OBJECTIVE:This study investigates treatment quality and survival outcomes in elderly patients (≥75 years) with early-stage (International Federation of Gynecology and Obstetrics stage I/II) epithelial ovarian cancer documented in the German national quality-assurance program. It examines associations between surgical and systemic treatment quality and disease-free and overall survival. METHODS:Patients with a first diagnosis of ovarian cancer during the third quarter of 2012, 2016, and 2021 were documented. Surgical quality was defined as optimal when no more than one required staging procedure was omitted and sub-optimal when two or more procedures were missing. Chemotherapy quality was considered optimal when aligned with national guidelines. Overall treatment quality was classified as optimal, mixed, or sub-optimal according to surgical and chemotherapy quality. RESULTS:A total of 228 elderly patients with presumed early-stage epithelial ovarian cancer were included. Among them, 24.6% received both optimal surgery and optimal chemotherapy, 10.1% received optimal surgery with sub-optimal chemotherapy, 25.4% received sub-optimal surgery with optimal chemotherapy, and 39.9% received sub-optimal treatment in both modalities, with marked differences in age, Eastern Cooperative Oncology Group performance status, and comorbidity burden across treatment groups. At 24 months, 64% (95% confidence interval, 58% to 71%) of elderly patients remained disease-free. Within the elderly cohort, 24-month disease-free and overall survival were 90% (95% confidence interval, 82% to 99%) and 98% (95% confidence interval, 94% to 100%) with optimal surgery and chemotherapy, 68% (95% confidence interval, 56% to 81%) and 79% (95% confidence interval, 68% to 90%) with sub-optimal surgery and optimal chemotherapy, and 49% (95% confidence interval, 32% to 76%) and 62% (95% confidence interval, 45% to 87%) with optimal surgery and sub-optimal chemotherapy. CONCLUSIONS:In elderly patients with assumed early-stage ovarian cancer, guideline-concordant surgery and chemotherapy showed deficits that were associated with unfavorable outcomes. Chemotherapy quality showed a strong association with outcome, underscoring the need to optimize evidence-based treatment in elderly patients. Nonetheless, these findings are associative only, given possible selection of fitter patients and treatment of occult advanced disease in surgically under-staged patients.

Mucinous ovarian carcinoma (MOC) is an epithelial ovarian cancer subtype that is frequently misclassified as extraovarian mucinous metastasis (EOM) because of overlapping features. To address this diagnostic challenge, we perform genome-wide DNA methylation profiling of 58 MOCs, 38 EOMs, and 18 mucinous borderline ovarian tumors (mBOTs) collected from six institutions. Methylation analysis defines two mBOT groups, one epigenetically similar to normal ovary and one resembling MOC. Unsupervised clustering reveals two distinct MOC methylation subtypes with potential prognostic relevance in the internal cohort. Using these data together with 389 external profiles, we develop and validate a three-step machine-learning classifier that distinguishes MOC from EOM with 95.5% accuracy. External validation of this classifier on 21 MOCs and 24 EOMs yields an accuracy of 91.11% for differentiating MOC from EOM. These findings establish an epigenetic framework for mucinous ovarian tumors and provide a robust clinical classification tool.

