Results. The results of the first interim analysis are reported. The analysis 

includes 50 patients with malignant ascites and catumaxomab treatment. 

Data for therapy management, clinical efficacy, quality of life and 

safety are presented. The collection of data is ongoing. 

Conclusion. We report here the data of an interim analysis with catumaxomab 

in malignant ascites. This is the first systematic report including 

a large patient number for the routine use of catumaxomab in clinical 

practice. 


0378 

Ifosfamide, Carboplatin and Etoposide (ICE) in combination with 

regional hyperthermia (RHT) in the treatment of chemo-refractory 

high-risk soft-tissue sarcoma (HR-STS) 

*V . Buecklein1,2 , C . Limmroth1 , V . Milani1,2 , L . Lindner1 , S . Abdel-Rahman1 , 

W . Hiddemann1 , R . Issels1,2 1LMU Munich, Department of Internal Medicine III, University Hospital 

Großhadern, Munich, Deutschland, 2HelmholtzZentrum Munich, CCG 

Hyperthermia, Institute of Molecular Immunology, Munich, Deutschland 

Background. A completed phase III trial (n=341, NCT00003052) showed 

that the addition of RHT to anthracycline-based chemotherapy was beneficial 

in terms of tumor response and survival in patients (pts) with 

locally advanced HR-STS (Lancet Oncol 2010). Treatment options in pts 

with chemo-refractory HR-STS remain limited; however retrospective 

data showed that ICE + RHT is safe and associated with tumor control 

in this situation (ASCO 2009 abstract 10581). Here, we analysed the efficacy 

in pts with progressive or recurrent disease treated prospectively 

in the aforementioned trial. 

Methods. Pts (≥18 years, PFS ≤2) with locally advanced HR-STS without 

(LA) or with metastases (LAM) showing progressive disease or relapse 

after chemotherapy were enrolled. ICE consisted of ifosfamide 1.5 g/m2, 

carboplatin 100 mg/m2 and etoposide 150 mg/m2 on days 1–4 followed 

by G-CSF support. RHT was performed on days 1 and 3. Treatment was 

repeated on day 28. Endpoints were toxicity (CTC criteria), response 

(RECIST), progression-free survival rates (PFR) after 3 and 6 months 

(EORTC criteria) and overall survival (OS). 

Results. 21 pts (10 female, 11 male, median age 57 years) with tumors located 

at the trunk, abdomen or retroperitoneum (n=14) or extremities 

(n=7) were analysed. Histological subtypes included liposarcoma (n=7), 

leiomyosarcoma (n=4), MPNST (n=3) and others (n=7) with G2 (10 pts) 

or G3 (11 its) tumors. 12 pts (57%) with LA and 9 pts (43%) with LAM 

entered the ICE + RHT protocol. A median of four (range 1–8) ICE 

cycles were applied combined with a median of six RHTs (range 2–16). 

Haematological toxicity grade III/IV occurred in 14 pts (67%); fever in 

cytopenia was seen in 4 pts (19%). Dose reduction was necessary in 43% 

of all pts. In 18 pts evaluable for response, the disease control rate (0 CR, 

2 PR, 8 NC) was 55%. The PFR after 3 and 6 months was 90% and 50%, 

respectively. Median OS in pts with LA was 23 months (CI 95: 1–77) and 

in pts with LAM 11 months (CI 95: 9.6–12.4). 

Conclusion. ICE chemotherapy combined with RHT offers an effective 

salvage therapy option in the treatment of chemo-refractory HR-STS, 

especially for pts with locally advanced tumors or limited metastatic 

disease. 

0391 

Can mathematical modelling help to cure glioblastoma multiforme? 

*A . Toma1 , A . Mang1 , S . Becker1 , T .A . Schütz1 , T .M . Buzug1 1Institut für Medizintechnik, Universität zu Lübeck, Lübeck, Deutschland 

Objective. Glioblastoma multiforme is the most aggressive primary 

brain tumour and has a quite worse prognosis due to the various and 

heterogeneous underlying processes. Most of these are complex and 

still not completely understood. To this end, we introduce mathematical 

methods for modelling tumour growth, providing means for simplifying 

the actual biological activities. We focus on the interaction and 

mutual dependence of the pre-dominant and most influencing factors 

only, to gain a better understanding of in-vivo processes. Mathematical 

modelling may open new ways for cancer prevention, clinical diagnostics 

and therapy. This requires the design of methods for simulating 

the spatio-temporal distribution and progression of a brain tumour. 

This can be achieved based on information obtained from in-vitro and 

animal models.

Methods. The computer simulation is controlled by a couple of different 

rules. For the migration of malignant glioma cells we use data obtained 

from a glioma cell invasion assay. The remaining parameters like the 

duration of the cell cycle are set according to values well-known from 

literature. Glucose, oxygen and the matrix degraded enzymes (MDE), 

such as the urokinase-type plasminogen activator or the matrix metalloproteinase 

are described as partial differential equations and are 

steering the tumour growth: the cells are attracted towards areas with 

higher nutrient concentration and may become necrotic in case of a 

high consumption rate of nutrients. The influence of the location of the 

tumour is described by the extracellular matrix. It is produced by cells 

and degraded by the MDE. To this end, the tumour cells are capable of 

migrating haptotactically through the extracellular space. 

Results. The simulated tumour depicts a distribution that can typically 

be observed in vivo: a big necrotic core surrounded by a rim of quiescent 

cells and an outer rim of strongly diffusive glioma cells. This is a strong 

characteristic of malignant brain tumours and is proven by in-vitro experiments. 

Conclusion. Mathematical methods for modelling glioblastoma are not 

yet ready for use in clinical practice. However, in the last few years the 

models made a big step in providing an accurate and realistic description 

of cancer progression. Hence, in near future, the question given in 

the title might be answered with “yes, indeed”. The model might then 

indicate the main processes that have to be inhibited for prevention. 

0441 

Trabectedin and heat-shock in human sarcoma cells in vitro 

*E . Kampmann1 , B . Otremba1 , S . Barth1 , E . Strozyk2 , R .D . Issels1,2 1Klinikum der LMU München, Medizinische Klinik III, München, Deutschland, 

2Helmholtz Zentrum München, KKG Hyperthermie, München, 

Deutschland 

Introduction. The completed randomized phase III EORTC/ESHO 

Intergroup trial (NCT 00003052) showed that regional hyperthermia 

combined with neoadjuvant chemotherapy is beneficial in terms of 

tumor response and survival of patients with high-risk soft tissue sarcoma 

(Lancet Oncol 2010). Trabectedin (ET-743), approved as secondline 

therapy for advanced STS, is a DNA minor groove binder with an 

unique mechanism of antiproliferative action. We investigate whether 

Trabectedin under heat conditions is more effective in human sarcoma 

cell lines. 

Methods. Trabectedin and heat-shock at clinically relevant temperatures 

were examined in 4 different human cell lines: Fibroblasts (MRC-5), 

leiomyosarcoma (SKUT-1), liposarcoma (SW872) and synovial sarcoma 

(SW982). Cells were treated with 0.1–1000 pM trabectedin followed by 

heat exposure in an incubator at 41.8°C and 43°C for 90 or 150 min. Cell 

viability was assessed using the WST-assay and measuring clonogenic 

survival. The expression of the heat-shock proteins HSP27, HSP70 and 

HSP90 was analysed by immunoblotting. 

Results. Human synovial sarcoma cells and leiomyosarcoma cells were 

most susceptible to any type of heat-shock whereas fibroblasts were almost 

resistant. In all investigated cell lines, HSP27 and HSP70 were induced 

immediately after heat-shock but not HSP90. Trabectedin did not 

influence the expression patterns of these HSPs. All cell lines showed 

reduced viability after low doses of trabectedin (approx. 10–100 pM) at 

37°C. Human synovial sarcoma cells were most susceptible and fibroblasts 

were most resistant. Trabectedin and heat-shock showed an additive 

effect in reducing clonogenic survival in human synovial sarcoma 

cells and at high temperature-time doses (150 min/43°C) in leiomyosarcoma 

cells. 

Conclusion. After in vitro heat exposure combined with trabectedin, heat-susceptible 

human synovial sarcoma and leiomyosarcoma cells show 

additive effects in terms of reduced cellular viability. The mechanisms 

of interaction between heat and trabectedin with regard to DNA repair 

(nucleotide excision repair, homologous recombination repair) in these 

human cell lines is under current investigation. 

0446 

Effectiveness of alkylating chemotherapy after chemo-radiotherapy 

with Temozolomide in patients with recurrent glioblastoma 

*A . Mohr1 , S . Rieken1 , T . Welzel1 , W . Wick2 , J . Debus1 , S .E . Combs1 1Univ .-Klinikum Heidelberg, Strahlentherapie, Heidelberg, Deutschland, 

2Univ .-Klinikum Heidelberg, Neuroonkologie, Heidelberg, Deutschland 

Introduction. Treatment of recurrent gliomas was often performed with 

alkylating nitrosoureas as a standard approach. However, the change 

of treatment standard after primary diagnosis fo glioblastomas (GBM) 

adding temozolomide (TMZ) has lead to the fact that most patients with 

recurrent gliomas have been treated by an alkylating chemotherapeutic 

agent. In the present work we analyzed efficacy of nitrosoureas applied 

for tumor progression after TMZ in patients with recurrent GBM. 

Patients and methods. From 1999 to 2008, we treated 242 patients with 

GBM with combined radio-chemotherapy with TMZ. At the time 

of progression, 30 of the 242 patients were treated with nimustine 

(ACNU). In 9 patients, ACNU as applied for first relapse, and in 15 and 

4 patients for the second and third recurrence. 17 patients were treated 

with ACNU mono, 13 with a combined therapy with ACNU and vepesid 

(VM26; n=11) or cytarabine (ARA-C; n=2). 

Results. The 6 and 12 months survival after therapy with ACNU was 

56.7% and 31.1% respectively. Median survival after therapy with ACNU 

was 7 months. The group of patients who received ACNU after the first 

relapse of the tumour showed a higher survival with 77.8% at 6 months 

compared to the group of patients treated with ACNU after the second 

and third relapse with 42.9% at 6 months; moreover, median survival 

was 9 months compared to 4 months after treatment for first compared 

to second or third recurrence. 

Conclusion. The treatment with ACNU seems to have advantages for 

survival of patients treated with TMZ mainly in an early state of relapse. 

0453 

Proton and carbon ion radiotherapy for primary brain tumors 

and meningiomas delivered with active rasterscanning at the 

Heidelberg Ion Therapy Center (HIT): early treatment results and 

study concepts 

*S . Rieken1 , D . Habermehl1 , T . Haberer2 , O . Jaekel2 , J . Debus1,2 , S .E . Combs1 1Univ .-Klinikum Heidelberg, Strahlentherapie, Heidelberg, Deutschland, 

2Universitätsklinikum Heidelberg, HIT, Heidelberg, Deutschland 

Purpose. To investigate toxicity and patterns of early failure after proton 

and carbon ion therapy for gliomas and meningiomas. 

Patients and treatment: 33 patients with gliomas (n=26) and meningiomas 

(n=7) were treated with carbon ion (n=26) and proton (n=7) radiotherapy. 

In 11 patients, particle irradiation was combined with photon 

therapy. Temozolomide-based chemotherapy was combined with particle 

therapy in 17 patients. Particle therapy as reirradiation was conducted 

in 7 patients. Target volume definition was based upon CT, MRI and 

PET imaging. Response was assessed by MRI examinations. Toxicity 

was classified according to CTCAE v4.0. 

Results. Treatment was completed and tolerated well in all patients. Toxicity 

was moderate and included fatigue (24.2%), intermittent cranial 

nerve symptoms (6%) and single episodes of seizures (6%). At first and 

second follow-up examinations, mean maximum tumor diameters had 

slightly decreased from 29.7 mm to 27.1 mm and 24.9 mm respectively. 

Nine glioma patients suffered from tumor relapse, among these 5 with 

infield relapses, causing death in 8 patients. There was no recurrence or 

progression in any meningioma patient. 

Conclusion. Particle radiotherapy is safe and feasible in patients with 

primary brain tumors. It is associated with little toxicity. Target volu- 


117

Abstracts 

me definition is recommended to take functional imaging analysis into 

account. A positive response of both gliomas and meningiomas, which 

is suggested in these preliminary data, must be evaluated in further clinical 

trials. 

0456 

Blood-derived miRNA as potential biomarkers for glioblastoma 

*P . Roth1 , J . Wischhusen2 , C . Happold1 , P . Anoop Chandran2 , S . Hofer1 , G . Eisele1 

, M . Weller1 , A . Keller3 1 2 UniversitätsSpital Zürich, Klinik für Neurologie, Zürich, Schweiz, Universität 

Würzburg, Würzburg, Deutschland, 3Universität Saarbrücken, 

Saarbrücken, Deutschland 

Background. Gliobastoma, one of the most aggressive human tumors, 

has a poor prognosis. The detection and later monitoring of the disease 

require biopsy or surgical resection and imaging technologies such as 

MRI. A simple and economical blood test would be desirable in order to 

allow for an early detection of progressive disease. 

Methods. In this study, we compared the miRNA expression profile 

in the peripheral blood from glioblastom patients compared to blood 

samples from age- and sex-matched healthy controls using a microarray 

platform. 

Results. Of 52 significantly deregulated miRNA, 27 were up-regulated 

(52%) while 25 miRNAs were down-regulated (48%). After correcting 

for multiple testing, 5 miRNA remained significant with a p-value of 

≤0.05. We then aimed at characterizing glioblastoma-specific miRNA 

fingerprints that allow for a classification of the samples as tumor or 

healthy controls. Using statistical learning techniques, a classification 

was obtained with an accuracy of 81%, specificity of 79%, and sensitivity 

of 83%. In a next step we analyzed the contribution of the deregulated 

miRNA to different biological pathways. This revealed a contribution 

of several miRNA to immune response mechanisms and an impact of 

others on cell cyle regulation and cellular proliferation. Some miRNA 

are involved in the process of apoptosis or angiogenesis. 

Conclusion. These findings suggest that the deregulated miRNA in glioblastoma 

patients may be linked to important biological pathways. Further, 

this proof-of-principle study demonstrates that blood-borne miR- 

NA profiles from glioblastoma patients contain characteristic patterns 

that warrant further exploration with regard to their potential use as 

disease-specific biomarkers. 

0467 

Chronic periodontitis as potential risk factor for the development 

of oral carcinoma – a retrospective case control study 

*M . Moergel1 , E .-J . Abt1 , B . Al-Nawas1 1Universitätsmedizin Mainz, MKG Chirurgie, Mainz, Deutschland 

Background. Recent findings strongly support the possibility of oral carcinoma 

induction by chronic inflammation apart from smoking and alcohol 

ingestion. Since western industrialized countries show increasing 

obsolescence and the incidence of chronic periodontitis rises with age, 

the present study investigated the presence of chronic periodontitis as 

independent risk factor for induction of oral carcinoma. 

Methods. The present retrospective study was designed as case control 

study. 186 patients treated for oral carcinoma at the Department for 

Oral and Maxillofacial Surgery, University Mainz between 2003 and 

2010 were included. 123 patients treated for affections other than malignancy 

(e.g. trauma) during the same period served as control. The 

mean alveolar bone loss as main symptom for chronic periodontitis was 

digitally measured on panoramic radiographs blinded to the patients 

clinical history. Tumor location and TNM status, smoking and alcohol 

consumption, age, gender, degree of education, body mass index and 

oral hygiene were noted by a detailed questionnaire. 


Results. The mean alveolar bone loss of patients with oral malignancy 

was 4.3 vs. 2.3 within the control group. The difference was highly significant 

(p≤0.0001, 95% CI of difference: 1.08–1.68). The effect was independent 

from age and gender and an independent influence still detectable 

after adjustment for confounder in a multiple logistic regression model. 

As side note a higher BMI (body mass index) and a lower educational 

level were negatively correlated with clinical parameter for oral hygiene 

as well known risk factors for the development of chronic periodontitis 

with rising age. 

Discussion. The present study strongly supports the theory of oral carcinoma 

induction by presence of chronic inflammation as it is seen in patients 

with chronic periodontitis. Furthermore, the amount of alveolar 

bone loss followed by epithelial migration which is seen only in a subpopulation 

of patients with inflammation of the periodontal mucosa, 

additionally characterizes a cohort of patients at risk for oral malignancy. 

Prospective clinical trials are needed to investigate this special phenomenon. 

First in vitro studies point at a potential interaction between 

specific periodontal bacteria and keratinocytes that might promote carcinogenesis 

or boost the invasive potential of carcinoma cells. 

0484 

Long circulating thermosensitive liposomes for triggered intravascular 

drug release 

*L . Lindner1 , M . Hossmann1 , R . Schmidt1 , L . Li2 , G . van Rhoon3 , H . Eibl4 , 

R . Issels5 , A .M .M . Eggermont6 , T . ten Hagen2 , G .A . Koning2 1Klinikum Großhadern, Medizinische Klinik III, München, Deutschland, 

2Erasmus Medical Center, Laboratory Experimental Surgical Oncology, Rotterdam, 

Niederlande, 3Erasmus Medical Center, Department Radiotherapy, 

Rotterdam, Niederlande, 4Max-Planck-Institute for Biophysical Chemistry, 

Göttingen, Deutschland, 5Helmholtz Zentrum Munich, Institute for Molecular 

Immunology, München, Deutschland, 6Institut de cancérologie Gustave 

Roussy, Villejuif, Frankreich 

Introduction. Thermosensitive liposomes (TSL) which become leaky 

after mild heating (40–41°C) offer the possibility of drug targeting for 

a variety of anticancer drugs. Synthetic 1,2-dipalmitoyl-sn-glycero-3phospho-glycero-glycerol 

(DPPG2) and 1,2-dipalmitoyl-sn-glycero-3phospho-glycero-glycero-glycerol 

(DPPG3) based TSL offer long circulation 

properties combined with fast drug release kinetics which are 

crucial prerequisites for intravascular drug release. Here, we compare 

DPPG2 and DPPG3 based DOX-TSL with low temperature sensitive liposomes 

(LTSL) based on lyso-PC with regard to PK, biodistribution 

and antitumor effectivity in vivo. 

Methods. TSL were prepared by the lipid film hydration and extrusion 

method. DOX was loaded actively with a pH gradient to preformed TSL. 

Tumor growth and tumor uptake studies with DOX-TSL were performed 

in BN 175 soft-tissue sarcoma extremity tumors of rats after 60 minutes 

of heating. Heat was applied by water bath or fiberoptic lamp. 

Results. Plasma peak levels of DOX were doubled for DPPG2- and 

DPPG3-based TSL as compared to LTSL (200 ng/µl vs. 100 ng/µl). This 

difference was even greater after 60 minutes with DOX 150 ng/µl vs. 

50 ng/µl, respectively. Within tumor tissue highest DOX concentrations 

were detected for animals treated with PG2 LT-DOX (24.3 ng/mg ±1.7) 

and PG3 LT-DOX (22.9 ng/mg ±0.2) compared to LTSL (9.93±1.6 ng/mg 

Dox) and free DOX (3.63±1.69 ng/mg). In tumor growth studies with 

DOX 2 mg/kg b.w. for DPPG3-TSL 4/6 complete tumor regressions and 

2/6 long lasting disease stabilizations were observed compared to 6/6 

progressions for standard DOX. For LTSL 1/6 delay in tumor growth 

was seen wheras 5/6 tumors progressed. 

Conclusion. Enabling high drug release rates at temperatures of 41°C and 

high stability at body temperature, DPPG2 and DPPG3 are ideal molecules 

to obtain optimally formulated TSL for intravascular drug release.

0506 

HLA-E contributes to an immune-inhibitory phenotype of glioblastoma 

stem-like cells 

*F . Wolpert 1 , P . Roth 1 , K . Lamszus 2 , G . Tabatabai 1 , M . Weller 1 , G . Eisele 1 

1University Hospital Zürich, Department of Neurology, Zurich, Schweiz, 

2University Hospital Hamburg-Eppendorf, Department of Neurosurgery, 

Hamburg, Deutschland 

Cancer stem cells are an attractive target for immunotherapeutic approaches 

to glioblastoma. However, an immune inhibitory phenotype 

of cells currently classified as glioma-initiating cells (GIC) might 

counteract recognition by immune effector cells. Here, we investigate 

the contribution of the non-classical MHC molecule HLA-E to the immunosuppressive 

phenotype of GIC. HLA-E is expressed in GIC lines 

and its expression is reduced upon differentiation of the GIC on serumcontaining 

conditions. HLA-E inhibits natural killer (NK) cell-mediated 

lysis of GIC since small-interfering RNA-mediated HLA-E gene 

silencing enhances the immunogenicity of GIC. Furthermore, the use 

of interferon-γ as a possible agent to boost an immune response against 

glioblastoma cells might be limited by the upregulation of HLA-E on 

the cell surface of GIC. 

Supportivmedizin/Palliativtherapie 

0012 

The breast care nurse (BCN ) – a key position in the breast centre 

team – the current situation 

*I .M . Rack1 , R . Saalmann1 , S . Kubo2 , S . Noeding1 , W . Bader3 1Klinikum Nordstadt, Frauenklinik, KRH, Kooperatives Brustzentrum, 

Hannover, Deutschland, 2Das Brustzentrum Niederrhein, Ev . Krankenhaus 

Bethesda, Brustzentrum, Mönchengladbach, Deutschland, 3Klinikum Region Hannover GmbH, Frauenklinik, Hannover, Deutschland 

In the last five years we can see how the career of BCNs, as nursing 

specialists for breast diseases, has developed. Following the example 

of English speaking countries, such as Great Britain, Ireland and 

Australia, this concept has expanded and is increasingly being put into 

practice. In many breast centres the BCN is so well established that one 

cannot imagine treating these patients without her active participation 

in the team. She has a number of responsibilities; she is the main contact 

person for the patients in the breast centre. From the time the diagnosis 

is made and all the way through to the end of the therapy the patient 

is accompanied and supported by the BCN. As far as the team is concerned, 

she is the coordinator and mediator in the breast centre as well 

as an important connection to the social network and the cooperation 

partners. At the German cancer convention in 2012 we would like to 

point out the significance of the BCN and her varied duties in breast 

centres. In the form of a lecture round we will talk about our experiences 

in the fields we work in, emphasising the positive effect our work has 

on everyone concerned with the treatment of breast cancer. We would 

like to show that the active involvement of BCNs results in a definite 

improvement in the quality of care. The good experience in the practice 

could prompt the inclusion of BCNs in the ONKOCERT certificate 

guidelines. A powerful team – the effect on the interdisciplinary communication 

and cooperation, and the quality of patient care – a doctor‘s 

viewpoint. May we have a little bit more? The support of patients who 

participate in national und international clinical drug trials – carving a 

niche! Staying power and gumption required – a BCN job description: 

introducing a structured concept of the work and importance of the 

BCN in the daily life of the breast centre. 

0041 

The role of the medical report for psychosocial support of cancer 

patients after discharge from the hospital 

*K . Book1 , P . Herschbach1 , C . Stuhr2 , M . Peuker2 , A . Heck2 , E . Brähler2 , K . Härtl3 1Klinikum rechts der Isar, Roman Herzog Krebszentrum, München, 

Deutschland, 2Universitätsklinikum Leipzig, Abteilung für Medizinische 

Psychologie und Medizinische Soziologie, Leipzig, Deutschland, 3Klinikum der Ludwig-Maximilians-Universität München, Klinik und Poliklinik für 

Frauenheilkunde und Geburtshilfe, München, Deutschland 

Background. Treatment of cancer involves different sectors within the 

health care system. An important role for communication between 

the sectors plays the medical report after discharge from the hospital. 

However, even though around 30% of cancer patients experience psychosocial 

distress, medical reports rarely contain information on distress 

which impedes continuous psychosocial support. The aim of this 

project was therefore to investigate whether the inclusion of a “psychooncological 

statement” within the medical report improves quality of 

treatment from the patient’s and doctor’s perspective. 

Methods. Patients with cancer were randomly allocated to the intervention 

or control group. Shortly before discharge, patients in the intervention 

group were assessed for their psychosocial distress with 

the psychooncological basic-documentation, a short semi-structured 

interview (t1). Results of the interview were included as a standardized 

psychooncological statement in the medical report. The control group 

received the medial report as usual. Few weeks after discharge (t2), patients 

in both groups were asked whether their doctor asked about their 

psychosocial distress and whether they were satisfied with treatment. 

Doctors in both groups received questions on whether the psychooncological 

statement (intervention group) or medical report (control group) 

was helpful for communication and further treatment and whether they 

asked the patient about psychosocial distress. 

Results. 1179 cancer patients and 596 doctors participated at t2. Doctors 

rated the psychooncological statement and medical report as helpful for 

communication and further treatment. Contrary to expectations, the 

psychooncological statement did not result in any differences between 

the intervention and control group concerning communication about 

psychosocial distress from the patient’s and doctor’s perspective or satisfaction 

with treatment. Overall, 40.8% of the patients and 74.3% of the 

doctors indicated that they discussed psychosocial distress. However, 

a correlation between satisfaction with treatment and communication 

about psychosocial distress was found; patients who were not asked about 

distress were less satisfied. 

Conclusion. Systematic inclusion of a psychooncological statement in 

the medical report based on a short interview is feasible in clinical practice. 

Further research is necessary to investigate the impact of the medical 

report and written information on doctor-patient communication. 

0043 

Do oncological patients in young adulthood have specific psychological 

motives behind the wish to have children? 

*K . Geue1 , D . Richter1 , R . Schmidt1 , E . Brähler1 1Universität Leipzig, Medizinische Psychologie und Medizinische Soziologie, 

Leipzig, Deutschland 

Objective. Many young people suffering from cancer had not been 

completed their family planning at the time of diagnosis. The issue of 

desiring to have children is gaining more and more importance considering 

the increasing long term survival and the possibilities of fertility 

preservation. Whereas during the acute phase of disease the desire to 

have children fades into the background, the fulfilling of own children 

comes to the fore after medical treatments and a good prognosis. The 

decision for or against a child is strongly determined by emotional 

motives. The aim of this study was to investigate whether and which 


119

Abstracts 

specific psychological motives oncological patients have behind the 

wish to have children. 

Methods. After a literature research the psychological motives behind 

the wish to have children of cancer patients were collected postally with 

a single questionnaire. Also experiences of experts in the oncological, 

psychooncological and reproductive medical field were analysed. The 

questionnaires mainly consisted of open questions. The evaluation was 

made by categorisation of two staff members. 

Results. Professional experience averaged over all experts (n=9, six 

women) was thirteen years. The following anxiety-provoking motives 

related to the wish for children were mentioned by the experts: the 

wish for a child remains unfulfilled (n=7), negative health effects for 

the child (n=8), concerns about the patient’s health risk (n=6), worries 

about an unrealisable child care (n=4) and concerns about couple difficulties 

(n=3). Positive motivation towards childbirth implicates positive 

recovery motivation and future prospects (n=9), symbolic immortality 

(n=3), the improvement of the couple relationship (n=1) and an increased 

importance of family life (n=1). Mean age of patients was 34 years 

at diagnosis, 80% want children in the future at this time. Patients’ major 

concerns about having a child were negative health prospects of the 

child (n=7) and cancer recurrence (n=5). Patients associated only few 

reasons in favour of childbirth. The results correspond essentially to the 

childbearing motives reported in the literature. 

Conclusion. The study clearly illustrates the existence of cancer-specific 

childbearing motives whose awareness of and knowledge about is fundamental 

for a psychosocial care adjusted to the needs of young oncological 

patients. 

0088 

Belastungserleben von Patienten mit Brustkrebs unter der primär 

systemischen Therapie in Abhängigkeit ihres Risiko-Scores 

*J . Schwickerath1 , V . Tschuschke2 , G . Karadaglis1 , K . Evangelou1 1 2 St .Martinus-Hospital, Frauenklinik, Olpe, Griechenland, Universität Köln, 

Medizinische Psychologie, Köln, Deutschland 

Fragestellung. Über die psychische Belastung bei Brustkrebs betroffenen 

Patientinnen gibt es genügend wissenschaftliche Erkenntnisse. 

Ebenso ist bekannt, dass die primär systemische Therapie eine nicht zu 

unterschätzende Therapieoption darstellt. Bei diesem Behandlungsweg 

wird aber nicht nur von den Frauen sondern auch von den Behandlern 

oftmals die unnötige psychische Belastung über die Belassung des Tumors 

in situ als zusätzliches Konfliktfeld diskutiert. Wir haben über 

unsere Studie, die wir bei 53 Patientinnen durchgeführt haben, diese 

Fragestellung untersucht. 

Methode. 53 Frauen, bei denen aus tumorbiologischer Sicht die Indikation 

zur Primärsystemischen Therapie bestand, wurden in die Studie 

aufgenommen. Hierbei handelte es sich um Patientinnen, die in der 

Frauenklinik/Brustzentrum zur Abklärung eines suspekten Tumors in 

der senologischen Ambulanz vorgestellt und mittels minimal invasiver 

Biopsie histologisch abgeklärt wurden. Nach Mitteilung des histologischen 

Befundes wurde ihnen ein Termin zur weiterführenden Abklärung 

im Rahmen eines stationären Aufenthaltes gegeben. Am 1. Tag 

der stationären Betreuung erfolgte dann sowohl ein standardisiertes 

Interview als auch die Übergabe der psychoonkologischen Fragebögen 

– HADS, BSI, F-SozU K14, POMS. Zu diesem Zeitpunkt hatten die Patientinnen 

keine Kenntnis über das genaue Staging ihrer Krebserkrankung. 

Sie waren somit blind vor ihrer weiteren (möglichen) Prognose. 

Erst in der nachfolgenden Zeit erfolgten die notwendigen Staginguntersuchungen. 

Nach Abschluss der Chemotherapie wurden die Patientinnen 

zur endgültigen sanierenden operativen Therapie wiederaufgenommen. 

Am Tag der stationären Aufnahme erfolgte wiederum das 

nun 2. standardisierte Interview. 

Ergebnisse. 53 Patientinnen wurden nach ihrer Einwilligung in die 

Studie aufgenommen. Nach den St.-Gallen-Kriterien erfolgte eine Einteilung 

in ein mittleres oder hohes Risikoprofil. 49 Patientinnen konn- 


ten letztendlich ausgewertet werden. 14 waren der Gruppe mit einem 

High-Score und 35 dem mit dem mittleren Risiko zu geordnet worden. 

Entsprechend dem Ulmer-Coping-Manual wurde das Interview 1 und 

2 (prä- und post-primär-systemischer Chemotherapie) nach folgendem 

Score ausgewertet: Pair 1 – Resignation – Hoffungslosigkeit/2 – Ablenkung 

v.d. Krankheit/3 – kognitive Strukturierung/4 – soziale Kontakte/5 

– Compliance/6 – Fighting Spirit/7 – aktives Coping. In beiden 

Gruppen zeigten sich schon beim 1. Interview deutliche Unterschiede 

in der Einstellung zu der Diagnose, in der Einschätzung der Krankheit 

– auch ohne genaue Kenntnis über den eigentlichen (fortgeschrittenen) 

Zustand der Erkrankung – und letztendlich auch in der Beurteilung 

ihres sozialen Umfelds. Diese Ergebnisse wurden auch bei der Auswertung 

des 2. Interviews bestätigt. Wobei sich hier erstaunliche Unterschiede 

im Wandel z. B betreffend Fighting Spirit, kognitive Strukturierung 

Ablenkung von der Krankheit gezeigt haben. 

Schlussfolgerungen. Im Rahmen der Präsentation werden wir die Ergebnisse 

in Bezug auf die einzelnen Pairs sehr dezidiert darstellen und 

entsprechend ihrer Wertigkeit diskutieren. 

0100 

Feasibility and barriers of bicycle training with patients undergoing 

haematopoietic stem cell transplantation 

*M . Götte1 , A . Fissmer2 , T . Elter2 , W . Bloch1 , F .T . Baumann1 1German Sport University, Department of Molecular and Cellular Sport 

Medicine, Cologne, Deutschland, 2University of Cologne, Department I of 

Internal Medicine, Center for Integrated Oncology, Cologne, Deutschland 

Introduction. The haematopoietic stem cell transplantation (HSCT) 

is associated with severe physical and psychological side effects, such 

as muscle atrophy, loss of physical fitness and other consequences of 

immobility. Since some studies have shown positive effects of physical 

activity during the inpatient stay for HSCT [1], this study focused on 

examining the implementation of controlled endurance training and 

analyzing the inhibitory factors for bicycle training during HSCT. 

Methods. This study included 32 patients undergoing autologous or allogene 

HSCT over a period of 10 weeks. Endurance training was performed 

with a bicycle ergometer four times a week for 10–35 minutes. 

Participation in bicycle training and the reasons for non-participation 

were ascertained. 

Results. Percentage participation on average was 43.9 % and showed a 

significant positive trend over the period of the study (on average 0.43% 

per day, p=0.008). Implementation of bicycle training was rarely possible 

on the day of HSCT and days 4 to 6 after HSCT. The most frequent 

causes for non-participation were medical contraindications (70.1%), in 

particular acute GvHD, infections and thrombocytopaenia (

1 . Jarden et al (2009) . DeFor et al (2007), Baumann et al (2005) 

2 . Vgl . Midtgaard et al (2009), Maddocks et al (2009) 

3 . Chang et al (2008), DeFor et al (2007), Kim & Kim (2006), Mello et al (2003) 

0102 

Muscle strength in patients with lung cancer associated with 

lung-cancer-specific symptoms: results of a pilot study 

*B . Hoffmann1 , S . Hummler2 , M . Zoz3 , M . Thomas3 , C .M . Ulrich2 , G . Huber1 , 

J . Wiskemann2 1Institut für Sport und Sportwissenschaft der Universität Heidelberg, 

Heidelberg, Deutschland, 2Nationales Zentrum für Tumorerkrankungen, 

Präventive Onkologie, Heidelberg, Deutschland, 3Thoraxklinik, Innere 

Medizin-Onkologie, Heidelberg, Deutschland 

Lung Cancer (LC) patients often experience physical and psychological 

impairment during the course of their disease. The aim of our pilot 

study was to analyse the difference of muscle strength values of LC patients 

compared to healthy people and to explore whether a correlation 

between muscle strength and lung cancer symptoms exists. 39 patients 

with lung cancer (56% NSCLC, 44% SCLC) with a median age of 62 

(range 44–83) from the Thoraxklinik in Heidelberg have been assessed 

for muscle strength by using Hand-Held Dynamometry. The following 

muscle groups were tested on both sides: elbow extension, elbow flexion, 

hip abduction, hip flexion, knee extension and knee flexion. Clinical 

symptoms were documented by using the FACT-L Lung cancer subscale 

(LCS). Almost all of the enrolled subjects (87%) were pretreated with 

chemotherapy. Reference data in healthy populations showed on average 

muscle strength values [measured in Newton (N)] of 364 N ±80 for 

knee extension, 238 N ±53 for hip abduction and 149 N ±39 for hip flexion 

(no data for knee flexion available). Values for lung cancer patients 

were considerably lower: 190 N ±73 (−47.62% ±19.38) for knee extension, 

130 N ±42 (−44.93% ±14.9) for hip abduction and 129 N ±47 (−13% ±24.17) 

for hip flexion. In the upper extremities the healthy reference values 

showed 209 N ±61 for elbow flexion and 144 N ±39 for elbow extension. 

