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Competing Interests: I took part in an advisory board and in a health economics interview regarding the progression-free survival data from the ENGOT-cx11/GOG-3047/KEYNOTE-A18 study previously published,(7) but was not involved in the current Article.(3) I report grants from AstraZeneca, Deciphera, and GSK; consulting fees from GSK, Ipsen, and MSD; speakers fees from AstraZeneca, BMS, GSK, Ipsen, MSD, Pfizer, and Pharmamar; support for meetings or travel from AstraZeneca, GSK, Ipsen, MSD, Pfizer, and Pharmamar; and participation on data safety monitoring board or advisory boards for AstraZeneca, BMS, Eisai, GSK, Ipsen, and MSD.

Until recently, patients diagnosed with locally advanced and metastatic endometrial cancer faced significant challenges in their treatment due to limited options and poor prognostic outcomes. The sequencing of tumors has been a major advancement in its management. It has led to The Cancer Genome Atlas classification currently used in clinical practice and the initiation of several clinical trials for innovative treatments targeting principally signaling pathways, immune checkpoints, DNA integrity, growth factors, hormonal signaling, and metabolism. Numerous clinical trials are investigating a combinatorial approach of these targeted therapies to counter tumoral resistance, cellular compensatory mechanisms, and tumor polyclonality. This review provides a comprehensive overview of historical, current, and promising therapies in advanced and metastatic endometrial cancer. It particularly highlights clinical research on targeted and hormonal therapies, but also immunotherapy, reflecting the evolving landscape of treatment modalities for this disease., Competing Interests: Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Christine Gennigens = All support for the present manuscrit: no disclosures. Grant/contracts: Astra-Zeneca, GSK, Deciphera. Consulting fees: Ipsen, GSK, MSD. Honoraria for lectures: MSD, BMS, Ipsen, Pfizer, Pharmamar, Astra-Zeneca, GSK. Support for meetings and/or travel: Ipsen, Pharmamar, Pfizer, MSD, GSK, Astra-Zeneca. Participation on a data safety monitoring board or advisory board: MSD, BMS, Ipsen, Astra-Zeneca. GSK, Eisai. Others authors – No conflict of interest., (Copyright © 2024 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Background: Part 1 of the RUBY trial (NCT03981796) evaluated dostarlimab plus carboplatin-paclitaxel compared with placebo plus carboplatin-paclitaxel in patients with primary advanced or recurrent endometrial cancer (EC). At the first interim analysis, the trial met one of its dual primary endpoints with statistically significant progression-free survival benefits in the mismatch repair-deficient/microsatellite instability-high (dMMR/MSI-H) and overall populations. Overall survival (OS) results are reported from the second interim analysis., Patients and Methods: RUBY is a phase III, global, double-blind, randomized, placebo-controlled trial. Part 1 of RUBY enrolled eligible patients with primary advanced stage III or IV or first recurrent EC who were randomly assigned (1 : 1) to receive either dostarlimab (500 mg) or placebo, plus carboplatin-paclitaxel every 3 weeks for 6 cycles followed by dostarlimab (1000 mg) or placebo every 6 weeks for up to 3 years. OS was a dual primary endpoint., Results: A total of 494 patients were randomized (245 in the dostarlimab arm; 249 in the placebo arm). In the overall population, with 51% maturity, RUBY met the dual primary endpoint for OS at this second interim analysis, with a statistically significant reduction in the risk of death [hazard ratio (HR) = 0.69, 95% confidence interval (CI) 0.54-0.89, P = 0.0020] in patients treated with dostarlimab plus carboplatin-paclitaxel versus carboplatin-paclitaxel alone. The risk of death was lower in the dMMR/MSI-H population (HR = 0.32, 95% CI 0.17-0.63, nominal P = 0.0002) and a trend in favor of dostarlimab was seen in the mismatch repair-proficient/microsatellite stable population (HR = 0.79, 95% CI 0.60-1.04, nominal P = 0.0493). The safety profile for dostarlimab plus carboplatin-paclitaxel was consistent with the first interim analysis., Conclusions: Dostarlimab in combination with carboplatin-paclitaxel demonstrated a statistically significant and clinically meaningful OS benefit in the overall population of patients with primary advanced or recurrent EC while demonstrating an acceptable safety profile., (Copyright © 2024 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Despite screening programs for early detection and the approval of human papillomavirus vaccines, around 6% of women with cervical cancer (CC) are discovered with primary metastatic disease. Moreover, one-third of the patients receiving chemoradiation followed by brachytherapy for locally advanced disease will have a recurrence. At the end, the vast majority of recurrent or metastatic CC not amenable to locoregional treatments are considered incurable disease with very poor prognosis. Historically, cisplatin monotherapy, then a combination of cisplatin and paclitaxel were considered the standard of care. Ten years ago, the addition of bevacizumab to chemotherapy demonstrated favorable data in terms of response rate and overall survival. Even with this improvement, novel therapies are needed for the treatment of recurrent CC in first as well as later lines. In the last decades, a better understanding of the interactions between human papillomavirus infection and the host immune system response has focused interest on the use of immunotherapeutic drugs in CC patients. Indeed, immune checkpoint inhibitors (pembrolizumab, cemiplimab, and others) have recently emerged as novel therapeutic pillars that could provide durable responses with impact on overall survival in patients in the primary (in addition to chemotherapy) or recurrent (monotherapy) settings. Tisotumab vedotin, an antibody-drug conjugate targeting the tissue factor, is another emerging drug. Several trials in monotherapy or in combination with immunotherapy, chemotherapy, or bevacizumab showed very promising results. There is a high need for more potent biomarkers to better accurately determine which patients would receive the greatest benefit from all these aforementioned drugs, but also to identify patients with specific molecular characteristics that could benefit from other targeted therapies. The Cancer Genome Atlas Research Network identified several genes significantly mutated, potentially targetable. These molecular data have highlighted the molecular heterogeneity of CC., Competing Interests: Disclosure CG grant/contracts: Astra-Zeneca; consulting fees: Ipsen, GlaxoSmithKline (GSK), Merck Sharp & Dohme (MSD); honoraria for lectures, etc.: MSD, Bristol Myers Squibb (BMS), Ipsen, Pfizer, Pharmamar, AstraZeneca, GSK; support for meetings and/or travel: Ipsen, Pharmamar, Pfizer, MSD; participation on a data safety monitoring board or advisory board: MSD, BMS, Ipsen, AstraZeneca, GSK, Eisai. GJ grant/contracts: Novartis, Roche, Pfizer; consulting fees: Novartis, Roche, Pfizer, Lilly, Amgen, BMS, AstraZeneca, Daiichi Sankyo, AbbVie; honoraria for lectures, etc.: Novartis, Roche, Amgen, Pfizer, BMS, Lilly, AstraZeneca, Seagen; support for meetings and/or travel: Novartis, Roche, Pfizer, Lilly, Amgen, BMS, AstraZeneca; participation on a data safety monitoring board or advisory board: Novartis, Roche, Pfizer, Lilly, Amgen, BMS, AstraZeneca, Daiichi Sankyo, AbbVie; other financial or non-financial interests: Novartis, Roche, Pfizer, Lilly, Amgen, BMS, AstraZeneca, MedImmune, Merck. FK grant/contracts: MSD, AstraZeneca, Pharmamar, Roche; consulting fees: MSD; honoraria for lectures, etc.: MSD, AstraZeneca, Pharmamar; support for meetings and/or travel: MSD, AstraZeneca, Roche; participation on a data safety monitoring board or advisory board: MSD, AstraZeneca. IR-C grant/contracts: BMS, MSD, GSK; consulting fees: GSK, AstraZeneca, Clovis, Pharmamar, Mersana, MSD, Novartis, Deciphera, Roche, Genentech; honoraria for lectures, etc.: GSK, AstraZeneca, Clovis, Pharmamar, Mersana, MSD, Novartis, Deciphera, Roche, Genentech; support for meetings and/or travel: GSK, Roche, AstraZeneca; participation on a data safety monitoring board or advisory board: Athena and Attend trials. All other authors have declared no conflicts of interest., (Copyright © 2022 The Author(s). Published by Elsevier Ltd.. All rights reserved.)