BACKGROUND:Epithelial ovarian cancer frequently recurs and becomes resistant to platinum chemotherapy. We investigated whether adding pembrolizumab to weekly paclitaxel, with or without bevacizumab, improves progression-free survival and overall survival compared with weekly paclitaxel, with or without bevacizumab, in participants with platinum-resistant recurrent ovarian cancer who had received one to two previous systemic regimens. METHODS:ENGOT-ov65/KEYNOTE-B96 is a randomised, double-blind, phase 3 study conducted at 187 gynaecologic oncology centres in 25 countries in the Americas, Asia, Europe, and Oceania. Adults (≥18 years) with histologically confirmed epithelial ovarian, fallopian tube, or primary peritoneal carcinoma, who received one to two previous systemic therapies including at least one platinum regimen and who progressed 6 months or less after the last platinum regimen, were eligible. Participants were randomly assigned 1:1 to intravenous pembrolizumab 400 mg every 6 weeks for up to 18 cycles plus open-label intravenous paclitaxel 80 mg/m2 on days 1, 8, and 15 of each 21-day cycle or intravenous placebo (saline solution) every 6 weeks for up to 18 cycles plus open-label intravenous paclitaxel 80 mg/m2 on days 1, 8, and 15 of each 21-day cycle; intravenous bevacizumab 10 mg/kg every 2 weeks was permitted per investigator. Randomisation was stratified by planned bevacizumab use, region, and PD-L1 combined positive score (CPS). The primary endpoint was investigator-assessed progression-free survival per RECIST version 1.1; the key secondary endpoint was overall survival. Results from two interim analyses and the final analysis are included in this Article. This study is registered with ClinicalTrials.gov, NCT05116189, and is now completed. FINDINGS:Between Dec 13, 2021, and July 3, 2023, 643 female participants were randomly assigned; 322 to pembrolizumab plus paclitaxel and 321 to placebo plus paclitaxel. At the first interim analysis, pembrolizumab plus paclitaxel significantly improved progression-free survival versus placebo plus paclitaxel in both the PD-L1 CPS 1 or higher (median 8·3 months vs 7·2 months; hazard ratio [HR] 0·72; 95% CI 0·58-0·89; p=0·0014 α=0·012]) and overall populations (median 8·3 months vs 6·4 months; HR 0·70, 95% CI 0·58-0·84; p<0·0001, [α=0·0023]), meeting the prespecified criteria for confirmatory efficacy. At the second interim analysis, overall survival was significantly improved in the PD-L1 CPS 1 or higher population (median 18·2 months vs 14·0 months; HR 0·76, 95% CI 0·61-0·94; p=0·0053, [α=0·0083]). At the final analysis, overall survival was significantly improved in the overall population (median 17·7 months vs 14·0 months; HR 0·82, 95% CI 0·69-0·97; p=0·011 [α=0·024]). Grade 3 or worse treatment-related adverse events occurred in 217 (68%) of 320 participants in the pembrolizumab plus paclitaxel group versus 176 (55%) of 318 participants in the placebo plus paclitaxel group. The most common treatment-related adverse events (any grade) included anaemia, peripheral neuropathy, alopecia, fatigue, and nausea. Treatment-related adverse events resulted in death in four participants (1%) in the pembrolizumab plus paclitaxel group (colitis, interstitial lung disease, acute myeloid leukaemia, and intestinal perforation) and in five participants (2%) in the placebo plus paclitaxel group (cardiac failure, intestinal perforation [in two participants], and large-intestine perforation [in two participants]). INTERPRETATION:Pembrolizumab plus weekly paclitaxel, with or without bevacizumab, significantly improved progression-free survival and overall survival in participants with platinum-resistant recurrent ovarian cancer who had received one to two previous systemic regimens, supporting this regimen as a new treatment option for this population. FUNDING:Funded by Merck Sharp & Dohme LLC, a subsidiary of Merck & Co, Inc, Rahway, NJ, USA.

Patients undergoing extended multivisceral, non-cardiac surgery require a high demand for intravenous fluid administration, leading to substantial positive fluid balances. This study aimed to perioperatively characterize extravasation as a correlate of capillary leakage and micro-arterial regulation, as well as venous return characteristics, as possible causes for the positive fluid balances. In this single center, observational trial we included patients undergoing abdominal debulking surgery due to ovarian cancer. The measurements were performed by a venous congestion plethysmography (VCP) protocol to determine extravasation, micro-arterial reagibility, and after deflation of congestion venous outflow characteristics at timepoints before and during surgery, and repeatedly during the postoperative course. Thirty patients with primary ovarian cancer undergoing cytoreductive surgery treated within a goal-directed hemodynamic algorithm (GDA) based on the esophageal Doppler were included in the analysis. Stroke volume index did not change throughout the procedure with an increase in heart rate and consequently an increase in cardiac index. The norepinephrine requirements to maintain mean arterial pressure increased during surgery. Patients received a median 1750[25-quartile 1075;75-quartile 2100]ml crystalloids and 1000[1000;1500]ml starches, transfusions of 0[0;1040]ml red-packed cells, and 360[0;2880]ml fresh-frozen plasma. The intraoperative fluid and blood loss of 1020[508;1695]ml resulted in a positive fluid balance (2820[1338;6075]ml). Extravasation did not increase during surgery, even in the presence of substantially positive fluid balances. On the third and fifth postoperative days, extravasation increased relative to the preoperative baseline value. The micro-arterial function deteriorated throughout the course of the surgery, recovering to baseline values within 4 h after surgery. The venous outflow characteristics of the limb after releasing the venous congestion deteriorated over the course of surgery. There was no increase in extravasation measured by VCP during surgery despite a substantial intraoperative positive fluid balance, showing that they were not associated with each other. The micro-arterial function and venous backflow characteristics deteriorated during surgery, indicating that vascular dilation rather than capillary leakage may contribute to the high fluid demands. Trial registration: ClinicalTrials.gov identifier: NCT01311297.

