Gynecologic oncology最新文献

{"title":"Clinical applications of antibody drug conjugates for gynecologic malignancies: Review of available medicines and emerging therapeutics","authors":"Alyssa C. Bujnak ,&nbsp;Samantha A. Solaru ,&nbsp;Krishnansu Tewari","doi":"10.1016/j.ygyno.2025.03.013","DOIUrl":"10.1016/j.ygyno.2025.03.013","url":null,"abstract":"<div><div>With significant overall survival benefits reported in several phase 3 randomized clinical trials, the integration of anti-PD-1 immunotherapy with systemic chemotherapy has transformed the therapeutic landscape in advanced endometrial cancer and PD-L1+ recurrent/metastatic cervical cancer. For patients with FIGO stage III-IVA locally advanced cervical cancer, irrespective of PD-L1 status, chemoradiation plus pembrolizumab followed by maintenance pembrolizumab also confers a survival benefit. For newly diagnosed advanced ovarian cancer responding to primary systemic chemotherapy, maintenance therapy using PARP inhibitors and/or bevacizumab according to germline and somatic mutational analysis have been demonstrated to improve progression-free survival. Tumor heterogeneity, acquired drug resistance, and adverse events limit long-term effectiveness. Antibody-drug conjugates (ADCs) represent an innovative new class of medicines with activity in gynecologic malignancies and distinct toxicity profiles attributable to ADC construction. Adverse event mitigation strategies, biomarker discovery, and sequencing are paramount in successfully exploiting the therapeutic window provided by these novel compounds. This review discusses the application of ADCs in gynecologic cancers, including the current FDA-approved drugs mirvetuximab soravtansine, tisotumab vedotin, and trastuzumab deruxtecan, as well as relevant ongoing clinical trials, including TROP2 ADCs.</div></div>","PeriodicalId":12853,"journal":{"name":"Gynecologic oncology","volume":"195 ","pages":"Pages 180-191"},"PeriodicalIF":4.5,"publicationDate":"2025-03-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143696086","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":"Which factors predict the effectiveness of adjuvant treatment in patients with non-high-risk early-stage cervical cancer? Ancillary analysis of KGOG-1028","authors":"Junhwan Kim ,&nbsp;Jieun Jang ,&nbsp;Myong Cheol Lim ,&nbsp;Moon-Hong Kim ,&nbsp;Yun Hwan Kim ,&nbsp;Eun Seop Song ,&nbsp;Seok Ju Seong ,&nbsp;Dong Hoon Suh ,&nbsp;Jong-Min Lee ,&nbsp;Chulmin Lee ,&nbsp;Chel Hun Choi ,&nbsp;Sokbom Kang","doi":"10.1016/j.ygyno.2025.03.015","DOIUrl":"10.1016/j.ygyno.2025.03.015","url":null,"abstract":"<div><h3>Objective</h3><div>To identify predictive factors for the effectiveness of adjuvant therapy (AT) in patients with non-high-risk early-stage cervical cancer.</div></div><div><h3>Methods</h3><div>A retrospective cohort study was conducted using data from the Korean Gynecologic Oncology Group-1028, which included 1109 low-risk and 360 intermediate-risk patients diagnosed with 2018 FIGO stage IB1-IIA cervical cancer from 2000 to 2008. Disease-free survival (DFS) according to AT was evaluated in restricted patients with certain prognostic factors, such as lymphovascular space invasion (LVSI), depth of invasion (DI) of 1/3, tumor size &gt;4 cm, or nonsquamous cell carcinoma (non-SCC). In addition to the prognostic factor of interest, clinicopathologic factors were balanced between the AT-naïve and AT groups using the inverse probability of treatment weighting.</div></div><div><h3>Results</h3><div>AT was administered to 281 (25.2 %) low-risk patients and 261 (72.5 %) intermediate-risk patients. Positive LVSI, DI of deep 1/3, tumor size &gt;4 cm, and adenocarcinoma histology were significantly prognostic when tested in the AT-naïve group. AT was effective in prolonging DFS in patients with positive LVSI (hazard ratio [HR] = 0.37; 95 % CI, 0.23–0.60), DI of deep 1/3 (HR = 0.29; 95 % CI, 0.17–0.49), and tumor size &gt;4 cm (HR = 0.28; 95 % CI, 0.11–0.70). However, AT was not effective in patients with non-SCC histology (HR = 0.69; 95 % CI, 0.41–1.16).