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Background This study seeks to evaluate the impact of breast cancer (BRCA) gene status on tumor dissemination pattern, surgical outcome and survival in a multicenter cohort of paired primary ovarian cancer (pOC) and recurrent ovarian cancer (rOC). Patients and Methods Medical records and follow-up data from 190 patients were gathered retrospectively. All patients had surgery at pOC and at least one further rOC surgery at four European high-volume centers. Patients were divided into one cohort with confirmed mutation for BRCA1 and/or BRCA2 (BRCAmut) and a second cohort with BRCA wild type or unknown (BRCAwt). Patterns of tumor presentation, surgical outcome and survival data were analyzed between the two groups. Results Patients with BRCAmut disease were on average 4 years younger and had significantly more tumor involvement upon diagnosis. Patients with BRCAmut disease showed higher debulking rates at all stages. Multivariate analysis showed that only patient age had significant predictive value for complete tumor resection in pOC. At rOC, however, only BRCAmut status significantly correlated with optimal debulking. Patients with BRCAmut disease showed significantly prolonged overall survival (OS) by 24.3 months. Progression-free survival (PFS) was prolonged in the BRCAmut group at all stages as well, reaching statistical significance during recurrence. Conclusions Patients with BRCAmut disease showed a more aggressive course of disease with earlier onset and more extensive tumor dissemination at pOC. However, surgical outcome and OS were significantly better in patients with BRCAmut disease compared with patients with BRCAwt disease. We therefore propose to consider BRCAmut status in regard to patient selection for cytoreductive surgery, especially in rOC.

Euglena gracilis is a photosynthetic flagellate. To acquire a suitable position in its surrounding aquatic environment, it exploits light and gravity primarily as environmental cues. Several physiological studies have indicated a fine-tuned relationship between gravity sensing (gravitaxis) and light sensing in E. gracilis. However, the underlying molecular mechanism is largely unknown. The photoreceptor photoactivated adenylyl cyclase (PAC) has been studied for over a decade. Nevertheless, no direct/indirect interaction partner (upstream/downstream) has been reported for PAC. It has been shown that a specific protein, kinase A (PKA), showed to be involved in phototaxis and gravitaxis. The current study reports the localization of the specific PKA and its relationship with PAC.

Objective Recurrent ovarian cancer is an incurable disease with variable but poor prognosis. Health-related quality of life (HRQoL) is a patient-reported outcome measure generally applied to measure effects of therapies. Our aim was the development and validation of a risk score for the prediction of short-term mortality using the combination of sociodemographic and clinical factors and HRQoL. Methods For exploratory and validation analysis, the North-Eastern German Society of Gynecological Oncology (NOGGO) and Working Group Gynecological Oncology (AGO) study databases were screened for trials. Only trials which obtained defined HRQoL measurements were included in the final analysis. Multivariable logistic regression analyses were used to identify risk factors and their weighting for the risk score. Modulation with cubic regression analyses revealed median survival and short-term mortality defined as 1-year mortality for each value. Results For exploration, 974 patients from three clinical studies of the NOGGO and for validation, 1235 patients from several clinical studies of the AGO were eligible. The risk score included platinum-free interval, performance status, age, global QoL and nausea/vomiting. Receiver operating characteristic analysis showed a good predictive value with an area under the curve of 0.81 for model 1 in the exploration and 0.74 in the validation. Short-term mortality in model 1 was 8.2%, 23.5% and 58.4% in the exploration sample, and 19.7%, 38.1% and 63.4% in the validation sample for patients under low, medium and high risk, respectively. Conclusions This risk score discriminates well between recurrent ovarian cancer patients under low, medium and high risk of short-term mortality. It may help to identify a risk group under high risk for short-term mortality that can be used for randomization in clinical trials and may support decision making for palliative chemotherapy., Highlights • This newly developed NOGGO-AGO QoL prognosis score clearly discriminates recurrent ovarian cancer (rOC) patients under low, medium and high risk for short-term survival (

