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Background: Low-grade serous and endometrioid ovarian cancers and adult-type granulosa cell tumors are rare ovarian malignancies that show high estrogen receptor positivity. Recurrences of these subtypes of ovarian cancer are often treated with conventional chemotherapy, although response rates are disappointing., Primary Objective: To determine the overall response rate of the combination therapy of abemaciclib and letrozole in patients with estrogen receptor-positive rare ovarian cancers., Study Hypothesis: The combination therapy of abemaciclib and letrozole will provide a clinically meaningful therapeutic benefit, with an overall response rate of >25%., Trial Design: This is a phase II, international, multicenter, open-label, single-arm study to evaluate the efficacy and safety of abemaciclib and letrozole in patients with advanced, recurrent, and/or metastatic estrogen receptor-positive, rare ovarian cancer. The study will follow a tandem two-stage design., Major Inclusion/exclusion Criteria: Patients must have histologically confirmed low-grade serous/endometrioid ovarian cancer or adult-type granulosa cell tumor with estrogen receptor positivity on immunohistochemistry. Patients need to have recurrent and measurable disease according to Radiologic Evaluation Criteria in Solid Tumors (RECIST) version 1.1. A maximum of two prior lines of endocrine therapy are allowed, and patients cannot have previously received a cyclin-dependent kinase inhibitor. Patients with platinum-refractory disease are not allowed in any stage of the study., Primary Endpoint: Investigator-assessed confirmed overall response rate, defined as the proportion of patients with a complete or partial response according to RECIST v1.1., Sample Size: 40 to 100 patients will be included, depending on the results of the interim analysis. Patients will be included in Belgium, France and the Netherlands., Estimated Dates for Completing Accrual and Presenting Results: Patient recruitment will be completed by the end of 2025 and reporting of the final study results will be done by the end of 2027., Trial Registration Number: NCT05872204., Competing Interests: Competing interests: EVN reports consulting fees from Regeneron, Oncoinvent, AstraZeneca, Roche, Seagen, Novartis, Merck and Verastem; and receipt of study drug abemaciclib for this study from Eli Lilly. TVG reports grants/contracts from the Fund for Scientific Research-Flanders (FWO); consulting fees (paid to the institution) from AstraZeneca, Eisai, OncXerna Therapeutics, MSD, GSK, ImmunoGen, Seagen, Tubulis and Zentalis; honoraria (paid to the institution) from ImmunoGen, GSK, AstraZeneca; and meeting/travel support from Amgen, Pfizer, Roche, GSK, Novartis, ImmunoGen, MSD, PharmaMar and Sanofi-Aventis. FK reports grants/contracts from GSK, PharmaMar and AstraZeneca; consulting fees from GSK and PharmaMar; honoraria from GSK; expert testimony for GSK and AstraZeneca; meeting/travel support from PharmaMar and AstraZeneca; and advisory board for AstraZeneca. TB reports grants/contracts from Roche; honoraria from Novartis, AstraZeneca and Eli Lilly; and meeting/travel support from AstraZeneca, GSK and MSD. HD reports grants/contracts (paid to the institution) from Gilead; consulting fees (paid to the institution) from GSK and Gilead; honoraria (paid to the institution) from AstraZeneca, GSK, Eli Lilly, Gilead, Amgen, Roche, Leo Pharma, MSD, Daiichi Sannkyo and Teva Pharmaceuticals; meeting/travel support (paid to the institution) from GSK, AstraZeneca, Gilead, Roche, MSD, Pfizer, Teva Pharmaceuticals and PharmaMar; and advisory board (paid to the institution) for GSK, AstraZeneca, MSD, Menarini, Eli Lilly, Pfizer, Gilead, Seagen. FS reports consulting fees from AstraZeneca, GSK Tesaro and MSD; and honoraria from AstraZeneca, GSK Tesaro, MSD and Eisai. IB reports grants from Springer Healthcare and GSK; honoraria from Status Plus Gynaecongres; and participation on the DSMB of the Direct2 study (no payments).TO, ASVR and DL have no competing interests to disclose., (© IGCS and ESGO 2024. Re-use permitted under CC BY-NC. No commercial re-use. Published by BMJ.)