</div></div><div><h3>Conclusions</h3><div>Patients with non-high-risk early-stage cervical cancer with any of the following conditions, including positive LVSI, DI of deep 1/3, and tumor size &gt;4 cm, can benefit from AT but not those with non-SCC histology.</div></div>","PeriodicalId":12853,"journal":{"name":"Gynecologic oncology","volume":"196 ","pages":"Pages 10-15"},"PeriodicalIF":4.5,"publicationDate":"2025-03-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143697995","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":"ENGOT-OV16/NOVA trial of niraparib in recurrent ovarian cancer: Survival and long-term safety","authors":"Ursula A. Matulonis ,&nbsp;Jørn Herrstedt ,&nbsp;Amit Oza ,&nbsp;Sven Mahner ,&nbsp;Andrés Redondo ,&nbsp;Dominique Berton ,&nbsp;Jonathan S. Berek ,&nbsp;Charlotte A. Haslund ,&nbsp;Frederik Marmé ,&nbsp;Antonio González-Martín ,&nbsp;Stéphanie Bécourt ,&nbsp;Anna V. Tinker ,&nbsp;Jonathan A. Ledermann ,&nbsp;Benedict Benigno ,&nbsp;Gabriel Lindahl ,&nbsp;Nicoletta Colombo ,&nbsp;Izabela A. Malinowska ,&nbsp;Wenlei Liu ,&nbsp;Manjinder Bains ,&nbsp;Bradley J. Monk ,&nbsp;Mansoor R. Mirza","doi":"10.1016/j.ygyno.2025.03.018","DOIUrl":"10.1016/j.ygyno.2025.03.018","url":null,"abstract":"<div><h3>Objective</h3><div>To evaluate secondary efficacy endpoints and safety for the ENGOT-OV16/NOVA (<span><span>NCT01847274</span><svg><path></path></svg></span>) trial of niraparib maintenance therapy after extended follow-up and vital-status-data retrieval. Previously reported analyses (data cutoff, October 1, 2020) indicated benefit of niraparib maintenance therapy beyond first progression, but overall survival (OS) analyses were limited by missing data.</div></div><div><h3>Methods</h3><div>Patients were randomized 2:1 to niraparib (300 mg once daily) or placebo. A vital status check was extended to retrieve last-known-alive status for patients with missing survival data. Prespecified secondary efficacy outcomes (OS, chemotherapy-free interval [CFI], time to first subsequent therapy [TFST], PFS2, time to second subsequent therapy [TSST]) and safety are reported based on the extended data cutoff (March 31, 2021).</div></div><div><h3>Results</h3><div>Survival status was available for 97.6% (540/553) of randomized patients (germline <em>BRCA</em> [g<em>BRCA</em>]<em>-</em>mutated, 203; non-g<em>BRCA</em>–mutated, 350). Median OS with niraparib and placebo was 40.9 and 38.1 months, respectively, in the g<em>BRCA</em>-mutated cohort (hazard ratio [HR], 0.85; 95% confidence interval [CI], 0.61–1.20) and 31.0 and 34.8 months, respectively, in the non-g<em>BRCA</em>–mutated cohort (HR, 1.06; 95% CI, 0.81–1.37). Medians for CFI, TFST, PFS2, and TSST numerically favored niraparib in both cohorts. No new safety signals were detected.</div></div><div><h3>Conclusions</h3><div>OS did not significantly differ between treatment arms. Prespecified secondary efficacy endpoints numerically favored niraparib. Long-term safety remained consistent with the established niraparib safety profile. Taken together with the significant improvements in PFS observed in the primary analysis, these data support a favorable overall benefit–risk profile for niraparib in the recurrent OC maintenance setting.