Gynecologic oncology最新文献

{"title":"Serum CA125 levels in the context of ProMisE molecular classification provides pre-operative prognostic information that can direct endometrial cancer management","authors":"Andrea Neilson ,&nbsp;Amy Jamieson ,&nbsp;Derek Chiu ,&nbsp;Samuel Leung ,&nbsp;Amy Lum ,&nbsp;Stefan Kommoss ,&nbsp;David G. Huntsman ,&nbsp;Aline Talhouk ,&nbsp;C. Blake Gilks ,&nbsp;Jessica N. McAlpine","doi":"10.1016/j.ygyno.2024.12.010","DOIUrl":"10.1016/j.ygyno.2024.12.010","url":null,"abstract":"<div><h3>Objective</h3><div>Previous research suggests serum CA125 reflects extra-uterine disease in patients with endometrial carcinoma (EC). Our objective was to determine if CA125 can identify patients with extra-uterine and/or nodal metastases, the association of this biomarker with EC molecular subtype, and to explore an optimal cutoff in this context.</div></div><div><h3>Methods</h3><div>We assessed the association of CA125 levels with clinicopathologic and outcomes data on a cohort of 1107 molecularly classified EC.</div></div><div><h3>Results</h3><div>Abnormal CA125 (&gt;35kU/L) was associated with higher stage and lymph node metastases (LNM) in all EC and in each molecular subtype on univariate (<em>p</em> &lt; 0.01) and multivariate (<em>p</em> &lt; 0.05) analyses. <em>POLE</em>mut had the lowest median CA125 level and proportion of CA125 abnormal patients, and p53abn the highest proportion (<em>p</em> &lt; 0.001). CA125 &gt; 35 kU/L had a sensitivity of 0.82, specificity 0.53, positive-predictive-value 0.92, and negative-predictive-value 0.31 for LNM, with similar values for stage&gt;I. CA125 &gt; 35 kU/L was associated with worse overall (OS), disease-specific (DSS), and progression-free survival (PFS) in all EC, p53abn (OS, DSS, PFS), NSMP (OS, DSS), and MMRd (OS, DSS) subtypes. CA125 &gt; 35 kU/L demonstrated a relative risk (RR) of 2.50 with presence of stage III/IV disease (<em>p</em> &lt; 0.001) and RR 18.4 for the presence of synchronous endometrial and ovarian carcinomas (SEOC)/co-existing adnexal malignancies (CAM) (p &lt; 0.001). An exploratory cut point, optimized for correlation with DSS (CA125 &gt; 24 kU/L) show similar association with clinical parameters and survival outcome.</div></div><div><h3>Conclusions</h3><div>CA125 levels are associated with molecular subtype, stage&gt;I disease, and SEOC/CAM. CA125 remains a useful clinical tool in the triage of EC in the era of molecular classification.</div></div>","PeriodicalId":12853,"journal":{"name":"Gynecologic oncology","volume":"193 ","pages":"Pages 1-11"},"PeriodicalIF":4.5,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142908844","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":"PD-L1-Expression in primary and recurrent vulvar squamous cell cancer","authors":"Frederik A. Stuebs ,&nbsp;Antje Knöll ,&nbsp;Arndt Hartmann ,&nbsp;Leah-Sophie Leikauf ,&nbsp;Christian Matek ,&nbsp;Nelson John ,&nbsp;Lothar Häberle ,&nbsp;Matthias W. Beckmann ,&nbsp;Carol I. Geppert","doi":"10.1016/j.ygyno.2025.01.001","DOIUrl":"10.1016/j.ygyno.2025.01.001","url":null,"abstract":"<div><h3>Background</h3><div>Squamous cell vulvar carcinoma is a rare malignant disease of women. In higher tumor stages survival rates are poor. Therapy options are limited. Immunoncology plays an increasing role in the treatment of gynecology cancers. Data on the expression of PD-L1 in vulvar cancer are rare and contradictory. We sought to describe the expression of PD-L1 in VSCC in respect to the clinicopathologic characteristics of the tumor.</div></div><div><h3>Study design</h3><div>We conducted a retrospective analysis including women with primary and recurrent vulvar cancer between 2000 and 2021. A next generation tissue micro array (ngTMA) was constructed for the analysis of PD-L1 expression.</div></div><div><h3>Results</h3><div>In total 238 women with primary VSCC and 66 cases of local or distant recurrent vulvar cancer were included. 