Gynecologic oncology最新文献

{"title":"Phase II study of enlonstobart (SG001), a novel PD-1 inhibitor in patients with PD-L1 positive recurrent/metastatic cervical cancer","authors":"Guiling Li ,&nbsp;Xiaofan Li ,&nbsp;Rutie Yin ,&nbsp;Mei Feng ,&nbsp;Jing Zuo ,&nbsp;Shuqing Wei ,&nbsp;Shan Kang ,&nbsp;Hongmei Sun ,&nbsp;Xiumin Li ,&nbsp;Yili Wang ,&nbsp;Yunyan Zhang ,&nbsp;Li Sun ,&nbsp;Daren Lin ,&nbsp;Xiaohong Ruan ,&nbsp;Zhitu Zhu ,&nbsp;Kui Jiang ,&nbsp;Hu Liu ,&nbsp;Wei Wang ,&nbsp;Deshun Hao ,&nbsp;Ying Chen ,&nbsp;Lingying Wu","doi":"10.1016/j.ygyno.2024.10.001","DOIUrl":"10.1016/j.ygyno.2024.10.001","url":null,"abstract":"<div><h3>Background</h3><div>Platinum-based chemotherapy with or without bevacizumab is the first-line treatment for patients with recurrent or metastatic cervical cancer (r/mCC), and the treatment options are limited for r/mCC after first-line treatment. Enlonstobart (SG001) is a fully humanized and high-affinity anti-PD-1 immunoglobulin G4 monoclonal antibody. Previous phase Ib study demonstrated that SG001 had a promising efficacy in patients with PD-L1 positive r/mCC.</div></div><div><h3>Methods</h3><div>In this multicenter, single-arm, open-label, phase II study, eligible patients were ≥ 18 years with PD-L1-positive cervical cancer who had progression on or intolerance to the first-line platinum-based chemotherapy. Patients received SG001 240 mg every two weeks for 24 months or until disease progression, intolerable toxicities, or other study discontinuation criteria were met. The primary endpoint was confirmed objective response rate (ORR) assessed by RECIST version 1.1 by independent review committee.</div></div><div><h3>Results</h3><div>107 patients were enrolled with median age of 53 years (range 26–72). 64.5 % of patients had a ECOG of 1. After a median follow-up of 14.0 months (range 0.4–21.9), confirmed ORR was 29.0 %, with two complete responses and twenty-nine partial responses. The disease control rate was 54.2 %. Median duration of response was 16.6 months (95 % CI 10.8-NA), median progression free survival was 3.1 months (95 % CI 2.2–6.9). Median overall survival was not reached. 104 patients (97.2 %) experienced at least one treatment emergent adverse events TEAEs, of which 38 patients (35.5 %) had grade 3 or higher TEAEs. The most common treatment-related adverse events were leukopenia (19.6 %), increased aspartate aminotransferase (18.7 %), anemia (17.8 %), increased alanine aminotransferase (15.9 %), hypothyroidism (15.0 %), neutropenia (15.0 %), and hyperthyroidism (11.2 %).</div></div><div><h3>Conclusion</h3><div>SG001 monotherapy demonstrated durable anti-tumor activity with acceptable safety in patients with PD-L1 positive r/mCC with progression on or intolerance to the first-line platinum-based chemotherapy.</div></div><div><h3>Trial registration</h3><div><span><span>ClinicalTrials.gov</span><svg><path></path></svg></span> (<span><span>NCT04886700</span><svg><path></path></svg></span>).</div></div>","PeriodicalId":12853,"journal":{"name":"Gynecologic oncology","volume":"191 ","pages":"Pages 165-171"},"PeriodicalIF":4.5,"publicationDate":"2024-10-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142499095","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":"Cold ischemia time and formalin fixation time in endometrial cancer: Should breast cancer guidelines for preanalytical variables be applied to hysterectomy specimens?","authors":"Paulina J. Haight ,&nbsp;Sydney Lammers ,&nbsp;Quinn Kistenfeger ,&nbsp;Chelsea Leipold ,&nbsp;Adrian A. Suarez ,&nbsp;Gary H. Tozbikian ,&nbsp;Ashwini Esnakula ,&nbsp;Casey Cosgrove ,&nbsp;Kristin L. Bixel","doi":"10.1016/j.ygyno.2024.10.015","DOIUrl":"10.1016/j.ygyno.2024.10.015","url":null,"abstract":"<div><h3>Objectives</h3><div>The American Society of Clinical Oncology (ASCO)/College of American Pathologists (CAP) recommend cold ischemia time (cIT) be &lt;60 min, and formalin fixation time (FFT) 6–72 h, to optimize immunohistochemistry (IHC) based on breast cancer data. We assessed whether cIT and FFT impact IHC in endometrial cancer (EC), and determined which factors affect cIT and FFT.