Pub Date : 2025-12-10DOI: 10.1016/j.ygyno.2025.11.020
Christina Washington , Bhavana Pothuri , Karen Cadoo , Yvette Drew , Rachel Miller-Garcia , Deborah K. Armstrong , Roisin E. O'Cearbhaill
This Society of Gynecologic Oncology review synthesizes updated data from pivotal trials of poly-ADP-ribose polymerase inhibitors (PARPi) in ovarian cancer. Multiple phase III trials established PARPi as effective maintenance therapy, demonstrating substantial progression-free survival across biomarker-defined subgroups, particularly for patients with BRCA-mutated and homologous recombination-deficient (HRD) ovarian cancer. However, mature overall survival analyses and safety signals prompted the US Food and Drug Administration to narrow indications, while the broader indications were maintained by the European Medicines Agency. We review the current FDA approvals that now prioritize patients with BRCA-mutated and HRD ovarian cancers, underscoring the importance of biomarker stratification and careful patient selection. We discuss the evolving regulatory landscape and potential mechanisms of PARPi resistance.
{"title":"Updates in US Food and Drug Administration approvals for poly-ADP-ribose polymerase inhibitors in Ovarian Cancer: A society of gynecologic oncology clinical practice review","authors":"Christina Washington , Bhavana Pothuri , Karen Cadoo , Yvette Drew , Rachel Miller-Garcia , Deborah K. Armstrong , Roisin E. O'Cearbhaill","doi":"10.1016/j.ygyno.2025.11.020","DOIUrl":"10.1016/j.ygyno.2025.11.020","url":null,"abstract":"<div><div>This Society of Gynecologic Oncology review synthesizes updated data from pivotal trials of poly-ADP-ribose polymerase inhibitors (PARPi) in ovarian cancer. Multiple phase III trials established PARPi as effective maintenance therapy, demonstrating substantial progression-free survival across biomarker-defined subgroups, particularly for patients with <em>BRCA</em>-mutated and homologous recombination-deficient (HRD) ovarian cancer. However, mature overall survival analyses and safety signals prompted the US Food and Drug Administration to narrow indications, while the broader indications were maintained by the European Medicines Agency. We review the current FDA approvals that now prioritize patients with <em>BRCA</em>-mutated and HRD ovarian cancers, underscoring the importance of biomarker stratification and careful patient selection. We discuss the evolving regulatory landscape and potential mechanisms of PARPi resistance.</div></div>","PeriodicalId":12853,"journal":{"name":"Gynecologic oncology","volume":"204 ","pages":"Pages 218-227"},"PeriodicalIF":4.1,"publicationDate":"2025-12-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145742210","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}
Pub Date : 2025-12-10DOI: 10.1016/j.ygyno.2025.12.002
Izildinha Maesta , Valdete Aparecida Ribeiro Silva , Roberto Antonio Araújo Costa , Thays Herbst Carvalho , Mariza Branco-Silva , Antonio Braga , Kevin M. Elias , Ross S. Berkowitz , Neil S. Horowitz
Objective
To compare the effectiveness and safety of home-based versus hospital-based chemotherapy with 8-day methotrexate/folinic acid (MTX/FA) for low-risk gestational trophoblastic neoplasia (GTN).
Methods
Retrospective multiple-cohort study with patients receiving first-line MTX/FA for low-risk GTN at either the Botucatu Trophoblastic Disease Center-UNESP, Brazil (home-based treatment – 80 patients) or the New England Trophoblastic Disease Center, USA (hospital-based treatment - 61 patients), from 1995 to 2020. Follow-up was ≥12 months. Study variables were pre-treatment hCG, FIGO staging/risk score, sustained complete response, failure due to resistance/recurrence/toxicity, number of chemotherapy cycles, time to remission, and survival.
Results
There was no significant difference between treatment settings regarding pre-treatment hCG, GTN stage, sustained complete remission rate (home: 72.5 %, vs. hospital: 78.7 %, p = 0.52), resistance rate (home: 20 % vs. hospital: 15 %, p = 0.56), and rate of toxicity requiring a shift in single-agent chemotherapy (home: 3.5 % vs. hospital: 3.3 %, p = 1.00). The remission rate remained consistent after multivariate adjustment for age and FIGO risk score. However, there was a significant difference in median risk score (home: 2 vs. hospital: 1, p < 0.01) and median number of cycles (home: 3 cycles vs. hospital: 2 cycles; p < 0.01). Time to remission was 14 days longer with home treatment (home: 57 days vs. hospital: 41 days; p < 0.01). All patients survived.
Conclusion
Home- and hospital-based treatments showed similar sustained complete remission rate, with no change in frequency of toxicity-related failure and survival. Low-risk GTN treatment with 8-day-MTX/FA at home is feasible, produces outcomes similar to those observed in a hospital setting and offers a more flexible and patient-centered approach to care.