Endometrial carcinosarcoma is a rare and aggressive high-grade endometrial carcinoma with secondary sarcomatous trans-differentiation (conversion theory). The clinical presentation and diagnostic work-up roughly align with those of the more common endometrioid counterpart, although endometrial carcinosarcoma is more frequently diagnosed at an advanced stage. Endometrial carcinosarcoma is not a single entity but encompasses different histological subtypes, depending on the type of carcinomatous and sarcomatous elements. The majority of endometrial carcinosarcomas are characterized by p53 abnormalities. The proportion of POLE and microsatellite instablity-high (MSI-H) is directly related to the epithelial component, being approximately 25% and 3% in endometrioid and non-endometrioid components.The management of non-metastatic disease is based on a multimodal approach with optimal surgery followed by (concomitant or sequential) chemotherapy and radiotherapy, even for early stages. Palliative chemotherapy is recommended in the metastatic or recurrent setting, with carboplatin/paclitaxel doublet being the first-line regimen. Although the introduction of immunotherapy plus/minus a tyrosine kinase inhibitor shifted the paradigm of treatment of patients with recurrent endometrial cancer, patients with endometrial carcinosarcoma were excluded from most studies evaluating single-agent immunotherapy or the combination. However, the US Food and Drug Administration (FDA) and the European Medicines Agency (EMA) approved the use of pembrolizumab and lenvatinib in endometrial cancer (all histotypes) after progression on chemotherapy and single-agent immunotherapy in MSI-H cancers. In the era of precision medicine, emerging knowledge on molecular endometrial carcinosarcoma is opening new promising therapeutic options for more personalized treatment. The present review outlines state-of-the-art knowledge and future directions for patients with endometrial carcinosarcoma., Competing Interests: Competing interests: GB: Novartis AG Pharma (C/A, H), Italian Ministry of Health (RG); NC: AstraZeneca (C/A, SH), Seattle Genetics (C/A, SH), MSD (SAB), Mersana (C/A, SH), eTheRNA immunotherapies NV (C/A, SH), Roche (travel expenses), Genmab (travel expenses), Amgen (travel expenses). IR-C: honoraria from AstraZeneca, Clovis, GSK/Tesaro, and PharmaMar; consulting/advisory board fees from AstraZeneca, Roche, Clovis, GSK/Tesaro, Genmab, PharmaMar, MSD, Mersana, Deciphera, OncXea, Esai, BMS, Novartis, and Pfizer; research funding from MSD; travel expenses from AstraZeneca, GSK, and Roche. YS: AstraZeneca (CA), GSK (CA). PW: Amgen (SH, RF, SAB), AstraZeneca (SH, RF, H, SAB), Clovis (SH, RF, SAB), Eisai (SH, SAB), GSK (SH, SAB), Lilly (SH, SAB), MSD (SH, RF, SAB), Novartis (SH, RF, SAB), Pfizer (SH, RF, SAB), Roche (SH, RF, H, SAB), TEVA (SH, SAB). NYLN: AstraZeneca (SH), Janssen (SH). KT: AstraZeneca (SH), Chugai (SH, RF), Eisai (SH), MSD (SH), Mochida (SH), Takeda (SH). TE: Takeda (SH), Astra Zeneca (SH), Eisai (SH), Chugai Pharma (SH, RF), MSD (SH), Mochida (SH). DL: AstraZeneca (H, CA), Clovis (H, CA, RF), GSK/Tesaro (H, CA), Roche (CA), Genmab (CA), PharmaMar (CA, RF), MSD (CA, RF), Esai (CA), Merck Serono (CA), Novartis (CA), and PharmaMar (H); consulting/advisory board fees from AstraZeneca, Roche, Clovis, GSK/Tesaro. DMP: AstraZeneca (CA, SH, SAB), GSK (CA, SH, SAB). NRA-R: NIH/NCI Cancer Center support grant P30 CA008748 (F). HD: Roche (CA, SH, SAB), Pfizer (CA, SH, SAB), AstraZeneca (SH, SAB), Lily (SAB), GSK (SAB), Novartis (SH), Pharmamar (SH); BJM: AstraZeneca (SH, SAB), GSK (SH, SAB), Incyte (SAB), Merck (SH, SAB), Roche/Genentech (SH, SAB), Eisai (SAB), GOG-Foundation (E), US Oncology (E)., (© IGCS and ESGO 2023. No commercial re-use. See rights and permissions. Published by BMJ.)

Objective: To report on the value of magnetic resonance imaging (MRI) and 2-deoxy-2-[18] fluoro-D-glucose positron emission tomography computed tomography (¹⁸FDG PET-CT) in predicting resectability and pathological response of primary locally advanced cervical cancer after neoadjuvant intensity-modulated arc therapy (IMAT) with or without cisplatin (C)., Methods and Materials: Twenty-seven patients with International Federation of Gynecology and Obstetrics stages IB2 to IVA cervical cancer were treated with IMAT-C followed by extrafascial hysterectomy (EH). All patients received MRI and ¹⁸FDG PET-CT after IMAT-C. The end points of this study were to: 1. Assess the ability of MRI to predict negative surgical margins (R0). 2. Assess the sensitivity, specificity, positive predictive value (PPV) and negative predictive value (NPV) of MRI in predicting the following situation at the EH specimen: "no residual disease or minimal microscopically visible residual tumor." 3. Assess the sensitivity, specificity, PPV, and NPV value of ¹⁸FDG PET-CT in predicting "no residual viable tumor cells" at the EH specimen., Results: An R0 resection was obtained in all patients. None of the EH specimens contained macroscopically visible tumor. In 13 patients, no viable tumor cells were found and only 14 had residual microscopic disease. Twenty-four of 27 MRIs were able to correctly predict R0 resection. A negative MRI was 100% predictive for the end point "R0 resection." The specificity and NPV of MRI (end point 2) were 74% and 100%, respectively. No sensitivity or PPV could be calculated. The sensitivity, specificity, PPV, and NPV of ¹⁸FDG PET-CT were 29%, 62%, 44%, and 44%, respectively (end point 3)., Conclusions: A negative MRI after IMAT-C predicts 100% correctly for R0 resection. The role of FDG PET-CT in predicting viable tumor cells at EH specimen is at least debatable.