</div></div>","PeriodicalId":12853,"journal":{"name":"Gynecologic oncology","volume":"195 ","pages":"Pages 192-199"},"PeriodicalIF":4.5,"publicationDate":"2025-03-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143696087","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":"Comparative efficacy and safety of low-dose versus high-dose bevacizumab in ovarian cancer: An indirect treatment comparison","authors":"Josée-Lyne Ethier ,&nbsp;Cal Shephard ,&nbsp;Diana P. Granados ,&nbsp;Nikkita Dutta ,&nbsp;Rana Qadeer ,&nbsp;Saima Ahmad ,&nbsp;Ellen Kasireddy ,&nbsp;Mir-Masoud Pourrahmat ,&nbsp;Mir Sohail Fazeli","doi":"10.1016/j.ygyno.2025.03.022","DOIUrl":"10.1016/j.ygyno.2025.03.022","url":null,"abstract":"<div><h3>Objective</h3><div>First-line therapy for ovarian cancer involves cytoreductive surgery and platinum-based chemotherapy, with or without bevacizumab. Bevacizumab can be administered at low (7.5 mg/kg every three weeks [Q3W]) or high dose (15 mg/kg Q3W). This study compared the efficacy and safety of these dosing strategies.</div></div><div><h3>Methods</h3><div>Systematic literature review of Embase, MEDLINE®, and CENTRAL (18/09/2023) identified randomized controlled trials (RCTs) evaluating bevacizumab versus any therapy or control in ovarian, fallopian tube, or primary peritoneal cancer. Indirect treatment comparisons (ITC) of response, survival, and safety outcomes were performed, including sensitivity/subgroup analyses adjusting for heterogeneity.</div></div><div><h3>Results</h3><div>Six RCTs (sample size: 24–1528 patients) were included for ITC. Five evaluated high-dose bevacizumab with chemotherapy. The common comparator was carboplatin + paclitaxel. Trials mainly included stage III (<em>n</em> = 4) or stage II-III (<em>n</em> = 1) ovarian cancer patients; one did not report cancer stage. Primary analyses showed no significant differences between low- versus high-dose bevacizumab for partial response (risk ratio [95 % confidence interval]: 0.66 [0.42, 1.02]), complete response (1.76 [0.76, 4.11]), objective response rate (1.01 [0.63, 1.61]), progressive disease (1.08 [0.38, 3.10]), clinical benefit (0.89 [0.76, 1.03]), any grade ≥ 3 adverse event (1.53 [0.96, 2.44]), specific grade ≥ 3 adverse events, overall survival (hazard ratio: 0.93 [0.77, 1.13]), or progression-free survival (1.02 [0.86, 1.22]). Sensitivity and subgroup analyses confirmed findings.</div></div><div><h3>Conclusions</h3><div>This ITC found no significant difference in clinical outcomes between low- and high-dose bevacizumab combination therapy. Despite limitations of small sample size and heterogeneities, findings suggest that bevacizumab dose may not significantly impact ovarian cancer outcomes.</div></div>","PeriodicalId":12853,"journal":{"name":"Gynecologic oncology","volume":"196 ","pages":"Pages 1-9"},"PeriodicalIF":4.5,"publicationDate":"2025-03-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143686810","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":"Patient outcomes in advanced ovarian cancer treated with an anti-FOLR1 antibody–drug conjugate","authors":"Paul Johannet ,&nbsp;Matthew Flint ,&nbsp;M. Herman Chui ,&nbsp;Jason Konner ,&nbsp;Claire Friedman ,&nbsp;Angela K. Green ,&nbsp;Robin Guo ,&nbsp;Martee L. Hensley ,&nbsp;Chrisann Kyi ,&nbsp;Ying Liu ,&nbsp;Vicky Makker ,&nbsp;Maria Rubinstein ,&nbsp;Paul Sabbatini ,&nbsp;William P. Tew ,&nbsp;Michael B. Foote ,&nbsp;Britta Weigelt ,&nbsp;Carol Aghajanian ,&nbsp;Rachel N. Grisham ,&nbsp;Roisin E. O’Cearbhaill","doi":"10.1016/j.ygyno.2025.03.023","DOIUrl":"10.1016/j.ygyno.2025.03.023","url":null,"abstract":"<div><h3>Background</h3><div>Mirvetuximab soravtansine-gynx (MIRV) is a FOLR1-binding antibody–drug conjugate (ADC) with a microtubule inhibitor payload. We investigated MIRV's efficacy, toxicity profile, and determinants of resistance in a cohort of patients with recurrent/persistent high FOLR1-expressing high-grade serous ovarian cancer (HGSOC).