International Journal of Gynecological Cancer最新文献

{"title":"Radical trachelectomy in Brazil: a multi-institutional review on fertility preservation and oncologic outcomes.","authors":"Renato Moretti-Marques, Victória Elizabeth de Moura, Ive Bahia Franca, Pedro Ernesto de Cillo, Gabriela Gomes Prates, Georgia Fontes Cintra, Marcelo Henrique Dos Santos, Glauco Baiocchi, Gustavo Guitmann, Suzana Arenhart Pessini, Gabriel Lowndes de Souza Pinto, Rosilene Jara Reis, Audrey Tieko Tsunoda, Jeancarllo de Sousa Silva, Fábio Roberto Fin, Vandré Cabral Gomes Carneiro, Marcelo Simonsen, Andressa Melina Severino Teixeira, Guilherme Bicudo Barbosa, Carlos Daniel Hernandez Antonello, Eldom de Medeiros Soares, Deraldo Fernando Falcão Filho, José Augusto Bellotti, Camilla Bandeira Soares, Reitan Ribeiro, Agnaldo Lopes da Silva-Filho, Marcelo de Andrade Vieira, Ricardo Dos Reis, Vanessa Alvarenga-Bezerra","doi":"10.1016/j.ijgc.2026.104978","DOIUrl":"10.1016/j.ijgc.2026.104978","url":null,"abstract":"<p><strong>Introduction: </strong>Fertility preservation has become an increasingly important goal in the management of young women with early-stage cervical cancer. Radical trachelectomy is an established fertility-sparing procedure with favorable oncologic and reproductive outcomes; however, evidence from low- and middle-income countries remains limited. This study aimed to evaluate perioperative, pathologic, oncologic, reproductive, and obstetric outcomes of radical trachelectomy in a large multi-center Brazilian cohort.</p><p><strong>Methods: </strong>This retrospective multi-center study included patients with an initial International Federation of Gynecology and Obstetrics 2018 stage IA1-IB3 cervical cancer who underwent radical trachelectomy between January 2010 and April 2026 at 19 Brazilian centers. Eligible histologic sub-types included squamous cell carcinoma, adenocarcinoma, and adenosquamous carcinoma. Demographic, surgical, pathological, oncologic, and reproductive data were collected from medical records. Comparisons between groups were performed using chi-square, Fisher exact, likelihood ratio, or Mann-Whitney tests, as appropriate. Recurrence-free survival was estimated using the Kaplan-Meier method and compared using the log-rank test. Statistical significance was set at p <.05.</p><p><strong>Results: </strong>A total of 141 women underwent radical trachelectomy. Median age was 32 years (Interquartile range, 29 to 35), and most patients had International Federation of Gynecology and Obstetrics 2018 stage IB1 disease (52.5%). Nodal assessment was performed in 98.6% of cases, with lymph node metastases identified in 6.5% (9/139). Parametrial involvement was observed in 2.1% (3/140) of patients. Most procedures were performed using a minimally invasive approach (83.7%). Adjuvant treatment was required in 9.9% of cases. After a median follow-up of 49.4 months, the 5-year recurrence-free survival rate (calculated from the date of surgery) was 91.3%, and no statistically significant difference was observed between patients undergoing minimally invasive and open surgery (p =.873). Cancer-related mortality was 2.8% (4/141). Among 51 women attempting conception, 23 (45.1%) achieved pregnancy, resulting in 32 pregnancies and 18 live births.</p><p><strong>Conclusion: </strong>Radical trachelectomy provided favorable oncologic outcomes while preserving reproductive potential in selected women with early-stage cervical cancer. The low rates of recurrence, nodal metastasis, and parametrial involvement observed in this study are consistent with contemporary evidence supporting less radical surgical approaches in carefully selected patients.