PURPOSE Constitutional epimutations arise early in development and are present across normal tissues, including peripheral blood. Constitutional BRCA1 promoter methylation has emerged as a risk factor for BRCA1 -associated cancers, such as ovarian cancer (OC), and may serve as a biomarker for OC risk. This study retrospectively evaluated the clinical relevance of constitutional BRCA1 promoter methylation in 473 patients with OC enrolled in the observational AGO-TR1 study (ClinicalTrials.gov identifier: NCT02222883 ). MATERIALS AND METHODS BRCA1 promoter methylation was quantified by the methylation-specific real-time polymerase chain reaction using whole blood-derived DNA from 476 female controls and 473 patients with OC along with 473 corresponding tumor-derived DNA samples. Methylation levels ≥1.0% were considered methylation-positive. RESULTS BRCA1 promoter methylation in blood-derived DNA was detected in 42 of 473 patients with OC and in 26 of 476 controls (8.9% v 5.5%; odds ratio [OR], 1.69 [95% CI, 1.02 to 2.80], P = .0432), with the strongest association observed with methylation levels ≥10% (OR, 6.17 [95% CI, 1.37 to 27.72], P = .018). Patients with BRCA1 promoter methylation in blood-derived DNA were diagnosed at a younger median age than those without (54.0 v 60.0 years, P = .018). Constitutional BRCA1 promoter methylation was less frequent in patients carrying pathogenic germline variants in OC predisposition genes than in noncarriers (4.1% v 10.5%; OR, 0.37 [95% CI, 0.14 to 0.96], P = .04) and showed no association with a family history of cancer or platinum-based chemotherapy before blood draw. BRCA1 promoter methylation in blood-derived DNA was correlated with tumor BRCA1 promoter methylation ( P < .001). Tumor BRCA1 promoter methylation was observed in 64 of 473 samples (13.5%), half (32 of 64) of which were attributable to constitutional BRCA1 promoter methylation also detectable in the blood. CONCLUSION Constitutional BRCA1 promoter methylation accounts for a substantial proportion of OCs and represents a robust biomarker for individual OC risk.

BACKGROUND/OBJECTIVES:Ovarian cancer is typically diagnosed in postmenopausal women, so there are limited data available for young adult cancer survivors (YACS). The aim was to assess the patient perspective of YACS. METHODS:In this international and multicenter cross-sectional survey study, patient history, long-term side effects, and patient perspective were assessed. Long-term survival was defined as survival of at least five years after cancer diagnosis. Two groups were defined: (1) 18-40 years and (2) ≥41 years. RESULTS:Altogether, 1833 long-term survivors (LTS) have been recruited, with 1771 patients ≥41 years and 62 patients 18-40 years at recruitment. FIGO stages were similar; among the patients, 99.0% had received primary surgery followed by chemotherapy in 90.3%. Almost 50% still experienced long-term side effects. Patients ≤ 40 years reported more frequently not only gastrointestinal symptoms such as nausea/vomiting (44.4%, p = 0.01), bloating (59.3%, p = 0.038), and constipation (60%, p = 0.015) but also depression (31.4%, p = 0.02), lymphedema (45.3%, p = 0.026), and concentration difficulties (30.6%, p = 0.002). Distress levels were also higher in YACS, especially concerning insurance/finances, work/school, child care, worries, and sadness. Polyneuropathy and secondary cancer were the only side effects that were more frequent in the elder cohort (polyneuropathy: 20.3% vs. 4.3%, p = 0.002, and secondary cancer: 8.4% vs. 0%, p = 0.014). YACS were more physically active (p = 0.003) and interested in studies about long-term cancer survivorship in 87.2%. CONCLUSIONS:Long-term side effects are equally common in YACS after ovarian cancer, but with a focus on practical problems, mental health, gastrointestinal problems, and sexuality. This knowledge should be incorporated into follow-up care of ovarian cancer patients in order to improve quality of life.

