Combination chemotherapy with immune checkpoint blockade has reshaped the treatment landscape for recurrent endometrial carcinoma (EC). However, subgroup analyses have demonstrated limited efficacy in patients previously treated with platinum-based adjuvant chemotherapy. To investigate how prior adjuvant chemotherapy affects the tumor microenvironment (TME) at recurrence, we analyzed 32 matched primary–recurrent EC pairs by performing multi-omic profiling in 20 pairs and multiplex immunohistochemistry (mIHC) in all cases. Recurrent tumors with prior platinum-based adjuvant chemotherapy exhibited increased variant allele frequencies of mutations in MYC signaling-related genes, with enrichment of glycolysis, regulatory T (Treg) cells, and M2 macrophage polarization. mIHC demonstrated increased Treg-cell infiltration and the M2/M1 macrophage ratio in recurrent tumors compared with matched primary tumors. Moreover, progression-free survival after recurrence correlated more strongly with the TME of recurrent tumors than with that of the primary tumors. Platinum-based adjuvant chemotherapy is associated with the emergence of immunosuppressive TME features in recurrent EC.

Gestational trophoblastic neoplasia (GTN) encompasses a wide range of diseases, which include choriocarcinoma, placental site trophoblastic tumor, epithelioid trophoblastic tumor, and post-molar persistent or rising levels of human chorionic gonadotrophin. Standardization of the diagnostic criteria and investigative approaches for this uncommon, potentially lethal, yet highly treatable disease is important. Adoption of an evidence-based staging and scoring system is essential to guide patient management and enable comparison of treatment outcomes. An updated staging system for GTN has been proposed and adopted by the Committee on Women's Cancer of the International Federation of Gynecology and Obstetrics (FIGO) for this purpose. This article highlights the changes introduced in the 2026 system and provide explanatory notes to facilitate interpretation.

Abstract Purpose Ovarian clear cell carcinoma (OCCC) is strongly associated with endometriosis and shows geographic variation in incidence. We investigated whether OCCC and adjacent endometriosis exhibit distinct transcriptional states and whether these patterns differ between United Kingdom (UK) and Japanese cohorts. Experimental Design We performed whole-transcriptome spatial profiling on specimens from 16 OCCC cases (8 UK, 8 Japan) in which tumor and endometriosis were both present. Gene expression was analyzed in tumor, endometriosis and stroma. ARID1A status was assessed by immunohistochemistry. Results Median age was 59 years (range 26–82). 13/16 cases (81.3%) had early-stage disease. Tissue compartment rather than cohort of origin was the dominant source of variation across endometriosis and tumor regions. Endometriosis was enriched for inflammatory and immune-related pathways compared to tumor, whilst there was greater representation of chromatin and protein–DNA complex assembly pathways in tumor regions. These patterns were conserved across both cohorts and after stratification by ARID1A status. Mesenchymal-associated gene expression scores also significantly differed across stroma, endometriosis and tumor with clear compartmental separation. Cell type deconvolution analyses showed clear compositional differences between stromal and epithelial disease compartments. Conclusions OCCC and coexisting endometriosis are transcriptionally distinct, with the dominant contrast being compartmental rather than geographic. ARID1A alone is unlikely to account for the principal spatial transcriptional states identified here. Further analyses will be required to ascertain whether these differences reflect genuine biological differences between OCCC and coexisting endometriosis or represent different stages of endometriosis-associated tumorigenesis. Translational Relevance Ovarian clear cell carcinoma often arises in association with endometriosis, yet the biological transition between these lesions remains poorly understood. Using spatial transcriptomics in matched tumor and adjacent endometriosis from Japanese and UK cohorts, we showed that endometriosis is characterized by inflammatory and antigen-presentation features, whereas tumor regions showed chromatin-organization and oncogenic transcriptional states. These patterns were largely maintained irrespective of ARID1A status and geographic background. In addition, spatial deconvolution suggested differences in local immune composition, with tumor regions showing relatively greater neutrophil- and T cell-associated signals. Together, our data suggest that OCCC and coexisting endometriosis share a spatially linked tissue context, but that tumor regions have distinct transcriptional profile and microenvironment that may be involved in the malignant transformation and inform interpretation of molecular classification in endometriosis-associated OCCC.