80 women with primary VSCC (33.6 %) had tumors with common positive score (CPS) &lt;1 and 63 women (26.5 %) had tumors with CPS 1- &lt; 10 and 95 women with CPS ≥10 (39.9 %). In the PD-L1 positive group the rates of p53+, groin metastasis, lymphatic invasion and tumor infiltration lymphocytes were higher as compared to PD-L1 negative (CPS &lt;1). There was no significant influence of CPS in overall survival in addition to other prognostic factors (<em>P</em> = 0.13, likelihood ratio test).</div></div><div><h3>Conclusion</h3><div>PD-L1 expression in primary vulvar cancer is associated with poorer prognosis. Hence, PD-L1 is a possible target for immune checkpoint inhibitors and women might benefit from special treatment options.</div></div>","PeriodicalId":12853,"journal":{"name":"Gynecologic oncology","volume":"193 ","pages":"Pages 98-104"},"PeriodicalIF":4.5,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142970386","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":"Primary prevention of post-molar gestational trophoblastic neoplasia in high-risk complete hydatidiform mole: A single-dose prophylactic actinomycin D, associated with uterine evacuation - a long retrospective cohort study","authors":"Elza Maria Hartmann Uberti ,&nbsp;Lidia Rosi de Freitas Medeiros ,&nbsp;Rodrigo Bernardes Cardoso ,&nbsp;Karine Paiva Muller ,&nbsp;Cassiano Burman Patias ,&nbsp;Thaís Feiten Nunes ,&nbsp;Rosilene Jara Reis ,&nbsp;Josenel Maria Barcelos Marçal","doi":"10.1016/j.ygyno.2025.01.003","DOIUrl":"10.1016/j.ygyno.2025.01.003","url":null,"abstract":"<div><h3>Objective</h3><div>To evaluate the efficacy of actinomycin D (Act<img>D) as prophylactic chemotherapy (P-chem) in patients with high-risk complete hydatidiform mole (Hr-CHM) on progression to gestational trophoblastic neoplasia (GTN).</div></div><div><h3>Methods</h3><div>From 1996 to 2023, 426 Hr-CHMs were selected in a cohort of 1623 patients with gestational trophoblastic disease (GTD). From 1996 to 2023, 290 patients with Hr-CHMs received a single bolus dose of Act-D at the time of uterine evacuation (Hr-CHM P-chem group); 136 with the same risk factors did not receive P-chem (Hr-CHM control group). The variables assessed in post-molar GTN were incidence and morbidity considering hCG serum level at diagnosis, relapse frequency, hysterectomy rates.</div></div><div><h3>Results</h3><div>Post-molar GTN was diagnosed in 19 % of the patients with Hr-CHM P-Chem (55/290) and in 39.7 % of the patients in the Hr-CHM control group (54/136) (<em>P</em> &lt; 0.001). The relative risk of developing post-molar GTN decreased by 52 % (RR = 0.48; 95 % CI: 0.35–0.66; <em>P</em> &lt; 0.001), with a number needed to treat (NNT) of 5. Patients in the P-chem group had a lower hCG serum level (<em>P</em> = 0.007), lower risk of recurrence (<em>P</em> = 0.001) and lower risk of hysterectomy (<em>P</em> = 0.04), with no effect on time to GTN diagnosis (<em>P</em> = 0.09), first line chemotherapy response (<em>P</em> = 0.50) and time to remission (<em>P</em> = 0.72).</div></div><div><h3>Conclusion</h3><div>A single bolus dose of Act-D (1.25 mg/m2) given as P-chem during uterine evacuation in patients with Hr-CHM may safely prevent the incidence of post-molar GTN and reduce the morbidity associated with GTN. This prophylactic approach can be adopted at any trophoblastic disease center (TDC).</div></div>","PeriodicalId":12853,"journal":{"name":"Gynecologic oncology","volume":"193 ","pages":"Pages 105-112"},"PeriodicalIF":4.5,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142970421","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":"Cost-effectiveness of an additional hysterectomy after initially conservative treatment for cervical adenocarcinoma in situ","authors":"M. Schaafsma ,&nbsp;T.N. Schuurman ,&nbsp;A.G. Siebers ,&nbsp;R.L.M. Bekkers ,&nbsp;M.C.G. Bleeker ,&nbsp;P.L.M. Zusterzeel ,&nbsp;C.H. Mom ,&nbsp;J. Berkhof ,&nbsp;K. Rozemeijer ,&nbsp;N.E. van Trommel","doi":"10.1016/j.ygyno.2025.01.005","DOIUrl":"10.1016/j.ygyno.2025.01.005","url":null,"abstract":"<div><h3>Objective</h3><div>Several European and American guidelines recommend to perform an additional hysterectomy in patients with cervical adenocarcinoma in situ (AIS), who initially received conservative treatment and who completed childbearing during follow-up. This study aimed to evaluate cost-effectiveness of performing an additional hysterectomy in comparison to expectative management.