</div></div><div><h3>Methods</h3><div>Surgical EC cases from 2019 to 2023 were reviewed. cIT was calculated by subtracting time of tissue devascularization intra-operatively from time the specimen was placed in formalin. Demographics, clinicopathologic and peri-operative factors, and IHC for estrogen receptor (ER), progesterone receptor (PR), human epidermal growth factor receptor 2 (HER2), and mismatch repair (MMR) proteins were compared between patients with cIT &lt;60 min versus ≥60 min (prolonged), and compliant FFT (6–72 h) versus non-compliant FFT (&lt;6 or &gt; 72 h). Categorical variables were compared using χ² tests.</div></div><div><h3>Results</h3><div>941 patients were included in the analysis. Median cIT was 33 min. Prolonged cIT occurred in 95 (10 %) cases. African American/Black race (<em>p</em> &lt; 0.001), advanced stage (p &lt; 0.001), mini-laparotomy (p &lt; 0.001), performance of surgical procedures beyond standard EC staging (p &lt; 0.001), longer surgical length (p &lt; 0.001), and increased uterine weight (p &lt; 0.001) were independently associated with prolonged cIT. There were no significant differences in ER, PR, HER2, or MMR protein expression based on cIT or FFT.</div></div><div><h3>Conclusion</h3><div>Prolonged cIT was not associated with differences in biomarker expression via IHC at time of surgical staging for EC. Despite variability in cIT, which is largely due to non-modifiable factors, tumor molecular features remain consistent and can reliably be utilized for prognostic and therapeutic decision-making.</div></div>","PeriodicalId":12853,"journal":{"name":"Gynecologic oncology","volume":"191 ","pages":"Pages 194-200"},"PeriodicalIF":4.5,"publicationDate":"2024-10-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142499077","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":"Imlunestrant, an oral selective estrogen receptor degrader, as monotherapy and combined with abemaciclib, in recurrent/advanced ER-positive endometrioid endometrial cancer: Results from the phase 1a/1b EMBER study","authors":"Kan Yonemori ,&nbsp;Valentina Boni ,&nbsp;Kim Gun Min ,&nbsp;Tarek M. Meniawy ,&nbsp;Janine Lombard ,&nbsp;Peter A. Kaufman ,&nbsp;Debra L. Richardson ,&nbsp;Laura Bender ,&nbsp;Meena Okera ,&nbsp;Koji Matsumoto ,&nbsp;Karthik V. Giridhar ,&nbsp;José Angel García-Sáenz ,&nbsp;Hans Prenen ,&nbsp;Bernard Doger de Speville Uribe ,&nbsp;Don S. Dizon ,&nbsp;Javier Garcia-Corbacho ,&nbsp;Els Van Nieuwenhuysen ,&nbsp;Yujia Li ,&nbsp;Shawn T. Estrem ,&nbsp;Bastien Nguyen ,&nbsp;Kalyan Banda","doi":"10.1016/j.ygyno.2024.10.006","DOIUrl":"10.1016/j.ygyno.2024.10.006","url":null,"abstract":"<div><h3>Objective</h3><div>Imlunestrant is a next-generation oral selective estrogen receptor degrader designed to deliver continuous estrogen receptor (ER) target inhibition. EMBER is a phase 1a/b trial of imlunestrant, as monotherapy and combined with targeted therapy, in patients with ER+ advanced breast cancer or endometrioid endometrial cancer (EEC). This report focuses on patients with ER+ EEC.</div></div><div><h3>Methods</h3><div>EMBER used an i3 + 3 dose-escalation design to determine the recommended phase 2 dose (RP2D) followed by dose-expansion cohorts (1:1 randomization): imlunestrant monotherapy and imlunestrant plus abemaciclib (150 mg twice daily). Eligible patients had measurable disease and progression or recurrence after platinum-containing chemotherapy. Prior fulvestrant or aromatase inhibitor was not allowed. Secondary endpoints included safety, pharmacokinetics and antitumor activity.