{"title":"Home-based treatment of low-risk gestational trophoblastic neoplasia with 8-day methotrexate/folinic acid","authors":"Izildinha Maesta , Valdete Aparecida Ribeiro Silva , Roberto Antonio Araújo Costa , Thays Herbst Carvalho , Mariza Branco-Silva , Antonio Braga , Kevin M. Elias , Ross S. Berkowitz , Neil S. Horowitz","doi":"10.1016/j.ygyno.2025.12.002","DOIUrl":"10.1016/j.ygyno.2025.12.002","url":null,"abstract":"<div><h3>Objective</h3><div>To compare the effectiveness and safety of home-based versus hospital-based chemotherapy with 8-day methotrexate/folinic acid (MTX/FA) for low-risk gestational trophoblastic neoplasia (GTN).</div></div><div><h3>Methods</h3><div>Retrospective multiple-cohort study with patients receiving first-line MTX/FA for low-risk GTN at either the Botucatu Trophoblastic Disease Center-UNESP, Brazil (home-based treatment – 80 patients) or the New England Trophoblastic Disease Center, USA (hospital-based treatment - 61 patients), from 1995 to 2020. Follow-up was ≥12 months. Study variables were pre-treatment hCG, FIGO staging/risk score, sustained complete response, failure due to resistance/recurrence/toxicity, number of chemotherapy cycles, time to remission, and survival.</div></div><div><h3>Results</h3><div>There was no significant difference between treatment settings regarding pre-treatment hCG, GTN stage, sustained complete remission rate (home: 72.5 %, vs. hospital: 78.7 %, <em>p</em> = 0.52), resistance rate (home: 20 % vs. hospital: 15 %, <em>p</em> = 0.56), and rate of toxicity requiring a shift in single-agent chemotherapy (home: 3.5 % vs. hospital: 3.3 %, <em>p</em> = 1.00). The remission rate remained consistent after multivariate adjustment for age and FIGO risk score. However, there was a significant difference in median risk score (home: 2 vs. hospital: 1, <em>p</em> < 0.01) and median number of cycles (home: 3 cycles vs. hospital: 2 cycles; p < 0.01). Time to remission was 14 days longer with home treatment (home: 57 days vs. hospital: 41 days; p < 0.01). All patients survived.</div></div><div><h3>Conclusion</h3><div>Home- and hospital-based treatments showed similar sustained complete remission rate, with no change in frequency of toxicity-related failure and survival. Low-risk GTN treatment with 8-day-MTX/FA at home is feasible, produces outcomes similar to those observed in a hospital setting and offers a more flexible and patient-centered approach to care.</div></div>","PeriodicalId":12853,"journal":{"name":"Gynecologic oncology","volume":"204 ","pages":"Pages 235-241"},"PeriodicalIF":4.1,"publicationDate":"2025-12-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145742158","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}
Pub Date : 2025-12-10DOI: 10.1016/j.ygyno.2025.12.001
Bryanna Patterson , Nikita Sinha , Emily Broaddus , Sydney Stocks , William Zamboni , Benjamin B. Albright , Paola Gehrig , Victoria Bae-Jump , Olivia D. Lara
Background
To determine the association between obesity and pembrolizumab response in racially diverse cohort of patients with advanced and recurrent endometrial cancer (EC).
Methods
We conducted a retrospective review of patients with advanced or recurrent endometrial cancer receiving pembrolizumab. Baseline clinical, demographic and cancer characteristics were collected. Progression free survival (PFS) and overall survival (OS) were estimated using the Kaplan–Meier method and modeled via Cox regression. Covariate differences were assessed using the log-rank test.
Results
Among the 179 patients, the median age was 65 years (IQR, 58–71 yrs) and the mean BMI was 33 (SD, 8.5). The cohort consisted of 55 Black patents (31 %) and 112 White patients (63 %); 99 patients (55 %) were obese. Forty-six patients received pembrolizumab alone, and 133 received combination therapy. Higher BMI was associated with shorter PFS (BMI >40: HR 1.91, CI 1.13–3.21, p = 0.014 and BMI 30–40: HR 1.55, CI 1.02–2.35, p = 0.041). In MMR stratified analysis, obesity was associated with lower response rates among patients with MMRp tumors (23.4 %; BMI ≥30 vs 40.0 %; BMI <30), whereas response remained high across BMI categories in MMRd tumors. In the subgroup treated with pembrolizumab and Lenvatinib (n = 79), both White and Black obese experienced worse PFS compared to White non-obese patients (p = 0.021 and p = 0.035, respectively). No significant differences in OS were observed between obese and non-obese groups.
Conclusions
In this diverse cohort, obesity was associated with worse PFS in patients treated with pembrolizumab for EC. MMRp tumors in obese patients had lowest response rates among subgroups. Further studies with long term follow up are needed to elucidate the biological mechanisms linking obesity to immunotherapy outcomes.
背景：在不同种族的晚期和复发子宫内膜癌（EC）患者队列中，确定肥胖与派姆单抗反应之间的关系。方法：我们对接受派姆单抗治疗的晚期或复发子宫内膜癌患者进行了回顾性研究。收集基线临床、人口学和癌症特征。使用Kaplan-Meier方法估计无进展生存期（PFS）和总生存期（OS），并通过Cox回归建模。使用log-rank检验评估协变量差异。结果：179例患者中位年龄65岁（IQR， 58 ~ 71岁），平均BMI为33 （SD, 8.5）。该队列包括55名黑人患者（31%）和112名白人患者（63%）；99例（55%）为肥胖。46例患者单独接受派姆单抗治疗，133例接受联合治疗。BMI越高，PFS越短（BMI bbb40: HR 1.91, CI 1.13-3.21, p = 0.014; BMI 30-40: HR 1.55, CI 1.02-2.35, p = 0.041）。在MMR分层分析中，肥胖与MMRp肿瘤患者较低的缓解率相关(23.4%;BMI≥30 vs 40.0%； BMI结论：在这个多样化的队列中，肥胖与接受派姆单抗治疗EC的患者较差的PFS相关。肥胖患者的MMRp肿瘤在亚组中反应率最低。需要进一步的长期随访研究来阐明肥胖与免疫治疗结果之间的生物学机制。
{"title":"Associations between obesity and outcomes in pembrolizumab-treated endometrial cancer","authors":"Bryanna Patterson , Nikita Sinha , Emily Broaddus , Sydney Stocks , William Zamboni , Benjamin B. Albright , Paola Gehrig , Victoria Bae-Jump , Olivia D. Lara","doi":"10.1016/j.ygyno.2025.12.001","DOIUrl":"10.1016/j.ygyno.2025.12.001","url":null,"abstract":"<div><h3>Background</h3><div>To determine the association between obesity and pembrolizumab response in racially diverse cohort of patients with advanced and recurrent endometrial cancer (EC).</div></div><div><h3>Methods</h3><div>We conducted a retrospective review of patients with advanced or recurrent endometrial cancer receiving pembrolizumab. Baseline clinical, demographic and cancer characteristics were collected. Progression free survival (PFS) and overall survival (OS) were estimated using the Kaplan–Meier method and modeled via Cox regression. Covariate differences were assessed using the log-rank test.