Fujiwara, Keiichi

5593 Background: We conducted an international survey to evaluate the differences in the systemic, radiotherapeutic and operative management of endometrial cancer (EC) in different regions of the world. Methods: In 2009 avalidated 15-item-questionnaire regarding surgical and adjuvant procedures of EC was sent to all German gynaecological clinics and in 2010 the English adapted questionnaire was set online as well as sent per post in most major gynaecological cancer societies. Results: 316 German institutions and 302 Institutions from 24 countries participated. We combined the different countries into regional groups: Central Europe (CE), southern Europe (SE), Asia and USA/UK. In Asian countries and in CE a lymph node dissection (LND) was performed routinely in 72.8% and in 55.6% of the cases, whereas in the USA/UK and in SE a LND was done mainly in selected cases when specific risk factors such as high-grade or non-endometrioid-histology applied (62.8% and 72.5%) than routinely (p < 0.001). A systematic pelvic and paraaortic LND was performed most frequently in CE 91.0%, in SE 76.9%, in Asia 70.9% and in USA/UK 68.6% (p < 0.001). A systematic LND with the intention of both adequate staging and for therapeutic value was performed in countries of central Europe to 74.6% and in Asia to 67.2%. In USA/UK the LND was seen merely as a staging instrument by 53.5% (p < 0.001). The LND was performed up to renal veins in CE in 86.8%, in Asia in 80.8%, in USA/UK in 51.2% and in SE in 45.1 %. A significant difference war found in the treatment for FIGO stage I (high risk factors (high grade, L1,V1)) and stage II disease between the countries: chemotherapy was applied in 84.8% of the participated centers in Asia,42.3% in SE, 21.2% in CE and only 13.6% in USK/UK (p<0.001).Vaginal brachytherapy was indicated as follows: USA/UK 84.1%, CE 78.8%, SE 78.8%, Asia 5.6% (p < 0.001). Conclusions: There is a large variety in the operative therapy and the clinical management of EC in different regions of the world. Future international prospective trials, will be necessary to improve and harmonize the evidence based treatment guidelines for EC- disease.

5087 Background: Indication, technique and extent of lymph-node-dissection (LND) in endometrial cancer (EC) remains controversial and is strongly debated in cancer community. We conducted a national- and at a second step an international-survey evaluating the current status-quo of the surgical and medical management of EC. Methods: A validated 15-item-questionnaire regarding surgical and adjuvant procedures of EC was sent to all major gynaecological cancer societies and study groups worldwide. The questionnaire could also be answered online. Results: In a phase-I-national trial, the questionnaire was validated on basis of 316 German institutions. On the phase-II-international survey a total of 302 questionnaires were answered from 24 countries, mainly from Japan (38.7%), Spain (8.3%), Austria (7%), United-Kingdom (6.3%), Italy (6%), USA (4.3%) and Canada (4%). The vast majority of the participating clinics were academic (62.8%), while 75.2% of them belonged to gynaecology. Only 0.7% of the clinics internationally reported never performing LND in EC. 62.3% of the clinics perform both a pelvic and paraaortic lymph node dissection. 59.1% of the participants performed a systematic lymph node dissection with the intention of both adequate staging and for therapeutic value. 15.05% of the clinics perform LND up to the common-iliac-arteries, 9.03% up to the inferior-mesenteric-artery and 70.6% up to the renal-veins. The most common risk-factors to indicate LND were: high-grading (93%), non-endometrioid-histology (90.1%), lymphovascular-invasion (55.3%), blood-vessel invasion (45.4%) and tumor-diameter >2cm (38.4%). For advanced stage III&IV disease the vast majority (60% and 80%, respectively) of the physicians indicated systemic chemotherapy alone. Conclusions: This study presents the large variety in clinical management of EC worldwide, underlining so the high need of future prospective randomised trials which will establish standard and evidence based treatment guidelines for EC- disease.

Abstract Purpose: GOG-0218, a double-blind placebo-controlled phase III trial, compared carboplatin and paclitaxel with placebo, bevacizumab followed by placebo, or bevacizumab followed by bevacizumab in advanced epithelial ovarian cancer (EOC). Results demonstrated significantly improved progression-free survival (PFS), but no overall survival (OS) benefit with bevacizumab. Blood samples were collected for biomarker analyses. Experimental Design: Plasma samples were analyzed via multiplex ELISA technology for seven prespecified biomarkers [IL6, Ang-2, osteopontin (OPN), stromal cell–derived factor-1 (SDF-1), VEGF-D, IL6 receptor (IL6R), and GP130]. The predictive value of each biomarker with respect to PFS and OS was assessed using a protein marker by treatment interaction term within the framework of a Cox proportional hazards model. Prognostic markers were identified using Cox models adjusted for baseline covariates. Results: Baseline samples were available from 751 patients. According to our prespecified analysis plan, IL6 was predictive of a therapeutic advantage with bevacizumab for PFS (P = 0.007) and OS (P = 0.003). IL6 and OPN were found to be negative prognostic markers for both PFS and OS (P &lt; 0.001). Patients with high median IL6 levels (dichotomized at the median) treated with bevacizumab had longer PFS (14.2 vs. 8.7 months) and OS (39.6 vs. 33.1 months) compared with placebo. Conclusions: The inflammatory cytokine IL6 may be predictive of therapeutic benefit from bevacizumab when combined with carboplatin and paclitaxel. Aligning with results observed in patients with renal cancer treated with antiangiogenic therapies, it appears plasma IL6 may also define those patients with EOC more or less likely to benefit from the addition of bevacizumab to standard chemotherapy.