International Journal of Gynecological Cancer最新文献

{"title":"Homologous recombination-deficient high-grade serous ovarian cancers exhibit distinct morphological features.","authors":"Kattreen Hanna, Gabriel Levin, Miryam Al Nasir, Roxanne Lacouline-Boulanger, Lawrie Shahbazian, Sarah-Slim Diwan, Joyce Li, Denia Hamidi, Léa Stephan, Mina Hmimas, Nicole Zhang, Phuong-Nam Nathalie Nguyen, Lara Richer, Karine Jacob, Andrea Gomez, Reitan Ribeiro, Victoria Mandilaras, Laurence Bernard, Xing Zeng, Robert A Soslow, Lucy Gilbert, Shuk On Annie Leung, Basile Tessier-Cloutier","doi":"10.1016/j.ijgc.2026.104690","DOIUrl":"10.1016/j.ijgc.2026.104690","url":null,"abstract":"<p><strong>Objective: </strong>Access to homologous recombination testing remains limited in many centers. We aim to correlate the morphology and immunophenotype of high-grade serous ovarian carcinoma with homologous recombination statuses.</p><p><strong>Methods: </strong>A retrospective analysis of a high-grade serous ovarian carcinoma tumors with known homologous recombination status. A pathological review of morphology was performed for each tumor, along with immunohistochemical profiling. Tumor morphology was classified as (1) solid, pseudo-endometrioid, or transitional (2) micropapillary or nested.</p><p><strong>Results: </strong>Overall, 81 tumors were included. The median age was 62 (interquartile range; 52-71). Of those, 27 (33.3%) tumors were BRCA1mut, 19 (23.5%) were BRCA2mut, 15 (18.5%) tumors had no BRCA1 or BRCA2 mutations but exhibited a genomic instability score ≥42 and were classified as BRCA1/2-wild-type with homologous recombinant deficient. The remainder 20 (24.7%) cases were homologous recombinant proficient. The proportion of tumors with solid transitional-like morphology was higher in BRCA1 (12/21, 57%) and BRCA2 (12/18, 67%) compared to the tumors with homologous recombinant proficient (3/17, 18%), p =.019. When stratified by genomic instability score, tumors with low score (genomic instability score <26) exhibited 0% solid transitional-like morphology versus 43% solid transitional-like morphology in high-score (genomic instability score >26), p =.03. PAX8 diffuse expression was detected in 71% of BRCA1, 65% of BRCA2, 92% of BRCA-wild-type homologous recombinant deficient tumors, and 100% of homologous recombinant proficient tumors, p =.071. The proportion of diffuse expression was higher in homologous recombinant proficient (100%) versus BRCA2 (65%) (Bonferroni-adjusted pairwise comparisons).</p><p><strong>Conclusions: </strong>Homologous recombinant deficient tumors are associated with the solid transitional-like morphology, with the BRCA1/2-mutated homologous recombinant deficient cases showing the strongest correlation. Genomic instability score alone may not fully capture the spectrum of homologous recombinant deficient-related phenotypes. The variation in solid transitional-like morphology features among BRCA1- or BRCA2-mutated, BRCA1/2- wild-type with homologous recombinant deficient, and homologous recombinant proficient cases may reflect the diverse biological spectrum of different homologous recombination alterations.</p>","PeriodicalId":14097,"journal":{"name":"International Journal of Gynecological Cancer","volume":" ","pages":"104690"},"PeriodicalIF":5.4,"publicationDate":"2026-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147837638","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Improving gynecological pathology access with the OpenFlexure Microscope.","authors":"Joe Knapper, Kelsey Hummel, Julian Stirling, William Wadsworth, Elisée Hategekimana, Fábio Coracin, Gustavo Teixeira, Beth Probert, Daniel Rosen, Richard Bowman","doi":"10.1016/j.ijgc.2026.104680","DOIUrl":"10.1016/j.ijgc.2026.104680","url":null,"abstract":"","PeriodicalId":14097,"journal":{"name":"International Journal of Gynecological Cancer","volume":" ","pages":"104680"},"PeriodicalIF":5.4,"publicationDate":"2026-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147855673","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"From evidence