Values for lung cancer patients were again clearly lower with 147 N ±53 

(−28.17% ±20.24) for elbow flexion and 125 N ±46 (−12.37% ±21.94) for 

elbow extension. Pearson correlation showed a positive correlation between 

LCS and muscle strength for men [elbow flexion r=0.44; p=0.045 

(dominant side), elbow extension r=0.51; p=0.018 (not dominant side), 

hip abduction r=0.65; p=0.001 (dominant side) and r=0.50; p=0.024 (not 

dominant side)]. Pearson correlation between LCS and muscle strength 

for women showed a negative but not statistically significant correlation. 

Our findings indicate that lung cancer patients experience muscular 

weakness especially in the lower extremities compared to the healthy 

reference population. Main differences compared to similar age 

groups were observed in knee extension, hip abduction and elbow flexion 

if analyzed by age. A positive correlation between LCS and muscle 

strength was observed in men, but surprisingly not among women. Further 

research in larger populations is needed to explore the differences 

in gender. 

0103 

Pilot study on fatigue levels in patients with lung cancer: correlations 

with muscle strength and 6-minute walk tests 

*S . Hummler1 , M . Zoz2 , M . Thomas2 , C .M . Ulrich1 , G . Huber3 , J . Wiskemann1,4 1Nationales Zentrum für Tumorerkrankungen, Präventive Onkologie, 

Heidelberg, Deutschland, 2Thoraxklinik, Innere Medizin-Onkologie, Heidelberg, 

Deutschland, 3Institut für Sport und Sportwissenschaft der Universität 

Heidelberg, Heidelberg, Deutschland, 4National Center for Tumor 

Diseases and University Clinic Heidelberg, Division of Medical Oncology, 


Lung cancer patients often suffer from fatigue due to their disease, side 

effects of treatment or the multidimensionality of burden. The aim of 

this pilot study was to explore associations between levels of fatigue and 

physical performance parameters. As part of this pilot study, a total of 

39 lung cancer patients were recruited in the Thoraxklinik Heidelberg 

(NSCLC 56%, SCLC 44%). Irrespective of current treatment and stage 

of disease patients were enrolled and assessed with the multidimensional 

fatigue inventory (MFI) questionnaire. Moreover, isometric muscle 

strength via hand-held dynamometry and 6-minute walk test (6MWT) 

was performed. The patient population comprised of 22 male patients 

and 17 female patients, with a median age of 62 (range 44–83). Initial 

Pearson correlation analyses revealed a significant correlation between 

the MFI subscore physical fatigue (PF) and 6 minute walk distance 

(6MWD) in male patients (r=−0.525, p=0.015), but no correlation in female 

patients. Also no correlations between isometric muscle strength 

and other fatigue variables were observed. Table 1 shows a summary of 

the mean values (± SD) for MFI, HHD and 6MWD for lung cancer pts. 

compared to the healthy reference population. 

These pilot data are in contrast to several published studies which reported 

significant correlations between fatigue levels and physical performance 

(e.g. for patients with breast cancer). Because of the low patient 

number we can only speculate, if this effect is an artifact of the sample 

size or reflects a difference in self-perception with respect to physical 

strength (and thus a difference in the severity of fatigue) in male and 

female lung cancer patients. Further studies with more patients are needed 

to discern possible gender-specific differences. 

Tab. 3 Mean values for MFI, HHD, 6MWD for LC pts . compared to the 

healthy reference population 

Lung cancer 

pts . (n=39) 

Healthy ref . 

population 

MFI 

(subscore PF) 

HHD 

(knee extension) 

6MWD 

(m) 

Male Female Male Female Male Female 

11,1 

(SD 4,6) 

9,1 

(SD 1,4) 

12,9 

(SD 4,0) 

9,7 

(SD 1,5) 

225 

(SD 64) 

419 

(SD 49) 

148 

(SD 60) 

297 

(SD 56) 

434 

(SD 

112) 

597 

(SD 97) 

411 

(SD 108) 

514 

(SD 68) 

0107 

Psychooncological interventions for gastrointestinal cancer 

patients 

*R . Hirth1 , E . van der Meer2 , M . Pross1 , B . Schicke3 1 2 DRK Kliniken Berlin, Klinik für Chirurgie, Berlin, Deutschland, Humboldt- 

Universität zu Berlin, Institut für Psychologie, Berlin, Deutschland, 3Tumor zentrum Berlin e .V ., Berlin, Deutschland 

Purpose. Gastrointestinal tumours are very common among male and 

female cancer patients. Diagnosis as well as subsequent therapy usually 

induces great emotional stress in these patients. They suffer from somatic 

(fatigue and exhaustion) and psychological (anxiety and tension) 

disorders. Emotion-regulation strategies are most important for these 


121

Abstracts 

patients to overcome the impacts resulting from the disease: physical 

impairments, bad constitution, and fundamental changes to their whole 

life. This study compares the effectiveness of two different psychooncological 

interventions: relaxation therapy vs. cognitive structured 

short-term psychotherapy, applied during the medical after-treatment 

of gastrointestinal cancer patients. 

Hypotheses. (1) Cancer patients who receive psychooncological interventions 

suffer from significantly less anxiety compared to a control 

group without intervention. (2) A cognitive structured short-term psychotherapy 

reduces the anxiety of cancer patients significantly more 

than a relaxation therapy. 

Background. The cognitive psychological intervention is based on a processing 

model of emotion regulation developed by Hwang (2006). The 

model describes the development of emotion as controlled by sensation 

and behaviour in the context of subjective appraisal. In a first step emotions 

are processed in a way to support social desirability. This leads to 

reappraisal of emotional events (Gross et al., 1989). In a second step the 

remaining negative emotions are suppressed. This results in adaptive vs. 

maladaptive behaviour, influenced by the level of anxiety, the capacity 

to suppress unwanted thoughts, and the sense of self-efficacy. 

Methods. The longitudinal study is being conducted during the medical 

after-treatment (chemotherapy or irradiation). Sample: approx. 

n=280 patients with gastrointestinal tumours in the Surgical Clinic of 

the German Red Cross Hospitals Berlin Koepenick, randomized sample. 

Sessions: 14 different measuring points (t1 to t14), 2 inpatient sessions, 

12 ambulant sessions. Cognitive psychological intervention: different 

topics (e.g. diagnosis, fatigue, resources), based on the cognitive 

structured short-term psychotherapy. Relaxation therapy: progressive 

muscular relaxation following Jacobson, the patient is lying or sitting. 

Variables collected: physical (skin conductance, pulse rate), questionnaire 

data (PO-Bado, HADS, ERQ, SAM), general information (tumour 

location, tumour progression, number of medical consultations). 

Results. First results are expected to be available by the end of 2011. 

0110 

Psychological distress of cancer patients and their partners – 

comparison on pair level and influence of sex 

*H . Götze1 , J . Ernst1 , R . Schmidt1 , J . Dorst2 , G . Romer3 , E . Brähler1 1Universitätsklinikum Leipzig, Department für Psychische Gesundheit, Abteilung 

für Medizinische Psychologie und Medizinische Soziologie, Leipzig, 

Deutschland, 2Universitätsklinikum, Hämatologie, Leipzig, Deutschland, 

3Universitätsklinikum Hamburg-Eppendorf, Klinik für Kinder- und Jugendpsychiatrie, 

-psychotherapie und -psychosomatik, Hamburg, Deutschland 

Background and objectives. It is undisputed that cancer represents a major 

psychological distress for patients and their partners. However, to 

date there are few studies about the characteristic of anxiety and depression 

of cancer patients and their partners which include the correlation 

within the couple considering gender aspects. This study was part of the 

German multi-site research project Psychosocial Services for Children 

of Parents with Cancer supported by the German Cancer Aid (Deutsche 

Krebshilfe, grant #108303) and was accomplished of 2009–2012 at five 

locations (Hamburg, Berlin, Heidelberg, Magdeburg and Leipzig). This 

investigation focused on the psychological distress of cancer patients 

with minor children on pair level and showed sex differences. 

Methods. In 113 cancer patients and their partners with minor children 

anxiety and depression after the acute treatment were explored using 

the Hospital Anxiety and Depression Scale (HADS). Correlation within 

the couples was computed depending on sex. 

Results. There was a great correlation between the psychological distress 

of the cancer patients with underage children and their partners (anxiety: 

r=0.323, p

0126 

Emotional memory in breast cancer survivors: Neuropsychological 

functioning and neuronal correlates 

*J . Wirkner 1 , C . Hamm 2 , A . Löw 1 , M . Weymar 3 , A .-M . Struck 1 , A .O . Hamm 1 

1 University of Greifswald, Department of Biological and Clinical Psychology, 

Greifswald, Deutschland, 2 University Medicine Greifswald, Department 

of Psychiatry and Psychotherapy, Greifswald, Deutschland, 3 University of 

Florida, NIMH Center for the Study of Emotion and Attention, Center for 

Psychophysiology, Gainesville, FL, USA 

Objective. Chemotherapy and endocrine therapy of breast cancer are 

accompanied by a wide spectrum of side effects, including a decline of 

cognitive functions that diminish quality of life and well-being. While 

such impairments are frequently described in self-reports, empirical 

findings are inconsistent and the underlying neuronal mechanisms are 

not fully understood. Here, we examine cognitive functioning of breast 

cancer survivors using neuropsychological testing as well as event-related 

potentials during an emotional long-term memory task. 

Methods. Female breast cancer survivors (n=12) after chemotherapy 

and endocrine therapy (tamoxifen, aromatase inhibitors) were compared 

with a sample of healthy matched controls. We assessed memory 

(WMS-R, VLMT) and attention (TAP). In addition, participants viewed 

a series of emotional and neutral pictures, followed by an unexpected 

recognition memory test one week later and high-density event-related 

potentials were recorded to examine underlying brain mechanisms 

of attention and emotional memory. 

Results. In neuropsychological testing, breast cancer survivors were 

characterized by subtle impairments and exhibited larger interindividual 

variance than controls. During encoding, emotional stimuli evoked 

larger late positive potentials signaling enhanced attention towards 

motivationally relevant materials in both groups. Brain potentials during 

recall showed enhanced positivity for correctly remembered old 

compared to correctly classified unseen items (‘old/new effect’) and 

were larger for emotional compared to neutral stimuli. This pattern of 

results was shown in breast cancer survivors as well as in matched controls. 

Conclusions. Cognitive changes following cancer therapy are subtle and 

objective measures of cognitive functions revealed no strong overall impairment 

in (emotional) memory and attention. 

0140 

Effects of a 15-month rehabilitative exercise program in prostate 

cancer patients following a radical prostatectomy – first results 

of the ProRehab Study 

*E .M . Zopf1 , M . Braun2 , S . Machtens3 , J . Zumbé4 , W . Bloch1 , F . Baumann1 1 Deutsche Sporthochschule Köln, Institut für Kreislaufforschung und Sportmedizin, 

Molekulare und Zelluläre Sportmedizin, Köln, Deutschland, 2 Heilig-Geist-Krankenhaus, 

Köln, Deutschland, 3 Marienkrankenhaus, Bergisch 

Gladbach, Deutschland, 4 Klinikum Leverkusen, Leverkusen, Deutschland 

Background. Over 60,120 new cases of prostate cancer (PCa) are reported 

annually in Germany. Despite the increasing incidence and the common 

treatment-related side effects there is a lack of supportive measures 

for male patients and only few studies have evaluated physical activities 

in the after-care of PCa. The Cancer Society North Rhine-Westphalia 

(NRW), the German Sport University Cologne and the State Sport Association 

NRW set themselves the goal to establish rehabilitative sports 

groups particularly for PCa patients and to evaluate the effects of the 

offered exercise program. 

Methods. In cooperation with 4 acute clinics 107 PCa patients following 

a radical prostatectomy were recruited into this randomized-controlled 

and patient-preference trial. Within a 15-month intervention patients 

exercise in a pre-established rehabilitative sports group once a week for 

60 minutes. Additionally patients are asked to exercise a second time 

independently. Patients in the control group do not participate in the 

intervention. The outcomes of the study include: aerobic endurance performance, 

PA levels, quality of life, incontinence, erectile dysfunction 

and specific blood values. 

Results. The study started off in October 2007 and will be completed by 

the end of the year 2011. First intermediate results concerning the effects 

of the offered exercise program show improvements in PA levels and 

quality of life and no significant changes in PSA or testosterone levels. 

Discussion. The ProRehab study is presumably the first randomizedcontrolled 

trial with such a long exercise intervention and is therefore 

likely to promote long-term lifestyle changes in PCa patients. By combining 

science, practice and public relations an interdisciplinary and 

multi-centric project was initiated. The findings of our study and future 

investigations will help optimize exercise recommendations for PCA 

patients. Further and more detailed results will be available at the time 

of the meeting. 

0153 

Distress, acceptance and knowledge of psychooncological facilities 

by patients with colorectal cancer – results of a representative 

study in Bavaria 

*A . Beraldi1 , 2 , E . Kukk2 , 3 , G . Schubert-Fritschle4 , J . Engel4 , P . Herschbach3 , 5 , 

P . Heußner1 1 LMU, Psychoonkologie Med III, München, Deutschland, 2 Tumorzentrum, 

München, Deutschland, 3 Technische Universität, Sektion Psychosoziale 

Onkologie, München, Deutschland, 4 Tumorregister, München, Deutschland, 

5 Roman-Herzog Krebszentrum, München, Deutschland 

Background. Psychooncological studies about distress usually take place 

during primary care and lack of representativeness. Little is known about 

distress and needs of patients when back in their familiar environment. 

In our study this absence of representativeness could be avoided 

by the recruitment procedure and by the cooperation with the Tumour 

Register of Munich (TRM). The following questions were investigated: 

1) What is the prevalence of distress, depression and anxiety in patients 

with colorectal cancer? 2) Which are predictive factors of distress, depression 

an anxiety? 3) How is the acceptance and knowledge of psychooncological 

facilities in the neighborhood? 4) Which are predictive 

factors of acceptance and knowledge of psychooncological facilities? 5) 

Which offers of psychooncological treatment can be found in the region? 

Method. Patients with a colorectal tumour were recruited by their hospital 

surgeon and received 3 months after inclusion a questionnaire 

concerning socio-demographic and medical information, acceptance 

and knowledge about psychooncological facilities as well as psychosocial 

distress, depression and anxiety. We adjusted our sample for age and 

sex according to the data of the TRM, so that the resulting sample was 

representative for the catchment area of the TRM. At the same time we 

carried out an internet research recording all psychooncological facilities 

in the catchment area of the TRM. 

Results. N=534 patients. Mean age was 68.9 years (SD=11.33). 27.6% of 

the patients presented metastases. 50.8% received chemotherapy. 26% of 

the sample presented distress. 12.4% of the patients had elevated anxiety 

and 14.8% elevated depression scores. 52% of the sample did not know 

any psychosocial support facility. Only 1.2% of the patients made use 

of support. 55.8% answered that they would accept or probably/perhaps 

accept support. Predicitive factors for psycho-social distress were not 

talking to the general practitioner, psychotherapy in the past and chemotherapy. 

Predictive factors for acceptance were psychotherapy in the 

past and distress. In our sample patients from rural regions were better 

informed than patients from the city. The outpatient care situation 

showed that 10% of the patients did not have a psycho-social support 

in the vicinity (20 km) of home. Outpatient psychooncological support 

and resident haemato-oncologists showed the strongest undersupply in 

rural regions. 


123

Abstracts 

0154 

Perception and attitudes of professionals regarding age and 

need oriented education of children of parents with cancer 

*A . Beraldi1 , M . Köllner1 , S . Tari2 , W . Hiddemann1 , P . Heußner1 1 2 LMU, Psychoonkologie Med III, München, Deutschland, lebensmut e .V ., 


The cancer disease of a parent affects the whole family and may present 

an enormous distress factor. Parents are often uncertain, if and how to 

talk about the disease to their children. 56% of the parents do not talk 

about the imminent death of the other parent although the correlation 

between deficient communication and the manifestation of mental disorders 

has been demonstrated (Siegel et al., 1996). The contribution of 

the family counseling funded by lebensmut e.V. at the university hospital 

Großhadern in Munich consists of the parents‘ support to prevent 

their children from developing mental disorders by education, consultation 

and therapeutic interventions. Another relevant contribution 

consists in sensibilizing all involved professionals (e. g. doctors, nurses, 

psychotherapists, teachers) in order to offer prevention or to recognize 

needs in time. Appropriate support may range from the correct information 

to specific questions (e.g. „May I tell my daughter that I have 

breast cancer? May I bring my children to the ward? Will they bear it?“) 

to therapy sessions for the children. The better all involved professionals 

are informed about how to deal with children of parents with cancer the 

better parents can be supported. The clinical experience however shows 

that professionals too, are often uncertain and ambivalent regarding the 

children‘s involvement in the disease management. The objective of present 

explorative study is to assess these observations. We aim to explore 

with the help of a questionnaire the perception, attitudes and cognitions 

of the different staff members (doctors, nurses, psychotherapists, pastoral 

care, social workers) regarding the education of children of cancer 

patients. Preliminary results will be presented. Depending on the study 

results, information and education programmes for professionals shall 

be developed and provided on the long run. 

0158 

Evaluation of a new course on teaching of erectile dysfunction 

following pelvic surgery in men with prostate or bladder cancer 

in undergraduate medical education 

V . Müller-Mattheis1 , C . Schulz1 , R . Schmelzer1 , A . Mortsiefer1 , T . Rotthoff1 , 

P . Albers1 , A . Karger1 1 Heinrich-Heine-Universität Düsseldorf, Urologie, Düsseldorf, Deutschland 

Introduction. Talking to patients who suffer from sexual problems is 

a relevant but under-represented issue in medical education. Besides 

knowledge for diagnosis and treatment of sexual disorders also specific 

communication skills (e.g. in history taking) are mandatory as much 

as an accepting mindset for talking about tabooed themes. As a part of 

the development and implementation of a longitudinal communication 

curriculum CoMeD, an interdisciplinary training course concentrating 

on erectile dysfunction was introduced in 2010 by the Departments of 

Urology and Psychosomatic Medicine & Psychotherapy. Training concept 

(a) and student’s evaluation (b) are presented. 

Methods. (a) The multi-stage development process included needs-assessment 

to determine student’s needs and interests, defining learning 

objectives and teaching methods. We produced instructional material 

and provided special training sessions for course teachers and simulated 

patients. (b) Participating students evaluated the training course in 

reference to subjective learning curve, practical relevance, and a global 

quality appraisal each by 5-point LIKERT scaling. 

Results. (a) We could develop a new CoMeD training course with following 

contents of teaching: urological knowledge especially of surgical 

pelvic anatomy and postoperative problems in patients having undergone 

radical cystectomy/prostatectomy, interview with simulated patients 


(sexual history taking), interview with real prostate cancer patients suffering 

from erectile dysfunction, feedback and discussion. (b) Student’s 

mean evaluation was good (overall results of three term cohorts, n=173). 

Conclusion. Introduction of an interdisciplinary training course providing 

explicit urological knowledge as well as communication skills 

could successfully be accomplished and was much appreciated by our 

students. The authors see this approach as highly valuable for further 

medical curriculum development and assimilating specific psychooncological 

skills. 

0161 

Quality of life in long-term survivors of breast, colorectal, and 

prostate cancer – First results from the CAESAR study 

*V . Arndt1 , L . Koch1 , H . Bertram2 , A . Eberle3 , S . Schmid-Höpfner4 , C . Stegmaier5 

, A . Waldmann6 , S . Zeissig7 , H . Brenner1 1German Cancer Research Center (dkfz), Clinical Epidemiology and Aging 

Research (C070 ), Heidelberg, Deutschland, 2Cancer Registry of North Rhine- 

Westphalia, (Münster Region), Münster, Deutschland, 3Bremen Cancer 

Registy, Bremen, Deutschland, 4Hamburg Cancer Registry, Hamburg, 

Deutschland, 5Saarland Cancer Registry, Saarbrücken, Deutschland, 

6University Hospital Schleswig-Holstein, Institute of Clinical Epidemiology, 

Lübeck, Deutschland, 7Cancer Registry Rhineland-Palatinate, Mainz, 

Deutschland 

Background. The CAESAR-study (Cancer Survivorship – a multi-regional 

population-based study) was started in October 2008 to study 

important quality of life aspects in long-term survivors (5+ years) after 

diagnosis of breast, colorectal or prostate cancer. 

Methods. The study is based on a joint analysis of several populationbased 

samples of cancer survivors from various cancer registries across 

Germany (Bremen, Hamburg, Münster/North Rhine-Westphalia, 

Rhineland-Palatinate, Saarland, Schleswig-Holstein). Potential study 

participants were identified by the participating cancer registries and 

were either contacted directly by the pertinent cancer registry or the 

treating physician, depending on the federal legislation. The questionnaire 

included internationally validated standardized instruments 

(e.g. EORTC Quality of Life Core Questionnaire, Fatigue Assessment 

Questionnaire, Geriatric Depression Scale, Benefit Finding Scale, Post 

Traumatic Growth Inventory). It was planned that a total of approximately 

6700–7000 survivors would be eligible and participate. 

Results. The recruitment started in August 2009 and lasted until April 

2011. The actual number of over 7100 cancer survivors who filled out 

the questionnaire exceeded the anticipated number. Depending on the 

region specific recruitment schemes up to 88% of all contacted survivors 

completed the questionnaire. First results from the Saarland VERDI cohort, 

a cohort which has been repeatedly contacted over the first ten years 

after diagnosis, indicate that long-term cancer survivors experience 

more restrictions in role, emotional, cognitive, and social functioning 

than controls from the general population. Further in-depth analysis as 

well as results from the other regions will be presented. 

Conclusions. Our preliminary results indicate that quality of life is a topic 

of high relevance for long-term survivors. Furthermore, detriments 

in psychosocial functioning persist over years even in cancer survivors 

considered to be cured.

0171 

Treatment decision-making at the end of life in oncology: results 

of a qualitative study on perceptions and ethical views of physicians 

in Germany and England 

*J . Schildmann1 , J . Tan1 , J . Vollmann2 1Ruhr-Universität Bochum, Institut für Medizinische Ethik und Geschichte 

der Medizin, NRW-Nachwuchsforschergruppe „Medizinethik am Lebensende: 

Norm und Empirie“, Bochum, UK, 2Ruhr-Universität Bochum, Institut 

für Medizinische Ethik und Geschichte der Medizin, Bochum, Deutschland 

Resarch question. Limitation of treatment is part of the care for patients 

with incurable cancer. We explored the perception and ethical views of 

oncologists working in Germany and the United Kingdom regarding 

these decisions. 

Methods. Qualitative semi-structured interviews with physicians working 

in oncology in Germany and England were carried out. Interviews 

were audiotaped and transcribed. Transcripts were coded by identifying 

major themes of the interviews using constant comparison, in order 

to examine similarities and differences between oncologists across the 

whole sample. 

Results. 17 (Germany) and 12 (United Kingdom) research interviews 

were analysed. Interviews varied in length between 27 and 73 minutes. 

Respondents from both countries named a variety of treatment modalities 

which may be limited in the context of care for patients with 

incurable cancer. After standard clinical criteria for decision-making 

(e.g. performance status), perception of the life circumstances of the patient 

(e.g. being a mother of young children) as well as highly individual 

aspects of the physician-patient relationship (e.g. parallels between the 

biographies of physicians and patients biographies) were reported to 

most influence these treatment decisions. Discussions with colleagues 

and the multidisciplinary team were emphasised as correctives to make 

the decisions less subjective; these were emphasised as strategies by oncologists 

working in the United Kingdom. Physicians in both countries 

reported that non-harming treatment was given to patients who did not 

accept the initial recommendation of oncologists to stop treatment. The 

duty not to harm was cited as the rationale to limit treatment even if 

there was a wish on side of the patients to receive further interventions. 

Conclusions. This study indicates that decisions about limitation of medical 

treatment are based on numerous medical and non-medical factors. 

Potential strategies for dealing with clinical and ethical challenges 

in end stage cancer will be discussed. 

0184 

Implementation of a multidisciplinary psychosocial screening 

tool with touch-screen technology in a German Comprehensive 

Cancer Center 

*A . Brechtel1 , J . Walther2 , K . Bikowski2 , D . Jäger2 , W . Herzog3 1Nationales Centrum für Tumorerkrankungen, Psychoonkologische Ambulanz, 

Heidelberg, Deutschland, 2Nationales Centrum für Tumorerkrankungen, 

Heidelberg, Deutschland, 3Klinik für Allgemeine Innere Medizin und 

Psychosomatik, Heidelberg, Deutschland 

Objective. The purpose of our presentation is to describe the implementation 

of a multidisciplinary psychosocial screening in a Comprehensive 

Cancer Center (CCC) setting using touch-screen technology illustrating 

barriers, necessary frameworks and setting-specific adaptations. 

Background. Psychosocial research emphasizes the need for early identification 

of distress, and there is an increasing empirical support for 

the importance of systematic psychosocial screening of cancer patients. 

However, the practical issues of implementing psychosocial screening 

as an integral part of a comprehensive and patient-oriented cancer treatment 

in a CCC have been rarely addressed or investigated so far. Besides 

various paper-based screening tools, there is a growing interest in 

the use of touch-screen technology. Experiences with this technology 

and respective advantages have been described in the international literature. 

Methods. We implemented a touch-screen screening instrument addressing 

not only psychosocial distress, but also nutritional aspects 

as well as patients’ interest in the offer of various counselling services. 

Revisions and necessary adaptations are made by a multidisciplinary 

working group. 

Results. We found various barriers to implement this technology as an 

integral part of the cancer treatment. A special challenge seemed to be 

to adopt the screening process to the existing or newly established clinical 

units of cancer treatment in our CCC. Each clinical unit has its own 

culture and needs to be addressed respectively. One major barrier was 

the attitude of involved personnel who felt that the screening would be 

burdensome for patients. 

Conclusions. The implementation of such a screening tool and procedure 

requires a lot of preparatory work and the adaptation to settingspecific 

frameworks. Besides specific technical requirements the multidisciplinary 

communication and exchange as well as the training of 

the involved personnel present important tasks. The acceptance from 

all involved disciplines represents a major prerequisite for the successful 

implementation and integration in routine care. 

0186 

Inwieweit profitieren Brustkrebs betroffene Frauen besonders 

bezüglich der Langzeitwirkung von psychoedukativen Seminaren? 

– Ergebnisse einer Nachbefragung 6 Jahre später 

*J . Schwickerath1 , E . Reuter1,2 1 2 St . Martinus-Hospital, Frauenklinik, Olpe, Deutschland, Psychonkologische 

Schwerpunktpraxis, Olpe, Deutschland 

Nach der Diagnose Brustkrebs entwickeln die betroffenen Frauen 

unterschiedliche Strategien, um mit der Erkrankung und ihren Folgen 

wieder ins Leben zurückzufinden. Um den Frauen in dieser schweren 

Zeit auf ihrem Weg zu helfen, bieten wir seit 2001 sog. psychoedukative 

Patientenseminare an. Ziel dieser Seminare ist es auch, die Patientenkompetenz 

der Betroffenen zu steigern. Wir verstehen unter diesem Begriff, 

dass die Frauen in hohem Maße wünschen und letztendlich auch 

in der Lage sind, bei der Behandlung ihrer Erkrankung gleichberechtigt 

und eigenverantwortlich mitzuarbeiten. Dafür sind Entwicklung von 

Sachverstand und Wissen erforderlich, sowie der Mut und das Selbstbewusstsein, 

mit den Behandlern auf gleicher Augenhöhe zu sprechen. 

Über die wissenschaftliche Evaluation unserer bisherigen 14 Seminare 

(n:195) haben wir nachweisen können, dass alle Teilnehmerinnen 

betreffs ihres Kohärenzgefühls und ihres Coping-Verhaltens in der 

Post-Befragung eine Steigerung angegeben haben. Uns hatte nun interessiert, 

wie weit diese positive Lebensveränderung trotz der Diagnose 

angehalten hat, respektive ob sich diesbezüglich Jahre später eine Änderung 

ergeben hat. Wir haben die Seminarteilnehmerinnen aus den Jahren 

2001 bis 2005 betreffs unserer Studie angeschrieben. 95 Frauen, mit 

einer durchschnittlichen Zeitspanne zwischen Patientenseminarende 

und Beginn der Befragung von 72 Monaten, konnten wir letztendlich 

in die Studie aufnehmen. Die Teilnehmerinnen haben auch Jahre später 

die durch die Seminare gewonnene Steigerung ihrer Lebensqualität 

über die emotionale Stabilisierung, Verbesserung der Selbstfürsorge 

und der Compliance beibehalten und – nach ihren Aussagen – noch 

steigern können. Die Ergebnisse unserer Studie zeigen, dass es sich auch 

bezüglich der Langzeitwirkung lohnt, den betroffenen Frauen solche 

Seminare anzubieten. 


125

Abstracts 

0190 

Exercise and cancer – how do physically active and inactive cancer 

patients differ in social cognitive variables from the Theory of 

Planned Behavior? 

*N . Ungar1,2 , M . Sieverding1 , C . Ulrich2 , J . Wiskemann2,3 1University of Heidelberg, Psychological Institute, Heidelberg, Deutschland, 

2National Center for Tumor Diseases, Preventive Oncology, German Cancer 

Research Center, Heidelberg, Deutschland, 3National Center for Tumor 

Diseases, University Clinic, Medical Oncology, Heidelberg, Deutschland 

Objectives. The current recommendation for cancer patients is to exercise 

moderately 150 minutes a week. Despite many positive effects of 

physical activity, many cancer patients are quite physically inactive. The 

Theory of Planned Behavior by Ajzen which is based on social cognitive 

variables can be helpful to explain physical activity. Do physically active 

and inactive patients differ in these social cognitive variables? That 

means, do they have a different intention, attitude, perceived behavioral 

control and subjective norm towards exercising? This pilot-study should 

furthermore identify which of these variables can predict the intention 

to be physically active. 

Methods. 63 patients (m=39, w=24; mean=60 years) of different cancer 

entities and different outpatient therapy regimes (50% chemotherapy at 

present) were recruited in the National Center for Tumor Diseases in 

Heidelberg. They had to fill out a questionnaire assessing their physical 

activity, variables of the Theory of Planned Behavior and socio-demographic 

variables. 

Results. 27 patients of the sample were classified as physically inactive 

(

0209 

Psychooncological support needs assessment in hematology – 

implementation, acceptance and results 

*A . Koch1 , M . Herold1 , H . Göbel2 1 4 HELIOS Klinikum Erfurt, . Medizinische Klinik, Hämatologie und internistische 

Onkologie, Hämostaseologie, Erfurt, Deutschland, 2HELIOS Klinikum 

Erfurt, Tumorzentrum, Erfurt, Deutschland 

Objectives. The psychosocial support of cancer patients with initial diagnosis 

has improved due to the certification of numerous organ tumor 

centers. However, it shows that the full supply by certified psychooncologists 

is currently not yet possible due to economic restrictions. A 

sustainable model needs to be implemented into hospital workflow that 

allows access to psychooncological support offers and is economical as 

well. 

Methods. Assignments of the patients to psychological support cannot 

happen solely by physicians or nursing staff, because they often do not 

assess the actual need properly. Realization of evidence based screening 

diagnostics to assess the need has proven to be reliable and valid in several 

studies. However, psychooncological screening methods in the hematology 

(diagnoses: ICD-10 C81-96) are quite new and are controversially 

discussed within other organ tumor centers. Aim of this study is 

to analyze the approach of the Hornheider Screening Instrument (HSI) 

in clinical routine and to evaluate the acceptance of the questionnaire. 

Results. The following results and conclusions are preliminary. The oneyear 

clinical outcomes will be presented at the congress. Within the first 

6 months period of survey, 179 patients with hematooncologic diagnosis 

were treated. The return ratio of the HSI questionnaire was 65%. For 

32% of the respondents, psychological treatment identified to be needed. 

Primarily, patients reported to be burdened physically (54%) and mentally 

(43%). 36% of the respondents considered their family especially 

burdened. 19% of the patients described information deficits concerning 

their tumor disease. 15% expressed the desire for psychological support 

and 3% were already in outpatient psychotherapy. 

Conclusions. The screening method used proves to be practical. The 

question about the best time to assess the patients’ burdens and wishes 

for psychooncological support remains. Furthermore, it could be 

observed that the mental strain and need for support increases under 

chemotherapy or occurrence of relapses. Continuous follow up surveys 

might be necessary. A consultation service cannot satisfy the needs. 

Psychooncological liaison services, which are integrated into the stationary 

routines, are useful and suitable. 

0263 

Effects of aquatic exercise on quality of life and activities of daily 

living in breast cancer patients with secondary arm lymphedema 

*B . Roling1 , *D . Hermann1 , F .T . Baumann1 1Deutsche Sporthochschule, Köln, Deutschland 

Introduction. Secondary arm lymphedema is one of the most feared and 

multidimensional complication following breast cancer disease and treatment 

(Micke et al. 2000). Patients suffer from progressive and chronic 

dysfunctions particularly of the upper extremity, resulting in physical, 

psychological and social impairments which may affect quality of life 

and activities of daily living (Hull 2000, Isermann 2006). The prevailing 

treatment of lymphedema is currently the complex physical therapy 

which can improve the physical condition. However, psychosocial 

impairments are not considered sufficiently. A holistic therapy is needed. 

Due to the specific hydrodynamic properties, aquatic exercise may 

present such a therapy approach. Although aquatic exercise has already 

been implemented in the oncological rehabilitation, it has not attracted 

much interest in research (Baumann & Schüle 2008). In order to reduce 

this gap between science and practice, this study investigated the effects 

of a semiweekly aquatic therapy over twelve weeks on quality of life and 

activities of daily living in breast cancer patients with secondary arm 

lymphedema. 

Methods. Nine women participated in a semiweekly aquatic therapy 

over twelve weeks. Findings were assessed via four questionnaires 

(FLQA-I, Freiburger Fragebogen zur körperlichen Aktivität, EORTC 

QLQ-C30, EORTC QLQ-BR23) and measurement of arm circumference 

at five times (baseline, after six and twelve weeks of the intervention, 

three- and six-months follow-up). 

Results. Aquatic exercise had immediate positive, partly statistically significant 

effects on quality of life and lymphedema symptoms, especially 

arm symptoms (baseline-after 12 weeks: p=0.022). But no long-term effects 

were noted. Conversely, activities of daily living decreased during 

the intervention and showed an increase in the follow-ups. 

Discussion and conclusion. This study provides first evidence of multidimensional 

effects of aquatic exercise not only on activities of daily 

living and quality of life in breast cancer patients, but also lymphedema 

condition itself. However, permanent positive effects can only be achieved 

by long-term and regular participation. In related studies of Tidhar 

& Katz-Leurer (2009), Hayes et al. (2009) and Box et al. (2004) similar 

results are shown. Further studies have to be conducted in order to specify 

the exact effects of aquatic therapy on lymphedema and to define 

precise exercise recommendations for breast cancer patients. 