OBJECTIVE Patients with platinum-resistant ovarian cancer (PROC) have a high need for reliable prognostic markers. Since significance of primary platinum resistance (PPR) versus secondary platinum resistance (SPR) was identified for patients receiving anti-angiogenic therapy, it has not been confirmed for chemotherapy only. METHODS PROC patients from 3 prospective trials of the NOGGO study group (TOWER, NOGGO-Treosulfan, and TRIAS) were included in this meta-analysis. Exploratory Cox and logistic regression analyses were performed to correlate progression-free survival (PFS) and overall survival (OS) with the timing when platinum resistance developed. RESULTS Of 477 patients, 264 (55.3%) were classified as PPR, compared to 213 (44.7%) with SPR. For patients receiving chemotherapy only, SPR was associated with a significantly longer median PFS of 3.9 compared to 3.1 months for PPR (hazard ratio HR=0.78; p=0.015). SPR versus PPR was confirmed to be an independent prognostic factor for better PFS in multivariate analysis (HR=0.74; p=0.029). Benefit from adding sorafenib to chemotherapy was mainly seen in PPR (HR=0.40; p{\textless}0.001) compared to SPR patients (HR=0.83; p=0.465). CONCLUSIONS Prognostic significance of SPR versus PPR could be elucidated for patients receiving chemotherapy only. In contrast to bevacizumab, the multi-kinase inhibitor sorafenib exhibits profound therapeutic efficacy in PPR patients indicating potential to overcome this negative prognostic impact.

Introduction: The aim of this analysis was to evaluate the health-related quality of life (HR-QoL) in patients with ovarian cancer using a patient-reported outcome (PRO) based questionnaire and to compare it to the healthy female population in Germany and to other ovarian cancer patients worldwide. Additionally, we looked for differences in the HR-QoL with respect to the patients’ ages in our cohort. Methods: The HR-QoL for 155 enrolled patients with ovarian cancer was assessed by the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire (EORTC QLQ-C30) prior to surgery and then compared with 501 healthy females in Germany, as well as to the previously published European Organization for Research and Treatment of Cancer (EORTC) reference data for 917 patients with ovarian cancer worldwide. Moreover, we grouped our cohort by ages &lt, 65 and &gt, 65 years and analyzed them for further differences. To identify the differences, T-tests were applied. Results: Overall, 155 patients were enrolled, and 126 patients had advanced-stage ovarian cancer (FIGO III–IV) (82.4%). Fifty-five (36%) patients were &gt, 65 years. Except for the physical functioning scale, all other domains of the functioning scales were significantly lower in our patients with ovarian cancer than in the healthy female population. The emotional (50 points versus 60 points, p = 0.02), cognitive (76 points versus 88 points, p = 0.005), and social functioning scales (68 points versus 81 points, p = 0.006) were lower in the younger subgroup. Further, the younger subgroup exhibited significantly more fatigue (40 points versus 29 points, p = 0.03) and financial difficulties (20 points versus 2 points, p &lt, 0.001) than the older subgroup. Discussion: Interestingly, the patients with ovarian cancer had no significant differences in the physical functioning scale when compared with the healthy women. In contrast, the patients, especially in the younger group, needed special support for the emotional and social areas of their daily lives.