Background: Given the challenges in early detection and diagnosis, understanding the molecular underpinnings of endometrioid ovarian cancer (EOC) is crucial for improving patient outcomes. This multi-level study provides a new perspective on EOC, focusing on the expression of ARID1a (BAF250a) and RIF1. Methods: This study evaluates patient cohorts with EOC through semi-quantitative immunohistochemical staining of BAF250a (protein encoded by ARID1a) and RIF1 proteins alongside mutations that influence the gene expression of ARID1a and RIF1. Besides survival analyses, platinum- and taxane-based treatment responsiveness with regard to ARID1a and RIF1 expression has been analyzed using an online available database. Results: Histological and immunohistochemical analysis of clinical samples revealed a significant reciprocal alteration in protein expression, characterized by a marked reduction in the tumor suppressor BAF250a (p < 0.0001) and a concomitant elevation of RIF1 (p < 0.0001) in EOC compared to controls. Tumors harboring mutations in BRCA1 exhibited significantly (p = 2.82 × 10−4) lower ARID1a expression levels compared with corresponding wild-type tumors, whereas LAMB3-mutant tumors showed a significant (p = 5.16 × 10−3) upregulation of RIF1 mRNA expression. Conclusions: In conclusion, our study offers a new perspective, emphasizing that EOC is a distinct clinical and molecular entity. We demonstrated the expression patterns of ARID1a/BAF250a and RIF1 in EOC, establishing their potential relevance in the context of tumor biology and malignant transformation.

Background/Objectives: Primary cytoreductive surgery for advanced ovarian cancer is associated with a high risk of postoperative complications, particularly surgical site infections, which may delay recovery and adjuvant treatment. This study aimed to evaluate the impact of a revised infection-prevention bundle, centered on chlorhexidine-alcohol skin antisepsis, on surgical site infection rates and cost-effectiveness. Methods: In this single-center cohort study, 636 patients undergoing primary cytoreductive surgery between January 2019 and December 2023 were included. A historical control group (n = 300) received povidone-iodine for intraoperative skin preparation, while a prospective intervention group (n = 336) received chlorhexidine gluconate 2% in 70% isopropyl alcohol. Both groups were managed within a standardized perioperative care pathway. Surgical site infections within 30 days were defined according to established criteria. Comparative and descriptive statistical analyses were performed. Results: Baseline clinicopathological characteristics were comparable between groups. The overall surgical site infection rate was significantly lower in the chlorhexidine-alcohol group compared with the povidone-iodine group (8.3% vs. 14.0%; p = 0.0226). The reduction was particularly evident in procedures lasting more than 180 min (9.5% vs. 17.1%; p = 0.0199), while no significant difference was observed in shorter procedures. Cost analysis demonstrated a net saving of approximately EUR 451 per procedure in the chlorhexidine group, driven by reduced infection-related costs and improved operating room efficiency. Conclusions: Baseline clinicopathological characteristics were comparable between groups. The overall surgical site infection rate was significantly lower in the chlorhexidine-alcohol group compared with the povidone-iodine group (8.3% vs. 14.0%; p = 0.0226). The reduction was particularly evident in procedures lasting more than 180 min (9.5% vs. 17.1%; p = 0.0199), while no significant difference was observed in shorter procedures. Cost analysis demonstrated a net savings of approximately EUR 451 per procedure in the chlorhexidine group, driven by reduced infection-related costs and improved operating room efficiency.

Objective Ovarian cancer remains a significant global health concern. Contemporary therapeutics have led to an increased number of long-term survivors. This research investigates the unmet needs of long-term ovarian cancer survivors in Spain, focusing on persistent side effects, patient concerns, lifestyle changes, and ongoing challenges. Methods This is a multi-center, cross-sectional, observational study, assessing the results from the international North-Eastern German Society of Gynecological Oncology survey, Expression VI - Long-term survival with ovarian cancer in Spain. Participants were identified during follow-up visits at oncology departments. A structured questionnaire of 68 items, including demographic, clinical, psychosocial, and lifestyle domains, was completed anonymously in printed format, with implied consent through survey completion. Results A total of 250 long-term ovarian cancer survivors from Spain, defined as patients diagnosed of malignant ovarian cancer with a survival ≥8 years since diagnosis (median age at diagnosis 52 years; median survival time 11 years), completed the survey. A substantial number of participants continued to experience long-term side effects, including gastrointestinal (90%), dermatologic (91.6%), and neurologic symptoms, such as memory problems (15.1%) and concentration difficulties (10.8%). Nearly half of the survivors (47.3%) expressed concerns about nervousness, 43.6% reported ongoing pain, and 40% struggled with sleep disturbances. Lifestyle changes after cancer diagnostic were significant, with 56.5% of smoker participants quitting or reducing smoking and 41.6% adopting healthier diets. Finally, our results indicate that most participants received some form of follow-up, primarily through blood biomarker monitoring (87.0%) and imaging tests (73.0%). Conclusions This study highlights the persistent challenges among long-term ovarian cancer survivors in Spain, stressing the need for more comprehensive, tailored aftercare. These findings may be generalized to other regions, emphasizing the importance of addressing ongoing side effects and unmet care needs to improve survivors’ long-term quality of life. Enhanced follow-up care, patient support, and effective communication are essential components of this effort.

