Gynecologic oncology最新文献

{"title":"A clinical study of tremelimumab, alone or in combination with olaparib, for recurrent epithelial ovarian cancer","authors":"Stéphanie Gaillard ,&nbsp;Neha Verma ,&nbsp;Maureen Berg ,&nbsp;Jeanne Harrison ,&nbsp;Peng Huang ,&nbsp;James M. Leatherman ,&nbsp;Michele Doucet ,&nbsp;Rupashree Sen ,&nbsp;Aditya Suru ,&nbsp;Hongyan Cai ,&nbsp;Jennifer Durham ,&nbsp;Danijela Jelovac ,&nbsp;Ashley Cimino-Mathews ,&nbsp;Christopher Cherry ,&nbsp;Sudipto Ganguly ,&nbsp;Leisha A. Emens","doi":"10.1016/j.ygyno.2025.01.015","DOIUrl":"10.1016/j.ygyno.2025.01.015","url":null,"abstract":"<div><h3>Objective</h3><div>PARP inhibitors may work synergistically to improve the efficacy of immunotherapy in patients with epithelial ovarian cancer (EOC). We performed a parallel-arm study of tremelimumab, alone or with olaparib, in patients with recurrent EOC.</div></div><div><h3>Methods</h3><div>Eligibility criteria included measurable disease and progression &lt;12 months from last platinum. Participants were randomized to Arm A (tremelimumab monotherapy, 10 mg/kg/dose intravenously [IV]) or Arm B (dose level 1 [DL1] olaparib orally 150 mg twice daily with tremelimumab IV 3 mg/kg/dose and DL2 olaparib orally 150 mg twice daily with tremelimumab IV 10 mg/kg/dose). Primary objectives were safety, change in peripheral ICOS⁺ T cells, and identification of optimal dose combination.</div></div><div><h3>Results</h3><div>Among 24 total patients (12 on Arm A, 6 on Arm B-DL1, 6 on Arm B-DL2), the most common grade 3 toxicities were rash (13 %), immune-mediated hepatitis (8 %), and colitis (8 %). No grade ≥ 4 toxicities were identified. No dose-limiting toxicities were identified. One patient (Arm B-DL2) experienced a partial response; no complete responses were observed. Ten patients (7 on Arm A, 2 on Arm B-DL2, and 1 on Arm B-DL1) had a best response of stable disease. There was a significant increase in CD4⁺ICOS⁺ and CD8⁺ICOS⁺ T cells at both C1D15 and C1D22 in groups treated with tremelimumab IV 10 mg/kg/dose, but not in those treated with tremelimumab 3 mg/kg/dose.</div></div><div><h3>Conclusions</h3><div>Tremelimumab IV 10 mg/kg/dose with olaparib 150 mg orally twice daily was safe and feasible. Tremelimumab 10 mg/kg/dose (as opposed to 3 mg/kg/dose) was required for immune activation, although this did not translate into clinical responses.</div></div>","PeriodicalId":12853,"journal":{"name":"Gynecologic oncology","volume":"194 ","pages":"Pages 41-47"},"PeriodicalIF":4.5,"publicationDate":"2025-02-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143394589","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 telehealth legislation on gynecologic oncology services: Policy updates","authors":"Elizabeth A. Tubridy ,&nbsp;Aaliyah Campbell ,&nbsp;Lakeisha Mulugeta-Gordon ,&nbsp;Leslie Andriani ,&nbsp;Emily G. Gleason ,&nbsp;Anna Jo Bodurtha Smith ,&nbsp;Emily M. Ko","doi":"10.1016/j.ygyno.2025.02.003","DOIUrl":"10.1016/j.ygyno.2025.02.003","url":null,"abstract":"","PeriodicalId":12853,"journal":{"name":"Gynecologic oncology","volume":"194 ","pages":"Pages 48-50"},"PeriodicalIF":4.5,"publicationDate":"2025-02-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143394587","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":"HER2 expression in a molecularly defined cohort of endometrial cancer patients: The SPECTRUM study","authors":"Alfonso Cortés-Salgado ,&nbsp;Esther Moreno-Moreno ,&nbsp;Irene Carretero-Barrio ,&nbsp;Tamara Caniego-Casas ,&nbsp;Eva Cristóbal ,&nbsp;Laura Del Campo-Albendea ,&nbsp;Eva Guerra ,&nbsp;Víctor Alía ,&nbsp;Patricia Pérez de Aguado ,&nbsp;Virginia Corraliza ,&nbsp;José Palacios ,&nbsp;Belén Pérez-Mies","doi":"10.1016/j.ygyno.2025.02.005","DOIUrl":"10.1016/j.ygyno.2025.02.005","url":null,"abstract":"<div><h3>Background</h3><div>HER2 antibody-drug conjugates like Trastuzumab deruxtecan (TDxd) have shown efficacy in HER2-low cancers, however the prevalence and clinical impact of HER2-low in endometrial cancer (EC) remains unclear. This study investigates HER2 expression in EC, focusing on HER2-low frequency, its distribution across histologic and molecular subtypes, intratumoral heterogeneity, and prognostic significance.