Gynecologic oncology最新文献

{"title":"Patterns of primary metastasis and recurrence in mismatch repair deficiency and p53 abnormal endometrial carcinoma","authors":"Matthew K. Wagar ,&nbsp;Eric Reetz ,&nbsp;Dandi Huang ,&nbsp;Mary J. Kao ,&nbsp;Ahmed N. Al-Niaimi ,&nbsp;Sumer K. Wallace ,&nbsp;Lisa M. Barroilhet ,&nbsp;Stephanie M. McGregor","doi":"10.1016/j.ygyno.2025.05.004","DOIUrl":"10.1016/j.ygyno.2025.05.004","url":null,"abstract":"<div><h3>Objectives</h3><div>Molecular classification of endometrial carcinoma(EC) provides relevant prognostication and is now being utilized to determine adjuvant therapy. It is currently unclear how molecular classification relates to disease dissemination and recurrence patterns in EC. The objective of this study was to characterize patterns of disease in mismatch repair-deficient (MMRd) and p53 abnormal (p53abn) carcinomas.</div></div><div><h3>Methods</h3><div>Immunohistochemistry molecular classification was performed to relate patterns of disease spread among EC patients undergoing surgical staging/cytoreduction. Dissemination patterns were assigned according to the most distant site of disease and subdivided as carcinomatosis, visceral organ, or lymphatic locations. Standard statistical methods were employed for comparisons, including multivariate logistic regression.</div></div><div><h3>Results</h3><div>Of 380 cases, 127 had advanced disease at presentation: 43.4 % pelvic, 44.8 % lower abdominal, 7.1 % upper abdominal and 4.7 % extra-abdominal. P53abn carcinomas were more likely to present with peritoneal-based disease compared to MMRd and p53wt tumors(30.8 %, 11.7 %, and 9.7 %, <em>p</em> &lt; 0.0001). Among 128 patients with recurrence, upper abdominal spread and carcinomatosis were more common with p53abn than MMRd or p53wt tumors(49.2 %, 10 %, 8.2 %, <em>p</em> &lt; 0.0001 and 60.8 %, 7.5 %, 18.9 %, p &lt; 0.0001). MMRd tumors were associated with lymphatic recurrences compared to p53abn or p53wt(55 %, 19.6 %, 35.1 %, <em>p</em> = 0.001). These associations remained significant in multivariate analysis.</div></div><div><h3>Conclusions</h3><div>EC recurrence patterns differ based on molecular classification. Patients with p53abn cancers are more likely to present with peritoneal-based disease and experience peritoneal recurrence. Patients with MMRd cancers are more likely to experience lymphatic-based recurrences. This information provides a model of biologic behavior of molecular subtypes that can inform prospective surgical and therapeutic trials.</div></div>","PeriodicalId":12853,"journal":{"name":"Gynecologic oncology","volume":"197 ","pages":"Pages 171-178"},"PeriodicalIF":4.5,"publicationDate":"2025-05-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143936103","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":"Assessing preventive gynecologic decisions in individuals with Lynch syndrome","authors":"Rebecca M. Waggoner ,&nbsp;Ryan P. Mahoney ,&nbsp;Deepika Nathan ,&nbsp;Jason A. Zell ,&nbsp;Julie O. Culver","doi":"10.1016/j.ygyno.2025.05.003","DOIUrl":"10.1016/j.ygyno.2025.05.003","url":null,"abstract":"<div><h3>Background</h3><div>Lynch syndrome causes increased risks of colorectal, endometrial, ovarian, and other cancers. Current guidelines for managing Lynch-associated ovarian and uterine cancer risks are vague and left to a clinician's discretion. This study aimed to identify factors associated with an individual's decision to undergo risk-reducing surgery or gynecologic screening.</div></div><div><h3>Methods</h3><div>A survey for individuals with Lynch syndrome was distributed to social media-based support groups. Eligible participants included individuals without a history of gynecologic cancer who had an intact uterus and/or ovaries when they were diagnosed with Lynch syndrome.