to practice: national patterns of hyperthermic intra-peritoneal chemotherapy use and survival in advanced ovarian cancer.","authors":"Gabriel Levin, Lucy Gilbert, Reitan Ribeiro, Rene Pareja, Raanan Meyer, Pedro T Ramirez","doi":"10.1016/j.ijgc.2026.104762","DOIUrl":"10.1016/j.ijgc.2026.104762","url":null,"abstract":"<p><strong>Objective: </strong>This study aimed to characterize national trends in hyperthermic intra-peritoneal chemotherapy utilization and associated survival outcomes among patients with stage III high-grade serous ovarian cancer undergoing interval cytoreductive surgery following the OVHIPEC-1 trial.</p><p><strong>Methods: </strong>A retrospective cohort study using the National Cancer Database. Women diagnosed with stage III high-grade serous ovarian cancer who underwent interval cytoreductive surgery, with or without hyperthermic intra-peritoneal chemotherapy, between 2004 and 2022 were included. hyperthermic intra-peritoneal chemotherapy utilization trends were assessed relative to the 2018 OVHIPEC-1 publication. Survival was analyzed with Kaplan-Meier and Cox proportional-hazards models adjusted for age, stage, and comorbidity. Sensitivity analysis was performed for propensity-matched cohort, and for a cohort restricted to patients treated at centers performing hyperthermic intra-peritoneal chemotherapy.</p><p><strong>Results: </strong>Among 15,946 women included, 335 (2.1%) received hyperthermic intra-peritoneal chemotherapy. Hyperthermic intra-peritoneal chemotherapy utilization was 1.4% before 2018 and 3.2% thereafter, with a 61% relative increase from 2018 to 2022, and an average annual percent change increase of 12.6% (p < .001). The median overall survival for hyperthermic intra-peritoneal chemotherapy cases was 66 months (95% confidence interval 56.7 to 75.2) versus 42 months (95% confidence interval 41.2 to 42.7), log rank p < .001. Cox regression adjusted for age, race, residual disease, and Charlson-Deyo comorbidity score-hyperthermic intra-peritoneal chemotherapy was associated with reduced risk of death; hazard ratio 0.71 (95% confidence interval 0.59 to 0.84). Following propensity matching for patients age, race, insurance type, median income, residual disease, and comorbidity score-hyperthermic intra-peritoneal chemotherapy was associated with a significantly longer median overall survival; 66 months (95% confidence interval 56.7 to 75.2) versus 45 months (95% confidence interval 39.9 to 50.1), log rank p = .013. When the analysis was restricted to patients treated at centers performing hyperthermic intra-peritoneal chemotherapy, it was associated with a significantly longer median overall survival; 66 months (95% confidence interval 56.7 to 75.2) versus 44 months (95% confidence interval 42.5 to 45.4), log rank p < .001. Hyperthermic intra-peritoneal chemotherapy was associated with a longer hospital stay and higher rates of 30-day readmission and mortality.</p><p><strong>Conclusions: </strong>Hyperthermic intra-peritoneal chemotherapy adoption, although limited nationally, has increased modestly since OVHIPEC-1, with probable survival benefits for selected patients. Translating pivotal trial evidence into widespread clinical practice continues to face implementation barriers.</p>","PeriodicalId":14097,"journal":{"name":"International Journal of Gynecological Cancer","volume":" ","pages":"104762"},"PeriodicalIF":5.4,"publicationDate":"2026-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148175815","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Platinum sensitivity: is time still enough?","authors":"Letícia Vecchi Leis, Leticia de Mello Graziano, Fernanda Moraes Schroeder, Aline Monte Sá, Samantha Cabral Severino da Costa","doi":"10.1016/j.ijgc.2026.104793","DOIUrl":"10.1016/j.ijgc.2026.104793","url":null,"abstract":"","PeriodicalId":14097,"journal":{"name":"International Journal of Gynecological Cancer","volume":"36 9","pages":"104793"},"PeriodicalIF":5.4,"publicationDate":"2026-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148360651","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Early