</p>","PeriodicalId":14097,"journal":{"name":"International Journal of Gynecological Cancer","volume":"36 10","pages":"104978"},"PeriodicalIF":5.4,"publicationDate":"2026-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149109291","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":"Radiotherapy and brachytherapy capacity, treatment timelines, and barriers to guideline-concordant curative care for cervical cancer in Latin America: the LATAM-CxRT study.","authors":"Florencia Noll, Fernando Heredia, Vanessa Alvarenga-Bezerra, Arthur Accioly Rosa, Catalina Dutari, Juliana Karassawa Helito, Luciana Brun, María Caicedo Martínez, Renato Affonso, José Máximo Barros, Lina María Loaiza Salazar, Raúl Puente-Vallejo, Max Fasano, Pamela Aquino Cardozo, Francisco Javier Lozano Ruiz, Enrique Flores Escudero, María Gabriela Villegas, Christian Vargas Del Río, Javier Calderón Hernández, Hernán Letelier, Mariluna García, David Antonio Martínez Pérez","doi":"10.1016/j.ijgc.2026.104980","DOIUrl":"https://doi.org/10.1016/j.ijgc.2026.104980","url":null,"abstract":"<p><strong>Objective: </strong>To describe national radiotherapy and brachytherapy capacity, treatment delivery, and barriers to guideline-concordant curative treatment among women with cervical cancer requiring definitive or adjuvant radiotherapy in Latin America.</p><p><strong>Methods: </strong>We conducted a cross-sectional survey of national radiation oncology coordinators from 14 Latin American countries using a standardized Research Electronic Data Capture questionnaire covering institutional mix, radiotherapy and brachytherapy infrastructure, imaging capacity, cervical cancer caseloads, external beam radiotherapy and brachytherapy practice, treatment timelines, and barriers and needs as perceived by coordinators. Data were cross-checked against International Atomic Energy Agency and vendor data where available.</p><p><strong>Results: </strong>Fourteen countries contributed data: all completed general characteristics, 13 completed the resources and workforce module, and 12 completed the full equipment and timelines module. Among these 12 countries, the median number of linear accelerators was 33.5 per country (interquartile range 9 to 101.75), reflecting a right skew driven by Brazil. The median annual caseload was 680.5 patients for International Federation of Gynecology and Obstetrics stages I to II disease and 800 patients for stages III to IV disease. Nearly all countries reported intensity-modulated radiotherapy, image-guided radiotherapy, and volumetric-modulated arc therapy capabilities. Gynecologic high-dose-rate brachytherapy was available in all 12 countries, although several reported insufficient coverage, with services concentrated in reference centers; magnetic resonance imaging-guided brachytherapy, interstitial techniques, and anesthesia support were available in only a subset. Half of countries reported 91% to 100% brachytherapy completion among women initiating curative chemoradiation, but overall treatment time from external beam radiotherapy start to brachytherapy completion exceeded 56 days in most countries. Coordinators identified limited brachytherapy and imaging capacity, workforce shortages, anesthesia constraints, and financial barriers as key impediments. These findings describe installed capacity and self-reported practice rather than direct measures of patient-level access.</p><p><strong>Conclusions: </strong>This 14-country survey demonstrates that, despite widespread availability of advanced external beam radiotherapy, cervical cancer care in Latin America remains constrained by heterogeneous and often insufficient brachytherapy and imaging resources and by treatment delays exceeding guideline recommendations. Targeted investment, workforce development, service organization, and financing reforms are needed to deliver guideline-concordant chemoradiation for women with cervical cancer in the region.</p>","PeriodicalId":14097,"journal":{"name":"International Journal of Gynecological Cancer","volume":"36 10","pages":"104980"},"PeriodicalIF":5.4,"publicationDate":"2026-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149109323","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 cancer prevention in motion: national impact of the Barretos Cancer Hospital model.","authors":"Júlio César Possati-Resende, Hanna Karolina de Araújo Batistão, Sinval Tadeu Biot, Welinton Yoshio Hirai, Renato José da Silva Oliveira, Rui Manuel Reis, Raphael Luiz Haikel Júnior, Edmundo Carvalho Mauad, Ricardo Dos Reis","doi":"10.1016/j.ijgc.2026.104968","DOIUrl":"https://doi.org/10.1016/j.ijgc.2026.104968","url":null,"abstract":"<p><strong>Objective: </strong>This study aims to describe the nationwide cervical cancer screening strategy implemented by the Barretos Cancer Hospital system through fixed and mobile units. It also aims to evaluate its impact on cervical cancer control through a quantitative and qualitative assessment of screening outcomes, comparing the organized Barretos Prevention Program with External Screening Units.