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

In epithelial ovarian cancer (EOC), accurate assessment of the lesions is crucial for determining the appropriate treatment strategy. We evaluated artificial intelligence (AI) for detecting peritoneal and small bowel dissemination in EOC using preoperative contrast-enhanced computed tomography (CT). We retrospectively analyzed 227 patients (254 CT scans) with histologically confirmed ovarian, fallopian tube, or peritoneal carcinoma who underwent surgery between October 2019 and December 2024 at two affiliated institutions. The mean patient age was 56.6 years. The FIGO stage was early in 118 cases and advanced in 136 cases. Histology included serous (n = 123) and non-serous (n = 131). The mean CA125 level and peritoneal cancer index (PCI) score were 2,243.9 U/mL and 5.8, respectively. Two AI models were developed: one for peritoneal dissemination (P-Model) and one for small bowel dissemination (SB-Model). Diagnostic performance was evaluated by sensitivity, specificity, and accuracy. For the P-Model, clinical factors were compared between high- and low-accuracy groups. The P-Model achieved 68.75% sensitivity, 85.84% specificity, and 77.30% accuracy; the SB-Model, 86.40%, 77.47%, and 81.93%, respectively. Low AI accuracy was linked to ascites volume, CA125 level, and PCI score. AI-based analysis of preoperative CT demonstrated favorable diagnostic performance for detecting dissemination in patients with EOC.

Understanding the tumor immune microenvironment, especially tumor-infiltrating lymphocytes (TILs), remains crucial in ovarian cancer. However, the distribution and prognostic significance of TILs across histological subtypes and genetic backgrounds remain unclear. As part of the JGOG3025-A1 study, diagnostic slides from 400 cases were collected. Two artificial intelligence-based cell classification models were used to evaluate the spatial distribution of TILs. The TIL score was calculated as the number of TILs divided by the analyzed area, and the immune-inflamed group was defined based on TIL scores. Among histological subtypes, high-grade serous carcinoma (HGSC) exhibited the highest TIL scores, clear cell carcinoma the lowest, and endometrioid carcinoma intermediate values. In HGSC, TIL scores did not significantly differ according to BRCA alteration or homologous recombination deficiency (HRD) status. The HRD/immune-inflamed group had the most favorable prognosis. In the homologous recombination-proficient population, the immune-inflamed group had better progression-free survival, whereas this trend did not appear for overall survival. In analyzes of the relationships between TIL levels and genomic structure, whole-genome doubling was associated with lower TIL infiltration in HRD tumors but showed no association in HRP tumors. In conclusion, HGSC showed the highest amount of TIL infiltration among subtypes, and prognostic stratification can be achieved by integrating pathology-based immunophenotypes and HRD status.

Transcriptomic classification methods have been proposed for ovarian clear cell carcinoma. However, their clinical significance and association with pathologically evaluated tumor-infiltrating lymphocytes (TILs) remain unclear. We established two large transcriptomic datasets and analyzed RNA-sequencing data from 189 (JGOG3025-TR1 cohort) and 38 (Kyoto cohort) ovarian clear cell carcinomas. Representative histopathological slides were also digitized (102 and 38, respectively). Cell types were classified by two state-of-the-art artificial-intelligence models, and TILs were quantified. The transcriptomically defined immune subtype was associated with significantly poor prognosis (hazard ratio, 2.54; 95