bird drinks fresh water: should chronoimmunotherapy be explored in gynecologic cancers?","authors":"Diego Lopes Paim Miranda, Mariana Carvalho Gouveia, Mariana Scaranti","doi":"10.1016/j.ijgc.2026.104812","DOIUrl":"10.1016/j.ijgc.2026.104812","url":null,"abstract":"","PeriodicalId":14097,"journal":{"name":"International Journal of Gynecological Cancer","volume":"36 9","pages":"104812"},"PeriodicalIF":5.4,"publicationDate":"2026-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148396613","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Clinical and pathological outcomes of brachytherapy application for the treatment of high-grade vaginal squamous intraepithelial lesions: a systematic review.","authors":"Carlos Felipe Durán Méndez, Juan Carlos Mendieta Redondo, Juan Sebastián Obando Rodríguez, Emmanuel Sánchez Díaz, Jonathan Peralta-Jiménez, Santiago Vieira-Serna, Carolina Morante-Caicedo, Núria Agustí, Santiago Ardila Giraldo, John Edwin Feliciano-Alfonso, Juliana Rodríguez, René Pareja","doi":"10.1016/j.ijgc.2026.104876","DOIUrl":"10.1016/j.ijgc.2026.104876","url":null,"abstract":"<p><strong>Objective: </strong>To evaluate the efficacy and safety of intracavitary brachytherapy for high-grade vaginal squamous intraepithelial lesions (HSIL/VaIN2-3) and clarify its role and dose-fractionation within the therapeutic algorithm.</p><p><strong>Methods: </strong>We conducted a Preferred Reporting Items for Systematic Reviews and Meta-Analyses 2020-compliant systematic review registered in International Prospective Register of Systematic Reviews (CRD420261292798). MEDLINE, Embase, and CENTRAL were searched from inception to February 2026 for clinical trials, analytical observational studies, and case series that included at least 5 women with biopsy-proven HSIL/VaIN2-3 treated with any brachytherapy modality. Two reviewers independently screened records, selected studies, and extracted data on local control, persistence, recurrence, progression to invasive cancer, and acute and late toxicity; methodological quality was appraised with the Joanna Briggs Institute case-series checklist.</p><p><strong>Results: </strong>Ten retrospective series comprising 225 women with vaginal intraepithelial neoplasia (214 HSIL/VaIN2-3) treated with low-, medium-, or high-dose-rate intracavitary brachytherapy were included. Median age ranged from 56 to 63 years, and follow-up duration from 26 to 127 months; most patients had prior cervical intraepithelial neoplasia, cervical or endometrial cancer, hysterectomy, or previous local treatments. Across studies, actuarial or crude local control ranged from 85% to 95%; 6 of 225 patients (2.7%) had persistent disease, 3 of 176 patients with vaginal intraepithelial neoplasia-specific data (1.7%) recurred, and 5 of 225 (2.2%) progressed to invasive or microinvasive vaginal carcinoma, usually within 2 to 3 years. Acute toxicity was predominantly grade 1 or 2 urinary, gynecologic, or anorectal and self-limited, whereas relevant late morbidity was mainly vaginal; severe rectal or bladder events were uncommon, but late grade ≥3 vaginal stenosis or ulceration increased at higher equivalent doses.</p><p><strong>Conclusions: </strong>Intracavitary brachytherapy achieves high local control with low persistence, recurrence, and progression rates in women with HSIL/VaIN2-3, particularly with contemporary high-dose-rate regimens around 45 to 55 Gy Equivalent dose in 2Gy fractions (EQD₂) at 3 to 5 mm depth. Given the small, noncomparative, methodologically heterogeneous series and the apparent rise in late vaginal toxicity beyond EQD₂ ≈70 Gy, brachytherapy should be reserved for carefully selected extensive, multifocal, recurrent, post-hysterectomy, or surgically high-risk cases, and future prospective multicenter studies comparing brachytherapy with surgery, laser, and topical treatments and incorporating standardized dosimetry and patient-reported outcomes are warranted.