e17613 Background: Recently, omentum has been suggested to be immunologically active. Therefore, we investigated the effect of prior omentectomy on the efficacy of lenvatinib + pembrolizumab (LP) therapy in patients with endometrial cancer (EC). Methods: This retrospective study included 95 patients with recurrent EC treated with LP between December 2021 and March 2025 at our institutions. The primary outcomes were progression-free survival (PFS) and overall survival (OS). Multivariable Cox regression analyses included factors such as omentectomy status, MMR status, FIGO stage (I/II or III/IV), histology (endometrioid or others), platinum-free interval (PFI) (<6 or ≥6 months) and the number of prior regimens (1 or ≥2). Results: Overall, 95 patients were enrolled in the study (omentectomy group, 50; no-omentectomy group, 45). Moreover, six patients in the no-omentectomy group, did not undergo primary surgery and predominantly presented with stage IV disease. Molecular profiling was used to identify 9 dMMR and 86 pMMR tumors. Advanced stage (III/IV), endometrioid histology, PFI <6 month, and ≥2 prior regimens were observed in 64%, 42%, 64%, and 30% of the patients in the omentectomy group and 58%, 60%, 60%, and 31% of the patients in the no-omentectomy group. Patients in the no-omentectomy had a significantly longer median PFS (15.4 vs. 8.2 months; p = 0.001) and OS (34.9 vs. 21.7 months; p = 0.090). Multivariable analysis revealed that omentectomy was independently associated with shorter PFS (HR 2.18; 95% CI, 1.23–3.88; p = 0.008), but was not an independent predictor of OS (HR 1.11; 95% CI 0.58–2.12; p = 0.750) [Table]. Histology-specific analyses of the major subtypes, including endometrioid carcinoma ( n = 48), serous carcinoma ( n = 20), and carcinosarcoma ( n = 18), revealed that omentectomy was associated with more favorable outcomes only in patients with serous carcinoma. Therefore, further analysis, excluding patients with serous carcinoma, was performed. In this non-serous cohort, multivariable Cox regression analyses demonstrated that omentectomy remained independently associated with shorter PFS (HR 3.29; 95% CI, 1.69–6.41; p < 0.001) and had a trend toward shorter OS (HR 1.99; 95% CI, 0.93–4.26; p = 0.076). Conclusions: Patients without prior omentectomy had better outcomes following LP therapy. Thus, omentum may contribute to antitumor immune regulation. Progression-free survival Overall survival Variables HR 95% CI p -value HR 95% CI p -value Omentectomy status OMTx vs No-OMTx 2.18 1.23–3.88 0.008 1.11 0.58–2.12 0.750 MMR status dMMR vs pMMR 0.36 0.13–1.00 0.051 0.19 0.04–0.87 0.032 FIGO stage III/IV vs I/II 1.00 0.58–1.75 0.992 1.48 0.74–2.98 0.272 Histology non-endometrioid vs endometrioid 1.09 0.63–1.88 0.768 2.47 1.22–5.00 0.012 PFI ≥6 vs <6 months 0.47 0.26–0.85 0.012 0.34 0.15–0.77 0.009 Number of prior regimens ≥2 vs 1 0.91 0.51–1.61 0.744 1.03 0.52–2.05 0.937

OBJECTIVE:Little is known about patients with advanced ovarian cancer (AOC) who do not undergo cytoreductive surgery but receive maintenance therapy with poly (ADP-ribose) polymerase inhibitors (PARPis). We aimed to investigate the efficacy of PARPi maintenance therapy in nonsurgical patients. METHODS:We retrospectively analyzed the clinical records of patients newly diagnosed with stage III/IV ovarian cancer between April 2014 and March 2024 who did not undergo cytoreductive surgery and responded to first-line chemotherapy. The Kaplan-Meier method was used to estimate the survival outcomes. Adjustment for confounding using propensity score matching (PSM) was performed to compare progression-free survival (PFS) and overall survival (OS) between patients who received PARPi maintenance therapy and those who did not. RESULTS:Eighty-six patients (11.5%) out of 751 newly diagnosed AOC patients were eligible; of these patients, 52 (60.5%) had received PARPi maintenance therapy, and 34 (39.5%) had not. The median PFS and OS for the PARPi maintenance group were 9.8 months (95% confidence interval [CI]=7.2-14.8 months) and 29.2 months (95% CI=21.9 months-not available), respectively. After PSM (27 matched pairs), PFS was prolonged in the PARPi maintenance group compared to the no PARPi maintenance group (log-rank test p<0.001; hazard ratio [HR]=0.34; 95% CI=0.18-0.64). Similarly, OS was prolonged in the PARPi maintenance group compared to the no PARPi maintenance group (p=0.019; HR=0.45; 95% CI=0.23-0.89). CONCLUSION:Patients with AOC who are not undergoing cytoreductive surgery may be a crucial population that benefits from PARPi maintenance therapy.