</div></div><div><h3>Results</h3><div>The majority of the 115 participants identified as women (98.3 %), were age 30–49 (61.8 %), were non-Hispanic White (93.0 %), had a college degree or higher (80 %), were premenopausal at the time of genetic testing (69.6 %), had no prior cancer diagnosis (66.0 %), and had at least one biological child (73.9 %). Overall, 71 (61.8 %) participants completed risk-reducing surgery. The survey found that increasing age, having less than a college degree, having children, not desiring future pregnancies, menopausal status, and having a previous non-gynecologic cancer were significantly associated with choosing to undergo risk-reducing surgery. However, cancer risk factors, including family history of gynecologic cancer or which Lynch-associated gene was involved, were not associated with surgical decisions. Participant comments also provided insight into emotional factors experienced while navigating screening or surgical decisions.</div></div><div><h3>Conclusion</h3><div>The results of this study may help clinicians better understand preventive decisions, which will ultimately empower patients to make confident, informed decisions about their gynecologic health.</div></div>","PeriodicalId":12853,"journal":{"name":"Gynecologic oncology","volume":"197 ","pages":"Pages 163-170"},"PeriodicalIF":4.5,"publicationDate":"2025-05-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143921729","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":"Peritoneal washings analysis in endometrial cancer: Comparison of somatic mutation detection with panel sequencing and traditional cytology","authors":"Maureen E. Byrne ,&nbsp;Pier Selenica ,&nbsp;Kimberly Dessources ,&nbsp;Arnaud Da Cruz Paula ,&nbsp;Sushmita Gordhandas ,&nbsp;Michelle Wu ,&nbsp;Fresia Pareja ,&nbsp;Kara Long Roche ,&nbsp;Jennifer J. Mueller ,&nbsp;Yukio Sonoda ,&nbsp;Nadeem R. Abu-Rustum ,&nbsp;Britta Weigelt","doi":"10.1016/j.ygyno.2025.05.002","DOIUrl":"10.1016/j.ygyno.2025.05.002","url":null,"abstract":"<div><h3>Objectives</h3><div>The prognostic significance of positive pelvic washings in endometrial cancer (EC) remains unknown, and little data exist regarding washings as a source of genetic information in relation to a patient's tumor. We sought to assess the feasibility of identifying EC mutations in peritoneal washings.</div></div><div><h3>Methods</h3><div>Peritoneal washings from 21 biopsy-confirmed newly diagnosed patients with EC across disease stages between 09/2018 and 07/2019 were collected. Peritoneal washings, primary EC, and normal DNA samples were subjected to next-generation sequencing targeting 468 cancer-related genes. Sequencing results were compared to cytological analysis.</div></div><div><h3>Results</h3><div>For the 21 EC cases included, cytology found 8 (38 %) of the peritoneal washings as positive, 7 (33 %) as negative, and 6 (29 %) as suspicious or rare-atypical cells. Based on molecular analysis, tumor mutations (TMs) were detected in 18/21 (86 %) of peritoneal washings. Overall, 11/21 (52 %) samples demonstrated concordant results between cytologic and molecular analysis, and all positive cytologic results were confirmed with molecular analysis. However, of cases with negative or suspicious cytology results, 77 % (10/13) were found to have TMs in washings. Five patients with negative cytology were positive on molecular analysis (5/7, 71 %), and 5 patients with suspicious washings demonstrated TMs (5/6, 83 %). Of the 10 EC patients who developed recurrences, regardless of stage, 5/10 (50 %) patients had positive cytology, whereas 9/10 (90 %) had TMs based on molecular analysis.</div></div><div><h3>Conclusions</h3><div>Mutational analysis of peritoneal washings using panel sequencing in EC is feasible. A substantial subset of patients with cytology-negative or suspicious washings had TMs detected.