0264 

The influence of a long hike on psychological parameters of 

patients after breast care treatment 

*S . Metzner1 , I . Germ1 , L . Thiele1 , S . Gräfingholt1 , W . Bloch1 , F . Baumann1 1Deutsche Sporthochschule Köln, Institut für Kreislaufforschung und 

Sportmedizin, Abteilung für molekulare und zelluläre Sportmedizin, Köln, 

Deutschland 

Years after the diagnosis, patients suffer of psychiatric problems that, 

to them, seem a lot more serious than their physical deficits. Of meaning 

are depressions, anxiety and attention disorders (Burgess et al. 

2005, Heckl & Weis 2006). Long hikes (810 km, 10,000 m high, 22 km/ 

day, 6 weeks) along the French Camino de Santiago are supposed to 

improve this psychological condition (Brämer 2001). Woman diagnosed 

with breast cancer (n=22, age: 53±7 years, post diagnosis 1,8±1 year, 

BMI: 23,5±3,58 kg/m2), whose acute treatment had been completed, were 

observed in relation to quality of life (EORTC QLQ C-30 and BR-23) 

attention/awareness (MAAS) and anxiety and depression (HADS). Test 

subjects were free to choose their own speed and resting periods. Questionnaires 

were completed at the beginning, after a 2-month training 

interval, and after the 2nd, 4th and 6th week of the hike. For the evaluation 

of long term effects, 6 and 12 months after the intervention all 

questionnaires were filled in again. The results show significant improvement 

in nearly every area, for example: global health status (T1=67.4, 

T7=77.1, p

Abstracts 

1 . Brämer B (2001) Wandern neu entdeckt . Warum es sich lohnt wieder mehr zu 

Fuß zu reisen (elektronische Version) . Burg & Steigen 3:22–28 

2 . Burgess C, Cornelius V, Love S, Graham J, Richards M, Ramirez A (2005) Depression 

and anxiety in women with early breast cancer: five year observational 

cohort study . BMJ (Clinical research ed .) 330:702–705 

3 . Gebhard U (1993) Erfahrung von Natur und seelische Gesundheit . In: Seel H-J, 

Sichler R, Fischerlehner B, Mensch und Natur . Psychologische Aspekte einer 

problematischen Beziehung . Opladen, S . 127–147 

4 . Heckl U, Weis J (2006) Medizinpsychologische Aspekte der Patientin mit 

Mammakarzinom . In: Kreienberg R, Jonat W, Volm T, Möbus V, Alt D (Hrsg .), 

Management des Mammakarzinoms . Springer Medizin Verlag, Heidelberg, 

S . 469–487 

5 . McNeely, ML, Campbell, KL, Rowe, BH, Klassen, TP, Mackey, JR & Courneya, KS 

(2006) Effects of exercise on breast cancer patients and survivors: a systematic 

review and meta-analysis . Canadian Medical Association Journal 175(1):34–41 

0293 

Attitudes towards euthanasia. The impact of the experience of 

supporting a dying relative 

*N . Köhler1 , H . Götze1 , L . Gansera1 , S . Berger1 , R .-D . Kortmann2 , E . Brähler1 1Universitätsklinikum Leipzig, Abteilung f . Medizinische Psychologie und 

Medizinische Soziologie, Leipzig, Deutschland, 2Universitätsklinikum Leipzig, 

Klinik für Strahlentherapie und Radioonkologie, Leipzig, Deutschland 

Introduction. It is a point of debate whether euthanasia should be part 

of medical practice. The current study investigates the attitudes of bereaved 

family members who had experienced end-of-life care towards 

euthanasia. In this abstract, we present preliminary results. The study 

was sponsored by the German Cancer Aid (Deutsche Krebshilfe e.V.). 

Methods. We have conducted an online survey with people who had lost 

a close relative to cancer during the last 12 months. Participants were 

asked whether indirect, passive, active euthanasia and assisted suicide 

should be part of medical practice. The results of this survey were compared 

with those of a survey of the general German population from 

2001 (Schröder 2003). The participants of the online survey were mostly 

female and of younger age than the general population, the two groups 

were matched according to age and sex. 

Results. In general, most bereaved family members approved the idea 

of indirect and passive euthanasia being part of medical practice. Bereaved 

family members of cancer patients (approx. 90%) significantly 

more often wanted indirect and passive euthanasia to be part of medical 

practice than the general population (approx. 66%). Regarding active 

euthanasia and assisted suicide, the differences between both groups 

were much smaller. 70% and 67% of the bereaved family members vs. 

55% and 60% of the general population wanted those forms of euthanasia 

to be part of medical practice. 

Conclusions. On possible explanation for the stronger support of euthanasia 

by bereaved family members may be the experience of supporting 

a dying relative. Since the survey of the general German population was 

conducted about ten years ago, it seems also possible that the acceptance 

of euthanasia may have increased since then in the general population. 

0298 

National survey of physicians’ communicative competence training 

in medical education 

*C . Kloepfer1 , A . Spieser1 , J . Weis1 1Klinik für Tumorbiologie, Psychosoziale Abteilung, Freiburg, Deutschland 

Purpose. Communication between physicians and patients is an important 

component in medical services. Compelling evidence from clinical 

trials indicates that good communication skills of health professionals 

show positive effects on physicians (burn-out prophylaxis, increased job 

satisfaction etc.) as well as on patients (particularly with regard to can- 


cer patients increased treatment adherence, psychological functioning 

etc.) and therefore influences therapeutic response. The National Cancer 

Plan of Germany, coordinated by the Federal Ministry of Health has 

in line with more patient-centred approach the aim to improve physician-patient 

communication in medical education and medical care of 

cancer patients. The aim of this study was to describe the status quo of 

the medical undergraduate and postgraduate education and residency 

training in terms of communication skills. 

Methods. In order to examine the status quo of training communication 

skills in medical services, a structured questionnaire was developed 

separate for undergraduate/ postgraduate medical education and for 

residency training programs. The undergraduate/ postgraduate questionnaire 

was applied between January and June 2011 at 1122 medical 

lecturers of German universities, accordingly the residency questionnaire 

was applied in July 2011 to 1164 directors of clinician institutes 

and oncology associated medical services. The questionnaires surveys 

educational objectives, pedagogic tools, didactics, time frames, structural 

circumstances, examination methods, etc. Descriptive analysis of 

the data (performed with SPSS for Windows, Version 18) includes mean 

values, standard deviation and percentage of the main questionnaire 

issues. 

Results and conclusions. The current study aspire an overview of training 

communication skills and social competencies in German medical education 

and medical care services of cancer patients. First results indicate 

complexity and heterogeneity with regard to structural conditions and 

with regard to implementation of communication skills training. The 

study results will provide important data to describe the need for improvement 

of communication skills training within medical education. 

0299 

Life goals, depression and quality of life in cancer patients 

*P . von Blanckenburg1 , M . Bodenbenner1 , N . Conrad1 , W . Rief1 , C . Exner1,2 , 

U . Seifart3 1Philipps Universität Marburg, Klinische Psychologie und Psychotherapie, 

Marburg, Deutschland, 2Universität Leipzig, Klinische Psychologie, Leipzig, 

Deutschland, 3Rehabilitation Clinic Sonnenblick, Marburg, Deutschland 

Purpose. A cancer diagnosis affects the pursuit of patients’ life goals. Discrepancies 

occur between the importance of a life goal and the success 

in achieving it. The aim of the present study was to compare subjective 

importance and success in attainment of life goals in cancer patients 

with a normative sample. Further objectives were to examine associations 

between life goal discrepancies and patients’ well-being (quality 

of life/depressive symptoms), and to identify the predictive value of life 

goal adjustment two years later. 

Methods. A sample of 82 inpatients (female: 5.9%; mean age: 52.6; SD: 

8.0) was recruited during oncological rehabilitation. Attributes of six 

different life goal domains were measured using the Life Goal Questionnaire 

(GOALS). Depressive symptoms were assessed with the Center 

for Epidemiologic Studies Depression Scale (CES-D) and global quality 

of life using the short WHO-Quality of Life Questionnaire (WHO- 

QOL-BREF). Relevant medical and demographic data were recorded. A 

subsample (n=28) was reassessed two years later. 

Results. Intimacy (e.g. to have a close relationship) was the most important 

life goal domain and significantly more important to oncological 

patients than to controls. Altruism (e.g. to act unselfishly), power 

(e.g. to exert influence) and variation (e.g. to live an exciting life) were 

less important. Patients experienced greater success in attaining the life 

goal intimacy and less success in the domains achievement (e.g. to improve 

skills continuously), affiliation (e.g. to have many social contacts), 

power and variation. With the use of hierarchical multiple regression 

analyses – after controlling for demographic variables – the overall life 

goal discrepancy was associated with depression (adjusted R2=0.180, 

p

the general life goal adaption was associated with higher global quality 

of life after two years and not associated with depressive symptoms. 

Discussion: Discrepancies in the importance and perceived success in 

attaining life goals were associated with the subjective well-being of 

cancer patients. Particularly relationship-orientated life goals seem to 

play a major role in patients’ well-being. The results suggest that patients 

could profit from psychological interventions that foster life goal adaptation 

to enhance the global quality of life in cancer survivors. 

0307 

Certified cancer centre and specialized outpatient palliative care 

*K . Neuwöhner1 , *R . Wildner2 1Klinik Dr . Hancken GmbH, Zentrum f . Palliativmedizin, Stade, Deutschland, 

2Klinik Dr . Hancken GmbH, Palliativteam Niederelbe, Stade, Deutschland 

Introduction. Since April 1st, 2007, in accordance with the Social Code 

Book V (SGB V), patients with statutory legal insurance are entitled to 

specialized outpatient palliative care (SAPV). The legislator intended 

these services for insured persons suffering from an incurable disease, 

with limited life expectancy and a special need for care. Following the 

directives of the Federal Joint Committee ca. 170 specialized palliative 

home care services were founded in Germany since 2007 and set to 

work until 2011. Only few were integrated in certified cancer centres. 

The reason is, cancer centres are often departments of hospitals and the 

medical and nursing staff members cannot cross the legal borderline 

between inpatient and outpatient services in Germany. 

Method. In the regional cancer centre of Stade, certified since 2004 by 

ESMO, a specialized palliative home care service was founded at January 

1st, 2011, with a coordinator and five cooperating oncologists with 

certificates in palliative medicine and three cooperating palliative care 

nurses. The managing board of the hospital offered the staff members to 

change the employment contracts and split their working time with the 

inpatient and outpatient service in a flexible way. 

Results. The specialized palliative home care service of the cancer centre 

attended 60 patients from January until July 1st, 2011 with advanced 

cancer disease and in a terminal status of the disease, with averaged 

27 days of care. Nursing and medical staff members of the hospital paid 

about 500 house visits to their patients. Further results will be presented. 

Conclusion. There was an increased demand for specialized palliative 

home care. The needs were on a high level of complexity and involved 

medical, nursing, psycho-social and spiritual requirements. The most 

impressing positive experience on both sides, staff members and patients 

and their families was the continuity of caring across the borderline 

between inpatient and outpatient services. 

0333 

Physical activity in colorectal cancer patients: a review of clinical 

trials 

*W . Jensen1 , K . Oechsle1 , C . Bokemeyer1 , W . Bloch2 , F .T . Baumann2 1University Medical Center Hamburg-Eppendorf, Department of Oncology/ 

Hematology/Bone marrow transplantation with section of Pneumology, 

Hamburg, Deutschland, 2German Sport University Cologne, Department of 

Molecular and Cellular Sport Medicine, Institute of Cardiovascular Research 

and Sport Medicine, Cologne, Deutschland 

Background. The positive effect of physical activity in primary prevention 

of colorectal cancer (CRC) is well known. In addition, recent 

studies suggest a positive impact of physical exercise on survival in patients 

(pts) with early stage CRC. The aim of this review analysis was to 

summarize feasibility and efficacy data on physical training programs 

in CRC pts. 

Methods. A PubMed database analysis was performed searching for clinically 

relevant trials on physical activity and training programs in pts 

with localized and advanced CRC. 

Results. A total of 8 studies (3261 pts) entered this analysis. Physical activity 

was assessed by questionnaires in 5 studies. Metabolic equivalent 

task-hours per week (MET/h/w), was calculated additionally in 4 of 

them. These 5 trials consistently demonstrate improved cancer-specific 

and overall survival in physically active pts with localized CRC compared 

with less active pts. In a further study, increased cardiovascular 

fitness was associated with improved quality of life after curative CRC 

treatment. Two studies showed a beneficial effect of low- and high-intensity 

exercise on markers of tumor inflammation and proliferation 

in pts with localized and advanced CRC. This represents still the only 

study in pts with advanced CRC. Interventional studies evaluating specific 

training programs are rare and, until today, convenience evidence 

of positive effects of physical activity on disease- or treatment-related 

symptoms in pts with advanced CRC is lacking. Furthermore, systematic 

analyses of dietary and other lifestyle factors should be included in 

these evaluations. 

Conclusion. Various positive effects of physical activity could be demonstrated 

in pts with CRC, but specific trials evaluating different training 

programs and their efficacy on tumor/treatment-related symptoms are 

needed for clinical practice recommendations. In addition, they should 

respect aspects of life style and nutrition. Therefore, we have initiated a 

randomized controlled trial to determine the impact of aerobic exercise 

or strength training program on physical capacity, quality of life, symptom 

control, as well as biological parameters in pts with advanced CRC 

undergoing palliative chemotherapy. 

0342 

Tobacco and alcohol consumption five years after partial laryngectomy 

*H . Danker1 , D . Wollbrück1 , A . Meyer1 1Universität Leipzig, Medizinische Psychologie und Medizinische Soziologie, 

Leipzig, Deutschland 

Background. Tobacco and alcohol consumption are major risk factors 

for the development of laryngeal cancer. As a high proportion of patients 

continue to smoke and drink after surgery, the risk for adverse health 

effects remains stable. The aim of the study was the identification of 

conditions that increase the probability of health risk behaviors among 

partial laryngectomy patients. 

Patients and methods. We surveyed 151 laryngeal cancer patients five years 

after partial laryngectomy. Post-operative alcohol and tobacco consumption, 

socio-demographic, medical, and psychosocial parameters 

were investigated. 

Results. At the time of the survey 22% were smokers. Patients who had 

no or little social support were at a higher risk (OR=8.67) to continue 

smoking in comparison to those with adequate social support. In 28% of 

the male participants alcohol consumption was at a harmful level. Only 

two of the respondents associated their alcohol consumption with the 

development of the disease. 44% of the participants identified smoking 

as the cause of the disease. Unlike smoking, the chance of alcohol consumption 

was increased by high social support after surgery (OR=11.20). 

Discussion. Health risk behavior is often maintained after an illness of 

laryngeal cancer. Whereas the harmfulness of smoking appears widely 

known, this is far less the case with respect to alcohol. This could also 

be reflected in the fact that social support stimulates the consumption 

of alcohol on the one hand and prevents smoking on the other hand. A 

need for professional education and support seems appropriate given 

the study results. 


129

Abstracts 

0347 

Fear of recurrence and disease progression in long-term 

(≥5 years) cancer survivors – a systematic review of quantitative 

studies 

*L . Koch1 , L . Jansen1 , H . Brenner1 , V . Arndt1 1German Cancer Research Center (dkfz), Division of Clinical Epidemiology 

and Aging Research, Heidelberg, Deutschland 

Background. Increasing proportions of men and women diagnosed with 

cancer will become long-term survivors (≥5 years post-diagnosis). However, 

survivors may continue to experience negative effects of cancer 

and/or treatment, including fear of recurrence (FoR). FoR was shown 

to be highly prevalent in cancer survivors and found to be negatively 

associated with quality of life (QoL) and related to a variety of possible 

determinants like race, or optimism. Only few studies have examined 

FoR specifically in long-term cancer survivors. Knowledge on FoR and 

other possible psychosocial burdens in long-term survivors is crucial to 

ensure adequate surveillance and support for this group of survivors. 

Methods. Multiple databases including PUBMED, EMBASE, and PsycINFO 

were searched to identify relevant articles. Seventeen articles 

were included. Data were extracted by two reviewers and summarized 

following a systematic scheme. 

Results. Even five or more years after initial diagnosis, cancer survivors 

suffer from FoR. Most studies report low or moderate mean FoR scores, 

suggesting that FoR is experienced in modest intensity by most longterm 

survivors. Studies including long-term and short-term survivors 

indicate no significant change of FoR over time. Lower level of education, 

lower level of optimism and being Hispanic or White/Caucasian 

were found to be associated with higher levels of FoR. Significant negative 

associations were reported between FoR and QoL as well as psychosocial 

well-being. All but three studies were conducted in the USA. 

General cut-offs for severity/clinical significance of FoR have not been 

defined yet. 

Conclusions. FoR at modest intensity is experienced by most long-term 

cancer survivors. Future studies should address determinants and consequences 

of FoR in more detail. Validated instruments providing cutoffs 

for severity/clinical significance of FoR should be developed and 

utilized. Efficient interventions should be implemented to reduce detrimental 

effects of FoR. 

0352 

Training physical activity in cancer patients 

*C . Kerschgens1 , J . Langenhorst1 , A . Holzgreve2 1 2 Vivantes Rehabilitation GmbH, Onkologie, Berlin, Deutschland, Vivantes 

Stiftung, Berlin, Deutschland 

Summary. A training program for cancer patients during chemo and/ 

or radiotherapy is feasible. Patients with metastatic disease show differences 

in physical status and psychosocial issues compared to patients 

treated in adjuvant settings. 

Introduction. Much information has been given concerning physical 

activity and exercise training in cancer patients, mostly related to prevention 

of cancer or cancer recurrence. Therefore patients in the adjuvant 

setting, namely women with breast cancer were targets of these 

interventions. Less is known about training activities in cancer patients 

treated in a palliative setting. Moreover most of these patients are not 

able to join the athletic program, which is financed by the German health 

insurance system (Rehasport). 

Material and methods. Beginning in August 2010 a weekly program 

was offered, which included a 90-minute training session, consisting of 

30 minutes of exercises in strength and endurance with sports equipment, 

30 minutes of coordination and balance and 30 minutes of relaxation 

(PMR). The program was open to all interested patients who 

underwent chemo and/or radiotherapy at the time. The program was 

conducted by sports therapists and constantly supervised by a trained 


oncologist. Each patient was scheduled to participate for 6 months. At 

the beginning and end of the program assessments were performed. 

These included a 6-minutes walking test, an assessment for CIPN and 

questionnaires concerning psychosocial issues and well-being (PHQ 

and EORTC-LQ). 

Results. From August 2010 to May 2011 17 patients were enrolled in the 

program, median age was 58.41 y, 6 male and 11 female pts. 7 patients 

had metastatic disease and were treated in palliative intention, 10 patients 

were women with breast cancer in an adjuvant therapy setting. 

The 6-MGT in pts with metastatic disease showed a median result of 

398 mts. (120–528) and in pts with adjuvant therapy 565.1 mts (435–670). 

The CIPN-assessments classified the neuropathy according to the CTC, 

highest level of CIPN in all pts was sensory CTC grade I, in 84% of the 

pts with metastatic disease and 20% of the pts in the adjuvant setting. 

Concerning the psychosocial evaluation depressive symptoms were detected 

in 62.5% of the adjuvant treated pts and 42.8% of the palliative 

treated pts. Quality of life according to the EORTC was equally scored 

by adjuvant and palliative treated pts. The majority of palliative treated 

pts. was not able to continue the program over 6 months, reasons were 

progressive disease and concomitant worse condition. An interview 

was done with all pts at the end of the program; all pts mentioned the 

program to be helpful to regain physical activity and well-being. 

Discussion. Our program showed good acceptance in adjuvant and palliative 

treated pts. In the performed assessments the palliative treated 

pts showed clearly poorer performance in their physical activity (6MGT 

and CIPN) but better or equivalent status in psychosocial issues and 

quality of life. 

0354 

Movement therapy in nature based on the Scandinavian philosophy 

of outdoor life (Friluftsliv) 

*S . Meier1 , S . Tari1 , W . Hiddemann1,2 , P . Heußner1,2, 1 2 lebensmut e .V ., Psycho-Onkologie, München, Deutschland, Klinikum der 

LMU, Medizinische Klinik und Poliklinik III, München, Deutschland 

The positive effects of moving and staying in motion on the quality of 

life of cancer patients have been scientifically proven many times. At 

the same time using the soothing effects of nature is a simple and valuable 

approach, but in contrast it is rarely implemented. In September 

2009, the Outdoor Active program of the Association lebensmut e.V. 

in cooperation with the Psycho-Oncology at the Medical Clinic III at 

the Hospital of the University of Munich has started. In a four-weekly 

period easy day hikes to the nearby surrounding are organized, which 

take place in any weather condition. The group is composed of a maximum 

of eight patients, a psycho-oncologist, a sports scientist and 

two dogs. Patients receive at registration a detailed consultation from 

the psycho-oncologist and then have to bring medical clearance from 

their doctor. The tours are selected according to a defined list of criteria 

and pre-tested. In addition to formal criteria such as distance, elevation 

profile, route conditions and the season, the legal insurance criteria 

have to be met. Furthermore, care is taken all the tours to be planned 

are easily performed, and the transfer of movement in everyday life is 

possible. The rediscovery of nature and discovering new things is an 

important aspect for the participants. Perception, relaxation or strengthening 

exercises as well as meditations are offered as part of the „Active 

Outdoors“ program; the following principle applies: In nature it is not 

important to measure how much one has moved or how far one has 

walked. The crucial thing is „to be“ and to be noted that one is moving, 

living and simply enjoying the moment. To date, a group of participants 

are regularly taking part in the tours. To be observed is that individuals 

are independently taking part in the active tours and making their own 

trips. And along with the development of new environment out of everyday 

life, also the living environment of many patients has expanded: 

they draw self-assurance and strength from their experience during the 

„Active Outdoors“ tours.

0368 

Benefit finding and posttraumatic growth in long-term colorectal 

cancer survivors: prevalence, determinants, and associations 

with quality of life 

*L . Jansen1 , M . Hoffmeister1 , J . Chang-Claude2 , H . Brenner1 , V . Arndt1 , 3 

1Deutsches Krebsforschungszentrum (dkfz), Klinische Epidemiologie 

und Alternsforschung, Heidelberg, Deutschland, 2Deutsches Krebsforschungszentrum 

(dkfz), Epidemiologie von Krebserkrankungen, Heidelberg, 

Deutschland, 3GEKID, Cancer Survival Working Group, Heidelberg, 

Deutschland 

Background. Research on quality of life of colorectal cancer survivors 

has mainly focused on downsides of cancer survivorship like long-term 

symptoms and restrictions in quality of life. But studies have shown that 

cancer survivors may also report positive changes in the context of their 

disease, like benefit finding (BF) and posttraumatic growth (PTG). To 

get further insight into BF and PTG in long-term colorectal cancer survivors, 

the aim of this study is to investigate the prevalence of BF and 

PTG and to determine what socio-demographic, clinical, and psychosocial 

factors distinguish colorectal cancer survivors who show a high 

level of BF and PTG from those who experience only low levels. 

Methods. This analysis includes patients with colorectal cancer from 

a population-based case-control study (DACHS-study) carried out in 

southwest Germany (Rhine-Neckar-Odenwald and Heilbronn Region). 

BF, PTG, and quality of life were assessed five years after diagnosis in 

483 colorectal cancer patients using the benefit finding scale, the posttraumatic 

growth inventory, and the EORTC QLQ-C30. Prevalence of 

BF and PTG, determinants of moderate to high BF and PTG, and the 

association between BF, PTG, and quality of life were investigated. 

Results. Almost all survivors experienced BF and PTG at least to some 

degree and 64% and 46% of the survivors experienced moderate to high 

levels of BF and PTG, respectively. Survivors with the highest level 

of education and with higher depression scores reported less BF and 

PTG. PTG increased with increasing stage and self-reported burden of 

diagnosis. Quality of life only correlated weakly with PTG (Pearson’s 

r=0.1180, p=0.0112) and not with BF (r=0.0537, p=0.2456). 

Conclusion. Our results show that BF and PTG are highly prevalent 

among long-term colorectal cancer survivors. Thus, to get a comprehensive 

understanding of the adjustment of cancer patients after diagnosis, 

negative as well as positive consequences of cancer survivorship 

need to be investigated. As quality of life was only weakly related to BF 

and PTG, the generally reported high global long-term quality of life 

after cancer cannot be directly explained by these positive adjustments. 

0390 

Effect of a four-week bicycle tour on the prostate specific 

antigen, total testosterone, and interleukin-6 value in prostate 

cancer patients 

*M . Müsgens1 1Deutsche Sporthochschule, Institut für Kreislaufforschung und Sportmedizin 

– Abteilung molekulare und zelluläre Sportmedizin, Köln, Deutschland 

Introduction. Prostate cancer is nowadays in the male population with 

about 20% one of the most common malignant tumor [4]. This urological 

tumor can occur at the age of 45 years and be diagnosed, but the 

probability is very low, succumb to this disease at such an early stage [2]. 

The framework for the diploma work is a four-week bicycle trip from 

Cologne to Marseille, with eight participants who suffer from prostate 

cancer. The focus of this study is on three medical parameters, namely 

the prostate-specific antigen, the total testosterone and the interleikin-6. 

These parameters are tested for the effect of a prolonged endurance performance 

on the bike. The measurements were made one week before 

and one week after the bike tour and six months after the intervention. 

Results. The follow-up measurements showed a slight reduction in PSA 

level, but this development can not be explained as the sole cause of the 

bike tour. Regarding the measured testosterone concentration, a significant 

reduction of the first to the third measurement was identified. These 

results support previous studies in which the cycling is an effective 

rehabilitative agent for prostate cancer patients to reduce the total testosterone 

value in the long term. The data of the cytokine interleukin-6 

showed no significant changes by the endurance bike ride and mostly 

remained at a constant concentration level. 

Discussion and conclusion. This study has no elevated PSA and interleukin-6 

levels after a four-week bicycle tour can be measured. Related to 

testosterone, there was a significant reduction in concentration in the 

follow-up measurement. Causes that may lead to an influence of testosterone 

has behavioral characteristics such as physical training, nutrition, 

sleep, alcohol consumption, smoking and stress [3]. Furthermore, 

it is scientifically proven that endurance sports often leads to a decrease 

in testosterone concentration [1]. However, further studies have to be 

conducted, in order to better understand the effects of a physical endurance 

stress on PSA, testosterone and interleukin-6 in prostate cancer 

patients. 

1 . Diederich S et al (2007) Hormonelle Veränderungen durch Ausdauersport . 

Blickpunkt der Mann 5(4):36–41 

2 . Hautmann R, Huland H (2006) Urologie 

3 . Sommer F (2006) Männergesundheit . Blickpunkt der Mann 4(3):5–10 

4 . Stenzl A (2009) Prostatakarzinom 

5 . Baumann FT, Herweg C, Schüle K (2008) Bewegungstherapie und Sport bei 

Krebs 

0392 

The attending physician between psychosocial challenge and 

medical requirement – Orientation to needs in an oncologic 

practice 

*U . Hoppenworth1 , *C . Sokol1 , M . Fischer2 , F . Adam2 1 2 Hoppenworth/Sokol, Hildesheim, Deutschland, megapharm, Sankt 

Augustin, Deutschland 

The integration of psychosocial care within medical treatment poses a 

special challenge to hospitals and oncological practices. According to 

epidemiological estimations about 40–50% of all cancer patients develop 

physical and mental problems as a result of their cancer. Studies 

show that early psychosocial and psychooncological support is useful to 

counter chronification, to improve the therapy compliance of patients 

and to improve their quality of life. With the aid of the Hornheider 

Fragebogen the Oncologist is able to recognize at an early stage whether 

patients are under psychological pressure. Our project is based on 

the analysis of more than 20,000 questionnaires, which were collected 

between 1998 and 2011. Through this survey it was possible to identify 

the care required by cancer patients with different tumours receiving 

ambulatory treatment, both on a singular and comparative basis. By 

analyzing the data it will be possible to gain insights on similarities 

and differences in the experiences of patients and their coping strategies 

taking into account their sociopsychologic and sociodemographic 

background. Furthermore specific core disorders will be identified. In 

summary this study is able to provide the empirical base for a more accurate 

indication for psychooncological treatment and not least could 

improve patients‘ quality of life. 


131

Abstracts 

0409 

Enhanced oxygen capacity results in fatigue-reduction and 

improvement of quality of life 

*M . Bernhörster1 , L . Vogt1 , K . Schmidt1 , A . Lungwitz1 , C . Thiel1 , E . Jäger2 , 

W . Banzer1 1 2 Goethe Universität, Sportmedizin, Frankfurt, Deutschland, Krankenhaus 

Nordwest GmbH, Hämatologie und Onkologie, Frankfurt, Deutschland 

Introduction. There is moderate evidence that physical activity is beneficial 

in cancer treatment. Patients improve in endurance and muscle 

strength as well as physical, social and psychological functioning. However, 

to our knowledge only limited data is available regarding the 

relationship between performance enhancement and quality of life 

improvements during cancer treatment. Therefore we aimed to explore 

the dependence of changes in oxygen uptake, quality of life and cancer 

related fatigue (CRF) during a 4-month period. 

Methods and materials. Aerobic exercise capacity (VO2peak), quality 

of life and fatigue symptom (EORTC QLQ-C30) were obtained in 101 

cancer patients (30–77 years). After initial examination patients were 

given the opportunity to engage in supervised and/or home-based training 

interventions. Patients were re-examined after 16 weeks and stratified 

into 3 sub-groups (terciles) with respect to the absolute change in 

VO2peak. 

Results. Depending on the absolute change of VO2peak (1.9±1.7; 1.8±0.8; 

5.7±2.8 ml/kg/min) there were significant differences in the quality of 

life improvement and cancer-related fatigue reduction. Nevertheless, 

patients in the upper third, with initially high levels of fatigue, were 

as likely to show a minimum 10% enhancement in VO2peak as patients 

with low or medium fatigue levels. Subjects with a minimum 10% 

VO2peak -increase had a 2.6 times higher chance to obtain a 20% fatigue 

symptom reduction. 

Conclusions. In the present study almost all patients of the mixed diagnosis 

cancer population improved their exercise capacity and demonstrated 

enhanced QoL after 16 weeks of supervised and/or home-based 

exercise training. The findings point toward a relationship of exercise 

capacity enhancement, quality of life improvement and fatigue symptom 

reduction during cancer treatment. Beside the retrospective analysis, 

that is not capable to clearly demonstrate causal dose-responserelationships, 

the study is limited in consideration of the fact, that CRF 

is a multidimensional complex of different affections. Additional data is 

necessary to determine the most effective parameters of exercise for fatigue 

management including the types, mode, intensity, frequency and 

duration of exercise regimes. Developing exercise programs that incorporate 

these factors will allow patients to reduce CRF in an optimum of 

time and energy expenditure. 

0419 

Integrating palliative care into comprehensive breast cancer 

therapy – first experiences 

*R . Wuerstlein1,2 , S . Frechen2,3 , J . Wolf2,4 , M . Hellmich2,3 , P . Mallmann2,5 , 

N . Harbeck1,2 , R . Voltz2,3 , J . Gaertner2,3 1 2 Universitätsklinik, Brustzentrum, Köln, Deutschland, CIO, Köln-Bonn, 

Deutschland, 3Universitätsklinik Köln, Z . für Palliativmedizin, Köln, Deutschland, 

4Universitätsklinik, Klinik für Innere Medizin I, Köln, Deutschland, 

5Universitätsklinik, Frauenklinik, Köln, Deutschland 

Background. The integration of palliative care (PC) early in the disease 

trajectory of life limiting diseases is explicitly recommended by the 

World Health Organisation (WHO). This recommendation was included 

in the administrative directives for principles of cancer care in our 

institution. The aim of this study was to assess, at what point in the disease 

trajectory patients with breast cancer (BC) were first provided PC 

and whether – over one year – an earlier integration of PC could be 

achieved. 


Objective. A retrospective systematic chart analysis of a two year period 

was performed. We assumed that seeing patients relatively early during 

the course of the illness would be reflected by seeing patients that would 

be not already in a reduced performance status and/or experiencing 

symptoms that are indicators for advanced disease (e.g. dyspnoea). Therefore, 

the first PC consultation for every BC patient seen by the PC 

support team was analyzed to assess in what physical condition patients 

receive first PC consultation and what burdening symptoms they already 

experienced. 

Results. Many patients were already in a reduced physical state and were 

experiencing burdening symptoms. After a one-year period, the number 

of burdening symptoms identified at first PC consultation and the 

admissions to the in-patient PC ward decreased while non-PC physicians 

increasingly requested PC support for psychosocial interventions. 

Conclusion. Though some degree of development towards a better understanding 

of PC competencies and the early integration approach 

could be demonstrated, the adoption of the WHO recommendation 

alone did not suffice to integrate PC into routine BC therapy early in 

the course of the illness. Therefore, the development of disease specific 

guidelines in an interdisciplinary comprehensive-cancer-care setting is 

advocated. A standard operating procedure for the CIO (centrum of integrated 

oncology) Cologne-Bonn was developed and will be presented. 

0433 

New German Hospice and Palliative Care Registry 

*L . Radbruch1 , T . Montag2 , K . Neuwöhner3 , G . Lindena4 , F . Nauck5 1 2 Universitätsklinikum, Klinik für Palliativmedizin, Bonn, Deutschland, Universitätsklinikum, 

Zentrum für Palliativmedizin, Köln, Deutschland, 3Uni versitätsklinikum Bonn, Abteilung für Palliativmedizin, Bonn, Deutschland, 

4 5 CLARA Klinische Forschung, Kleinmachnow, Deutschland, Universitätsmedizin, 

Abteilung Palliativmedizin, Göttingen, Deutschland 

Introduction. Data from clinical studies should be rounded off with 

clinical practice data especially in patients with multiple comorbidities 

or end of life state for improving processes of care. The German 

Palliative Care Association (DGP) starts a hospice and palliative care 

registry collecting a defined core data set and subsequent feedback and 

benchmarking for quality improvement of hospice and palliative care 

in Germany. 

Methods. Interested outpatient and inpatient institutions providing 

specialized hospice and palliative care SHPC announce their participation. 

Precondition is the collection of the core data set electronically 

and patient consent. The core data set includes patient demographic 

data, diagnoses and impact, disease severity, symptom incidence and 

severity, selected drug and other treatment options as well as outcome 

death or discharge – in inpatients –, admission to a hospital – in outpatients 

– and evaluation of the care process by the team. These data sets 

are to be de-identified and uploaded to the registry via a secure line. The 

evaluation is fed back to the participating facilities of SHPC and they 

additionally receive comparison data of other centers, also summarized 

by facility type for benchmark purposes. 

Results. The core data set was defined in 2009, newly discussed and 

slightly changed considering the experiences. Primary program providers 

were made interested to include the core data set in their programs. 