Background: Complete macroscopic tumor resection is the strongest prognostic factor for patients with ovarian cancer, which requires complex surgery for achievement. Based on the mostly advanced tumor stage and high symptom burden many patients are classified as frail which may limit optimal surgical outcome. Aim of this study is to evaluate the predictive ability of Frailty Index for surgical outcomes in patients with ovarian cancer. Methods: This prospective study enrolled patients with ovarian cancer undergoing cytoreductive surgery. We classified frailty proposed by Mitnitski et al. regarding the cumulative deficit model of frailty. Utilizing Receiver Operator Characteristic (ROC) analysis and logistic regression, we determined predictive clinical factors for severe postoperative complications. The Kaplan-Meier method and log-rank test were used for overall survival analysis. Results: Out of f 144 enrolled patients, the overall prevalence of frailty based on a Frailty Index >0.26 and Frailty Index >0.15 was 33% and 74%, respectively. The logistic regression shows that frail patients with a Frailty Index >0.26 (Odds ratio (OR): 3.64, 95% CI: 1.34–9.85, p = 0.01), ECOG PS > 1 (OR 6.33, 95% CI:1.31–30.51, p = 0.02) and high surgical complexity score (OR 8.86, 95% CI:1.88–41.76, p = 0.006) had a significant higher risk for severe postoperative complications. According to multivariable cox regression Frailty Index >0.15 (hazard ratio (HR) (HR 1.87, 95% CI: 1.01–3.47, p = 0.048), residual tumor 1 cm (HR 5.00, 95% CI: 2.74–9.13, p < 0.001) and albumin 1 and recurrent surgery, Frailty Index >0.26 is associated with severe postoperative complications in patients with ovarian cancer. Besides tumor residuals and low albumin levels a Frailty Index >0.15 predicts poor survival. © 2021, AstraZeneca Roche, This study was funded by the ALLIMOGI-Foundation ., MGI reports grants from ALLIMOGI-Foundation during the conduct of the study; JS reports other from Medac, Roche, AstraZeneca, PharmaMar, personel fee and others outside the submitted work; HWs travel expenses were sponsored by Medac. The other authors declare no conflict of interest.

PURPOSE: To evaluate the practice patterns among centers and physicians worldwide regarding sentinel lymph node biopsies (SLNB) in cervical cancer (CC) patients. METHOD: A validated 35-item questionnaire regarding SLNB in CC supported by the Gynecologic Cancer Intergroup (GCIG), and sponsored by the North-Eastern German Society of Gynaecologic-Oncology (NOGGO) was sent to all major gynecological cancer societies across the globe for further distribution from October 2015 and continued for a period of 7 months. RESULTS: One hundred and sixty-one institutions from around the world participated. One hundred and six (66%) of the participants were from university centers and one hundred and eleven (69%) were gynecologic oncologists. One hundred and fifty-two (97%) performed lymphadenectomy (LNE), and one hundred and forty-seven (94%) did so systematically; Ninety-seven (60%) used SLNB, due to lower morbidity (73%), reliability (55%) and time-saving (27%). In cases of positive SLNB (pN+), 39% of respondents stopped the operation and sent the patient for chemoradiation (CRT), 45% completed pelvic and paraaortic LNE, whereas 26% went on to perform a radical hysterectomy (RH) and systematic pelvic and paraaortic LNE. In case of negative SLNB (pN0), 39% of institutions still performed a systematic pelvic and paraaortic LNE. CONCLUSION: In this survey worldwide SLNB adoption is an encouraging 60%, yet ample differences exist regarding strategy, and to a lower extent the techniques used. Lack of experience is the most common reason SLNB is not performed. Efforts to increase surgical education on SLNB technique and multicenter prospective trials providing evidence-based guidelines are warranted.

Human papillomavirus (HPV) infection is a frequent cause of malignant and non-malignant disease, in particular among persons with HIV. HPV serotype-specific anti L1 antibodies protect against HPV infection but little is known about prophylactic HPV vaccine-induced cell-mediated immunity against HPV in high-risk individuals. We recently showed that both HPV vaccines (Gardasil® and Cervarix®) induce solid, serological immune responses in HIV-infected persons. This study aimed to characterize HPV-specific CD4 T cells in HIV-infected HPV-vaccine recipients, T cell responses being critical for B cell activation and antibody-isotype switching. Thirty HIV-infected patients on long-term antiretroviral treatment (ART) received 3 doses of either Cervarix (n = 15) or Gardasil (n = 15) vaccine at month 0, 1.5 and 6. Cryopreserved peripheral blood mononuclear cells (PBMC) from baseline, 7 and 12 months were subjected to 24-hour stimulation with specific pools of HPV L1-peptides (HPV6, 11, 16, 18, 31 and 45) and HPV E6/E7-peptide pools (HPV6/11 and HPV16/18). Fluorescence-activated cell sorting with intracellular staining (IC-FACS) against CD4, CD154, IL-2, and IFNγ was performed. Frequencies (%) of HPV-antigen specific CD4+ T cells (CD154+/IL-2+ or CD154+/ IFNγ+) were determined. Both HPV-vaccines significantly and comparably enhanced cell-mediated vaccine L1 antigen-specific immunity in HIV-positive adults receiving ART therapy at month 7 and 12 after first vaccine dose. This suggests that the vaccines induce CD4 T cellular memory despite HIV-induced immune compromisation.