</div></div><div><h3>Results</h3><div>Among the 179 patients, the median age was 65 years (IQR, 58–71 yrs) and the mean BMI was 33 (SD, 8.5). The cohort consisted of 55 Black patents (31 %) and 112 White patients (63 %); 99 patients (55 %) were obese. Forty-six patients received pembrolizumab alone, and 133 received combination therapy. Higher BMI was associated with shorter PFS (BMI >40: HR 1.91, CI 1.13–3.21, <em>p</em> = 0.014 and BMI 30–40: HR 1.55, CI 1.02–2.35, <em>p</em> = 0.041). In MMR stratified analysis, obesity was associated with lower response rates among patients with MMRp tumors (23.4 %; BMI ≥30 vs 40.0 %; BMI <30), whereas response remained high across BMI categories in MMRd tumors. In the subgroup treated with pembrolizumab and Lenvatinib (<em>n</em> = 79), both White and Black obese experienced worse PFS compared to White non-obese patients (<em>p</em> = 0.021 and <em>p</em> = 0.035, respectively). No significant differences in OS were observed between obese and non-obese groups.</div></div><div><h3>Conclusions</h3><div>In this diverse cohort, obesity was associated with worse PFS in patients treated with pembrolizumab for EC. MMRp tumors in obese patients had lowest response rates among subgroups. Further studies with long term follow up are needed to elucidate the biological mechanisms linking obesity to immunotherapy outcomes.</div></div>","PeriodicalId":12853,"journal":{"name":"Gynecologic oncology","volume":"204 ","pages":"Pages 228-234"},"PeriodicalIF":4.1,"publicationDate":"2025-12-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145742189","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}
Pub Date : 2025-12-10DOI: 10.1016/j.ygyno.2025.12.003
Italo Fernandes , Anjali Sachdeva , Farideh Tavangar , Matthew Lafreniere , Paul Yip , Teresa Petrella , Paaladinesh Thavendiranathan , Helen MacKay
Objectives
The primary objective of this study was to report on the clinical utility of serial troponin T (cTnT) monitoring in patients with gynecological cancers receiving immune checkpoint inhibitors (ICIs). Secondary objectives were to describe the experience of a single centre within a public healthcare system and to discuss the associated increase in healthcare utilization resulting from this intense monitoring strategy.
Methods
We conducted a retrospective cohort study of all patients with endometrial, cervical, and vaginal cancers treated with ICIs at Sunnybrook Health Sciences Centre, Toronto, Canada, until June 2024. Serial cTnT was measured at baseline and prior to each cycle. Comprehensive clinical data was collected. Associations between cTnT elevation and outcomes were analyzed.
Results
Sixty-eight patients were included: 41 (60.3 %) with endometrial, 25 (36.8 %) with cervical, and 2 (2.9 %) with vaginal cancer. At baseline, 37.9 % had elevated cTnT. During therapy, 63.2 % experienced at least one troponin elevation above the upper normal limit. Troponin increases were associated with age, hypertension, and other immune-related adverse events, but not with overall survival. Two patients (2.9 %) developed confirmed ICI-induced myocarditis. In total, over 1400 cTnT assays were performed, leading to multiple downstream investigations and treatment delays without consistent clinical benefit.
Conclusions
Serial cTnT monitoring frequently identified biomarker elevations but was not associated with outcomes in gynecologic cancer patients receiving ICIs. Despite a 63.2 % rate of elevated troponin, ICI-induced myocarditis occurred in 2.9 %. These findings suggest the need for evidence-based guidelines that balance early toxicity detection with safety, treatment continuity, and resource stewardship.
{"title":"Evaluating the clinical utility and impact on healthcare utilization of serial troponin T monitoring in gynecologic cancer patients receiving immune checkpoint inhibitors – A single centre experience","authors":"Italo Fernandes , Anjali Sachdeva , Farideh Tavangar , Matthew Lafreniere , Paul Yip , Teresa Petrella , Paaladinesh Thavendiranathan , Helen MacKay","doi":"10.1016/j.ygyno.2025.12.003","DOIUrl":"10.1016/j.ygyno.2025.12.003","url":null,"abstract":"<div><h3>Objectives</h3><div>The primary objective of this study was to report on the clinical utility of serial troponin T (cTnT) monitoring in patients with gynecological cancers receiving immune checkpoint inhibitors (ICIs). Secondary objectives were to describe the experience of a single centre within a public healthcare system and to discuss the associated increase in healthcare utilization resulting from this intense monitoring strategy.</div></div><div><h3>Methods</h3><div>We conducted a retrospective cohort study of all patients with endometrial, cervical, and vaginal cancers treated with ICIs at Sunnybrook Health Sciences Centre, Toronto, Canada, until June 2024. Serial cTnT was measured at baseline and prior to each cycle. Comprehensive clinical data was collected. Associations between cTnT elevation and outcomes were analyzed.</div></div><div><h3>Results</h3><div>Sixty-eight patients were included: 41 (60.3 %) with endometrial, 25 (36.8 %) with cervical, and 2 (2.9 %) with vaginal cancer. At baseline, 37.9 % had elevated cTnT. During therapy, 63.2 % experienced at least one troponin elevation above the upper normal limit. Troponin increases were associated with age, hypertension, and other immune-related adverse events, but not with overall survival. Two patients (2.9 %) developed confirmed ICI-induced myocarditis. In total, over 1400 cTnT assays were performed, leading to multiple downstream investigations and treatment delays without consistent clinical benefit.</div></div><div><h3>Conclusions</h3><div>Serial cTnT monitoring frequently identified biomarker elevations but was not associated with outcomes in gynecologic cancer patients receiving ICIs. Despite a 63.2 % rate of elevated troponin, ICI-induced myocarditis occurred in 2.9 %. These findings suggest the need for evidence-based guidelines that balance early toxicity detection with safety, treatment continuity, and resource stewardship.</div></div>","PeriodicalId":12853,"journal":{"name":"Gynecologic oncology","volume":"204 ","pages":"Pages 210-217"},"PeriodicalIF":4.1,"publicationDate":"2025-12-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145742153","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}
Pub Date : 2025-12-05DOI: 10.1016/j.ygyno.2025.11.022
Mark S. Shahin , Raina Mathur , Anju Parthan , Prakirthi Yerram , Amanda Kesner-Hays , Rachel Myers , Iulia Cristina Tudor , Darin Dobler , Adrian M. Jubb , Robert L. Coleman
Objective
To compare the real-world effectiveness and safety of monotherapy nab-paclitaxel and paclitaxel in patients with platinum-resistant ovarian cancer (PROC).