The registry allows comparing the structure and indication quality of 

SHPC facilities, benchmarking processes and results, each with deidentified 

data for the participating institutions. It also offers data for 

scientific evaluation of major interest across settings. 

Discussion. Hospice and palliative care treatment SHPC facilities are 

working under regionally varying conditions with room for improvement 

concerning provision of care, kind of care and interdisciplinary 

cooperation, qualification, quality of care and reimbursement. A specific 

issue is the recognition and definition of the patient’s referral to 

specialized hospice and palliative care in time. The participation in the 

registry is voluntary and the motivation of facilities is crucial to share

the adjunctive costs. DGP is optimistic to successfully implement and to 

achieve the necessary supra-regional and supra-institutional participation. 

The experiences with the preliminary quality improvement project 

hospice and palliative care evaluation HOPE provide confidence. 

0461 

Evaluation of the impact of a 3-month strength training on 

immune system, fatigue and quality of life in women with breast 

cancer undergoing chemotherapy 

*S . Frisse1 , L . Gerland2 , S . Latta1 , W . Bloch2 , N . Harbeck1 , F .T . Baumann2 1 2 Uniklinik Köln, Frauenklinik, Brustzentrum, Köln, Deutschland, Deutsche 

Sporthochschule Köln, Institut für Kreislaufforschung und Sportmedizin, 

Abteilung für molekulare und zelluläre Sportmedizin, Köln, Deutschland 

Background. 80–96% of breast cancer patients experience fatigue during 

chemotherapy (Bardwell 2008), causality remains unexplained (Glaus 

1996). Most patients are subjectively more restricted by fatigue than by 

pain or nausea (Arndt 2006). Studies showed positive effects of endurance 

training on the intensity of fatigue. The range of studies about feasibility 

and efficiency of exclusive strength training in the rehabilitation 

of breast cancer patients experiencing fatigue is so far insufficient (De 

Backer 2009). The impact of physical activity on the immune system is 

not yet resolved unambiguously. 

Objective. The study aims at analyzing the development of parameters 

of the immune system, fatigue and quality of life in breast cancer patients 

executing strength training during chemotherapy. 

Methods. 40 breast cancer patients in adjuvant chemotherapy are involved 

6–12 weeks after surgery: 20 patients each are assigned to the 

intervention and to the control group. Strength training is executed twice 

a week for about 60 minutes for a period of 12 weeks. The following 

parameters are analyzed at the beginning and after 12 weeks: parameters 

of the immune system (e.g. erythrocyte-flexibility and cytokines), 

fatigue via standardized questionnaire MFI-20 as well as quality of life 

based on the questionnaires EORTC QLQ-30 and QLQ-23. Fatigue and 

quality of life are examined additionally in week 6. 

Results. The analysis of all results is expectedly done in the end of 2011. 

Bettering of fatigue is noticeable by trend. Parameters of the immune 

system are not yet interpreted. By the time of presentation, more comprehensive 

data will be available. 

Discussion. A positive tendency concerning fatigue can be considered as 

a surplus for breast cancer patients. Although the number of test persons 

is comparatively small, a heterogeneous collective of patients becomes 

apparent. Improvement of quality of life and attenuation of fatigue 

would be considered as a major success. 

0463 

Evaluation of the impact of a 3-month strength training on 

strength parameters, EMG and oxidative stress of breast cancer 

patients during chemotherapy 

*L . Gerland1 , S . Frisse2 , S . Latta2 , W . Bloch1 , N . Harbeck2 , F .T . Baumann1 1Deutsche Sporthochschule Köln, Institut für Kreislaufforschung und 

Sportmedizin, Abteilung für molekulare und zelluläre Sportmedizin, Köln, 

Deutschland, 2Unifrauenklinik, Brustzentrum, Köln, Deutschland 

Background. Evaluations of the effect of strength training in oncological 

rehabilitation are rare. The impact of physical activity on the immune 

system is not yet verified definitely. It is assumed that regular physical 

activity has positive effects on oxidative stress (Gago-Dominguez 2007). 

Studies have shown significant improvement of muscular strength of 

cancer patients after intensive strength training (Quist et al 2006, Galvao 

et al 2007, Battaglini et al 2007). Studies implementing EMG-measurement 

in strength tests of breast cancer patients could not be found. 

Aims. The study aims at analyzing the development of strength parameters, 

EMG and oxidative stress and antioxidative capacity of breast 

cancer patients executing strength training during chemotherapy. 

Methods. The study is organized as a prospectively randomized and 

controlled preference study. 40 breast cancer patients in adjuvant chemotherapy 

are involved 6–12 weeks after surgery for 12 weeks: 20 probands 

each are assigned to the intervention and to the control group. 

Strength training is executed twice a week for about 60 minutes, consisting 

of 7 routines in 3 sets of 8–12 dynamic repetitions. The training is 

constantly supervised. Subjective intensity is controlled during exercise 

by modificated RPE-scale, aiming at local muscular exhaustion. The 

following parameters of both control and intervention group are analyzed 

in the beginning and after the 12 weeks: parameters of the immune 

system (oxidative stress, antioxidative capacity), strength is examined 

by isometric and isokinetic tests of upper and lower extremities including 

EMG-measurement. 

Results. The examination of all results is scheduled for the end of the 

year 2011. An increase of muscular strength is noticeable by trend. Parameters 

of the immune system have not yet been interpreted. By the time 

of presentation, more comprehensive data will be available. 

Discussion. A significantly positive tendency concerning strength parameters 

can be considered a surplus for cancer patients. Although the 

number of test persons is comparatively small, a heterogeneous collective 

of patients becomes apparent. The current tendencies suggest the 

integration of an intensive strength training program into the rehabilitation 

of mastocarcinoma patients. 

0470 

Subjective performance of memory and concentration in patients 

with brain metastases before and after radiotherapy 

A . Cole1 , S . Janssen1 , M . Bremer1 , *D . Steinmann1 1MHH, Strahlentherapie, Hannover, Deutschland 

Purpose. To prospectively assess the progress of neurocognitive functions 

in patients with brain metastases from any solid primary treated 

with radiotherapy to the brain. 

Patients and methods. Adult patients with brain metastases (n=50) with 

or without surgery (n=10 vs. n=40) were treated with radiotherapy (RT) 

based on different dose-fraction schemes according to the patient’s status: 

whole-brain RT (n=29) or hypofractionated stereotactic RT (n=21) 

were performed. In the control group breast cancer patients without 

cranial involvement (n=29) were treated with whole-breast radiotherapy 

to the breast or chest wall after surgical excision of the tumourous 

breast tissue. Patients were recruited between May 2008 and December 

2010 to subjectively evaluate cognitive function before RT, 6 weeks, 3 

and 6 months after irradiation. For assessment of the neurocognitive 

status the relatively new German questionnaires for self-perceived deficits 

in attention (FEDA) and for acquisition of experiences with every 

day memory (FEAG) were used. 

Results. After a limited survival in patients with BM (4.3 months), 20 patients 

(40%) died. Patients with operation (4.1 mo) lived longer than patients 

without surgery (6.8 mo) and hfSRT (9.9 mo) provided a better 

survival than WBRT (2.9 mo). In patients with BM attention and memory 

status decreased at every point of time while it stayed relatively 

stable in the control group. Differences in progress explored between 

the two groups were significant in all three FEDA scales distractibility 

and deceleration of mental processes (p=0.049), exhaustion and deceleration 

of activities (p=0.002) and decrease in motivation (p=0.035) 

but not in every day memory as assessed with the FEAG questionnaire. 

Without operation patients had a better memory (p=0.039). As a trend 

patients with hfSRT rather then WBRT had better performances in all 

subscales. 

Conclusion. NCF in patients with BM declined for all 4 scales at every 

point of time after RT while breast cancer patients stayed more stable. 


133

Abstracts 

0471 

Occurrence and impact of pain, insomnia, fatigue symptom 

cluster in 207 cancer patients with pain treatment: a secondary 

data analysis 

*M . Gunga1 , M . Landenberger1 , P . Jahn1 1MLU Halle, IGPW, Halle, Deutschland 

Objective. Cancer patients experience a variety of symptoms either as 

a result of their disease or in consequence of their treatment. These 

symptoms occur frequently, in a non random distribution, in groups 

or clusters. In a definition from Kim et al. (2005) „A symptom cluster 

is defined as consisting of 2 or more symptoms that are related to each 

other and that occur together” (p. 278). The intention of this secondary 

data analysis was to examine patterns of symptom clusters over time at 

four different measuring times and their impact on global health status 

and functionality. 

Method. The basis of this analysis is a cluster-randomized multicenter 

trial with the title “Improvement of pain related self management for 

oncologic patients through a transinstitutional modular nursing intervention” 

(Jahn et al. 2010). Patients were included if they had diagnosed 

malignancy, persistent pain >3 days and average pain intensity ≥3/10. 

The trial was conducted on 18 wards in 2 German university hospitals. 

The analysis of the present study is carried out with the help of the “PIFcluster” 

(pain-insomnia-fatigue-cluster), a common cancer symptom 

cluster. A patient in the study complied the “PIF-cluster” conditions if 

in each case pain-, insomnia- and fatigue-measured values were higher 

than 30 out of 100. 

Results. 207 patients participated (average age: 56.8±12.3 years, 57.5% 

male). 160 (77.3%) participants showed a PIF-cluster at baseline. 136 

(65.7%) of these patients met the terms of the PIF-cluster at the secondary 

measurement (the day before discharge). Furthermore 113 (54.6%) 

persons matched the PIF-cluster seven days after discharge and 68 

(32.9%) persons matched it 28 days after discharge. It becomes apparent 

that if somebody showed a new occurred PIF-cluster at a later measuring 

point, his global health status and functionality values were ordinarily 

significant poorer. Such a patient shows on average a −12.7 points 

lower value for global health status, −9.4 points for physical function, 

−39.2 points for role function, −2.8 points for emotional function, −4.5 

points for cognitive function and −18.2 points compared with the first 

measuring point. 

Conclusion. To sum up this longitudinal research shows that symptom 

clusters are relative stable during a certain period and that the occurrence 

or loss of symptom clusters has direct effects on the patient’s quality 

of life and his functionality. 


Urologische Tumoren 

0031 

Combined anti-inflammatory, immunomodulatory and angiostatic 

treatment in patients with castration-refractory prostate 

cancer: a phase II study of Imatinib with Pioglitazone, Etoricoxib, 

Dexamethasone and low-dose Treosulfan 

*A . Reichle1 , M . Vogelhuber1 , S . Feyerabend2 , T . Südhoff3 , M . Schulze4 , 

J . Hübner5 , R . Oberneder6 , M . Baier7 , A . Rübel7 , K . Birkholz7 , A . Bakhshandeh- 

Bath8 , R . Andreesen1 1University Hospital, Department of Hematology and Oncology, Regensburg, 

Deutschland, 2University Hospital, Department of Urology, Tübingen, 

Deutschland, 3Hospital, Department of Hematology and Oncology, Passau, 

Deutschland, 4Outpatient Center, Urology and Oncology, Markkleeberg, 

Deutschland, 5J .W . Goethe University, Department of Oncology, Frankfurt, 

Deutschland, 6Hospital, Department of Urology, Planegg, Deutschland, 

7 8 Novartis Pharma GmbH, BU Oncology, Nürnberg, Deutschland, Outpatient 

Center, medical oncology, Hamburg, Deutschland 

Background. With a median overall survival of about 19 months, therapeutic 

options for patients (pts) with castration-refractory prostate 

cancer (CRPC) are still limited. Release and continuous production of 

pro-inflammatory cytokines may account for its resistance towards cytotoxic 

drugs. Therefore, this phase II study analyzed the PSA-response 

rate in pts with CRPC to combined biomodulatory agents in pts with 

CRPC. 

Methods. In 11 German centers, 69 pts with histologically confirmed 

CRPC (according to EAU guidelines) were enrolled. In the 6 months 

core phase pts were continuously treated with daily doses of imatinib 

mesylate, pioglitazone, etoricoxib, treosulfan and dexamethasone until 

PSA progression. Pts responsive to study medication were allowed to 

enter an extension phase until disease progression or intolerable toxicity 

occurred. During the study, PSA-values, ECOG performance status 

and QoL were continuously assessed. 

Results. The core phase of this study was finished in July 2009. 18 patients 

were allowed to enter the extension of the study and two of these 

pts are still ongoing As of June 2011 they have been on study medication 

for 27 months. At baseline the median PSA value was 45.3 ng/ml (range 

5–3603). The majority of pts had PSA doubling times of 50 to 100 days. 

Of the 61 evaluable pts, 23 pts (37.7%) were considered as PSA responders 

with a confirmed PSA decline of at least 50%. Within the responders 

PSA decreased from 278.9 (±784.1) to 8.8 (±11.6) ng/ml during the 

treatment period. Median time to PSA progression, PSA response and 

overall survival were not achieved. 14 of the 38 non-responders (36.8%) 

showed a stable disease. A total of 32 patients (52%) showed a decrease 

in PSA during treatment in the core phase of the study. In some pts the 

therapy led to complete resolution of bone lesions. 

Conclusions. The study evaluated a new multi-targeted approach for pts 

with CRPC. This multi-targeted approach led to an impressive response 

rate of 37.7%, although the substances have shown limited efficacy in 

single therapeutic use. Two patients are still ongoing in the extension 

phase and have received study medication for 27 months (as of June 

2011). A good PSA response and manageable toxicity make this combination 

treatment to an alternative treatment option to present regimens.

0033 

Effect of intravenous zoledronic acid (ZOL) on bone metabolism 

in patients (pts) with metastatic bone disease in prostate cancer 

(PC) and breast cancer (BC): the ZOTECT study 

*J . Gschwend1 , T . Maurer1 , T . Heck1 , M . Muth2 , A . Rübel2 , K . Birkholz2 , 

T . Bauer3 , M . Ziller3 , P . Hadji3 1Klinikum rechts der Isar, Technische Universität, Urologische Klinik, 

München, Deutschland, 2Novartis Pharma GmbH, BU Oncology, Nürnberg, 

Deutschland, 3Phillips-Universität, Klinik für Gynäkologie, Gynäkologische 

Endokrinologie und Onkologie, Marburg, Deutschland 

Background. Approximately 75% of pts with BC or PC will develop bone 

metastases (BM), which influence bone metabolism and increase the 

incidence of skeletal related events (SREs). The treatment of pts with 

ZOL reduces the incidence and delays the onset of SREs. The primary 

objective of this study was to access the course of several bone markers 

under therapy with ZOL and the correlation with disease outcomes, 

as recent studies showed strong correlations between the level of bone 

markers and SREs. 

Methods. This prospective, single arm, open-label study investigated 

the effect of ZOL (4 mg IV q4wks given for 4 continuous months) on 

bone markers (CTX, PINP, RANKL, OPG) in PC and BC pts with BM. 

A final follow-up was conducted after 12 months. Secondary objectives 

included the relationship between metastatic sites assessed by bone scan 

and the level of bone markers at study entry, analgesics score and pain 

assessment, the relationship between pain and SREs and the course of 

bone markers, SRE rate, quality of life, Estradiol and PSA changes. 

Results. Between May 06 and August 08, 99 BC pts and 301 PC pts were 

recruited at 98 German sites. The course of OPG and RANKL was not 

significantly influenced by ZOL, however the level of PINP and CTX 

significantly decreased to stable values (p

Abstracts 

0084 

TCAM2-celline: the right model for seminoma studies? 

*U . Eppelmann 1 , F . Gottardo 1 , J . Wistuba 1 , F . Wübbeling 2 , M . Burger 2 , 

S . Schlatt 1 , S . Kliesch 1 , C . Mallidis 1 

1 Universitätsklinikum Münster, Centrum für Reproduktionsmedizin und 

Andrologie, Münster, Deutschland, 2 Universität Münster, Institut für Numerische 

und Angewandte Mathematik, Münster, Deutschland 

Background. Germ cell tumours (GCTs) constitute over 60% of all malignancies 

diagnosed in men between the ages of 17 and 45 years. Of 

these, the most frequent are seminomas and embryonal carcinomas. 

Although testicular tumours have excellent cure rates, the success of 

the therapy is dependant on the accuracy of diagnosis and choice of 

treatment. Derived from a human seminoma, TCAM2 cells constitute 

the main model for in vitro studies of the condition. Despite their wide 

spread use, they have only been partially characterised, hence questions 

remain regarding the homogeneity of TCAM2 and as a consequence 

there are doubts as to how representative the cell line is of the true pathological 

state. Raman microspectroscopy is a laser based non invasive 

technique which can provide a detailed chemical fingerprint of a living 

cell and as such is being increasingly employed in medical research. 

Our aim was to systematically assess the Raman spectral profiles of our 

TCAM2 cell line, in order to determine its homogeneity and to identify 

any cellular sub populations. 

Materials and methods. TCAM2 cells were streaked onto suprasil microscope 

slides and either air dried or dessicated. Raman spectra were 

obtained using the Horiba LabRAM ARAMIS system. After determination 

of the optimal analytical settings, a map consisting of a 200 spectral 

array was obtained from 20 cells/grouping. A further 200 cells/ 

grouping were assessed using duoscan providing an overall spectral 

average of the cells’ constituents. Beyond broad peak assignments, spectra 

were further analysed using Principal Component Analysis (PCA), 

Clustering Methods, Sparsity Separation and Harmonic Analysis. Results 

were compared to control spectra obtained from the previously 

characterised mouse embryonic fibroblast cell line. 

Results. Overall spectral accumulations showed the assessed TCAM2 

cells to possess one of three distinct patterns. Closer examination of 

peak distribution and relative size indicated that although there were 

similarities in the spectra differences were prominent in Raman shifts 

in the 809, 1002, 1032, 1450 and 1608 cm−1 regions. Desiccated samples 

did not differ substantially from the air dried samples indicating that 

Raman vibrations were not influenced by the presence/absence of water. 

Comparisons with spectra obtained from mouse embryonic fibroblasts 

showed distinct differences. 

Conclusions. Our findings of three differing spectral fingerprints is suggests 

that TCAM2 comprise three differing cell populations and adds 

further credence to the proposal that the cell line is not homogeneous 

but is made up of seminoma cells, apoptotic cells and differentiated embryonic 

carcinoma cells. 

0086 

Patient education for radical prostatectomy: Physician’s point of 

view of multimedia support vs. standard procedure 

*A . Ihrig1 , J . Huber2 1Universitätsklinik Heidelberg, Klinik für Allgemeine Innere Medizin und 

Psychosomatik, Heidelberg, Deutschland, 2Universität, Urologische Klinik, 


Objective. Objective of this study is to assess physician’s point of view of 

multimedia support in preoperative patient education for radical prostatectomy. 

Methods. Eight physicians educated more than two hundred patients 

for radical prostatectomy randomized either multimedia supported or 

with standard procedure. We interviewed the physicians to assess their 

point of view concerning possible advantages and differences. 


Results. All physicians rated multimedia supported education significantly 

better than standard procedure. Main reasons were better comprehensibility, 

the visual presentation, and greater ease in explaining 

complex issues. Objective time measurement showed no difference 

between both educations. Nevertheless major disadvantage was the impression 

that multimedia supported education lasted longer. Moreover, 

physicians had the impression that some details could be further improved. 

Given the choice, every physician would decide for multimedia 

support. 

Conclusion. Physicians appreciate multimedia support in preoperative 

education. Contrary to their impression, multimedia support does not 

prolong patient education. Therefore, patients and physicians likewise 

profit from multimedia support for education and counseling. The readiness 

of physicians is a possible obstacle to this improvement, as their 

view is a key factor for the transition to everyday routine. Therefore, our 

results could alleviate this possible barrier for establishing multimedia 

supported education in clinical routine. 

0091 

Patho-histological correlation of MRI findings with the results 

of biopsies and radical prostatectomies in MRI-guided prostate 

biopsy at 1.5T 

*D .G . Engehausen1 , K . Engelhard2 1Universitätsklinikum Erlangen, Urologische Klinik, Erlangen, Deutschland, 

2Martha Maria Krankenhaus Nürnberg, Abteilung für Radiologie, Nürnberg, 

Deutschland 

Introduction. In diagnostic management of patients with elevated or raising 

PSA levels the described method offers a reasonable alternative to a 

repeated systematic multi-site TRUS guided prostate biopsy. Purpose is 

to investigate the diagnostic valency of MRI-guided biopsy in detecting 

and localizing prostate cancer. 

Method and materials. 65 patients with elevated PSA levels (PSA>4 ng/ 

ml, mean 10.6 ng/ml) and episodes of prior tumor negative TRUS-guided 

biopsies (1–5, mean 1.6) underwent MRI-guided prostate biopsy in 

a 1.5T scanner (Magnetom Espree, Siemens Healthcare, Erlangen). Localization 

of tumor suspected areas was done with an endorectal and 

two body-phased array coils using a T2-weighted TSE sequence, a diffusion 

weighted (DWI) protocol inclusive an ADC-map and a gadolinium 

contrast enhanced 3D-gradient echo sequence. After removing the 

endorectal coil the biopsy device was inserted into the rectum and 2 to 

6 (mean 4.5) core biopsies were taken manually in a supine position of 

the patient. A patho-histological correlation was done between tumor 

suspected MRI areas and biopsy results of these regions. In 23 men with 

radical prostatectomy following cancer diagnosis each of 104 tumor 

containing biopsy cores of the suspected regions was correlated with 

the sites of tumor location in the pathological specimens. 

Results. All tumor-suspected areas could be successfully punctured. 

Prostate cancer was found in 43%, benign prostate hyperplasia (BPH) in 

66%, prostatitis in 38% and normal prostate tissue in 5%. With respect 

to cancer depiction MRI-guided biopsy showed a sensitivity, specificity, 

accuracy, negative and positive predictive value of 75%, 100%, 86%, 100% 

and 75% respectively. With reference to the correlation of tumor localization 

in the pathological specimens and biopsy sides in MRI of tumor 

containing biopsy cores a sensitivity of 96%, a specificity of 98%, an 

accuracy of 97% could be demonstrated. The negative predictive value 

was 96% by a positive predictive value of 98%. In 9 patients with at first 

tumor negative MRI-guided biopsy results cancer was found in follow 

up over 26 months by TRUS-guided biopsy or transurethral resection 

(TUR). 

Conclusion. MRI-guided prostate biopsy is suitable and accurate in detecting 

and localizing prostate cancer, missing a rest of tumors which 

can only be diagnosed in clinical follow up.

0106 

MicroRNAs in renal cell carcinoma: Diagnostic implications of 

serum miR-1233 levels 

*J . Ellinger1 , L .M . Wulfken1 , R . Moritz2 , C . Ohlmann3 , S . Holdenrieder4 , 

V . Jung3 , F . Becker3 , E . Herrmann2 , G . Walgenbach-Brünagel4 , A . von Ruecker5 

, S . Müller1,5 1Universitätsklinikum Bonn, Klinik und Poliklinik für Urologie und Kinderurologie, 

Bonn, Deutschland, 2Universitätsklinikum Münster, Klinik und 

Poliklinik für Urologie, Münster, Deutschland, 3Universitätsklinikum des 

Saarlandes, Klinik und Poliklinik für Urologie, Homburg/Saar, Deutschland, 

4Universitätsklinikum Bonn, Institut für Klinische Chemie und Klinische 

Pharmakologie, Bonn, Deutschland, 5Universitätsklinikum Bonn, Institut für 

Pathologie, Bonn, Deutschland 

Objective. MicroRNA expression is altered in cancer cells, and microR- 

NAs could serve as diagnostic/prognostic biomarker for cancer patients. 

Our study was designed to analyze circulating serum microRNAs 

in patients with renal cell carcinoma (RCC). 

Methods. We first explored microRNA expression profiles in tissue and 

serum using TaqMan Low Density Arrays in each six malignant and benign 

samples. The findings were validated using quantitative real-time 

PCR (TaqMan MicroRNA Assays). 

Results. The Low Density Arrays identified 109 microRNAs circulating 

at higher levels in cancer patients’ serum, and 36 microRNAs were upregulated 

in serum and tissue of RCC patients. Seven candidate microRNAs 

were selected for verification based on the finding of up-regulation 

in serum and tissue of RCC patients (analysis of miR-7-1*, miR-93, 

miR-106b*, miR-210, miR-320b, miR-1233 and miR-1290 levels in serum 

of healthy controls (n=30) and RCC (n=33) patients). miR-1233 was increased 

in RCC patients, and thus validated in a multicentre cohort of 

84 RCC patients and 93 healthy controls (sensitivity 77.4%, specificity 

37.6%, AUC 0.588). We also studied 13 samples of patients with angiomyolipoma 

or oncocytoma, whose serum miR-1233 levels were similar 

to RCC patients. Circulating microRNAs were not correlated with clinical-pathological 

parameters. 

Conclusions. MicroRNA levels are distinctly increased in cancer patients, 

although only a small subset of circulating microRNAs has a 

tumor-specific origin. We identify circulating miR-1233 as a potential 

biomarker for RCC patients. 

0138 

The accreditation of an interdisciplinary prostate cancer centre: 

a survey among regional urologists 

*J . Kramer1 , D . Baumunk1 , A . Magheli1 , C . Stephan1 , M . Schostak1 , K . Miller1 , 

S . Weikert1 1Charité – Universitätsmedizin Berlin, Urologie, Berlin, Deutschland 

Introduction. Interdisciplinary Prostate Cancer Treatment Centres 

(IPC) according to the criteria of German Cancer Society (DKG) aim at 

improving the quality of care for prostate cancer patients. The perception 

of such treatment centres among regional urologists is unknown. 

We report the results of a survey among urologists of the region 2 years 

after accreditation of the Charité Berlin IPC. 

Methods. Two years after the DKG accreditation an anonymous survey 

was conducted among the outpatient urologists of the region. The 

effects of the IPC accreditation on the quality of the treatment, the intersectional 

cooperation and the admission policy of the urologists were 

evaluated. Moreover, the acceptance of the centre’s medical education 

program and adherence to treatment recommendations were studied. 

The survey was based on questions applying the Likert scale for measurements 

of personal views. 

Results. A total of 134 urologists of the region were asked to take part 

in the survey. Of these, 61 (46%) completed the questionnaire. IPCs accredited 

by the DKG are generally well accepted by the majority (n=40, 

66%) of the queried urologists. However, only 17 (28%) confirmed im- 

provements in the intersectional cooperation between outpatient and 

hospital urologists, while 36% refused this fact and 36% were unsure. 

Only 18 (30%) experienced a higher quality of the patient care following 

the IPC accreditation, but 20 (33%) neglected this explicitly. As few as 16 

(26%) changed their admission policy in favour of the centre, and 11% 

admitted fewer patients to the IPC. For the remaining 46% the accreditation 

of the IPC had no impact on their admission policy. The majority 

of the interviewed urologists regularly made use of the medical education 

offered by the centre. Only 16 (26%) never participated in educational 

activities of the centre. The work of the centre in general was rated 

“good” or “very good” by the majority, but 8% still felt the work to be 

“inadequate”. The majority of urologists (77%) adhered to the treatment 

recommendations given by the centre, while only 8% neglected to do so. 

Conclusion. IPC’s in general are well accepted among urologist of the 

outpatient sector. However, improvements of the quality of care were 

not observed by the queried urologists and consequently the accreditation 

of the IPC had no relevant impact on the admission rate. IPC may 

facilitate evidence based treatment for prostate cancer through educational 

activities and treatment recommendations. 

0142 

Timing of catheter removal after radical retropubic prostatectomy 

(RRP): Has delayed catheter removal due to anastomotic 

leakage adverse effects on early continence? 

*P .J . Olbert1 , K . Simonis1 , A . Hegele1 , R . Hofmann1 1Universitätsklinikum Giessen und Marburg GmbH, Standort Marburg, 

Klinik für Urologie und Kinderurologie, Marburg, Deutschland 

Introduction. Early catheter removal within the first week is a common 

strategy in the postoperative management after RRP. Patient convenience 

is increased, however, the patients expectations as well. In case 

of anastomotic leakage, catheter removal is usually delayed for 1 to 

2 weeks, and many patients are concerned about detrimental effects of 

later catheter removal, especially in terms of continence. This work was 

conducted to compare early continence in patients with early vs. delayed 

catheter removal in cases of anastomotic leakage. 

Patients and methods. 128 consecutive patients have been evaluated 

prospectively between Jan. and November 2008. In 70% of patients, the 

catheter was removed on POD5 or 6 after documentation of a sufficient 

vesicourethral anastomosis by cystogram. In 30%, the cystogram revealed 

anastomotic leakage. In these patients, the catheter was removed 1 

or 2 weeks later, depending on the extent of the paravasation. Early continence 

was assessed before hospital discharge (in average 3 days after 

catheter removal) and after 3 months by a standardized Pad-Test and 

documentation of Pads needed/24 h. 

Results. The standardized PAD test showed comparable results postoperatively 

(17 vs. 12 g) and after 3 months (2.5 vs. 2.7 g). The number of pads 

needed/24 h was 3.2 vs. 3.5/24 h at hospital discharge and 2,3 vs. 4,0/24 h 

at 3 months. The differences detected were not statistically significant. 

The portion of patients needing 0 and 1 pads/24 h was 28 vs. 7% postoperatively 

and 40 vs. 25% at 3 months in favor of the early catheter removal 

cohort. This difference reached statistical significance (p

Abstracts 

0155 

Percentage of positive nodes after radical prostatectomy and 

pelvic lymphadenectomy: correlation with oncological outcome 

measures 

*P .J . Olbert1 , J . Hoffmann1 , F . Brüning1 , A . Hegele1 , R . Hofmann1 1Universitätsklinikum Giessen und Marburg GmbH, Standort Marburg, 

Klinik für Urologie und Kinderurologie, Marburg, Deutschland 

Introduction. Lymphadenectomy is an integral part of oncological surgery 

in many tumor entities. In prostate cancer (PC), pelvic lymphadenectomy 

gives essential staging- and prognostic information and might 

trigger adjuvant therapy. In low volume lymph node involvement, it 

can be curative as well with excellent long term survival data. However, 

the body of evidence is limited as far as lymphadenectomy in low risk 

patients and the extent of lymphadenectomy are concerned. This work 

was conducted to evaluate whether the number of removed nodes and 

lymph node density could serve as prognosticators after radical protatectomy. 

Patients and methods. The institutional PC database was evaluated for 

classical clinical and pathological data (age, pTNM-stage, preoperative 

PSA and Gleason grading) and for the numbers of all removed lymph 

nodes and of lymph node metastases. Lymphadenectomy included external 

iliac, obturator fossa and hypogastric nodes. χ2 and Mann Whitney 

U test were performed to compare sets of variables, multivariate 

regression analysis was used to evaluate the influence of other parameters 

on lymph node status. Kaplan Meier curves and log rank tests were 

done to display and compare time-event correlations. 

Results. 914 patients were included in the analysis, 10.8% were node positive. 

Mean Follow up was 51 months. The presence of lymph node metastases 

was independently predicted by T-stage, Gleason score and initial 

PSA. N-stage was significantly associated with biochemical Progression 

and with reduced cancer specific survival, but not with OS. In our patient 

cohort and in the given follow up, a higher lymph node yield was 

associated with better progression free and overall survival, without 

reaching statistical significance. In N+ patients, lymph node density did 

not affect survival, nor did the presence of extranodal tumor growth. 

Conclusions. Within the limitations of this retrospective study (mid 

term FU, consequently low number of events), the total number of removed 

lymph nodes appears to be more important than the ratio of 

affected nodes in N+ patients. This implicates a pivotal role of pathologically 

undetected lymph node metastases and supports the concept of 

extended lympadenectomy in intermediate to high risk patients. More 

prospective studies on lymphadenectomy in PC are warranted. 

0170 

Family history of prostate cancer and psychosocial distress in 

affected men 

*K . Herkommer1 , A . Dinkel2 , M . Kornmayer1 , P . Herschbach2 , J . Gschwend1 1Klinikum rechts der Isar der TU München, Klinik für Urologie, München, 

Deutschland, 2Klinikum rechts der Isar der TU München, Klinik für Psychosomatik 

und Psychotherapie, München, Deutschland 

Objective. Positive family history is a strong risk factor for the development 

of prostate cancer (PC). Thus, it seems reasonable that patients 

with a familial history of prostate cancer might worry about passing 

their disease to their kin, which might lead to the experience of distress. 

This study aimed at investigating the effect of family history of prostate 

cancer on psychosocial distress in affected men. 

Material and methods. Nationwide 3527 patients who were treated 

with radical prostatectomy between 2000 and 2005 were included in 

this study and completed a mail survey in 2009. Mean current age 

was 71.2 years (SD=6.5; range 45–92). The patients were divided into 3 

subgroups according to their family history: 68.0% (n=2.399) sporadic, 

25.9% (n=915) familial (at least one first-degree relative with PC), and 

6.1% (n=213) hereditary (according to the Johns Hopkins criteria). Can- 


cer-specific distress was assessed with the Questionnaire on Distress in 

Cancer Patients – Short Form (QSC-R10), depression and anxiety were 

assessed with a short form of the Patient Health Questionnaire (PHQ-2, 

GAD-2). We investigated the influence of family history, age at diagnosis 

(

0220 

Evaluation of CEA and Ca19-9 in transitional cell carcinoma of the 

bladder – serological and immunhistological findings 

*A . Hegele1 , V . Mecklenburg1 , P . Barth1 , P . Olbert1 , R . Hofmann1 1Philipps Universität, Klinik f . Urologie, Marburg, Deutschland 

Introduction and objectives. Following prostate cancer bladder cancer 

represents the second most frequent malignancy of the GU tract and the 

ninth most common cause of cancer worldwide with rising incidence. 

Since reliable markers predicting presence, muscle invasiveness or metastatic 

TCC have not been established up to now, cystoscopy, causing 

discomfort to the patients (pat), represents still the goldstandard in diagnosis 

of TCC. The aim of the present study was to evaluate the clinical 

value of CEA and Ca19-9 as a tumor marker in the diagnosis of TCC 

and to determine the relationship between the marker levels and the 

histopathological results. 

Material and methods. Between 06/2008 and 02/2010 CEA and Ca19-9 

were prospectively determined in 231 pat (173 m, 58 f, mean age 70 y) before 

undergoing TUR-B of a suspect bladder tumor. Additionally 11 pat 

(9 m, 2 f, median age 66 y) were presented initially with metastatic TCC. 

Immunhstochemical examinations (CEA and Ca19-9 staining) were 

performed in TUR-B specimens of 83 pat. 

Results. After TUR-B no malignant bladder tumors were found in 

71 pat. These pat served as controls. 14 pat with malignant bladder tumors 

but histological excluded TCC were excluded from analysis. In 146 

pat histological examination showed TCC: 74% (n=108) with superficial, 

non-muscle invasive (NMIBC) and 26% (n=38) with muscle-invasive 

(MIBC) bladder cancer. Compared to controls pat with TCC showed 

neither significant different CEA (p=0.234) nor Ca19-9 (p=0.061) levels. 