</div></div>","PeriodicalId":12853,"journal":{"name":"Gynecologic oncology","volume":"197 ","pages":"Pages 155-162"},"PeriodicalIF":4.5,"publicationDate":"2025-05-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143928313","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":"FRα expression in advanced endometrial carcinoma: Clinicopathological, molecular, and prognosis correlates","authors":"Yinbo Xiao ,&nbsp;Junyi Pang ,&nbsp;Yang Zhou,&nbsp;Junliang Lu,&nbsp;Longyun Chen,&nbsp;Hangqi Liu,&nbsp;Jing Shi,&nbsp;Xiaohua Shi,&nbsp;Zhiyong Liang","doi":"10.1016/j.ygyno.2025.05.001","DOIUrl":"10.1016/j.ygyno.2025.05.001","url":null,"abstract":"<div><h3>Background</h3><div>Advanced endometrial carcinoma (EC) is a therapeutic challenge with limited treatment options. Folate receptor alpha (FRα)-targeted antibody-drug conjugates (ADCs) are being explored for EC treatment. However, the molecular profiles of FRα-expressing ECs remain understudied. This study aims to evaluate FRα expression in advanced EC and its associations with clinicopathological features, molecular alterations, and prognosis value.</div></div><div><h3>Methods</h3><div>We analyzed a cohort of 111 advanced ECs from our institution (PUMCH). We used immunohistochemistry (IHC) to quantify FRα expression and next-generation sequencing (NGS) to determine genomic mutations. In parallel, a cohort from the TCGA database was included as an external cohort for validation.</div></div><div><h3>Results</h3><div>In the PUMCH cohort, 21 out of 111 (18.9 %) cases were graded as FRα-high. FRα-high ECs were significantly associated with aggressive histotypes and the p53abn molecular subtype. A significant correlation between FRα and CA125 was demonstrated at the protein level in the PUMCH cohort and the RNA level in the TCGA cohort. Molecularly, FRα-high ECs were more often associated with <em>TP53</em> mutations, while FRα-low ECs were characterized by <em>PTEN</em> mutations. In survival analysis, high FRα expression was closely correlated with poor outcomes, especially in Stage III ECs. Additionally, FRα could significantly stratify prognosis within a limited cohort of mismatch repair-deficient (MMR-d) ECs.</div></div><div><h3>Conclusion</h3><div>FRα positivity in advanced ECs corresponds with a unique molecular landscape, particularly the p53abn subgroup. The prognostic value of FRα in advanced ECs, especially in MMR-d ECs, warrants clinical attention.</div></div>","PeriodicalId":12853,"journal":{"name":"Gynecologic oncology","volume":"197 ","pages":"Pages 146-154"},"PeriodicalIF":4.5,"publicationDate":"2025-05-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143921726","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":"TROP2 expression and therapeutic targeting in uterine carcinosarcoma","authors":"Sara Moufarrij ,&nbsp;Higinio Dopeso ,&nbsp;David N. Brown ,&nbsp;Hunter Green ,&nbsp;Kaitlyn Gill ,&nbsp;Julia Tengelin ,&nbsp;Melica N. Brodeur ,&nbsp;William A. Zammarrelli III ,&nbsp;Nancy Varice ,&nbsp;Michelle Wu ,&nbsp;Achim Jungbluth ,&nbsp;Yingjie Zhu ,&nbsp;Xiaoping Chen ,&nbsp;Arnaud Da Cruz Paula ,&nbsp;Thais Basili ,&nbsp;Elisa de Stanchina ,&nbsp;Nadeem R. Abu-Rustum ,&nbsp;Carol Aghajanian ,&nbsp;Lora H. Ellenson ,&nbsp;M. Herman Chui ,&nbsp;Britta Weigelt","doi":"10.1016/j.ygyno.2025.04.590","DOIUrl":"10.1016/j.ygyno.2025.04.590","url":null,"abstract":"<div><h3>Objective</h3><div>Uterine carcinosarcoma (UCS) is a rare and aggressive type of endometrial carcinoma (EC), and novel therapeutic strategies are needed. We sought to assess TROP2 expression in archival UCSs and TROP2 antibody–drug conjugate (ADC) targeting in patient-derived UCS organoid (PDO) and xenograft (PDX) models.</div></div><div><h3>Methods</h3><div>TROP2 protein (immunohistochemistry) and mRNA (qRT-PCR) expression were assessed in 72 archival UCS tissues. Nine UCS PDO models were established and molecularly characterized by panel sequencing; then, TROP2 levels were determined and the efficacy of the TROP2 ADC sacituzumab govitecan (SG) defined in the UCS PDO and PDX models (<em>n</em> = 2).