Methods
COMPASS is a retrospective, observational study using deidentified patient data from the longitudinal US Flatiron Health Research Database in patients with PROC who received monotherapy nab-paclitaxel or paclitaxel. Real-world progression-free survival (rwPFS), overall survival (OS), and prespecified real-world adverse events (rwAEs) were assessed. Cohorts were weighted by the inverse probability of treatment (IPTW) approach.
Results
Of the 225 patients included, 67 received nab-paclitaxel and 158 received paclitaxel monotherapy. Most patients were > 65 years old with an Eastern Cooperative Oncology Group performance status of 0–1 and were treated in the community setting. rwPFS and OS were comparable across cohorts (rwPFS: unadjusted hazard ratio [HR],1.11; 95 % CI, 0.82–1.49; IPTW-adjusted HR, 1.03; 95 % CI, 0.66–1.63; OS: unadjusted HR, 0.95; 95 % CI, 0.69–1.3; IPTW-adjusted HR, 1.11; 95 % CI, 0.79–1.56). A sensitivity analysis using doubly robust IPTW showed consistent results. Incidence rates of anemia, diarrhea, fatigue, infusion-related reactions, nausea/vomiting, peripheral neuropathy, and thrombocytopenia were lower with nab-paclitaxel than with paclitaxel, while those of neutropenia, febrile neutropenia, and leukopenia were higher. The frequency of peripheral neuropathy in the nab-paclitaxel cohort (14 %) was half that of the paclitaxel cohort (28 %). The observed trends in rwAEs persisted when adjusted for duration of exposure.
Conclusions
Nab-paclitaxel demonstrated comparable effectiveness to paclitaxel with a lower rate of peripheral neuropathy, suggesting that nab-paclitaxel is an effective treatment option and a relevant comparator for clinical trials of patients with PROC.
{"title":"Comparative outcomes of nab-paclitaxel and paclitaxel in platinum-resistant ovarian cancer (COMPASS)","authors":"Mark S. Shahin , Raina Mathur , Anju Parthan , Prakirthi Yerram , Amanda Kesner-Hays , Rachel Myers , Iulia Cristina Tudor , Darin Dobler , Adrian M. Jubb , Robert L. Coleman","doi":"10.1016/j.ygyno.2025.11.022","DOIUrl":"10.1016/j.ygyno.2025.11.022","url":null,"abstract":"<div><h3>Objective</h3><div>To compare the real-world effectiveness and safety of monotherapy nab-paclitaxel and paclitaxel in patients with platinum-resistant ovarian cancer (PROC).</div></div><div><h3>Methods</h3><div>COMPASS is a retrospective, observational study using deidentified patient data from the longitudinal US Flatiron Health Research Database in patients with PROC who received monotherapy nab-paclitaxel or paclitaxel. Real-world progression-free survival (rwPFS), overall survival (OS), and prespecified real-world adverse events (rwAEs) were assessed. Cohorts were weighted by the inverse probability of treatment (IPTW) approach.</div></div><div><h3>Results</h3><div>Of the 225 patients included, 67 received nab-paclitaxel and 158 received paclitaxel monotherapy. Most patients were > 65 years old with an Eastern Cooperative Oncology Group performance status of 0–1 and were treated in the community setting. rwPFS and OS were comparable across cohorts (rwPFS: unadjusted hazard ratio [HR],1.11; 95 % CI, 0.82–1.49; IPTW-adjusted HR, 1.03; 95 % CI, 0.66–1.63; OS: unadjusted HR, 0.95; 95 % CI, 0.69–1.3; IPTW-adjusted HR, 1.11; 95 % CI, 0.79–1.56). A sensitivity analysis using doubly robust IPTW showed consistent results. Incidence rates of anemia, diarrhea, fatigue, infusion-related reactions, nausea/vomiting, peripheral neuropathy, and thrombocytopenia were lower with nab-paclitaxel than with paclitaxel, while those of neutropenia, febrile neutropenia, and leukopenia were higher. The frequency of peripheral neuropathy in the nab-paclitaxel cohort (14 %) was half that of the paclitaxel cohort (28 %). The observed trends in rwAEs persisted when adjusted for duration of exposure.</div></div><div><h3>Conclusions</h3><div>Nab-paclitaxel demonstrated comparable effectiveness to paclitaxel with a lower rate of peripheral neuropathy, suggesting that nab-paclitaxel is an effective treatment option and a relevant comparator for clinical trials of patients with PROC.</div></div>","PeriodicalId":12853,"journal":{"name":"Gynecologic oncology","volume":"204 ","pages":"Pages 202-209"},"PeriodicalIF":4.1,"publicationDate":"2025-12-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145690379","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}
Pub Date : 2025-12-05DOI: 10.1016/j.ygyno.2025.11.021
John Nakayama , Michael McGaughey , Grace Pindzola , Eirwen Miller , Thomas Krivak , Christopher Morse , Sarah Crafton , Alyssa Wield , Jeffrey Toole , Tiffany Summerscales
Objective
To evaluate the effectiveness of machine learning survival models to predict time to recurrence using information from patient medical records known at the completion of frontline chemotherapy.
