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Findings from clinical trials have led to advancement of care for patients with gynecologic malignancies. However, restrictive inclusion of patients into trials has been widely criticized for inadequate representation of the real-world population. Ideally, patients enrolled in clinical trials should represent a broader population to enhance external validity and facilitate translation of outcomes across all relevant groups. Specifically, there has been a systematic lack of data for underrepresented groups, with many studies failing to report or differentiate study participants based on sociodemographic domains, such as race and ethnicity. As such, the impact of treatment in these underrepresented groups is poorly understood, and clinical outcomes according to various sociodemographic factors are infrequently assessed. Inclusion of diverse trial participants, with different racial and ethnic background, is essential for the understanding of factors that may impact clinical outcomes. Therefore, we conducted a multi-national meeting of clinical trial groups and industry with the goal of increasing equity, diversity, and inclusion in gynecologic cancer clinical trials and to address barriers to recruitment, participation, and harmonization of data collection and reporting. These Gynecologic Cancer Intergroup (GCIG) statements present recommendations and strategies for the gynecologic cancer research community to improve equity, diversity, and inclusion in gynecologic cancer clinical trials., Competing Interests: Competing interests: Alison Brand reports grants/contracts from the Australian Government Department of Health and Aged Care Medical Research Future Fund, Australia and New Zealand Gynaecological Oncology Group (ANZGOG); and is Director ANZGOG, Chair GCIG. Michael Bookman reports consultancy fees paid to the institution from Immunogen independent DSMB. Sabrina Chiara Cecere reports travel support from AstraZeneca, Clovis, GSK, MSD; honoraria from AstraZeneca, Clovis, GSK, MSD; participation on a Data Safety Monitoring Board or Advisory Board from AstraZeneca, Clovis, GSK, MSD. Paul A. Cohen reports grants/contracts from the Australian Government Department of Health and Aged Care Medical Research Future Fund, Cancer Council Western Australia, Australia and New Zealand Gynaecological Oncology Group (ANZGOG); honoraria and educational events from AstraZeneca, MSD; advisory boards with AstraZeneca, Reliis; non-remunerated leadership roles as Director ANZGOG, Chair Research Advisory Committee ANZGOG, Education Committee Chair, International Gynecological Cancer Society, Expert Advisory Group Australian Centre for Prevention of Cervical Cancer, Editorial Board Member International Journal Gynecological Cancer; stock in Reliis Ltd. Jennifer Croke reports honoraria from American Society of Radiation Oncology (Member, Sexual and Gender Minority Affinity Working Group), Canadian Association of Radiation Oncology (Annual Scientific Meeting lead), Merck. Josie Ethier reports consultancy fees from AstraZeneca; honoraria from AstraZeneca, GSK, Merck; advisory board participation with AstraZeneca, Eisai, GSK, Merck. Franziska Geissler reports grants/contracts from International Research Fellowship, Swiss Cancer Research Foundation & Swiss Cancer League and Research Fund for Excellent Junior Researchers University of Basel 2024. Rosalind Glasspool reports grants/contracts from Clovis Oncology; consultancy fees from Clovis Oncology, GSK, Novartis; honoraria from GSK; travel support from GSK, MSD; participation on a Data Safety Monitoring Board or Advisory Board from IDMC Matao trial; leadership or fiduciary roles at IGCS Advocacy committee chair, IGCS board member, Chair of Scottish Gynaecological Cancer Trials Group; receipt of equipment, materials, drugs, medical writing, gifts or other services from AstraZeneca, GSK, Novartis; other financial or non-financial interests with Allarity Therapeutics, AstraZeneca, Immunogen, GSK. Philipp Harter reports grants/contracts from AstraZeneca, Clovis, Genmab, GSK, Immunogen, Novartis, Roche, Seagen; consultancy fees from Miltenyi; honoraria from Amgen, AstraZeneca, Clovis, Daiichi Sankyo, Eisai, Exscientia, GSK, Immunogen, Karyopharm, Mersana, MSD, Roche, Sotio, Stryker, Zai Lab; travel support from AstraZeneca; participation on a Data Safety Monitoring Board or Advisory Board at AstraZeneca, Clovis, Eisai, GSK, Immunogen, MSD, Miltenyi, Novartis, Roche. Chee Khoon Lee reports grants/contracts from Amgen, AstraZeneca, Merck, Roche; honoraria from Amgen, AstraZeneca, Gilead, GSK, Janssen, Merck, Merck kGA, Novartis, Roche, Takeda. Kristina Lindemann reports grants/contracts from GSK (research funding paid to institution); honoraria, consultancy fees, or advisory board fees from AstraZeneca, Eisai, GSK, MSD, Nycode; part of the Data Safety Monitoring Committee for Karyopharm.Ainhoa Madariaga reports honoraria from AstraZeneca, Clovis, GSK, MSD, Pharma & PharmaMar; travel support from AstraZeneca, GSK, MSD; participation on a Data Safety Monitoring Board or Advisory Board from AbbVie, AstraZeneca, GSK, MSD. Asima Mukhopadhyay reports grants/contracts from the Indian Council of Medical Research for the IPIRIC academic study which endorses the principles of EDIM; honoraria from KGOG; advisory board at CannariaBio; Secretary KolGoTrg, Executive Board Member GCIG; part funding support for the IPIROC trial for drug procurement from BDR Pharma. Amit Oza reports grants/contracts from Amgen, AstraZeneca; consultancy fees from BMS; advisory board participation with AstraZeneca and GSK; other financial or non-financial interests with AstraZeneca, GSK. Elisa Piovano reports travel support from AstraZeneca, GSK. Bhavana Pothuri reports grants/contracts from Agenus, Alkermes, AstraZeneca, Acrivon, Celgene, Celsion/Immunon, Clovis Oncology, Duality Bio, Eisai, Immunogen, Incyte, Imab, InxMed, Karyopharm Therapeutics, Lily, LOXO/Lily, Merck, Mersana, Novocure, Onconova, NRG Oncology, Roche/Genentech, Seagen, Sutro, Takeda, Tesaro/GSK, Toray, VBL Therapeutics, Xencor; consultancy fees from AstraZeneca, Celsion, Duality Bio, Eisai, GOG Foundation, Imvax Inc, Incyte Corporation, InxMed, Lily, Onconova Therapeutics, Regeneron, SeaGen, Signatera, Sutro Biopharma, Tesaro/GSK; honoraria from Albert Einstein-Montefiore, Bioascend, Colorado University, Curio, Lankenau Hospital, OncLive, PERS, PeerView, Vanium, Yale University; travel support from GOG Partners; advisory boards with AstraZeneca, Celsion/Immunon, GOG Foundation, Imab, Imvax, Incyte, InxMed, Lily, Merck, Mersana, Nuvation, Sutro, Tesaro/GSK; leadership or fiduciary roles in GOG Partners, NYOB Society VP, SGO Board of Directors, SGO Clinical Practice Committee Chair, SGO COVID-19 Taskforce co-chair. Jose Alejandro Rauh-Hain reports grants/contracts from NIH, Department of Defense, American Cancer Society; support for the present manuscript from Guidepoint Consulting, Sago. Ora Rosengarten reports consultancy fees from AstraZeneca, Medison, MSD, Neopharm; travel support from AstraZeneca, MSD; lecture honoraria from AstraZeneca. Jalid Sehouli reports grants/contracts from AstraZeneca, Eisai, GSK, Merck, MSD, Novocure, Roche, Tesaro; consultancy fees from AstraZeneca, Clovis, Eisai, GSK, Immunogen, Incyte, MSD, Novocure; honoraria from AstraZeneca, Bristol Myers Squibb, Clovis, Eisai, GSK, Immunogen, Incyte, MSD, Novartis, Novocure; travel support from AstraZeneca, Eisai, GSK, Immunogen, Incyte, MSD, Novocure, Roche; advisory boards with AstraZeneca, Bayer, Bristol Myers Squibb, Clovis, GSK, Immunogen, Incyte, MSD, Novocure, PharmaMar; leadership or fiduciary roles at AGO, ASCO, Deutsche Stiftung Eierstockkrebs, ENGAGE, ESGO, GCIG, Medical writing (MSD). David Tan reports receiving research funding from the National Medical Research Council (NMRC) Clinician Scientist Award Senior Investigator Grant (CSASI21jun-0003), the Pangestu Family Foundation Gynaecological Cancer Research Fund; and product samples from AstraZeneca, Eisai, MSD (non-financial interest) for research trials. Institutional research grants from AstraZeneca, Bayer, Karyopharm Therapeutics, Roche; personal fees for advisory board membership from AstraZeneca, Bayer, BioNTech, Boehringer Ingelheim, Daiichi Sankyo, Eisai, Genmab, GSK, MSD, PMV Pharma, Roche; personal fees as an invited speaker from AstraZeneca, Eisai, GSK, Merck Serono, MSD, Roche, Takeda; travel support from AstraZeneca, Eisai, GSK, Merck Serono, MSD, Roche, Takeda; current non-renumerated role as protocol chair of Asia Pacific Gynecologic Oncology Trials Group (APGOT); previous non-renumerated role as Chair of the Asia Pacific Gynecologic Oncology Trials Group (APGOT); a previous non-renumerated role as the Society President of the Gynecologic Cancer Group Singapore; non-renumerated membership of the Board of Directors of the GCIG; ownership of stocks/shares of Asian Microbiome Library (AMiLi). Toon Van Gorp reports consultancy fees (via institution) from AbbVie, AstraZeneca, BioNTech, Cancer Communications and Consultancy Ltd, Eisai, GSK, ImmunoGen, Incyte, Karyopharm, MSD/Merck, OncXerna Therapeutics, Seagen, Tubulis, Zentalis; corporate sponsored research (via institution) from Amgen, AstraZeneca, Roche; honoraria for lectures (via institution) from AstraZeneca, Eisai, GSK, ImmunoGen, MSD; travel support from AstraZeneca, ImmunoGen, MSD, PharmaMar; grants/contracts from Amgen, AstraZeneca, Roche; chair of the Belgian and Luxembourg Gynaecological Oncology Group. Stephen Welch reports honoraria from AstraZeneca, Eisai, GSK, Merck; advisory boards with Eisai, Incyte, GSK, Roche, Takeda.All other authors declare no conflict of interest., (© IGCS and ESGO 2024. Re-use permitted under CC BY-NC. No commercial re-use. Published by BMJ.)

Background: Pembrolizumab plus chemotherapy provides clinically meaningful benefit as first-line therapy for advanced (locoregional extension and residual disease after surgery)/metastatic/recurrent mismatch repair-proficient (pMMR) and mismatch repair-deficient (dMMR) endometrial cancer, with greater magnitude of benefit in the dMMR phenotype. We evaluated the addition of pembrolizumab to adjuvant chemotherapy (with/without radiation therapy) among patients with newly diagnosed, high-risk endometrial cancer without any residual macroscopic disease following curative-intent surgery., Methods: We included patients with histologically confirmed high-risk [International Federation of Gynecology and Obstetrics (FIGO) stage I/II of non-endometrioid histology or endometrioid histology with p53/TP53 abnormality, or stage III/IVA of any histology] endometrial cancer following surgery with curative intent and no evidence of disease postoperatively, with no prior radiotherapy or systemic therapy. Patients were randomised to pembrolizumab 200 mg or placebo every 3 weeks (Q3W) for six cycles added to carboplatin-paclitaxel followed by pembrolizumab 400 mg or placebo every 6 weeks (Q6W) for six cycles per treatment assignment. Radiotherapy was at the investigator's discretion. The primary endpoints were investigator-assessed disease-free survival (DFS) and overall survival in the intention-to-treat population., Results: A total of 1095 patients were randomised (pembrolizumab, n = 545; placebo, n = 550). At this interim analysis (data cut-off, 4 March 2024), 119 (22%) DFS events occurred in the pembrolizumab group and 121 (22%) occurred in the placebo group [hazard ratio 1.02, 95% confidence interval (CI) 0.79-1.32; P = 0.570]. Kaplan-Meier estimates of 2-year DFS rates were 75% and 76% in the pembrolizumab and placebo groups, respectively. The hazard ratio for DFS was 0.31 (95% CI 0.14-0.69) in the dMMR population (n = 281) and 1.20 (95% CI 0.91-1.57) in the pMMR population (n = 814). Grade ≥3 adverse events (AEs) occurred in 386 of 543 (71%) and 348 of 549 (63%) patients in the pembrolizumab and placebo groups, respectively. No treatment-related grade 5 AEs occurred., Conclusions: Adjuvant pembrolizumab plus chemotherapy did not improve DFS in patients with newly diagnosed, high-risk, all-comer endometrial cancer. Preplanned subgroup analyses for stratification factors suggest that pembrolizumab plus chemotherapy improved DFS in patients with dMMR tumours. Safety was manageable., Trial Registration: ClinicalTrials.gov, NCT04634877; EudraCT, 2020-003424-17., Research Support: Merck Sharp & Dohme LLC, a subsidiary of Merck & Co., Inc., Rahway, NJ, USA., (Copyright © 2024 Merck Sharp & Dohme LLC, a subsidiary of Merck & Co., Inc., Rahway, NJ, USA., The Author(s). Published by Elsevier Ltd.. All rights reserved.)