OBJECTIVE:This study aimed to investigate the impact of ileostomy on both short- and long-term renal function in patients with advanced ovarian cancer. METHODS:This retrospective, multi-institutional study included patients diagnosed with stage II-IV ovarian cancer who underwent primary or interval debulking surgery with rectal resection at five institutions in Japan between April 2013 and March 2022. We assessed renal function during and up to 12 months following postoperative adjuvant chemotherapy (AC), using estimated glomerular filtration rate (eGFR) values and the incidence of chronic kidney disease (CKD) in patients with or without ileostomy. RESULTS:A total of 215 patients were included in the study, of whom 87 patients (40.5 %) underwent ileostomy. When comparing patients with and without ileostomy, those with ileostomy had a lower eGFR from the first cycle of chemotherapy up to 12 months after AC (p < 0.0001). Additionally, patients who underwent ileostomy were more likely to develop CKD 12 months after AC (p < 0.0001). Logistic regression analysis identified age (p = 0.039), baseline renal dysfunction (p = 0.013), and ileostomy (p < 0.001) as independent risk factors for CKD at 12 months after AC. Furthermore, stoma closure did not result in an improvement in eGFR. In patients who underwent ileostomy, high stoma output (>1500 mL/day) was independently associated with CKD development at 12 months after AC. CONCLUSIONS:In patients with ovarian cancer, ileostomy can impair renal function following AC, and this effect persists even after stoma closure.

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:Advanced ovarian clear cell carcinoma (OCCC) is associated with poor outcomes owing to chemoresistance. Bevacizumab (Bev) is increasingly being used to treat advanced ovarian cancer; however, its efficacy in OCCC remains unclear. This study evaluated the treatment outcomes of frontline bevacizumab chemotherapy in patients with OCCC. METHODS:This retrospective multi-institutional study included patients diagnosed with advanced OCCC at eight institutions in Japan between 2008 and 2018. Patients were categorized into pre and post-market groups based on the Bev approval dates. Progression-free survival (PFS) and overall survival (OS) were analyzed using univariate and multivariate methods. Additionally, patients were classified into Bev-treated (Bev+) and non-Bev-treated (Bev-) groups, and their prognoses were compared. RESULTS:A total of 96 patients were in the pre-market group and 82 in the post-market group. The post-market group had a significantly higher proportion of patients with poor performance status and patients who underwent interval debulking surgery (p<0.01 and p<0.01, respectively). Univariate analysis demonstrated a better PFS in the post-market group (p=0.041). In multivariate analysis, better PFS (hazard ratio [HR]=0.52; p=0.002) and OS (HR=0.47; p=0.002) were observed in the post-market group than in the pre-market group. Bev+ patients had significantly better PFS and OS than Bev- patients in univariate (p<0.001 and p<0.001, respectively) and multivariate analyses (PFS: HR=0.36; p<0.001 and OS: HR=0.21; p=0.001, respectively). CONCLUSION:Incorporating Bev into frontline chemotherapy may improve outcomes in patients with advanced OCCC.

Background: The prognosis of gynecological malignancies has improved with the recent advent of molecularly targeted drugs and immune checkpoint inhibitors. However, these drugs are expensive and contribute to the increasing costs of medical care. Methods: The Japanese Clinical Oncology Group (JCOG) Health Economics Committee conducted a questionnaire survey of JCOG-affiliated facilities from July 2021 to June 2022 to assess the prevalence of high-cost regimens. Results: A total of 57 affiliated facilities were surveyed regarding standard regimens for advanced ovarian and cervical cancers for gynecological malignancies. Responses were obtained from 39 facilities (68.4%) regarding ovarian cancer and 37 (64.9%) concerning cervical cancer, with respective case counts of 854 and 163. For ovarian cancer, 505 of 854 patients (59.1%) were treated with regimens that included PARP inhibitors, costing >500 000 Japanese yen monthly, while 111 patients (13.0%) received treatments that included bevacizumab, with costs exceeding 200 000 Japanese yen monthly. These costs are similar to 20 and similar to 10 times higher than those of the conventional regimens, respectively. For cervical cancer, 79 patients (48.4%) were treated with bevacizumab regimens costing >200 000 Japanese yen per month, similar to 10 times the cost of conventional treatments. Conclusions: In this survey, >70% of patients with ovarian cancer were treated with regimens that included poly (adenosine diphosphate-ribose) polymerase (PARP) inhibitors or bevacizumab; similar to 50% of patients with cervical cancer were treated with regimens containing bevacizumab. These treatments were similar to 10 and similar to 20 times more expensive than conventional regimens, respectively. These findings can inform future health economics studies, particularly in assessing cost-effectiveness and related matters.