OBJECTIVE:Growing evidence suggests potential ethnic and geographical variations in chemotherapy efficacy. The CA125 ELIMination rate constant K score is a pragmatic and reproducible indicator of tumor chemosensitivity in newly diagnosed ovarian cancer. We compared ELIMination rate constant K distributions and prognostic performances between patients enrolled in Japanese and Western trials who had stage III/IV serous ovarian cancer from the Gynecologic Cancer InterGroup individual-patient-data Meta-Analysis in OVarian cancer. METHODS:The ELIMination rate constant K values were previously estimated for 5884 women receiving first-line chemotherapy for ovarian cancer. Data from 246 women enrolled in the Japanese JGOG-3016 trial were compared to 2561 patients from Western trials. ELIMination rate constant K was analyzed as a binary variable (favorable ≥1.0 vs unfavorable <1.0). Prognostic value for progression-free survival and overall survival was assessed using univariable and multi-variable models. A standardization cut-off specific to patients enrolled in the Japanese trial was explored using maximally selected rank statistics. RESULTS:KELIM was significantly higher in patients enrolled in the Japanese trial (median 0.071 day-1 vs 0.056 day-1; p <.0001). Using the standard cut-off, favorable ELIMination rate constant K was independently associated with improved progression-free survival (hazard ratio 0.59, 95% confidence interval 0.43 to 0.83) and overall survival (hazard ratio 0.53, 95% confidence interval 0.36 to 0.79) in patients from the Japanese trial. Applying the exploratory cut-off of 0.07 day-1 strengthened prognostic discrimination (progression-free survival: hazard ratio 0.35, 95% confidence interval 0.25 to 0.49, p <.0001; overall survival: hazard ratio 0.40, 95% confidence interval 0.26 to 0.61, p <.0001). CONCLUSIONS:Potential higher ELIMination rate constant K-assessed chemosensitivity is suggested in patients from Japan with advanced serous ovarian cancer, warranting further prospective validation and investigation into underlying biological and environmental determinants and implications for personalized therapeutic strategies.

Objective: Radical trachelectomy (RT) is an established fertility-preserving treatment for selected patients with early-stage cervical cancer; however, optimal patient selection remains controversial, particularly in the presence of lymph node metastasis or larger tumors. We evaluated the prognostic significance of quantitative lymph node tumor burden and tumor size in patients scheduled for RT.Methods: We retrospectively analyzed 44 consecutive patients with early-stage cervical cancer scheduled for RT. Lymph node status was classified into no metastasis, micrometastasis/oligometastasis, and macrometastasis. Progression-free survival (PFS) was assessed using Kaplan–Meier analysis and Cox proportional hazards models. Subgroup analyses evaluated perioperative treatment strategies, including neoadjuvant chemotherapy followed by RT (NAC-RT).Results: RT was completed in 40 patients (91%), while 4 required conversion to radical hysterectomy due to nodal metastasis. During follow-up, recurrence occurred in five patients. Macrometastatic lymph node involvement (HR 7.94, 95% CI 1.32–47.89, p = 0.024) and tumor size ≥3 cm (HR 7.72, 95% CI 1.29–46.27, p = 0.025) were significantly associated with recurrence. No recurrence was observed in patients with micrometastasis/oligometastasis. Among NAC-RT patients (n = 4), no recurrence occurred. Fertility outcomes were favorable, with 15 pregnancies, including 9 live births and 1 ongoing pregnancy. Notably, two patients with stage IIIC1 low-volume nodal disease achieved pregnancy following adjuvant systemic chemotherapy without recurrence.Conclusions: Recurrence after RT is primarily determined by lymph node tumor burden and tumor size rather than nodal positivity alone. Selected patients with limited nodal disease may safely undergo fertility-preserving surgery with individualized systemic therapy, thereby avoiding pelvic radiotherapy and preserving reproductive potential.