Methods
Five survival models – Penalized Cox Proportional Hazards (PenCoxPH), Random Survival Forest (RSF), Gradient Boosted Survival Analysis (GBSA), DeepSurv, and FastCPH — were trained on medical record data and used to predict time to recurrence. The models were trained on both the full set of patients and high-stage (III and IV) patients only. They were trained on the full-length (total time to recurrence) data as well as short-horizon (restricted to 15 months) recurrence data to increase prediction accuracy for the first year following completion of frontline chemotherapy. Feature hazard ratios for the PenCoxPH model were evaluated.
Results
GBSA received the highest performance scores when predicting full-length time to recurrence, while the DeepSurv and RSF models did best on predictions for short-horizon recurrence. GBSA achieved CD-AUC (cumulative/dynamic AUC) measures above 0.8 at 2 and 3 years. Stage I, HRD Negative, NACT and a rise in CA125 over the course of frontline chemotherapy were significant predictors of recurrence. PenCoxPH and FastCPH achieved a 6-month CD-AUC of 0.74 the high-stage, high-grade serous cohort for full-horizon recurrence.
Conclusion
Machine learning survival models can predict time to recurrence with sufficient accuracy to be clinically useful. While confirmatory studies are needed to validate these findings, providers could potentially use this information to tailor treatment strategies in maintenance therapy and select patients for clinical trial enrollment.
{"title":"Machine-learning survival models for predicting time to recurrence in epithelial ovarian cancer","authors":"John Nakayama , Michael McGaughey , Grace Pindzola , Eirwen Miller , Thomas Krivak , Christopher Morse , Sarah Crafton , Alyssa Wield , Jeffrey Toole , Tiffany Summerscales","doi":"10.1016/j.ygyno.2025.11.021","DOIUrl":"10.1016/j.ygyno.2025.11.021","url":null,"abstract":"<div><h3>Objective</h3><div>To evaluate the effectiveness of machine learning survival models to predict time to recurrence using information from patient medical records known at the completion of frontline chemotherapy.</div></div><div><h3>Methods</h3><div>Five survival models – Penalized Cox Proportional Hazards (PenCoxPH), Random Survival Forest (RSF), Gradient Boosted Survival Analysis (GBSA), DeepSurv, and FastCPH — were trained on medical record data and used to predict time to recurrence. The models were trained on both the full set of patients and high-stage (III and IV) patients only. They were trained on the full-length (total time to recurrence) data as well as short-horizon (restricted to 15 months) recurrence data to increase prediction accuracy for the first year following completion of frontline chemotherapy. Feature hazard ratios for the PenCoxPH model were evaluated.</div></div><div><h3>Results</h3><div>GBSA received the highest performance scores when predicting full-length time to recurrence, while the DeepSurv and RSF models did best on predictions for short-horizon recurrence. GBSA achieved CD-AUC (cumulative/dynamic AUC) measures above 0.8 at 2 and 3 years. Stage I, HRD Negative, NACT and a rise in CA125 over the course of frontline chemotherapy were significant predictors of recurrence. PenCoxPH and FastCPH achieved a 6-month CD-AUC of 0.74 the high-stage, high-grade serous cohort for full-horizon recurrence.</div></div><div><h3>Conclusion</h3><div>Machine learning survival models can predict time to recurrence with sufficient accuracy to be clinically useful. While confirmatory studies are needed to validate these findings, providers could potentially use this information to tailor treatment strategies in maintenance therapy and select patients for clinical trial enrollment.</div></div>","PeriodicalId":12853,"journal":{"name":"Gynecologic oncology","volume":"204 ","pages":"Pages 184-193"},"PeriodicalIF":4.1,"publicationDate":"2025-12-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145690380","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}
Pub Date : 2025-12-05DOI: 10.1016/j.ygyno.2025.11.023
Holly E. Evans , Amber-Marie Firriolo , Rachel Houweling , Lauren Kelada , Gill Stannard , Jacinta Frawley , Brittany C. McGill , Susan J. Ramus , Yeh Chen Lee , Michael Friedlander , Jennifer Duggan , Claire E. Wakefield
Objective
The Ovarian Tumor Tissue Analysis consortium - Stratified Prognosis of Ovarian Tumors (OTTA-SPOT) 101 gene expression signature, predicts 5-year survival on a tumor biopsy at diagnosis and identifies the 20 % of patients with a 10 % probability of 5-year survival with standard of care therapy, who may benefit from alternate treatments. This study aims to understand how patients with ovarian cancer perceive the potential advantages and disadvantages of OTTA-SPOT, their willingness for the test, and preferred methods of receiving test results.
Methods
Participants were eligible if they had a diagnosis of ovarian cancer and resided in Australia or New Zealand. Participants completed a mixed-methods questionnaire, co-designed with consumers, which investigated their perspectives about prognostic tests for ovarian cancer. Participants could opt-in to a 1–1.5-h online focus group to discuss their perspectives further.
Results
Thirty-three participants completed the online questionnaire. Participants perceived the potential advantages of the prognostic test outweighed the disadvantages, and 88 % would be ‘very willing’ or ‘willing’ to undergo prognostic testing if available. Nine participants took part in focus groups. We developed four themes from thematic analysis of these discussions: (1) Cancer journey and context, (2) Advantages and disadvantages of knowing prognosis, (3) The complexities of when to receive prognostic information, and (4) Communication and service delivery.
Conclusion
Participants with ovarian cancer viewed prognostic testing positively. However, successful implementation will require a patient-centred approach that accommodates diverse preferences around how the test is introduced, and results are communicated.