</p><p><strong>Methods: </strong>Data were collected from the Barretos Prevention Program screening database and institutional cytological and histopathological registries, covering the period from January 2012 to December 2025. Two screening groups were analyzed: women screened, recalled, and treated through Barretos Cancer Hospital internal units (Barretos Prevention Program group; n =1,258,295) and women screened through External Screening Units whose cytological samples were centrally processed at Barretos Cancer Hospital (External Screening Units group; n =1,375,759). Categorical variables were compared using chi-square or Fisher's exact test. Statistical significance was set at p < .05.</p><p><strong>Results: </strong>The organized cervical cancer screening strategy implemented by Barretos Cancer Hospital, combining fixed and mobile prevention units and a centralized electronic information system, demonstrated superior performance indicators compared with opportunistic screening, with higher cytological positivity rates, lower unsatisfactory sample rates, improved target age-group adherence, and a markedly earlier stage distribution at diagnosis.</p><p><strong>Conclusion: </strong>These findings reinforce the critical role of organized, population-based screening in reducing the cervical cancer burden in Brazil and highlight the need for nationwide expansion of structured screening strategies integrated with human papillomavirus vaccination, human papillomavirus-based primary testing, and guaranteed access to diagnostic and therapeutic services.</p>","PeriodicalId":14097,"journal":{"name":"International Journal of Gynecological Cancer","volume":"36 10","pages":"104968"},"PeriodicalIF":5.4,"publicationDate":"2026-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149109357","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":"Early experience with mirvetuximab soravtansine in the treatment of recurrent low- grade serous ovarian carcinoma.","authors":"Elio Tahan, Charlotte C Sun, Aradhana M Venkatesan, Lauren P Cobb, Anil K Sood, Travis T Sims, Jolyn S Taylor, Shannon N Westin, Shrina Patel, David M Gershenson","doi":"10.1016/j.ijgc.2026.105601","DOIUrl":"https://doi.org/10.1016/j.ijgc.2026.105601","url":null,"abstract":"<p><strong>Objective: </strong>Low-grade serous ovarian carcinoma is a rare subtype of epithelial ovarian cancer characterized by relative resistance to chemotherapy and limited treatment options at recurrence. Mirvetuximab soravtansine, a folate receptor alpha-targeting antibody-drug conjugate, has demonstrated efficacy in folate receptor alpha-positive ovarian cancer; however, data on low-grade serous ovarian cancer are limited. This study aimed to evaluate the efficacy and safety of mirvetuximab in patients with recurrent low-grade serous ovarian carcinoma.</p><p><strong>Methods: </strong>This is a retrospective review of patients with recurrent low-grade serous ovarian carcinoma treated with mirvetuximab at MD Anderson Cancer Center from 2024 to 2026. Demographic, clinicopathologic, molecular, treatment, and outcome data were collected. Best overall treatment response was assessed using the Response Evaluation Criteria in Solid Tumors, version 1.1, on serial imaging obtained at 3-month intervals. Duration of response and progression-free survival were evaluated.