In March 2024, 12 European Network of Young Gynae Oncologists- International Journal of Gynaecological Cancer (ENYGO-IJGC) Editorial Fellows conducted 10 interviews with senior opinion leaders on original and controversial topics in the field of gynecologic oncology presented during the 25th European Society of Gynaecological Oncology (ESGO) Congress in Barcelona, Spain. This article provides a summary and overview of the content of these discussions summarizing key points presented at the meeting. These selected interviews were chosen by consensus by the ENYGO-IJGC Editorial Fellows based on novelty and relevance to the field of gynecologic oncology., Competing Interests: Competing interests: None declared., (© IGCS and ESGO 2024. No commercial re-use. See rights and permissions. Published by BMJ.)

Background: At the first interim analysis of the phase 3 ENGOT-cx11/GOG-3047/KEYNOTE-A18 study, the addition of pembrolizumab to chemoradiotherapy provided a statistically significant and clinically meaningful improvement in progression-free survival in patients with locally advanced cervical cancer. We report the overall survival results from the second interim analysis of this study., Methods: Eligible patients with newly diagnosed, high-risk (FIGO 2014 stage IB2-IIB with node-positive disease or stage III-IVA regardless of nodal status), locally advanced, histologically confirmed, squamous cell carcinoma, adenocarcinoma, or adenosquamous cervical cancer were randomly assigned 1:1 to receive five cycles of pembrolizumab (200 mg) or placebo every 3 weeks with concurrent chemoradiotherapy, followed by 15 cycles of pembrolizumab (400 mg) or placebo every 6 weeks. Pembrolizumab or placebo and cisplatin were administered intravenously. Patients were stratified at randomisation by planned external beam radiotherapy type (intensity-modulated radiotherapy [IMRT] or volumetric-modulated arc therapy [VMAT] vs non-IMRT or non-VMAT), cervical cancer stage at screening (FIGO 2014 stage IB2-IIB node positive vs III-IVA), and planned total radiotherapy (external beam radiotherapy plus brachytherapy) dose (<70 Gy vs ≥70 Gy [equivalent dose of 2 Gy]). Primary endpoints were progression-free survival per RECIST 1.1 by investigator or by histopathological confirmation of suspected disease progression and overall survival defined as the time from randomisation to death due to any cause. Safety was a secondary endpoint., Findings: Between June 9, 2020, and Dec 15, 2022, 1060 patients at 176 sites in 30 countries across Asia, Australia, Europe, North America, and South America were randomly assigned to treatment, with 529 patients in the pembrolizumab-chemoradiotherapy group and 531 patients in the placebo-chemoradiotherapy group. At the protocol-specified second interim analysis (data cutoff Jan 8, 2024), median follow-up was 29·9 months (IQR 23·3-34·3). Median overall survival was not reached in either group; 36-month overall survival was 82·6% (95% CI 78·4-86·1) in the pembrolizumab-chemoradiotherapy group and 74·8% (70·1-78·8) in the placebo-chemoradiotherapy group. The hazard ratio for death was 0·67 (95% CI 0·50-0·90; p=0·0040), meeting the protocol-specified primary objective. 413 (78%) of 528 patients in the pembrolizumab-chemoradiotherapy group and 371 (70%) of 530 in the placebo-chemoradiotherapy group had a grade 3 or higher adverse event, with anaemia, white blood cell count decreased, and neutrophil count decreased being the most common adverse events. Potentially immune-mediated adverse events occurred in 206 (39%) of 528 patients in the pembrolizumab-chemoradiotherapy group and 90 (17%) of 530 patients in the placebo-chemoradiotherapy group. This study is registered with ClinicalTrials.gov, NCT04221945., Interpretation: Pembrolizumab plus chemoradiotherapy significantly improved overall survival in patients with locally advanced cervical cancer These data, together with results from the first interim analysis, support this immuno-chemoradiotherapy strategy as a new standard of care for this population., Funding: Merck Sharp & Dohme, a subsidiary of Merck & Co., Competing Interests: Declaration of interests DL, YX, KH, GS, ML, PR-E, AA, JC, LR, AJPdSG, FCM, LH, HA, J-YL, VS, FZ, LG, JS, ET, KL, NC, C-LC, MB, HZ, AO, MC, EP, TU, SP, and LRD received funding to their institutions from Merck Sharp & Dohme, a subsidiary of Merck & Co, Rahway, NJ, USA (MSD) to support the study. DL reports grants or contracts from AstraZeneca, Clovis Oncology, Pharma&, Genmab, GSK, Immunogen, MSD, Pharmamar, Novartis, Seagen, Alkermes, Incyte, Roche, and Corcept; consulting fees from AstraZeneca, Corcept, Clovis Oncology, Daiichi Sankyo, Genmab, GSK, Immunogen, MSD, Novartis, Oncoinvest, Novocure, Seagen, and Sutro; speaker fees from AstraZeneca, Corcept, Genmab, GSK, Immunogen, MSD, and Seagen; travel grants from AstraZeneca, Menarini, GSK, and MSD; advisory board participation for AstraZeneca, Corcept, Clovis Oncology, Daiichi Sankyo, Genmab, GSK, Immunogen, MSD, Oncoinvest, Novocure, Seagen, and Sutro; and leadership or fiduciary role in other board, society, committee, or advocacy group, paid or unpaid, for GCIG, MITO, and ENGOT. YX reports study funding, paid to the Peking Union Medical College Hospital, and support for attending meetings or travel from MSD. KH reports research contracts from Daiichi Sankyo, Eisai, MSD, and Takeda; advisory board fees from Chugai, Eisai, Takeda, MSD, Roche, Genmab, Sanofi, GSK, and Zymeworks; honoraria from Daiichi Sankyo, AstraZeneca, Chugai, Eisai, Genmab, MSD, Takeda, Sanofi, Kyowa Kirin, Kaken, and GSK; and travel support from Regeneron and Seagen. GS reports consulting fees from AstraZeneca, MSD, Coviden AG (a Medtronic company), Johnson & Johnson, and TESARO Bio Italy; and payment or honoraria for lectures, presentations, speakers bureaus, manuscript writing, or education events from Baxter Healthcare, Olympus Europa, Intuitive Surgical, GSK, and Clovis Oncology Italy. ML reports payment for expert testimony from MSD, support for attending meetings or travel from MSD and AstraZeneca; and other financial or non-financial interests from MSD, AstraZeneca, and Roche. PR-E reports honoraria for educational events from MSD, AstraZeneca, Novartis, Asofarma, Pfizer, and Roche; support for attending ESMO and ASCO meetings from AstraZeneca, Pfizer, and Asofarma; and honoraria for advisory boards from MSD, Roche, AstraZeneca, Asofarma, BMS and Novartis. LR reports medical writing support from Merck, institutional grants from Merck, Zentalis, Karyopharn, GOG Foundation, Regeneron, ImmunoGen, Acrivon, CanariaBio, Corcept Therapeutics, and Seagen; consulting fees from AstraZeneca, Merck, GSK, Genmab, Seagen, GOG Foundation, Zentalis, ImmunoGen, Semline, Eisai, Caris, Nykode, and Clovis; payment or honoraria for lectures, presentations, speakers bureaus, manuscript writing, or educational events from Seagen and Genmab; and leadership or fiduciary role in other board, society, committee or advocacy group, paid or unpaid, from GOG Foundation. AJPdSG reports consulting fees and payment for expert testimony from Bayer, Astellas, and Janssen; payment or honoraria for lectures, presentations, speakers bureaus, manuscript writing, or educational events for expert testimony from Astellas, AstraZeneca, Bayer, and Janssen; and participation on a data safety monitoring board or advisory board for Astellas, Bayer, and Janssen. FCM reports honoraria for presentations from MSD and BMS; support for attending meetings or travel from AstraZeneca and MSD; and advisory board participation from Janssen and MSD. J-YL reports support for the present manuscript from MSD; grants or contracts from Advenchen, Ascendis Pharma, Alkermes, AstraZeneca, Beigene, BergenBio, BMS, CanariaBio, Corcept, Cellid, CKD, Clovis Oncology, Eisai, Genmab, Genemedicine, GII, GSK, ImmunoGen, Janssen, Kelun, Merck, Mersana, MSD, Novartis, Onconic Therapeutics, ONO, Regeneron, Roche, Seagen, Sutro, Synthon, and Takeda; payment or honoraria for lectures, presentations, speakers bureaus, manuscript writing, or educational events from AstraZeneca, Janssen, MSD, Roche, Takeda, and ONO; and leadership or fiduciary role in other board, society, committee or advocacy group, paid or unpaid, for AstraZeneca, CanariaBio, Genmab, GII, ImmunoGen, Seagen, Merck, Sutro, Regeneron, and MSD. FZ reports payment or honoraria for lectures, presentations, speakers bureaus, manuscript writing, or educational events, consulting fees, support for attending meetings or travel, and data safety monitoring board and advisory board participation for AstraZeneca, Daiichi, Eli-Lilly, Merck, Novartis, MSD, Pfizer, Genesis-Pharma, and Roche. LG reports institutional grants from IMV, Pfizer, Sutro Bio, Pharma, Merck Sharpe Dohme, Corcept Therapeutics, ImmunoGen, Shattuck Labs, Roche, Tesaro, K-Group, Beta Inc., GOG Foundation, GSK, AstraZeneca, OncoQuest Pharmaceuticals, Novocure, Alkermes, Espersas, and Mersana; consulting fees from Merck and GSK; payment or honoraria for lectures and presentations from Merck and GSK; support for attending meetings or travel from GSK, Merck, EndomERA, and Zentalis; and participation on advisory board meetings for GSK, Merck, Eisai, Novocure, Kora Health, Corcept, ImmunoGen, Canariabio, and Repare Therapeutics. JS reports grants or contracts from Roche, MSD, GSK, Tesaro, AstraZeneca, Eisai, Merck, and Novocure; consulting fees from Immunogen, Incyte, GSK, AstraZeneca, Clovis, Novocure, MSD, Eisai, and Merck; payment or honoraria for lectures, presentations, speakers bureaus, manuscript writing, or educational events from Immunogen, Incyte, GSK, AstraZeneca, Clovis, Novocure, BMS, Eisai, and Novartis; support for attending meetings or travel from GSK, Astra Zeneca, Roche, Novocure, Immunogen, Incyte, MSD, and Eisei; participation on a data safety monitoring board or advisory board for Immunogen, Incyte, GSK, AstraZeneca, Clovis, Novocure, Bristol Myers Squibb, MSD, Merck, Bayer, and PharmaMar; leadership or fiduciary role in other board, society, committee or advocacy group, paid or unpaid, for ENGAGE, ESGO, ASCO, ESGO, GCIG, Deutsche Stiftung Eierstockkrebs, and AGO; and medical writing assistance from MSD. ET reports honoraria for presentations and meeting travel support from Elektra. KL reports study funding from MSD; grants or contracts from GSK; lecture honoraria from Eisai and AstraZeneca; participation on a data safety monitoring board for Karyopharm; participation on an advisory board for Eisai, MSD, Nykode, AstraZeneca, and GSK; and serving as deputy medical director for the Nordic Society of Gynecological Oncology Clinical Trial Unit. NC reports institutional grants from AstraZeneca and Roche; payment or honoraria for lectures, presentations, speakers bureaus, manuscript writing, or educational events from GSK and MSD; payment for participation on a data safety monitoring board or advisory board for AstraZeneca, Clovis Oncology, Eisai, GSK, ImmunoGen, Mersana, MSD, Merck, Nuvation Bio, Onxerna, Pfizer, PharmaMar, Pieris, Roche, and Novocure; and non-remunerated leadership role as Chair of the Alleanza Contro il Tumore Ovarico Scientific Committee. MB reports honoraria for lectures and educational events from Roche, AstraZeneca, and GSK; and support for attending meetings from Roche, AstraZeneca, and Viatris. AO reports consulting fees from Agenus, AstraZeneca, Clovis Oncology, Corcept Therapeutics, Deciphera Pharmaceuticals, Daïichi Sankyo, Debiopharm International, Eisai, Exelisis, F. Hoffmann-La Roche, Genmab, GSK, ImmunoGen, Itheos, MSD, Mersana Therapeutics, Myriad Genetics, Novocure, OncoXerna Therapeutics, PharmaMar, Regeneron, Sattucklabs, Seagen–Pfizer, Sutro Biopharma, TORL Therapuetics, Zentalis, and Zymeworks; payment or honoraria for lectures, presentations, speakers bureaus, manuscript writing, or educational events from NSGO, Peerview, Peervoice, Medscape, Asociación Colombiada de Ginecológos Oncólogos, ESO, AstraZeneca, and GSK; support for attending meetings or travel from AstraZeneca, PharmaMar, and Roche; participation on a data safety monitoring board or advisory board from Agenus, AstraZeneca, Clovis Oncology, Corcept Therapeutics, Deciphera Pharmaceuticals, Daïichi Sankyo, Debiopharm International, Eisai, Exelisis, F Hoffmann-La Roche, Genmab, GSK, ImmunoGen, Itheos, MSD, Mersana Therapeutics, Myriad Genetics, Novocure, OncoXerna Therapeutics, PharmaMar, Regeneron, Sattucklabs, Seagen–Pfizer, Sutro Biopharma, TORL Therapuetics, Zentalis, and Zymeworks; leadership or fiduciary role in other board, society, committee or advocacy group, paid or unpaid, for Gynecologic Cancer Intergroup and European Society for Medical Oncology; and other financial or non-financial interests in Gynecologic Cancer Intergroup, European Society for Medical Oncology, American Society of Clinical Oncology, Spanish Society of Medical Oncology, and GOG Foundation. EP reports provision of study material from MSD; honoraria for lectures, presentations, and educational events from MSD, Roche, GSK, and AstraZeneca; and receipt of investigational drug for study treatment from MSD. PL, KY, ST, and SMK are current or former full-time employees of MSD and hold stock or restricted stock units in the company. SP reports research funding from Roche, MSD, GSK, Pfizer, and AstraZeneca; payment or honoraria for lectures, presentations, speakers bureaus, manuscript writing, or educational events from AstraZeneca, MSD, Roche, Pfizer, Novartis, and GSK; and participation on a Data Safety Monitoring Board or Advisory Board for GSK, MSD, Eisai, Biontech, and AstraZeneca. LRD reports institutional grants from Merck, Genentech, Roche, AbbVie, Acrivon, Advaxis, Aduro BioTech, Alkermes, Blueprint, Constellation, Eisai, GSK, Novartis, Immunogen, Inovio, Iovance, Karyopharm, KSQ Therapeutics, Lycera, Morab, MorphoTek, Naveris, Nurix, OncoQuest, Pfizer, Syndax, Tesaro, and Zentalis; royalties or licenses from UpToDate, Wiley, and ASCO; editing for ASCO Connection; payment or honoraria for lectures, presentations, speakers bureaus, manuscript writing, or educational events from Advance Medical, CEA Group, and Clinical Care Options; participation on a data safety monitoring board for Innovia and Aegenus (payment to institution); and roles as Secretary Treasurer for SGO (unpaid) and on the Editorial Board of the British Journal of Obstetrics and Gynaecology., (Copyright © 2024 Elsevier Ltd. All rights reserved, including those for text and data mining, AI training, and similar technologies.)