{"title":"Evaluating patient perspectives about the acceptability of a novel prognostic gene expression signature for high grade serous ovarian cancer: The OTTA-SPOT study","authors":"Holly E. Evans , Amber-Marie Firriolo , Rachel Houweling , Lauren Kelada , Gill Stannard , Jacinta Frawley , Brittany C. McGill , Susan J. Ramus , Yeh Chen Lee , Michael Friedlander , Jennifer Duggan , Claire E. Wakefield","doi":"10.1016/j.ygyno.2025.11.023","DOIUrl":"10.1016/j.ygyno.2025.11.023","url":null,"abstract":"<div><h3>Objective</h3><div>The Ovarian Tumor Tissue Analysis consortium - Stratified Prognosis of Ovarian Tumors (OTTA-SPOT) 101 gene expression signature, predicts 5-year survival on a tumor biopsy at diagnosis and identifies the 20 % of patients with a 10 % probability of 5-year survival with standard of care therapy, who may benefit from alternate treatments. This study aims to understand how patients with ovarian cancer perceive the potential advantages and disadvantages of OTTA-SPOT, their willingness for the test, and preferred methods of receiving test results.</div></div><div><h3>Methods</h3><div>Participants were eligible if they had a diagnosis of ovarian cancer and resided in Australia or New Zealand. Participants completed a mixed-methods questionnaire, co-designed with consumers, which investigated their perspectives about prognostic tests for ovarian cancer. Participants could opt-in to a 1–1.5-h online focus group to discuss their perspectives further.</div></div><div><h3>Results</h3><div>Thirty-three participants completed the online questionnaire. Participants perceived the potential advantages of the prognostic test outweighed the disadvantages, and 88 % would be ‘very willing’ or ‘willing’ to undergo prognostic testing if available. Nine participants took part in focus groups. We developed four themes from thematic analysis of these discussions: (1) Cancer journey and context, (2) Advantages and disadvantages of knowing prognosis, (3) The complexities of when to receive prognostic information, and (4) Communication and service delivery.</div></div><div><h3>Conclusion</h3><div>Participants with ovarian cancer viewed prognostic testing positively. However, successful implementation will require a patient-centred approach that accommodates diverse preferences around how the test is introduced, and results are communicated.</div></div>","PeriodicalId":12853,"journal":{"name":"Gynecologic oncology","volume":"204 ","pages":"Pages 150-157"},"PeriodicalIF":4.1,"publicationDate":"2025-12-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145690381","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}
Pub Date : 2025-12-05DOI: 10.1016/j.ygyno.2025.11.016
Rebekah M. Peplinski, Jesse D. Riordan, Jacob L. Schillo, Elizabeth C. Hannan, Silvana Pedra Nobre, Yasmin A. Lyons, Keely K. Ulmer, Michael J. Goodheart, Adam J. Dupuy
Objective
Low-grade serous ovarian cancer (LGSOC) frequently harbors genetic alterations that activate the MAPK pathway, providing an oncogenic target for therapeutic intervention. Recent clinical trials utilizing inhibitors of MEK (a key mediator of MAPK signaling), particularly trametinib or avutometinib/defactinib combination, have shown efficacy in patients with recurrent LGSOC. Unfortunately, however, nearly all patients eventually develop therapeutic resistance and progressive disease, which confers a dismal prognosis. Here, we aim to characterize biological responses of LGSOC to MEK inhibition at the molecular level.
Methods
We performed a kinome-focused CRISPR knockout screen in LGSOC cell lines to identify synthetic lethal interactions between trametinib treatment and loss of specific protein kinases. Candidates were evaluated using western blotting and cell viability assays.
Results
CRISPR kinome screens identified several protein kinases, particularly within the PI3K-Akt pathway, whose loss correlated with outgrowth of trametinib-resistant LGSOC cell populations, indicative of synthetic lethal interaction. Western blotting confirmed upregulation of Akt signaling upon MEK inhibition in a panel of LGSOC cell lines, and preventing this upregulation by co-inhibiting AKT with capivasertib produced synergistic antiproliferative effects in vitro.
Conclusion
LGSOC responds to MEK inhibition by upregulating PI3K-Akt signaling, thereby promoting cell survival and proliferation. Our research identified significant upregulation of the PI3K-Akt pathway in response to MEK inhibition. While targeted inhibition of AKT had minimal impact alone, combination with MEK inhibitors produced strong synergistic suppression of proliferation in LGSOC cells. This combination strategy could potentially be used to prevent or reverse the emergence of MEK inhibitor resistance in LGSOC patients.
{"title":"Co-targeting the PI3K-Akt pathway improves response to MEK inhibition in low-grade serous ovarian cancer cell lines","authors":"Rebekah M. Peplinski, Jesse D. Riordan, Jacob L. Schillo, Elizabeth C. Hannan, Silvana Pedra Nobre, Yasmin A. Lyons, Keely K. Ulmer, Michael J. Goodheart, Adam J. Dupuy","doi":"10.1016/j.ygyno.2025.11.016","DOIUrl":"10.1016/j.ygyno.2025.11.016","url":null,"abstract":"<div><h3>Objective</h3><div>Low-grade serous ovarian cancer (LGSOC) frequently harbors genetic alterations that activate the MAPK pathway, providing an oncogenic target for therapeutic intervention. Recent clinical trials utilizing inhibitors of MEK (a key mediator of MAPK signaling), particularly trametinib or avutometinib/defactinib combination, have shown efficacy in patients with recurrent LGSOC. Unfortunately, however, nearly all patients eventually develop therapeutic resistance and progressive disease, which confers a dismal prognosis. Here, we aim to characterize biological responses of LGSOC to MEK inhibition at the molecular level.</div></div><div><h3>Methods</h3><div>We performed a kinome-focused CRISPR knockout screen in LGSOC cell lines to identify synthetic lethal interactions between trametinib treatment and loss of specific protein kinases. Candidates were evaluated using western blotting and cell viability assays.</div></div><div><h3>Results</h3><div>CRISPR kinome screens identified several protein kinases, particularly within the PI3K-Akt pathway, whose loss correlated with outgrowth of trametinib-resistant LGSOC cell populations, indicative of synthetic lethal interaction. Western blotting confirmed upregulation of Akt signaling upon MEK inhibition in a panel of LGSOC cell lines, and preventing this upregulation by co-inhibiting AKT with capivasertib produced synergistic antiproliferative effects in vitro.</div></div><div><h3>Conclusion</h3><div>LGSOC responds to MEK inhibition by upregulating PI3K-Akt signaling, thereby promoting cell survival and proliferation. Our research identified significant upregulation of the PI3K-Akt pathway in response to MEK inhibition. While targeted inhibition of AKT had minimal impact alone, combination with MEK inhibitors produced strong synergistic suppression of proliferation in LGSOC cells. This combination strategy could potentially be used to prevent or reverse the emergence of MEK inhibitor resistance in LGSOC patients.</div></div>","PeriodicalId":12853,"journal":{"name":"Gynecologic oncology","volume":"204 ","pages":"Pages 194-201"},"PeriodicalIF":4.1,"publicationDate":"2025-12-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145690479","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}
Pub Date : 2025-12-04DOI: 10.1016/j.ygyno.2025.11.024
Koji Matsuo , Matthew W. Lee , Emmeline L. Friedman , Hadi Erfani , Alice J. Lee , Jennifer A. Yao , Alexia J. Ouzounian , Mariya Kobayashi , Shinya Matsuzaki , Michiko Kodama , Hiroyuki Kanao , Lynda D. Roman
Objective
The PHENIX-I clinical trial in China demonstrated that sentinel lymph node (SLN) biopsy alone without additional lymphadenectomy for early cervical cancer had oncologic outcomes non-inferior to SLN biopsy and additional lymphadenectomy. This study examined overall survival associated with SLN biopsy alone without additional lymphadenectomy for early cervical cancer using real-world data in the United States.