</div></div><div><h3>Results</h3><div>TROP2 protein and mRNA expression were detected in ≥90 % of primary UCSs, and those with a predominant carcinomatous component or with homologous differentiation had higher TROP2 expression than those with a predominant sarcomatous component or with heterologous differentiation (<em>p</em> &lt; 0.001 and <em>p</em> = 0.022, respectively). UCS PDOs displayed TROP2 expression and molecular profiles (median 88 %, range 50–100 % of mutation in primary UCSs present in PDOs) reflective of their respective primary UCSs. All 9 UCS PDOs responded in a dose-dependent manner to SG treatment, with a median IC₅₀ of 167.7pM (range 51.4pM–3.2 nM). In addition, both UCS PDX models with high and low TROP2 protein expression had a significant reduction in tumor volume with SG treatment (<em>p</em> = 0.03 and <em>p</em> = 0.02, respectively).</div></div><div><h3>Conclusions</h3><div>We demonstrate that the majority of UCSs have detectable TROP2 expression. Our findings on the SG response in UCS PDO and PDX models warrant further studies on TROP2 targeting for patients with this aggressive disease.</div></div>","PeriodicalId":12853,"journal":{"name":"Gynecologic oncology","volume":"197 ","pages":"Pages 129-138"},"PeriodicalIF":4.5,"publicationDate":"2025-05-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143921724","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":"Cognitive outcomes after premenopausal risk-reducing salpingo-oophorectomy: The role of hormone therapy.","authors":"Martha Hickey, Leah Rubin, Efrosinia O Krejany, Alison Brand, Pauline Maki","doi":"10.1016/j.ygyno.2025.04.587","DOIUrl":"https://doi.org/10.1016/j.ygyno.2025.04.587","url":null,"abstract":"","PeriodicalId":12853,"journal":{"name":"Gynecologic oncology","volume":" ","pages":""},"PeriodicalIF":4.5,"publicationDate":"2025-05-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144003197","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":"Splenectomy as an indicator for ovarian cancer spread and complete cytoreduction","authors":"Evelina Karlsson,&nbsp;Oksana Vorobii,&nbsp;Ilvars Silins,&nbsp;Inger Sundström Poromaa,&nbsp;Karin Stålberg,&nbsp;Marta Lomnytska","doi":"10.1016/j.ygyno.2025.04.592","DOIUrl":"10.1016/j.ygyno.2025.04.592","url":null,"abstract":"<div><h3>Objective</h3><div>Complete cytoreductive surgery (CRS) is a gold standard in advanced ovarian cancer (OC) treatment, and most of the time, requires upper abdominal procedures. However, there is an enormous variation regarding the reported incidence of splenectomies, and the safety and prognosis of this procedure is largely unknown. The aim of this study was to evaluate the impact of splenectomy on surgical outcomes, complications and overall survival (OS) in primary OC surgery.</div></div><div><h3>Methods</h3><div>This prospective observational cohort study comprised patients with stage IIIC-IV OC who underwent primary CRS. Cases and controls were defined based on whether splenectomy had been performed or not. Comparisons between the groups were made using logistic regression models, receiver-operator characteristics and survival analyses i.e. Kaplan-Meier and Cox proportional hazard models.</div></div><div><h3>Results</h3><div>Splenectomy was performed in 206/354 (58 %) patients, and among these - 170 (82.5 %) spleen metastases were identified. High peritoneal cancer index (PCI) was an independent predictor of splenectomy (aOR = 1.27 [95 % CI: 1.21–1.34]), with a PCI cut-off of 16 indicating need for splenectomy (AUC = 0.884). Splenectomy, PCI and surgical complexity score were all independent predictors of high-grade postoperative complications. Splenectomy, high PCI and completeness of cytoreduction were independent predictors of worse OS. Type of spleen metastasis (hilar/capsular versus parenchymal) did not influence OS.</div></div><div><h3>Conclusions</h3><div>Splenic metastatic involvement is common in OC and splenectomy is predicted by high PCI. Survival prognosis is equally impaired by all types of spleen metastasis. Splenectomy is an indicator of high tumour burden, high surgical complexity and high-grade postoperative complications, impaired survival and, indirectly, of cytoreduction success.