Objective: The treatment for stage IB grade 3 endometrioid endometrial adenocarcinoma is challenging with variable practice. Molecular characterization may help identify adjuvant therapy strategies beyond stage. We aimed to better understand the molecular features of these tumors by characterizing them by ProMisE classification, mutational signature, and commonly mutated genes., Methods: Patients with stage IB grade 3 EEC at two institutions were included. Immunohistochemistry and whole exome sequencing were performed on archival FFPE tissue sections to determine ProMisE classification. Personal Cancer Genome Reporter was used for somatic variant annotation, and mutational signatures were generated based on COSMIC single base substitution mutational signatures., Results: 46 patients were included with variable adjuvant treatment. Nine patients recurred (19.6%), most with extra-abdominal disease (n = 5, or 55.6%). 10 had POLE mutations (21.7%), 18 were MMR deficient (39.1%), 6 had abnormal p53 (13.0%), and 12 were p53 wildtype (26.1%). There were no recurrences in the POLE subgroup. A dominant mutational signature was identified in 38 patients: 17 SBS5 signature (44.7%), 10 SBS15 or SBS44 signature (26.3%), 7 SBS10a or SBS10b signature (18.4%), 3 SBS14 signature (7.9%), and 1 SBS40 signature (2.6%). The six patients that recurred had a SBS5 signature. Frequently mutated genes included ARID1A (n = 30, 65%), PTEN (n = 28, 61%), MUC16 (n = 27, 59%), and PIK3CA (n = 25, 54%)., Conclusions: This comprehensive evaluation found a molecularly diverse cohort of tumors, despite the same histology, stage and grade. Mutational signature SBS5 correlated with a high risk of recurrence. Further refining of endometrial cancer classification may enable more precise patient stratification and personalized treatment approaches., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

Objective: The aim of this study was to investigate the association of co-medication with metformin, a statin, or beta blocker with survival in patients with primary ovarian cancer., Methods: Individual data from three phase III, randomized controlled trials (AGO-OVAR 11, AGO-OVAR 12, and AGO-OVAR 16) and one phase II trial (AGO-OVAR 15) were pooled and analyzed. Patients were classified as ever user if the specific co-medication was documented at least once during the trial, and were compared with never users as controls. Association of co-medications and outcomes were adjusted for potential confounders (age, International Federation of Gynecology and Obstetrics stage, histology, residual disease after surgery, Eastern Cooperative Oncology Group (ECOG) performance status, body mass index, Charlson Comorbidity Index, and assigned treatment within the trial) in multivariate Cox regression analyses., Results: Overall, n=2857 patients were included. Ever users were: 100 patients received metformin (3.5%), 226 patients received statins (7.9%), and 475 (16.6%) patients received beta blockers (n=391 selective beta blockers; 84 non-selective beta blockers) as co-medication. There were no significant differences regarding the baseline characteristics except that ever users were significantly older, more obese, and had more comorbidities, according to the Charlson Comorbidity Index, compared with controls. Multivariate analyses for progression free survival and overall survival revealed neither a significant impact of metformin on survival (progression free survival hazard ratio (HR) 0.94, 95% confidence interval CI 0.69 to 1.29, p=0.7; overall survival HR 0.82, 95% CI 0.58 to 1.17, p=0.28) nor for statins (progression free survival HR 0.98, 95% CI 0.82 to 1.18, p=0.87; overall survival HR 0.91, 95% CI 0.74 to 1.12, p=0.37). In contrast, ever users of selective beta blockers had a significantly higher risk for recurrence and death (progression free survival HR 1.22, 95% CI 1.05 to 1.41, p=0.009; overall survival HR 1.25 95% CI 1.06 to 1.47, p=0.009)., Conclusions: In this analysis, co-medication with metformin or statins had no significant impact on survival in patients with primary ovarian cancer. In contrast, co-medication with a beta blocker was associated with worse survival. However, whether this observation is related to the underlying condition rather than a direct negative impact on tumor biology remains unclear., Competing Interests: Competing interests: DD: honoraria: AstraZeneca, GSK, Intuitive, KLS Martin, Merck Sharp & Dohme (MSD); travel/accommodation/expenses: AstraZeneca; Data Safety Monitoring Board/Advisory Board: AstraZeneca, Eisai, GSK, KLS Martin, MSD, PharmaMar, Seagen. FH: personal fees and non-financial support: AstraZeneca, Roche, Tesaro, GSK, Clovis; personal fees: Zailabs and PharmaMar, outside the submitted work. JF: honoraria: Medupdate, Decision Resources, Simon-Kucher and Partners, Juniper, Bionest Partner, Vox Bio, Axiam Healthcare Strategies, Prosapient, Lilly, MedPartners; research funding: Roche Pharma AG, GSK/Tesaro; travel/accommodation/expenses: Roche Pharma AG. PH: grants, personal fees and non-financial support: Astra Zeneca, GSK; grants and personal fees: Roche, MSD, Clovis, Immunogen; personal fees: Sotio, Stryker, Zai Lab, Mersana, Miltenyi; grants: Boehringer lngelheim, Medac, Genmab, Deutsche Krebshilfe, Deutsche Forschungsgemeinschaft, outside the submitted work. PW: Advisory Board Member and received honoraria: Amgen, AstraZeneca, MSD, Novartis, Pfizer, Lilly, Roche Pharma, Eisai, Clovis, GSK, Daiichi Sankyo. MRM: honoraria: Astra Zeneca, Eisai, Genmab, GSK, Mersana, Takeda, Zailab; travel/accommodation/expenses: AstraZeneca, GSK, Takeda; Advisory Board: Allarity Therapeutics, Astra Zeneca, Biontech, Daiichi-Sankyo, Eisai, Genmab, GSK, lmmunogen, Incyte, Merck/MSD, Mersana, Regeneron, Zailab; Chairman (2020-2022) of the European Network of Gynaecological Oncology Trials group; Vice-President of the European Society of Gynaecological Oncology; Faculty member of the European Society of Medical Oncology; Scientific Chair of the International Gynecologic Cancer Society; stock options: Karyopharm Therapeutics, Sera Prognostics. IRC: grants/contracts: Astra Zeneca, Clovis, GSK, Mersana, BMS, MSD; honoraria: Astra Zeneca, Clovis, GSK, Mersana, BMS, MSD, Roche, PharmaMar, Seagen, ESAI, Novartis; travel/accommodation/expenses: Roche, GSK, Astra Zeneca, PharmaMar, MSD; Data Safety Monitoring Board/Advisory Board: Clovis, Deciphera, AdaptImmune, Sutro, Immunogen. GS: grants: MSD Italia S.r.l; consulting fees: Tesaro Bio Italy S.r.l, Johnson & Johnson; payment for expert testimony: Clovis Oncology Italia S.r.l; NC: grants: GSK, Astrazeneca; consulting fees: AstraZeneca, Clovis Oncology, Eisai, GSK, Immunogen, Mersana, MSD/Merck, Nuvation Bio, Onxerna, Pfizer, Pieris, Roche; honoraria: AstraZeneca, Novartis, Clovis Oncology,GSK, MSD/Merck; Data Safety Monitoring Board/Advisory Board: AstraZeneca, Clovis Oncology, Eisai, GSK, Immunogen, Mersana, MSD/Merck, Nuvation Bio, Onxerna, Pfizer, Pieris, Roche. AO: Grants to institution: AbbVie Deutschland, Advaxis Inc., Aeterna Zentaris, Amgen, Aprea Therapeutics AB, Clovis Oncology Inc., Eisai Ltd, F. Hoffmann-La Roche Ltd, Regeneron Pharmaceuticals, lmmunogen Inc, Merck, Sharp & Dohme de Esparsia SA, Millennium Pharmaceuticals Inc, PharmaMar SA, Tesaro Inc., Bristol Myers Squibb; consulting fees and honoraria: AstraZeneca, Clovis Oncology, Deciphera, Genmab, GSK, lmmunogen, Mersana Therapeutics, PharmaMar, MSD de Esparia SA, Agenus, Sutro, Corcept Therapeutics, EMD Serono, Novocure, Sattucklabs, Itheos, Eisai; travel/accommodation/expenses: AstraZeneca, PharmaMar, Roche; Data Safety Monitoring Board/Advisory Board: AstraZeneca, Clovis Oncology, Deciphera, Genmab, GSK, Immunogen, Mersana Therapeutics, PharmaMar, MSD de Esparia SA, Agenus, Sutro, Corcept Therapeutics, EMD Serono, Novocure, Sattucklabs, Itheos, Eisai; JS: study funding to institution: GSK, AstraZeneca, MSD, Clovis, Tesaro; consulting fees: GSK, Astra Zeneca, Tesaro, MSD, Elisei, Clovis, Riemser, Roche; travel/accomodation/expenses: Roche; Data Safety Monitoring Board/Advisory Board: GSK, PharmaMar, Novocure, Astra Zeneca, Clovis, GSK, Tesaro; ESGO Faculty; NOGGO President; PARSGO President. KL: grants: GSK; honoraria: Eisai; Data Safety Monitoring Board/Advisory Board: Eisai, MSD, Nycode, Astra Zeneca, GSK. CL: honoraria: IMSD, GSK, Eisai, Clovis Oncology; travel/accommodation/expenses: MSD, GSK; Data Safety Monitoring Board/Advisory Board: GSK. ME: stock/stock options: GSK. AdB: honoraria: Zodiac, AMGEN, GSK/Tesaro; Data Safety Monitoring Board/Advisory Board: AstraZeneca/MSD, AMGEN, Pfizer, GSK/Tesaro. All other authors declare no competing interests., (© IGCS and ESGO 2024. No commercial re-use. See rights and permissions. Published by BMJ.)