</div></div><div><h3>Methods</h3><div>This post-hoc analysis was based on a retrospective cohort of patients diagnosed with AIS, who were conservatively treated by a radical (i.e., negative surgical margins) large loop excision of the transformation zone (LLETZ) or cold-knife conisation (CKC) in the Netherlands between 1990 and 2021. Based on these data, we estimated and compared the harms, benefits, and costs in 1000 simulated patients, both with and without an additional hysterectomy five years after conservative treatment for AIS. In the sensitivity analyses, we varied the timing of the additional hysterectomy, the risk of recurrent high-grade cervical dysplasia and cervical cancer risk after AIS treatment, and the utility loss for hysterectomy.</div></div><div><h3>Results</h3><div>Less than 2 % of the patients who did not receive an additional hysterectomy after AIS developed cervical cancer. When an additional hysterectomy was performed, no quality adjusted life-years (QALYs) were gained and costs were 863 % higher (€6203,485 versus €644,238). Only when assuming no utility loss for a hysterectomy, QALYs were gained resulting in a cost-effectiveness ratio of €144,273, which is far above the cost-effectiveness threshold of €20,000.</div></div><div><h3>Conclusion</h3><div>It is not cost-effective to perform an additional hysterectomy after completion of childbearing in patients who were primarily treated by a radical LLETZ or CKC.</div></div>","PeriodicalId":12853,"journal":{"name":"Gynecologic oncology","volume":"193 ","pages":"Pages 113-118"},"PeriodicalIF":4.5,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143004315","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":"Molecular classification of endometrial cancers (EC) and association with relapse-free survival (RFS) and overall survival (OS) outcomes: Ancillary analysis of GOG-0258","authors":"Aine Clements ,&nbsp;Danielle Enserro ,&nbsp;Kyle C. Strickland ,&nbsp;Rebecca Previs ,&nbsp;Daniela Matei ,&nbsp;David Mutch ,&nbsp;Matthew Powell ,&nbsp;Ann Klopp ,&nbsp;David Scott Miller ,&nbsp;William Small Jr. ,&nbsp;Paul DiSilvestro ,&nbsp;Nick Spirtos ,&nbsp;Casey Cosgrove ,&nbsp;Greg Sfakianos ,&nbsp;J. Rebecca Liu ,&nbsp;Roberto Vargas ,&nbsp;Mark Shahin ,&nbsp;Bradley Corr ,&nbsp;Kimberly Dessources ,&nbsp;Frederick Ueland ,&nbsp;Angeles Alvarez Secord","doi":"10.1016/j.ygyno.2025.01.006","DOIUrl":"10.1016/j.ygyno.2025.01.006","url":null,"abstract":"<div><h3>Purpose</h3><div>Determine if molecular classification using mismatch repair (MMR) and p53 protein expression predicts recurrence-free survival (RFS) and overall survival (OS) in endometrial cancer (EC) patients treated with chemotherapy and radiation (CRT) versus chemotherapy (CT).</div></div><div><h3>Methods</h3><div>GOG-0258, a phase III randomized trial (<span><span>NCT00942357</span><svg><path></path></svg></span>), compared CRT to CT. Immunohistochemistry assessed MMR and p53 status. Kaplan-Meier curves and adjusted Cox models analyzed survival outcomes by molecular subtype.</div></div><div><h3>Results</h3><div>ECs classified as deficient MMR (dMMR) (27 %), p53 abnormal (p53abn) (24 %), and p53 wild type (p53wt) (49 %). p53abn were more frequent in patients that were older, Black, and had serous histology (<em>p</em> &lt; 0.001). Median follow up was 113 months. Five-year RFS and OS were worse with p53abn (29 % [Hazard Ratio (HR) = 3.39 (95 % Confidence Interval (CI): 2.34–4.91)] and 39 % [HR = 4.64 (95 % CI: 3.16–6.79)] compared to those with p53wt (referent) (p &lt; 0.001). The five-year RFS and OS for dMMR cancers were (58 % [HR = 1.30 (95 % CI: 0.85–1.97)] and 77 % [HR = 1.53 (95 % CI: 0.99–2.36)] compared to those with p53wt (69 % and 85 %). After adjusting for age, gross residual disease, and treatment, p53wt improved RFS with CRT compared to CT in an exploratory analysis (77 % vs 60 %; HR = 0.54 (95 % CI: 0.32–0.94). The 5-year and 10-year OS rates were similar in CRT compared to CT in all subgroups.