[Immunotherapy in oncogynaecology]. / Immunothérapies validées en oncogynécologie.

Immune checkpoint inhibitors have deeply changed treatment paradigm of many tumor types, notably by providing long-term remissions, even in the metastatic setting. These immunotherapies aim to restore T-cells activity against tumour cells, in particular via the inhibition of PD1/PD-L1 interaction. As for lung or renal carcinomas, and melanomas, the management of endometrial and uterine cervical cancers has been disrupted by PD1/PD-L1 inhibitors efficacy. In locally advanced or metastatic cervical carcinomas, the combination of platinum-based chemotherapy with pembrolizumab demonstrated improved overall and progression-free survival in all subgroups of patients, and became the new standard of care. Regarding endometrial cancers, while single-agent immunotherapies have shown very limited activity in an unselected population, dostarlimab and pembrolizumab have been associated with remarkable antitumor activity in case of microsatellite instability (dMMR/MSI), detected in around 30% of patients. Finally, in endometrial cancer that has progressed after first-line chemotherapy, the association of pembrolizumab with an oral antiangiogenic kinase inhibitor (lenvatinib) has demonstrated its superiority over second-line chemotherapy regimens, regardless molecular subgroups, and has become the new standard of care in this indication.

The impact of sarcopenia on survival and treatment tolerance in patients with head and neck cancer treated with chemoradiotherapy.

BACKGROUND: Sarcopenia appears to be a negative prognostic factor for poor survival outcomes and worse treatment tolerance in patients with head-and-neck squamous cell carcinoma (HNSCC). We evaluated sarcopenia's impact on overall survival (OS), disease-free survival (DFS) and chemo-radiation tolerance in patients with head-and-neck cancer (HNC) treated with chemoradiotherapy (CRT) from a monocentric observational study. METHODS: We identified patients with HNC treated by CRT between 2009 and 2018 with pretreatment imaging using positron emission tomography-computed tomography scans (PET/CT). Sarcopenia was measured using the pretreatment PET/CT at the L3 vertebral body using previously published methods. Clinical variables were retrospectively retrieved. RESULTS: Of 216 patients identified, 54 patients (25.47%) met the criteria for sarcopenia. These patients had a lower mean body mass index before treatment (21.92 vs. 25.65 cm/m2 , p < 0.001) and were more likely to have a history of smoking (88.89% vs. 71.52%, p = 0.01), alcohol use (55.56% vs. 38.61%, p = 0.03) and positive human papilloma virus status (67.74% vs. 41.75%, p = 0.011). At 3 years of follow-up, OS and DFS were 75% and 70% versus 82% and 85% for sarcopenic and non-sarcopenic patients, respectively (p = 0.1 and p = 0.00015). On multivariate analysis, sarcopenia appeared as a pejorative factor on DFS (hazard ratio 2.174, p = 0.0001) in the overall cohort. Sarcopenic patients did not require more chemotherapy and radiation-treatment interruptions and did not suffer from more chemo-induced and radiation-induced grade 3-4 toxicities than their non-sarcopenic counterparts. CONCLUSION: Sarcopenia in HNSCC patients is an independent adverse prognostic factor for DFS after definitive chemoradiotherapy.

Outcomes of Patients With Active Cancer and COVID-19 in the Intensive-Care Unit: A Multicenter Ambispective Study.

Background: Several studies report an increased susceptibility to SARS-CoV-2 infection in cancer patients. However, data in the intensive care unit (ICU) are scarce. Research Question: We aimed to investigate the association between active cancer and mortality among patients requiring organ support in the ICU. Study Design and Methods: In this ambispective study encompassing 17 hospitals in France, we included all adult active cancer patients with SARS-CoV-2 infection requiring organ support and admitted in ICU. For each cancer patient, we included 3 non cancer patients as controls. Patients were matched at the same ratio using the inverse probability weighting approach based on a propensity score assessing the probability of cancer at admission. Mortality at day 60 after ICU admission was compared between cancer patients and non-cancer patients using primary logistic regression analysis and secondary multivariable analyses. Results: Between March 12, 2020 and March 8, 2021, 2608 patients were admitted with SARS-CoV-2 infection in our study, accounting for 2.8% of the total population of patients with SARS-CoV-2 admitted in all French ICUs within the same period. Among them, 105 (n=4%) presented with cancer (51 patients had hematological malignancy and 54 patients had solid tumors). 409 of 420 patients were included in the propensity score matching process, of whom 307 patients in the non-cancer group and 102 patients in the cancer group. 145 patients (35%) died in the ICU at day 60, 59 (56%) with cancer and 86 (27%) without cancer. In the primary logistic regression analysis, the odds ratio for death associated to cancer was 2.3 (95%CI 1.24 - 4.28, p=0.0082) higher for cancer patients than for a non-cancer patient at ICU admission. Exploratory multivariable analyses showed that solid tumor (OR: 2.344 (0.87-6.31), p=0.062) and hematological malignancies (OR: 4.144 (1.24-13.83), p=0.062) were independently associated with mortality. Interpretation: Patients with cancer and requiring ICU admission for SARS-CoV-2 infection had an increased mortality, hematological malignancy harboring the higher risk in comparison to solid tumors.