The objective of the present study was to characterize the molecular features of endometrial carcinomas with ambiguous histology. Eighteen carcinomas that could not be conclusively typed based on morphology and immunohistochemistry underwent analysis of mismatch repair (MMR) status, microsatellite status, and whole-exome sequencing. None of the tumors had pathogenic POLE mutation. Twelve tumors (67%) were microsatellite stable, and 6 (33%) had microsatellite instability. Fourteen tumors (78%) harbored TP53 mutations, and 2 (11%) had mutations in MMR genes. Eleven carcinomas (61%) were classified as copy number high and 7 (39%) as MSI-hypermutated, the latter including 3 tumors with TP53 mutation who concomitantly had MSI or mutation in a MMR gene. Other mutations that were found in > 1 tumor affected MUC16 (7 tumors), PIK3CA (6 tumors), PPP2R1A (6 tumors), ARID1A (5 tumors), PTEN (5 tumors), FAT1 (4 tumors), FAT4 (3 tumors), BRCA2 (2 tumors), ERBB2 (2 tumors), FBXW7 (2 tumors), MET (2 tumors), MTOR (2 tumors), JAK1 (2 tumors), and CSMD3 (2 tumors). At the last follow-up (median = 68.6 months), 8 patients had no evidence of disease, 1 patient was alive with disease, 8 patients were dead of disease, and 1 patient died of other cause. In conclusion, based on this series, the molecular landscape of endometrial carcinomas with ambiguous histology is dominated by TP53 mutations and the absence of POLE mutations, with heterogeneous molecular profile with respect to other genes. A high proportion of these tumors is clinically aggressive., (© 2024. The Author(s).)

Objectives: In patients with epithelial ovarian cancer (EOC), the clinical efficacy of monotherapy with immune checkpoint inhibitors (ICIs) against PD-1/PD-L1 is modest. To enhance response rates to these immunotherapeutic agents and broaden the indications for their use, new approaches involving combinational therapy are needed. The immune regulator CD73 is a potential target, as it promotes tumor escape by producing immunosuppressive extracellular adenosine in the tumor microenvironment. Here, we present the results from the NSGO-OV-UMB1/ENGOT-OV-30 trial evaluating the activity of combining the anti-CD73 antibody oleclumab with the anti-PD-L1 checkpoint inhibitor durvalumab in patients with recurrent EOC., Methods: In this phase II open-label non-randomized study, patients with CD73-positive relapsed EOC were intravenously administered oleclumab (3000 mg, Q2W) and durvalumab (1500 mg, Q4W). The primary endpoint was disease control rate (DCR) at 16 weeks. The expression of PD-L1 and CD8 was assessed by immunohistochemistry of archival tumors., Results: This trial included 25 patients with a median age of 66 years (47-77 years). Twenty-two patients were evaluable for treatment activity analysis. The DCR was 27%, the median progression-free survival was 2.7 months (95% CI: 2.2-4.2) and the median overall survival was 8.4 months (95% CI: 5.0-13.4). Infiltration of CD8 + cells and PD-L1 expression on tumor cells were observed in partially overlapping sets of 74% of the tumor samples. Neither CD8- nor PD-L1-positivity were significantly associated with better DCR., Conclusions: Combined treatment with oleclumab and durvalumab was safe and demonstrated limited anti-tumor activity in patients with recurrent EOC., Competing Interests: Declaration of competing interest The authors declare the following financial interest / personal relationship which may be consider as potential competing interests: MRM reports receiving an institutional study grant and investigational medicinal product from AstraZeneca (no personal grants were received). JM reports having received consulting fee payments from GlaxoSmithKline, AstraZeneca and Eisai; receiving payment or honoraria for lectures, presentations, speakers' bureaus, manuscript writing or educational events from Eisai; and participation on a data safety monitoring board or advisory board of Eisai. KL reports receiving research funding from GlaxoSmithKline; receiving consulting fee payments from AstraZeneca, Merck Sharp and Dohme, Nykode, Eisai and GlaxoSmithKline; and being on the safety monitoring board of Karyopharm. AA reports participation on the advisory boards of GlaxoSmithKline and Merck Sharp and Dohme. LAA reports receiving grants or contracts from the Research Council of Norway. LCVT reports receiving personal fees for lectures, presentations, speakers' bureaus, manuscript writing or educational events from Bayer and AstraZeneca; and receiving personal fee payments from Eisai for participating on a data safety monitoring board or Advisory Board. KM reports receiving speakers' honoraria from GlaxoSmithKline and AstraZeneca; receiving compensation for travel expenses from GlaxoSmithKline and AstraZeneca; participating in a trial-specific safety review committee for Kancera AB; and being the deputy medical director for NSGO-CTU. LB reports receiving speakers' honoraria from GlaxoSmithKline, and Merck Sharp and Dohme; having leadership roles in Onkologisk Forum between 2018 and 2022, and in the NSGO and NSGO-CTU since 2021; and receiving investigational medicinal product from AstraZeneca for a researcher-initiated trial. LT, JRH, RdPC, MW, HR and SNL report no personal conflicts of interest., (Copyright © 2024. Published by Elsevier Inc.)

The objective of this study was to identify clinicopathologic parameters associated with disease outcome in FIGO stage I vulvar squamous cell carcinoma (vSqCC). The cohort consisted of 126 patients diagnosed with vSqCC in the period 2006-2016 who underwent primary vulvar surgery and evaluation of groin lymph node status. Tumors were reviewed by an experienced gynecologic pathologist. p16 and p53 protein expression by immunohistochemistry and HPV status were analyzed in 116 tumors. Clinicopathologic parameters, protein expression and HPV status were analyzed for association with progression-free and overall survival (PFS, OS). p16 expression and aberrant p53 were found in 49 (42%) and 61 (53%) tumors, respectively. Sixty-six tumors were HPV-associated (57%). Relapse was diagnosed in 35/126 (28%) of patients, and 23 (18%) died of disease. Tumor diameter > 4 cm (p = 0.013), lymphovascular space invasion (LVSI; p < 0.001), the presence of lichen sclerosus (p = 0.019), p16 expression (p = 0.007), p53 expression (p = 0.012), HPV status (p = 0.021), lymph node metastasis (p < 0.001) and post-operative radiotherapy (p < 0.001) were significantly related to OS in univariate analysis. Tumor diameter > 4 cm (p = 0.038), LVSI (p = 0.003), the presence of lichen sclerosus (p = 0.004), p16 expression (p = 0.004), HPV status (p = 0.039), lymph node metastasis (p < 0.001) and post-operative treatment (p < 0.001), were significantly related to PFS in univariate analysis. Age, BMI and surgical resection involvement were not significantly associated with OS or PFS. In multivariate Cox analysis, LVSI and p16 expression were independent prognosticators of OS (p < 0.001 and p = 0.02, respectively) and PFS (p = 0.018, p = 0.037). In conclusion, LVSI and p16 expression are independent prognostic factors in stage I vSqCC., (© 2023. The Author(s).)

Background and Purpose: Improvements in treatment outcome for patients with locally advanced cervical cancer (LACC) require a better classification of patients according to their risk of recurrence. We investigated whether an imaging-based approach, combining pretreatment hypoxia and tumor response during therapy, could improve risk classification., Material and Methods: Ninety-three LACC patients with T2-weigthed (T2W)-, dynamic contrast enhanced (DCE)- and diffusion weighted (DW)-magnetic resonance (MR) images acquired before treatment, and T2W- and, for 64 patients, DW-MR images, acquired at brachytherapy, were collected. Pretreatment hypoxic fraction (HF pre ) was determined from DCE- and DW-MR images using the consumption and supply-based hypoxia (CSH)-imaging method. Volume regression at brachytherapy was assessed from T2W-MR images and combined with HF pre . In 17 patients with adequate DW-MR images at brachytherapy, the apparent diffusion coefficient (ADC), reflecting tumor cell density, was calculated. Change in ADC during therapy was combined with volume regression yielding functional regression as explorative response measure. Endpoint was disease free survival (DFS)., Results: HF pre was the strongest predictor of DFS, but a significant correlation with outcome was found also for volume regression. The combination of HF pre and volume regression showed a stronger association with DFS than HF pre alone. Patients with disease recurrence were selected to either the intermediate- or high-risk group with a 100 % accuracy. Functional regression showed a stronger correlation to HF pre than volume regression., Conclusion: The combination of pretreatment hypoxia and volume regression at brachytherapy improved patient risk classification. Integration of ADC with volume regression showed promise as a new tumor response parameter., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024. Published by Elsevier B.V.)

Recent research has documented that the effect of parental separation on children's educational outcomes depends on socioeconomic background. Yet, parental separation could lead to a stable single-parent family or to a further transition to a stepfamily. Little is known about how the effect of family structure transitions on educational outcomes depends on the education of parents and stepparents, and there has been limited empirical research into the mechanisms that explain heterogeneity in the effects of family transitions. Using longitudinal data from the German Socio-Economic Panel and models with entropy balancing and sibling fixed effects, I explore the heterogeneous effects of family transitions during early and middle childhood on academic secondary school track attendance, grades and aspirations. I find that family transitions only reduce the academic school track attendance among children of less educated parents living in stepfamilies or with a single mother after parental separation, and among children of highly educated fathers living in single-mother families. The mechanisms that partly explain these effects relate to reduced income and exposure to poverty after parental separation. The findings underscore the importance of considering the stepparent's educational level, indicating that the adverse consequences of parental separation on educational outcomes are mitigated when a highly educated stepfather becomes part of the family. Overall, these findings align more closely with the resource perspective than the family stability perspective., (Copyright © 2024 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Background: Response to hormonal therapy in advanced and recurrent endometrial cancer (EC) can be predicted by oestrogen and progesterone receptor immunohistochemical (ER/PR-IHC) expression, with response rates of 60% in PR-IHC > 50% cases. ER/PR-IHC can vary by tumour location and is frequently lost with tumour progression. Therefore, we explored the relationship between ER/PR-IHC expression and tumour location in EC., Methods: Pre-treatment tumour biopsies from 6 different sites of 80 cases treated with hormonal therapy were analysed for ER/PR-IHC expression and classified into categories 0-10%, 10-50%, and >50%. The ER pathway activity score (ERPAS) was determined based on mRNA levels of ER-related target genes, reflecting the actual activity of the ER receptor., Results: There was a trend towards lower PR-IHC (33% had PR > 50%) and ERPAS (27% had ERPAS > 15) in lymphogenic metastases compared to other locations ( p = 0.074). Hematogenous and intra-abdominal metastases appeared to have high ER/PR-IHC and ERPAS (85% and 89% ER-IHC > 50%; 64% and 78% PR-IHC > 50%; 60% and 71% ERPAS > 15, not significant). Tumour grade and previous radiotherapy did not affect ER/PR-IHC or ERPAS., Conclusions: A trend towards lower PR-IHC and ERPAS was observed in lymphogenic sites. Verification in larger cohorts is needed to confirm these findings, which may have implications for the use of hormonal therapy in the future.