Introduction/BackgroundIn advanced ovarian cancer (aOVCa), debulking surgery often involves diverting ileostomy (IL) alongside bowel resection for complete tumor removal. IL can lead to complications, including dehydration, which may jeopardize renal function. We conducted a retrospective study to assess the short- and long-term impact of IL on renal function in these patients.MethodologyWe reviewed patients with newly diagnosed aOVCa who underwent debulking surgery with bowel resection and post-operative platinum chemotherapy (Cx) across four affiliated institutions between April 2012 and March 2022. Using propensity score, we paired cases between IL and non-IL groups based on age, stage, CA125, histological subtype, primary or interval debulking surgery, and residual tumor status. Renal function was assessed using estimated glomerular filtration rate (eGFR, mL/min/1.73m2) at several time points, including baseline, post-surgery, after the third Cx cycle, and 1–3 and 7–12 months after the last Cx dose.ResultsOf the 215 eligible patients, 66 were successfully matched in each group. Baseline eGFR values were comparable (IL: 79.5 vs. non-IL: 80.2, p = 0.8). In the short term, eGFR at 1–3 months post-Cx was significantly lower in the IL group compared to the non-IL group (IL: 59.5 vs. non-IL: 73.8, p < 0.001). In the long term, eGFR at 7–12 months post-Cx was also significantly lower in the IL group (IL: 56.6 vs. non-IL: 70.5, p < 0.001). Additionally, the IL group exhibited a higher prevalence of chronic kidney disease (CKD) classification G3 or higher (IL: 63.8% vs. non-IL: 30.2%, p = 0.003). Among the 35 patients who underwent IL reversal, there was no significant change in eGFR.ConclusionIL is associated with an increased risk of renal impairment, potentially leading to CKD. IL reversal does not appear to significantly improve it.DisclosuresI certify that all my affiliations or financial involvement with any organization or financial conflict with the subject matter discussed in the manuscript are completely disclosed in the acknowledgement section of the manuscript.

Background: Endometriosis-associated ovarian cancer (EAOC) is a well-known type of cancer that arises from ovarian endometrioma (OE). OE contains iron-rich fluid in its cysts due to repeated hemorrhages in the ovaries. However, distinguishing between benign and malignant tumors can be challenging. We conducted a retrospective study on magnetic resonance (MR) relaxometry of cyst fluid to distinguish EAOC from OE and reported that this method showed good accuracy. The purpose of this study is to evaluate the accuracy of a non-invasive method in re-evaluating pre-surgical diagnosis of malignancy by a prospective multicenter cohort study. Methods: After the standard diagnosis process, the R2 values were obtained using a 3T system. Data on the patients were then collected through the Case Report Form (CRF). Between December 2018 and March 2023, six hospitals enrolled 109 patients. Out of these, 81 patients met the criteria required for the study. Results: The R2 values calculated using MR relaxometry showed good discriminating ability with a cut-off of 15.74 (sensitivity 80.6%, specificity 75.0%, AUC = 0.750, p < 0.001) when considering atypical or borderline tumors as EAOC. When atypical and borderline cases were grouped as OE, EAOC could be distinguished with a cut-off of 16.87 (sensitivity 87.0%, specificity 61.1%). Conclusions: MR relaxometry has proven to be an effective tool for discriminating EAOC from OE. Regular use of this method is expected to provide significant insights for clinical practice.