Introduction:Energy-based therapies for genitourinary syndrome of menopause (GSM) remain controversial, and evidence for vaginal high-intensity focused ultrasound (HIFU) is limited. The aim of this study was to evaluate the safety and exploratory efficacy of vaginal HIFU in women with GSM. Methods:In this prospective, single-arm, exploratory study, women with GSM underwent vaginal HIFU and were followed for 24 weeks. Women with prior gynecologic surgery or treated malignancy were eligible if ≥6 months had elapsed and clinical stability was confirmed. Patient-reported outcomes included visual analog scale (VAS) scores for GSM symptoms, the Vulvovaginal Symptoms Questionnaire (VSQ), the Female Sexual Function Index (FSFI), and the International Consultation on Incontinence Questionnaire-Short Form (ICIQ-SF). Objective measures included the Vaginal Health Index (VHI), vaginal pressure, pelvic organ prolapse quantification, vaginal pH, and vaginal microbiome profiling. The primary endpoint was the percent change from baseline to 12 weeks in the VAS score of the participant-identified most bothersome GSM symptom. Results:Eighteen women comprised the full analysis set. The primary endpoint showed a reduction in symptom severity (mean percent change -67.7%; 95% confidence interval [CI], -87.6% to -47.7%). Individual VAS scores decreased over time and were generally maintained throughout follow-up. The VSQ improved at 24 weeks (-40.4%; 95% CI, -64.6% to -16.2%), and the ICIQ-SF improved at 12 weeks (-29.0%; 95% CI, -54.6% to -3.4%), although this improvement was not sustained at 24 weeks. Total FSFI scores did not change. Improvements were observed in VHI and vaginal pressure, while vaginal pH and microbiome composition remained stable. No Grade ≥3 adverse events occurred. Discussion:In this exploratory study, vaginal HIFU was associated with improvements in the most bothersome GSM symptom and selected objective measures without serious adverse events. However, given its single-arm design and small sample size, no definitive conclusions regarding its efficacy or safety can be drawn, and further studies are needed to elucidate the mechanisms of action, optimize treatment parameters, characterize the safety profile, and determine the clinical utility of vaginal HIFU.

Immune checkpoint inhibitors (ICIs) have transformed cancer treatment by leveraging the immune system's capacity to fight gynecologic cancer. This review summarizes the current status and future perspectives of ICIs in the treatment of cervical, endometrial, and ovarian cancers and rare tumors. ICIs have demonstrated significant efficacy in tumors with high tumor mutational burden and immune markers such as PD-L1 expression and microsatellite instability. In cervical cancer, the integration of ICIs has shown promise at various stages of treatment, including advanced and recurrent settings. In endometrial cancer, molecular classification has facilitated targeted immunotherapy strategies, with notable success in mismatch repair-deficient (dMMR) tumors. However, challenges remain in the treatment of microsatellite stable endometrial and epithelial ovarian cancers due to their relatively low immunogenicity. Combination therapies, including ICIs with angiogenesis inhibitors, poly (ADP-ribose) polymerase (PARP) inhibitors, or chemotherapy, are being actively investigated to improve response rates. Several phase II and case series showed promising response to ICIs in vulvar/vaginal cancer and gestational trophoblastic neoplasia, though the efficacy in genital tract melanoma is still unclear. Despite these advances, the management of immune-related adverse events and the identification of reliable biomarkers for patient selection remain critical. ICIs are poised to redefine the therapeutic landscape of gynecologic oncology, offering hope for improved outcomes and personalized treatment strategies.