</div></div><div><h3>Methods</h3><div>This retrospective analysis included EC patients categorized histologically and molecularly, using ASCO/CAP HER2 scoring guidelines for endometrial, gastric, and breast cancers. The main aim was to determine HER2-low frequency by molecular subtype, with secondary goals of assessing HER2 heterogeneity, changes between primary and recurrent tumors, guidelines concordance and the impact of HER2 status on recurrence-free (RFS) and overall survival (OS).</div></div><div><h3>Results</h3><div>193 EC patients were included, 111 low grade endometrioid EC and 82 high grade EC with various histotypes. Based on endometrial criteria, 69.9 % were HER2-negative, 25.8 % HER2-low, and 4.3 % HER2-positive, with HER2-low being most common in POLEmut (66.7 %) and p53abn (45.1 %) subtypes. Low heterogeneity in HER2 expression was observed between different tumors areas and between primary tumors and their recurrences. The endometrial and gastric criteria had high concordance (88.7 %), with endometrial guidelines detecting more HER2-low cases. Neither HER2-low nor HER2-positivity versus HER2-negativity had an impact on RFS or OS, with the stage at diagnosis being the only factor associated with survival, while age was associated only with OS.</div></div><div><h3>Conclusions</h3><div>This study highlights the distribution of HER2-low across EC molecular subtypes, with endometrial criteria proving more sensitive for identifying HER2-low cases, though HER2 status had no prognostic value in this cohort.</div></div>","PeriodicalId":12853,"journal":{"name":"Gynecologic oncology","volume":"194 ","pages":"Pages 33-40"},"PeriodicalIF":4.5,"publicationDate":"2025-02-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143394588","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Rechallenge with platinum-based chemotherapy in patients with platinum-resistant ovarian carcinoma: A cohort study","authors":"Carmine Valenza ,&nbsp;Marta Mongillo ,&nbsp;Maria Vittoria Visconti ,&nbsp;Jalissa Katrini ,&nbsp;Dario Trapani ,&nbsp;Laura Boldrini ,&nbsp;Lorenzo Guidi ,&nbsp;Alessia Farfalla ,&nbsp;Daniela Malengo ,&nbsp;Giuseppe Caruso ,&nbsp;Silvia Derio ,&nbsp;Mariateresa Lapresa ,&nbsp;Gabriella Parma ,&nbsp;Elena Biagioli ,&nbsp;Emanuela Omodeo Salé ,&nbsp;Giuseppe Curigliano ,&nbsp;Nicoletta Colombo","doi":"10.1016/j.ygyno.2025.01.014","DOIUrl":"10.1016/j.ygyno.2025.01.014","url":null,"abstract":"<div><h3>Background</h3><div>According to the 2018 ESMO-ESGO consensus conference recommendations on ovarian cancer, platinum rechallenge could be considered in patients with platinum-resistant disease following a treatment with a non‑platinum regimen, if they had not progressed during prior platinum therapy. However, few data are available in this specific setting, especially after the incorporation of novel agents in the current treatment algorithm for ovarian cancer.</div></div><div><h3>Methods</h3><div>We conducted a single-center, retrospective, cohort study to evaluate the activity of platinum rechallenge in patients with high-grade ovarian cancer, progressing on at least one non‑platinum regimen for platinum-resistant disease, from January 2010 to June 2024, at the European Institute of Oncology (Italy). A sample size of 30 patients allowed to estimate a 6-month progression-free survival (PFS) rate of 30 %, with a 95 % confidence interval (CI) ranging from 14 % to 47 %.</div></div><div><h3>Results</h3><div>30 patients were included: 23 (77 %) received rechallenge with carboplatin and 7 (23 %) with cisplatin. The median number of previous treatment lines was 3 (interquartile range: 3–4). The objective response rate was 27 % (95 % CI: 12–46 %) and the disease control rate was 80 % (95 % CI: 61–92). After a median follow-up of 14.1 months (range: 3.3–52.7), the median PFS was 5.4 months (95 % CI: 2.5–8.2) and the 6-month PFS rate was 47 % (95 % CI: 28–63 %).