</div></div><div><h3>Conclusion</h3><div>Molecular classification appears to be predictive and prognostic, with worse survival in those with p53abn tumors. In an exploratory analysis, p53wt appears to predict improved RFS, favoring CRT over CT. There was no difference in treatment efficacy based on molecular subtype for OS.</div></div>","PeriodicalId":12853,"journal":{"name":"Gynecologic oncology","volume":"193 ","pages":"Pages 119-129"},"PeriodicalIF":4.5,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143038155","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":"What happens after menopause? (WHAM): A prospective controlled study of cognition 24 months after premenopausal risk-reducing salpingo-oophorectomy","authors":"Pauline M. Maki ,&nbsp;Leah H. Rubin ,&nbsp;Efrosinia O. Krejany ,&nbsp;Alison Brand ,&nbsp;Martha Hickey","doi":"10.1016/j.ygyno.2025.01.008","DOIUrl":"10.1016/j.ygyno.2025.01.008","url":null,"abstract":"<div><h3>Objective</h3><div>Women with BRCA1/2 pathogenic variants considering risk-reducing bilateral oophorectomy (RRSO) may be concerned about potential effects of surgical menopause on cognition. Whether RRSO affects cognition and whether hormone therapy (HT) modifies this effect remains uncertain. This study aimed to prospectively measure the effect of premenopausal RRSO on cognition and the modifying effects of HT up to 24 months.</div></div><div><h3>Methods</h3><div>The design was a prospective, multisite (4 sites in Australia), 24-month observational study. Participants were premenopausal BRCA1/2 carriers (<em>n</em> = 83) planning RRSO referred from gynecology-oncology and familial cancer centers and a premenopausal comparison group (<em>n</em> = 98) not planning oophorectomy or pregnancy who self-referred. Baseline data were collected within 8 weeks of eligibility screening, and RRSO was scheduled between baseline and 3 months. Of 687 screened, 181 were analysed. Cognitive performance (verbal learning and memory, psychomotor speed, fluency) was assessed at baseline, 3, 12 and 24 months with the a priori outcomes of verbal learning and memory.</div></div><div><h3>Results</h3><div>After RRSO, 65 % initiated HT. In multivariable models of group differences in cognitive performance over time, RRSO and comparison groups showed similar performance improvements except for verbal learning. The RRSO group showed a small, statistically significant lower improvement in verbal learning vs comparisons, after adjustment for HT and other factors (<em>p</em> = 0.03). After RRSO, verbal learning was higher in HT users vs non-users (<em>p</em> = 0.04).</div></div><div><h3>Conclusions and relevance</h3><div>Over 24 months RRSO minimally impacted cognition except for a small adverse effect on verbal learning, partly offset by HT.</div></div><div><h3>Trial registration</h3><div>Australian and New Zealand Clinical Trials Registry (<span><span>anzctr.org.au</span><svg><path></path></svg></span>); Identifier #: ACTRN12615000082505; URL: <span><span>https://www.anzctr.org.au/Trial/Registration/TrialReview.aspx?id=363554&amp;isReview=true</span><svg><path></path></svg></span></div></div>","PeriodicalId":12853,"journal":{"name":"Gynecologic oncology","volume":"193 ","pages":"Pages 141-147"},"PeriodicalIF":4.5,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143065183","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":"Prognostic significance of serum complement activation, neutrophil extracellular traps and extracellular DNA in newly diagnosed epithelial ovarian cancer","authors":"Jason Ricciuti ,&nbsp;Qian Liu ,&nbsp;A.N.M. Nazmul H. Khan ,&nbsp;Janine M. Joseph ,&nbsp;Bert Veuskens ,&nbsp;Thejaswini Giridharan ,&nbsp;Sora Suzuki ,&nbsp;Tiffany Emmons ,&nbsp;Michael Yaffe ,&nbsp;Taco W. Kuijpers ,&nbsp;Ilse Jongerius ,&nbsp;Mieke Brouwer ,&nbsp;Richard B. Pouw ,&nbsp;Kunle