Gynecologic oncology最新文献

{"title":"Age-specific incidence and five-year relative survival of endometrial cancer histotypes by race and ethnicity among US women, 2000 to 2019","authors":"Megan A. Clarke ,&nbsp;Nicolas Wentzensen ,&nbsp;Martin Köbel ,&nbsp;Britt K. Erickson ,&nbsp;Akemi T. Wijayabahu ,&nbsp;Andrea G. Kahn ,&nbsp;Michael D. Toboni ,&nbsp;Rebecca C. Arend ,&nbsp;Ruth M. Pfeiffer","doi":"10.1016/j.ygyno.2025.07.011","DOIUrl":"10.1016/j.ygyno.2025.07.011","url":null,"abstract":"<div><h3>Introduction</h3><div>Endometrial cancer is now recognized as a heterogeneous disease with distinct clinicopathologic and molecular features; however, population-based studies have traditionally focused on two broad histological groups (endometrioid and non-endometrioid). This study aims to delineate the epidemiology of individual endometrial cancer histotypes by analyzing age-specific incidence and five-year relative survival by race and ethnicity.</div></div><div><h3>Methods</h3><div>We estimated hysterectomy-corrected, age-specific incidence rates of endometrial cancer histotypes by race and ethnicity among women aged 30+ years, diagnosed from 2000 to 2019 in the Surveillance and Epidemiology and End Results database (SEER22; <em>N</em> = 390,805). We assessed five-year relative survival by age group (30–49 vs. 50+), race/ethnicity, histotype, and stage.</div></div><div><h3>Results</h3><div>Endometrioid carcinoma rates were similar by race and ethnicity in younger groups but much higher in non-Hispanic White women ages 50+ years (104.1 per 100,000) versus other groups (51.1–68.5). Non-endometrioid histotypes were rare in younger women, with mixed carcinomas being the most common. Carcinosarcoma, clear cell, and serous carcinoma rates increased sharply at ages 50–54, especially in non-Hispanic Black women. Median age at diagnosis was youngest in Hispanic and non-Hispanic Asian/Pacific Islander women, particularly for endometrioid carcinomas. Survival was highest for endometrioid carcinomas (90.2 %) followed by mixed carcinomas (77.0 %) and other non-endometrioid histotypes (range 39.6 %–59.1 %).</div></div><div><h3>Conclusions</h3><div>Our findings suggest potential differences in age-related risk factors and carcinogenic pathways across histotypes that may also vary by race and ethnicity. Increasing rates of serous, carcinosarcomas, and clear cell carcinomas around 50–54 years may indicate menopause as an etiologically relevant window or critical period for risk of these cancers.</div></div>","PeriodicalId":12853,"journal":{"name":"Gynecologic oncology","volume":"200 ","pages":"Pages 137-144"},"PeriodicalIF":4.1,"publicationDate":"2025-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144749347","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":"The challenge of molecular stratification in No Specific Molecular Profile endometrial cancer","authors":"Matteo Marchetti ,&nbsp;Tommaso Vezzaro ,&nbsp;Massimo Carollo ,&nbsp;Emma Facchetti ,&nbsp;Laura Masatti ,&nbsp;Livia Xhindoli ,&nbsp;Diletta Costeniero ,&nbsp;Tiziano Maggino ,&nbsp;Roberto Tozzi ,&nbsp;Carlo Saccardi ,&nbsp;Marco Noventa ,&nbsp;Giulia Spagnol","doi":"10.1016/j.ygyno.2025.07.020","DOIUrl":"10.1016/j.ygyno.2025.07.020","url":null,"abstract":"<div><h3>Objective</h3><div>In this study, we aimed to evaluate the prognostic impact of molecular alterations beyond those included in the Proactive Molecular Risk Classifier for Endometrial Cancer (ProMisE), in order to identify biomarkers that could improve prognostic stratification within the No Specific Molecular Profile (NSMP) subgroup of endometrial cancers.