Carcinosarcoma (CS) is an uncommon and clinically aggressive malignancy. The objective of the present study was to characterize the molecular features of CS at various anatomic locations, including serous effusions. Specimens (n = 32) consisted of 25 biopsies/surgical resection specimens and 7 serous effusions (6 peritoneal, 1 pleural) from 25 patients. Fresh-frozen cell pellets and surgical specimens underwent targeted next-generation sequencing covering 50 unique genes. A total of 31 mutations were found in 25 of the 32 tumors studied, of which 1 had 3 mutations, 4 had 2 different mutations, and 20 had a single mutation. The most common mutations were in TP53 (n = 25 in 24 tumors; 1 tumor with 2 different mutations), with less common mutations found in RB1 (n = 2), MET (n = 1), KRAS (n = 1), PTEN (n = 1), and KIT (n = 1). Patient-matched specimens harbored the same TP53 mutation. Tumors with no detected mutations were more common in serous effusion specimens (3/7; 43%) compared with surgical specimens (4/25; 16%). In conclusion, the molecular landscape of CS is dominated by TP53 mutations, reinforcing the observation that the majority of these tumors develop from high-grade serous carcinoma. Whether CS cells in serous effusions differ from their counterparts in solid lesions remains uncertain., (© 2024. The Author(s).)

We have developed a peer-teaching program for student assistants involved in medical education. The offer comprises (1) an inventory of potentially relevant courses offered by other institutions at our university and (2) our own peer-teaching curriculum on pedagogy and teaching methodology. We describe a pilot scheme to implement the curriculum., Competing Interests: Competing InterestsThe authors declare no competing interests., (© The Author(s) 2024.)

Background and Purpose: This large population-based, retrospective, single-center study aimed to identify prognostic factors in patients with brain metastases (BM) from gynecological cancers., Material and Methods: One hundred and forty four patients with BM from gynecological cancer treated with radiotherapy (RT) were identified. Primary cancer diagnosis, age, performance status, number of BM, presence of extracranial disease, and type of BM treatment were assessed. Overall survival (OS) was calculated using the Kaplan-Meier method and the Cox proportional hazards regression model was used for multivariable analysis. A prognostic index (PI) was developed based on scores from independent predictors of OS., Results: Median OS for the entire study population was 6.2 months. Forty per cent of patients died within 3 months after start of RT. Primary cancer with the origin in cervix or vulva (p = 0.001),  Eastern Cooperative Oncology Group (ECOG) 3-4 (p < 0.001), and the presence of extracranial disease (p = 0.001) were associated with significantly shorter OS. The developed PI based on these factors, categorized patients into three risk groups with a median OS of 13.5, 4.0, and 2.4 months for the good, intermediate, and poor prognosis group, respectively., Interpretation: Patients with BM from gynecological cancers carry a poor prognosis. We identified prognostic factors and developed a scoring tool to select patients with better or worse prognosis. Patients in the high-risk group have a particular poor prognosis, and omission of RT could be considered.

Background: Ovarian cancer (OC) is the leading cause of death from gynecologic malignancies in the Western world. Contributing factors include a high frequency of late-stage diagnosis, the development of chemoresistance, and the evasion of host immune responses. Currently, debulking surgery and platinum-based chemotherapy are the treatment cornerstones, although recurrence is common. As the clinical efficacy of immune checkpoint blockade is low, new immunotherapeutic strategies are needed. Chimeric antigen receptor (CAR) T cell therapy empowers patients' own T cells to fight and eradicate cancer, and has been tested against various targets in OC. A promising candidate is the MUC16 ectodomain. This ectodomain remains on the cell surface after cleavage of cancer antigen 125 (CA125), the domain distal from the membrane, which is currently used as a serum biomarker for OC. CA125 itself has not been tested as a possible CAR target. In this study, we examined the suitability of the CA125 as a target for CAR T cell therapy., Methods: We tested a series of antibodies raised against the CA125 extracellular repeat domain of MUC16 and adapted them to the CAR format. Comparisons between these candidates, and against an existing CAR targeting the MUC16 ectodomain, identified K101 as having high potency and specificity. The K101CAR was subjected to further biochemical and functional tests, including examination of the effect of soluble CA125 on its activity. Finally, we used cell lines and advanced orthotopic patient-derived xenograft (PDX) models to validate, in vivo, the efficiency of our K101CAR construct., Results: We observed a high efficacy of K101CAR T cells against cell lines and patient-derived tumors, in vitro and in vivo. We also demonstrated that K101CAR functionality was not impaired by the soluble antigen. Finally, in direct comparisons, K101CAR, which targets the CA125 extracellular repeat domains, was shown to have similar efficacy to the previously validated 4H11CAR, which targets the MUC16 ectodomain., Conclusions: Our in vitro and in vivo results, including PDX studies, demonstrate that the CA125 domain of MUC16 represents an excellent target for treating MUC16-positive malignancies., Competing Interests: Competing interests: SW, EMI, DJW, NPC and EB have filled a patent application on chimeric antigen receptor for ovarian cancer. The other authors declare no conflict of interest., (© Author(s) (or their employer(s)) 2024. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Background: Pembrolizumab has shown efficacy in persistent, recurrent, or metastatic cervical cancer. The effect of chemoradiotherapy might be enhanced by immunotherapy. In this phase 3 trial, we assessed the efficacy and safety of adding pembrolizumab to chemoradiotherapy in locally advanced cervical cancer., Methods: In this randomised, double-blind, placebo-controlled, phase 3 ENGOT-cx11/GOG-3047/KEYNOTE-A18 clinical trial, adults (age ≥18 years) at 176 medical centres in 30 countries with newly diagnosed, high-risk, locally advanced cervical cancer were randomly assigned (1:1) using an interactive voice-response system with integrated web response to receive 5 cycles of pembrolizumab (200 mg) or placebo every 3 weeks plus chemoradiotherapy, followed by 15 cycles of pembrolizumab (400 mg) or placebo every 6 weeks. Randomisation was stratified by planned external beam radiotherapy type (intensity-modulated radiotherapy or volumetric-modulated arc therapy vs non-intensity-modulated radiotherapy or non-volumetric-modulated arc therapy), cervical cancer stage at screening (International Federation of Gynecology and Obstetrics 2014 stage IB2-IIB node positive vs stage III-IVA), and planned total radiotherapy (external beam radiotherapy plus brachytherapy) dose (<70 Gy vs ≥70 Gy equivalent dose in 2 Gy fractions). Primary endpoints were progression-free survival per Response Evaluation Criteria in Solid Tumours version 1.1-by investigator or by histopathologic confirmation of suspected disease progression-and overall survival. Primary analysis was conducted in the intention-to-treat population, which included all randomly allocated participants. Safety was assessed in the as-treated population, which included all randomly allocated patients who received at least one dose of study treatment. This study is registered with ClinicalTrials.gov, NCT04221945, and is closed to new participants., Findings: Between June 9, 2020, and Dec 15, 2022, 1060 participants were randomly assigned to treatment, with 529 assigned to the pembrolizumab-chemoradiotherapy group and 531 to the placebo-chemoradiotherapy group. At data cutoff (Jan 9, 2023), median follow-up was 17·9 months (IQR 11·3-22·3) in both treatment groups. Median progression-free survival was not reached in either group; rates at 24 months were 68% in the pembrolizumab-chemoradiotherapy group versus 57% in the placebo-chemoradiotherapy group. The hazard ratio (HR) for disease progression or death was 0·70 (95% CI 0·55-0·89, p=0·0020), meeting the protocol-specified primary objective. Overall survival at 24 months was 87% in the pembrolizumab-chemoradiotherapy group and 81% in the placebo-chemoradiotherapy group (information fraction 42·9%). The HR for death was 0·73 (0·49-1·07); these data have not crossed the boundary of statistical significance. Grade 3 or higher adverse event rates were 75% in the pembrolizumab-chemoradiotherapy group and 69% in the placebo-chemoradiotherapy group., Interpretation: Pembrolizumab plus chemoradiotherapy significantly improved progression-free survival in patients with newly diagnosed, high-risk, locally advanced cervical cancer., Funding: Merck Sharp & Dohme, a subsidiary of Merck & Co (MSD)., Competing Interests: Declaration of interests DL, YX, KH, GS, ML, PR-E, AAc, VSu, NC, AJPdSG, FCM, AR, AAy, J-YL, VSa, FZ, LG, JS, ET, KLin, RLaz, C-LC, RLam, HZ, AO, MC, SPo, TU, SPi, and LRD received funding to their institutions from MSD to support the study. DL reports consulting fees from AstraZeneca, Clovis Oncology, GSK, MSD, ImmunoGen, Genmab, Seagen, Novartis, and PharmaMar; payment or honoraria for lectures, presentations, speakers' bureaus, manuscript writing, or educational events from AstraZeneca, ImmunoGen, GSK, Seagen, and Genmab; support for attending meetings or travel from AstraZeneca, Clovis Oncology, and GSK; participation on a data safety monitoring board or advisory board for Oncoinvest, Corcept, Sutro, AstraZeneca, ImmunoGen, GSK, Seagen, Genmab, Clovis Oncology, GSK, MSD, and PharmaMar; leadership or fiduciary role in other board, society, committee, or advocacy group, paid or unpaid, for GCIG; receipt of equipment, materials, drugs, medical writing, gifts, or other services from Clovis Oncology, GSK, MSD, and PharmaMar; and other financial or non-financial interests in AstraZeneca, Clovis Oncology, Genmab, GSK, ImmunoGen, Incyte, MSD, Roche, Seagen, and Novartis. YX reports participation on a data safety monitoring board or advisory board for MSD. KH reports research contracts from Daiichi Sankyo, Eisai, MSD, and Takeda; advisory board fees from Chugai, Eisai, Takeda, MSD, Roche, Genmab, and Sanofi; honoraria from Daiichi Sankyo, AstraZeneca, Chugai, Eisai, Genmab, MSD, Takeda, Sanofi, Kyowa Kirin, and Kaken; and support for attending meetings or travel from Regeneron. GS reports grants or contracts from MSD Italia; consulting fees from Tesaro and Johnson & Johnson; and payment or honoraria for lectures, presentations, speakers' bureaus, manuscript writing, or educational events from Clovis Oncology Italy. ML reports grants or contracts from MSD, AstraZeneca, and Roche; speaker fees from AstraZeneca and Roche; and meeting support from Roche. PR-E reports payment or honoraria for lectures, presentations, speakers' bureaus, manuscript writing, or educational events from MSD, Asofarma, Novartis, Janssen, and AstraZeneca; support for attending meetings or travel from Roche, Novartis, Asofarma, and AstraZeneca; and participation on a data safety monitoring board or advisory board for Pfizer, Asofarma, Bristol Myers Squibb, and AstraZeneca. NC reports participation on a data safety monitoring board or advisory board for GSK, Toray, Tarveda Therapeutics, Umoja, Kartos, Zentalis, Profound, and Novita Pharmaceuticals. AJPdSG reports consulting fees, payment or honoraria for lectures, presentations, speakers' bureaus, manuscript writing, or educational events, and participation on a data safety monitoring board or advisory board for AstraZeneca, Astellas, Bayer, and Janssen; payment for expert testimony from Janssen; and support for attending meetings or travel from Janssen, MSD, and Bayer. FCM reports speaker fees from MSD, Bristol Myers Squibb, GSK, Eli Lilly, and BMS; payment for expert testimony from MSD, Janssen, GSK, Eli Lilly, and Bristol Myers Squibb; and meeting and travel support from MSD and Amgen. AR reports advisory board fees from MSD Israel. J-YL reports grants or contracts from Advenchen, Ascendis Pharma, Alkermes, AstraZeneca, BeiGene, BerGenBio, Bristol Myers Squibb, Cellid, Clovis Oncology, Eisai, Genmab, GII, GSK, ImmunoGen, Janssen, Merck, Mersana, MSD, Novartis, Onconic Therapeutics, OncoQuest, Ono, Regeneron, Roche, Seagen, Sutro, Synthon, and Takeda; and payment or honoraria for lectures, presentations, speakers' bureaus, manuscript writing, or educational events from AstraZeneca, Janssen, MSD, Roche, Takeda, and Ono. FZ reports grants or contracts, consulting fees, payment for expert testimony, support for attending meetings or travel, participation on a data safety monitoring board or advisory board, and leadership or fiduciary role in other board, society, committee, or advocacy group, paid or unpaid, from AstraZeneca, Eli Lilly, MSD, Pfizer, Roche, Daiichi Sankyo, Merck, Novartis, Genesis Pharma, and Gilead. LG reports institutional grants from GSK, Pfizer, MSD, Karyopharm, Tesaro, IMV, Alkermes, Clovis Oncology, ImmunoGen, Roche, Mersana, and AstraZeneca; consulting fees from GSK, Merck, Eisai, and Novocure; payment or honoraria for lectures, presentations, speakers' bureaus, manuscript writing, or educational events from GSK, Merck, Eisai, Novocure, and Corcept; and support for attending meetings or travel from Corcept, GSK, AstraZeneca, and Merck. JS reports grants or contracts from Roche, MSD, GSK, Tesaro, AstraZeneca, Eisai, Merck, and Novocure; consulting fees from ImmunoGen, Incyte, GSK, AstraZeneca, Clovis Oncology, Novocure, MSD, Eisai, and Merck; payment or honoraria for lectures, presentations, speakers' bureaus, manuscript writing, or educational events from ImmunoGen, Incyte, GSK, AstraZeneca, Clovis Oncology, Novocure, Bristol Myers Squibb, Eisai, and Novartis; support for attending meetings or travel from GSK, AstraZeneca, Roche, Novocure, ImmunoGen, Incyte, MSD, and Eisei; participation on a data safety monitoring board or advisory board for ImmunoGen, Incyte, GSK, AstraZeneca, Clovis Oncology, Novocure, Bristol Myers Squibb, MSD, Merck, Bayer, and PharmaMar; and leadership or fiduciary role in other board, society, committee, or advocacy group, paid or unpaid, for ENGAGE, ESGO, ASCO, ESGO, GCIG, Deutsche Stiftung Eierstockkrebs, and AGO. KLin reports grants or contracts from GSK (paid to institution); payment or honoraria for lectures, presentations, speakers' bureaus, manuscript writing, or educational events from Eisai; and participation on a data safety monitoring board or advisory board for Eisai, MSD, Nykode, AstraZeneca, and GSK. HZ reports contracted research and payment or honoraria for lectures, presentations, speakers' bureaus, manuscript writing, or educational events for MSD. AO reports grants or contracts from AbbVie Deutschland, Advaxis, Aeterna Zentaris, Amgen, Aprea Therapeutics, Bristol Myers Squibb, Clovis Oncology, Eisai, Roche, ImmunoGen, MSD de España, Millennium Pharmaceuticals, PharmaMar, Regeneron, and Tesaro (paid to institution); consulting fees and participation on a data safety monitoring board or advisory board from Agenus, AstraZeneca, Clovis Oncology, Corcept, Deciphera Pharmaceuticals, Eisai, Exelixis, EMD Serono, Roche, Genmab, GSK, ImmunoGen, iTeos, MSD de España, Mersana, Novocure, OncXerna Therapeutics, PharmaMar, Regeneron, Sattucklabs, Seagen, and Sutro; payment or honoraria for lectures, presentations, speakers' bureaus, manuscript writing, or educational events from NSGO, Peerview, Peervoice, Medscape, Asociación Colombiana de Ginecológos Oncólogos, ESO, AstraZeneca, and GSK; and support for attending meetings or travel from AstraZeneca, PharmaMar, and Roche. SPo reports consulting fees from MSD, AstraZeneca, GSK, and Eisai; payment or honoraria for lectures, presentations, speakers' bureaus, manuscript writing, or educational events, support for attending meetings or travel, and advisory board fees from MSD, AstraZeneca, and GSK; and leadership or fiduciary role in other board, society, committee, or advocacy group for the Austrian Association of Gynecologic Oncology (unpaid). SPi reports research funding from Roche, MSD, AZ, Pfizer, and GSK; and honoraria from AZ, Roche, MSD, GSK, and PharmaMar. LRD reports research funding (paid to institution) from and acting as an expert advisor (unpaid) for Merck & Co; writing fees for expert content for UpToDate; participation on a scientific advisory board for Aadi Bioscience; and serving on the Editorial Board of the British Journal of Obstetrics and Gynaecology. KLi, KY, ST, and SMK are full-time employees of MSD and hold stock or restricted stock units in the company., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

