European Society of Gynaecological Oncology (ESGO) Guidelines for Ovarian Cancer Surgery.

METHODS: The European Society of Gynaecological Oncology council nominated an international multidisciplinary development group made of practicing clinicians who have demonstrated leadership and interest in the care of ovarian cancer (20 experts across Europe). To ensure that the statements are evidence based, the current literature identified from a systematic search has been reviewed and critically appraised. In the absence of any clear scientific evidence, judgment was based on the professional experience and consensus of the development group (expert agreement). The guidelines are thus based on the best available evidence and expert agreement. Before publication, the guidelines were reviewed by 66 international reviewers independent from the development group including patients representatives. RESULTS: The guidelines cover preoperative workup, specialized multidisciplinary decision making, and surgical management of diagnosed epithelial ovarian, fallopian tube, and peritoneal cancers. The guidelines are also illustrated by algorithms.

Evaluation of potentially predictive markers for anti-angiogenic therapy with sunitinib in recurrent ovarian cancer patients.

INTRODUCTION: In ovarian cancer, new therapeutic strategies are needed because the vast majority of patients develop a recurrence and resistance to platinum derivates. Attached to the AGO-OVAR2.11 study investigating the multityrosine kinase inhibitor sunitinib in recurrent platinum refractory ovarian cancers, this translational research project assesses the potential value of serum vascular endothelial growth factor (VEGF), soluble VEGF receptor-3 (sVEGFR-3), and angiopoietin-2 (Ang-2) levels for progression-free survival (PFS). MATERIALS AND METHODS: Longitudinal serum samples were taken while the patient was on study drugs. Serum concentration of VEGF, sVEGFR-3, and Ang-2 was determined by ELISA. The slope of the markers was correlated to the PFS. RESULTS: Patients showing a decrease in VEGF concentration had a median PFS of 10.5 months [confidence interval (CI), 2.89-12.25] compared to 2.9 months (CI, 1.48-5.32) in the case of an increase (P = .17). The stratified log-rank test showed a trend for longer PFS if a decrease of Ang-2 was observed (P = .089). Dichotomized in absolute decrease or increase, the PFS was 8.4 months (CI, 2.89-12.26) versus 2.7 months (CI, 1.05-5.32), respectively. Patients with a reduction of the sVEGFR-3 concentration had a median PFS of 4.76 months (CI 2.86-10.65) versus 8.61 months (CI, 1.05-not estimable) in patients with an increase of sVEGFR-3. This observation was statistically not significant in the log-rank test (P = .81). CONCLUSION: Ang-2 could potentially identify a patient population that might have a better PFS when under anti-angiogenic treatment, like the tyrosine kinase inhibitor sunitinib.

2010 Gynecologic Cancer InterGroup (GCIG) consensus statement on clinical trials in ovarian cancer: report from the Fourth Ovarian Cancer Consensus Conference.

2010 Gynecologic Cancer InterGroup (GCIG) consensus statement on clinical trials in ovarian cancer. This report provides the outcomes from the Fourth Ovarian Cancer Consensus Conference.

First-line therapy in ovarian cancer trials.

At the 4th Ovarian Cancer Consensus Conference of the Gynecologic Cancer InterGroup (GCIG) held in Vancouver, Canada, in June 2010, representatives of 23 cooperative research groups studying gynecologic cancers gathered to establish international consensus on issues critical to the conduct of large randomized trials. The process focused on 13 predetermined questions. Group A, 1 of the 3 discussion groups, addressed the first 5 questions, examining first-line therapies in newly diagnosed ovarian cancer patients. A1: What are the appropriate end points for different trials (maintenance, upfront chemotherapy trials including molecular drugs)? A2: Are there any subgroups defined by tumor biology who need specific treatment options/trials? A3: Is the 2004 GCIG-recommended standard comparator arm still valid? A4: What is the role of modifying dose, schedule, and delivery of chemotherapy? A5: What role does surgery play today?

Incidence of venous thromboembolism in patients with ovarian cancer undergoing platinum/paclitaxel-containing first-line chemotherapy: an exploratory analysis by the Arbeitsgemeinschaft Gynaekologische Onkologie Ovarian Cancer Study Group.

PURPOSE: Venous thromboembolism (VTE) has been associated with negative prognosis in cancer patients. Most series reporting on VTE have included different tumor types not differentiating between recurrent or primary disease. Data regarding the actual impact of VTE on primary advanced ovarian cancer (AOC) are limited. PATIENTS AND METHODS: Between 1995 and 2002, the Arbeitsgemeinschaft Gynaekologische Onkologie Ovarian Cancer Study group (AGO-OVAR) recruited 2,743 patients with AOC in three prospectively randomized trials on platinum paclitaxel-based chemotherapy after primary surgery. Pooled data analysis was performed to evaluate incidence, predictors, and prognostic impact of VTE in AOC. Survival curves were calculated for the VTE incidence. Univariate analysis and Cox regression analysis were performed to identify independent predictors of VTE and mortality. RESULTS: Seventy-six VTE episodes were identified, which occurred during six to 11 cycles of adjuvant chemotherapy; 50% of them occurred within 2 months postoperatively. Multivariate analysis identified body mass index higher than 30 kg/m(2) and increasing age as independent predictors of VTE. International Federation of Gynecology and Obstetrics stage and surgical radicality did not affect incidence. Overall survival was significantly reduced in patients with VTE (median, 29.8 v 36.2 months; P = .03). Multivariate analysis identified pulmonary embolism (PE), but not deep vein thrombosis alone, to be of prognostic significance. In addition, VTE was not identified to significantly affect progression-free survival. CONCLUSION: Patients with AOC have their highest VTE risk within the first 2 months after radical surgery. Only VTE complicated by symptomatic PE have been identified to have a negative impact on survival. Studies evaluating the role of prophylactic anticoagulation during this high risk postoperative period are warranted.

Vaccination of patients with advanced ovarian carcinoma with the anti-idiotype ACA125: immunological response and survival (phase Ib/II).

PURPOSE: A Phase I/IIb multicenter study was conducted to evaluate the safety and immunogenicity of the anti-idiotypic antibody vaccine ACA125 that functionally imitates the tumor antigen CA125 in 119 patients with advanced ovarian carcinoma. A preliminary report on the initial 42 patients demonstrated safety and immunogenicity. EXPERIMENTAL DESIGN: Using the complete intention-to-treat population (n = 119) who received a mean of 9.7 ACA125 applications, survival was analyzed with respect to immunological responses. RESULTS: In 81 patients (68.1%), a specific anti-anti-idiotypic antibody (Ab3) response could be induced. Additionally, the development of CA125-specific antibodies (Ab1') and antibody-dependent cell-mediated cytotoxicity of CA125-positive tumor cells was observed in 50.4% and 26.9% of patients, respectively. The median survival of all patients was 19.4 months (range, 0.5-56.1 months). Ab3-positive patients showed a significantly longer survival (median, 23.4 months; P < 0.0001) as compared with Ab3-negative patients (median, 4.9 months). A positive Ab3 response remained associated with longer survival when controlling for other prognostic factors including FIGO (International Federation of Gynecologists and Obstetricians) stage, response to and type of first-line chemotherapy, number of previous treatments, or concomitant antitumor therapy. With regard to safety, repeated vaccination was well tolerated. No serious adverse events related to the application of ACA125 occurred. CONCLUSIONS: Although the uncontrolled design of this study prevents definitive conclusions with respect to subgroups, the data support a relationship between Ab3 response and survival time. Thus, the need for further randomized, controlled clinical trials to establish efficacy of the vaccine ACA125 seems to be indicated.