</div></div><div><h3>Methods</h3><div>This systematic review and meta-analysis was conducted according to PRISMA guidelines. We searched PubMed, Scopus and Web of Science for studies published up to December 2024. We included prospective and retrospective studies assessing the prognostic impact of molecular alterations not included in the ProMisE classification, reporting outcomes as hazard ratios (HRs). The primary outcome was progression-free survival (PFS), and the secondary outcome was overall survival (OS), analyzed in both the overall endometrial cancer population and specifically within the NSMP subgroup.</div></div><div><h3>Results</h3><div>A total of 19 studies met the inclusion criteria and were included in the final analysis: 17 retrospective and 2 prospective, all observational in design. L1CAM overexpression and ER loss were identified as unfavorable prognostic factors in the overall endometrial cancer population (PFS HR 3.44 [2.57, 4.59; 95 % CI] and 3.13 [2.45, 4.00; 95 % CI], respectively) and within the NSMP subgroup (PFS HR 3.34 [2.05, 5.44; 95 % CI] and 3.14 [2.00, 4.91; 95 % CI], respectively). <em>ARID1A</em> mutation showed a negative prognostic impact limited to NSMPs (PFS HR 2.35 [1.09, 5.06; 95 % CI]). Conversely, β-catenin/<em>CTNNB1</em> and <em>PIK3CA</em>/<em>PTEN</em> mutations did not demonstrate consistent prognostic significance in either group.</div></div><div><h3>Conclusions</h3><div>These findings underscore the potential of ER loss and L1CAM overexpression as prognostic markers within the NSMP subgroup, supporting more personalized adjuvant strategies. Further research is needed to clarify the prognostic role of other alterations, such as <em>ARID1A</em>, specifically within NSMP tumors.</div><div>PROSPERO registration number: CRD420250654207.</div></div>","PeriodicalId":12853,"journal":{"name":"Gynecologic oncology","volume":"200 ","pages":"Pages 145-154"},"PeriodicalIF":4.1,"publicationDate":"2025-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144757512","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":"Analysis of the use of prophylactic ureteral stents in preventing iatrogenic ureteral injury during radical hysterectomy for cervical Cancer","authors":"Yaping Wang,&nbsp;Zongyang Jia,&nbsp;Jun Jiao,&nbsp;Xiaoyu Yue,&nbsp;Siyu Wu,&nbsp;Peihai Zhang","doi":"10.1016/j.ygyno.2025.07.022","DOIUrl":"10.1016/j.ygyno.2025.07.022","url":null,"abstract":"<div><h3>Objective</h3><div>To assess the use of prophylactic ureteral stent for preventing ureteral injury in patients with cervical cancer undergoing radical hysterectomy.</div></div><div><h3>Methods</h3><div>This retrospective study included 304 patients with cervical cancer who underwent abdominal radical hysterectomy at Qilu Hospital of Shandong University (Qingdao) from June 2018 to June 2023. Patients were divided into the ureteral stent group (129 cases) and the control group (175 cases). The value of the use of prophylactic ureteral stents was compared between two groups in terms of ureteral and bladder injury rates, ureteral strictures, urinary system complications and cost-effectiveness.</div></div><div><h3>Results</h3><div>There was no statistically significant difference in the incidence of ureteral and bladder injury between the two groups (<em>P</em> &gt; 0.05). Postoperative radiotherapy was given to 59 patients in the stent group and 89 patients in the control group. There were 16 (27.1 %) and 5 (5.6 %) cases of ureteral stricture in the stent and control groups after the end of radiotherapy. The prevalence of ureter stricture in the two groups were significantly different (<em>P</em> &lt; 0.05). There was no statistically significant difference in the incidence of newly emerged ureteral strictures caused by radiotherapy between the two groups (6.5 % <em>vs.</em> 2.3 %, <em>P</em> &gt; 0.05). The incidences of urinary complications were statistically significant between the two groups (<em>P</em> &lt; 0.05). Operation time, surgery cost and hospitalization expenses were higher in the stent group, which increased the total medical cost.