Introduction: The incidence of cancer during pregnancy and within first year post-delivery, ie pregnancy-associated cancer (PAC), is increasing in many countries, but little is known about risk factors for these trends. This study quantified incidence of PAC by trimesters and post-delivery periods, and assessed the role of maternal age, parity, immigrant status, education, smoking and body mass index for the risk and incidence trends of PAC., Material and Methods: We used data from the national birth and cancer registers in Sweden during 1973-2017 to define a register-based cohort of women aged 15-44 years. Incidence rates of PAC during pregnancy and up to 1 year post-delivery were calculated per 100 000 deliveries per year. Poisson regression with multiple imputation estimated incidence rate ratios with 95% confidence intervals adjusted by year, age, previous parity, immigrant status, education, smoking and BMI during 1990-2017, when information on risk factors was available., Results: Among 4 557 284 deliveries, a total of 1274 (during pregnancy) and 3355 (within 1 year post-delivery) cases of PAC were diagnosed, with around 50 cases/year diagnosed during pregnancy and 110 cases/year during the first year post-delivery in the latest period 2015-2017. The most common cancer types during pregnancy were malignant melanoma, breast and cervical cancer, together accounting for 57% of cases during pregnancy and 53% during the first year post-delivery. The numbers of PAC were lower during pregnancy than during post-delivery for all tumor types with lowest numbers during first trimester. The PAC incidence rates increased over calendar time. High maternal age at diagnosis, smoking, nulliparity and non-immigrant background were associated with significantly higher risks of PAC. The increasing PAC incidence was in part explained by higher maternal age over time, but not by the other factors., Conclusions: High maternal age is the strongest risk factor for PAC. We show for the first time that smoking, nulliparity and non-immigrant background are also contributing risk factors for PAC. However, only high maternal age contributed significantly to the increasing incidence. Further studies on other potential risk factors for PAC are warranted, since our results indicate that age on its own does not fully explain the increase., (© 2023 The Authors. Acta Obstetricia et Gynecologica Scandinavica published by John Wiley & Sons Ltd on behalf of Nordic Federation of Societies of Obstetrics and Gynecology (NFOG).)

Introduction: The role of molecular classification in patients with low/intermediate risk endometrial cancer (EC) is uncertain. Higher precision in diagnostics will inform the unsettled debate on optimal adjuvant treatment. We aimed to determine the association of molecular profiling with patterns of relapse and survival., Material and Methods: This retrospective cohort study included patients referred to The Norwegian Radium Hospital, Oslo University Hospital from 2006-2017. Patients with low/intermediate risk EC were molecularly classified as pathogenic polymerase epsilon (POLE)-mutated, mismatch repair deficient (MMRd), p53 abnormal, or no specific molecular profile (NSMP). The main outcomes were time to recurrence (TTR) and cancer-specific survival (CSS)., Results: Of 626 patients, 610 could be molecularly classified. Fifty-seven patients (9%) had POLE-mutated tumors, 202 (33%) had MMRd tumors, 34 (6%) had p53 abnormal tumors and 317 (52%) had NSMP tumors. After median follow-up time of 8.9 years, there was a statistically significant difference in TTR and CSS by molecular groups. Patients with p53 abnormal tumors had poor prognosis, with 10 of the 12 patients with relapse presenting with para-aortic/distant metastases. Patients with POLE mutations had excellent prognosis. In the NSMP group, L1CAM expression was associated with shorter CSS but not TTR., Conclusions: The differences in outcome by molecular groups are driven by differences in relapse frequency and -patterns and demand a higher precision in diagnostics, also in patients with low/intermediate risk EC. Tailored adjuvant treatment strategies need to consider systemic treatment for patients with p53 abnormal tumors and de-escalated treatment for patients with POLE mutated tumors., Competing Interests: Declaration of Competing Interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Outside the submitted work, the authors report the following conflicts: Kristina Lindemann: Receipt of grants/research supports: GSK, research funding paid to Institution; Receipt of honoraria or consultation fees: Advisory board fees: Astra Zeneca, Nycode, GSK, Eisai, MSD. Gunnar Kristensen: Stockholder: Novo Nordic. All remaining authors have declared no conflicts of interest., (Copyright © 2024. Published by Elsevier Ltd.)

Introduction: The National Comprehensive Cancer Network (NCCN) distress thermometer and problem list (DTPL) is a brief self-report screening measure for use in follow-up cancer care. The aims of this study were to explore the correlations between scores on the DTPL and scores on longer measures of anxiety/depression and health-related quality of life among women treated for gynecological cancer, and to define a cutoff score on the DT representing high levels of psychological distress in this patient group., Material and Methods: During outpatient visits, 144 women filled in the DTPL, the Hospital Anxiety and Depression Scale (HADS) and the RAND-36-Item Short Form Health Survey (RAND-36) between October 2019 and March 2020. We assessed the agreement between the DT-scores and the HADS scores, explored variables associated with high levels of distress on the DT, and studied the associations between DTPL-scores and scores of health-related quality of life (HRQoL) from RAND-36., Results: In receiver operating characteristic curve analysis between the distress score from the DT and a HADS total score ≥15 (defining high levels of anxiety/depression symptoms), the area under the curve was 0.81 (95% CI: 0.74-0.89). Using a cutoff of ≥5 on the DT (scale 0-10), we found a balanced level of sensitivity (81%) and specificity (71%) towards a HADS total score of ≥15. The scores of distress and problems reported on the DTPL correlated significantly with the majority of HRQoL function scales from RAND-36., Conclusions: The NCCN DTPL can be used as a screening measure for self-reported distress and problems after treatment for gynecological cancer. A score of ≥5 on DT may indicate high level of anxiety/depression as measured by HADS. The tool may help identify patients in need of referral to supportive care and rehabilitation facilities., (© 2023 The Authors. Acta Obstetricia et Gynecologica Scandinavica published by John Wiley & Sons Ltd on behalf of Nordic Federation of Societies of Obstetrics and Gynecology (NFOG).)