Methods
This retrospective cohort study queried the Commission-on-Cancer's National Cancer Database. The study population included 465 patients aged 18–65 years-old with cervical cancer (preoperative stage IA1 with lympho-vascular space invasion, IA2, IB1, and IIA1 with tumor size of ≤3 cm) who underwent primary radical hysterectomy and SLN biopsy from 2012 to 2022. Exposure was additional lymphadenectomy at SLN biopsy (SLN biopsy alone n = 231, SLN biopsy and additional lymphadenectomy n = 234). Outcome measure was overall survival, assessed with Cox proportional hazard regression model adjusting for preoperative factor-derived propensity score and postoperative confounders (pathological lymph node metastasis, radiotherapy, and chemotherapy).
Results
The 5-year overall survival rates were 98.6% (95% confidence interval 94.3 to 99.7) for the SLN biopsy alone group and 96.8% (95% confidence interval 93.0 to 98.6) for the SLN biopsy and additional lymphadenectomy group (P = .69). Adjusted-hazard ratio for SLN biopsy alone compared to SLN biopsy and additional lymphadenectomy was 0.94 (95% confidence interval 0.24 to 3.67). Exploratory analysis showed similar results for squamous histology, preoperative stage IB1 with tumor size of ≤3 cm, and robotic-assisted surgery (all, P > .05).
Conclusion
The results of this real-world data in the United States suggested that SLN biopsy alone without additional lymphadenectomy for early cervical cancer meeting the PHENIX-I trial criteria may not have negative effects on short-term overall survival, warranting further validation.
{"title":"Survival assessment of sentinel lymph node biopsy alone without lymphadenectomy for early cervical cancer in real-world data","authors":"Koji Matsuo , Matthew W. Lee , Emmeline L. Friedman , Hadi Erfani , Alice J. Lee , Jennifer A. Yao , Alexia J. Ouzounian , Mariya Kobayashi , Shinya Matsuzaki , Michiko Kodama , Hiroyuki Kanao , Lynda D. Roman","doi":"10.1016/j.ygyno.2025.11.024","DOIUrl":"10.1016/j.ygyno.2025.11.024","url":null,"abstract":"<div><h3>Objective</h3><div>The PHENIX-I clinical trial in China demonstrated that sentinel lymph node (SLN) biopsy alone without additional lymphadenectomy for early cervical cancer had oncologic outcomes non-inferior to SLN biopsy and additional lymphadenectomy. This study examined overall survival associated with SLN biopsy alone without additional lymphadenectomy for early cervical cancer using real-world data in the United States.</div></div><div><h3>Methods</h3><div>This retrospective cohort study queried the Commission-on-Cancer's National Cancer Database. The study population included 465 patients aged 18–65 years-old with cervical cancer (preoperative stage IA1 with lympho-vascular space invasion, IA2, IB1, and IIA1 with tumor size of ≤3 cm) who underwent primary radical hysterectomy and SLN biopsy from 2012 to 2022. Exposure was additional lymphadenectomy at SLN biopsy (SLN biopsy alone <em>n</em> = 231, SLN biopsy and additional lymphadenectomy <em>n</em> = 234). Outcome measure was overall survival, assessed with Cox proportional hazard regression model adjusting for preoperative factor-derived propensity score and postoperative confounders (pathological lymph node metastasis, radiotherapy, and chemotherapy).</div></div><div><h3>Results</h3><div>The 5-year overall survival rates were 98.6% (95% confidence interval 94.3 to 99.7) for the SLN biopsy alone group and 96.8% (95% confidence interval 93.0 to 98.6) for the SLN biopsy and additional lymphadenectomy group (<em>P</em> = .69). Adjusted-hazard ratio for SLN biopsy alone compared to SLN biopsy and additional lymphadenectomy was 0.94 (95% confidence interval 0.24 to 3.67). Exploratory analysis showed similar results for squamous histology, preoperative stage IB1 with tumor size of ≤3 cm, and robotic-assisted surgery (all, <em>P</em> > .05).</div></div><div><h3>Conclusion</h3><div>The results of this real-world data in the United States suggested that SLN biopsy alone without additional lymphadenectomy for early cervical cancer meeting the PHENIX-I trial criteria may not have negative effects on short-term overall survival, warranting further validation.</div></div>","PeriodicalId":12853,"journal":{"name":"Gynecologic oncology","volume":"204 ","pages":"Pages 174-183"},"PeriodicalIF":4.1,"publicationDate":"2025-12-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145687229","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}
Pub Date : 2025-12-04DOI: 10.1016/j.ygyno.2025.11.017
Seongyun Lim, Young Eun Chung, Jun-Hyeong Seo, Yooyoung Lee, Tae-Joong Kim, Jeong-Won Lee, Byoung-Gie Kim , Chel-Hun Choi
Objective
Uterine carcinosarcoma (UCS) is a rare, aggressive endometrial cancer with limited treatment options for recurrence. The role of immunotherapy in UCS remains unclear. This study aimed to evaluate the efficacy and safety of pembrolizumab with or without lenvatinib in recurrent UCS.