</div></div><div><h3>Conclusions</h3><div>Platinum rechallenge can be a viable treatment option for selected patients with platinum-resistant ovarian cancer who have previously received a non‑platinum regimen. This study suggests that we could dynamically reassess whether platinum is the best option during the patient's treatment history.</div></div>","PeriodicalId":12853,"journal":{"name":"Gynecologic oncology","volume":"194 ","pages":"Pages 11-17"},"PeriodicalIF":4.5,"publicationDate":"2025-02-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143350424","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":"Real-world efficacy and toxicity of olaparib maintenance therapy in Korean ovarian cancer patients with an exploratory analysis of BRCA mutations","authors":"Junhwan Kim ,&nbsp;So-Yeon Park ,&nbsp;Ju-Hyun Kim ,&nbsp;Shin-Wha Lee ,&nbsp;Jeong-Yeol Park ,&nbsp;Jong-Hyeok Kim ,&nbsp;Yong-Man Kim ,&nbsp;Dae-Yeon Kim","doi":"10.1016/j.ygyno.2025.01.013","DOIUrl":"10.1016/j.ygyno.2025.01.013","url":null,"abstract":"<div><h3>Objective</h3><div>To evaluate the real-world efficacy and toxicity of olaparib maintenance therapy in Korean patients with <em>BRCA</em>-mutated ovarian cancer (OC), with an exploratory analysis of <em>BRCA</em> mutations.</div></div><div><h3>Methods</h3><div>We conducted a retrospective analysis of Korean <em>BRCA</em>-mutated OC patients treated with olaparib maintenance therapy as first-line (1Lm) or second−/subsequent-line (2Lm +) at Asan Medical Center, South Korea, from August 2015 to April 2023. Survival outcomes, including progression-free survival (PFS) and overall survival (OS), as well as toxicity, were analyzed with patient characteristics and <em>BRCA</em> mutations.</div></div><div><h3>Results</h3><div>In 1Lm (<em>n</em> = 70), the 2-year PFS was 75.5 % and the 3-year OS was 98.5 %. In 2Lm + (<em>n</em> = 83), the 2-year PFS was 54.8 % and the 3-year OS was 87.3 %. The pathogenic p.Leu1780Pro <em>BRCA1</em> mutation was a poor prognostic factor for PFS in 1Lm (hazard ratio [HR], 5.66). In 2Lm +, platinum-free interval ≥ 12 months was associated with better PFS (adjusted HR [aHR], 0.48) and OS (aHR, 0.31), whereas CA-125 ≥ 10 IU/mL at olaparib initiation was a poor prognostic factor (aHR, 2.12). A longer time interval between the last chemotherapy and maintenance therapy in 1Lm correlated with reduced hematologic toxicity ≥ grade 3 (odd ratio, 0.75) during maintenance therapy. Drug discontinuation due to toxicity occurred in 1.4 % of 1Lm and 6.0 % of 2Lm + .</div></div><div><h3>Conclusions</h3><div>Olaparib maintenance therapy was effective and tolerable in Korean <em>BRCA</em>-mutated OC patients, though the poor prognosis of the p.Leu1780Pro <em>BRCA1</em> mutation in 1Lm warrants further investigation.</div></div>","PeriodicalId":12853,"journal":{"name":"Gynecologic oncology","volume":"194 ","pages":"Pages 25-32"},"PeriodicalIF":4.5,"publicationDate":"2025-02-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143350423","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":"Metformin for patients with advanced stage ovarian cancer: A randomized phase II placebo-controlled trial","authors":"Iris L. Romero ,&nbsp;Ernst Lengyel ,&nbsp;Andrea E. Wahner Hendrickson ,&nbsp;Gustavo C. Rodriguez ,&nbsp;Charles A. Leath III ,&nbsp;Rodney P. Rocconi ,&nbsp;Michael J. Goodheart ,&nbsp;Summer Dewdney ,&nbsp;Theodore Karrison ,&nbsp;Gini F. Fleming ,&nbsp;S. Diane Yamada","doi":"10.1016/j.ygyno.2025.02.001","DOIUrl":"10.1016/j.ygyno.2025.02.001","url":null,"abstract":"<div><h3>Objective</h3><div>The primary aim of this study was to determine if metformin, an oral biguanide administered with first-line chemotherapy and continued as maintenance therapy, improves progression-free survival (PFS) for patients with advanced-stage ovarian cancer.