The revised World Health Organization classification of cervical cancer divides adenocarcinomas into human papillomavirus-associated (HPVa) and -independent (HPVi) types; the HPVi type is represented by the gastric type. The treatment outcomes of locally advanced adenocarcinoma (LaAC), based on this classification, are understudied. We investigated the outcomes of patients with HPVa and HPVi LaACs. Data for all consecutive patients with stage IB3 to IIIC1 adenocarcinoma who received treatment at 12 institutions throughout Japan between 2004 and 2009 were retrieved to analyze progression-free and overall survival. Central pathological review classified 103 and 48 patients as having HPVa and HPVi tumors, respectively. Usual- (84%) and gastric- (90%) type adenocarcinomas were the most frequent subtypes. Surgery was the primary treatment strategy for most patients. Progression-free and overall survival of patients with HPVi were worse than those of patients with HPVa (p = 0.009 and 0.032, respectively). Subgroup analysis by stage showed that progression-free survival was significantly different for stage IIB. The current surgical treatment strategy for LaACs is less effective for HPVi tumors than for HPVa tumors, especially those in stage IIB.

Objective Direct oral anticoagulants (DOACs) are increasingly being used for the treatment of cancer-associated venous thromboembolism (CAT). However, there is limited evidence of the efficacy of DOACs for the treatment of gynecological CAT. Thus, this study aimed to investigate the efficacy and safety of edoxaban for the treatment of gynecological CAT using Japanese real-world data. Methods We reviewed the medical records of patients with 371 gynecological cancer who received edoxaban or vitamin K antagonist (VKA) between January 2011 and December 2018. Results Altogether, 211 and 160 patients were treated with edoxaban and VKA, respectively. Fourteen patients (6.8%) in the edoxaban group and 22 (13.8%) in the VKA group showed recurrence of venous thromboembolism (VTE). Cumulative VTE recurrence was not significantly different between the 2 groups (p=0.340). Adverse events occurred in 15 (7.1%) and 11 (6.9%) patients in the edoxaban and VKA groups, respectively (p=0.697). Subgroup analysis of the edoxaban and VKA groups according to different tumor types, including ovarian, endometrial, and cervical cancer, showed equivalent outcomes in terms of VTE recurrence and adverse events. Patients without pulmonary embolism (PE) were mostly omitted from initial unfractionated heparin (UFH) therapy prior to administration of edoxaban. However, this did not increase the recurrence of VTE. Conclusion This study confirmed that edoxaban is effective and safe for the treatment of gynecological CAT. This finding was consistent for different types of gynecological cancer. Additionally, initial UFH therapy prior to the administration of edoxaban may be unnecessary for patients without PE.

BACKGROUND/AIM:We investigated the predictive value of scoring systems of peritoneal disseminations for complete surgery (CS) at primary debulking surgery (PDS) in advanced ovarian cancer.PATIENTS AND METHODS:We retrospectively enrolled eligible patients with clinical stages III or IVA selected for PDS from January 2015 to December 2019. Concern variables were predictive index value (PIV) and peritoneal cancer index (PCI) from operative and pathological reports. Primary endpoints were cutoffs to predict operative completeness using the receiver operating characteristic curve.RESULTS:Among 111 patients, PIV ≥8 and PCI ≥13 were the best predictors of incomplete PDS, including optimal and suboptimal surgeries (AUC=0.821 and 0.855, respectively). CS rates in PIV ≤6 and PCI ≤12 were significantly higher than in PIV ≥8 (89.3% vs. 47.2%; p<0.05) and PCI ≥13 (90.9% vs. 41.2%: p<0.05).CONCLUSION:PIV and PCI are potential predictors for CS at PDS.