</p><p><strong>Results: </strong>Twelve patients with recurrent low-grade serous carcinoma were identified. The median age at diagnosis was 47.5 years. Most patients had advanced-stage disease at diagnosis and had received a median of 4 prior lines of systemic treatment. High folate receptor alpha expression (≥75% staining) was observed in 83.3% of tumors. Patients received a median of 13.5 mirvetuximab cycles, and 4 patients received concomitant bevacizumab. The best overall responses were partial response (n = 4, 33.3%), stable disease (n = 7, 58.33%), and progressive disease (n = 1, 8.33%). The disease control rate was 91.67%. The median duration of response among responders was 8.37 months, and the median duration of stable disease was 12.10 months. The median progression-free survival was not reached at the time of analysis because 6 patients remained on treatment. The most common adverse events included ocular toxicity, gastrointestinal symptoms, peripheral neuropathy, and pneumonitis. Toxicities led to dose modifications in 58.33% of cases and drug discontinuation in 25% of patients.</p><p><strong>Conclusions: </strong>Mirvetuximab demonstrated promising efficacy in patients with recurrent low-grade serous ovarian carcinoma. These findings warrant further prospective studies of folate receptor alpha-targeted antibody-drug conjugates.</p>","PeriodicalId":14097,"journal":{"name":"International Journal of Gynecological Cancer","volume":" ","pages":"105601"},"PeriodicalIF":5.4,"publicationDate":"2026-09-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149165410","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":"Low anterior resection syndrome and bowel dysfunction after ovarian cancer cytoreductive surgery: a narrative review.","authors":"David Viveros-Carreño, Nathalia Mora-Soto, Isabel Beshar, Martina A Angeles, Vicente Bebia, Ana Luzarraga Aznar, Naia Seminario, Gabrielle H van Ramshorst, Alejandro Rauh-Hain, René Pareja","doi":"10.1016/j.ijgc.2026.105005","DOIUrl":"https://doi.org/10.1016/j.ijgc.2026.105005","url":null,"abstract":"<p><p>Post-operative bowel dysfunction is an important survivorship issue in ovarian, fallopian tube, and primary peritoneal cancer. Cytoreductive surgery often includes rectosigmoid resection, placing patients at risk for low anterior resection syndrome, in which disordered bowel function after sphincter-preserving rectal resection impairs quality of life. Symptoms may precede surgery and worsen after cytoreduction. This review aims to synthesize the available evidence on low anterior resection syndrome and post-operative bowel dysfunction after ovarian cancer cytoreductive surgery and to define research priorities. Its presentation after ovarian cancer surgery may differ from that after rectal cancer surgery because of differences in disease distribution, pelvic dissection, radiotherapy exposure, systemic therapy, stoma practice, and baseline gastrointestinal symptoms. In some ovarian cancer cohorts, constipation-predominant dysfunction has been reported and requires complementary assessment because the low anterior resection syndrome score measures different symptom domains. Candidate factors include ultra-low rectal resection, low anastomotic height, multiple bowel anastomoses, extensive pelvic dissection, autonomic nerve disruption, para-aortic lymphadenectomy, recurrent disease, stoma-related factors, and pre-existing bowel dysfunction. Evidence remains largely observational and heterogeneous, with limitations related to inconsistent definitions, variable assessment timing, and a lack of standardized outcome measurement. Prevention should not compromise complete macroscopic tumor resection when rectosigmoid resection is oncologically required, but surgical planning should include preservation of rectal length and pelvic autonomic function when feasible, documentation of anastomotic height, and selective stoma use with restoration of continuity when appropriate. Management is largely extrapolated from the colorectal literature and should be symptom-directed, beginning with systematic assessment, stool regulation, diet, and medication, and escalating to pelvic floor rehabilitation, transanal irrigation, or specialist pelvic floor care when needed. Prospective ovarian cancer-specific studies with baseline assessment, standardized time points, and validated patient-reported outcomes are needed to estimate prevalence and guide survivorship care.