</div></div><div><h3>Results</h3><div>In total, 72 patients with a median of 2 prior anticancer therapies were treated. Among the 39 patients who received imlunestrant (400 mg [RP2D], <em>n</em> = 33; 800 mg, <em>n</em> = 6), the most common treatment-emergent adverse events (TEAEs) were grade 1–2 nausea (35.9 %), diarrhea (25.6 %), urinary tract infection (25.6 %), and abdominal pain (20.5 %). Overall response rate (ORR) was 10.3 %, clinical benefit rate (CBR) was 33.3 %, and median progression-free survival (mPFS) was 3.8 months (95 % CI, 1.8–6.7). Among the 33 patients who received imlunestrant (400 mg [RP2D], <em>n</em> = 29; 800 mg, <em>n</em> = 4) plus abemaciclib, the most common TEAEs were diarrhea (87.9 %), nausea (66.7 %), fatigue (48.5 %), and anemia (45.5 %). ORR was 18.2 %, CBR was 42.4 %, and mPFS was 6.8 months (95 % CI, 2.1–12).</div></div><div><h3>Conclusion</h3><div>Imlunestrant, as monotherapy and combined with abemaciclib, has a manageable safety profile with preliminary evidence of antitumor activity in patients with ER+ EEC.</div></div>","PeriodicalId":12853,"journal":{"name":"Gynecologic oncology","volume":"191 ","pages":"Pages 172-181"},"PeriodicalIF":4.5,"publicationDate":"2024-10-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142499079","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":"Five-year quality-of-life assessment by urinary diversion type after pelvic Exenterations","authors":"Sara Moufarrij ,&nbsp;Christian Dagher ,&nbsp;Olga T. Filippova ,&nbsp;Qin Zhou ,&nbsp;Alexia Iasonos ,&nbsp;Nadeem R. Abu-Rustum ,&nbsp;Jennifer J. Mueller ,&nbsp;Mario M. Leitao ,&nbsp;Jaspreet Sandhu ,&nbsp;Bernard Bochner ,&nbsp;Jeanne Carter ,&nbsp;Dennis S. Chi ,&nbsp;Yukio Sonoda","doi":"10.1016/j.ygyno.2024.10.016","DOIUrl":"10.1016/j.ygyno.2024.10.016","url":null,"abstract":"<div><h3>Objective</h3><div>To determine whether urinary diversion procedures performed at time of pelvic exenteration affect quality of life in patients with recurrent gynecologic malignancies.</div></div><div><h3>Methods</h3><div>We performed a retrospective secondary longitudinal analysis of quality of life according to type of urinary diversion patients received. Participants completed a series of validated questionnaires at various time points. We allocated patients based on urinary diversion type to either the continent group (CD; 29 [55 %]) or noncontinent group (NCD; 24 [45 %]).</div></div><div><h3>Results</h3><div>We noted a significant improvement in global health scores from baseline over time (time <em>p</em> = 0.027). Physical functioning scores showed a statistically significant difference over time (at 24 months: NCD, −4.3 [95 % CI, −14.1 to 5.4]; CD, 0.4 [95 % CI, −7.1 to 7.9]. <em>p</em> &lt; 0.001). Social functioning scores were persistently higher for the CD vs NCD group at all time points but did not differ significantly between the groups at baseline (<em>p</em> = 0.75) or over time within the same group (time <em>p</em> = 0.122). Body image scores significantly decreased (reduced burden) over time for both groups (<em>p</em> = 0.044) and were consistently higher in the NCD vs CD group.</div></div><div><h3>Conclusions</h3><div>Patients experienced a return to their baseline quality of life within a year of surgery. Clinicians should prioritize and improve identifying and discussing postoperative challenges such as changes in physical and social functioning and body image.</div></div>","PeriodicalId":12853,"journal":{"name":"Gynecologic oncology","volume":"191 ","pages":"Pages 212-218"},"PeriodicalIF":4.5,"publicationDate":"2024-10-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142499078","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":"ATR inhibition increases reliance on PARP-mediated DNA repair revealing an improved therapeutic strategy for cervical cancer","authors":"Sugantha Priya Elayapillai ,&nbsp;Samrita Dogra ,&nbsp;James Lausen ,&nbsp;Madison Parker ,&nbsp;Amy Kennedy ,&nbsp;Doris M. Benbrook ,&nbsp;Katherine M. Moxley ,&nbsp;Bethany N. Hannafon","doi":"10.1016/j.ygyno.2024.10.009","DOIUrl":"10.1016/j.ygyno.2024.10.009","url":null,"abstract":"<div><h3>Objective</h3><div>Cervical cancer results from persistent infection with high-risk human papillomavirus (HR-HPV) and the expression of E6 and E7 oncoproteins. E6 and E7 compromise the activity of p53 and Rb, the G1-S cell cycle checkpoint, and ATM-mediated DNA damage repair (DDR), which in turn increases reliance on ATR- and PARP-mediated DDR at the G2 cell cycle checkpoint. This study aimed to determine the effects of an ATR inhibitor (ATRi, AZD6738) and a PARP-inhibitor (PARPi, AZD2281) on HR-HPV+ cervical cancer cell lines.