</div></div><div><h3>Conclusion</h3><div>The use of prophylactic ureteral stent did not reduce the occurrence of ureteral injuries in patients undergoing abdominal radical hysterectomy, nor prevent the incidence of ureteral stricture after radiotherapy. On the contrary, the use of ureteral stent increased the incidence of urinary complications and medical cost.</div></div>","PeriodicalId":12853,"journal":{"name":"Gynecologic oncology","volume":"200 ","pages":"Pages 155-160"},"PeriodicalIF":4.1,"publicationDate":"2025-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144757634","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":"Ovarian mixed low- and high-grade serous carcinoma as a synchronous or metachronous phenomenon: A clinicopathologic study of 39 cases","authors":"Allison L. Brodsky ,&nbsp;Charlotte Sun ,&nbsp;Lauren Cobb ,&nbsp;Shannon N. Westin ,&nbsp;Anais Malpica ,&nbsp;David M. Gershenson","doi":"10.1016/j.ygyno.2025.07.025","DOIUrl":"10.1016/j.ygyno.2025.07.025","url":null,"abstract":"<div><h3>Objective</h3><div>Low-grade serous ovarian carcinoma (LGSOC) and high-grade serous ovarian carcinoma (HGSOC) are distinct entities. Although typically occurring in pure forms, some present as synchronous or metachronous mixed histotypes.</div></div><div><h3>Methods</h3><div>This retrospective study examined patients with mixed LGSOC and HGSOC treated between 1994 and 2024 at MD Anderson Cancer Center (MDACC). Diagnoses were confirmed by MDACC gynecologic pathologists. Demographics, clinical characteristics, diagnosis rendered by referral institution, treatment, immunohistochemistry, somatic tumor testing, and survival outcomes were collected. Progression-free survival (PFS) and overall survival (OS) were estimated using the Kaplan-Meier method, with log-rank tests to compare cohorts, <em>p</em> &lt; 0.05 significant.</div></div><div><h3>Results</h3><div>Among 39 cases, 85 % were synchronous, and 15 % were metachronous. Seven (25 %) of patients tested for germline mutations (<em>n</em> = 28) had germline <em>BRCA</em> mutations. Of the 35 cases diagnosed at referral institutions, only eight (23 %) were correctly identified as mixed. Sixteen (41 %) patients underwent somatic tumor testing, revealing three <em>KRAS</em>, one <em>NRAS</em>, and eight <em>TP53</em> mutations. All patients underwent cytoreductive surgery, with 97 % receiving adjuvant therapy and 26 % maintenance therapy. Recurrence occurred in 90 % of cases. Median PFS was 17 months, and median OS was 56.7 months, with a 5-year survival rate of 48.5 %. There was no statistically significant difference when comparing PFS or OS by <em>BRCA</em> status, primary vs interval cytoreduction, residual disease, tumor presentation, or maintenance therapy.</div></div><div><h3>Conclusion</h3><div>Diagnosing mixed LGSOC and HGSOC remains challenging. Despite low <em>TP53</em> mutation rates, survival outcomes resembled those of HGSOC. These findings advocate for further investigations to identify risk factors and biomarkers for low-grade to high-grade transformation and to improve treatment strategies.</div></div>","PeriodicalId":12853,"journal":{"name":"Gynecologic oncology","volume":"200 ","pages":"Pages 130-136"},"PeriodicalIF":4.1,"publicationDate":"2025-07-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144749346","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 adenocarcinoma risk stratification using histotype and invasion pattern: a multicenter retrospective study by the KAMOGAWA Study Group","authors":"Motonori Matsubara ,&nbsp;Tomoyuki Otani ,&nbsp;Fumi Kawakami ,&nbsp;Ayami Koike ,&nbsp;Takahiro Hirayama ,&nbsp;Yukio Yamanishi ,&nbsp;Naoki Horikawa ,&nbsp;Ikuko Emoto ,&nbsp;Masayo Ukita ,&nbsp;Masahiro Sumitomo ,&nbsp;Hiroshi Sato ,&nbsp;Takahito Ashihara ,&nbsp;Kosuke Murakami ,&nbsp;Yasushi Kotani ,&nbsp;Kaoru Abiko ,&nbsp;Yoshiki Mikami ,&nbsp;Masaki Mandai ,&nbsp;Noriomi Matsumura","doi":"10.1016/j.ygyno.2025.07.017","DOIUrl":"10.1016/j.ygyno.2025.07.017","url":null,"abstract":"<div><h3>Objective</h3><div>To validate the clinical utility of the Silva classification (a risk-stratification system based on invasion pattern for HPV-associated cervical adenocarcinoma; HPVA) using Japanese cohort data; and to determine how HPV-independent adenocarcinoma (HPVI) should be positioned relative to Silva-classified HPVA.