</p>","PeriodicalId":14097,"journal":{"name":"International Journal of Gynecological Cancer","volume":" ","pages":"104876"},"PeriodicalIF":5.4,"publicationDate":"2026-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148712321","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Personalizing endometrial cancer care beyond histology: clinical applications and limits of molecular classification.","authors":"Matteo Marchetti, Eleonora Panizzolo, Giuseppe Caruso, Susanna Delfrati, Teresa L Pan, Tommaso Meschini, Stephanie Gill, Elise Yates, Maria Clara Santía, Paula Mateo-Kubach, Pedro T Ramirez","doi":"10.1016/j.ijgc.2026.104882","DOIUrl":"10.1016/j.ijgc.2026.104882","url":null,"abstract":"<p><p>Endometrial cancer is a biologically heterogeneous disease whose management has been reshaped by molecular classification. This review summarizes the current evidence supporting the integration of molecular subgroups into prognostic assessment and treatment personalization across stages of disease. The Cancer Genome Atlas classification and its clinically applicable surrogates identify four major molecular categories: POLE-mutated, mismatch repair-deficient, p53-abnormal, and no specific molecular profile tumors. These groups differ substantially in biology, prognosis, treatment sensitivity, and areas of unmet need. POLE-mutated tumors have an excellent prognosis and represent the clearest candidates for adjuvant treatment de-escalation, particularly in early-stage disease. Mismatch repair-deficient tumors show intermediate prognosis but strong sensitivity to immune checkpoint inhibition, which has transformed the management of advanced and recurrent disease and is now being tested in earlier settings. p53-abnormal tumors represent the highest-risk subgroup, requiring multimodal treatment and offering opportunities for biomarker-driven strategies including HER2-directed therapy and DNA damage repair targeting. No specific molecular profile tumors remain the most heterogeneous category, increasingly refined by estrogen receptor status, grade, L1 cell adhesion molecule overexpression, and other biomarkers. Mismatch repair-proficient advanced/recurrent disease should be interpreted as a composite clinical trial population rather than a molecular class. Molecular classification should be integrated with traditional clinicopathologic factors, emerging biomarkers, and local implementation strategies to support equitable, biologically informed treatment selection in endometrial cancer.</p>","PeriodicalId":14097,"journal":{"name":"International Journal of Gynecological Cancer","volume":"36 9","pages":"104882"},"PeriodicalIF":5.4,"publicationDate":"2026-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148792932","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Nodal staging in endometrial cancer: quality of life, patient-reported outcomes, and survivorship.","authors":"Alessandro Buda, Michele Bollino, Jessica Mauro, Jvan Casarin, David Viveros-Carreno","doi":"10.1016/j.ijgc.2026.104787","DOIUrl":"10.1016/j.ijgc.2026.104787","url":null,"abstract":"<p><strong>Objectives: </strong>To evaluate quality of life, patient-reported outcomes, and survivorship after different nodal staging strategies in endometrial cancer, with a focus on lower-extremity lymphedema after sentinel lymph node mapping versus lymphadenectomy.</p><p><strong>Methods: </strong>A systematic literature search was performed according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses checklist. MEDLINE (through PubMed), Embase, and Scopus were searched for studies published from 2010 to 2025. Eligible studies included women with endometrial cancer who underwent surgical nodal staging with sentinel lymph node mapping, lymphadenectomy, or combined approaches and reported validated quality-of-life or patient-reported outcomes.