</div></div><div><h3>Methods</h3><div>The effects of ATRi and PARPi, alone and in combination, on metabolic viability, cell cycle arrest, apoptosis, and DDR pathways in cervical cancer cell lines were evaluated in vitro, and the in vivo tumor response was evaluated using a xenograft model.</div></div><div><h3>Results</h3><div>Cervical cancer cells were sensitive to ATRi and PARPi monotherapy. The combination therapy was only synergistic in reducing metabolic viability when exposed to ATRi first, followed by PARPi, owing to ATRi-mediated upregulation of PARP expression. Combination of ATRi and PARPi induced G2 cell cycle arrest and apoptosis. PARPi induced DNA damage and γH2AX phosphorylation, which was further increased by ATRi treatment. However, PARPi-induced Rad51 foci formation was reduced by ATRi treatment, suggesting the inhibition of homologous recombination repair. ATRi significantly reduced cervical cancer xenograft tumor growth and was not affected by simultaneous PARPi treatment at the doses studied.</div></div><div><h3>Conclusions</h3><div>Our findings show that ATRi increased reliance on PARP for metabolic viability, the combination of ATRi and PARPi induced synthetic lethality in cervical cancer in vitro, and reduced tumor burden in vivo.</div></div>","PeriodicalId":12853,"journal":{"name":"Gynecologic oncology","volume":"191 ","pages":"Pages 182-193"},"PeriodicalIF":4.5,"publicationDate":"2024-10-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142463324","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":"Mild symptoms matter: Results from a prospective, longitudinal study on the relationship between symptoms, lymphedema and health-related outcomes post-gynecological cancer","authors":"Melanie L. Plinsinga ,&nbsp;Sheree Rye ,&nbsp;Tamara Jones ,&nbsp;Dimitrios Vagenas ,&nbsp;Leigh Ward ,&nbsp;Monika Janda ,&nbsp;Andreas Obermair ,&nbsp;Sandra C. Hayes","doi":"10.1016/j.ygyno.2024.10.011","DOIUrl":"10.1016/j.ygyno.2024.10.011","url":null,"abstract":"<div><h3>Objectives</h3><div>To describe lower-limb symptoms pre- through to 2-years post-surgery following newly diagnosed gynecological cancer; to explore relationships between lower-limb symptoms, lower-limb lymphedema, body image, quality of life, anxiety and depression; and to determine whether lower-limb symptoms predict lower-limb lymphedema.</div></div><div><h3>Methods</h3><div>Fourteen lower-limb symptoms, lymphedema, body image, anxiety, depression, and quality of life were prospectively collected in 408 women with gynecological cancer pre-surgery, and at 6-, 12-, and 24-months post-surgery. Point prevalence and cumulative incidence were calculated for symptoms. Cross-sectional relationships were explored between symptoms, lower-limb lymphedema and health-related outcomes at all timepoints, while regression analyses were used to assess the predictive relationships between lower-limb symptoms at 6-months post-surgery, and lymphedema at 12- and 24-months post-surgery.</div></div><div><h3>Results</h3><div>Participants were on average 59 (SD: 11) years of age, and 58 %, 28 %, 9 % and 5 % were diagnosed with endometrial, ovarian, cervical, and vulvar/vaginal cancer, respectively. Prevalence of any given lower limb symptom among all cancer types ranged between 11 and 59 %, with the most prevalent symptoms being pain, stiffness, and aching (prevalence &gt;40 % across all time-points). The presence of symptoms was associated with higher anxiety and depression, poorer overall quality of life and body image (<em>p</em> &lt; 0.01). Compared to those without symptoms, one or more lower limb symptoms of at least mild severity increased the odds of developing lymphedema up to 24 months post-surgery (OR &gt; 1.3).