Background: The GOG240 trial established bevacizumab with chemotherapy as standard first-line therapy for metastatic or recurrent cervical cancer. In the BEATcc trial (ENGOT-Cx10-GEICO 68-C-JGOG1084-GOG-3030), we aimed to evaluate the addition of an immune checkpoint inhibitor to this standard backbone., Methods: In this investigator-initiated, randomised, open-label, phase 3 trial, patients from 92 sites in Europe, Japan, and the USA with metastatic (stage IVB), persistent, or recurrent cervical cancer that was measurable, previously untreated, and not amenable to curative surgery or radiation were randomly assigned 1:1 to receive standard therapy (cisplatin 50 mg/m 2 or carboplatin area under the curve of 5, paclitaxel 175 mg/m 2 , and bevacizumab 15 mg/kg, all on day 1 of every 3-week cycle) with or without atezolizumab 1200 mg. Treatment was continued until disease progression, unacceptable toxicity, patient withdrawal, or death. Stratification factors were previous concomitant chemoradiation (yes vs no), histology (squamous cell carcinoma vs adenocarcinoma including adenosquamous carcinoma), and platinum backbone (cisplatin vs carboplatin). Dual primary endpoints were investigator-assessed progression-free survival according to Response Evaluation Criteria in Solid Tumours version 1.1 and overall survival analysed in the intention-to-treat population. This study is registered with ClinicalTrials.gov, NCT03556839, and is ongoing., Findings: Between Oct 8, 2018, and Aug 20, 2021, 410 of 519 patients assessed for eligibility were enrolled. Median progression-free survival was 13·7 months (95% CI 12·3-16·6) with atezolizumab and 10·4 months (9·7-11·7) with standard therapy (hazard ratio [HR]=0·62 [95% CI 0·49-0·78]; p<0·0001); at the interim overall survival analysis, median overall survival was 32·1 months (95% CI 25·3-36·8) versus 22·8 months (20·3-28·0), respectively (HR 0·68 [95% CI 0·52-0·88]; p=0·0046). Grade 3 or worse adverse events occurred in 79% of patients in the experimental group and in 75% of patients in the standard group. Grade 1-2 diarrhoea, arthralgia, pyrexia, and rash were increased with atezolizumab., Interpretation: Adding atezolizumab to a standard bevacizumab plus platinum regimen for metastatic, persistent, or recurrent cervical cancer significantly improves progression-free and overall survival and should be considered as a new first-line therapy option., Funding: F Hoffmann-La Roche., Competing Interests: Declaration of interests AO reports personal fees for participation in the advisory boards of AstraZeneca, Clovis Oncology, Deciphera, Genmab, GSK, Immunogen, Mersana Therapeutics, PharmaMar, MSD de España, Agenus, Sutro, Corcept Therapeutics, EMD Serono, Novocure, Shattuck Labs, iTeos, and Eisai; travel and accommodation support from AstraZeneca, PharmaMar, and Roche; and funding paid to institution from AbbVie Deutschland, Advaxis, Aeterna Zentaris, Amgen, Aprea Therapeutics AB, Clovis Oncology, Eisai, F Hoffmann-La Roche, Regeneron Pharmaceuticals, Immunogen, MSD de España, Takeda, PharmaMar, Tesaro, and Bristol Myers Squibb. LG reports support for attending meetings or travel from Viatris, GSK, and MSD; consulting fees paid to institution for participation in the advisory boards of Clovis, GSK, AstraZeneca, and Seagen; and speaker honoraria paid to institution from AstraZeneca, GSK, and Eisai. JM-G reports personal fees for participation in the advisory boards of AstraZeneca, Clovis, GSK, and PharmaMar; research grants paid to institution from GSK and Roche; and travel and accommodation expenses from GSK−Tesaro, Pfizer, and PharmaMar. GV reports honoraria for speaker engagements from MSD, Pierre Fabre, GSK, and Pfizer; and consulting fees from Reveal Genomics. UDG reports personal consulting fees from Amgen, AstraZeneca, Pfizer, BMS, Clovis Oncology, Dompé Farmaceutici, Merck, MSD, PharmaMar, Astellas, Bayer, Ipsen, Novartis, Eisai, and Janssen; other funding paid to institution from AstraZeneca, Sanofi, and Roche; and support for attending meetings or travel from Pfizer, Ipsen, and AstraZeneca. KL reports personal honoraria from Eisai; participation on data safety monitoring or advisory boards of Eisai, MSD, Nykode, AstraZeneca, and GSK (honoraria paid to institution); and funding paid to institution from GSK. LW reports personal honoraria for participation in the advisory boards of AstraZeneca, Pfizer, GSK, Roche, MSD–Merck, Eisai, and Seagen; personal honoraria for speaker engagements from AstraZeneca, Eisai, GSK, Pfizer, Roche, MSD–Merck, and Seagen; and support for attending meetings or travel from GSK and MSD. NC reports consultancy or advisory roles for AstraZeneca, Clovis Oncology, Eisai, GSK, Immunogen, Mersana, MSD−Merck, Nuvation Bio, OncXerna, Pfizer, Pieris, and Roche; promotional speaker roles for AstraZeneca, Novartis, Clovis Oncology, MSD−Merck, and GSK; research grants from AstraZeneca, GSK, and Roche; and support for attending meetings or travel from AstraZeneca and GSK. LD reports personal fees for scientific advisory boards from Aadi Bioscience and Regeneron; fees paid to institution for scientific advisory boards from Merck; membership of the British Journal of Obstetrics and Gynaecology Editorial Board; personal royalties for writing expert content for UpToDate, Wiley, and the American Society of Clinical Oncology; personal fees for continuing medical education activities for Advance Medical, CEA Group, and Clinical Care Options; research funding paid to institution for investigator-initiated trials from Merck; clinical trial grants paid to institution from Genentech−Roche, AbbVie (GOG 3005), Acrivon, Advaxis, Aduro BioTech, Alkermes, Blueprint, Constellation, Eisai, GSK–Novartis, Immunogen, Inovio, Iovance, Karyopharm, KSQ Therapeutics, Lycera, Merck, Morab, MorphoTek, Naveris, Nurix, OncoQuest, Pfizer, Syndax, Tesaro, and Zentalis; and fees paid to institution for membership of data and safety monitoring committees for Agenus and Inovio. AL reports personal fees for presentations or educational events from Medscape and PeerVoice; consulting fees paid to institution from Owkin; speaker honoraria paid to institution from MSD, GSK, AstraZeneca, and Eisai; fees paid to institution for participation in the advisory boards of AstraZeneca, MSD, Seagen, GSK, Genmab, Zentalis, and Blueprint; non-remunerated independent data safety monitoring board participation for Clovis and BMS; an educational grant paid to institution from AstraZeneca; and support for attending meetings or travel from OSE Immunotherapeutics. AG-O reports honoraria paid to institution for participation in the advisory board of Novartis; personal honoraria for speaker engagements from AstraZeneca, Pfizer, Novartis, and Lilly; and support for attending meetings or travel from Pfizer and Novartis. MJR reports personal fees for participation in the advisory boards of AstraZeneca, Clovis Oncology, GSK, PharmaMar, MSD de España, Eisai, and Roche; personal fees for speaker engagements from MSD, AstraZeneca, Clovis Oncology, GSK, and PharmaMar; and travel and accommodation from AstraZeneca, PharmaMar, Roche, GSK, and MSD de España. LF-M reports honoraria paid to institution for participation in the advisory boards of GSK; honoraria paid to institution for speaker engagements from GSK, AstraZeneca–MSD, and Eisai; and support for attending meetings or travel from AstraZeneca–MSD and GSK. DL reports personal fees for participation in the advisory boards of AstraZeneca, Clovis Oncology, Corcept, Genmab, GSK, Immunogen, MSD, Oncoinvent, PharmaMar, Seagen, and Sutro; personal fees for consultancy roles from AstraZeneca, Clovis Oncology, Genmab, GSK, Immunogen, MSD, Novartis, PharmaMar, and Seagen; clinical trial or research funding to institution from Clovis Oncology, GSK, MSD, and PharmaMar; other financial or non-financial interests from AstraZeneca, Clovis Oncology, Corcept, Genmab, GSK, Immunogen, Incyte, MSD, Novartis, Oncoinvent, PharmaMar, Roche, Seagen, and Sutro; and travel grants from AstraZeneca, Clovis Oncology, and GSK. IR-C reports personal honoraria for participation in the advisory boards of Adaptimmune, Agenus, Amgen, AstraZeneca, BMS, Clovis, Daiichi Sankyo, Deciphera, Eisai, EQRx, GSK, Merck Serono, MacroGenics, Mersana, Novartis, Onxeo, Roche, and Sutro Biopharma; honoraria paid to institution for participation in the advisory boards of MSD (translational research); and funding paid to institution for translational research from BMS. LM reports participation in the advisory board of Roche; and honoraria for speaker engagements from Roche, GSK, Clovis Oncology, AstraZeneca, Pfizer, Novartis, and Lilly. FJ reports honoraria for lectures, expert boards, and educational events from AstraZeneca, Clovis Oncology, GSK, and Seagen; travel and accommodation support from GSK, Eisai, and MSD; and financial support for national academic GINECO trials from GSK and AstraZeneca. JA reports honoraria for speaker bureaus from GSK, Roche, AstraZeneca, MSD, PharmaMar, and Clovis; and advisory boards for GSK, MSD, AstraZeneca, and Clovis. PF reports personal fees for expert testimony from Daiichi; personal fees for invited speaker engagements from GSK and MSD; and support for attending meetings or travel from Lilly, Novartis, and GSK. IR reports personal fees for advisory boards from AstraZeneca, Clovis Oncology, GSK, PharmaMar, Roche, and MSD; and travel and accommodation from AstraZeneca, PharmaMar, Roche, and GSK. CL reports honoraria for advisory board participation from GSK; personal honoraria for speaker engagements from GSK, Clovis Oncology, Eisai, and MSD; and support for attending meetings or travel from MSD and GSK. JAP-F reports honoraria for speaker engagements from AstraZeneca, PharmaMar, Pharma&, Clovis, and GSK; payment for expert testimony from AstraZeneca, GSK, Roche, and PharmaMar; support for attending meetings or travel from Karyopharm, AstraZeneca, Roche, and PharmaMar; grants paid to institution from GSK and PharmaMar; equipment, materials, drugs, medical writing, gifts, or other services paid to institution from GSK; participation on data safety monitoring or advisory boards for Ability Pharma; and has a patent pending in breast cancer. HD reports personal honoraria for advisory board participation from AstraZeneca. LMR reports honoraria for speaker engagements from Genmab−Seagen, Blueprint Oncology, Curio Science, and Physicians Education Resource; honoraria for participation in the advisory boards of AstraZeneca, Clovis Oncology, GOG Foundation, Aadi Biosciences, Seagen, OnTarget Laboratories, Merck, Mersana, Rubius Therapeutics, Myriad Genetics, Genentech−Roche, Eisai, Novocure, and Immunogen; consulting fees from the GOG Foundation; and funding paid to institution from Genentech−Roche, On Target Laboratories, Pfizer, Aivita Biomedical, Tesaro, AstraZeneca, Merck, Akeso Biopharma, and Grupo Español de Investigación en Cáncer ginecologico. All other authors declare no competing interests., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

Objectives: The aim of this study was to provide real-world efficacy and safety data on niraparib maintenance treatment in patients with non-germline (gBRCA)1/2 mutated platinum-sensitive recurrent ovarian cancer., Methods: This retrospective multi-center cohort study included 94 platinum-sensitive recurrent ovarian cancer patients without known gBRCA1/2 mutation treated in an individual patient access program in Norway. The primary outcome was time from start of niraparib treatment to first subsequent treatment. Secondary endpoints included progression-free survival, safety, and tolerability., Results: After median follow-up of 13.4 months (95% confidence interval (CI) 10.0 to 16.8), 68.1% had progressed and 22.3% had died. Of the entire cohort, 61.7% had commenced a new line of treatment, and 24.5% were still receiving niraparib. The median duration of niraparib treatment was 5.0 months (range 0.4 to 27.3), and the median time to first subsequent treatment was 10.7 months (95% CI 8.4 to 13.0). Patients with elevated CA125 prior to start of niraparib had shorter time to first subsequent treatment (7.3 months, 95% CI 4.2 to 10.3) than patients with normalized CA125 (12.2 months, 95% CI 10.9 to 13.7 (p=0.002). Patients who started on individual dose based on weight and platelet counts had fewer dose reductions (p<0.001) and interruptions (p=0.02)., Conclusion: In a real-world setting, niraparib maintenance treatment in patients with non-gBRCA1/2 mutated recurrent platinum-sensitive ovarian cancer showed effectiveness comparable with published phase III studies and acceptable safety. Individualized dosing is essential to minimize adverse events. CA125 levels at start of niraparib treatment may help to estimate the individual prognosis., Competing Interests: Competing interests: No., (© IGCS and ESGO 2023. Re-use permitted under CC BY-NC. No commercial re-use. Published by BMJ.)