5502 Background: Advanced ovarian clear cell carcinoma (ACCC, stage III/IV disease) is a rare tumor characterized by chemoresistance. Bevacizumab (Bev) was approved in November 2013 in Japan and became incorporated in the treatment of advanced ovarian cancer. However, the efficacy of Bev against ACCC remain unknown. We investigated the survival outcomes for ACCC, following first-line chemotherapy with or without Bev. Methods: Patients diagnosed with ACCC at seven institutions between 2008 and 2018 were enrolled in this study. Patients underwent cytoreductive surgery and taxane-carboplatin chemotherapy (78: triweekly regimen; 30: weekly regimen; 25: dose-dense regimen; 12: others) with or without concurrent and maintenance Bev (15 mg/kg/3 weeks). We compared the progression-free survival (PFS) and overall survival (OS) before (group A, n = 102) and after (group B, n = 43) Bev approval, using Kaplan–Meier method and Cox regression model. We excluded patients with poor performance status (PS) in group A, and patients who did not receive Bev due to poor PS or thrombosis in group B. Results: There was no significant difference between two groups in terms of age (p = 0.135) and initial CA125 level (p = 0.674). Thirteen (13%) and 11 (26%) patients had stage IV disease (p = 0.058) and 2 (3%) and 7 (16%) patients were of poor PS (PS ≥2) (p = 0.004) in group A and B, respectively (p = 0.058). More patients (29/43, 67%) in group B were achieved complete resection than in A group (52/102, 51%) (p = 0.068). The median cycle of Bev in B group was 16 (interquartile range: 6-21). The median follow-up time was 36 months. The median PFS increased from 12.5months in A group to 29.7 months in B group (log-rank test: p = 0.023, Wilcoxon test: p = 0.006). The median OS increased from 34.7 months in A group to 51.4 months in B group (log-rank test: p = 0.085, Wilcoxon test: p = 0.027). Multivariate analysis revealed that Bev use (Hazard ratio (HR): 0.54, p = 0.011; HR: 0.54, p = 0.019), PS <2 (HR: 0.33, p = 0.013; HR: 0.29, p = 0.006) and completeness of resection (HR: 0.38, p < 0.001; HR: 0.37, p <0.001) were independent prognostic factors for PFS and OS. Conclusions: Incorporating Bev in first-line chemotherapy may improve PFS in patients with ACCC. [Table: see text]

Objectives The treatment strategy for locally advanced non-squamous cell cervical cancer (non-SCC) remains controversial, with the existence of human papillomavirus (HPV)-independent adenocarcinoma, particularly the gastric-type (GAS), provoking this controversy in recent years given its aggressive nature. We conducted a multi-institutional retrospective study to explore the optimal treatment strategy for non-SCC. Methods Clinical records of patients with stage IB2 to IIB (FIGO2008) non-SCC who underwent primary treatment between 2004 and 2009 were retrieved to analyze treatment outcomes, such as loco-regional progression-free survival (loco-PFS), progression-free survival (PFS), and overall survival (OS). Central pathological review was performed by a panel of gynecologic pathologists. Results A total of 168 patients were enrolled, with the most common histological type being usual-type adenocarcinoma (UEA; n = 87), followed by gastric-type adenocarcinoma (GAS; n = 43). Treatment options included surgery in 147 patients and definitive radiation or concurrent chemoradiotherapy (RT/CCRT) was administered in 21 patients. Older patients tended to receive RT/CCRT (p < 0.001). Surgery promoted greater loco-PFS (HR: 0.47 0 95% CI 0.23–0.96 p = 0.04) and OS (HR: 0.38, 95%CI; 0.20–0.72 p = 0.003) compared to RT/CCRT. Subgroup analysis for UEA with propensity score matching showed that patients with UEA exhibited significantly higher loco- PFS, PFS, and OS with surgery than with RT/CCRT. Patients with GAS showed some radiosensitivity but unsatisfying outcomes regardless of treatment. Conclusions Surgery can be an optimal treatment option for locally advanced non-SCC cancer of the uterine cervix, except for GAS, suggesting the need for establishing a novel treatment strategy for the disease.

• This is the first report of aseptic meningitis due to immune checkpoint inhibitor treatment in endometrial cancer. • The meningitis was severe and relapsed multiple times unlike in other reported cases. • Oncologic outcome was excellent after overcoming this severe adverse event.