</p><p><strong>Results: </strong>Nine comparative studies including 3298 patients treated between 2006 and 2023 were included. Sentinel lymph node mapping alone was performed in 1334 women, 1508 underwent lymphadenectomy with or without sentinel lymph node mapping, and 456 underwent hysterectomy alone. Patient-reported lower-extremity lymphedema was consistently less frequent after sentinel lymph node mapping than after lymphadenectomy. Reported lymphedema prevalence ranged from 2% to 36% after sentinel lymph node mapping versus 21% to 51% after lymphadenectomy. Studies using multi-variable analyses consistently identified more extensive nodal dissection as an independent predictor of increased lymphatic morbidity. Global quality-of-life scores showed no consistent differences between nodal staging strategies; however, symptom-specific and functional outcomes, particularly lower-extremity symptoms and physical functioning, more often favored sentinel lymph node mapping. Considerable heterogeneity was observed in surgical approach, outcome measures, and timing of assessment.</p><p><strong>Conclusion: </strong>Although differences in global quality of life remain inconsistent, sentinel lymph node mapping appears to reduce patient-reported lymphatic morbidity compared with more extensive nodal dissection. These findings support the integration of patient-reported outcomes into nodal staging decision-making and reinforce the survivorship advantages of less extensive surgical staging strategies in endometrial cancer.</p>","PeriodicalId":14097,"journal":{"name":"International Journal of Gynecological Cancer","volume":"36 9","pages":"104787"},"PeriodicalIF":5.4,"publicationDate":"2026-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148420801","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Not all artificial intelligence large language models are created equal: heterogeneous performance in therapeutic decision-making for recurrent epithelial ovarian cancer.","authors":"Fulvio Borella, Stefano Fucina, Pietro Denti, Niccolò Gallio, Luca Bertero, Antonino Ditto, Isabelle Ray-Coquard, Nicolas Chopin, Domenico Ferraioli, Stefano Cosma","doi":"10.1016/j.ijgc.2026.105598","DOIUrl":"https://doi.org/10.1016/j.ijgc.2026.105598","url":null,"abstract":"<p><strong>Objective: </strong>To evaluate the concordance between therapeutic recommendations generated by 3 widely used consumer large language models (Gemini, Microsoft Copilot, and ChatGPT) and the decisions of a multidisciplinary tumor board in the management of the first recurrence of high-grade serous ovarian cancer. Secondary objectives were to characterize recurrent error patterns and to assess the safety of model-generated recommendations using a 3-tier taxonomy.</p><p><strong>Methods: </strong>A retrospective observational analysis was conducted on 44 consecutive patients with a first recurrence of high-grade serous ovarian cancer treated at a tertiary referral center. For each case, an identical, anonymized, structured zero-shot prompt was submitted to the 3 models. The multidisciplinary tumor board decision served as the reference comparator. Overall concordance and concordance for the chemotherapy backbone, maintenance or targeted-agent class, and surgical indication were compared between models using Cochran's Q test and pairwise McNemar tests (Holm-adjusted). Discordant recommendations were categorized as true hallucinations, unsafe, or suboptimal but guideline-concordant.</p><p><strong>Results: </strong>Concordance varied substantially across models (Cochran's Q p<.001): Gemini 77.3% (95% confidence interval 62.2 to 88.5), Microsoft Copilot 36.4% (95% confidence interval 22.4 to 52.2), and ChatGPT 18.2% (95% confidence interval 8.2 to 32.7); Gemini differed significantly from the other 2 models (Holm-adjusted p<.001), whereas the difference between Microsoft Copilot and ChatGPT did not reach significance after adjustment (p=.057). Component-level analysis localized the divergence to systemic therapy: surgical-indication agreement was uniformly high (93.2% to 95.5%, p=.85). All 3 models generated unsafe recommendations for the re-use of poly (ADP-ribose) polymerase) inhibitors in patients with documented prior progression on poly (ADP-ribose) polymerase inhibitor maintenance, with marked differences in frequency (Microsoft Copilot 10, ChatGPT 3, and Gemini 2; 15 of 74 total discordances). The remaining discordances were suboptimal but guideline concordant.