TPS5626 Background: The patients with an advanced epithelial ovarian cancer (EOC) treated with a neo-adjuvant platinum-based chemotherapy who are not amenable to a complete interval debulking surgery (IDS) due to a poorly chemosensitive disease (CA-125 KELIM score <1.0) have a particular poor prognosis (~20% overall survival at 5 years). Several studies suggested that these patients may have a benefit from a chemotherapy densification with the weekly dose-dense carboplatin-paclitaxel regimen. Methods: SALVOVAR trial (NCT06476184) is an academic pragmatic open-label multicentre international randomized phase III trial, including stage III-IV high-grade EOC patients who present 2 poor prognostic features after 3-4 cycles of standard neo-adjuvant chemotherapy with carboplatin-paclitaxel administered every 3 weeks: 1) an unfavorable standardized KELIM score <1.0; and 2) a disease considered to be not amenable to a complete IDS. The enrolled patients are randomly allocated (ratio 1:1) to an experimental arm (weekly dose-dense regimen: carboplatin AUC5 and paclitaxel 80 mg/m 2 on day1, day8, and day15, with 3 week cycles) or a control arm (continuation of the standard regimen given every 3 weeks) for 3 cycles. Bevacizumab will be added at investigator discretion. The stratification factors are: Planned administration of bevacizumab (yes, vs no); BRCA mutation (yes, vs no/unknown); and KELIM score strate (moderately unfavorable ≥0.7, vs very unfavorable <0.7). The objective is to show the superiority of the experimental arm with 2 co-primary endpoints: 1) percentage of patients achieving late complete cytoreductive surgery after chemotherapy densification (15% increase), and of overall survival (Hazard-ratio, 0.61). 250 patients will be randomized. The secondary endpoints include overall response rate, progression-free survival, percentage of patients receiving PARP inhibitor and safety. Social human sciences are planned with assessment of the patient/physician perceptions in the shared-decision-making; quality-of-life/patient-reported-outcomes; medico-economic investigation, along with surgical definition of standardized criteria for non-resectability, and inventory of BRCA/homologous-recombination assays used in real-life. The trial is activated in France and Japan. It will be open in United Kingdom, The Netherlands, Italy, Czech Republic, Slovenia, Hungary, Slovakia, and Israel. The recruitment started in July 2024. On January 15 2024, 62 patients had been pre-screened and 18 patients had been randomized. SALVOVAR trial is funded by a European Union HORIZON-MISS-CANCER-2022-01 research program, sponsored by ARCAGY-GINECO (France), and coordinated by Lyon University Hospital (HCL, France). Clinical trial information: NCT06476184 .

Objective: Adult-type granulosa cell tumors of the ovary (aGCTs) show ambiguous morphology and may be misdiagnosed as other tumors. Recently, heterozygous FOXL2 C402G mutations and TERT promoter C228T mutation have been reported as diagnostic and prognostic biomarkers of aGCTs. The objective of this study was to identify the characteristics of true aGCT cohort using these biomarkers in 72 aGCT samples. Methods: FOXL2 and TERT promoter mutational statuses of 64 primary and matched 8 recurrent aGCT samples were assessed. Non-aGCTs were excluded by the combination of FOXL2 mutational analysis and the pathological review. The characteristics and prognosis of molecularly/pathologically confirmed aGCTs (MP-aGCTs) were analyzed. Results: Of 18 FOXL2 wild-type (WT) tumors, 3 were excluded as they were of other histotype. None of 20 samples with the FOXL2 C402G mutation include other histotype. Clinical stage and age were prognostic factors for recurrence. Of the 61 MP-aGCTs, 46 harbored FOXL2 C402G mutation (44 heterozygous, 2 homozygous/hemizygous) and 15 had WT FOXL2. The presence of the FOXL2 mutation was associated with a worse prognosis. The mutational status of the TERT promoter in MP-aGCTs was 10 heterozygous and 51 WT. The TERT promoter mutation was highly identified in older patients and in larger tumors but had no prognostic impact. Conclusion: This is the first study to clearly demonstrate its practical application of FOXL2 in the diagnosis of aGCTs. Application of the molecular analysis to a large aGCT cohort is crucial for understanding true characteristics and establishing novel treatment strategy of this disease.

