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Objective Low-grade epithelial ovarian cancers (EOC), constitute the minority among all epithelial cancers. Our study objective was to focus on low-grade recurrent EOC and compare the survival with high-grade disease, as well as in regard to “platinum-sensitive” and “-resistant” recurrences according to platinum-free interval. Methods This is an exploratory analysis within the North-Eastern German Society of Gynecological Oncology (NOGGO) database including five randomized phase II/III trials comparing different chemotherapy regimens in recurrent EOC. We conducted survival analyses and cox-proportional regression models. Results Out of 1050 patients having the first recurrence, 42 (4%) patients had low-grade and 1008 (96%) patients had high-grade disease. In the subgroup of platinum-sensitive recurrences, progression-free survival (PFS) (8.7 m vs 9.7 m, p = 0.7) and overall survival (OS) (23.9 m vs 24.8 m, p = 0.9) did not differ between low-grade and high-grade diseases. In platinum-resistant recurrences, patients with low-grade ovarian cancer had significantly better PFS (7.6 m vs 3.6 m, p = 0.03) and OS (41.9 m vs 9.5 m p = 0.002) in comparison to those with high-grade cancer. At low-grade EOC, there were no significant PFS (p = 0.91) and OS (p = 0.25) differences between platinum-sensitive and –resistant recurrences. Patients with low-grade non-serous histology had lower PFS with compared to those with low-grade serous histology (p = 0.004). At cox regression analysis presence of ascites and residual disease after secondary cytoreductive surgery were independently associated with poor PFS within low-grade recurrent EOC. Conclusion Our study indicates, platinum-free interval does not have any prognostic significance at recurrent low-grade EOC and non-serous histology is associated with poorer outcome in recurrence. Secondary surgical cytoreduction to no-gross residual disease and ascites are independently associated with disease progression.

Ovarian cancer is usually a cancer of the older age group. Comorbidities and comedications increase with rising age. Aim of this study was to evaluate association of comorbidity and comedication with grade III/IV toxicities and prior cessation of chemotherapy in ovarian cancer patients.As an individual participant data meta-analysis this study analyzes the original data of three phase II/III chemotherapy studies of the North-Eastern German Society of Gynecological Oncology (NOGGO). Risk scores for certain combinations of risk factors were calculated based on stepwise regression analyses.Altogether, 1213 patients were included in the study. Cardiovascular disease was the most frequent comorbidity (47.5%). In multivariate analyses it was associated with hematological, non-hematological, pulmonary and renal grade III/IV toxicities (p=0.002; p0.001; p=0.005; p0.001). Renal toxicity was more frequent when using diuretics and ACE-inhibitors (p0.001; p=0.002). Prior cessation of therapy was e.g. associated with use of diuretics, insulin and digitalis (p=0.001; p=0.04; p=0.03). The risk for renal grade III/IV toxicities was more than 16 times higher when using both a diuretic and an ACE-inhibitor.Regimens of ovarian cancer treatment should not be restricted to direct cancer therapy but rather include additional individualized treatment of comorbidities. Comedications such as diuretics increase grade III/IV toxicities and patients at risk should be closely monitored.

Objectives Epithelial ovarian cancer (EOC) is the major cause of death due to gynecological malignancies. The most important prognostic factors are residual tumor mass after surgery and platinum-response. No predictive biomarkers are available to identify patients who will benefit from standard treatment. The aim of our study was to analyze the role of HE4 in predicting surgical and clinical outcome in primary EOC. Methods In the European multicentric project "OVCAD", 275 consecutive patients with primary EOC were enrolled. Patients were eligible if radical cytoreductive surgery was performed and platinum-based chemotherapy was applied. Plasma and ascites samples were collected before or during surgery. The concentrations of HE4 and CA125 was determined using ELISA and Luminex technique, respectively. Results Median age at first diagnosis was 58years (range 18–85years). Most patients presented with advanced stage disease, FIGO III or IV (94.6%), grades II–III (96%) and serous histology (86.2%). In most cases a complete cytoreduction to no residual tumor mass was achieved (68.4%). Higher plasma HE4 levels correlated with poor surgery outcome in terms of macroscopically residual tumor mass (p Conclusions The presented data are showing that the combination of HE4 and CA125 expression in plasma might predict the surgical outcome in EOC and by this may have a prognostic impact on PFS and OS.

Ovarian cancer is mostly diagnosed in the elderly woman who is likely to have comorbid disease and to take several comedications on a regular basis. Aim of this study was to evaluate the influence of polypharmacy on grade III/IV toxicity, prior discontinuation of chemotherapy and survival.In this individual participant data meta-analysis the original data of three phase II/III studies of the North-Eastern German Society of Gynecological Oncology (NOGGO) were analyzed using multivariate logistic and Cox regression.Overall, 1213 patients with recurrent ovarian cancer were included in these analyses. An increasing amount of medication was associated with overall grade III/IV toxicity (p0.001; OR 1.120), and hematological (p0.001; OR 1.056) and non-hematological (p0.001; OR 1.134) toxicities. Prior discontinuation of chemotherapy was not influenced by an increasing amount of medication (p=0.196). There was no association of polypharmacy with overall survival (p=0.068).As polypharmacy does not influence survival ovarian cancer patients taking several comedications may be included in clinical trials and should not be deprived of adequate cancer treatment. However, a thorough monitoring is mandatory due to the increased risk of toxicities.