Pat with MIBC (n=38) showed significant elevated CEA (p=0.008) and 

Ca19-9 serum levels (p>0.001) compared to NMIBC (n=108). In local 

advanced MIBC and/or presence of lymph node metastases (≤pT3±N+, 

n=19) only Ca19-9 was significantly elevated (p=0.04) compared to 

MIBC confined on the bladder muscle (pT2No, n=19). Concerning 

TCC-grading significant higher CEA (p=0.031) and Ca19-9 (p=0.001) 

serum levels were found with rising grading. Pat with metastatic TCC 

showed compared to non-metastatic TCC the highest serum levels of 

Ca19-9 (p=0.003) but not for CEA (p=0.105). Immunhistochemical staining 

in 83 patients revealed a strong correlation between staining intensitiy 

and serum levels for Ca19-9 (p=0.004) but not for CEA (p=0.478) 

Conclusion. In conclusion our prospective data clearly show that neither 

CEA nor Ca19-9 serum levels are helpful tools in primary diagnosis 

of TCC. When during routine examination CEA and Ca19-9 levels are 

elevated and a gastrointestinal malignancy can be excluded you have to 

keep in mind existence of CEA/Ca-19-9 producing TCC and consecutively 

to check the urologic tract. Our date show a correlation of CEA 

and Ca19-9 serum levels with stage and grade of TCC disease confirmed 

by immunhistochemical findings. Ca19-9 is more promising as CEA. 

Utility of Ca19-9 serum levels monitoring response to therapy have to 

be checked in further studies as well as role of Ca19-9 as a prognostic 

factor in TCC. 

0225 

Influence of prostate volume on oncological and clinical outcome 

after radical prostatectomy due to prostate cancer 

*A . Hegele1 , T . Laumeier1 , F . Brüning1 , P . Olbert1 , R . Hofmann1 1Philipps Universität, Klinik f . Urologie, Marburg, Deutschland 

Introduction. Enlarged prostate volumes (PV) aggravate radical surgery 

in prostate cancer (f. e. radical prostatectomy). How far PV influence R1resection 

and clinical outcome after radical prostatectomy is unclear. 

Aim of this study was to investigate the possible relationship between 

PV and intra-, post- and pathological parameters after radical retropubic 

prostatectomy (RRP). 

Materials and methods. Between 01/2007 and 06/2010 RRP was performed 

in 454 men. Data were analyzed using the data bank of the “Prostate 

Cancer Center” Marburg. 

Results. Median PV was 59.4 g (20–209). Due to R2-resection 2 patients 

were excluded from analyses. Patients with a R1-resection (n=91, 20%) 

showed compared to R0-resection (n=361, 79,6%) a significantly lower 

PV (54 g vs. 60 g, p=0.048). PV>60 g (n=168) showed significantly elevated 

iPSA (p

Abstracts 

0250 

Prediction of favourable outcome in metastatic castration-resistant 

prostate cancer patients treated with docetaxel rechallenge 

*M . Heck1 , M . Thalgott1 , M . Retz1 , P . Wolf2 , T . Maurer1 , J . Gschwend1 , 

H . Kübler1 1Technische Universität München, Urologische Klinik, Klinikum rechts der 

Isar, München, Deutschland, 2Technische Universität München, Institut für 

Medizinische Statistik und Epidemiologie, München, Deutschland 

Objective. Chemotherapy with docetaxel is the standard first-line cytotoxic 

treatment in metastatic castration-resistant prostate cancer 

(mCRPC). In patients with good clinical response at first-line chemotherapy, 

docetaxel rechallenge has been proposed for further treatment. 

In the present study, we analysed the effectiveness of docetaxel rechallenge 

and sought to identify clinical variables predicting favourable oncological 

outcome. 

Patients and methods. We retrospectively evaluated the outcome of 

44 patients with mCRPC who were treated with 3-weekly docetaxel at 

first-line chemotherapy and rechallenge plus prednisone/ prednisolone 

between 1999 and 2011. All patients received at least 2 cycles of docetaxel 

rechallenge. The endpoints were PSA-progression-free survival (PSA- 

PFS), overall survival (OS). Furthermore, we analysed the impact of pretreatment 

variables on PSA-PFS and OS. Median PSA-PFS and OS were 

determined by Kaplan-Meier curves. The effect of clinical variables on 

PSA-PFS and OS was statistically analysed by a log-rank test or Cox 

regression with hazard ratios. All analyses were performed using a 0.05 

level of significance. 

Results. 44 patients were included on analysis. At a median follow-up 

of 26.4 months (range 9.8–89.8 months) after the first administration 

of docetaxel, 24 (54.5%) patients had died. Median PSA-PFS was 

5.9 months (95% CI 3.5–6.8 months) and median OS was 21.8 months 

(95% CI 19.9–23.7 months) after initiation of docetaxel rechallenge. 

36 patients achieved PSA-reduction ≥50% at first-line chemotherapy. 

Out of these 10 (27.8%) patients also responded with PSA-reduction 

≥50% at docetaxel rechallenge. PSA-reduction ≥50% at first-line chemotherapy 

with docetaxel was the only pre-treatment variable that correlated 

significantly with prolonged PSA-PFS (p=0.01) and OS (p=0.03). 

Patients with PSA-reduction ≥50% at first-line chemotherapy showed a 

median OS of 22.1 months since initiation of docetaxel rechallenge in 

comparison to 7.2 months in patients with

in young RARC compared to ORC patients (16 [8–25] vs. 22 [10–116], 

p=0.018). Transfusion rate was lower in RARC patients (0 [0–4] vs. 2 

[0–12] PRBC intraoperative, p=0.038) while no difference in blood loss 

was observed. Neither in the analysis of the whole groups nor subgroup 

analysis revealed differences in the rate of postoperative complications. 

Conclusions. Despite prolonged operation time, especially older patients 

seem to profit from RARC (faster reconvalescence, lower blood loss). 

Restricting new operation techniques to the young and fit might underestimate 

the advantages of these techniques. Further prospective 

validation of these results is needed, e.g. within multi-centric databases. 

0289 

Clinical outcome of combined Iodine-125 seed brachytherapy 

and image-guided intensity modulated external-beam radiotherapy 

for low intermediate risk prostate cancer 

*J . Boda-Heggemann1 , G . Welzel1 , S . Mohamed1 , M . Bohrer1 , *Y . Abo Madyan1 

, M . Polednik1 , M .-S . Michel1 , J . Schaefer1 , J . Kosakowski1 , N . Behnam1 , 

F . Wenz1 1Universtiät Medizin Mannheim, Strahlentherapie, Mannheim, Deutschland 

Purpose. Combination of low-dose rate (LDR) brachytherapy and external-beam 

radiotherapy (EBRT) has been shown to be a promising 

treatment modality in low intermediate risk prostate cancer. We retrospectively 

assessed clinical outcome, acute and late toxicity of combined 

image-guided intensity-modulated EBRT with Iodine-125 seed implantation 

for low intermediate risk prostate cancer (patients with one parameter 

violating the criteria for low risk disease). 

Patients and Methods. Between 2004 and 2009, 25 consecutive low 

intermediate risk prostate cancer patients (median age 66 years, median 

initial PSA 6.5 mg/dl, median Gleason-score 7) received LDR-brachytherapy 

with Iodine-125-seed implantation (120 Gy MPD) followed by 

IG-IMRT (image-guided intensity modulated radio therapy) with a 

median dose of 45 Gy. Image guidance was performed with stereotactic 

ultrasound and cone-beam CT. Primary end points of this retrospective 

evaluation were overall survival (OS), biochemical disease free survival 

(BDFS), acute and chronic gastrointestinal (GI) and genitourinary (GU) 

toxicity based on RTOG and LENT-Soma scales. Both acute and late 

toxicity were compared to pre-radiation symptoms (graded by LENT- 

Soma scores) on a patient-to-patient basis. 

Results. Median follow-up (FU) was 42 months. Except one patient, 

who died of a glioblastoma multiforme 49 months after radiotherapy, 

all patients are alive. Actuarial 2-year and 4-year BDFS rates were 95.8% 

and 91%, respectively. Two patients did not reach an adequate PSA-nadir 

and received further therapy. The only statistically significant risk 

factor for biochemical relapse was the value of PSA nadir (p=0.007). 

Before therapy, no GI symptoms higher >2 in any patient were observed, 

maximal level of GU symptoms was LENT-Soma °2 in 3 patients. 

Two patients had complete erectile dysfunction (°4) and 2 patients had 

a °2 prae-therapeutic erectile dysfunction. In the acute phase, maximal 

GI/GU toxicity was RTOG °2. At the end of IMRT treatment, 3 patients 

had RTOG °2 GU toxicity, and 5 patients had RTOG °2 GI toxicity. At 

the first FU (median: 6 weeks after IMRT), 7 patients had RTOG °2 GU 

toxicity, and 2 patients had RTOG °2 GI toxicity. Maximal late GI toxicity 

at last FU (median 39 months, range 8-70 months) was LENT-Soma 

°2 in 8 patients, and GU toxicity °3 and °4 in 1 patient each. By last FU, 

2 patients suffered °2, 9 patients °3 and 7 patients °4 erectile dysfunction. 

Conclusions. Iodine-125 seed brachytherapy in combination with imageguided 

IMRT is an effective and low-toxicity treatment option for low 

intermediate risk prostate cancer patients. The only significant toxicity 

observed is erectile dysfunction. The rate compares favorably to literature 

data after surgery and high dose EBRT. 

0315 

Two clinical trials assessing safety and efficacy of trastuzumab 

(Herceptin) as a monotherapy or in combination with gemcitabine/cisplatin 

in patients with metastasized urothelial cell 

carcinoma overexpressing HER2 

U . Rebmann1 , T . Klotz2 , *G . Melhorn1 1Diakonissenkrankenhaus Dessau, Urologische Klinik, Dessau, Deutschland, 

2Klinikum Weiden, Urologische Abteilung, Weiden, Deutschland 

Background. Prognosis for invasive urothelial cell carcinomas (UCC) is 

poor. Since HER2 is overexpressed in about 30% of patients, two clinical 

trials assessed Trastuzumab (T) treatment in patients with metastasized 

urothelial cell carcinomas overexpressing HER2. 

Methods. Patients (pts) with HER2 overexpression (score 2+ or 3+) 

UCC, ECOG performance status 0–2, at least one measurable lesion, 

and adequate organ function. Trial ML17599 included pts with tumor 

progression after previous platinum-based chemotherapy. T monotherapy 

with initial dose of 4 mg/kg T, weekly maintenance dose of 2 mg/kg 

was given until progression or intolerable toxicity. Trial ML17600 included 

chemotherapy naïve pts. T (4 mg/kg loading dose, 2 mg/kg weekly) 

was given in combination with gemcitabine (1200 mg/m2 on day 1, 8 

and 15) and cisplatin (70 mg/m2 on day 2). After 6 cycles, T maintenance 

continued until progression or toxicity. The primary endpoint was progression-free 

survival (PFS) for both studies. 

Results. Both trials were prematurely terminated due to low recruitment. 

ML17599: 5 pts were included. The median age was 66 years, all 

pts were male. There were 2 pts with HER2 score 2+ and 3 pts with score 

3+. Median PFS was 2.5 months and median overall survival (OS) 

14.7 months. One patient achieved stable disease, resulting in an OS of 

39 months. Most adverse events (AEs) were of mild to moderate severity. 

Only one pt experienced grade 3 toxicity (dyspnea). ML17600: 13 patients 

were included (10 male, 3 female pts). The median age was 69 years. 

There were 8 pts with HER2 score of 2+ and 5 pts with score 3+. Median 

PFS was 11.0 months and median OS 14.9 months. 5 pts achieved a response 

(2/13 complete response, 3/13 partial response), and 6/13 pts had 

stable disease, resulting in a clinical benefit rate of 84.6%. Hematological 

toxicities grade 3/4 occurred in 9 pts (69.2%). Other grade 3/4 toxicities 

included cardiac arrhythmia in 2 pts, constitutional symptoms in 2 pts 

and hypertension in 1 pt. 

Conclusion. As a result of low patient numbers in both trials, it is not 

possible to make a general statement about the efficacy of T either as 

a monotherapy or in combination with chemotherapy in patients with 

metastasized UCC. Some patients may benefit from well tolerated monotherapy. 

For combination therapy, response rate, PFS and OS appear 

to be higher. 

0327 

MARC-2: An open label, single arm trial to characterize patients 

with metastatic renal cell carcinoma treated with everolimus 

after failure of the first VEGF-targeted therapy 

M . Staehler1 , L . Bergmann2 , V . Grünwald3 , U . Keilholz4 , C .-H . Ohlmann5 , 

F . Schaller6 , *L . Strassl6 , K . Junker7 1Ludwig-Maximilians-Universität München Klinikum Großhadern, Urologische 

Klinik und Poliklinik, München, Deutschland, 2Johann-Wolfgang Goethe 

Universitätsklinikum, Frankfurt, Deutschland, 3Medizinische Hochschule 

Hannover, Hannover, Deutschland, 4Charitè Campus Benjamin Franklin, 

Berlin, Deutschland, 5Universitätsklinikum des Saarlandes, Homburg/Saar, 

Deutschland, 6iOMEDICO AG, Freiburg, Deutschland, 7Universitätsklinikum Jena, Jena, Deutschland 

Introduction. Clinical research in metastatic renal cell carcinoma is ongoing 

and the number of treatment options is going to increase. Characterization 

of patients most likely to benefit from a specific targeted agent 

has not yet been sufficiently addressed. Most patients are treated with 


141

Abstracts 

sequenced systemic medications based on the clinical course of the disease. 

So far, no reliable biomarkers exist to predict treatment outcome 

of the selected regimen in the individual patient. Thus, further investigation 

is needed to understand the treatment outcome and effects of 

the selected drugs in vivo. In the MARC-2-study, patients treated with 

everolimus will be characterized by serum and tissue markers in order 

to identify a pattern which could be suggestive of treatment outcome of 

everolimus after one VEGF-targeted therapy. 

Methods. Over a period of 2 years 80 patients are to be enrolled at about 

12 study centers in Germany. Major inclusion criteria are confirmed 

predominantly clear cell renal cell carcinoma, metastatic disease, failure 

of exactly 1 prior VEGF-TKI therapy, no pretreatment with mTOR 

inihibitors or bevacizumab. Tumor response will be assessed according 

to RECIST 1.1. Safety assessments include recording adverse events and 

monitoring of laboratory parameters. Primary objective is to assess 

the rate of patients free of disease progression after 6 months of treatment 

with everolimus. Secondary objectives are assessment of relation 

of biomarkers to the clinical benefit, progression free survival, overall 

survival, objective response rate and the safety profile. Part of MARC- 

2 are extensive explorative assessments: Blood samples for biomarker 

projects are taken pre-treatment and at different time points during the 

treatment until the end of study treatment. Histopathological classification 

of tumor samples will be performed. Biomarker projects include: 

Serum protein profiling by using SELDI-TOF-MS; quantification of 

Treg cells in blood samples; identification of serum metabolic biomarkers; 

polymorphisms in genes related to the VEGFR signaling pathway; 

expression analysis of the mTOR-pathway in tumor samples. Pre-dose 

blood samples for everolimus trough levels will be collected for pharmacokinetics. 

Tumor assessments by functional MRI will be performed 

within a substudy at selected sites. 

Results. MARC-2 was initiated in February 2011; the 1st patient was 

enrolled in March 2011. Until July 2011, 9 sites have been initiated and 

9 patients were recruited. 

0369 

Perioperative outcome in laparoscopic and da Vinci assisted 

partial nephrectomy in tumours >4 cm 

*H . Zenginli1 , M . Giessing1 , P . Albers1 , R . Rabenalt1 1Uniklinik Düsseldorf, Urologie, Düsseldorf, Deutschland 

Background. EAU Guidelines recommend partial nephrectomy as standard 

treatment for renal tumours smaller than 4 cm. Data on outcome 

up to date is rare and needs to be elucidated in further studies. We present 

the results of our series of laparoscopic (LPN) and da Vinci assisted 

partial nephrectomy (daViPN) in kidney tumours larger than 4 cm. 

Objective. To analyze the outcome regarding technical feasibility, morbidity, 

mortality, efficacy and complicationrate of LPN and daViPN for 

tumours ≥4 cm. 

Methods. In total, 190 patients were treated for renal tumours at our institution 

from 08/2008 through 03/2011. In 61 patients, elective LPN and 

5 da Vinci assisted partial nephrectomies (01/2011 through 03/2011) were 

performed. Patients were grouped according to tumour size: group A 

(40 patients) with tumours

litaxel. In addition to the MDR1-phenotype the polymorphisms in the 

MDR1-gene contributes to drug resistance. Therefore, after analyzing 

the MDR1-phenotype we defined the polymorphisms in the MDR1-gene 

C3435T, G2677T and G1199A in a model of two chromophobe RCC 

cell lines (chrompho-A and -B) with an „intrinsic paclitaxel resistance” 

and a model of two RCC cell lines of the clear cell type (clearCa-21sens 

and clearCa-21res) with an „acquired paclitaxel resistance”. 

Methods. MTT-Assay, RT-PCR, Rhodamin-efflux-assay, flow cytometry, 

DNA-sequencing. 

Results. 1.) After exposure to paclitaxel the model with the intrinsic resistance 

showed an IC50 of 0,08 µM in the paclitaxel-sensitive chrompho-A 

and 387,5 µM in the paclitaxel-resistent chrompho-B whereas in 

the acquired model an IC50 of 0,38 µM in clearCa-21sens and >1000 µM 

in clearCa-21res was detected by MTT-assay. In all cell lines exposure 

to paclitaxel in combination with curcumin resulted in an additive 

growth inhibitory effect. 2.) It has been proven on mRNA-level that Pglycoprotein 

(P-gp) was expressed in all cell lines. 3.) By flow cytometry 

an amount of 18% ±2 of P-gp positive cells in chrompho-A and 30% ±3 

P-gp positive cells in chrompho-B was detected while the clear cell lines 

have a comparable amount of P-gp positive cells in clearCa-21sens 

(41% ±2) and in clearCa-21res (42,5% ±1). 4.) The functionality of P-gp 

was detected in all cell lines by Rhodamin-efflux-assay whereas in the 

cell line clearCa-21res an eight-fold higher efflux than in the cell line 

clearCa-21sens became evident. 5.) Analyzing the polymorphisms in 

the MDR1-gene in untreated cells the “silent” C3435T polymorphism is 

evident in both models. The intrinsic model showed the G2677T polymorphism 

in the paclitaxel-resistant chrompho-B and G1199A in both 

cell lines proven by DNA sequencing. In the acquired model the G2677T 

polymorphism could be observed in both cell lines, but the G1199A polymorphism 

only in the cell line clearCa-21sens. 

Conclusion. The MDR1-phenotype is associated with the sensitivity to 

paclitaxel in human renal cell carcinoma. Furthermore our results show 

first evidence for association of MDR1-polymorphism and sensitivity to 

paclitaxel in a model of “intrinsic” and “acquired” paclitaxel resistance. 

0438 

Plasmacytoid urothelial carcinomas of the bladder harbor complex 

genomic aberrations 

*B . Keck1 , S . Wach1 , C . Ellmann1 , F . Kunath1 , R . Stoehr2 , H . Taubert1 , A . Hartmann2 

, B . Wullich1 1 Urologische Universitätsklinik Erlangen, Urologie, Erlangen, Deutschland, 

2 Universitätsklinikum, Pathologisches Institut, Erlangen, Deutschland 

Aim. To investigate whether plasmacytoid urothelial carcinomas (PUC) 

are characterized by distinct chromosomal aberrations differing them 

from conventional muscle invasive transitional cell carcinomas (TCC) 

of the bladder and whether there are molecular events leading to the 

known loss of membranous E-cadherin expression. 

Methods. Analysis of 25 PUC was performed by conventional comparative 

genomic hybridization (CGH). Chromosomal regions were defined 

as characteristic if they were found in at least 20% of the tumors analyzed. 

Regions differing from whole-chromosomal signal ratio by at least 

three standard deviations (SD) were classified as chromosomal gains 

or losses. Heterochromatic and centromeric regions known to display 

unreliable signal ratios were excluded from analysis. Additionally copy 

number variation of CDH1 (E-Cadherin) was analyzed using polymerase 

chain reaction (PCR; n=19). 

Results. Chromosomal aberrations were found in all PUCs analyzed. In 

an average, 11.0 (1–17) aberrations per tumor were detected. Recurrent 

gains were found at 1q (40%), 3p (24%), 6p (32%), 7q (20%), 11q (64%), 15q 

(32%), 16q (40%), 17p (76%), 17q (88%), 20q (72%), 21q (32%), recurrent 

losses at 4q (72%), 5q (36%), 6q (60%), 13q (24%), and Xq (40%). PCR analysis 

showed heterozygous deletion of CDH1 in 68% of the PUC, whereas 

amplification was detected in only 3%. 

Conclusion. PUCs are characterized by a high genomic instability with 

aberrations that are even more complex than what has been described 

for conventional muscle invasive TCCs. However, no specific aberrations 

were detected that would allow to discriminate PUCs from conventional 

TCCs. Gains at 11q, 17q, 17p and 20q as well as losses at 4q and 6q 

are found in the vast majority of PUCs and could therefore represent 

important chromosomal regions that are involved in PUC carcinogenesis. 

These chromosomal aberrations are in line with other molecular 

variations of PUC like loss of membranous E-cadherin that are linked 

to the aggressive behaviour of PUC. Copy number variation analysis 

indicates heterozygous deletion of CDH1 as one underlying mechanism 

of this molecular event. 

0443 

The incidence of intrathoracic lymph node metastases and longterm 

outcome after pulmonary metastasectomy for metastatic 

renal cell carcinoma 

*N . Kudelin1 , S . Bölükbas1 , M . Eberlein1 , 2 , J . Schirren1 1 Dr . Horst Schmidt Klinik, Thoraxchirurgie, Wiesbaden, Deutschland, 2 Carver 

College of Medicine, Division of Pulmonary, Critical Care and Occupational 

Medicine, Iowa City, USA 

Objective. To investigate the incidence of intrathoracic lymph node metastases 

and long-term outcome after pulmonary metastasectomy (PM) 

for metastatic renal cell carcinoma (RCC). 

Methods. The office records of 116 consecutive patients (82 men, age 

61.7±9.0 years) who underwent PM and systematic lymph node dissection 

with curative intend from January 1999 through December 2009 

were reviewed from a prospective database. Patients’ characteristics 

and the following data were recorded: disease-free-intervall (DFI) from 

nephrectomy to the diagnosis of metastasis, systematic chemotherapy 

before surgical intervention, surgical procedures, pathohistological 

results, morbidity, mortality, survival and possible prognostic factors 

were analyzed 

Results. The overall 5-year-survival and 10-year survival rates were 49% 

and 21%, respectively. Morbidity and mortality rates were 13.8% and 0.9 

%, respectively. 40 patients (34.5%) had systematic therapy before metastasectomy. 

Partial regression was observed in 27.5% (11/40). Complete 

resections (R0) could be achieved in 108 patients (93.1%). Intrathoracic 

(hilar and/or mediastinal) lymph node metastases were found in 46.6 % 

of the study population. Median survival was 56.6±9.2 months. Patients’ 

age (≥70 years; p=0.003), female gender (p=0.016) and number of metastases 

(≥2 metastases; p=0.012) were associated with inferior survival 

after pulmonary metastasectomy in the univariate analysis. Short DFI 

(

Abstracts 


0006 

Multiprofessional cooperation in the Oncological Centre in 

Berlin-Spandau 

*J . Potenberg1 , G . Sproßmann-Günther2 1Ev . Waldkrankenhaus, Innere Abteilung, Berlin, Deutschland, 

2Ev . Waldkrankenhaus, Apotheke, Berlin, Deutschland 

Before the certification of the centre itself some components of the 

Oncological Centre had to have certified: 2000 Pharmacy of the Paul 

Gerhard Diakonie/2005 Breast Centre/2009 Centre of colorectal cancers/2009 

Centre of gynecological cancers. The first certification was 

the manufacturing of cytotoxic agents. 2010 396 patients were treated 

with antineoplastic drugs in our hospital. Calculated doses were checked 

by the pharmaceutical software Zenzy. Before the application of 

the cytostatics the informed consent of the patient was obtained. This 

consent describes side effects of each single drug that is to be given (e.g. 

heart failure by trastuzumab). After the treatment the side effects was 

estimated and the objective response of the tumour was evaluated using 

RECIST criteria. Therapy protocols describe the course of events and 

the handling of side effects of chemotherapy and the complications caused 

by the tumour. 

Nausea and Emesis/Treatment of pain/Fever and neutropenia/Infections/Mucositis, 

diarrhea, constipation/Handling of thrombosis. 

For a structural detection of side effects and the estimation of the performance 

status of the patient a „therapy check was developed. This 

therapy check is orientated on the CTC criteria, suited also for patients 

in studies. 2010 the haematological laboratory performed 5000 tests, including 

blood pictures, diagnosing leucaemias and neoplastic diseases 

in ascites und pleura fluid. Studies are an integral part of the quality assurance 

in the treatment of neoplastic diseases. Patients have the possibility 

getting drugs that aren’t approved yet. The high rate proportion of 

patient (e.g. 20% in breast centre) is a great challenge. In 2008 the outpatient 

cancer centre in the Ev. Waldkrankenhaus was created. It contains 

20 places for infusion therapy. Hospital doctors and free practicing physicians 

are working together under one roof. This collaboration made 

sure a 24 h/7 d care of patients including CT-scans and intensive care 

around the clock. Quality circles and the tumour conferences facilitate 

the compliance of guidelines. The tumor conferences are the core of 

the oncological centre. Here alls the tumour specialists are represented 

enabling the multiprofessional decision pondering several therapeutic 

options: 

Visceral, thorakal and orthopaedic surgeons/Pathology, Radiology, 

Pharmacy/Radiotherapy, Oncology. 

Several other professions are represented: Psychooncology, breast care 

nurses, social workers and the palliative care team. The concerted deliberation 

gives the effective decision, which is recorded and filed. The 

individual patient gets his or her file containing all the important findings. 

With the complete file the patient can obtain every opinion if he 

or she wishes so. 

0050 

Patients with metastatic solid tumors who receive their treatment 

in a community based oncology group practice live longer. 

*R . Weide1 , S . Feiten2 , V . Friesenhahn2 , J . Heymanns1 , K . Kleboth2 , U . Mergenthaler2 

, J . Thomalla1 , C . van Roye1 , H . Köppler1 1 Praxisklinik für Hämatologie und Onkologie, Koblenz, Deutschland, 

2 Institut für Versorgungsforschung in der Onkologie, Koblenz, Deutschland 

Background. Overall survival of patients (pts) with metastatic (met) solid 

tumors is known from controlled prospective trials (CPT). Results 

from CPT are biased due to necessary patient selection. No data exist 


so far about the outcome of unselected pts with met solid tumors who 

receive routine care treatment in a community based oncology group 

practice. 

Patients and methods. Retrospective overall survival analysis of all pts 

with met breast cancer, non small cell lung cancer, colorectal cancer and 

pancreatic cancer who received their treatment between 1995–2011 in an 

oncology group practice in Germany. Overall survival was determined 

from the start of palliative therapy until death. 

Results. Median overall survival in 403 pts with met breast cancer was 

30 months [Weide R et al (2009), Onkologie 32(3):107–113] compared to 

24–28 months in CPT. Median overall survival of 86 pts with Her2-positive 

met breast cancer was 33 months [Weide R et al (2010), Senologie, 

7:159–160] compared to 25 months in CPT. Median overall survival in 

119 pts with met NSCLC was 11 months [Köppler et al (2009), Clin Med 

Oncol, 3:63–70] compared to 6–9 months in CPT. Median overall survival 

in 206 pts with met colorectal cancer was 21 months [Köppler et 

al (2010), Eur J Cancer Care 19:795–802] compared to 20–24 months in 

CPT. Median overall survival in 84 pts with met pancreatic cancer was 

42 weeks [Köppler et al (2004), J Support Oncol 2:159–163] compared 

to 12–24 weeks in CPT. Psychosocial distress has been shown to be lower 

compared to hospital settings [Mergenthaler et al (2011) Ann Oncol 

22:931–938]. Additional data will be presented. 

Conclusions. Overall survival of patients with metastatic solid tumors 

who receive their treatment in a community based oncology group 

practice compares favorably with the survival achieved in CPT. This 

survival advantage may be due to the cumulative oncology experience, 

continuity of care due to a constant patient-oncologist relationship, better 

patient compliance and lower psychosocial distress of patients and 

caregivers. 

0054 

Cancer patients’ use of dietary supplements and non prescription 

drugs – An evaluation of the Cancer Information Service, 

German Cancer Research Center, Heidelberg 

*B . Hiller1 1Deutsches Krebsforschungszentrum, Krebsinformationsdienst, 


Introduction. Many cancer patients believe that standard treatment is 

not enough. They use antioxidants during chemotherapy or radiation, 

detoxifying agents after treatment, homeopathy to cope with side effects 

and immune boosters to reduce the risk of relapse, often without 

telling their physicians. Problems are well documented, e.g. unwanted 

side effects and pharmacokinetic interaction with conventional cancer 

treatment. Even a negative impact on therapy outcome is discussed. 

Methods. To evaluate prevalence and patterns of self-medication among 

cancer patients in Germany, the National Cancer Information Service 

at the German Cancer Research Center conducted a telephone survey in 

2010. 659 Cancer patients using the service’s toll free information hotline 

were asked, whether they used any over-the-counter (OTC) drugs, 

dietary supplements or other medication on their own initiative. Answers 

were indexed according to lists of pharmaceuticals licensed within 

Germany or the European Union. For classification of substances 

without registration, dietary supplements etc., the Cancer Information 

Service’s own database was used as a reference. 

Results. 51 % of the callers used self-administered drugs or supplements 

at the time of the interview, most often without telling their physicians. 

The 338 patients named 620 different substances. Most common 

were selenium, zinc and multivitamins, followed by soy proteins, phytoestrogens, 

pomegranate juice, mushrooms, enzymes, laetrile, but also 

NSAID and other registered prescription free drugs. There were, however, 

substantial differences concerning the patterns of use: Some patients 

indicated, that they had taken an aspirin or a laxative the evening 

before. Others told the interviewers, that they regularly took a multivitamin-multi-mineral 

nutrient and combined it with extra doses of

vitamin A, C, E and zinc on the same day. Women added phytoestrogens, 

men selenium and pomegranate to this potpourri. 

Discussion. The data show how frequently German cancer patients use 

dietary supplements or non prescription drugs. Most of them are not 

aware of problems arising from polypharmacy. Therefore, limits and 

risks of self-administered medication should be an issue in the counseling 

and informing of cancer patients by health professionals. 

0065 

Quality of life (QoL) and function results of the minimal-invasive 

implantable, subcutaneous ureter prothesis (Detour®) for geriatric 

and palliative care patients with cancer therapy associated 

ureter strictures 

*A . Janitzky1 , M . Porsch1 , J . Borski1 , J .J . Wendler1 , D . Baumunk1 , M . Schostak1 , 

U .-B . Liehr1 1Universitätsklinikum Magdeburg A . ö . R ., Klinik für Urologie, Magdeburg, 

Deutschland 

Purpose. Urinary diversion, such as DJ catheter and nephrostomy, are 

used in case of extensive and severe ureter strictures if surgical corrections 

are impossible. The Quality of life (QoL) is limited by periodically 

and partly difficult catheter changing procedures, catheter associated 

complications and external urinary diversion. In contrast to that the 

Detour® system as a permanent subcutaneous alloplastic ureter prothesis 

(inner silicone tube with a diameter of 5 mm and a Dacron® coating) 

is an alternative. A regular change is not necessary. The system is implanted 

percutaneously into the renal pelvis, tunnelled subcutaneously 

and typically introduced into the bladder via a small suprapubic incision. 

An introduction into replacement bladders as well as into cutaneous 

stoma is possible too. 

Methods. A prospective single center study of 25 Detour® prothesis implanted 

patients between 2004 and 2011 was performed. Surgical feasibility 

as well as QoL (EORTC QLQ-C30), clinical parameters, prothesis 

function and complications were evaluated in acute, subacute and chronic 

post-treatment period. 

Results. 29 Detour® systems (Coloplast®, Hamburg, Germany) implantations 

were performed in 25 patients (4 bilateral), 26 renovesical, 2 into an 

ileum conduit and 1 into a neo-bladder. 17 patients were supplied by nephrostomy, 

11 with double-J or mono-J catheter, 1 with ureterocutaneostomy. 

Causes of implantation: 9 radiogenic stenosis, 3 iatrogenic long 

segment ureter lesions, 4 metastatic tumors, 8 post-surgery ureteral 

strictures, 1 revision of an ureterocutaneostomy. Intraoperative complications: 

1 intestinal lesion (suture and uncomplicated implantation of 

the system in the same session), 3 bleedings of the renal pelvis or into the 

tube with temporary nephrostomy or drainage. Urinary tract infections 

and 3 secondary wound healings were found post-operatively. 3 infected 

or occluded systems had to be explanted (1 in an ileum conduit, 1 in a 

neo-bladder, 1 normal). Two patients died because of tumor. Renal function 

is stable or improved in the follow-up (3 month to 7 years). Patient’s 

satisfaction is high. The analysis of the EORTC QLQ-C30 QoL forms 

shows an overall QoL of 90% (43–98%, mean 85%). 

Conclusions. The Detour® system is a useful alternative to standard urinary 

tract diversion not only in palliative care. Possible complications 

are manageable. QoL and social reintegration, and in particular active 

participation in social life are improved significantly. 

0070 

Information about medical rehabilitation in breast center 

hospitals – status quo, information needs and associations with 

hospital characteristics 

*G . Nellessen-Martens1 , C . Kowalski1 , L . Ansmann1 , H . Pfaff1 1 IMVR, Köln, Deutschland 

Background. The S3-guidline for diagnostics, therapy and post-operative 

care recommends early patient information about medical rehabilitation. 

This paper investigates the status quo of information about 

medical rehabilitation during the hospital stay and information needs – 

both from the patients’ point of view. Additionally, differences between 

hospitals were analyzed. 

Methods. Newly-diagnosed breast cancer patients treated in breast center 

hospitals in North Rhine-Westphalia in 2010 were asked to complete 

the Cologne Patient Questionnaire for Breast Cancer, a standardized 

postal questionnaire. The survey data were supplemented with clinical 

data by medical personnel. The data were also combined with data from 

key informants of breast center hospitals, providing information on 

teaching status, number of hospitals per breast center and cooperation 

with rehabilitation clinics. 

Results. 3840 patients from 93 breast cancer hospitals participated in 

the study. 79% reported having been given information on medical 

rehabilitation and 21% have not been informed. 27% reported a need 

for more information. A multilevel model found differences between 

the hospitals concerning the information about medical rehabilitation 

(interclass correlation coefficient of 0.11). Whereas in some hospitals all 

patients have been informed, in other hospitals only 22% of the patients 

have been informed. Model 1 found some statistically significant associations 

on patient-level, e.g. information about rehabilitation is significantly 

higher for patients without partner, for patients with German as 

their native language and for patients with adjuvant chemotherapy. The 

chance for receiving information was significantly lower for patients 

with UICC-stage 0, stage 2, stage 3 and stage 4 compared to patients 

with stage 1. In Model 2, hospital-level characteristics were added. No 

statistically significant associations were found on hospital level. 