</div></div><div><h3>Conclusions</h3><div>Self-reported symptoms are associated with adverse health-related outcomes. Assessment and management of symptoms, irrespective of symptom severity, has potential for improving health outcomes, including lymphedema, in those following gynecological cancer.</div></div>","PeriodicalId":12853,"journal":{"name":"Gynecologic oncology","volume":"191 ","pages":"Pages 158-164"},"PeriodicalIF":4.5,"publicationDate":"2024-10-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142445878","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":"Less is more? Comparison between genomic profiling and immunohistochemistry-based models in endometrial cancer molecular classification: A multicenter, retrospective, propensity-matched survival analysis.","authors":"Emanuele Perrone, Ilaria Capasso, Diana Giannarelli, Rita Trozzi, Luigi Congedo, Elisa Ervas, Vincenzo Tarantino, Giovanni Esposito, Luca Palmieri, Arianna Guaita, Anne-Sophie van Rompuy, Giulia Scaglione, Gian Franco Zannoni, Giovanni Scambia, Frédéric Amant, Francesco Fanfani","doi":"10.1016/j.ygyno.2024.10.010","DOIUrl":"https://doi.org/10.1016/j.ygyno.2024.10.010","url":null,"abstract":"<p><strong>Background: </strong>Genomic profiling-based model (GP-M) is the gold-standard for endometrial cancer (EC) molecular classification, but several issues related to the availability of genomic sequencing in low-income settings remain and health disparities in the management are increasing. This study aims to investigate the non-inferiority of the immunohistochemistry-alone model in classifying ECs compared to the standard genomic profiling-based model in terms of oncologic outcomes.</p><p><strong>Methods: </strong>All preoperative uterine-confined ECs undergoing surgical staging were retrospectively included. Patients classified by IHC-M were stratified into: MMR-proficient (MMRp), p53 wild type (p53wt) and estrogen receptor (ER) positive, 2) MMRp, p53wt and ER-negative, 3) MMRd, and 4) p53abn. A case-control comparison was performed between the IHC-M and GP-M cohorts. Then, a propensity-matched analysis was performed: ECs classified by IHC-M were matched in a 3:1 ratio with patients classified by GP-M.</p><p><strong>Results: </strong>1587 patients with EC were included. The Kaplan-Meier survival curves for disease-free survival and overall survival demonstrated that the two models performed similarly in risk-stratifying the study population (p < 0.0001). Moreover, the AUC-ROC showed overlapping results: 0.77 (0.66-0.87) for IHC-M and 0.72 (0.63-0.81) for GP-M, indicating that both models were able to successfully identify patients at high-risk and low-risk of disease recurrence/progression.</p><p><strong>Conclusion: </strong>The IHC-M showed overlapping classification performance compared to the GP-M in terms of oncologic outcomes. This study may lay the basis to further investigate the real-life clinical impact of POLE sequencing in molecular classification and the potential stand-alone prognostic role of ER status for further allocation of EC patients into risk classes.</p>","PeriodicalId":12853,"journal":{"name":"Gynecologic oncology","volume":"191 ","pages":"150-157"},"PeriodicalIF":4.5,"publicationDate":"2024-10-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142463325","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":"Surgery after upfront chemoradiation in locally advanced squamous cell vulvar cancer: Analysis of postoperative outcomes and survival","authors":"Alex Federico ,&nbsp;Valentina Lancellotta ,&nbsp;Simona M. Fragomeni ,&nbsp;Gabriella Macchia ,&nbsp;Sara Ammar ,&nbsp;Tina Pasciuto ,&nbsp;Angela Santoro ,&nbsp;Giacomo Corrado ,&nbsp;Alessia Piermattei ,&nbsp;Valerio Gallotta ,&nbsp;Luca Tagliaferri ,&nbsp;Gianfranco Zannoni ,&nbsp;Maria A. Gambacorta ,&nbsp;Giovanni Scambia ,&nbsp;Giorgia Garganese","doi":"10.1016/j.ygyno.2024.10.005","DOIUrl":"10.1016/j.ygyno.2024.10.005","url":null,"abstract":"<div><h3>Objective</h3><div>The aim of the study was to assess the survival rates and surgery-related toxicity in patients with locally advanced squamous cell vulvar cancer (LAVC) managed by upfront chemoradiation (CRT) with/without following by surgery.