</div></div><div><h3>Methods</h3><div>We retrospectively analyzed 264 cases of surgically treated FIGO 2008 stage I–II cervical adenocarcinoma from eight institutions participating in the KAMOGAWA Study. Tumors were classified as HPVA or HPVI. HPVA cases were further categorized as low-risk or high-risk using the binary Silva classification, which incorporates invasion pattern and lymphovascular space invasion. Outcome measures included lymph node metastasis, disease-free survival (DFS), and overall survival (OS).</div></div><div><h3>Results</h3><div>Of the 264 cases, 27 % were classified as low-risk HPVA, 49 % as high-risk HPVA, and 23 % as HPVI. Lymph node metastasis was observed in 0 %, 12 %, and 38 % of cases, respectively (<em>p</em> &lt; 0.001). The 5-year DFS was 98 %, 83 %, and 53 %, and the 5-year OS was 100 %, 97 %, and 63 % (both p &lt; 0.001). Multivariable analysis showed that low-risk HPVA was associated with longer DFS (HR 0.12, 95 % CI 0.015–0.87) and HPVI was associated with shorter DFS (HR 2.76, 95 % CI 1.44–5.30), after adjusting for tumor size (≤2 cm, 2–4 cm, &gt;4 cm) and age. Tumor size &gt;4 cm, but not ≤2 cm was an independent prognostic factor.</div></div><div><h3>Conclusions</h3><div>The three-tier system combining the histotype and binary Silva classification outperformed tumor size in prognostic stratification. The low-risk group showed excellent outcomes, supporting the potential for conservative management such as uterine preservation after conization.</div></div>","PeriodicalId":12853,"journal":{"name":"Gynecologic oncology","volume":"200 ","pages":"Pages 112-121"},"PeriodicalIF":4.1,"publicationDate":"2025-07-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144725076","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 chemotherapy provider specialty on outcomes in ovarian cancer","authors":"Joyce Y. Wang ,&nbsp;Elise J. Simons ,&nbsp;Aleksei Dingel ,&nbsp;Mindy M. Pike ,&nbsp;Lucas Chen ,&nbsp;Barbara A. Goff","doi":"10.1016/j.ygyno.2025.07.018","DOIUrl":"10.1016/j.ygyno.2025.07.018","url":null,"abstract":"<div><h3>Objectives</h3><div>Gynecologic oncologist (GO) surgeons are associated with improved outcomes for ovarian cancer (OC) patients, but evidence is limited for GOs as chemotherapy providers. We evaluated the impact of different chemotherapy provider specialties on survival in epithelial OC.</div></div><div><h3>Methods</h3><div>In this retrospective cohort study from January 2015 to December 2021 at an academic medical institution, we classified chemotherapy provider type into three groups: A) exclusively GO (all chemotherapy provided by a GO); B) shared model (chemotherapy provided by both a GO and a medical oncologist); and C) primarily non-GO (chemotherapy provided by a medical oncologist and a GO was only involved at times of disease progression or less frequently). Primary outcomes were overall survival (OS) and progression-free survival (PFS).</div></div><div><h3>Results</h3><div>Of 319 patients, 162 (50.8 %) were classified into chemotherapy provider type group A, 116 (36.4 %) into group B, and 41 (12.9 %) into group C. Provider group patient populations varied by demographic and clinical characteristics. Older age and increased distance to a GO were associated with decreased odds of GO chemotherapy involvement. Chemotherapy provider group was not significantly associated with OS (group B: HR 0.94 95 % CI 0.57–1.57, group C: HR 1.75 95 % CI 0.92–3.33) or PFS (group B: HR 1.20 95 % CI 0.84–1.71, group C: HR 1.36 95 % CI 0.83–2.21).