</div></div><div><h3>Methods</h3><div>Patients with pathologically confirmed advanced-stage ovarian cancer undergoing primary debulking or neoadjuvant platinum-based chemotherapy followed by surgery were eligible to participate. Patients were randomized 1:1 to receive platinum/taxane-based chemotherapy with metformin 850 mg orally twice per day or placebo, followed by maintenance therapy (metformin or placebo) for two years from the date of randomization.</div></div><div><h3>Results</h3><div>108 evaluable patients were enrolled; 54 were randomly assigned to metformin, and 54 to placebo. Sixty-six percent (<em>n</em> = 71) received neoadjuvant therapy, 31 % (<em>n</em> = 33) primary debulking surgery, and 88 % (<em>n</em> = 93) had tumors of high-grade serous histology. The primary endpoint, PFS, was not significantly different between the treatment groups (1-sided <em>p</em>-value = 0.31; adjusted hazard ratio [HR] = 0.87, 95 % confidence interval [CI]: 0.56–1.36). Median PFS was 15.4 months (95 % CI: 11.2–23,5) for metformin and 14.3 months (95 % CI: 11.6–18.0) for placebo. Overall survival (OS) was not significantly different (2-sided p-value = 0.21; adjusted HR = 1.49, 95 % CI: 0.86–2.59), with a median of 40.7 months (95 % CI: 28.0–48.2) for metformin versus 43.8 months (95 % CI: 35.3–57.2) for placebo. The addition of metformin was well tolerated, and there were no differences in toxicity between the two groups.</div></div><div><h3>Conclusion</h3><div>Although it was well-tolerated, adding metformin to first-line platinum/taxane-based therapy does not improve PFS or OS for patients with newly diagnosed advanced stage ovarian cancer.</div></div>","PeriodicalId":12853,"journal":{"name":"Gynecologic oncology","volume":"194 ","pages":"Pages 18-24"},"PeriodicalIF":4.5,"publicationDate":"2025-02-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143348769","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":"Chemotherapy Response Score (CRS): A comprehensive review of its prognostic and predictive value in High-Grade Serous Carcinoma (HGSC)","authors":"Gian Franco Zannoni ,&nbsp;Giuseppe Angelico ,&nbsp;Saveria Spadola ,&nbsp;Emma Bragantini ,&nbsp;Giancarlo Troncone ,&nbsp;Filippo Fraggetta ,&nbsp;Angela Santoro","doi":"10.1016/j.ygyno.2025.01.012","DOIUrl":"10.1016/j.ygyno.2025.01.012","url":null,"abstract":"<div><div>Ovarian carcinoma, the second most common gynecological cancer in Western countries, is frequently diagnosed at advanced stages, necessitating complex treatment strategies. While cytoreductive surgery remains the standard for improving survival, neoadjuvant chemotherapy (NACT) has become essential for cases unsuitable for immediate surgery, aiming to reduce tumor burden preoperatively. Introduced in 2015, the Chemotherapy Response Score (CRS) is now a key histopathological tool for assessing response to NACT, stratifying patients into three response categories. CRS3 is associated with improved progression-free survival (PFS) and overall survival (OS), while CRS1 and CRS2 are linked to poorer outcomes. Validated across clinical cohorts, CRS has proven valuable not only as a prognostic tool but also as a predictor for molecular-targeted therapies, such as PARP inhibitors, especially in BRCA wild-type patients. Studies also suggest a potential role for CRS in guiding the use of PD-L1 inhibitors, especially in partial responders (CRS1 and CRS2), where immunotherapy may complement chemotherapy. In the present paper we exlored the actual knowledge on CRS scoring for ovarian carcinoma. Diagnostic and prognostic implications of CRS as well as its correlation with therapeutic response and other biomarkers are discussed.