Odunsi ,&nbsp;Peter Frederick ,&nbsp;Katherine LaVigne Mager ,&nbsp;Shashikant Lele ,&nbsp;Nicole Gaulin ,&nbsp;Christiane Hakim ,&nbsp;Robert P. Edwards ,&nbsp;Brahm Segal","doi":"10.1016/j.ygyno.2024.12.006","DOIUrl":"10.1016/j.ygyno.2024.12.006","url":null,"abstract":"<div><h3>Purpose</h3><div>We observed that the tumor microenvironment (TME) in metastatic epithelial ovarian cancer (EOC) and in other solid tumors can reprogram normal neutrophils to acquire a complement-dependent suppressor phenotype characterized by inhibition of stimulated T cell activation. This study aims to evaluate whether serum markers of neutrophil activation and complement at diagnosis of EOC would be associated with clinical outcomes.</div></div><div><h3>Experimental design</h3><div>We conducted a two-center prospective study of patients with newly diagnosed EOC (<em>N</em> = 188). Blood and ascites fluid were collected at diagnosis for biomarker analysis. Patients were evaluated for progression-free survival (PFS) and overall survival (OS).</div></div><div><h3>Results</h3><div>The median OS was 47 months (95 % CI: 34–58) and the median PFS was 12 months (95 % CI: 11–15). Pre-treatment serum levels of genomic DNA (gDNA), markers of neutrophil degranulation (myeloperoxidase [MPO]) and neutrophil extracellular traps (NETs) (citrullinated histone H3 [CitH3]), and complement activation (C3b/c) were each associated with worse OS in univariate analysis. In multivariate analyses controlling for age, stage, and optimal debulking, serum gDNA, MPO, and CitH3 remained associated with worse OS, while C3b/c levels were not. In an exploratory analysis, the largest magnitude of difference in 2-year OS occurred in patients with low C3b/c and low CitH3 compared to all other patients (87 % vs 46 % survival, respectively). In ascites fluid, increased factor H, a negative regulator of complement activation, was associated with improved OS in univariate analysis.</div></div><div><h3>Conclusions</h3><div>These results point to serum gDNA, NETs, and complement activation as potential prognostic biomarkers in patients with newly diagnosed EOC.</div></div>","PeriodicalId":12853,"journal":{"name":"Gynecologic oncology","volume":"193 ","pages":"Pages 49-57"},"PeriodicalIF":4.5,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143070854","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":"Prevention of gestational trophoblastic neoplasia with actinomycin -D at the time of evacuation: A matter of routine practice or reserve for special circumstances?","authors":"Neil S. Horowitz ,&nbsp;Jessica D. St. Laurent ,&nbsp;Ross S. Berkowitz","doi":"10.1016/j.ygyno.2025.02.009","DOIUrl":"10.1016/j.ygyno.2025.02.009","url":null,"abstract":"","PeriodicalId":12853,"journal":{"name":"Gynecologic oncology","volume":"193 ","pages":"Pages A1-A2"},"PeriodicalIF":4.5,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143508610","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":"Incorporating immune checkpoint inhibitors in epithelial ovarian cancer","authors":"Giorgio Bogani ,&nbsp;Kathleen N. Moore ,&nbsp;Isabelle Ray-Coquard ,&nbsp;Domenica Lorusso ,&nbsp;Ursula A. Matulonis ,&nbsp;Jonathan A. Ledermann ,&nbsp;Antonio González-Martín ,&nbsp;Jean-Emmanuel Kurtz ,&nbsp;Eric Pujade-Lauraine ,&nbsp;Giovanni Scambia ,&nbsp;Giuseppe Caruso ,&nbsp;Francesco Raspagliesi ,&nbsp;Nicoletta Colombo ,&nbsp;Bradley J. Monk","doi":"10.1016/j.ygyno.2024.12.011","DOIUrl":"10.1016/j.ygyno.2024.12.011","url":null,"abstract":"<div><h3>Objective</h3><div>Therapeutic interventions for epithelial ovarian cancer (EOC) have increased greatly over the last decade but improvements outside of biomarker selected therapies have been limited. There remains a pressing need for more effective treatment options that can prolong survival and enhance the quality of life of patients with EOC. In contrast to the significant benefits of immunotherapy with immune checkpoint inhibitors (CPI) seen in many solid tumors, initial experience in EOC suggests limited efficacy of CPIs monotherapy.