</div></div><div><h3>Conclusions</h3><div>There was no survival difference across the three designated chemotherapy provider groups. Shared chemotherapy responsibility may be a reasonable care model, especially for patients with difficulty accessing GO care. Responsibility sharing between GOs and medical oncologists is heterogenous and requires further characterization.</div></div>","PeriodicalId":12853,"journal":{"name":"Gynecologic oncology","volume":"200 ","pages":"Pages 122-129"},"PeriodicalIF":4.1,"publicationDate":"2025-07-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144739148","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":"Enhancing predictive accuracy: Assessing the laparoscopic hysterectomy readmission score in a diverse endometrial cancer population","authors":"Michelle D.S. Lightfoot ,&nbsp;Jennifer A. Sinnott ,&nbsp;Caitlin E. Meade ,&nbsp;David A. Barrington ,&nbsp;Casey M. Cosgrove ,&nbsp;Laura M. Chambers ,&nbsp;Ashley S. Felix","doi":"10.1016/j.ygyno.2025.07.021","DOIUrl":"10.1016/j.ygyno.2025.07.021","url":null,"abstract":"<div><h3>Objective</h3><div>The laparoscopic hysterectomy readmission score (LHRS) was developed to identify patients at low risk for readmission following laparoscopic surgery. Its performance in patients with endometrial cancer (EC), a population increasingly undergoing laparoscopic hysterectomy, remains unassessed, particularly across racial and ethnic groups. This study evaluates LHRS discrimination and calibration in predicting readmission among patients with EC overall and by race and ethnicity.</div></div><div><h3>Methods</h3><div>Using the National Surgical Quality Improvement Program database (2014–2020), we identified patients who underwent laparoscopic hysterectomy. The LHRS was calculated as previously described by Jennings et al. Model performance was assessed using the area under the receiver operating curve (AUC), true positive rate (TPR) and false positive rate (FPR). Logistic regression estimated 30-day readmission odds in the overall cohort and by race and ethnicity. The LHRS was analyzed as a continuous (0–8) and dichotomous (&lt;3 <em>vs.</em> ≥3) variable.</div></div><div><h3>Results</h3><div>Among 27,981 patients with EC (Asia<em>n</em> = 1367; American Indian/Alaska Native = 115; Black = 2120; Latine = 1676; Native Hawaiian/Pacific Islander = 305; White = 22,398), readmission rates were low (3.1 %). The LHRS demonstrated poor discrimination, with an AUC only marginally better than chance overall (0.52, 95 % CI = 0.51, 0.53) across all racial and ethnic groups. TPRs and FPRs were uniformly low. Patients with LHRS ≥3 has higher readmission odds (OR = 3.10, 95 % CI = 2.31, 4.15) with similar associations in race and ethnicity-stratified models.</div></div><div><h3>Conclusions</h3><div>Although a higher LHRS was associated with increased readmission odds, the score failed to predict readmission better than chance in this EC cohort, underscoring the need for improved risk stratification tools for readmission in this population.</div></div>","PeriodicalId":12853,"journal":{"name":"Gynecologic oncology","volume":"200 ","pages":"Pages 105-111"},"PeriodicalIF":4.1,"publicationDate":"2025-07-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144721841","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":"Molecular comparison reveals distinct transcriptomic differences between uterine carcinosarcoma and papillary serous carcinoma distinguishable by DNA damage","authors":"Kevin J. Lee ,&nbsp;Sagar Chokshi ,&nbsp;Tanvi Joshi ,&nbsp;Mackenzie Cummings ,&nbsp;Veronica Ramirez-Alcantara ,&nbsp;Elba A. Turbat-Herrera ,&nbsp;Rodney P. Rocconi ,&nbsp;Jennifer Scalici ,&nbsp;Jennifer Pierce ,&nbsp;Nathaniel Jones","doi":"10.1016/j.ygyno.2025.07.016","DOIUrl":"10.1016/j.ygyno.2025.07.016","url":null,"abstract":"<div><h3>Objectives</h3><div>The role of mismatch repair deficiency (MMRd) or DNA damage &amp; response (DDR) mechanisms in general are under-explored in rare endometrial cancer subtypes. We therefore sought to characterize the immune, inflammatory, and DNA damage profiles of uterine papillary serous carcinoma (UPSC) and uterine carcinosarcoma (UCS) to better define the role of immunotherapy (IO) in these tumors.