Conclusions. The results on patient-level lead to the discussion, whether 

information should be tailored to patients depending on their native 

language or family status. Furthermore, differences between breast center 

hospitals exist but cannot be explained by the included hospital characteristics. 

Nevertheless, the results show that for most hospitals the 

extent and manner of information about medical rehabilitation should 

be improved. 

0119 

Group class for patients and families: “Chemotherapy – What I 

need to know” in the Center for Integrated Oncology 

*B . Strohbücker1 , T . Elter2 , S . Stock1 , M . Schwartzkopff2 , J . Wolf2 1 Uniklinik Köln, Institut für Gesundheitsökonomie und klinische Epidemiologie, 

Köln, Deutschland, 2 Uniklinik Köln, Centrum für integrierte Onkologie, 

Köln, Deutschland 

Objectives. Patients receiving cancer treatment in the ambulatory setting 

need targeted information on management of chemotherapy and 

its side effects. Well informed patients can take an active part in the 

therapeutic procedure and make their own decisions. Information will 

also reduce stress and anxiety and support the coping process. We wanted 

to develop a model of an easy accessible, cost efficient group class for 

patients who receive chemotherapy and their families. 

Method. The topics of the group class were based on the literature as 

well as on a small patient survey we performed in our clinic. We also 

considered recommendations concerning the organization of a group 

class from the literature. Group classes were designed in a teamteaching 


145

Abstracts 

format, involving a physician and a nurse form the clinic. Evaluation of 

the class was done by a semi-structured questionnaire. 

Results. We carried out two pilot group classes. Many patients were accompanied 

by a family member seeking for information, too. The focus 

was on participants’ questions; they were collected at the beginning of 

the class and documented on a flip chart. A short lecture on requested 

topics was expanded by the following group discussion. The main topics 

were: the organizational procedure of chemotherapy, nausea and 

vomiting, oral care, hair loss, fatigue, dietary recommendations as well 

as risk of infection and bleeding. Participants valued the information 

received and exchange of experience as very helpful. They appreciated 

having sufficient time for discussing their questions. 

Discussion. Group classes are an adequate forum to present and discuss 

relevant information. Physicians and nurses in the clinic will safe time 

since many questions of patients and families are dealt with before 

starting chemotherapy. A group class on a regular basis, organized as 

a walk-in class may help to facilitate organizational procedure for both 

patients and administrators. 

0130 

Changes in the quality of psychosocial care by urologists in longterm 

treatment of localized prostate cancer: the patients’ view 

*N . Ernstmann1 , J . Jung1 , O . Ommen1 , H . Pfaff1 , L . Weißbach2 1 2 Universität zu Köln, IMVR, Köln, Deutschland, Stiftung Männergesundheit, 


Background. Whilst much is known as to the met and unmet communication 

needs of prostate cancer patients, few studies have been conducted 

on the changes in communication between provider and patient 

over time. The aim of our study is to examine a) whether there are changes 

over time in the quality of psychosocial care in long-term treatment 

of localized prostate cancer and b) whether those changes are associated 

with the treatment decision. 

Methods. Data were collected within a five year prospective, multicenter 

observational study starting in 2008 in Germany. At 6-months intervals 

general clinical data, tumour stage and data reported by the patient about 

quality of life, provider-patient-interaction, treatment satisfaction 

and individual costs are documented. Data of n=1216 patients (T0 = initial 

diagnosis and T1 = 6 months after initial diagnosis) were collected 

until now. Provider-patient-interaction is assessed with a 13 item instrument 

with the subscales devotion by physicians (5 items), support by 

physicians (3 items), information by physicians (2 items), and shared 

decision making (3 items). 

Results. After 6 months the assessment of shared decision making has 

significantly declined in the group of patients undergoing a prostatectomy 

and the hormonal therapy group compared to the time of initial diagnosis. 

Further, patients undergoing a prostatectomy report the lowest 

level of support by their urologists at the time of initial diagnosis. The 

ratings differ significantly from the hormonal therapy group. 

Conclusions. Our results indicate that the overall quality of psychosocial 

care as assessed by our patients is very high. However, we found 

significant changes over time and differences between the treatment 

groups. Future analyses of our 5-year prospective data will allow us to 

investigate whether the results are stable in the long run. The reasons for 

the differences between surgically treated patients and other treatments 

groups should be subject to further studies, preferably in a qualitative 

approach. 


0189 

In- and outpatient psychosocial care for cancer patients – comparison 

of cancer incidence rates, psychosocial needs and psychosocial 

care at a University centre 

*S . Singer1,2 , D . Müller-Briel2 , A . Dietz2 , E . Brähler2 , K . Schröter2 , A . Lehmann- 

Laue2 1 Bergische Universität Wuppertal, Gesundheitspsychologie, Wuppertal, 

Deutschland, 2 Universität, Leipzig, Deutschland 

Objectives. The aim of this study was to determine rates of psycho-oncological 

care for cancer in- and outpatients under routine conditions 

in a large University hospital. We analyzed the percentage of patients 

who received care comparing it with self- and expert-rated supportive 

care needs. 

Methods. The percentage of inpatients who received psycho-oncological 

care was calculated by comparing the number of cancer patients treated 

at the hospital as documented by the local tumor registry (n=1979) with 

the number of patients treated by a psycho-oncologist in that hospital as 

documented by the hospital’s psycho-oncological consultation-liaison 

service. The percentage of outpatients who received psycho-oncological 

care was calculated by comparing the number of incident cancer cases 

as documented by the local tumor registry (n=5886) with the number of 

patients who received at least one consultation at the local tumor counseling 

centre. Supportive care needs were estimated by analyzing data 

of a prospective patient survey in the same hospital (n=1803) using the 

Hospital Anxiety and Depression Scale and single items to determine 

social burden and the wish for emotional support. 

Results. 11% of in- and of outpatients (n=234 and n=638) received psycho-oncological 

care. Social care needs were prevalent in 37% and 

psychological care needs in 52% of the patients during the stay at the 

hospital and in 42% (social and psychological) half a year later. 41% of 

the patients expressed the need to see a social worker and 29% to see a 

psychologist. Large differences between patients of different tumor entities 

occurred. 

Conclusion. Psycho-oncological care delivered to cancer patients under 

routine conditions was below the actual needs rate as estimated by 

screening instruments and as expressed by the patients. 

0229 

Relevance and occurrence of phase IV studies in clinical cancer 

research – a situation analysis 

*M . Hartmann1 1European Consulting & Contracting in Oncology, Medical-Clinical Affairs, 

Trier, Deutschland 

Background. Historically, phase IV studies do not play a relevant role 

in clinical cancer research. The new EU pharmacovigilance legislation, 

issued on 31 December 2010, will strengthen and rationalize the current 

system for monitoring the safety of medicines on the European market 

and enables drug authorities for the first time ever to mandate the conduct 

of post-authorization studies. 

Methods. The existing requirements for and definitions of post authorization 

(i.e. phase IV) studies in Germany and other European key 

countries (France, Italy, Spain, Netherlands, UK) were analyzed. Comparative 

official figures relative to the conduct of phase IV studies in 

these countries over the last decade were collected. Using descriptive 

statistics, the proportion of phase IV trials and trends in the conduct of 

these trials were determined. 

Results. The definitions of, what constitutes a “post authorization study”, 

are widely differing across Europe. Some consistency exists only 

regarding the requirements for interventional phase IV studies. For 

non-interventional phase IV studies, including the “Anwendungsbeobachtungen” 

as defined by the German Medicines Law and other types of 

pharmacoepidemiological studies, the requirements for the ethical and

egulatory supervision, informed consent, insurance and data protection 

as well as for data management and reporting are not harmonized 

at all. Taking into account these national differences in the supervision 

of observational and quasi-observational clinical studies, available figures 

from drug authorities indicate a rise in the number of phase IV 

drug trials in several countries including Germany, where the number 

of phase IV drug trials augmented annually by 6% over the last decade. 

Phase IV drug trials currently represent 10–15% of all clinical trials in 

the above-mentioned EU countries with Germany serving as the rear 

end light. With regard to the low number of phase IV trials currently 

reported at cancer conferences, it is assumed that currently the reporting 

of phase IV study results at cancer congresses is rather not habitual. 

Conclusion. With the coming-into force of the new EU pharmaceutical 

legislation in 2012, the relevance and occurrence of phase IV trials will 

further increase with an impact on clinical cancer research and cancer 

conferences. Pharmacovigilance and pharmacoepidemiological studies 

will contribute in the future much more to the evidence-building and 

decision-making in oncology and hematology. 

0285 

Fruit, vegetable and red meat consumption before and after 

rehabilitation among breast cancer patients 

*A .-K . Exner1 , H . Kähnert1 , B . Leibbrand2 , I . Biester3 , D . Gharaei4 , C . Niehues5 , 

M . Trapp6 1Salzetalklinik, IFR, Norderney – Bad Salzuflen, Bad Salzuflen, Deutschland, 

2 3 Salzetalklinik, Onkologie, Bad Salzuflen, Deutschland, MediClin Rose 

Klinik, Onkologie, Horn-Bad Meinberg, Deutschland, 4Klinik Porta-Westfalica, 

Onkologie, Bad Oeynhausen, Deutschland, 5Median Kliniken am 

Burggraben, Onkologie, Bad Salzuflen, Deutschland, 6Median Klinik am 

Park, Onkologie, Bad Oeynhausen, Deutschland 

Introduction. Several studies report associations between diet as well as 

an increased body mass index (BMI) and breast cancer. Breast cancer 

patients (BCP) are advised to follow a healthy diet. The German Society 

of Nutrition and the World Cancer Research Fund recommend the following: 

daily consumption of 2 fruit and 3 vegetable servings as well as 

weekly 300 grams red meat (approx. 2 servings). The aim of the study 

was to explore dietary patterns (fruit, vegetables and red meat) of BCP 

before and 6 months after rehabilitation. Moreover, the impact of nutritional 

counseling (NC) on dietary patterns during rehabilitation has 

been investigated. 

Methods. During the INOP-study, 450 BCP were interviewed at 2 points 

in time using questionnaires: at the beginning (t1) and 6 months 

after rehabilitation (t3). The participants were interviewed regarding the 

frequency of their daily fruit and vegetable intake as well as weekly red 

meat consumption. The analyses are based on a subsample of BCP due 

to yet finished follow-up at the time of the study. A statistical analysis 

comparing dietary patterns of BCP who received NC during rehabilitation 

with BCP without NC was carried out at t1 and t3 using t-test 

analysis. 

Results. The proportion of BCP following the above named recommendations 

increased significantly from t1 to t3 as follows: fruit consumption 

from 76–81%, vegetable consumption from 20–24% and red meat 

intake from 63–72%. At t1, no significant differences regarding fruit, vegetable 

and red meat consumption has been found between BCP receiving 

NC (n=233) and BCP without NC (n=185). However, BCP receiving 

NC exhibited a significantly elevated BMI as compared to BCP without 

NC at t1. BCP with NC stated “loss of weight” as well as “healthier diet” 

as major targets for the participation in NC. Compared to BCP without 

NC, BCP with NC exhibited a significant increase in fruit consumption 

between t1 and t3 (p

Abstracts 

aspects of hospital care along the progress of the breast center implementation 

and (2) to analyze differences between breast center hospitals 

concerning these aspects. 

Methods. Breast centers in NRW participate in annual patient surveys. 

After surgery, newly-diagnosed breast cancer patients were surveyed on 

their perception of several aspects of hospital care. This poster presents 

trends in patient satisfaction with hospital care between 2006 and 2010 

by displaying mean scores of 17 single items measuring diverse dimensions 

of satisfaction over all hospitals. To investigate whether differences 

between breast center hospitals in patient satisfaction have been decreasing 

over time, intraclass-correlation coefficients (ICCs) were calculated 

using multilevel modeling. 

Results. The mean values of almost all patient satisfaction dimensions 

were gradually increasing over time and they express a very high level of 

patient satisfaction. Simultaneously, for most dimensions the ICCs were 

decreasing between 2006 and 2010, although linear trends could rarely 

be identified over time. 

Conclusion. The results imply that, overall in NRW patients are very satisfied 

with the care of breast center hospitals. The slightly increasing 

satisfaction between 2006 and 2010 might be a result of the breast center 

concept and the benchmarking results of the patient surveys as it can be 

used for quality improvement. Nevertheless, causality cannot be assumed. 

Moreover, the ICCs indicate that, over time, there are fewer differences 

between hospitals in most aspects of patient satisfaction. Thus, 

the progressing fulfilment of the certification criteria may be reflected 

in consistently high levels of patients’ perceived quality of hospital care. 

Moreover, the idea to investigate variations between health care facilities 

by multilevel modeling presents a useful approach for evaluating 

the implementation of new concepts in health care and could also be 

applied to other measures of quality of care, such as performance indicators. 

0317 

Development of a “best practice model” assuring medication 

safety in cancer patients 

*A . Wilmer1 , N . Döhler1 , K . Ruberg2 , Y . Ko3 , U . Jaehde1 1Pharmazeutisches Institut, Universität Bonn, Klinische Pharmazie, Bonn, 

Deutschland, 2Kronen-Apotheke, Wesseling, Deutschland, 3Johanniter- Krankenhaus, Bonn, Deutschland 

Objective. To enhance patient safety in anticancer drug therapy by 

structured and standardized multiprofessional inpatient care. 

Methods. A module-based approach was chosen to define “best practice”. 

Care modules consisting of evidence-based supportive care, task 

assignment to the involved professionals, and patient information were 

developed based on a literature review and previous experience with 

multiprofessional patient care. 

Results. So far, six care modules were developed for medication reconciliation 

and management, detection of drug interactions and management 

of four common adverse events (AE): nausea and emesis, 

mucositis, fatigue and pain. For each module a working algorithm was 

constructed illustrating the care process and facilitating multiprofessional 

accomplishment by physicians, pharmacists and nurses. The 

modules for medication reconciliation and the interaction check are to 

be applied routinely for each patient treated with anticancer drugs. In 

contrast, the four modules for AE management can be applied individually 

depending on patient status and anticipated AE. Each AE module 

comprises a supportive care leaflet providing current guideline recommendations 

for physicians and pharmacists and a specific information 

brochure for the patient providing recommendations for daily living 

and supporting material like diaries and questionnaires. 

Conclusion. Our best practice model can be individualized to a great 

extent by combining different modules for each patient according to his 

medication and the anticipated toxicity. Moreover, it can be expanded 

by further modules addressing other AE or minimizing further pro- 


blems, e.g. adherence. The model will be assessed and evaluated at the 

Johanniter-Krankenhaus in Bonn, Germany. 

0331 

The “NorthGerman Tumorbank of Colorectal Cancer” as part of 

the priority program “Tumor Biobanks” funded by the German 

Cancer Aid Foundation 

*M . Oberländer1 , M . Linnebacher2 , E . Yekebas3 , A . König3 , V . Bogoevska3 , 

C . Brodersen3 , J . Kisro4 , L .-I . Partecke5 , C . Thorns6 , J . Büning7 , T . Laubert1 , 

R . Kaatz1 , S . Matula1 , F . Prall8 , G . Sauter9 , T . Jungbluth10 , M . Strik11 , I . Fichtner12 , 

U .J . Roblick13 , B . Vollmar14 , C .-D . Heidecke5 , J .R . Izbicki3 , E . Klar2 , H .-P . Bruch13 , 

J .K . Habermann1 1Universität zu Lübeck – Klinik für Chirurgie, Chirurgisches Forschungslabor, 

Lübeck, Deutschland, 2Universität Rostock, Klinik für Chirurgie, 

Rostock, Deutschland, 3Universitätsklinikum Hamburg-Eppendorf, Klinik 

für Chirurgie, Hamburg, Deutschland, 4Onkologische Schwerpunktpraxis, 

Lübeck, Deutschland, 5Ernst-Moritz-Arndt Universität Greifswald, Klinik für 

Chirurgie, Greifswald, Deutschland, 6Universität zu Lübeck, Institut für Pathologie, 

Lübeck, Deutschland, 7Universität zu Lübeck, Medizinische Klinik 

I, Gastroenterologie, Lübeck, Deutschland, 8Universität Rostock, Institut für 

Pathologie, Rostock, Deutschland, 9Universitätsklinikum Hamburg-Eppendorf, 

Institut für Pathologie, Hamburg, Deutschland, 10Asklepios Klinik, 

Abteilung für Chirurgie, Bad Oldesloe, Deutschland, 11Helios Klinikum, 

Klinik für Chirurgie, Berlin-Buch, Deutschland, 12Epo GmbH – Experimental 

Pharmacology & Oncology, Berlin-Buch, Deutschland, 13Universität zu 

Lübeck, Klinik für Chirurgie, Lübeck, Deutschland, 14Universität Rostock, 

Institut für Experimentelle Chirurgie, Rostock, Deutschland 

Introduction. The German Cancer Aid Foundation (Deutsche Krebshilfe 

e.V.) funds four biobank networks focusing on CNS tumors (Düsseldorf, 

Bochum, Leipzig), melanomas (Essen, Mannheim, Heidelberg), 

breast carcinomas (Freiburg, Tübingen, Kiel), and colorectal carcinomas 

(Lübeck, Rostock, Hamburg, Greifswald). The latter one, briefly 

called ColoNet is managed by surgeons, pathologists, gastroenterologists 

and oncologists. 

Methods. One common steering committee for all four networks guides 

the harmonization of standard operating procedures (SOPs) concerning 

all biobanking aspects and initiates overall quality measures and 

scientific projects. 

Results. All networks have harmonized SOPs for sample collection and 

processing of e.g., native material, DNA and serum. Crucial steps for 

quality assurance have therefore been implemented. Further objectives 

are the expansion of the sample and clinical data collections. Such 

repository will be used for research projects in order to improve early 

diagnosis, therapy, follow-up and prognosis. Apart from the routine 

sample storage at −170°C, “ColoNet’s” unique characteristic is the 

participation of outpatient clinics and oncologists in private practice. 

Furthermore, a quality management system according to DIN EN ISO 

9001:2008 is currently being implemented to guarantee the compliance 

of standard processes and a consistent quality of tissue samples. 

Summary. The funding by the German Cancer Aid has already led to 

a closer scientific connection between the participating institutions. 

Furthermore, the common steering committee facilitates harmonization 

and networking at the national and international level.

0339 

Incidence of secondary tumors in patients of the population-based 

tumor registry – or is academic research based on a clinical 

cancer registry possible? 

M . Holzinger1 , B . Trilling1 , *J . Hartmann2 1Südwestdeutsches Tumorzentrum, CCC Tübingen, Tübingen, Deutschland, 

2Universitätsklinikum Schleswig-Holstein Kiel, Klinik für Innere Med . 

II, Hämatologie und Internistische Onkologie, Kiel, Deutschland 

Introduction. The aim of the study was to investigate the risk of development 

of a secondary malignancy after a primary cancer. 

Methods. The report is based on data from 58,015 patients (pts) of the 

clinical cancer registry of Southwest Germany in Tübingen, collected 

between 1983 and 2006. The analysis includes descriptive parameters, 

uni- und multivariate regression, logistic regression, and cumulative 

incidence. 

Results. The median follow-up period was 8.7 years (yrs) for all pts. Six 

percent of all pts (3552 of 58,015 pts, 6.1%) developed a secondary tumor. 

The rate was 6.3 % for male pts (1784 of 28,148) and 5.9% for female pts 

(1768 of 29,867). Average time between dates of diagnosis of the primary 

and secondary tumor was 4.3 years (yrs) for all pts, 4.7 yrs for females, 

and 3.9 yrs for males. Secondary cancers occurred most frequently following 

skin tumors (18.7 %, except for melanomas) and least frequently 

following ALL (0.6%). Secondary tumors were diagnosed an average 

2.4 yrs after neuroendokrine tumors und 10.6 yrs after Hodgkin’s lymphoma. 

The following parameters affected the development of a secondary 

tumor: age (higher incidence with increasing age), T-stage (higher 

incidence with more advanced T-stage), M-stage (higher incidence with 

more advanced M-stage), und chemotherapy (higher incidence limited 

to period between 3 and 10 yrs). The cumulative incidence of secondary 

tumors was 3.5% after 3 yrs, 5.3% after 5 yrs, and 9% after 10 yrs. The 

cumulative incidence varies for different types of cancer. Skin tumors 

(except for melanomas) (35%), head and neck tumors (25.2%), kidney/ 

urinary tract tumors (21%), and lung cancers (20.3%) show the highest 

cumulative incidence within 10 years. ALL (1.8%), germ cell tumors 

(3.5%), AML (4.3%), and Hodgkin’s lymphoma (4.4%) have the lowest 

rate. 

Conclusion. Our results are limited by the restricted follow-up period. 

Even though there were 48 yrs between first and last inclusion, the follow-up 

period is relatively short, and we were unable to use our results 

for a risk assessment of radiation-induced secondary malignancies. 

Chemotherapy does result in an increased risk of secondary tumors 

between 3 to 10 yrs following treatment. The varying risks of primary 

cancers for the development of secondary malignancies have implications 

for treatment and follow-up care of cancer patients. 

0361 

Encourage to Exercise – a concept of therapeutic exercise for 

patients during clinical treatment of an SCT 

*J . Arndt1 , S . Wilke2 , W . Hiddemann3 , J . Braess4 , A . Günzel5 1Klinikum der Universität München – Großhadern, Medizinische Klinik und 

Poliklinik III, Station L21 , München, Deutschland, 2Klinikum der Universität 

München, Klinik und Poliklinik für Physikalische Medizin und Rehabilitation, 

München, Deutschland, 3Klinikum der Universität München – 

Großhadern, Medizinische Klinik und Poliklinik III, München, Deutschland, 

4Krankenhaus Barmherzige Brüder Regensburg, Klinik für Onkologie und 

Hämatologie, Regensburg, Deutschland, 5Steinbeis- Hochschule Berlin, 


Hematopoietic stem cell transplantation (SCT) involves aggressive chemo 

or radio therapy, which leads to a suppression of the immune system 

and requires protective isolation. These factors considerably reduce the 

patients‘ radius of movement and restrict their mobility. This marks the 

beginning of a downward spiral, leading to symptoms such as pain or 

further immobility caused by a lack of activity. Numerous scientific stu- 

dies have shown the positive effects of well-balanced physical exercise 

on the physical and mental condition of patients. For this reason, the 

Medical Clinic III has developed the „Encourage to Exercise“ project 

in addition to the established physiotherapy during SCT. The idea behind 

the project is to advise, instruct, and train patients with the aim 

of preventing the possible consequences of a lack of activity. Not only 

physiotherapists, but also doctors, nursing staff, and psycho-oncologists 

take on a motivating role. All patients are given an individually 

tailored program, based on exercises while lying, sitting, or standing. 

During clinical treatment, the exercises are adapted to each patient‘s 

general condition. At the same time, patients can join group exercises 

with other patients, depending on their general condition, to prevent 

isolation. In order to keep the patients motivated, a handout lists the 

positive effects of exercise as well as the consequences of a lack of exercise. 

A patient diary, which is used to record whether the patient could 

perform the exercises and whether they had a positive effect on the patient‘s 

mood, helps to evaluate the project. A further goal of the project 

is to find out during which phase of an SCT patients need instruction or 

motivation. At discharge, patients are given exercise recommendations 

to take home. All staff involved receive intensive training for the project. 

While not requiring additional staff, the project expands the amount 

of physical therapy and enables patients to actively participate in their 

recovery. 

0389 

Quality of life and ascites symptoms in patients with malignant 

ascites after treatment with catumaxomab – results from a multicenter 

phase II/III study 

*P . Wimberger1 , A .-K . Gonschior2 , H . Gilet3 , M .M . Heiss4 , M . Hennig2 , M . Moehler5 

, B . Schmalfeldt6 , E . Schulze2 , S .L . Parsons7 1University of Duisburg-Essen, Clinic for Gynaecology and Obstetrics, 

Essen, Deutschland, 2Fresenius Biotech GmbH, Munich, Deutschland, 3Mapi Values, Lyon, Frankreich, 4Cologne-Merheim Medical Center, Cologne, 

Deutschland, 5Johannes-Gutenberg University, Mainz, Deutschland, 6Tech nical University Munich, Munich, Deutschland, 7Nottingham University 

Hospitals NHS Trust, Nottingham, UK 

Background. Malignant ascites (MA) is associated with a poor prognosis. 

Patients with MA suffer from a number of burdensome symptoms 

and impaired quality of life (QoL). The trifunctional antibody catumaxomab 

is approved for the treatment of MA. Its superiority over paracentesis 

including a positive trend in overall survival has been demonstrated 

in a pivotal phase II/III study (AC-01, Fresenius Biotech). The 

objective of this analysis was to analyse the evolution of ascites symptoms 

and QoL as reported by patients treated with paracentesis plus 

catumaxomab vs. paracentesis alone. 

Methods. The AC-01 study was a randomized, open-label, multicenter 

study in patients with symptomatic MA due to EpCAM-positive cancer. 

QoL as well as ascites symptoms were assessed for patients randomized 

to catumaxomab (n=170) and control (n=88). QoL was assessed by the 

EORTC QLQ-C30 at screening and during the study with assessments 

scheduled at month 1, month 3, month 7, and repuncture. The severity 

of ascites symptoms were assessed at screening, 8 days after treatment, 

month 1 and month 3 using a symptom questionnaire. QoL was assessed 

by measuring the time to first deterioration in QLQ-C30 scores defined 

as decrease in the score of at least 5 points. Time to first deterioration 

was compared between catumaxomab and control groups using survival 

methods with log-rank test and Cox models adjusted for screening 

score, region and primary tumour type. The rate of symptom-free patients 

was compared between treatment groups using Fisher’s exact test. 

Results. Deterioration in QoL scores appeared more rapidly in control 

than in the catumaxomab group (median: 16–28 days vs. 45–49 days). 

The difference in time to first deterioration in QoL between groups was 

statistically significant for all 15 QLQ-C30 scores (p

Abstracts 

ratios ranging from 0.08–0.42 corresponding to a statistically significant 

risk reduction of 92–58%. Reduction of ascites symptoms was more 

pronounced in the catumaxomab group. At the visits 8 days, 1 month 

and 3 months after treatment more patients in the catumaxomab group 

were symptom-free compared to control (33% vs. 11%, 20% vs. 5%; 6% vs. 

0%, respectively). 

Conclusion. Catumaxomab maintains patients at a health status with a 

better QoL for a longer period of life and a prolonged reduction of ascites 

symptoms compared to paracentesis. 

0412 

Measuring the capture efficiency of a cancer registry by using 

standard administrative data 

*K . Funke1 , M . Meyer1 , J . Wolf1 , J .-P . Glossmann1 1Uniklinik Köln, Centrum für Integrierte Onkologie, Köln, Deutschland 

Introduction. In 2008, the Clinical Cancer Registry (CCR) of the Center 

for Integrated Oncology (CIO) at the University Hospital Cologne was 

founded. One of the challenges during the build-up was to establish a 

method to measure the overall performance as well as the efficiency for 

each cancer type within one of the largest Comprehensive Cancer Centers 

(CCCs) in Germany. 

Method. We calculate the capture efficiency by using the fraction of patients 

registered in the CCR as compared to all cancer patients treated 

in our center. The denominator is the number of all in- and outpatients 

with a cancer diagnosis (ICD-10 C**.**) treated within our center. This 

information is derived from standard administrative billing data. As 

numerator we use the number of matching patients from the CCR database. 

Only pseudonymized data is used. 

“Number of matching patients registered in the CCR” divided by “Number 

of cancer patients treated according to billing data” ×100 = X% capture 

efficiency. 

Results. In 2010 a total of 10,577 patients were treated according to billing 

data and of these patients 6067 were registered in the CCR. The 

overall capture efficiency of the CCR was 58%. Within the cancer types 

(ICD subgroups) the capture rate varied between 8% and 100%. 

Discussion. The aimed capture rate of our CCR is 100% and in 2010 

we have achieved 58%. To us this is a positive result given the limited 

resources. The work of the CCR is currently not financed by sickness 

funds and depending on third party spending. The capture efficiency 

will be used to monitor the progress of the CCR with the aim to achieve 

100% capture rate by 2012. A possible bias could be wrong coding of diagnosis. 

In conclusion we have successfully established an efficient method 

to measure the performance of a clinical cancer registry by using 

standard administrative data. This method can be easily used by other 

centers with cancer registries. 

0449 

“Cancer in Germany” 2012 – Current developments in epidemiological 

cancer statistics in Germany 

*K . Kraywinkel1 , U . Wolf1 , J . Haberland1 , B . Barnes1 , J . Bertz1 , S . Dahm1 1Robert Koch-Institut, Zentrum für Krebsregisterdaten, Berlin, Deutschland 

The (German) Centre for Cancer Registry Data (ZfKD) at the Robert 

Koch Institute (RKI) in Berlin and the Association of Population-based 

Cancer Registries in Germany (GEKID) are jointly publishing the 8th 

edition of the biennial booklet «Cancer in Germany» to coincide with 

this year‘s 30th German Cancer Congress. This edition deals with new 

cancer cases up to 2008. The figures are now recorded with blanket coverage 

in virtually all Länder (federal states) and sent on to the ZfKD 

for nationwide evaluation. The booklet contains texts, charts and tables 

with information on the incidence and mortality of cancers in Germany 

according to age and gender. It also analyses current trends and categorizes 

the results in international comparisons. Further points of empha- 


Tab. 4 Estimated number of new cancer cases in Germany in 2008 

Cancer site ICD-10 men women 

Oral cavity and 

pharynx 

C00-C14 9 .520 3 .490 

Oesophagus C15 4 .800 1 .380 

Stomach C16 9 .210 6 .660 

Colon and rectum C18-21 35 .350 30 .040 

Liver C22 5 .270 2 .340 

Gallbladder and biliary 

tract 

C23-24 2 .270 2 .890 

Pancreas C25 7 .390 7 .570 

Larynx C32 3 .610 510 

Lung C33-34 33 .960 15 .570 

Malignant melanoma 

of the skin 

C43 8 .910 8 .890 

Breast C50 520 71 .660 

Cervix C53 4 .880 

Uterus C54-55 11 .280 

Ovaries C56 7 .790 

Prostate C61 63 .440 

Testis C62 3 .970 

Kidney C64 8 .960 5 .540 

Bladder C67 11 .460 4 .510 

Central nervous 

system 

C70-72 3 .810 2 .990 

Thyroid gland C73 1 .710 4 .160 

Hodgkin's lymphoma C81 1 .160 920 

Non-Hodgkin lymphomas 

C82-85 7 .270 6 .430 

Plasmacytoma C90 2 .980 2 .650 

Leukemias C91-95 6 .340 5 .080 

Other cancer 14 .760 15 .870 

Total cancer* C00-C97 w/o 

C44 

246.700 223.100 

* except non-melanotic skin cancer 

sis are statistics on prevalence and 5-year survival. Information on the 

distribution of tumour stages at first diagnosis has been included for the 

first time. The range of cancer sites covered has also been extended and 

now includes new cases of liver and gall-bladder cancer. 

Topical figures from the booklet are presented here. The RKI estimates 

that there were a total of 470.000 new cases of cancer (246.700 men, 

223.100 women) in Germany in 2008. Compared to previous years, 

therefore, there was an overall annual increase of approx. 10.000 cases. 

The most common cancer types were again prostate cancer among men 

(approx. 63.400 cases) and breast cancer among women (71.700 cases), 

followed in each case by colorectal cancer (35.400 and 30.000 cases respectively; 

see table 1). 

This year for the first time, in line with the Federal Cancer Registry Data 

Act, the RKI can also make the data analysed for this issue of »Cancer 

in Germany« available to external scientists for further analyses on 

application to the ZfKD. The aim is to enable the data of the population-based 

cancer registries to be used more intensively for research as 

data quality improves. Furthermore, the ZfKD‘s website is currently 

being extended to also improve the range of information available to 

the interested public. Among other things, annual updates of the most 

important population-based cancer statistics for Germany will in future 

complement the information provided in the biannual „Cancer in 

Germany“ on the Internet.

0473 

Cancer survival in East and West Germany within two decades 

after the fall of the Iron Curtain 

*L . Jansen1 , A . Gondos1 , A . Eberle2 , B . Holleczek3 , A . Katalinic4 , H . Brenner1,5 1Deutsches Krebsforschungszentrum (dkfz), Klinische Epidemiologie und 

Alternsforschung, Heidelberg, Deutschland, 2Universität Bremen, Bremer 

Krebsregister, Bremen, Deutschland, 3Krebsregister Saarland, Saarbrücken, 

Deutschland, 4Krebsregister Schleswig-Holstein, Lübeck, Deutschland, 

5GEKID Cancer Survival Working Group, Deutschland 

Background. Recent international collaborative studies have indicated 

that a major cancer survival gap between Eastern and Western Europe 

has persisted after the fall of the Iron Curtain, although survival rates 

in Eastern Europe have improved for several cancer sites. Prior to the 

German reunification, cancer survival was much lower in East than in 

West Germany. Our study aimed to compare cancer survival between 

East and West Germany in the early 21st century, i.e. the second decade 

after the German reunification. 

Methods. The study was based on survival data provided by 11 population-based 

German cancer registries covering 33 million people (40% 

of the population). Patients diagnosed with cancer in 1997–2006 were 

included in the analyses. Period analysis was used to calculate 5-year 

age-standardized relative survival rates for the 25 most common cancers 

for 2002–2006. 

Results. Patients diagnosed in West Germany had better 5-year prognosis 

than patients in East Germany for most (19 of 25) cancer sites. 

However, most cancer specific differences in survival between East and 

West Germany were below 3 percent units. Exceptions were cancer of 

the gallbladder, skin melanoma and Non-Hodgkin’s lymphoma, with 

5-year relative survival being 5.8, 3.6 and 3.8 percent units higher in the 

West, and leukemia, showing higher 5-year relative survival in the East 

(52.9%) then in the West (48.8%). 

Conclusion. Within two decades after the fall of the Iron Curtain, differences 

in cancer survival between East and West Germany are small. 

The German reunification prompted a rapid assimilation of the East 

German political and health care system into the West German system. 

Even though the economic conditions have remained difficult in 

East Germany, the present study is encouraging in that it suggests that 

comparable health care provision may nevertheless enable comparable 

levels of cancer survival within a relatively short period of time. 

0505 

Employee survey in oncology practices in outpatient medical 

care 

*S . Osburg1 , T . Walawgo1 , E . Girma1 , R . Buschmann-Maiworm1 , S . Schmitz1 , 

W . Baumann1 1WINHO, Köln, Deutschland 

Background. WINHO’s first employee survey was conducted in summer 

2011.The aim was to analyse the work situation of medical personnel in 

oncology practices nationwide. The basic idea was to establish a peer to 

peer benchmarking between office-based haematologists and oncologists 

working in practices in outpatient medical care allowing a comparison 

with the best practice. 