Aim. The purpose of the present study was to analyze the predictive and prognostic role of soluble (pro)renin receptor (sPRR) as a biomarker for clinicopathological outcome in patients with primary epithelial ovarian cancer (EOC). As part of the renin-angiotensin system (RAS) whose activity is known to increase in ovarian cancer patients, the relation of sPRR and ovarian cancer should be further investigated.Patients and Methods. In this study 197 patients with primary EOC in our institution from 2000 to 2011 were included. sPRR was determined by enzyme-linked immunosorbent assay (ELISA) in preoperative taken blood sera. Associations with clinicopathological outcome were analyzed and serum levels of sPRR in patients have been compared to those in healthy specimen. Kaplan-Meier and logistic/Cox regression assessed the impact of the markers on progression-free survival (PFS) and overall survival (OS).Results. There have been no correlations proved of sPRR levels with neither clinicopathological factors nor prognostic data. Also the distribution of sPRR in patients and controls was normal.Conclusion. sPRR seems to have no predictive, prognostic, or diagnostic value in EOC. As several factors of the RAS which might indicate cancer events have been shown, sPRR seems not to be affected.

Elena Ioana Braicu,1 Hrvoje Luketina,1 Rolf Richter,1 Dan Cacsire Castillo-Tong,2 Sandrina Lambrechts,4 Sven Mahner,5 Nicole Concin,6 Monika Mentze,1 Robert Zeillinger,2,3 Ignace Vergote,4 Jalid Sehouli1 1Department of Gynecology, European Competence Center for Ovarian Cancer, Charité – Universitätsmedizin Berlin, Berlin, Germany; 2Department of Obstetrics and Gynecology, Comprehensive Cancer Center, Medical University of Vienna, 3Ludwig Boltzmann Cluster Translational Oncology, General Hospital of Vienna, Vienna, Austria; 4Department of Obstetrics and Gynecology, Universitaire Ziekenhuizen Leuven, Katholieke Universiteit Leuven, Leuven, Belgium; 5Department of Gynecology and Gynecologic Oncology, University Medical Center Hamburg-Eppendorf, Hamburg, Germany; 6Department of Obstetrics and Gynecology, Innsbruck Medical University, Innsbruck, AustriaPurpose: Hypoxia is a common phenomenon encountered in solid cancers, leading to chemotherapy resistance and therefore to aggressiveness of the disease. The homeostatic response to hypoxia is mediated by hypoxia-inducible factor-1 (HIF-1). The aim of this study was to investigate the impact of HIF1α in patients with primary epithelial ovarian cancer.Methods: In this multicentric study, 275 patients with advanced primary epithelial ovarian cancer were included. All patients underwent cytoreductive surgery with maximal surgical effort and adjuvant platinum-based chemotherapy. HIF1α expression was analyzed in tissue lysates, using an enzyme-linked immunosorbent assay.Results: HIF1α was detected in 79.3% of the tissue samples. Patients with increased HIF1α expression (cutoff: 80 pg/mg protein) in tumoral tissue lysates were more likely to have less favorable survival. HIF1α (P=0.009, hazard ratio [HR] 2.505, 95% confidence interval [95% CI] 1.252–5.013) together with International Federation of Gynecology and Obstetrics (III versus IV) (P=0.013, HR 0.540, 95% CI 0.332–0.878), histology (P=0.007, HR 2.748, 95% CI 1.315–5.743), presence of peritoneal carcinomatosis (P=0.014, HR 2.176, 95% CI 1.170–4.046), residual tumor mass (P=0.017, HR 1.641, 95% CI 1.091–2.468), and response to platinum-based chemotherapy (P