</div></div>","PeriodicalId":12853,"journal":{"name":"Gynecologic oncology","volume":"197 ","pages":"Pages 121-128"},"PeriodicalIF":4.5,"publicationDate":"2025-05-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143921723","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":"Whole-exome sequencing provides assessment of homologous recombination deficiency for identification of PARPi-responsive ovarian tumors","authors":"Elizabeth Evans ,&nbsp;Jhalak Dholakia ,&nbsp;Jim Abraham ,&nbsp;Andrew Hinton ,&nbsp;Jian Zhang ,&nbsp;Joanne Xiu ,&nbsp;Todd Maney ,&nbsp;Matt Oberley ,&nbsp;Premal Thacker ,&nbsp;Thomas J. Herzog ,&nbsp;David Spetzler ,&nbsp;Rebecca C. Arend","doi":"10.1016/j.ygyno.2025.04.586","DOIUrl":"10.1016/j.ygyno.2025.04.586","url":null,"abstract":"<div><h3>Background/objectives</h3><div>Homologous recombination repair deficiency (HRD) is frequently detected in gynecological cancers and is associated with sensitivity to poly-ADP ribose polymerase inhibition (PARPi). BRCA1/2 mutations have been approved as biomarkers for PARPi therapy, along with genomic patterns such as genomic loss of heterozygosity (gLOH) and large-scale transitions (LSTs). Clinical applications of various HRD assays are still under investigation. Here we validate the performance of a novel HRD assay based on whole-exome sequencing (WES).</div></div><div><h3>Methods</h3><div>WES was used to evaluate gLOH, LST, and <em>BRCA</em> mutations and this data was compared to standard assays. An optimized genomic scar score (GSS) was based on combined gLOH and LST. A comprehensive HRD score was then developed, combining GSS and <em>BRCA</em> status. Survival data from 1661 PARPi-treated ovarian cancer patients was queried to optimize GSS and HRD scores associated with PARPi response.</div></div><div><h3>Results</h3><div>A comparison of WES results to the OncoScan CNV assay and Myriad MyChoice assay showed high concordance for LOH values and GSS values, respectively. Median overall survival in PARPi-treated patients was 50.8 months for GSS-high, BRCA1/2-mut, 42.7 months for GSS-high, BRCA1/2-WT, and 36.6 months for GSS-low, BRCA1/2-WT patients with significant differences between each group. Combining the BRCA1/2-mut and WT GSS-high groups resulted in a median OS value of 47.8 months, significantly higher than the GSS-low BRCA1/2-WT group.</div></div><div><h3>Conclusions</h3><div>The use of a WES assay to assess <em>BRCA</em> results, along with a GSS method incorporating gLOH and LST, produced a HRD test that is predictive for PARPi therapy.</div></div>","PeriodicalId":12853,"journal":{"name":"Gynecologic oncology","volume":"197 ","pages":"Pages 139-145"},"PeriodicalIF":4.5,"publicationDate":"2025-05-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143921725","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":"A phase 2 trial of pembrolizumab for recurrent Lynch-like versus sporadic endometrial cancers with microsatellite instability (NCT02899793): Updated survival and response analyses","authors":"Victoria M. Ettorre ,&nbsp;Stefania Bellone ,&nbsp;Michelle Greenman ,&nbsp;Blair McNamara ,&nbsp;Luca Palmieri ,&nbsp;Namrata Sethi ,&nbsp;Cem Demirkiran ,&nbsp;Katyayani Papatla ,&nbsp;Aparna Kailasam ,&nbsp;Eric R. Siegel ,&nbsp;Elena Ratner ,&nbsp;Alessandro D. Santin","doi":"10.1016/j.ygyno.2025.04.591","DOIUrl":"10.1016/j.ygyno.2025.04.591","url":null,"abstract":"<div><h3>Objective</h3><div>Microsatellite instability-high (MSI-H)/mismatch repair deficiency (dMMR) is a biomarker for response to immune checkpoint inhibitors. We report updated results including objective response rate, progression free survival, and overall survival data with 5-year follow-up in recurrent platinum-resistant, MSI-H, endometrial cancer (EC) patients fully sequenced using whole exome sequencing (WES) and treated within a prospective phase II study with pembrolizumab (<span><span>NCT02899793</span><svg><path></path></svg></span>).