</p>","PeriodicalId":14097,"journal":{"name":"International Journal of Gynecological Cancer","volume":" ","pages":"105005"},"PeriodicalIF":5.4,"publicationDate":"2026-09-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149030504","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":"Response to: evolving global governance in gynecologic oncology trials: toward trilateral academic collaboration.","authors":"Robert L Coleman, Isabelle Ray-Coquard","doi":"10.1016/j.ijgc.2026.104879","DOIUrl":"https://doi.org/10.1016/j.ijgc.2026.104879","url":null,"abstract":"","PeriodicalId":14097,"journal":{"name":"International Journal of Gynecological Cancer","volume":" ","pages":"104879"},"PeriodicalIF":5.4,"publicationDate":"2026-09-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149206825","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":"Robot-assisted resection of oligometastatic recurrence involving hepatoceliac lymph nodes in a patient with a BRCA1 pathogenic variant.","authors":"Jachym Liebich, Munachiso Iheme Ndukwe, Petra Bretova, Jan Laco, Igor Sirak, Jan Zajak","doi":"10.1016/j.ijgc.2026.105626","DOIUrl":"https://doi.org/10.1016/j.ijgc.2026.105626","url":null,"abstract":"","PeriodicalId":14097,"journal":{"name":"International Journal of Gynecological Cancer","volume":"36 12","pages":"105626"},"PeriodicalIF":5.4,"publicationDate":"2026-09-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149192861","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":"Metastasis to the fetoplacental unit during gestation: a scoping review.","authors":"José Richard Tenazoa-Villalobos, Clara Huertas-Burgos, Sara Burgos-Muñoz, Marilia Aguirre-Mendoza, Jannis Pozo-Calle, Vladimir Villoslada-Terrones","doi":"10.1016/j.ijgc.2026.105002","DOIUrl":"https://doi.org/10.1016/j.ijgc.2026.105002","url":null,"abstract":"<p><strong>Objective: </strong>This study systematically maps and synthesizes the clinical characteristics, histopathological invasion patterns, and perinatal outcomes of the mother-placenta-fetus triad in cases of maternal malignancies metastasizing to the fetoplacental unit.</p><p><strong>Methods: </strong>A scoping review was conducted in accordance with Preferred Reporting Items for Systematic Reviews and Meta-Analyses extension for Scoping Reviews guidelines and Joanna Briggs Institute methodology. Systematic searches were performed in PubMed, Embase, Scopus, Cumulative Index to Nursing and Allied Health Literature, and Web of Science for studies published from 1950 to 2026. Using the population, concept, and context framework, the review included studies involving pregnant women with malignancies confirmed by histopathology and evidence of metastatic spread to the placenta, umbilical cord, or fetus.</p><p><strong>Results: </strong>A total of 104 cases were identified. Melanoma was the most common primary malignancy (36.5%), followed by hematologic neoplasms (18.3%), breast cancer (15.4%), and lung cancer (11.5%). Placental metastasis was detected incidentally in 76.0% of cases during post-partum histopathological examination and in 20.2% prenatally. Confirmed fetal metastasis occurred in 20.2% of cases, with melanoma exhibiting the highest transmission rate, at 31.6%. A prognostic paradox was observed: despite a high maternal mortality rate of 80.8%, neonatal survival at follow-up was 68.3%. Obstetric complications were frequent and included iatrogenic prematurity (65.4%) and cesarean section (67.3%).</p><p><strong>Conclusions: </strong>Metastasis to the fetoplacental unit indicates advanced maternal disease and is associated with a poor maternal prognosis. Because most metastases are not detected before birth, universal histopathological examination of the placenta is essential in all cases of gestational cancer to inform neonatal staging and risk assessment. Fetal metastasis may manifest after birth; therefore, infants require at least 1 year of clinical surveillance.