OBJECTIVE:Despite curative surgery and adjuvant chemotherapy, a significant number of early stage I to II ovarian cancers relapse. The CA125 ELIMination rate constant K (KELIM) is a pragmatic indicator of tumor intrinsic chemosensitivity in advanced epithelial ovarian cancer. We assessed the prognostic value of KELIM in patients with early-stage ovarian cancer, with respect to 5-year recurrence-free survival and overall survival, using the Meta-Analysis in Ovarian Cancer, which is the Gynecologic Cancer InterGroup individual patient-data meta-analysis of randomized trials evaluating different adjuvant chemotherapy regimens. METHODS:Individual patient KELIM values were previously estimated in 5884 patients from the Meta-Analysis in Ovarian Cancer. The prognostic value of KELIM was assessed using univariable & multivariable analyses in patients with resected International Federation of Gynecology and Obstetrics stage I and II disease. RESULTS:Overall, 1143 patients were identified, including clear cell (46.7%); serous (23.7%); endometrioid (12.4%); and mucinous carcinomas (3.9%). In multivariable analyses, a favorable KELIM score (≥1.0) was associated with higher 5-year recurrence-free survival (68.3% vs 55.9%; HR 0.61, 95% CI 0.48 to 0.77) and 5-year overall survival (80.7% vs 72.8%; HR 0.50, 95% CI 0.36 to 0.68), as was the histological sub-type. In exploratory analyses, KELIM score was a prognostic factor regarding 5-year recurrence-free survival and overall survival across all sub-types (especially clear cell carcinoma and serous, with HR ranging from 0.45 to 0.63) with baseline CA125 ≥15 IU/L, except for mucinous histology. CONCLUSIONS:The pragmatic KELIM score is an independent prognostic factor in patients with a non-mucinous stage I to II ovarian cancer optimally resected and treated with adjuvant chemotherapy. KELIM may help identify the patients at higher risk of relapse and death requiring closer follow-up or treatment intensification.

Background:Patients with epithelial ovarian cancer (EOC) receiving neoadjuvant platinum-based chemotherapy (NACT) who remain ineligible for complete interval cytoreductive surgery (ICS) due to poor chemosensitivity (CA-125 KELIM™ score <1.0) have a poor prognosis (~20% 5-year survival). A weekly dose-dense carboplatin-paclitaxel regimen may improve outcomes in this high-risk subgroup. Objectives:To demonstrate the superiority of a salvage weekly dose-dense carboplatin-paclitaxel regimen over continuation of the standard 3-weekly regimen in poor-prognosis EOC patients after 3-4 cycles of standard NACT. Design:SALVOVAR is a pragmatic, open-label, multicenter, international, randomized phase III trial. Methods and analysis:Patients with stages III-IV high-grade EOC are eligible if they present (1) an unfavorable standardized KELIM score <1.0, and (2) a disease not amenable to complete ICS after 3-4 cycles of standard 3-weekly carboplatin-paclitaxel. Patients are randomized (1:1) to either the experimental arm (dose-dense carboplatin AUC5 day 1 plus paclitaxel 80 mg/m2 on days 1, 8, and 15, every 3 weeks) or the control arm (continuation of the standard regimen) for 3 cycles. Bevacizumab use is allowed at investigator discretion. Stratification factors include planned bevacizumab administration, BRCA mutation status, and KELIM strata. The two co-primary endpoints are (1) improvement in late complete cytoreduction rates (from 5% in the control arm to 20% in the experimental arm), and (2) overall survival (target hazard-ratio, 0.61). Total 250 patients will be randomized. Secondary endpoints include objective response rate, progression-free survival, and safety. Additional planned analyses include quality-of-life, cost-effectiveness, surgical standardization, human sciences, and biology studies. Ethics:The protocol was approved by the national ethics committee and health authorities. Discussion:SALVOVAR will evaluate whether chemotherapy densification improves outcomes in poorly chemosensitive advanced EOC. If positive, this pragmatic strategy could be implemented in large-scale studies, independent of resource setting. Trial registration:ClinicalTrials.gov NCT06476184 (June-2024). Available at: https://clinicaltrials.gov/study/NCT06476184.