</div></div><div><h3>Methods</h3><div>This retrospective study included 170 patients with recurrent/persistent FOLR1-high (≥75 % of tumor cells with ≥2+ membranous staining intensity) HGSOC who received standard-of-care MIRV monotherapy. We evaluated progression-free survival (PFS) and overall survival (OS) using the Kaplan-Meier method and multivariable Cox proportional hazards models. We classified adverse events using CTCAE v5.0.</div></div><div><h3>Results</h3><div>Overall, median PFS was 3.5 months (95 % CI, 3.0–4.1). However, 22.4 % had PFS ≥6 months and were less likely to have progressed on or within one month of prior taxane-based therapy (<em>P</em> = 0.008). Patients with previous progression on a taxane had worse PFS (HR, 1.69; 95 % CI, 1.19–2.40; <em>P =</em> 0.003) and OS (HR, 2.34; 95 % CI, 1.45–3.77; adjusted <em>P =</em> 0.0005). FOLR1 expression was lower in post-MIRV samples (<em>n</em> = 12; <em>P =</em> 0.005). New or worsening neuropathy was observed in 37.6 % of patients. Among the 34.1 % who experienced ocular toxicity, median onset was 42.5 days. Treatment was discontinued in 5.3 % of patients due to toxicity.</div></div><div><h3>Discussion</h3><div>MIRV confers meaningful PFS benefit for a subset of individuals with HGSOC. Resistance may be associated with decreased FOLR1 target expression or payload resistance. FOLR1-targeted ADCs with a different payload should be evaluated for patients who progress on MIRV but retain high tumor FOLR1 expression.</div></div>","PeriodicalId":12853,"journal":{"name":"Gynecologic oncology","volume":"195 ","pages":"Pages 173-179"},"PeriodicalIF":4.5,"publicationDate":"2025-03-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143683279","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":"Diagnostic and therapeutic advances for HER2-expressing or amplified gynecologic cancers","authors":"Elizabeth K. Lee ,&nbsp;David L. Kolin ,&nbsp;Ursula A. Matulonis ,&nbsp;Britt K. Erickson","doi":"10.1016/j.ygyno.2025.03.011","DOIUrl":"10.1016/j.ygyno.2025.03.011","url":null,"abstract":"<div><div>HER2-targeting therapies are well-described in breast, gastric, and lung cancers, however accumulating data supports a role for HER2-targeted therapies in gynecologic cancers. Despite varied methodologies for HER2 testing, evidence supports that a substantial proportion of endometrial, ovarian, cervical, and vulvar cancers overexpress HER2. This underscores the rationale for HER2-targeted therapies in these malignancies, including the use of HER2-directed tyrosine kinase inhibitors, antibody-drug conjugates, and immune-stimulating antibody conjugates. Understanding mechanisms of resistance to HER2-targeted therapies will inform possible combinatorial strategies.</div></div>","PeriodicalId":12853,"journal":{"name":"Gynecologic oncology","volume":"195 ","pages":"Pages 152-164"},"PeriodicalIF":4.5,"publicationDate":"2025-03-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143673356","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":"Development and validation of an ovarian cancer risk assessment tool for first-degree relatives of patients in the Chinese population","authors":"Yuan Li ,&nbsp;Manqi Wu ,&nbsp;Qiyu Liu ,&nbsp;Cuiyu Huang ,&nbsp;Yiming Fan ,&nbsp;Mengyang Wang ,&nbsp;Yikun Jin ,&nbsp;Liyuan Tao ,&nbsp;Xielan Yang ,&nbsp;Hongyan Guo","doi":"10.1016/j.ygyno.2025.03.017","DOIUrl":"10.1016/j.ygyno.2025.03.017","url":null,"abstract":"<div><h3>Objective</h3><div>To develop and validate an ovarian cancer risk assessment tool for first-degree relatives of patients in the Chinese population.</div></div><div><h3>Methods</h3><div>A bidirectional multicenter cohort was established, including 529 probands and 3141 first-degree relatives. Cancer incidence was analyzed using the standardized incidence ratio (SIR). Significant variables were identified through Cox regression analyses and visualized via a nomogram. Model performance was evaluated using the C-index, with first-degree relatives stratified into high- and low-risk groups based on a 10 % cancer risk threshold.