Background/Aims: The supply of docosahexaenoic acid (DHA, 22:6ω–3), important for fetal/infant neurodevelopment, depends on the maternal fatty acid (FA) status, which may be marginal in central Europe. Therefore, we investigated the effect of a daily vitamin/mineral supplement with and without 200 mg DHA from mid-pregnancy through lactation on the DHA concentrations in maternal and infant red blood cell phospholipids (RBC%), and in breast milk FA (%). Methods: At 21 weeks’ gestation, 144 women were enrolled into a randomised, double-blind clinical trial receiving daily: (1) a basic vitamin-mineral supplement (Vit/Min group), (2) Vit/Min plus 4.5 g fructo-oligosaccharide (FOS group), or (3) Vit/Min plus 4.5 g FOS plus 200 mg fish oil-derived DHA (DHA-FOS group). FAs were determined by capillary gas-liquid chromatography. Results: While maternal RBC-DHA% at enrolment was not different, at 37 weeks gestation, and 3 months after delivery RBC-DHA% were significantly higher in the DHA-FOS group. The breast milk DHA% was twice as high in the DHA-FOS group (0.50%) than in the two others (0.25 %) (p < 0.001), and the ratio ARA/DHA in the DHA-FOS group was 1.0 ± 0.43, in the others 2.1 ± 0.43 (p < 0.001). The RBC-DHA% of the infants in the DHA-FOS group was also significantly higher, and correlated significantly with maternal RBC-DHA% before and 3 months after delivery. Conclusions: In central Europe, a dose of 200 mg/day DHA from mid-pregnancy through lactation seems appropriate to improve the DHA status of mothers and infants.

Background Palliative systemic treatment in elderly gynaecological cancer patients remains a major challenge. In recurrent ovarian cancer (ROC), treosulfan an active alkylating drug showed similar cytotoxicity whether as oral (p.o.) or intravenous (i.v.) application. The aim of this innovative trial was to evaluate the preference of elderly patients (≥65 years) for p.o. or i.v. chemotherapy focusing compliance, outcome, toxicities, and geriatric aspects as secondary endpoints. Methods Patients with ROC had the free choice between treosulfan i.v. (7000 mg/m2 d1, q29d) or p.o. (600 mg/m2 daily d1-28, q57d). Only indecisive participants were randomized. Results Overall 123 patients with 2nd to 5th recurrence were registered and 119 received at least one cycle of chemotherapy. 85.7% preferred treosulfan i.v. and 14.3% oral, where only three patients were randomized. Main reasons for i.v. preference associated with individual expectations of lower rate of gastrointestinal disorders, higher activity and tolerability of treatment. Median of applied chemotherapies was three (range 1–12 cycles), with most common grade 3/4 toxicities thrombopenia (18.7%), leukopenia (15.7%), ascites (7.6%), bowel obstruction (6.7%), and abdominal pain (4.2%). Median time until progression/overall survival was 5.2/7.8 months (i.v.), and 5.6/10.4 months (p.o.), respectively, without significant differences in efficacy. Conclusions Elderly patients with recurrent ovarian cancer asked and demonstrated active participation in the decision-making process of their oncological treatment and favoured predominantly the i.v. application. Treosulfan was generally well-tolerated despite comorbidities and heavy pre-treatment. Our study demonstrates that patients’ preference did not influence prognosis negatively and remains important in gynaecologic oncology decision practice. EudraCT Nr. 2004-000719-25; NCT 00170690