Cancer diagnoses in patients of reproductive age require balancing urgent oncological treatment with the need to preserve fertility. This FIGO Best Practice Advice outlines key considerations for fertility management in this population given the rising cancer incidence among young women and the reproductive risks posed by cancer treatments. The guidance evaluates the impact of chemotherapy, radiotherapy, surgery, and emerging therapies-such as targeted agents and immunotherapies-on gonadal function and fertility. Established fertility preservation methods, including oocyte/embryo cryopreservation, sperm banking, and ovarian tissue freezing, are detailed alongside barriers to their adoption, such as cost and limited access. Early collaborative counseling with oncologists and fertility specialists is central to addressing timelines, psychological impacts, and priorities. Post-treatment pathways, including assisted reproduction and surrogacy, are also explored. The guidance stresses the importance of integrating fertility-sparing interventions and fertility preservation into cancer care while advocating for equitable access to resources. Further research is needed to refine preventive interventions, evaluate long-term outcomes, and expand options for survivors globally. By prioritizing fertility preservation within oncological care, healthcare providers can better support the holistic needs of young individuals facing cancer.

Postpartum bleeding is commonly addressed with uterine compression using absorbable sutures; however, possible complications associated with non-absorbable threads are not well documented. We present a case in which a non-absorbable thread was mistakenly used to perform uterine compression sutures to treat postpartum uterine bleeding. Non-invasive methods, such as magnetic resonance imaging and hysteroscopy, failed to assess the sutures. As the patient wanted to have another child, diagnostic laparoscopy was performed one year later; the suture thread was still present, and a gap had formed between the thread and uterus, posing a risk for intestinal obstruction. The suture thread was successfully removed, and fertility treatment was resumed. This case highlights the dangers of using a non-absorbable thread for uterine compression sutures and the importance of promptly removing these sutures to avoid complications. Simulation training and pre-prepared suture materials are essential to prevent such errors. This case highlights the clinical risks associated with the use of non-absorbable sutures for uterine compression and the necessity of prompt identification and intervention to protect reproductive health.

Evidence regarding chemosensitivity to different therapeutic regimens in epithelial ovarian cancer (EOC) remains limited. This study aimed to investigate EOC implementation in daily clinical practice and reveal favorable regimens for EOC among Japanese patients. We retrospectively collected clinical data of patients newly diagnosed with EOC from 2012 to 2021 at our affiliated institutions. We evaluated overall survival (OS) and progression-free survival (PFS) of conventional paclitaxel plus carboplatin (TC) vs. dose-dense TC (ddTC) according to the eligibility of GOG262 and JGOG3016 and those with bevacizumab (BEV) vs. without BEV based on GOG218. Further, we evaluated OS and PFS of ddTC and ddTC + BEV to TC + BEV among patients with stage III/IV. The ddTC group (n = 402) demonstrated longer PFS and OS than the TC group (n = 165) (adjusted hazard ratios [aHRs] [95

PARP inhibitors have changed the management of advanced high-grade epithelial ovarian cancer (EOC), especially homologous recombinant (HR)-deficient advanced high-grade EOC. However, the effect of PARP inhibitors on HR-proficient (HRP) EOC is limited. Thus, new therapeutic strategy for HRP EOC is desired. In recent clinical study, the combination of PARP inhibitors with anti-angiogenic agents improved therapeutic efficacy, even in HRP cases. These data suggested that anti-angiogenic agents might potentiate the response to PARP inhibitors in EOC cells. Here, we demonstrated that anti-angiogenic agents, bevacizumab and cediranib, increased the sensitivity of olaparib in HRP EOC cells by suppressing HR activity. Most of the γ-H2AX foci were co-localized with RAD51 foci in control cells. However, most of the RAD51 were decreased in the bevacizumab-treated cells. RNA sequencing showed that bevacizumab decreased the expression of CRY1 under DNA damage stress. CRY1 is one of the transcriptional coregulators associated with circadian rhythm and has recently been reported to regulate the expression of genes required for HR in cancer cells. We found that the anti-angiogenic agents suppressed the increase of CRY1 expression by inhibiting VEGF/VEGFR/PI3K pathway. The suppression of CRY1 expression resulted in decrease of HR activity. In addition, CRY1 inhibition also sensitized EOC cells to olaparib. These data suggested that anti-angiogenic agents and CRY1 inhibitors will be the promising candidate in the combination therapy with PARP inhibitors in HR-proficient EOC.