</div><div>CRT is the primary treatment for patients with unresectable locally advanced squamous cell vulvar carcinoma (LAVC), followed by surgery in case of residual tumor.</div></div><div><h3>Methods</h3><div>Patients with AJCC stage II-IV squamous cell vulvar carcinoma referred to Gynecologic Oncology Unit at Fondazione Policlinico Universitario Agostino Gemelli I.R.C.C.S. from January 2016 to February 2023, managed by upfront CRT, were included.</div></div><div><h3>Results</h3><div>63 patients were included, 21 (33 %) had complete response (cCR) to CRT, 26 (41 %) had partial response (cPR), 1 (2 %) stable disease (cSD), 15 (24 %) had disease progression (cPD).</div><div>In the whole population, cPR/SD and cPD were associated with reduced PFS (<em>p</em> &lt; 0.001) and overall survival (OS) (p &lt; 0.001), p16 expression was associated with improved PFS (p &lt; 0.001) and OS (<em>p</em> = 0.001).</div><div>Among patients with clinical residual disease after CRT, 23 patients undergoing surgery experienced improved PFS (<em>p</em> = 0.003) and OS (p = 0.003) compared to those receiving other treatments.</div><div>Eight (35 %) patients experienced severe (grade ≥ III) postoperative complications; vulvar and groin wound dehiscence/infection were the most common complications; one (4 %) patient died in the postoperative. Patients with pathological residual disease experienced worse PFS (<em>p</em> = 0.013) and OS (<em>p</em> = 0.034).</div></div><div><h3>Conclusions</h3><div>Clinical response to CRT and p16 expression strongly predict survival in LAVC. Surgery for residual disease might be associated with improved survival but is burdened by high rates of complications. Pathologic residual disease correlates with high recurrence rates and poor survival.</div></div>","PeriodicalId":12853,"journal":{"name":"Gynecologic oncology","volume":"191 ","pages":"Pages 106-113"},"PeriodicalIF":4.5,"publicationDate":"2024-10-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142442529","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":"Immunological impact of intraperitoneal and intravenous chemotherapy in ovarian cancer, translational analyses of the Phase 3 iPocc trial","authors":"Aiko Ogasawara ,&nbsp;Hirokazu Matsushita ,&nbsp;Tuan Zea Tan ,&nbsp;Daisuke Shintani ,&nbsp;Jieru Ye ,&nbsp;Shoji Nagao ,&nbsp;Ayako Demachi-Okamura ,&nbsp;Daisuke Muraoka ,&nbsp;Yukari Kobayashi ,&nbsp;Kazuhiro Kakimi ,&nbsp;Rui Yamaguchi ,&nbsp;Keitaro Matsuo ,&nbsp;Kouji Yamamoto ,&nbsp;Keiichi Fujiwara ,&nbsp;Ruby Yun-Ju Huang ,&nbsp;David Shao Peng Tan ,&nbsp;Kosei Hasegawa","doi":"10.1016/j.ygyno.2024.09.023","DOIUrl":"10.1016/j.ygyno.2024.09.023","url":null,"abstract":"<div><h3>Background</h3><div>The iPocc trial, a randomized, global phase 3 study that compared intraperitoneal (IP) and intravenous (IV) carboplatin with dose-dense paclitaxel chemotherapy in epithelial ovarian cancer (EOC) patients, demonstrated improved progression-free survival in patients who received IP chemotherapy. The present study aimed to investigate the role of preexisting tumor immunity in the clinical outcomes of patients receiving IP chemotherapy.</div></div><div><h3>Methods</h3><div>This study involved analyzing patient data from the iPocc trial, selectively of those whose tumor specimens were preserved at the time of primary surgery. A total of 116 cases ((IP; <em>n</em> = 59), (IV; <em>n</em> = 57)) were subjected to microarray analysis. Single-sample gene set enrichment analyses were performed to evaluate the tumor immune microenvironment.