There are conflicting narratives over what drives demand for add-ons. We undertook an online survey of IVF patients to determine whether patients perceive that use of IVF add-ons is driven by patients or practitioners. People who underwent IVF in the UK in the previous five years were recruited via social media Survey questions focussed on the roles of clinician offer and patient request, including who first suggested use of add-ons in IVF consultations, where patients first heard about them, and which information sources they trusted. From a total of 261 responses, 224 met the inclusion criteria. Overall, 67% of respondents had used one or more IVF add-ons, most commonly: time-lapse imaging (27%), EmbryoGlue (27%), and endometrial scratching (26%). Overall, 81% of the add-ons used were offered to participants by clinicians (compared to 19% requested by themselves). Half (54%) reported being offered add-ons during consultations, compared to 24% who initiated discussion about add-ons. Higher proportions of private patients reported being offered (90%), requesting (47%) and using (74%) add-ons than those with NHS funding (74%, 29%, 52%, respectively). The main limitations of this study are the small sample size, recruitment via a convenience sample, and the self-reported data capture which is subject to recall bias.

Background: Cognitive impairment has a negative impact on older patients with cancer., Objectives: The aim of this study was to evaluate for interindividual differences in 2 subjective measures of cognitive function in older patients (n = 112), as well as determine which demographic, clinical, and symptom characteristics, and levels of physical function, were associated with initial levels and with the trajectory of each of these 2 measures., Methods: Cognitive function was assessed using the cognitive function scale from the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire Core 30 and the Attentional Function Index at the initiation of chemotherapy and at 1, 3, 6, 9, and 12 months after its initiation. Hierarchical linear modeling was used to assess for interindividual differences in and characteristics associated with initial levels and changes in cognitive function., Results: Characteristics associated with decreases in Quality of Life Questionnaire Core 30 scores at the initiation of chemotherapy were longer time since the cancer diagnosis and higher depression scores. Characteristics associated with poorer Attentional Function Index scores at enrollment were lower levels of education and higher depression scores. No characteristics were associated with worse trajectories of either cognitive function measure., Conclusion: Some older patients undergoing chemotherapy experience decrements in cognitive function., Implications for Practice: Our findings suggest that clinicians need to assess for depressive symptoms in older patients before the initiation of chemotherapy. Evidence-based interventions (eg, cognitive stimulation, increased physical activity) can be recommended to maintain and increase cognitive function in older oncology patients., Competing Interests: The authors have no funding or conflicts of interest to disclose., (Copyright © 2022 Wolters Kluwer Health, Inc. All rights reserved.)

Background: Pelvic exenteration may be the only curative treatment for some patients with primary advanced or recurrent vulvar cancer but is associated with high morbidity. This study evaluated the clinical outcome of patients treated at a centralized service in Norway., Methodology: This retrospective study included patients treated with pelvic exenteration for primary locally advanced or recurrent vulvar cancer between 1996 and 2019 at Oslo University Hospital, Norway. Complications were coded according to the contracted Accordion classification. Relapse free survival (RFS), cancer specific survival (CSS) and overall survival (OS) were estimated with the Kaplan Meier method., Results: The 30 patients were followed for a median of 4.94 years (95%CI: 3.37-NR). Exenteration due to primary vulvar cancer was carried out in 16 (53%) patients, 14 (47%) had recurrent vulvar cancer. Free histopathological margins were achieved in 28 (93%) patients. The 90 days morbidity for grade 3 complications was 63%, predominantly wound/surgical flap infections, 7% had no complications. 90 days mortality was 3%. Five-year RFS was 26% (95% CI 8-48%), OS was 50% (95%CI: 29-69%) and CSS was 64% (95% CI 43-79%). There was no significant difference in survival between patients with primary vs recurrent disease. The 3-year CSS for patients with negative lymph nodes and positive lymph nodes was 70% (95% CI 47-84%) and 30% (95% CI 1-72%), respectively., Conclusions: Acceptable oncologic outcomes after pelvic exenteration for primary and recurrent vulvar cancer can be achieved if surgery is centralized. Careful patient selection is imperative due to significant postoperative morbidity and considerable risk of relapse., Competing Interests: Declaration of competing interest The authors have no conflicts of interest., (Copyright © 2023 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Introduction: Many advances in the understanding of the pathologic and molecular features of endometrial cancer have occurred since the FIGO staging was last updated in 2009. Substantially more outcome and biological behavior data are now available regarding the several histological types. Molecular and genetic findings have accelerated since the publication of The Cancer Genome Atlas (TCGA) data and provide improved clarity on the diverse biological nature of this collection of endometrial cancers and their differing prognostic outcomes. The goals of the new staging system are to better define these prognostic groups and create substages that indicate more appropriate surgical, radiation, and systemic therapies., Methods: The FIGO Women's Cancer Committee appointed a Subcommittee on Endometrial Cancer Staging in October 2021, represented by the authors. Since then, the committee members have met frequently and reviewed new and established evidence on the treatment, prognosis, and survival of endometrial cancer. Based on these data, opportunities for improvements in the categorization and stratification of these factors were identified in each of the four stages. Data and analyses from the molecular and histological classifications performed and published in the recently developed ESGO/ESTRO/ESP guidelines were used as a template for adding the new subclassifications to the proposed molecular and histological staging system., Results: Based on the existing evidence, the substages were defined as follows: Stage I (IA1): non-aggressive histological type of endometrial carcinoma limited to a polyp or confined to the endometrium; (IA2) non-aggressive histological types of endometrium involving less than 50% of the myometrium with no or focal lymphovascular space invasion (LVSI) as defined by WHO criteria; (IA3) low-grade endometrioid carcinomas limited to the uterus with simultaneous low-grade endometrioid ovarian involvement; (IB) non-aggressive histological types involving 50% or more of the myometrium with no LVSI or focal LVSI; (IC) aggressive histological types, i.e. serous, high-grade endometrioid, clear cell, carcinosarcomas, undifferentiated, mixed, and other unusual types without any myometrial invasion. Stage II (IIA): non-aggressive histological types that infiltrate the cervical stroma; (IIB) non-aggressive histological types that have substantial LVSI; or (IIC) aggressive histological types with any myometrial invasion. Stage III (IIIA): differentiating between adnexal versus uterine serosa infiltration; (IIIB) infiltration of vagina/parametria and pelvic peritoneal metastasis; and (IIIC) refinements for lymph node metastasis to pelvic and para-aortic lymph nodes, including micrometastasis and macrometastasis. Stage IV (IVA): locally advanced disease infiltrating the bladder or rectal mucosa; (IVB) extrapelvic peritoneal metastasis; and (IVC) distant metastasis. The performance of complete molecular classification ( POLEmut , MMRd, NSMP, p53abn) is encouraged in all endometrial cancers. If the molecular subtype is known, this is recorded in the FIGO stage by the addition of "m" for molecular classification, and a subscript indicating the specific molecular subtype. When molecular classification reveals p53abn or POLEmut status in Stages I and II, this results in upstaging or downstaging of the disease (IICm p53abn or IAm POLEmut )., Summary: The updated 2023 staging of endometrial cancer includes the various histological types, tumor patterns, and molecular classification to better reflect the improved understanding of the complex nature of the several types of endometrial carcinoma and their underlying biologic behavior. The changes incorporated in the 2023 staging system should provide a more evidence-based context for treatment recommendations and for the more refined future collection of outcome and survival data., Competing Interests: All funding stated here is unrelated to the present document. JSB received research funds from Eisai, Immunogen, Karyopharm, and Tesaro (paid to the institution); he participated in the Data Safety Monitoring Board or Advisory Board of Merck and Novocure. CC participated in the Data Safety Monitoring Board of Merck and received compensation for her time; she was Chair of the Endometrial Committee of the Gynecological Cancer Intergroup (GCIG) and Member of the Guidelines Committee of the European Society of Gynecological Oncology (ESGO); her institution received the Oncentra Research Platform for a clinical study from Elekta. CF received payment or honoraria for her participation in the Advisory Boards from Roche, AstraZeneca/MSD, Clovis, Tesaro, Ethicon, and GSK; she received support for attending meetings and/or travel from Roche and GSK. DG received an NCI UG1 LAPS grant for NCI clinical trials and a grant from Elekta for a clinical trial; he received payment or honoraria for attending the ANZGOG annual meeting; he was Chair for the DSMC Cervix Trial for Merck; he was Co-Chair of the Gynecology Committee of NRG Oncology. SK participated in the Advisory Board for Truscreen Ltd; he was a Council Member of the British Gynaecological Cancer Society and a Trustee for OVACOME. KL received a research grant from GSK; she received payment or honoraria from Eisai, GSK, and Nycode; she participated in the Data Safety Monitoring Board or Advisory Board of Eisai, GSK, AstraZeneca, and MSD; she was on the Board of NSGO-CTU. NC received grants or contracts from the European Commission (FP7 Framework Program); she received consulting fees from Akesobio, Eisai, GSK, AstraZeneca, Mersana, Seattle Genetics, eTheRNA Immunotherapies NV, Seagen, and Immunogen; she received payment or honoraria for lectures or presentations from GSK, Kartos, MSD, Medscape Oncology, and TouchIME; she received support for attending meetings and/or travel from Roche, Genmab, and Armgen; she participated in a Data Safety Monitoring Board or Advisory Board of Akesobio, Eisai, GSK, AstraZeneca, Mersana, Seattle Genetics, eTheRNA Immunotherapies NV, Seagen, and Immunogen; she was ESGO President and Co-Chair of ENGOT Early Drug Development Network. XM-G and DM have no conflicts of interest., (© 2023. Asian Society of Gynecologic Oncology, Korean Society of Gynecologic Oncology, and Japan Society of Gynecologic Oncology.)

Objective: To analyze the expression and prognostic role of L1CAM in tubo-ovarian high-grade serous carcinoma (HGSC)., Methods: L1CAM protein expression by immunohistochemistry was analyzed in 644 HGSC (413 effusions, 231 surgical specimens). Expression was analyzed for association with clinicopathologic parameters and survival., Results: L1CAM protein expression was found in 401/413 (97%) effusions and 209/231 (90%) surgical specimens, with significantly higher staining extent in effusions (p < 0.001). L1CAM protein expression in effusions was unrelated to clinicopathologic parameters (p > 0.05). In surgical specimens, higher L1CAM expression was significantly related to primary (intrinsic) chemoresistance (p = 0.017). High (>25%) L1CAM expression in HGSC effusions (p = 0.02), older patient age (p = 0.013), FIGO stage IV disease (p < 0.001) and larger residual disease volume (p = 0.001) were significantly associated with shorter overall survival (OS) in univariate analysis. In Cox multivariate analysis, only FIGO stage (p = 0.001) and residual disease volume (p = 0.003) were independent prognosticators of OS. L1CAM expression in effusions was unrelated to progression-free survival (PFS). There was no association between L1CAM expression in surgical specimens and survival., Conclusion: L1CAM is overexpressed in HGSC effusions compared to surgical specimens. Its overexpression in effusions is significantly associated with shorter OS, but not independently of established prognostic factors such as FIGO stage and residual disease volume., Competing Interests: Declaration of Competing Interest None declared., (Copyright © 2023 The Author(s). Published by Elsevier Inc. All rights reserved.)