</div></div>","PeriodicalId":12853,"journal":{"name":"Gynecologic oncology","volume":"194 ","pages":"Pages 1-10"},"PeriodicalIF":4.5,"publicationDate":"2025-02-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143347594","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Barriers to early detection: Insurance denials for breast MRI screening in women with germline BRCA1/2 mutations","authors":"S. Gordhandas ,&nbsp;C. Gellman ,&nbsp;S. Ingber ,&nbsp;T. Yen ,&nbsp;R. Kahn ,&nbsp;S. Kyana ,&nbsp;A. Taffuri ,&nbsp;S. Sokolowski ,&nbsp;D. Martinez ,&nbsp;P. Garcia ,&nbsp;S. Mullangi ,&nbsp;K. Long Roche ,&nbsp;N. Abu-Rustum ,&nbsp;D. Mangino ,&nbsp;M. Pilewskie ,&nbsp;E. Sutton ,&nbsp;E. Aviki","doi":"10.1016/j.ygyno.2024.12.016","DOIUrl":"10.1016/j.ygyno.2024.12.016","url":null,"abstract":"<div><h3>Objectives</h3><div>Women with germline <em>BRCA1/2</em> pathogenic variants (<em>gBRCA1/2</em>) are recommended to undergo annual breast MRI and mammography. Our objective was to describe the frequency of insurance denials for annual breast MRIs in women with g<em>BRCA1/2</em> and determine denial trends.</div></div><div><h3>Methods</h3><div>Women with g<em>BRCA1/2</em> following in a high-risk breast cancer clinic with breast MRIs ordered from 2020 to 2021 were identified and cross-referenced with a database of insurance denials. Radiology records were queried to determine if screening breast MRIs were performed in 2020 and 2021. Rates of MRI denials and outcomes after appeal were determined.</div></div><div><h3>Results</h3><div>There were 682 women with g<em>BRCA1/2</em> who had screening breast MRIs ordered from 2020 to 2021, including 318 (47 %) <em>BRCA1</em>, 356 (52 %) <em>BRCA2</em>, and 8 (1 %) with both. 73 women (11 %) had an MRI denied. Women insured through Medicaid had the highest rates of denials (2020: 7 %, 2021: 18 %), followed by commercial insurance (2020: 6 %, 2021: 9 %). There were significantly more denials in 2021 compared to 2020 (<em>p</em> = 0.044), and 2021 denials were more likely to be denied on appeal. Of women with denials, 4 (14 %) in 2020 and 5 (11 %) in 2021 did not have a screening MRI performed. One patient with DCIS had an MRI denial prior to diagnosis.</div></div><div><h3>Conclusion</h3><div>Breast MRI insurance denials were present in 11 % of this high-risk cohort, and 14 % of women with denials did not undergo annual screening. There were significantly more denials in 2021, suggesting worsening barriers for these patients and added burden on providers to appeal for appropriate screening tests.</div></div>","PeriodicalId":12853,"journal":{"name":"Gynecologic oncology","volume":"193 ","pages":"Pages 20-23"},"PeriodicalIF":4.5,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142927092","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":"Cervical stromal invasion and molecular characterization in stage II-IV endometrial cancers","authors":"Luigi A. De Vitis ,&nbsp;Fiorella E. Reyes-Baez ,&nbsp;Gabriella Schivardi ,&nbsp;Maryam Shahi ,&nbsp;Angela J. Fought ,&nbsp;Michaela E. McGree ,&nbsp;Ilaria Capasso ,&nbsp;Leah Grcevich ,&nbsp;Ilaria Betella ,&nbsp;Mariacristina Ghioni ,&nbsp;Elena Guerini-Rocco ,&nbsp;Giovanni D. Aletti ,&nbsp;William Cliby ,&nbsp;Francesco Multinu ,&nbsp;Carrie L. Langstraat ,&nbsp;Andrea Mariani ,&nbsp;Gretchen E. Glaser","doi":"10.1016/j.ygyno.2024.12.013","DOIUrl":"10.1016/j.ygyno.2024.12.013","url":null,"abstract":"<div><h3>Objective</h3><div>The optimal treatment for patients with cervical stromal invasion (CSI) in endometrial cancer (EC) remains unclear. We aimed to test the prognostic role of molecular classification in EC patients with CSI.</div></div><div><h3>Methods</h3><div>A retrospective, multicenter review of EC patients with CSI was performed. EC cases were assigned to one of the molecular classes: <em>POLE</em> mutated (POLEmut), MMR deficient (MMRd), p53 abnormal (p53abn), or no specific molecular profile (NSMP). Three-year recurrence-free survival (RFS) from surgery was estimated using the Kaplan-Meier method. Cox proportional hazards regression models were fit to adjust for confounders.