</p><p><strong>Conclusions: </strong>Consumer large language models showed heterogeneous and clinically meaningful differences in reproducing Multidisciplinary Tumor Board decisions in recurrent ovarian cancer; none were free of unsafe recommendations. Their current performance does not support independent clinical use, and expert supervision is required to ensure patient safety.</p>","PeriodicalId":14097,"journal":{"name":"International Journal of Gynecological Cancer","volume":"36 11","pages":"105598"},"PeriodicalIF":5.4,"publicationDate":"2026-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149181613","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Intermittent olaparib with neoadjuvant platinum-based chemotherapy in BRCA-mutated un-resectable ovarian cancer: the NUVOLA trial.","authors":"Vanda Salutari, Claudia Marchetti, Elena Giudice, Camilla Nero, Diana Giannarelli, Viola Ghizzoni, Sara Lardino, Carolina Maria Sassu, Barbara Costantini, Giulia Ponti, Gian Franco Zannoni, Giovanni Scambia, Anna Fagotti","doi":"10.1016/j.ijgc.2026.104816","DOIUrl":"10.1016/j.ijgc.2026.104816","url":null,"abstract":"<p><strong>Objective: </strong>Maintenance therapy with poly(adenosine diphosphate-ribose) polymerase inhibitors following first-line platinum-based chemotherapy has improved survival outcomes in patients with BRCA-mutated advanced epithelial ovarian cancer. Although pre-clinical data support a synergistic interaction between poly(adenosine diphosphate-ribose) polymerase inhibitors and platinum agents, the clinical value of their concurrent administration in the neoadjuvant setting remains unclear. This study evaluated the feasibility and efficacy of adding olaparib to neoadjuvant chemotherapy in patients with newly diagnosed BRCA-mutated advanced epithelial ovarian cancer.</p><p><strong>Methods: </strong>This open-label, single-arm phase II study (NCT04261465) enrolled 36 patients with newly diagnosed BRCA-mutated advanced epithelial ovarian cancer. Patients received three cycles of neoadjuvant chemotherapy with weekly carboplatin (area under the curve 2) and paclitaxel (60 mg/m² on days 1, 8, and 15 of a 28-day cycle), administered concurrently with intermittent oral olaparib 150 mg twice daily (300 mg/d) on days 1 to 3, 8 to 10, 15 to 17, and 22 to 24. The primary end point was complete pathological response at interval debulking surgery with ≥5 complete pathological responses among 35 patients required for the study to be considered positive. Secondary end points included objective response rate, progression-free survival, overall survival, and safety.</p><p><strong>Results: </strong>Among 35 patients who received at least two cycles of neoadjuvant therapy, complete pathological response was achieved in three patients (8.6%). The overall response rate was 89%, assessed at the completion of neoadjuvant treatment prior to interval debulking surgery. At a median follow-up of 42.9 months, median progression-free survival was 39.7 months (95% confidence interval 22.4 to not reached), while median overall survival was not reached (95% confidence interval 47.6 to not reached). Treatment-related adverse events occurred in 86% of patients. Dose reductions were required in 58%, and treatment discontinuation occurred in 11% of patients.</p><p><strong>Conclusions: </strong>Concurrent administration of olaparib with platinum-based neoadjuvant chemotherapy did not increase complete pathological response. These findings suggest that the benefit of poly(adenosine diphosphate-ribose) polymerase inhibitors in BRCA-mutated advanced epithelial ovarian cancer may be driven mainly by post-chemotherapy maintenance rather than concurrent neoadjuvant use.</p>","PeriodicalId":14097,"journal":{"name":"International Journal of Gynecological Cancer","volume":"36 9","pages":"104816"},"PeriodicalIF":5.4,"publicationDate":"2026-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148420881","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}