</div></div><div><h3>Methods</h3><div>A systematic review of phase III studies testing the role of CPIs in ovarian cancer was performed.</div></div><div><h3>Results</h3><div>Seven randomized trials testing CPIs in newly diagnosed (<em>n</em> = 3) and recurrent (<em>n</em> = 4) EOC are evaluated. Overall, those trials included data of 5671 patients. Single-agent PD-L1 inhibitor trials have not shown significant efficacy in newly diagnosed ovarian cancer. Triplet maintenance with bevacizumab plus olaparib and durvalumab is associated with longer progression-free survival than maintenance with bevacizumab alone in patients without tumor BRCA mutations. CPIs were not effective in platinum-sensitive (<em>n</em> = 1031) and platinum-resistant (<em>n</em> = 1420) EOC.</div></div><div><h3>Conclusions</h3><div>The value of adding CPI to standard treatment including poly (ADP-ribose) polymerase (PARP) inhibitors with or without bevacizumab remains unclear and is being addressed in ongoing clinical trials. The combination of cytotoxic T-lymphocyte associated protein 4 (CTLA-4) and programmed cell death protein 1 (PD-1) inhibitors may enhance the efficacy of immunotherapy in EOC and studies are underway to investigate the combination of CPI with other emerging treatment modalities.</div><div>PROSPERO registration ID: CRD42024536017.</div></div>","PeriodicalId":12853,"journal":{"name":"Gynecologic oncology","volume":"193 ","pages":"Pages 30-40"},"PeriodicalIF":4.5,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143136578","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":"Spatial transcriptomic analysis reveals significant differences in tumor microenvironment in HPV-dependent and HPV-independent vulvar squamous cell carcinoma","authors":"Hasan B. Mirza ,&nbsp;Ashton Hunt ,&nbsp;Darren P. Ennis ,&nbsp;Jacqueline McDermott ,&nbsp;Iain A. McNeish","doi":"10.1016/j.ygyno.2025.01.002","DOIUrl":"10.1016/j.ygyno.2025.01.002","url":null,"abstract":"<div><h3>Objective</h3><div>Vulvar squamous cell carcinoma (VSCC) can be either HPV-dependent (HPVd) or HPV-independent (HPVi). HPVd VSCC typically occurs in younger women, has a more favorable prognosis, and develops from high-grade squamous intraepithelial lesions (HSIL). HPVi VSCC predominantly affects older women and arises within areas of chronic inflammation, particularly lichen sclerosis (LS). We utilized sequencing-based spatial transcriptomics to explore gene expression in a cohort of patients with HPVi and HPVd VSCC.</div></div><div><h3>Methods</h3><div>We analysed gene expression in distinct areas (SCC, inflammation, LS, HSIL) from four early-stage VSCC cases (two HPVi, two HPVd) using the 10× Genomics Visium spatial transcriptomics platform. Cell-specific type expression was inferred using CIBERSORTx.</div></div><div><h3>Results</h3><div>28,183 Visium spots were detected; each contained an estimated 20–50 cells. Reads per spot ranged from 9903 to 68,527. More genes were upregulated in HPVd (<em>N</em> = 601) than HPVi (<em>N</em> = 72) with distinct differences in Keratin and Collagen genes between etiologies. Gene expression was strikingly similar between SCC and adjacent inflammatory areas, regardless of etiology. IL-17 signaling was upregulated in HPVd samples. Surprisingly, CIBERSORTx inferred significantly more CD45+ cells in HPVi tissues than HPVd, especially CD4+ resting memory and follicular helper T cells in SCC areas. Immune cells moved from resting states in the pre-invasive tissues to activated states in the SCC and peri-tumoral inflammatory areas.</div></div><div><h3>Conclusions</h3><div>This study represents the first application of spatial transcriptomics in VSCC, with significantly more immune cells identified in HPVi SCC than in HPVd SCC. These data will act as a baseline for future studies.</div></div>","PeriodicalId":12853,"journal":{"name":"Gynecologic oncology","volume":"193 ","pages":"Pages 65-72"},"PeriodicalIF":4.5,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142947784","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}