</div></div><div><h3>Results</h3><div>Overall, 162 EC patients with CSI were identified: 70 (43.2 %) NSMP, 49 (30.2 %) p53abn, 40 (24.7 %) MMRd, 3 (1.9 %) POLEmut. POLEmut cases were excluded from further analysis, because of the small number of patients identified. At univariate analysis, molecular class was significantly associated with recurrence within 3 years after surgery (<em>p</em> = 0.04). Three-year RFS was 59.9 % (95 % confidence interval [CI], 46.1–77.8 %) for NSMP, 50.6 % (95 % CI, 34.9–73.2 %) for MMRd, and 33.1 % (95 % CI, 19.7–55.3 %) for p53abn. After adjusting for stage and grade, molecular class was no longer significantly associated with recurrence within three years (<em>p</em> = 0.28).</div></div><div><h3>Conclusions</h3><div>Traditional risk factors such as grade and stage remain critical in determining the prognosis of endometrial cancer with cervical stromal invasion. This study highlights the importance of integrating both molecular and morphological features in determining the prognosis of endometrial cancer, with particular emphasis on endometrioid histotypes.</div></div>","PeriodicalId":12853,"journal":{"name":"Gynecologic oncology","volume":"193 ","pages":"Pages 81-88"},"PeriodicalIF":4.5,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142970382","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":"High prevalence of FAP+ cancer-associated fibroblasts predicts poor outcome in patients with high-grade serous ovarian cancer with high CD8 T-cell density","authors":"Sara Corvigno ,&nbsp;Josefin Fernebro ,&nbsp;Josefin Severin Karlsson ,&nbsp;Artur Mezheieusky ,&nbsp;Alfonso Martín-Bernabé ,&nbsp;Laura Martin De La Fuente ,&nbsp;Sofia Westbom-Fremer ,&nbsp;Joseph W. Carlson ,&nbsp;Christian Klein ,&nbsp;Paivi Kannisto ,&nbsp;Ingrid Hedenfalk ,&nbsp;Susanne Malander ,&nbsp;Arne Östman ,&nbsp;Hanna Dahlstrand","doi":"10.1016/j.ygyno.2025.01.010","DOIUrl":"10.1016/j.ygyno.2025.01.010","url":null,"abstract":"<div><h3>Objective</h3><div>Studies have implied that fibroblasts may act as regulators of immune cells in the tumor microenvironment (TME). We investigated the clinical relevance of fibroblast activation protein (FAP) positive stroma in high-grade serous ovarian cancer (HGSC) in relation to CD8+ lymphocyte's infiltration.</div></div><div><h3>Methods</h3><div>In a discovery cohort (<em>N</em> = 113) of HGSC, expression of FAP and CD8 in the TME was analyzed with immunohistochemistry. Results were correlated with overall survival (OS) and progression-free survival (PFS). The findings were validated in an independent cohort of HGSC (<em>N</em> = 121) and in public available datasets.</div></div><div><h3>Results</h3><div>High infiltration of CD8+ cells in the TME of HGSC was found to be associated with longer OS, as previously known. Increased expression of FAP was associated with shorter median PFS (11.4 vs. 18.6 months) in tumors with high density of CD8+ cells (HR 4.03, CI 95 % 1.38–11.72, <em>p</em> = 0.01). Similarly, in the validation cohort, high intensity of FAP in cases with high density of CD8+ cells was associated with shorter OS, 31.5 vs 76.9 months (HR 2.83; 95 % CI 1.17–6.86, <em>p</em> = 0.02). The results were consistent in multivariable analyses. The association between high FAP expression and poor outcome in high density CD8 HGSC was also confirmed in publicly available datasets.</div></div><div><h3>Conclusions</h3><div>The TME infiltration of FAP-positive fibroblasts is associated with poor prognosis in HGSC with high CD8+ cells density. Targeting the FAP+ subset of fibroblasts may unlock the local immune-activation in the TME thus enhance the positive prognostic effect of T-cells in ovarian cancer.</div></div>","PeriodicalId":12853,"journal":{"name":"Gynecologic oncology","volume":"193 ","pages":"Pages 148-155"},"PeriodicalIF":4.5,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143212369","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}