</div></div><div><h3>Results</h3><div>Among 1596 first-degree female relatives, 57 ovarian cancer cases were identified, demonstrating a significant increase in SIR (SIR = 9.19; 95 % CI, 7.03–11.83; <em>p</em> &lt; 0.001). In 980 relatives with germline mutations, elevated SIRs were observed for ovarian cancer (SIR = 23.33; 95 % CI, 16.51–32.09; <em>p</em> &lt; 0.001) and breast cancer (SIR = 3.56; 95 % CI, 2.46–5.00; p &lt; 0.001). Cox regression analyses identified key risk factors, including the proband's age of onset, tumor histology, gene mutation status, family history of breast cancer, and relationship to the proband. The nomogram demonstrated good predictive accuracy, with C-indices of 0.75 (training set), 0.75 (internal validation), and 0.71 (external validation). Calibration plots and Kaplan-Meier curves confirmed strong agreement and significant differences between high- and low-risk groups (cut-off value = 2.1).</div></div><div><h3>Conclusions</h3><div>This study develops and preliminarily validates a risk assessment tool for first-degree relatives of ovarian cancer patients in China, utilizing accessible clinical and familial data to enable early identification of high-risk individuals.</div></div>","PeriodicalId":12853,"journal":{"name":"Gynecologic oncology","volume":"195 ","pages":"Pages 165-172"},"PeriodicalIF":4.5,"publicationDate":"2025-03-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143673276","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":"Endometrial cancer somatic testing practice patterns among gynecologic oncologists","authors":"J.A. DeMari ,&nbsp;D. Glassman ,&nbsp;S. Smith ,&nbsp;J.P. Darby ,&nbsp;E.V. Dressler ,&nbsp;K.E. Weaver ,&nbsp;C.M. Cosgrove","doi":"10.1016/j.ygyno.2025.03.020","DOIUrl":"10.1016/j.ygyno.2025.03.020","url":null,"abstract":"","PeriodicalId":12853,"journal":{"name":"Gynecologic oncology","volume":"195 ","pages":"Pages 149-151"},"PeriodicalIF":4.5,"publicationDate":"2025-03-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143669783","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":"Anaplastic carcinoma of the ovary: A single-institution experience and molecular analysis","authors":"Mackenzie W. Sullivan ,&nbsp;M. Herman Chui ,&nbsp;Pier Selenica ,&nbsp;Kara Long Roche ,&nbsp;Yukio Sonoda ,&nbsp;Rachel N. Grisham ,&nbsp;Chrisann Kyi ,&nbsp;Amir Momeni-Boroujeni ,&nbsp;Nadeem R. Abu-Rustum ,&nbsp;Britta Weigelt ,&nbsp;Roisin E. O'Cearbhaill","doi":"10.1016/j.ygyno.2025.03.021","DOIUrl":"10.1016/j.ygyno.2025.03.021","url":null,"abstract":"<div><h3>Objective</h3><div>We describe a tertiary referral center's experience with anaplastic ovarian carcinoma and characterize the genetic landscape of these rare tumors.</div></div><div><h3>Methods</h3><div>Anaplastic ovarian carcinomas were retrospectively identified from institutional databases from 2013 to 2023. Clinical data and survival outcomes were abstracted from the electronic medical record. Molecular data were obtained from clinical tumor-normal panel sequencing.</div></div><div><h3>Results</h3><div>Thirteen tumors were identified; 12 (92 %) were associated with or arose from a mucinous carcinoma, and 6 (46 %) were found in a mural nodule. Median age at diagnosis was 39 years (range, 19–77); 6 patients had stage I disease (3 stage IA), 1 had stage II, 5 had stage III, and 1 had stage IV. All patients underwent surgery. First-line postoperative therapy included carboplatin-paclitaxel doublet (<em>n</em> = 8), a 5-fluorouracil-oxaliplatin-based regimen (FOLFOX, <em>n</em> = 1; XELOX, <em>n</em> = 2), and ifosfamide/paclitaxel (n = 1). Two patients did not receive adjuvant chemotherapy for early-stage disease. Six patients had progression or recurrence; 5 had platinum-refractory disease and 1 had an initial progression-free interval of 6.8 months. For the 7 patients without recurrence, median follow-up was 79.7 months. Median overall survival for all patients was 28.1 months (range, 7.8–139.2). Five patients died of their disease. Ten patients had clinical panel sequencing, revealing recurrent somatic <em>KRAS</em> G12D/V hotspot mutations (8 of 10, 80 %) and genetic alterations affecting cell cycle-related genes, including <em>TP53</em> (6 of 10, 60 %) and <em>CDKN2A</em> (6 of 10, 60 %).