</div></div><div><h3>Methods</h3><div>Total DNA damage was analyzed in 53 UPSC and 43 UCS FFPE samples collected at our institution using repair-assisted damage-detection (RADD). RNA was isolated from a subset of patients and expression was analyzed using the Nanostring nCounter PanCancer IO 360 panel.</div></div><div><h3>Results</h3><div>A 3.6-fold increase (<em>p</em> &lt; 0.0001) in DNA repair capacity was seen in UCS samples compared to UPSC. Transcriptional analysis confirmed increased expression of DNA repair genes in UCS. Decreased expression of DNA repair genes was noted in UPSC despite nearly 4 times the amount of unrepaired DNA damage. As expected, the immune system was activated in response to this increased DNA damage with higher levels of markers of immune cells noted. However, there was also increased expression of immune evasive genes and markers of immune exhaustion. This suggests DNA damage tolerance and immune exhaustion are hallmarks of UPSC.</div></div><div><h3>Conclusions</h3><div>We present here a detailed, treatment-oriented molecular comparison between two histologically distinct endometrial cancer subtypes, UPSC and UCS. Assessment of unrepaired DNA damage and, by proxy, DNA repair capacity, gives context to the immune transcriptomic landscape. Our data suggests that the immune exhausted molecular landscape of UPSC may be more amenable to IO than that of UCS, while the DNA repair-robust UCS may be more vulnerable to agents targeting DNA Damage repair such as PARP inhibitors. Further, our data suggests that estimation of DNA repair capacity via RADD may be as treatment informative as molecular sequencing.</div></div>","PeriodicalId":12853,"journal":{"name":"Gynecologic oncology","volume":"200 ","pages":"Pages 80-87"},"PeriodicalIF":4.5,"publicationDate":"2025-07-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144686636","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":"Safety and efficacy of mirvetuximab soravtansine, a folate receptor alpha (FRα)–targeting antibody-drug conjugate (ADC), in combination with pembrolizumab in patients with platinum-resistant ovarian cancer","authors":"Ursula A. Matulonis ,&nbsp;Ignace Vergote ,&nbsp;Kathleen N. Moore ,&nbsp;Lainie P. Martin ,&nbsp;Cesar M. Castro ,&nbsp;Lucy Gilbert ,&nbsp;Yu Xia ,&nbsp;Michael Method ,&nbsp;James Stec ,&nbsp;Michael J. Birrer ,&nbsp;David M. O'Malley","doi":"10.1016/j.ygyno.2025.06.016","DOIUrl":"10.1016/j.ygyno.2025.06.016","url":null,"abstract":"<div><h3>Objective</h3><div>Evaluate the efficacy and safety of mirvetuximab soravtansine-gynx (MIRV) plus pembrolizumab in dose escalation and expansion cohorts of heavily pretreated patients with platinum-resistant ovarian cancer (PROC).</div></div><div><h3>Methods</h3><div>Participants with recurrent epithelial ovarian, fallopian tube, or primary peritoneal cancer whose disease relapsed ≤6 months from last platinum-based treatment received MIRV (6 mg/kg adjusted ideal body weight) and pembrolizumab (200 mg) intravenously once every 3 weeks. Tumor FRα expression thresholds were ≥25 % (dose escalation cohort) and ≥50 % (dose expansion cohort) of cells with ≥2+ membrane staining intensity. The primary efficacy endpoint was objective response rate (ORR). Secondary endpoints included duration of response (DOR), progression-free survival (PFS), and safety.