Objective: Extended field chemoradiation is recommended for patients with locally advanced cervical cancer (LACC) and para-aortic lymph node (PALN) metastases. The radiation planning may be based on PET/CT while others recommend to rely on surgical staging. We report the rate of patients for whom the radiation field defined on PET/CT was modified by the histological PALN status., Methods: Between March 2010 and December 2016, 168 consecutive patients with LACC underwent a pre-therapeutic PET/CT and PALN dissection. The data were reviewed retrospectively. The diagnostic performance of the PET/CT for definition of PALN status was calculated. We determined the percentage of patients for whom PALN dissection altered the external beam radiotherapy (EBRT) field defined on the PET/CT basis., Results: Of 151 patients with negative PALNs on PET/CT, 26 had histological PALN metastases. Of 17 patients with positive PALNs on PET/CT, 9 were negative on histology of which 7 were located in the common iliac region. Sensitivity, specificity, positive and negative predictive value of PET/CT were 23.5, 93.3, 47.1 and 82.8% respectively. In total, 35 out of 168 patients underwent EBRT - field adaptation (pelvic vs extended field). The rate of radiation field modification (27,7%) was particularly high in the subgroup of patients with metastatic pelvic lymph nodes (PLNs) on PET/CT., Conclusion: Para-aortic surgical staging contributes significantly to individualize the radiation treatment of patients with LACC, particularly for those with positive PLNs at PET/CT. Indication of surgical staging deserves particular attention when the PET/CT suggests positive LNs in the common iliac region., (Copyright © 2019 Elsevier Ltd, BASO ~ The Association for Cancer Surgery, and the European Society of Surgical Oncology. All rights reserved.)

Adipsic diabetes insipidus is a rare complication of intracranial tumors in which impaired antidiuretic hormone secretion is associated with the loss of thirst sensation. Here, we present the case of a patient with bifocal intracranial germinoma, diagnosed due to symptoms mainly caused by adipsic diabetes insipidus. This is, to our knowledge, the first case of adipsic diabetes insipidus revealing an intracranial germinoma reported in the literature. We describe the diagnostic procedures and the three-year follow-up of this patient. Management of intracranial germ-cell tumors is made complex by the wide range of histological features. Although germinomas have a generally better prognosis than most nongerminomatous tumors, they can have severe or even life-threatening presentations. Adipsic diabetes insipidus is one such severe presentation and its rarity can make it difficult to recognize and manage. Awareness of this potential entity is therefore important for clinical practice., (Copyright © 2017 Elsevier Masson SAS. All rights reserved.)