Materials and methods. The anonymous survey was based on the questionnaire 

“MIKE” developed by IMVR** and utilized by 780 employees 

working in 53 oncology practices in outpatient care. The used questionnaire 

contained 18 modules (consisting of 132 items in total) about 

working conditions, work situation, workload, overall job satisfaction, 

communication, education and training, and support by the management. 

For each module an aggregate value was calculated. Each oncology 

practice (with a minimum of ten survey responses) was compared to 

all participating oncology practices. 

Results. 570 employees (response rate 73%) out of 53 practices participated 

in the survey. Almost all of the interviewed employees are females 

working in therapy, reception and laboratory. 60% of them have been 

employed from 1 to less than 3 years. The highest scores were reached 

in the modules: “overall job satisfaction” (85.0%), “work equipment” 

(82.8%), “protection of health and safety standards at work” (79.3%), and 

“education/training” (78.8%). “Good working atmosphere”, “communication” 

and “workload” (54.2%) had the lowest scores. Results for the 

module “death and mourning” show, that most of the practices provide 

supportive measures for the employees. A small percentage of the employees 

would like to have additional support. An additional qualitative 

analysis about further “education/training” indicates that employees 

would like to receive more background knowledge about haematology 

and oncology, patient care, organisation of practices, and psycho-oncology. 

Conclusions. The first employee survey in WINHO’s oncology practices 

has been completed. It would be interesting to compare these results 

with data from employees of hospital-based oncology services. The 

results indicate that oncology practices could optimize their performance 

by improving employee management and leadership, as well as 

corporate communication. Oncology practices should focus on social 

relationships between members of the organisation expressed by “cohesiveness” 

and “support by the management”. 

KOK 

0104 

The transition from living despite cancer to living with cancer – 

A qualitative study of self-perception and life of breast cancer 

survivors 

*J . Breuer1 , H . Mayer1 1Universtität Wien, Institut für Pflegewissenschaft, Wien, Österreich 

Background. Breast cancer is the most prevalent malignancy among 

women in the industrialized world. Due to early detection and improved 

treatment methods, the rate of long-term breast cancer survivors 

increased over the last years and ranges now between 40 and 45%. 

Research questions. Based on the experiences of breast cancer survivors 

aspects of lifestyle and self-perception should be described and associated 

with theories of chronic disease. Insights into the experience of 

affected women should be given using the following questions: To what 

extent are the lives of breast cancer survivors still affected by cancer? 

Which coping strategies do breast cancer survivors use? Do breast cancer 

survivors experience themselves as chronically ill? 

Method. Nine qualitative interviews with breast cancer survivors were 

conducted, transcribed and analysed using the qualitative content analysis 

according to Mayring. 

Results. The diagnosis of breast cancer means the entry in a new reality 

for the women concerned. After completing treatment breast cancer 

survivors still are confronted with after-effects and fear of recurrence 

on the one hand. On the other hand they aspire to get back to normality. 

Trying to accept the cancer experience and the new perception of 

cancer being a thing of the past is an effective way to integrate illness 

in their lives. The findings of the conducted study show a transition of 

self perception from an ill patient to a healthy breast cancer survivor. 

This shift of perspectives between illness and health turns out to be a 

continuous challenge for the women concerned. However, breast cancer 

survivors cope with this situation and end up dealing with a new appreciation 

of life. Living despite cancer turns out to be living with cancer. 

This important shift means the unconscious transition from a patient to 

a breast cancer survivor for the women concerned. 

Conclusion. Surviving breast cancer means for the women concerned to 

have reached a milestone. Professional care needs to be supportive, offer 

guidance and meet the needs of breast cancer survivors. 


151

Abstracts 

KOK 

0195 

Evaluation of the satisfaction with naturopathic treatments and 

consultations offered by specialised nurses for patients with 

breast and gynaecologic cancers 

P . Neuberger1 , K . Wettich-Hauser2 , C . Trautmann1 , A . Schneeweiss1 , 

C . Sohn1,3 , T . Strowitzki4,5 , *C . v . Hagens4,5 1Universitäts-Klinikum, Gynäkologische Onkologie, NCT (Nationales Centrum 

für, Heidelberg, Deutschland, 2Universitäts-Hautklinik, Heidelberg, 

Deutschland, 3Universitätsfrauenklinik, Allgemeine Frauenheilkunde & Geburtshilfe, 

Heidelberg, Deutschland, 4Universitätsfrauenklinik, Gynäkologische 

Endokrinologie und Fertilitätsstörungen, Heidelberg, Deutschland, 

5Universitätsfrauenklinik, Ambulanz für Naturheilkunde, Gynäkologische 

Endokrinologie und Fertilitätsstörungen, Heidelberg, Deutschland 

Objective. During and after chemotherapy patients often complain of 

side effects which might improve with naturopathic treatments agreed 

with the physicians. They can be applied by specialized nurses or taught 

by them and practised at home as self help. A specialised nurse who 

is also part of the regular staff at the day-unit for chemotherapy of a 

large university breast and gynaecologic cancer centre had completed 

additional qualification courses in different methods of naturopathy 

and complementary medicine and offers this care to patients in need of 

it. These treatments and consultations were evaluated by the patients on 

the last day of their chemotherapy. 

Methods. Naturopathic treatments included the application of warm 

compresses and pads with various aromatic oils, a selection of different 

herbal teas, rhythmic massages following the method of Wegmann and 

Hauschka, inunctions with herbal oils and consultation and advice for 

the prevention and treatment of frequent side effects of chemotherapy. 

The evaluation was done during a period of 5 months. It consisted of a 

non-validated questionnaire which was adapted from another project 

and could be completed by the patients anonymously at the end of their 

chemotherapy. The evaluation was supplemented by checklists completed 

by the nursing staff when practising respective treatments and 

consultations during the same period. This allowed documentation of 

the amount of care given and the reactions observed. Data analysis was 

done in SPSS by one of the authors without contact to the patients. 

Results. Response rate was 81% (76 of 94) questionnaires and breast cancer 

was the diagnosis in 74 of the responders. Mean age was 54 ranging 

from 28 to 78 years. 66% of them had previous experience with a variety 

of complementary methods including Chinese or Oriental medicine, 

herbal therapy mainly as teas, fomentations and homeopathy. 96% of 

the responders had received at least one application and the most popular 

were herbal teas, compresses with lavender oil and consultations for 

the prevention and treatment of oral mucositis. 75% of the responders 

continued self help applications at home. Satisfaction with application 

and consultations was high and the offering was rated as very good or 

good by all responders. 

Conclusions. The application of naturopathic treatments and consultations 

during chemotherapy by specialized nurses was appreciated by 

patients with breast and gynaecologic cancers and rated as a valuable 

add-on method during chemotherapy 


KOK 

0322 

National survey of communication competence training in nursing 

education and further qualification 

*A . Spieser1 , C . Kloepfer1 , J . Weis1 1Klinik für Tumorbiologie, Reha-Forschung, Freiburg, Deutschland 

Purpose. Communication skills are needed for nursing staff working 

with cancer patients and their relatives. Within the German National 

Cancer Plan a working group (AG IV patient orientation) is addressing 

the topic how to improve a more patient-centered approach in cancer 

care. Against this background the Federal Ministry of Health has funded 

a national survey to get an overview of the training of communication 

skills in the basic education and post graduate qualification of 

nurses and physicians. This paper is only focusing on the study of the 

nurses’ qualification. 

Methods. Based on the previous work of the members of the working 

group in the National Cancer Plan as well as on an analysis of the requirements 

in the German Federal States guidelines for the education 

and post graduate qualification in communication skills for nurses, two 

questionnaires have been developed addressing the topic of communication 

skills: one questionnaire for the basic education of nurses and 

one for the post-graduate qualification of nurses working in oncology. 

The first questionnaire was sent to all German schools for nursing 

(n=655), the second questionnaire was sent to 355 institutes of post-graduate 

training for nurses. 

Results. The following results are focussing only on the survey of the 

basic education of nurses. The response rate was 36.5%. All focused modules 

are taught in all Federal States of Germany. Communication with 

oncology patients is taught in most of the schools (86.2%). The means of 

lesson-units concerning communication skills were: in the module about 

informing, instructing and advising 24.1 units of 45 min; theoretical 

basis of communication 20.2 units; communication skills 19.7 units and 

communication in the process of dying 19.4 units. Nearly all schools use 

methods of role playing partially with video recording in the basic education 

of communication (90%). Role playing (RP) and video recording 

(VR) are less used for the education of communication with oncology 

patients (RP 47.6%; VR 21.4%) and patients in the process of dying (RP 

59.2%; VR 21.9%). 

Conclusions. In the nursing education in Germany teaching and training 

of communication skills is a basic module. However, the practical 

training of communication especially with cancer patients and their 

relatives could be improved.