Methods
We retrospectively analyzed 43 patients with recurrent UCS treated with pembrolizumab monotherapy (n = 9) or in combination with lenvatinib (n = 34) at a single center between 2018 and 2025. We analyzed clinicopathologic features, treatment response, survival outcomes and adverse events (AEs) graded per the Common Terminology Criteria for Adverse Events (CTCAE) v5.0.
Results
Median progression-free survival (PFS) was 5 months and overall survival (OS) was 14 months. Objective response rate (ORR) was 37.5 % and disease control rate (DCR) was 67.5 %. The combination showed longer median PFS (5 vs. 3 months) and OS (19 vs. 7 months) compared with monotherapy, without statistical significance (PFS p = 0.99; OS p = 0.25). In exploratory multivariable analyses, larger tumor size was associated with shorter PFS (HR 2.73, 95 % CI 1.18–6.28) and OS (HR 5.36, 95 % CI 1.84–15.63). The most frequent AEs were hand-foot syndrome (29.4 %) and hypothyroidism (26.5 %), but no treatment-related deaths were observed.
Conclusions
Pembrolizumab with or without lenvatinib demonstrated modest efficacy with a manageable safety profile in recurrent UCS, although monotherapy outcomes remain exploratory due to the small sample size. This real-world study supports the potential role of immunotherapy for select UCS patients and highlights the need for prospective trials.
目的：子宫癌肉瘤（UCS）是一种罕见的侵袭性子宫内膜癌，复发治疗方案有限。免疫治疗在UCS中的作用尚不清楚。本研究旨在评估派姆单抗联合或不联合lenvatinib治疗复发性UCS的疗效和安全性。方法：我们回顾性分析了2018年至2025年在单中心接受派姆单抗单药治疗（n = 9）或联合lenvatinib （n = 34）的43例复发性UCS患者。我们根据不良事件通用术语标准（CTCAE） v5.0分析了临床病理特征、治疗反应、生存结局和不良事件（ae）。中位无进展生存期（PFS）为5个月，总生存期（OS）为14个月。客观有效率（ORR）为37.5%，疾病控制率（DCR）为67.5%。与单药治疗相比，联合治疗的中位PFS（5个月vs 3个月）和OS（19个月vs 7个月）更长，但无统计学意义（PFS p = 0.99; OS p = 0.25）。在探索性多变量分析中，较大的肿瘤大小与较短的PFS （HR 2.73, 95% CI 1.18-6.28）和OS （HR 5.36, 95% CI 1.84-15.63）相关。最常见的ae是手足综合征（29.4%）和甲状腺功能减退（26.5%），但未观察到与治疗相关的死亡。结论：Pembrolizumab联合lenvatinib或不联合lenvatinib在复发性UCS中表现出适度的疗效和可管理的安全性，尽管由于样本量小，单药治疗的结果仍处于探索性阶段。这项现实世界的研究支持免疫疗法对选择性UCS患者的潜在作用，并强调了前瞻性试验的必要性。
{"title":"Efficacy and safety of pembrolizumab with or without lenvatinib in recurrent uterine carcinosarcoma: a real-world single-center study","authors":"Seongyun Lim, Young Eun Chung, Jun-Hyeong Seo, Yooyoung Lee, Tae-Joong Kim, Jeong-Won Lee, Byoung-Gie Kim , Chel-Hun Choi","doi":"10.1016/j.ygyno.2025.11.017","DOIUrl":"10.1016/j.ygyno.2025.11.017","url":null,"abstract":"<div><h3>Objective</h3><div>Uterine carcinosarcoma (UCS) is a rare, aggressive endometrial cancer with limited treatment options for recurrence. The role of immunotherapy in UCS remains unclear. This study aimed to evaluate the efficacy and safety of pembrolizumab with or without lenvatinib in recurrent UCS.</div></div><div><h3>Methods</h3><div>We retrospectively analyzed 43 patients with recurrent UCS treated with pembrolizumab monotherapy (<em>n</em> = 9) or in combination with lenvatinib (<em>n</em> = 34) at a single center between 2018 and 2025. We analyzed clinicopathologic features, treatment response, survival outcomes and adverse events (AEs) graded per the Common Terminology Criteria for Adverse Events (CTCAE) v5.0.</div></div><div><h3>Results</h3><div>Median progression-free survival (PFS) was 5 months and overall survival (OS) was 14 months. Objective response rate (ORR) was 37.5 % and disease control rate (DCR) was 67.5 %. The combination showed longer median PFS (5 vs. 3 months) and OS (19 vs. 7 months) compared with monotherapy, without statistical significance (PFS <em>p</em> = 0.99; OS <em>p</em> = 0.25). In exploratory multivariable analyses, larger tumor size was associated with shorter PFS (HR 2.73, 95 % CI 1.18–6.28) and OS (HR 5.36, 95 % CI 1.84–15.63). The most frequent AEs were hand-foot syndrome (29.4 %) and hypothyroidism (26.5 %), but no treatment-related deaths were observed.</div></div><div><h3>Conclusions</h3><div>Pembrolizumab with or without lenvatinib demonstrated modest efficacy with a manageable safety profile in recurrent UCS, although monotherapy outcomes remain exploratory due to the small sample size. This real-world study supports the potential role of immunotherapy for select UCS patients and highlights the need for prospective trials.</div></div>","PeriodicalId":12853,"journal":{"name":"Gynecologic oncology","volume":"204 ","pages":"Pages 165-173"},"PeriodicalIF":4.1,"publicationDate":"2025-12-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145687287","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}
扫码关注我们
求助内容：
应助结果提醒方式：
京公网安备 11010802042870号