</div></div><div><h3>Conclusions</h3><div>Anaplastic ovarian carcinoma is characterized by <em>KRAS</em>, <em>TP53</em>, and <em>CDKN2A</em> alterations. Novel treatment approaches are needed due to the high rate of platinum-refractory disease.</div></div>","PeriodicalId":12853,"journal":{"name":"Gynecologic oncology","volume":"195 ","pages":"Pages 144-148"},"PeriodicalIF":4.5,"publicationDate":"2025-03-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143669734","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":"Validating the predicted impact of HPV vaccination on HPV prevalence, cervical lesions, and cervical cancer: A systematic review of population level data and modelling studies","authors":"Daniël de Bondt ,&nbsp;Emi Naslazi ,&nbsp;Erik Jansen ,&nbsp;Rachel Kupets ,&nbsp;Bronwen McCurdy ,&nbsp;Christine Stogios ,&nbsp;Inge de Kok ,&nbsp;Jan Hontelez","doi":"10.1016/j.ygyno.2025.03.008","DOIUrl":"10.1016/j.ygyno.2025.03.008","url":null,"abstract":"<div><h3>Background</h3><div>We compared model predictions with independently published primary data from population-based studies on the impact of HPV vaccination on HPV prevalence, cervical cancer and its precursors.</div></div><div><h3>Methods</h3><div>We searched Cochrane Library, EMBASE, MEDLINE, Web of Science for studies concerning high-income countries published between 2005 to June 2, 2023. Relative risk (RR) for HPV-related outcomes comparing the pre-vaccination and post-vaccination periods were collected from observational and modelling studies. The relationship between vaccination coverage and observed relative reductions was determined using meta-regressions, and we compared model prediction to observations.</div></div><div><h3>Findings</h3><div>We identified a total of 5649 potential articles, of which one systematic review, 14 observational studies and 32 modelling studies met our inclusion criteria. A clear relation was found between the RR of HPV diseases related outcomes in the pre- versus post-vaccination era and the vaccination coverage, with 23 out of 28 data points and 19 out of 20 data points showing significant reductions in HPV prevalence and CIN2+ prevalence respectively. Around 67 % (n/<em>N</em> = 12/18) of model predictions were more optimistic on HPV prevalence reductions compared to the 95 % CI of the meta-regression derived from observational studies. For CIN2+ lesions, 48 % (n/<em>N</em> = 31/64) of model predictions for CIN2+ outcomes fell within the 95 % CI.</div></div><div><h3>Interpretation</h3><div>Model predictions and observational data agree that HPV vaccination can have a substantial impact on HPV related outcomes on a population level. Despite large heterogeneity in observational data and modelling studies, it is particularly encouraging that model predictions on the impact of HPV vaccination on CIN2+ model lesions align with observational studies.</div></div><div><h3>Funding</h3><div>Ontario Health (formerly known as Cancer Care Ontario).</div></div>","PeriodicalId":12853,"journal":{"name":"Gynecologic oncology","volume":"195 ","pages":"Pages 134-143"},"PeriodicalIF":4.5,"publicationDate":"2025-03-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143641839","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}