</div></div><div><h3>Results</h3><div>Fifty-six participants received the doublet. Median age was 62 years (range, 40–78). Twenty percent of participants had 3 prior lines of systemic treatment, 43 % had ≥4 prior lines, 43 % had prior bevacizumab exposure, and 41 % had prior PARP inhibitor exposure. Among 55 response-evaluable participants, ORR was 31 % (95 % CI, 19–45), median DOR was 8.0 months (95 % CI, 4.2-NR), and median PFS was 4.2 months (95 % CI, 2.8–5.6). Efficacy persisted in patients with multiple prior lines of treatment. Treatment-emergent adverse events were consistent with the profiles of each agent; the most common were diarrhea (all grades, 57 %; grade 3, 4 %), nausea (55 %; 5 %), and fatigue (50 %; 2 %). Treatment-emergent pneumonitis occurred in 25 % of participants, with grade ≥3 events occurring in 2 (4 %) participants.</div></div><div><h3>Conclusions</h3><div>MIRV plus pembrolizumab demonstrated anti-cancer efficacy and a tolerable safety profile in heavily pretreated patients with PROC. However, the efficacy benefit may be mainly attributable to MIRV alone.</div></div>","PeriodicalId":12853,"journal":{"name":"Gynecologic oncology","volume":"200 ","pages":"Pages 96-104"},"PeriodicalIF":4.5,"publicationDate":"2025-07-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144686638","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 II, randomized, double-blind study of the use of rucaparib vs. placebo maintenance therapy in metastatic and recurrent endometrial cancer","authors":"Bradley R. Corr ,&nbsp;Ashley Haggerty ,&nbsp;Stefan M. Gysler ,&nbsp;Sarah Taylor ,&nbsp;Kian Behbakht ,&nbsp;Jill Alldredge ,&nbsp;Carolyn Lefkowits ,&nbsp;Lindsay W. Brubaker ,&nbsp;Catherine Bouts ,&nbsp;Lisa Marie Babayan ,&nbsp;Lainie P. Martin ,&nbsp;James Costello ,&nbsp;Benjamin G. Bitler ,&nbsp;Junxiao Hu ,&nbsp;Saketh R. Guntupalli","doi":"10.1016/j.ygyno.2025.07.008","DOIUrl":"10.1016/j.ygyno.2025.07.008","url":null,"abstract":"<div><h3>Objective</h3><div>Rucaparib is a poly(ADP-ribose) polymerase (PARP) inhibitor with proven efficacy in multiple tumor types. The efficacy of PARP inhibition in endometrial cancer remains unclear.</div></div><div><h3>Methods</h3><div>We conducted a multi-institutional, double-blind, placebo-controlled, randomized phase II trial. Eligible patients had stage III, IV or recurrent endometrial cancer. We assigned patients with measurable, or non-measurable disease following completion of first- or second-line chemotherapy in a 1:1 ratio to receive oral rucaparib (600 mg twice daily) or placebo until disease progression. The primary endpoint was progression-free survival. Secondary outcomes were overall survival and safety. Exploratory outcomes evaluated response in relation to tumor molecular profiles and transcriptomic profiles.</div></div><div><h3>Results</h3><div>79 patients were randomized, 39 received rucaparib and 40 received placebo. Median progression free survival was 28.1 months in the rucaparib arm compared to 8.7 months in the placebo group, hazard ratio 0.45; (95 % confidence interval [CI] (0.24–0.87); <em>p</em> = 0.02). Median overall survival was not reached in the rucaparib arm compared to 28.4 months in the placebo arm; hazard ratio 0.43 (95 % CI, 0.18–1.05). In patients treated with rucaparib, the most common grade ≥ 3 adverse events were anemia, fatigue, and neutropenia. Loss of p53 activity correlated to improved rucaparib response by transcriptomic evaluation. Traditional DNA repair homologous recombination biomarkers did not correlate with response.</div></div><div><h3>Conclusions</h3><div>Maintenance use of rucaparib after first- or second-line chemotherapy demonstrates promising activity and warrants further evaluation in a phase III evaluation. Adverse events were aligned with previous use of rucaparib in other tumor types and no new safety signals were identified. <span><span>ClinicalTrials.gov</span><svg><path></path></svg></span> identifier: <span><span>NCT03617679</span><svg><path></path></svg></span></div></div>","PeriodicalId":12853,"journal":{"name":"Gynecologic oncology","volume":"200 ","pages":"Pages 58-67"},"PeriodicalIF":4.5,"publicationDate":"2025-07-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144679648","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}