INTRODUCTION:We present the rare case of a 29-year-old patient with uterine adenosarcoma who received fertility-sparing treatment, subsequently conceived spontaneously, and gave birth to a healthy infant. CASE:In August 2022, the nulliparous patient presented with acyclic uterine bleeding. Diagnostic hysteroscopy and targeted resection of a polyp located at the cervicouterine junction revealed uterine adenosarcoma without sarcomatous overgrowth (FIGO stage T1a). Imaging confirmed no residual tumor or metastasis. A fertility-sparing management strategy was chosen, avoiding hysterectomy but involving close oncological surveillance with quarterly MRI scans. During follow-up, a concurrent diagnosis of symptomatic endometriosis introduced therapeutic challenges. The patient spontaneously conceived in 2023 and delivered a healthy infant by cesarean section at term in 2024. Subsequent hysteroscopy and imaging in 2025 showed no evidence of recurrence, therefore fertility-preserving management was continued. PATIENT PERSPECTIVE:A short narrative of the patient's perspective on her initial diagnosis, possible fertility loss, and the emotional turmoil of pregnancy after uterine adenosarcoma is presented. DISCUSSION:Treating young patients diagnosed with uterine adenosarcoma poses a challenge to the treating physician due to the lack of guidelines and evidence regarding fertility-preserving treatment of this rare tumor. This report adds to the limited literature on successful pregnancy after uterine adenosarcoma and discusses indications and limitations of fertility-sparing treatment. CONCLUSION:Fertility preservation may be possible in selected early-stage uterine adenosarcoma cases without high-risk features such as sarcomatous overgrowth or myometrial invasion, with thorough counseling and strict follow-up. Further research is needed to develop standardized protocols and improve management in this context.

5595 Background: Low-grade serous ovarian cancer (LGSOC), a rare ovarian malignancy, exhibits a very limited responsiveness to chemotherapy. There is a pressing need for new therapeutic combinations with modern agents to enhance response rates and prognosis in this patient subgroup. Immune checkpoint inhibitors offer a promising pathway, having shown effectiveness in various malignant diseases, including selected cases of ovarian cancer. If our trial should show pembrolizumab effectivity in LGSOC, it would be a signal and impulse for future clinical studies in this rare disease. Methods: This multi-center, single-arm phase II study evaluates pembrolizumab in combination with platinum-based chemotherapy (carboplatin plus pegylated liposomal doxorubicin [PLD] or carboplatin plus gemcitabine) and as maintenance therapy in recurrent LGSOC. Eligible patients include those with disease progression or recurrence ≥6 months post prior platinum-based therapy and ECOG performance status 0-1. The primary endpoint is the 12-month progression-free survival (PFS) rate. Secondary endpoints include response rate (RR), PFS and ORR based on Ki67 expression. Using Simon’s two-stage design, 33 patients were enrolled. Success is defined as ≥11 patients achieving 12-month PFS. Assuming a true PFS rate of 40%, the study has 5% type I error and 80% power. Results: Data from 33 patients were evaluated. At data cut-off, 12 patients were progression free at 12-months (median PFS 15.5 months) while 19 patients progressed or died within 12 months (median PFS 5.6 months). Overall PFS median was 8.4 months. Comparing the subgroups of pre-treatment Ki67 expression <3.6% vs. ≥ 3.6%, the median PFS was 5.1 vs. 8.8 months. Four patients remain on pembrolizumab treatment; two of these have not yet reached the 12-month PFS endpoint. Median patient age was 52 years (range: 37-81), with ECOG performance status 0 in 30 patients (90.9%). Most patients had one prior chemotherapy line (61.1%; range: 1-5). Chemotherapy regimens included carboplatin + PLD (75.8%) and carboplatin + gemcitabine (24.2%). SAEs were reported in 22 patients (66.7%), with 11 (33.3%) considered treatment-related. Conclusions: The study achieved its primary objective in terms of the 12-months PFS and thus suggests efficacy of pembrolizumab in patients with platinum-sensitive recurrent LGSOC. Clinical trial information: 2023-508155-40-00.