</div></div><div><h3>Results</h3><div>Patients with enhanced tumor infiltration of T cells, natural killer (NK) cells, and cytotoxic lymphocytes in the IP group had a longer overall survival (OS) than those in the IV group, but not in the group with low infiltration. IP therapy improved the OS of patients with high expression of immune-related genes such as CD8A and FOXP3. In patients' subdivided into “immune Hot” and “immune Cold” groups based on hierarchical clustering analysis using four parameters representing “Innate immunity,” “T cells,” “IFNG response” and “Inhibitory molecules,” IP therapy significantly improved prognosis in the “immune Hot” group, but not in the “immune Cold” group compared to that of IV therapy.</div></div><div><h3>Conclusions</h3><div>IP chemotherapy enhances the survival rates of patients with EOC with an immune-Hot phenotype in the tumor microenvironment prior to treatment.</div><div>(Japan Registry of Clinical Trials number, jRCTs031180141.)</div></div>","PeriodicalId":12853,"journal":{"name":"Gynecologic oncology","volume":"191 ","pages":"Pages 124-131"},"PeriodicalIF":4.5,"publicationDate":"2024-10-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142442530","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 analysis of hormonal therapy in low-grade endometrial stromal sarcoma: A retrospective study","authors":"Reem Saab ,&nbsp;Bryan M. Fellman ,&nbsp;Alejandra Flores Legarreta ,&nbsp;Larissa A. Meyer ,&nbsp;Nicole D. Fleming ,&nbsp;Ravin Ratan ,&nbsp;Elise F. Nassif Haddad ,&nbsp;Michael Frumovitz ,&nbsp;Pamela T. Soliman","doi":"10.1016/j.ygyno.2024.10.008","DOIUrl":"10.1016/j.ygyno.2024.10.008","url":null,"abstract":"<div><h3>Objective</h3><div>To evaluate the disease course of patients with low grade endometrial stromal sarcoma (LG-ESS) and compare oncologic outcomes associated with hormonal therapy in primary and recurrent disease.</div></div><div><h3>Methods</h3><div>This is a retrospective study of patients with LG-ESS who underwent active treatment between January 2000 and July 2023. Recurrence-free survival (RFS) and overall survival (OS) were estimated using the Kaplan-Meier product-limit estimator and modeled via Cox proportional hazards regression.</div></div><div><h3>Results</h3><div>A total of 221 patients were included; 58 % of patients (91/157) were stage I, 12 % (19/157) stage II, 13 % (20/157) stage III, and 17 % (27/157) stage IV. Surgery was the primary treatment for 98 % (213/218). Only 79 patients received hormonal adjuvant therapy, 58 % (46/79) Megace, 24 % (19/79) Letrozole, and 18 % (14/79) received other hormonal therapy. There was no significant difference in RFS (<em>p</em> = 0.159) and OS (<em>p</em> = 0.167) between patients receiving Megace versus Letrozole as adjuvant therapy. At first recurrence, patients given Megace had a similar RFS to those on Letrozole (<em>p</em> = 0.302), but a better OS (27 vs 10 months, <em>p</em> = 0.018).  Negative status of estrogen, smooth muscle actin, and desmin were associated with lower RFS (<em>p</em> = 0.039, <em>p</em> = 0.002, and <em>p</em> = 0.015, respectively) and OS (<em>p</em> = 0.008, <em>p</em> = 0.012, and <em>p</em> = 0.013, respectively). Lymphovascular invasion was associated with lower RFS (<em>p</em> = 0.033), and negative status of progesterone was associated with lower OS (<em>p</em> = 0.003).</div></div><div><h3>Conclusion</h3><div>There was no difference in oncologic outcomes between Megace and Letrozole in patients who received adjuvant therapy for LG-ESS. Megace may have potential survival advantage in recurrent disease. Further study is warranted to determine the most effective agents and their sequence in the treatment of LG-ESS.</div></div>","PeriodicalId":12853,"journal":{"name":"Gynecologic oncology","volume":"191 ","pages":"Pages 143-149"},"PeriodicalIF":4.5,"publicationDate":"2024-10-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142419819","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}