</p>","PeriodicalId":14097,"journal":{"name":"International Journal of Gynecological Cancer","volume":" ","pages":"105002"},"PeriodicalIF":5.4,"publicationDate":"2026-09-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148955839","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":"Beyond platinum resistance: time to retire a 34-year-old definition and prevent reflex oncology.","authors":"Jalid Sehouli, Elena Ioana Braicu","doi":"10.1016/j.ijgc.2026.105608","DOIUrl":"https://doi.org/10.1016/j.ijgc.2026.105608","url":null,"abstract":"","PeriodicalId":14097,"journal":{"name":"International Journal of Gynecological Cancer","volume":" ","pages":"105608"},"PeriodicalIF":5.4,"publicationDate":"2026-09-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149167386","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":"BEHOLD-1 and -2: phase 1/2 randomized studies evaluating the B7 homolog 4 protein-targeted antibody-drug conjugate mocertatug rezetecan in patients with solid tumors, including endometrial and ovarian cancers.","authors":"Stephanie Lheureux, Diane Provencher, Sofia Baka, Ruben Kowalyszyn, Tim Schutte, Yüksel Ürün, Xing Zeng, Ana Oaknin, Domenica Lorusso, Isabelle Ray-Coquard, Victor Moreno, Katriina Jalkanen, Lisa Liu Burström, Marloes G J van Dongen, Valentina Boni, Jung-Yun Lee, Philippe L Bedard, Izabela A Malinowska, Morrys Kaisermann, William McKean","doi":"10.1016/j.ijgc.2026.105607","DOIUrl":"https://doi.org/10.1016/j.ijgc.2026.105607","url":null,"abstract":"<p><strong>Background: </strong>B7 homolog 4 protein (B7-H4) is an immunoregulatory protein that is overexpressed in gynecological cancers and has limited expression in normal tissues. Mocertatug rezetecan (Mo-Rez; GSK5733584) is a novel antibody-drug conjugate comprising an anti-B7-H4 antibody conjugated to a topoisomerase 1 inhibitor payload via a protease-cleavable linker and has shown early clinical activity in gynecological cancers.</p><p><strong>Primary objective: </strong>The BEHOLD program is evaluating the safety, tolerability, and preliminary anti-tumor activity of mocertatug rezetecan as monotherapy (BEHOLD-1) and as combination therapy (BEHOLD-2) in gynecological cancers.</p><p><strong>Study hypothesis: </strong>Mocertatug rezetecan monotherapy or combination therapy has a manageable safety profile and clinically meaningful anti-tumor activity in gynecological cancers.</p><p><strong>Trial design: </strong>BEHOLD-1 is a phase 1a/b study evaluating doses of intravenous mocertatug rezetecan in advanced solid tumors (phase 1a: dose escalation; phase 1b: randomized dose optimization/expansion). The phase 1/2 BEHOLD-2 study evaluates doses of intravenous mocertatug rezetecan with intravenous dostarlimab in endometrial cancer or with intravenous bevacizumab in ovarian cancer (part A: dose exploration; part B: dose expansion).</p><p><strong>Major inclusion/exclusion criteria: </strong>Eligible patients are defined as follows: BEHOLD-1 phase 1a: patients with advanced solid tumors; BEHOLD-1 phase 1b: patients with platinum-resistant ovarian cancer or advanced or recurrent endometrial cancer; BEHOLD-2 part A: patients with advanced or recurrent endometrial cancer or advanced ovarian cancer; BEHOLD-2 part B: patients with second-line-or-later mismatch repair proficient or microsatellite stable endometrial cancer or second-line-or-later platinum-sensitive ovarian cancer. For both studies, patients must have measurable disease per Response Evaluation Criteria in Solid Tumors version 1.1 (RECIST v1.1).</p><p><strong>Primary endpoints: </strong>BEHOLD-1 phase 1a: dose-limiting toxicities. BEHOLD-1 phase 1b: confirmed objective response rate per RECIST v1.1. BEHOLD-2 part A: dose-limiting toxicities and safety. BEHOLD-2 part B: confirmed objective response rate per RECIST v1.1.</p><p><strong>Sample size: </strong>BEHOLD-1: approximately 675 patients. BEHOLD-2: approximately 305 patients.</p><p><strong>Estimated dates for completing accrual and presenting results: </strong>BEHOLD-1: September 2027. BEHOLD-2: June 2027.</p><p><strong>Trial registration: </strong>BEHOLD-1: NCT06431594. BEHOLD-2: NCT06796907.</p>","PeriodicalId":14097,"journal":{"name":"International Journal of Gynecological Cancer","volume":" ","pages":"105607"},"PeriodicalIF":5.4,"publicationDate":"2026-09-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149136488","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}