Autorenregister 


A 

Abdel-Rahman, S. 378 

Abel, K. 394 

Abel, U. 113 

Abeln, T. 137 

Abendroth, B. 364 

Abenhardt, W. 26, 58 

Abo Madyan, Y. 289 

Abt, E. -J. 467 

Adam, A. 332 

Adam, F. 392 

Adamietz, B. 452 

Adamietz, I. A . 75, 78, 136, 137 

Adeberg, S. 424 

Agaimy, A. 465, 466 

AGO Study Group and 

Mimosa Investigators 160 

Ahlborn, K. 498 

Aigner, J. 115, 199, 201 

Aktas, B. 80, 247 

Alakus, H. 311, 385 

Al-Batran, S. -E . 51, 503 

Albers, P. 81, 158, 196, 240, 

260, 369 

Albert, U. S. 24, 246 

Alizadeh, A. 233 

Allen, P. J. 504 

Allmendinger, A. J. 426 

Al-Nawas, B. 135, 467 

Alt, C. 228 

Altevogt, P. 39, 168, 169 

Al-Yacoub, N. 172 

Amthauer, H. 151 

Andergassen, U. 407, 437, 455 

Andreesen, R. 31 

Annecke, K. 94, 407 

Anoop Chandran, P. 456 

Ansell, S. M. 302 

Ansmann, L. 70, 306, 408 

Antoch, G. 196 

Armbruster, F. -P. 282 

Arndt, J. 361 

Arndt, V. 161, 347, 368 

Arnold, D. 371 

Arpe, N. 16 

Arsov, C. 196 

Aschoff, R. 468 

Attenberger, U. 198 

Atzpodien, J. 489 

Auer, G. 77 

Augustin, D. 94, 318 

Aumann, J. 251 

B 

Baccelli, I. 429, 448 

Bache, M. 167 

Bachmann, C. 272, 459 

Bachmann, E. 481 

Bachmann, S. 459 

Bader, P. 309 

Bader, W. 12 

Baier, M. 24, 31 

Bakhshandeh-Bath, A. 31 

Bandour, M. 252 

Bani, M. 181, 200, 452 

Baños, A. 180 

Banys, M. 497, 500 

Banz, C. 434 

Banzer, W. 409 

Bao, Q. 323, 395, 404 

Baraniskin, A. 174 

Barnes, B. 449 

Barski, D. 81 

Barth, M. 35 

Barth, P. 220 

Barth, S. 441 

Bartolozzi, C. 151 

Bartsch, H. H . 457, 487, 492 

Bartscht, T. 338 

Bauer, A. 145 

Bauer, J. 332 

Bauer, R. 64 

Bauer, S. 210, 277 

Bauer, T. 24, 33 

Bauerschlag, D. O. 387, 397 

Baum, S. 442 

Baumann, A. 337 

Baumann, F. 99, 140, 264 

Baumann, F. T. 100, 263, 333, 

461, 463 

Baumann, K. 139, 160, 224 

Baumann, K. H. 205 

Baumann, W. 305, 505 

Baumunk, D. 65, 138, 215 

Bayer, C. 181 

Bayer, C. M. 200 

Bayerl, A. 468 

Bazhin, A. 286, 303, 382 

Bechstein, W. 274 

Beck, A. 233 

Beck, D. 357 

Beck, T. 257 

Becker, C. 59 

Becker, F. 106 

Becker, H. 131, 133, 259, 304, 

308, 427, 435, 498, 499 

Becker, N. 290, 294 

Becker, S. 77, 391, 414, 497, 500 

Beckmann, M. 160, 279 

Beckmann, M. W. 67, 181, 200, 

205, 237, 241, 257, 423, 428, 437, 

452, 455, 472 

Begus-Nahrmann, Y. 208 

Behnam, N. 289 

Behrens, O. 112 

Behrmann, P. 417 

Beigel, F. 416 

Beißbarth, T. 499 

Beissbarth, T. 259, 304, 308, 

403, 427, 435 

Belau, A. 117, 160 

Benavente, Y. 294 

Beraldi, A. 153, 154 

Berchtold, S. 479 

Berger, A. 27, 32, 275 

Berger, F. 59 

Berger, M. 197, 202 

Berger, M. R. 282, 426 

Berger, S. 197, 202, 293, 426 

Bergmann, F. 168 

Bergmann, L. 52, 327 

Berking, C. 489 

Bernhörster, M. 409 

Bertram, H. 161 

Bertz, H. 73 

Bertz, J. 449 

Bhaskaran, K. 193 

Bhoorie, S. 89 

Bian, Y. 69 

Biedermann, T. 488 

Biester, I. 283, 285 

Bikowski, K. 68, 184 

Bilkenroth, U. 447 

Bingöl, C. 240 

Birkenkamp-Demtroder, K. 174 

Birkholz, K. 24, 31, 33 

Bischofs, E. 114 

Bitz, U. 152 

Bitzer, E. M. 454 

Blank, E. 358 

Blaschke, M. 398 

Blau, W. 346 

Blettner, M. 46, 60 

Bleul, T. 303 

Bloch, W. 99, 100, 140, 264, 

333, 461, 463 

Blohmer, J. -U. 300, 485 

Blondin, D. 196 

Blumenstengel, K. 312 

Blüthgen, N. 18 

Boch, A. 358 

Böcher, E. 51 

Boda-Heggemann, J. 198, 289 

Bode, C. 400 

Bodem, J. 87, 273 

Bodenbenner, M. 299 

Boffetta, P. 294 

Bogdanova, N. 40 

Bogoevska, V. 331 

Bohle, R. M. 35, 381 

Böhm, D. 175 

Böhm, M. 460 

Böhm, W. -D. 375 

Bohrer, M. 289 

Bohus, M. 334, 335, 335 

Bokemeyer, C. 333, 371, 417 

Bollschweiler, E. 311, 385 

Bolten, W. W. 60 

Bölükbas, S. 432, 436, 439, 443 

Bondong, S. 39 

Bonin, M. 487, 492, 495 

Book, K. 41 

Boos, J. 118, 309 

Bootz, F. 276 

Bornemann, A. 332 

Borschitz, T. 483 

Borski, J. 65 

Borutta, B. 454 

Böse, S. 145 

Bossow, S. 479 

Braess, J. 361 

Brähler, E. 41, 43, 98, 110, 

189, 293 

Braicu, E. 451 

Braicu, E. I. 485 

Braicu, I. 39 

Braisch, U. 128 

Brand, S. 416 

Brandes, M. 118 

Brandt, I. 241 

Brase, J. C. 367 

Braun, F. 172 

Braun, M. 140 

Braun, S. 18 

Braunschweig, T. 77 

Bräutigam, K. 387, 397 

Brechtel, A. 184 

Breindl, S. 82 

Breitenbücher, F. 129 

Bremer, M. 270, 470 

Brennan, B. 218 

Brennan, P. 294 

Brenner, H. 90, 161, 179, 347, 

368, 473, 476 

Breuer, F. 360 

Breuer, J. 104 

Brinkmann, A. 118 

Brock, M. 431 

Brocker, K. 228 

Brockhoff, G. 76, 82, 109 

Brodersen, C. 331 

Bronger, H. 182 

Bruch, H. -P. 77, 331 

Brucker, C. 108 

Brückl, W. 475 

Brümmendorf, T. 29 

Brummer, T. 18 

Brüning, F. 155, 225 

Brunner, A. 280 

Brunner, G. 489 

Brunner, M. 277 

Brunner, T. 274 

Bruno, B. 45 

Bruns, C. 274, 395 

Bruns, C. J. 227, 249, 323, 

404, 416 

Bubendorf, L. 423 

Bucan, V. 239 

Buchbender, C. 196 

Buchholz, M. 222, 223 

Buchholz, S. 76, 82, 109, 236 

Budach, V. 346 

Buecklein, V. 378 

Bühler, H. 136, 137 

Bühne, C. 319 

Bulashevska, S. 382 


153


Bulut, D. 222, 223 

Bünger, S. 314 

Büning, J. 331 

Bunse, J. 17 

Büntzel, H. 413 

Büntzel, J. 413 

Burger, M. 84 

Burges, A. 117, 139, 160, 

205, 340 

Burke, T. 277 

Burock, S. 355 

Burwinkel, B. 201, 429 

Busch, C. 275, 321, 332 

Buschmann-Maiworm, R. 305, 

505 

Büttner, M. 296 

Buttstädt, N. 32 

Buzug, T. M. 224, 391 

C 

Cadron, I. 39 

Cahill, M. A. 493 

Camaj, P. 227, 249, 395, 404 

Cameron, S. 393, 398 

Canto, M. I. 504 

Canzler, U. 117, 160 

Castillo-Tong, D. 39 

Chan, K. 233 

Chang-Claude, J. 368 

Chekerov, R. 485 

Chen, R. 302 

Chen, Z. 175 

Chin, R. K. 233 

Choschzick, M. 243 

Christgen, M. 318 

Christiansen, H. 393 

Chromik, A. 222, 223 

Clemens, M. 318 

Cocco, P. L. 294 

Cohen, J. D. 477 

Cohnert, T. 337 

Cole, A. 470 

Combs, S. E. 424, 446, 453 

Connors, J. M. 302 

Conrad, N. 299 

Conradi, L. C. 259, 304, 308, 435 

Contreras-Trujillo, H. 233, 477 

Cornely, O. A. 207 

Craft, A. 218 

Croner, R. 141, 217, 288, 465, 

466, 486 

Csernok, A. 162 

Cuk, K. 429 

D 

Dahlmann, M. 261 

Dahm, S. 449 

Dal Molin, M. 504 

Dalerba, P. 477 

Dall, P. 67, 108 

Daniel, P. 34 

Danker, H. 71, 342 

Dannhardt, G. 482 

Darb-Esfahani, S. 451 

Däßler, K. -U. 51 

de Gregorio, N. 160 

de Sanjosé, S. 294 

de Wit, M. 29 

Debatin, K. -M. 57, 63 

Debus, J. 424, 446, 453 

Decker, T. 26 

Degenhardt, T. 318 

Dehnke, E. 326 

Delorme, S. 290 

Demirel, C. 137 

Dengler, J. 266 

Deniz, M. 163 

Denkert, C. 451 

Di Fazio, P. 351, 353, 356, 362 

Diaz, L. A. 504 

Dieckmann, C. 169 

Diedrich, K. 224 

Dienemann, H. 290, 367 

Dierks, M. -L. 454 

Diermeier-Daucher, S. 76, 82, 

109 

Dietrich, D. 469 

Dietz, A. 189 

Difilippantonio, M. 77 

Dinkel, A. 170, 474 

Dinsart, C. 372 

Dirksen, U. 218, 309, 341 

Distel, L. 296, 364, 421, 430 

Distelrath, A. 266 

Distler, J. 469 

Dittmar, J. -O. 424 

Dittmer, A. 241 

Dittmer, C. 434 

Dittmer, J. 241 

Dittrich, R. 237, 241, 279 

Djafarzadeh, R. 323 

Doehn, C. 52 

Döhler, N. 317 

Dold, S. 183, 185 

Domschke, C. 448 

Dönges, T. 439 

Dörk, T. 162 

Dörk-Bousset, T. 40 

Dorst, J. 110 

Douglas, C. 218 

Drebber, U. 379 

Dreger, P. 334, 335, 335 

Dreier, M. 454 

Driller, E. 123 

Drücke, D. 326 

du Bois, A. 61, 117, 139, 203, 

205, 287, 330 

du Bois, O. 330 

Dünisch, P. 64 


E 

Eberle, A. 161, 473 

Eberle, J. 32, 34, 172, 178 

Eberlein, M. 432, 436, 439, 443 

Eckel, R. 122, 295 

Eckert, A. W. 167, 447, 460 

Edil, B. H. 504 

Eggemann, H. 300 

Eggermont, A. M. M. 484 

Eggert, K. 276 

Eggert, T. 431 

Ehlert, K. 309 

Eibl, H. 484 

Eich, H. -T. 379 

Eichbaum, M. 114, 115, 228, 273 

Eichenseder-Seiss, U. 468 

Eichinger, M. 290 

Eickhoff, R. 114 

Eidtmann, H. 300 

Eiermann, W. 300 

Eimer, C. 498 

Eisele, G. 456, 506 

Ellinger, J. 106 

Ellmann, C. 438 

Ellwart, J. W . 395, 416 

Elser, G. 61 

Elter, T. 100, 119 

Emeny, R. 122, 295 

Emons, G. 67, 117, 160, 396, 

498, 499 

Engehausen, D. G. 91 

Engel, J. 122, 127, 128, 153, 295 

Engel, M. 87 

Engelhard, K. 91 

Engels, A. 58 

Engert, A. 302 

Englhart, E. 59 

Eppelmann, U. 84 

Erdmann-Reusch, B. 464 

Ernst, G. 468 

Ernst, J. 98, 110 

Ernstmann, N. 123, 130 

Eshleman, J. R. 504 

Eshraghi, P. 208 

Essing, M. M. 360 

Ettl, J. 182 

Eulenburg, C. 243 

Evangelou, K. 88 

Ewald, C. 64 

Ewald-Riegler, N. 330 

Exner, A. -K. 283, 285 

Exner, C. 299 

Ezziddin, S. 81 

F 

Faber, M. 230, 231, 232 

Fabry, B. 241 

Fait, I. 187 

Farthmann, J. 330 

Fasching, P. A. 181, 200, 241, 

247, 407, 452 

Fechner, H. 178 

Fecker, L. F. 178 

Fehlker, M. 72 

Fehm, T. 80, 111, 114, 214, 247, 

265, 407, 459, 479, 487, 488, 491, 

492, 494, 495, 496, 497, 500 

Feiten, S. 50 

Feldmann, E. -M. 168 

Fernebro, E. 180 

Fersis, N. 114 

Feyerabend, S. 31 

Fichtmer, I. 13 

Fichtner, I. 251, 261, 331 

Fichtner-Feigl, S. 344 

Ficker, J. 475 

Field, J. 469 

Fietkau, R. 143, 274, 421 

Finas, D. 224, 360, 437 

Fischer, A. 436 

Fischer, D. 434 

Fischer, M. 392 

Fisseler-Eckhoff, A. 432 

Fissmer, A. 100 

Fleischhacker, M. 469 

Flemming, N. 469 

Flier, A. 222, 223 

Foretova, L. 294 

Förtsch, T. 288 

Fotopoulou, C. 330, 451, 485 

Frank, M. 256 

Frank, N. 256 

Frank, O. 266 

Franke, B. 207 

Frauenfeld, A. 198 

Frechen, S. 177, 419 

Freier, K. 68, 87, 156 

Fretault, N. 191 

Freudlsperger, C. 69 

Frey, B. 143 

Freyberger, H. 269 

Fricke, H. -C. 114 

Friebel, K. 32 

Friedrichs, K. 108, 300 

Fries, S. 52 

Friese, K. 94, 257, 407, 437, 

455, 472 

Friesen, C. 55, 56, 57, 63 

Friesenhahn, V. 50 

Frisse, S. 461, 463 

Fritsche, R. 18 

Fritze, F. 17 

Fritzsche, K. 73 

Fruehauf, S. 360 

Fruhmann, J. 337 

Fuchs, M. 188 

Funke, K. 412 

Funke, S. 328, 480 

Fuxius, S. 329 

G 

Gabbert, H. E. 165, 328, 410, 480 

Gade, S. 367 

Gädeken, T. 338 

Gaedcke, J. 259, 304, 308, 427, 

435, 498, 499 

Gaertner, J. 177, 419 

Gaipl, U. 143 

Gaisser, A. 411, 418 

Galalae, R. 136 

Galle, P. R. 372, 383, 481 

Galonske, K. 75, 78 

Gamelin, E. 180 

Gamper, E. 193 

Gansera, L. 293 

Garbe, C. 275, 321, 332, 357 

Gargula, S. 120, 121 

Gärtner, J. 95, 96 

Gasser, M. 230, 231, 232, 

256, 258 

Gauler, T. C . 129 

Gebauer, G. 114, 500

Gebhard, S. 175 

Gehrmann, M. 175 

Geigl, J. 337 

Geinitz, H. 188, 468 

Geismann, C. 168 

Geissler, E. K. 89, 211, 284, 336 

Gellert, K. 17 

Gemoll, T. 77, 314 

Gerber, B. 191, 407 

Gerecke, C. 187 

Gerland, L. 461, 463 

Germ, I. 264 

Germer, C. -T. 230, 231, 232, 

256, 258 

Gerstein, J. 270 

Gerstenhauer, M. 363 

Gerstner, A. 116 

Gerstner, A. O . 276 

Geue, K. 43 

Ghadimi, B. M. 427, 435 

Ghadimi, M. 259, 304, 308, 

498, 499 

Gharaei, D. 283, 285 

Ghezel-Ahmadi, D. 432 

Gieseking, F. 243 

Gieseler, F. 338, 440 

Giesler, J. 457 

Giessing, M. 369 

Gilet, H. 389 

Gillissen, B. 34 

Girma, E. 505 

Gitsch, G. 83, 148 

Glebe, D. 362 

Glenz, A. 192 

Glossmann, J. -P. 66, 177, 

207, 412 

Gluz, O. 318, 319 

Göbel, H. 209 

Goebell, P. J. 52 

Goepfert, K. 383 

Goetze, T. 245 

Goggins, M. G. 504 

Göhl, J. 486 

Göhler, T. 26 

Golcher, H. 216, 274 

Goldmann, T. 112 

Gölz, T. 73 

Gondos, A. 90, 473, 476 

Gonschior, A. -K. 389 

Gonsior, A. 375 

Gopal, A. K. 302 

Görse, R. 363 

Gosheger, G. 118 

Gottardo, F. 84 

Götte, M. 100 

Götze, H. 110, 293 

Gowda, N. 494 

Grabenbauer, G. 274 

Grade, M. 259, 304, 308, 427, 

435, 498, 499 

Gräfingholt, S. 264 

Grage-Griebenow, E. 168 

Greil, R. 180 

Greiner, M. 35 

Greiner, W. 45 

Griesser, H. 423 

Grimm, M. -O. 400 

Grimmel, C. 488 

Grimmer, D. 464 

Grimmig, T. 230, 231, 232, 

256, 258 

Grinstein, E. 480 

Grischke, E. 459 

Grischke, E. -M. 272 

Grobholz, R. 35 

Groh, N. 241 

Grohé, C. 97 

Gros, S. 395 

Groschek, M. 26, 51 

Groß, M. -L. 290 

Grosu, A. L. 105 

Grube, S. 64 

Gründker, C. 67, 396 

Grünwald, V. 327, 346 

Gruss, O. 426 

Gschwend, J. 33, 170, 176, 

250, 252 

Guderian, G. 52 

Guilherme, G. 233 

Gunga, M. 471 

Günzel, A. 361 

Gust, R. 507 

H 

Haas, M. 430 

Haase, S. 173 

Haberer, T. 453 

Haberland, J. 449 

Häberle, L. 386 

Habermann, J. 77 

Habermann, J. K. 331 

Habermehl, D. 424, 453 

Hack, C. 452 

Hackl, C. 211 

Hadaschik, B. A . 5 

Hadji, P. 24, 33, 46, 60 

Hagenbeck, C. 407 

Hagmann, R. 411, 418 

Hahn, S. 174, 222, 223 

Haidinger, R. 46 

Hallek, M. 177 

Hallscheidt, P. 228 

Hamm, A. 269 

Hamm, A. O. 126 

Hamm, C. 126, 269 

Hamm, H. J. 15 

Hamm, T. 51 

Hammad, S. 175 

Hammer, T. 74 

Hanf, V. 326 

Hänggi, D. 19 

Hanker, L. 160 

Hanker, L. C. 67, 139, 205, 329 

Hannig, C. V. 51 

Happold, C. 456 

Harbeck, N. 46, 60, 94, 177, 226, 

318, 319, 407, 419, 461, 463 

Hardes, J. 118 

Häring, J. 204 

Harter, P. 61, 67, 139, 160, 

203, 287, 329 

Hartkopf, A. 479, 497 

Härtl, K. 41 

Hartmann, A. 200, 216, 304, 

438, 475 

Hartmann, D. 208 

Hartmann, J. 326, 339, 346 

Hartmann, M. 229 

Hartmann, P. 488 

Hasenburg, A. 160, 205, 330 

Hatina, J. 125 

Hauss, J. 274 

Hautmann, S. 428 

Hecht, G. 144 

Heck, A. 41 

Heck, M. 250, 252 

Heck, T. 33 

Hedderich, J. 287 

Hedderich, M. 434 

Hegele, A. 142, 155, 220, 225 

Hegewisch-Becker, S. 26, 51 

Heidecke, C. -D. 331 

Heidrich-Lorsbach, E. 329 

Heikaus, S. 81, 165, 328, 480 

Heil, J. 90, 376 

Heilenkötter, U. 112 

Heim, M. E. 58 

Heimann, S. 207 

Hein, A. 181 

Heinecke, A. 489 

Heinrich, B. 383 

Heinrich, G. 437 

Heinrich, K. 224 

Heinrichs, A. 434 

Heiss, M. M. 340, 371, 389 

Heitland, W. 188 

Hellerbrand, C. 336 

Hellman, U. 77 

Hellmich, M. 419 

Hellwig, B. 175 

Hempel, A. M. 287 

Hengstler, J. 175 

Hennig, M. 371, 389 

Henrici, A. 356 

Henze, N. 365 

Hepp, P. 407, 437, 472 

Herbold, T. 311, 385 

Herkommer, K. 170 

Hermann, B. 358 

Hermann, D. 263 

Herold, M. 209 

Herr, D. 316 

Herr, R. 18 

Herrmann, E. 106 

Herrmann, P. 261 

Herschbach, P. 41, 153, 170, 474 

Herth, F. F. 367 

Hertrampf, K. 16 

Herzog, W. 184 

Hess, C. F. 393 

Heubner, M. 124 

Heusinger, K. 452 

Heussel, C. P. 290 

Heußner, P. 153, 154, 354 

Heymanns, J. 50 

Heywang-Köbrunner, S. H. 128 

Hiddemann, W. 154, 354, 

361, 378 

Hielscher, T. 39 

Hierner, R. 19 

Hilbig, J. 79 

Hildebrandt, T. 181 

Hilfrich, J. 300 

Hilfrich, R. 423, 428 

Hillemanns, P. 160 

Hiller, B. 54 

Hilpert, F. 61, 67, 160, 205, 287 

Hindenburg, H. -J. 60 

Hinke, A. 108 

Hinske, C. 51 

Hinz, A. 193 

Hipp, M. 468 

Hirnle, P. 500 

Hirschfeld, M. 83, 148 

Hirth, R. 107 

Hjorth, L. 218 

Ho, P. L. 233 

Hoek, K. 332 

Hof, H. 199 

Hofele, C. 68 

Hofer, S. 456 

Hoffmann, B. 102 

Hoffmann, C. 118, 341 

Hoffmann, I. 163, 237, 241, 279 

Hoffmann, J. 68, 87, 155, 

156, 495 

Hoffmann, O. 111 

Hoffmann, T. 19 

Hoffmeister, M. 368 

Hofheinz, R. 180, 503 

Hofmann, R. 142, 155, 220, 225 

Hofstädter, F. 363 

Hohenberger, W. 120, 121, 131, 

133, 141, 216, 217, 274, 288, 402, 

465, 466, 486 

Hohenfellner, M. 5 

Hoiczyk, M. 277 

Holdenrieder, S. 106 

Holleczek, B. 127, 179, 473, 476 

Hollerbuhl, H. 17 

Hölscher, A. H. 311, 385 

Hölzel, D. 128 

Holzgreve, A. 352 

Holzheu, I. 316 

Holzinger, M. 339 

Homann, N. 503 

Honegger, J. 332 

Hönig, A. 437 

Hoppenworth, U. 392 

Horger, M. 234, 235 

Horke, S. 135 

Hormann, I. 55, 56, 57, 63 

Horn, L. -C. 375 

Hossmann, M. 484 

Hozaeel, W. 503 

Hristamian, A. 67 

Hruban, R. H. 504 

Huber, B. 183 

Huber, G. 102, 103, 335 

Huber, J. 86 

Huber, P. E. 424 

Hübner, J. 31 

Hug, S. 39 

Hummler, S. 102, 103, 113 

Hünerbein, M. 134 

Hunger, A. 343 

Huober, J. 500 


155

I 


Igl, B. -W. 77 

Ihorst, G. 73 

Ihrig, A. 86 

Illerhaus, G. 503 

Illmer, T. 266 

Imkamp, F. 40 

Ischenko, I. 227, 249, 404 

Issels, R. 374, 378, 441, 484 

Ivascu, C. 469 

Izbicki, J. 331, 395 

J 

Jabar, S. 309 

Jabari, S. 351 

Jackisch, C. 46, 60, 117, 160, 300 

Jacob, A. L. 151 

Jaehde, U. 317 

Jaekel, O. 453 

Jaenicke, F. 243 

Jäger, B. 257 

Jäger, D. 184, 210, 334, 335 

Jäger, E. 409, 503 

Jäger, M. 83, 148 

Jahn, P. 145, 471 

Jakob, A. 52, 173 

Jallal, N. 410 

Janitzky, A. 65, 215 

Janjetovic, S. 417 

Janni, W. 94, 247, 257, 407, 

437, 455, 500 

Jansen, L. 347, 368, 473, 476 

Janssen, J. 52 

Janssen, S. 40, 470 

Jauch, K. -W. 227, 249, 323, 

404, 416 

Jensen, K. 273 

Jensen, W. 333 

Jo, P. 141, 259, 304, 308, 427, 435 

Joens, T. 451 

Johannes, M. 367 

Johannsen-Wrana, J. 15 

Joist, A. 267 

Jönsson, L. 277 

Jordan, A. 134 

Jörnvall, H. 77 

Josten, K. M. 462 

Jückstock, J. 257 

Jud, S. M. 181, 452 

Judson, I. 218 

Jueckstock, J. 94, 472 

Juhasz-Böss, I. 381, 394, 442 

Jung, J. 123, 130 

Jung, K. 259, 304, 308 

Jung, V. 35, 106 

Jungbluth, T. 331 

Jungnickel, H. 274 

Junker, K. 327, 400 

Junkermann, H. 201 

Jürgens, H. 218, 309, 341 

Just, L. 332 


K 

Kaatz, R. 331 

Kächele, V. 51 

Kaduthanam, S. 367 

Kahmann, L. 181, 200 

Kähnert, H. 283, 285 

Kaiser, T. 214 

Kalder, M. 24 

Kalender, W. A. 241 

Kalff, R. 64 

Kampmann, E. 374, 441 

Kannisto, P. 203 

Kappler, M. 167, 447, 460 

Karadaglis, G. 88 

Karakhanova, S. 286 

Karger, A. 158 

Karstens, J. H. 40 

Karthaus, M. 180 

Kasimir-Bauer, S. 80, 111, 

124, 247 

Kaskel, P. 277 

Kasper, S. 129 

Katalinic, A. 473, 476 

Kates, R. 318 

Kaufmann, M. 300 

Kauka, A. 24 

Kaul, M. 343 

Keck, B. 438 

Keilholz, U. 327 

Keimling, M. 162, 163 

Keller, A. 358, 456 

Kellermann, J. 141 

Kemmner, W. 72 

Kendziorra, E. 498, 499 

Kennedy, D. A . 302 

Kerschgens, C. 352 

Keschke, C. B . 447 

Kesselring, R. 344 

Khillimberger, K. 481, 482 

Kiechle, M. 94, 182, 407 

Kiehl, M. 360 

Kieschke, J. 144 

Kiesilewicz, G. 363 

Kim, M. 232, 256 

Kim, Y. -J. 35 

Kimmig, R. 111, 124 

Kindler, M. 52 

Kinzler, K. W. 504 

Kisro, J. 331 

Kitz, J. 304 

Klar, E. 331 

Klare, P. 329 

Klasen, J. 196 

Kleboth, K. 50 

Kleeberg, U. R. 305 

Klein, A. P . 504 

Klein, G. 214 

Klein, G. 305 

Klein, O. 462 

Klein, P. 60, 465 

Kleinert, E. 98 

Kleinschmidt, J. 343 

Kliesch, S. 84 

Klinische Krebsregister 

Sachsen 375 

Klinitzke, G. 98 

Klinkhammer-Schalke, M. 128, 

363 

Klockmeier, K. 355 

Kloepfer, C. 298, 322 

Klotz, T. 315 

Klug, S. J. 375 

Kluge, E. 246 

Klumpen, H. -J. 151 

Knetzger, S. -M. 181 

Kniemeyer, O. 400 

Ko, Y. 317 

Kobelt, D. 251 

Koch, A. 125, 209 

Koch, L. 161, 347 

Koch, M. 423 

Koch, T. 241 

Kochanneck, A. 136, 137 

Koenig, J. 163 

Koepke, A. 152 

Kohl, S. 120 

Köhler, A. 52 

Köhler, N. 293 

Köhne, C. -H. 74, 180 

Kölbl, H. 175 

Koller, M. 16 

Kollmar, O. 93, 183, 185 

Köllner, M. 154 

König, A. 331 

König, K. 60 

Königsberg, R. 280 

Königsmann, M. 51 

Koning, G. A. 484 

Konrad, R. 316 

Kootz, B. 265, 487, 492 

Köpke, T. 52 

Koppitz, F. 241 

Köppler, H. 50 

Korf, U. 403 

Korfee, S. 464 

Korniienko, O. 169 

Kornmayer, M. 170 

Kortmann, R. -D. 293 

Kosakowski, J. 289 

Koter, S. 337 

Kovacheva, M. 197 

Kowalski, C. 70, 306, 408 

Koziolek, E. 343 

Kraemer, B. 500 

Kramer, F. 427 

Kramer, J. 138 

Kramer, S. 454 

Kraus-Tiefenbacher, U. 358 

Krawczyk, N. 497, 500 

Kraywinkel, K. 449 

Krebs, S. 227 

Kreienberg, R. 46, 60, 146, 

163, 316, 437 

Kreipe, H. 318, 319 

Kreppel, M. 379 

Kreusel, I. 454 

Kriegel, C. 375 

Kröger, M. 266 

Kröger, N. 400 

Kröning, H. 51, 301 

Kross, H. 326 

Kruell, A. 243 

Krüger, A. 169 

Krüger, M. 135 

Kube, U. 52, 176 

Kübler, A. 25 

Kübler, H. 250 

Kubo, S. 12 

Kudelin, N. 443 

Kuhfahl, J. 365 

Kuhlemann, J. 196 

Kuhlmann, J. D. 124 

Kühn, T. 300 

Kuhnt, S. 58 

Kühr, L. J. 113 

Kukk, E. 153 

Kulms, D. 357 

Kümmel, S. 300, 485 

Kunath, F. 438 

Kuner, R. 367 

Kunz, M. 27 

Kunzmann, V. 360 

Kurbacher, C. M. 360 

Kurtova, A. V. 233 

Kuru, T. H. 5 

Kurzeder, C. 61, 117, 146 

Kuß, O. 145 

L 

Ladenstein, R. 218, 309 

Laffers, W. 116, 276 

Lammer, J. 151 

Lampe, J. 479 

Lamszus, K. 506 

Landenberger, M. 145, 471 

Landfeldt, E. 277 

Landvogt, C. 462 

Lang, D. S. 112 

Lang, S. 19 

Lang, S. A. 211, 284, 336 

Lange, J. 274 

Langenhorst, J. 352 

Langer, P. 27 

Langheinrich, M. 217, 402 

Larsen, E. K. 302 

Lathan, B. 58 

Latta, S. 461, 463 

Lattrich, C. 204 

Lau, A. 145 

Laubert, T. 331 

Lauer, U. M. 479 

Laumeier, T. 225 

Lautner, M. H. W. 460 

Lavall-Gottschalt, M. 192 

Lazaridis, A. 239 

Lazariotou, M. 230 

le Coutre, P. 266 

Le Deley, M. -C. 218 

Lebahn, H. 305 

Lebrecht, A. 175 

Lechel, A. 208 

Lee, H. -W. 208 

Lehmann-Laue, A. 189 

Lehnerdt, G. 19 

Lehnert, H. 440 

Leib, O. 55, 56, 57 

Leibbrand, B. 283, 285, 388 

Leingartner, A. 442 

Lemm, M. 261

Lengerke, C. 496 

Lenz, F. 114 

Lerchenmüller, C. 26, 51 

Lerner, S. 233 

Letocha, H. 180 

Lewis, I. 218 

Li, L. 484 

Lichtenegger, W. 191, 437, 

455, 485 

Lichter, P. 201 

Lie, B. 112 

Liebenberg, V. 469 

Liedtke, C. 318, 319 

Liehr, U. -B. 65, 213, 215 

Liersch, T. 131, 133, 308 

Liloglou, T. 469 

Limmroth, C. 378 

Lincke, T. 193 

Lindena, G. 433 

Lindhofer, H. 371 

Lindner, L. 378, 484 

Linnebacher, M. 331 

Linnig, M. 481 

Linxweiler, J. 35 

Linxweiler, M. 35 

Litzenburger, U. 320 

Liu, L. 494 

Loehberg, C. R . 241, 452 

Löhberg, C. R . 181, 200 

Lohr, F. 198 

Löppenberg, B. 431 

Lordick, F. 188 

Lorenz, R. 257, 455 

Lotan, Y. 233 

Lottspeich, F. 141 

Lotz, L. 237, 241, 279 

Lotze, C. 464 

Löw, A. 126 

Löwenstein, Y. 187 

Lubbe, D. 205 

Lück, H. -J. 46, 500 

Lüdtke-Buzug, K. 224 

Lungwitz, A. 409 

Lütge, M. 423 

Lux, M. P. 181, 200, 241, 452 

M 

M. Hossini, A. 34 

Maass, N. 45, 387, 397 

Maché, Y. -N. 387 

Machleidt, A. 76, 109, 236 

Machtens, S. 140 

Maden, Z. 203 

Mäder, U. 128 

Madhavan, D. 429 

Magheli, A. 138 

Maghnouj, A. 174 

Mahner, S. 39, 117, 160, 205, 

243, 329, 330 

Mahotka, C. 165, 328, 480 

Maintz, C. 51 

Mair, R. 404 

Maisel, T. 128 

Maitra, A. 504 

Malfertheiner, P. 72, 151 

Malik, E. 74 

Mallidis, C. 84 

Mallmann, P. 419 

Mang, A. 391, 414 

Marec Bérard, P. 218 

Markmann, S. 300, 318 

Marmé, F. 39, 90, 115, 199, 

201, 448 

Marschner, N. 26, 173 

Marten-Mittag, B. 474 

Marti, L. 274 

Martin, M. 344 

Martin, R. 116, 477 

Marx, S. 55, 56, 57 

Massacesi, C. 191 

Matthaei, H. 504 

Matthes, N. 230, 231, 232, 258 

Matula, S. 331 

Maurer, T. 33, 250 

Mauz-Körholz, C. 145 

Mavrova, R. 381, 442 

May, C. 97 

Mayer, A. 381 

Mayer, C. 114 

Mayer, F. 346 

Mayer, H. 104 

Maynadié, M. 294 

Mazzaferro, V. 89 

Mecklenburg, V. 220 

Mehlhorn, G. 423, 428 

Mehrholz, J. 464 

Meier, F. 275, 332, 357 

Meier, R. 204 

Meier, S. 354 

Meier, W. 117, 139, 160 

Meier-Meitinger, M. 452 

Meincke, M. 266 

Meinhold-Heerlein, I. 387, 397 

Meister, E. F. 71 

Meister, M. 367 

Melhorn, G. 315 

Mellstedt, H. 451 

Melzer, M. 439 

Menger, M. D. 93, 183, 185 

Mentze, M. 485 

Mergenthaler, H. -G . 346 

Mergenthaler, U. 50 

Merkel, S. 120, 121, 131, 133, 

274, 288, 402, 486 

Metzger, R. 311, 385 

Metzner, S. 264 

Meyer, A. 40, 71, 270, 342 

Meyer, M. 128 

Meyer, M. 412 

Michel, M. -S. 289 

Michelfelder, S. 343 

Michon, J. 218 

Miese, F. 196 

Milani, V. 378 

Milanova, G. 497 

Milanovic, D. 105 

Milde-Langosch, K. 380 

Miller, K. 138 

Miltner, E. 55, 56, 57, 63 

Mineur, L. 180 

Möbs, M. 172 

Modugno, C. 429, 448 

Moehler, M. 383, 389, 481, 482 

Moergel, M. 135, 467 

Mögele, M. 109, 236 

Mohamed, S. 289 

Möhler, M. 372 

Mohr, A. 446 

Molchanov, A. 507 

Moldenhauer, G. 169 

Molls, M. 188 

Monasterio, C. 210 

Montag, M. 279 

Montag, T. 433 

Montalbano, R. 351, 353, 362 

Moorahrend, E. 51 

Moreno, J. 55, 56, 57 

Moritz, R. 106 

Mortsiefer, A. 158 

Moser, C. 211, 284, 336 

Motsch, E. 290 

Moussavian, M. R. 185 

Mtsariashvilli, M. 62 

Mueck, A. O. 493 

Mueller, A. 237, 241 

Mueller, V. 288 

Muley, T. 367 

Müller, A. 279 

Müller, A. 304 

Müller, A. 481, 482 

Müller, C. 118 

Müller, C. K. 62 

Müller, L. 329 

Müller, O. 19 

Müller, R. 462 

Müller, S. 106 

Müller, V. 80, 247, 380 

Müller-Briel, D. 189 

Müller-Mattheis, V. 81, 158, 

158, 158, 255 

Müller-Richter, U. 25 

Murga Penas, E. M . 417 

Murthy, S. 494 

Musayev, A. 277 

Müsgens, M. 390 

Muth, M. 24, 33 

Mycielska, M. 284, 336 

Mysliwietz, J. 395, 416 

N 

Naas, A. 127 

Nacke, A. 108 

Nagata, H. 42 

Naschberger, E. 141, 217 

Nauck, F. 433 

Nawroth, R. 252 

Negri, G. 423 

Nellessen-Martens, G. 70 

Nelson, P. J . 323 

Nestoriuc, Y. 246 

Neubauer, H. 265, 487, 488, 

491, 492, 494, 495, 496 

Neuberger, P. 195 

Neubert, W. 479 

Neugebauer, J. 407, 437 

Neumann, A. 375 

Neumann, H. 81 

Neumann, M. 123 

Neumann, V. 83 

Neuwöhner, K. 307, 433 

Niedermann, G. 105 

Niedostatek, A. 127 

Niegisch, G. 260 

Niehues, C. 283, 285 

Nies, R. 335, 335 

Niess, H. 323 

Niessner, H. 275, 332, 357 

Nieters, A. 294 

Nimmrich, I. 97 

Nischwitz, M. 398 

Nitz, U. 318, 319 

Noeding, S. 12 

Noldus, J. 431 

Nonnenmacher, L. 57, 63 

Nusch, A. 26 

O 

Oberländer, M. 331 

Oberlin, O. 218 

Obermann, E. 423 

Oberneder, R. 31 

Ochs, K. 320 

Ocker, M. 351, 353, 356, 362 

Oechsle, K. 333 

Oeckl, K. 402 

Oeser, S. 241 

Ohlmann, C. 106 

Ohlmann, C. -H. 327 

Olbert, P. 220, 225, 248 

Olbert, P. J. 142, 155 

Ollek, J. -T. 134 

Ommen, O. 130 

Opitz, C. 320 

Optazaite, D. -E . 290 

Orthmann, A. 13 

Ortmann, O. 76, 82, 109, 

204, 236, 363 

Ortmann, U. 257 

Osburg, S. 505 

Ose, C. 58 

Ostermann, H. 45 

Ostgathe, C. 177 

Otremba, B. 305, 441 

Ott, M. 371 

Ottmann, O. G. 266 

Overkamp, F. 26, 52, 176 

P 

Paepke, S. 182 

Palisaar, J. 431 

Panse, J. 29 

Pantel, C. 448 

Pantel, K. 247, 429, 455 

Paolucci, V. 245 

Papadopoulos, N. 504 

Parsons, S. L. 340, 371, 389 

Partecke, L. -I. 331 

Pauligk, C. 503 

Paulussen, M. 218 

Pazhanisamy, S. K. 233 

Pech, M. 213 

Pelz, J. 230 

Perner, S. 496 


157


Petat-Dutter, K. 487, 492 

Petersen, C. 243 

Petersen, V. 51, 108 

Petsch, S. 128 

Peuker, M. 41 

Peynircioglu, B. 151 

Pfaff, H. 70, 123, 130, 306, 408 

Pfeiler, G. 280 

Pfisterer, J. 117, 160, 287 

Pham, D. 496 

Piendl, G. 76 

Pietzner, K. 451 

Pink, D. 152 

Platten, M. 281, 320 

Plötz, M. 34, 172 

Plutizki, S. 482 

Poetsch, M. 124 

Pogorzelski, M. 129 

Polednik, M. 289 

Polier, A. 241 

Polz, K. 75, 136, 137 

Pop, C. 485 

Porsch, M. 65, 213, 215 

Possinger, K. 45 

Potenberg, J. 6, 478 

Poths, S. 487, 492, 495 

Pott, D. 51 

Potzner, M. 191 

Prall, F. 331 

Priesch, B. 136 

Proneth, A. 89 

Pross, M. 107 

Prott, F. -J. 462 

Puderbach, M. 290 

Pujade-Lauraine, E. 117, 

205, 287 

Pukrop, T. 498 

Pulte, D. 476 

Putz, F. 296, 364, 421 

Q 

Quast, S. -A. 27, 32 

Quentin, M. 196 

Quint, K. 351, 353 

Quintanilla-Fend, L. 332 

R 

Raab, R. 131, 133 

Rabenalt, R. 260, 369 

Rack, B. 94, 247, 257, 407, 437, 

455, 472 

Rack, I. M. 12 

Radbruch, L. 433 

Radosa, J. 381, 442 

Raftery, D. 494 

Rahm, J. 152 

Raji, O. 469 

Ramadori, G. 393, 398 

Ranft, A. 218, 309, 341 

Rau, B. 134 

Rau, J. 61 

Rauch, G. 90 

Rausch, S. 469 

Rave-Fränk, M. 393, 498, 499 

Rea, N. 334 

Rebmann, U. 315 

Reichardt, A. 277 

Reichardt, P. 29, 152, 277 

Reichle, A. 31 

Reimers, K. 239 

Reinacher-Schick, A. 174 

Reinecke, P. 410 

Reinmuth, N. 97 

Reiser, M. 59 

Renges, H. 388 

Renner, A. 395, 404 

Renner, C. 210 

Retz, M. 250, 252 

Reuss, A. 139 

Reuter, E. 186 

Rexrodt von Fircks, A. 46 

Rezai, M. 257, 300, 407 

Richter, B. 160, 205 

Richter, D. 43 

Richter, R. 451, 485 

Ricke, J. 151, 213 

Ried, T. 77, 498 

Rieder, H. 125 

Rief, W. 60, 246, 299 

Rieken, S. 424, 446, 453 

Riess, O. 487, 492, 495 

Riethdorf, S. 247, 429, 448 

Roblick, U. 77, 331 

Rödel, C. 131, 133 

Roethke, M. 5 

Rohsbach, D. 243 

Roling, B. 263 

Rom, J. 273 

Romer, G. 110 

Romics, I. 400 

Rommelaere, J. 372 

Roscher, M. 55, 56, 57, 63 

Rösel, S. B. 26 

Rosenbaum, D. 118, 341 

Rosenberg, R. 188 

Rosenblatt, J. D. 302 

Rosenwald, A. 25 

Rosien, B. 74 

Rosmorduc, O. 151 

Rot, S. 167 

Roth, P. 456, 506 

Roth, S. 372 

Rotthoff, T. 158 

Ruan, X. 490 

Rübel, A. 31, 33 

Ruberg, K. 317 

Rubner, Y. 143 

Rudolph, K. L. 208 

Ruemmele, P. 344 

Ruf, P. 340 

Rüffer, J. -U. 58 

Ruhland, B. 224 

Rupertus, K. 93 

Rusch, T. 382 

Rüschoff, J. 304 


S 

Saalmann, R. 12 

Sack, U. 261 

Sagasser, J. 360 

Sahm, F. 281, 320 

Sahm, S. 79 

Sahoo, D. 233 

Salat, C. 26 

Salendo, J. 259, 427, 435 

Sallmann, A. 316 

Salmen, J. 257, 437 

Sandalcioglu, I. E. 19 

Sander, H. 423 

Sangro, B. 151 

Sassen, A. 76 

Sauer, A. 266 

Sauer, R. 131, 133 

Sauter, G. 331 

Savage, K. J. 302 

Schacht, L. 397 

Schaefer, I. -M. 393 

Schaefer, J. 289 

Schäfer, C. 468 

Schäfer, H. 168, 169 

Schäfer, K. -L. 328 

Schäfer, P. 383 

Schaller, F. 327 

Schally, A. V. 236 

Scharding, B. J. 462 

Scheer, M. 379 

Scheeren, F. A. 477 

Scheible, V. 496 

Scheid, C. 266 

Scheiffert, E. 284 

Scheller, T. P. 336 

Schellerer, V. 141, 216, 217 

Schemmer, P. 273 

Schenkirsch, G. 128 

Schicke, B. 107 

Schiel, R. 47 

Schilcher, R. B. 75, 78 

Schildhaus, H. -U. 276 

Schildmann, J. 171 

Schilling, G. 417 

Schilling, M. K. 183, 185 

Schindlbeck, C. 455 

Schirmacher, P. 208 

Schirren, J. 432, 436, 439, 443 

Schlag, P. M. 72, 251, 261, 355 

Schlatt, S. 84 

Schlegel, F. 266 

Schlegel, T. 469 

Schlehe, B. 192 

Schlehofer, B. 192 

Schlemmer, H. -P. 5 

Schlemmer, M. 59 

Schlesinger-Raab, A. 122, 295 

Schlitt, H. J. 89, 211, 284, 

336, 344 

Schmalfeldt, B. 117, 160, 

360, 389 

Schmelzer, R. 158 

Schmid, F. 355 

Schmid, K. W. 129 

Schmid-Höpfner, S. 161 

Schmidt, A. 123 

Schmidt, B. 469 

Schmidt, D. 272 

Schmidt, H. 145 

Schmidt, K. 409 

Schmidt, M. 114, 175, 251 

Schmidt, M. C. 504 

Schmidt, N. 18 

Schmidt, P. 108 

Schmidt, R. 43, 110, 484 

Schmidt-Rimpler, C. 340 

Schmiegel, W. 174 

Schmitt, J. 231 

Schmitz, J. 52 

Schmitz, S. 305, 505 

Schmoll, H. -J . 145 

Schnabel, P. 290 

Schneck, H. 488 

Schneeweiss, A. 39, 90, 114, 115, 

192, 195, 199, 201, 257, 273, 300, 

403, 407, 429, 448, 455, 472 

Schneider, C. 123 

Schneider, F. 198 

Schneider, T. 25 

Schneider-Kappus, W. 51, 266 

Schneider-Stock, R. 304 

Schnitzbauer, A. A. 89, 336 

Schnitzler, P. 294 

Schöder, W. 385 

Schoenfisch, B. 448 

Scholtka, B. 187 

Schönherr, R. 32 

Schönig, K. 426 

Schönmayr, R. 439 

Schostak, M. 65, 138, 213, 215 

Schott, S. 265, 275, 448 

Schramm, N. 59 

Schrauder, M. G. 181, 200, 

241, 452 

Schreiber, S. 193, 274 

Schreier, J. 437 

Schrezenmeier, H. 163 

Schröder, W. 311 

Schröder, W. 139, 160 

Schrodi, S. 122, 127, 128 

Schroeder, C. 380 

Schroeder, W. 117 

Schroff, M. 251 

Schröter, K. 189 

Schubert, J. 167, 447, 460 

Schubert, U. 74 

Schubert-Fritschle, G. 122, 127, 

153, 295 

Schuler, M. 129 

Schuler, P. 19 

Schüler, S. 204 

Schulick, R. D . 504 

Schulte, T. 193 

Schultz, S. 487, 492 

Schultze-Mosgau, S. 62 

Schulz, C. 158 

Schulz, H. 360 

Schulz, W. A. 125 

Schulze, E. 340, 371, 389 

Schulze, H. -J. 489 

Schulze, M. 31, 52, 235 

Schulz-Wendtland, R. 200, 452 

Schumacher, U. 380 

Schumm, W. 112 

Schuricht, F. 246 

Schuster, T. 252 

Schütte, K. 151 

Schütz, T. A. 391, 414

Schwartz, A. 393 

Schwartzkopff, M. 95, 96, 119 

Schwarz, B. 323, 395 

Schwarz, E. B. 416 

Schwarz, R. 58 

Schwarzenbach, H. 124 

Schwegler, M. 296, 364, 421 

Schwentner, L. 146 

Schwerdtfeger, R. 334, 335, 335 

Schwickerath, J. 88, 150, 186 

Sebens, S. 168, 169 

Seeberger, R. 156 

Seeger, H. 265, 491, 494 

Seegers, S. 76 

Seel, N. 249 

Seeliger, H. 249 

Sehlen, S. 474 

Sehouli, J. 39, 61, 67, 117, 139, 

160, 191, 205, 329, 360, 451, 485 

Seidel, G. 454 

Seidl, A. 188 

Seifart, U. 299 

Seimetz, D. 371 

Seitz, S. 109, 236 

Senger, S. 183 

Serke, M. 97 

Sers, C. 18 

Serth, J. 40 

Sevim, M. 141 

Shak, S. 318 

Shetje, J. 451 

Shortliffe, L. 233 

Sieben, M. 372 

Siebenlist, K. 198 

Sieber, A. 18 

Siehl, S. 58 

Siepert, E. -M . 444 

Sieverding, M. 190 

Sievers, E. L . 302 

Simon, R. 112 

Simon, W. 94, 407 

Simonis, K. 142 

Sindermann, H. 67 

Singer, C. 280 

Singer, S. 98, 189, 193, 194, 350 

Sinistra, J. 93 

Sinn, H. P. 199, 201, 403 

Sinn, P. 429 

Sinnberg, T. 275 

Smetanay, K. 115, 199, 201, 273 

Smirnow, I. 479 

Smith, S. E. 302 

Sohn, C. 39, 90, 114, 115, 192, 

195, 199, 201, 228, 273, 429, 448 

Sokol, C. 392 

Solomayer, E. -F. 114, 160, 247, 

272, 381, 394, 442, 459, 500 

Sommer, H. 94, 407, 455, 472 

Sonntag, J. 403 

Sotlar, K. 487, 492 

Souchay, M. 252 

Sperling, J. 183 

Spieser, A. 298, 322 

Spira, D. 234 

Spitzner, M. 259, 427, 435, 

498, 499 

Spohn, C. 312 

Sprick, M. 448 

Springsguth, F. 372 

Sproßmann-Günther, G. 6 

Stabenow, R. 375 

Staebler, A. 117, 160, 495, 496 

Staehler, M. 327 

Stahl, M. 388 

Stähle, A. 67 

Stähler, M. 52 

Staines, A. 294 

Staratschek-Jox, A. 123 

Staudigl, C. 280 

Steffens, C. -C. 26, 85 

Stegelmann, F. 266 

Stegerer, A. 204 

Stegmaier, C. 127, 161 

Stein, U. 261 

Stein, U. S. 355 

Steinbach, M. 134 

Steiner, T. 52, 400 

Steinmann, D. 270, 468, 470 

Steinmetz, T. 305 

Stephan, C. 138 

Stern, S. 266 

Sterry, W. 172 

Stickeler, E. 83, 148 

Stieglmaier, J. 97, 191 

Stier, G. 266 

Stirkat, F. 486 

Stock, S. 95, 96, 119 

Stockfleth, E. 34 

Stoehr, R. 438 

Stoelting, S. 440 

Stoer, R. 125 

Stöhr, R. 216 

Stoll, O. 145 

Stölting, S. 338 

Stöltzing, O. 42 

Stolzenburg, J. -U. 375 

Storm, T. 233 

Strahl, O. 200 

Strassl, L. 327 

Strauss, A. 287 

Strauß, H. -G. 330 

Strehl, A. 25 

Strick, R. 241 

Strik, M. 331 

Strissel, P. 241 

Strohbücker, B. 95, 96, 119 

Ströhlein, M. 371 

Strowitzki, M. 185 

Strowitzki, T. 192, 195 

Strozyk, E. 374, 441 

Struck, A. -M. 126 

Struck, B. 168 

Stuhr, C. 41 

Sturm, I. 346 

Stürzl, M. 141, 217 

Stutz, U. 49 

Südhoff, T. 31 

Sujeva, V. 374 

Sultan, S. 393 

Sültmann, H. 367 

Sure, U. 19 

Suschek, C. V. 480 

Suter, L. 489 

Sütterlin, M. 358 

Szendröi, A. 400 

Szymczak, S. 77 

T 

Tabatabai, G. 506 

Tan, J. 171 

Tang, C. 233 

Tari, S. 154, 354 

Taubert, H. 167, 438, 447, 460 

Teich, K. 269 

Teichgräber, V. 210 

Tempelhoff, G. -F. 360 

ten Hagen, T. 484 

Tesch, H. 45, 312, 313, 472 

Tetzner, R. 216 

Teufel, I. 214 

Tewes, M. 80 

Thaler, J. 180 

Thalgott, M. 250 

Thamm, R. 188 

Theodorou, M. 468 

Thiel, C. 409 

Thiel, F. C. 181 

Thiele, L. 264 

Thiele, O. 156 

Thies, B. 116 

Thill, M. 434 

Thomalla, J. 50 

Thomas, M. 97, 102, 103, 113 

Thomssen, C. 318 

Thorns, C. 331 

Tillack, A. 127 

Ting, S. 129 

Tirier, C. 51 

Tischendorf, L. 22, 23 

Tögl, A. 488 

Toma, A. 391, 414 

Tomov, S. 67 

Töppich, J. 454 

Trandafir, L. 191 

Trapp, M. 283, 285 

Trautmann, C. 195 

Treeck, O. 204 

Tremper, J. 290 

Trepel, M. 343 

Treszl, A. 236 

Trilling, B. 339 

Trillsch, F. 330 

Trumpp, A. 429, 448 

Tschuschke, V. 88, 150 

Tsui, T. Y. 42 

Tusche, S. 129 

U 

Uder, M. 386 

Ufen, M. -P. 74 

Uhl, W. 222, 223 

Uleer, C. 318 

Ulrich, C. 113, 190, 334, 335 

Ulrich, C. M . 102, 103 

Ungar, N. 190 

Ungefroren, H. 338, 440 

Urbschat, I. 144 

Ückert, F. 253 

V 

v. Hagens, C. 192, 195 

van de Rijn, M. 233 

van den Berg, H. 218 

van den Berg, L. 165 

van der Meer, E. 107 

van der Ven, H. 279 

van Glabekke, M. 218 

van Rhoon, G. 484 

van Roye, C. 50 

Van Waes, C. 69 

Vandenbergh, D. 334 

Varga, D. 163 

Vassos, N. 465, 466 

Vehreschild, J. 207 

Vehreschild, M. J. G. 207 

Venturelli, S. 275 

Vergote, I. 39 

Verpoort, K. 58 

Verslype, C. 151 

Vetterlein, M. 230 

Vieth, M. 72 

Villanueva, M. -T. 131, 133 

Vitzthum, L. 252 

Vogel, U. 494 

Vogelhuber, M. 31 

Vogelstein, B. 504 

Vogt, L. 409 

Vogt, P. M. 239 

Volcic, M. 162 

Völkel, P. 182 

Volkmer, A. K. 477 

Volkmer, J. -P. 233, 477 

Vollmann, J. 171 

Vollmar, B. 331 

Vollmer, E. 112 

Voltz, R. 177, 419 

von Blanckenburg, P. 246, 299 

von Bodmann, C. 431 

von Deimling, A. 281, 320 

von der Assen, A. 108 

von der Heyde, S. 403 

von Eggeling, F. 400 

von Heesen, M. 185 

von Klot, C. 40 

von Mautner, V. -F. 29 

von Ruecker, A. 106 

von Stebut, E. 483 

von Verschuer, U. 312 

von Wollf, M. 279 

Vordermark, D. 167, 468 

W 

Waaga-Gasser, A. M. 230, 231, 

232, 256, 258 

Wach, S. 438 

Wachter, D. 279 

Wachter, D. L. 241 

Wackwitz, B. 500 

Wagener, M. 95, 96 

Wagenmann, M. 19 

Wagner, C. 284 

Wagner, F. 386 

Wagner, S. 365 

Wagner, U. 117, 205 


159


Walawgo, T. 505 

Walburga, E. -R. 149 

Waldmann, A. 161 

Walecki, J. 151 

Walgenbach-Brünagel, G. 106 

Wallwiener, D. 60, 111, 214, 272, 

459, 479, 487, 491, 492, 495, 497, 

500 

Wallwiener, M. 114, 265, 429, 

448 

Walter, B. 37, 38 

Walter, J. 64 

Walter, M. 266 

Walter, M. 400 

Walter, M. 487, 492, 495 

Walter, U. 454 

Walther, J. 184 

Walther, W. 251 

Wang, Q. 72 

Warm, M. 300 

Waschke, A. 64 

Weber, F. 236 

Wedel, B. 434 

Wedemeyer, I. 379 

Wei, S. 494 

Weide, R. 50, 266 

Weikert, S. 138 

Weil, M. 330 

Weirich, G. 252 

Weis, J. 298, 322, 457 

Weiskopf, K. 477 

Weiss, A. 423 

Weiss, C. 198 

Weiss, E. -M. 143 

Weiss, G. 216 

Weißbach, L. 130 

Weißflog, G. 98 

Weissman, I. 233 

Weissman, I. L. 477 

Weller, M. 456, 506 

Welslau, M. 173, 176, 312, 360 

Welzel, G. 289, 358 

Welzel, T. 424, 446 

Wendler, J. J. 65, 213, 215 

Wendtner, C. -M. 277 

Wenkel, E. 200 

Wenz, F. 198, 289, 358 

Wenz, H. -J. 16 

Werner, C. 127 

Werner, J. 286, 303, 382 

Wethkamp, N. 328, 480 

Wettich-Hauser, K. 195 

Wex, T. 72 

Weymar, M. 126 

Whelan, J. 218 

Wick, W. 281, 320, 446 

Wieland, B. 162 

Wiemann, S. 403 

Wiese, B. 270 

Wiesmüller, L. 162, 163 

Wilde, C. 202 

Wildner, R. 307 

Wilke, S. 361 

Willingham, S. B. 233, 477 

Wilmer, A. 317 

Wiltfang, J. 16 

Wimberger, P. 61, 67, 117, 124, 

139, 160, 205, 330, 360, 389 

Windemuth-Kieselbach, C. 46 

Winkel, A. 253, 267 

Winter, C. 118, 341 

Winter, Ch. 240 

Wirkner, J. 126 

Wirth, M. 375 

Wirtz, R. 380, 475 

Wischhusen, J. 456 

Wischnewsky, M. 146 

Wischnik, A. 94, 407 

Wiskemann, J. 102, 103, 113, 

190, 334, 335 

Wisplinghoff, H. 207 

Wistuba, J. 84 

Wittekind, C. 98 

Wittenberg, T. 386 

Witzel, F. 18 

Witzel, I. 300, 380 

Witzigmann, H. 274 

Wöckel, A. 146 

Woelber, L. 243 

Wohland, D. 483 

419 

Wolf, J. 66, 95, 96, 119, 123, 

177, 412, 

Wolf, P. 250 

Wolf, U. 449 

Wolff, A. 346 

Wolff, H. A . 259, 304, 308, 

427, 435 

Wolfgang, C. L. 504 

Wollbrück, D. 71, 342 

Wollina, K. 464 

Wollschlaeger, K. 160 

Wolpert, F. 506 

Wolters, R. 146 

Wood, L. D. 504 

Woopen, H. 451 

Worring, A. 311, 385 

Wu, J. 504 

Wübbeling, F. 84 

Wuerstlein, R. 177, 419 

Wulff, C. 316 

Wulfken, L. M. 106 

Wullich, B. 438 

Wünsch, A. 73 

Wypior, H. -J. 468 


Y 

Yalcin, S. 151 

Yecebas, E. 331, 395 

Younes, A. 302 

Z 

Zaba, O. 97 

Zaldivar Wither, C. 68 

Zapatka, M. 201 

Zaun, S. 45, 46, 60, 61 

Zeilinger, R. 39 

Zeisig, R. 13 

Zeissig, S. 161 

Zeman, F. 89 

Zenginli, H. 369 

Zepp, M. 282 

Zhang, J. 494 

Zhao, Y. 323, 395, 404, 416 

Ziegler, A. 77 

Ziegler, E. 396 

Zieker, D. 36 

Ziller, M. 24, 33 

Zimmermann, F. 188 

Zimmermann, M. 479 

Zimmermann, R. 35 

Zipfel, P. 400 

Zöller, J. E. 379 

Zöllner, H. 174 

Zopf, E. M. 140 

Zoz, M. 102, 103, 113 

Zucknick, M. 429 

Zumbé, J. 140 

Zwingers, T. 407, 437, 455 

Zwirner, M. 491

30th German Cancer Congress - February 2012, Berlin

Create successful ePaper yourself

Delete template?

Save as template?