</div></div><div><h3>Methods</h3><div>Tumors from patients with measurable MSI-H/dMMR endometrial cancer confirmed by immunohistochemistry, polymerase chain reaction, and MLH-1 methylation assays were sequenced using whole exome sequencing and the FoundationOne platform for the identification of Lynch, Lynch-like, and MLH-1 methylated characteristics before receiving pembrolizumab 200 mg every 3 weeks for up to 24 months. The primary endpoint was objective response rate (ORR), and secondary endpoints were progression free survival (PFS), and overall survival (OS).</div></div><div><h3>Results</h3><div>After almost 97 person-years of follow-up, the Lynch-like subgroup (<em>n</em> = 6) of MSI-H/dMMR patients continues to exhibit better ORR than the methylated (<em>n</em> = 18) subgroup (100 % versus 44 %, Fisher's exact <em>P</em> = 0.024), as well as improved PFS (unreached for Lynch-like versus 14.6 months, Log-Rank <em>P</em> = 0.005) and improved OS (unreached for Lynch-like versus 32.6 months, Log-Rank <em>P</em> = 0.058). Toxicity was manageable in both groups of MSI-H patients.</div></div><div><h3>Conclusion</h3><div>Mature follow-up results continue to suggest the prognostic significance of Lynch-like versus methylated MSI-H/dMMR features in endometrial cancer patients treated with pembrolizumab in terms of ORR, PFS, and OS. Stratification for these translational aspects may be warranted in future clinical trials with immune checkpoint inhibitors in MSI-H/dMMR endometrial cancer patients.</div></div>","PeriodicalId":12853,"journal":{"name":"Gynecologic oncology","volume":"197 ","pages":"Pages 110-115"},"PeriodicalIF":4.5,"publicationDate":"2025-05-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143906637","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":"Impact of mismatch repair (MMR) status on recurrence in high intermediate risk endometrial cancer","authors":"Kelsey Jean Keverline,&nbsp;Breana Hill,&nbsp;Marianne Hom-Tedla,&nbsp;Marni Jacobs,&nbsp;Ramez N. Eskander","doi":"10.1016/j.ygyno.2025.04.588","DOIUrl":"10.1016/j.ygyno.2025.04.588","url":null,"abstract":"<div><h3>Background</h3><div>Approximately 25 % of endometrial cancers harbor deficiencies in mismatch repair (dMMR). The clinical impact of this molecular aberration remains undefined in patients with high intermediate risk (HIR) endometrial cancer.</div></div><div><h3>Methods</h3><div>We conducted a retrospective chart review of women diagnosed with Stage I high-intermediate risk endometrioid endometrial cancer in two hospital systems in Southern California between 2016 and 2018. We collected demographic information, mismatch repair status, pathology reports, and time to recurrence.</div></div><div><h3>Results</h3><div>244 patients met inclusion criteria, of which 86 (35 %) were found to be dMMR. The dMMR patient population had higher relative risks of lymphovascular space invasion (relative risk 1.63, 95 % confidence interval 1.26–2.10, <em>p</em>-value 0.0002) but were less likely to have deep myometrial invasion (relative risk 0.81, 95 % confidence interval 0.66–0.99, <em>p</em>-value 0.047) when compared to the pMMR EC cohort. No differences were found in the rate of recurrence or time to recurrence based on MMR status.</div></div><div><h3>Conclusions</h3><div>In this large, multi-institution, cohort study there were no significant differences identified between Stage I HIR dMMR and pMMR endometrioid endometrial cancer populations with regards to recurrence rates or alternate cancer-related outcomes.</div></div>","PeriodicalId":12853,"journal":{"name":"Gynecologic oncology","volume":"197 ","pages":"Pages 116-120"},"PeriodicalIF":4.5,"publicationDate":"2025-05-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143906638","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}