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Few data are available on the impact of KRAS mutation in patients with advanced non-squamous non-small cell lung cancer (aNSCLC) treated with immunotherapy. This analysis assessed the impact of KRAS mutation on the efficiency of first-line pembrolizumab immunotherapy in aNSCLC patients with PD-L1 ≥ 50 %.This was a secondary analysis of the ESCKEYP study, a retrospective, national, multicenter study which included consecutively all metastatic NSCLC patients who initiated first-line treatment with pembrolizumab monotherapy from May 2017 (date of pembrolizumab availability in this indication in France) to November 22, 2019 (pembrolizumab-chemotherapy combination approval). Progression-free survival (PFS) and overall survival (OS) were calculated from the start of pembrolizumab treatment by the Kaplan-Meier method. Tumor response and PFS were assessed locally.Among the 681 non-squamous aNSCLC PD-L1 ≥ 50 % patients treated with pembrolizumab in the first line, 227 (33.0 %) had a KRAS mutation (KRAS G12C, 12.5 %; KRAS non-G12C, 20.5 %). Except among non-smokers (KRAS G12C, 0 %; KRAS non-G12C, 2.9 %; no KRAS mutation, 9.2 %), patients presented no differences in terms of sex, age, number and sites of metastatic disease at diagnosis, use of corticosteroids, use of antibiotics, and for biological factors between wild-type KRAS, KRAS G12C and non-KRAS G12C groups. Median (95 % CI) PFS in months were 7.0 (3.7-14) for KRAS G12C, 4.8 (3.4-6.7) for KRAS non-G12C and 8.5 (7.3-10.6) for wild-type KRAS genotypes (p = 0.23). Median OS were 18.4 (12.6-NR), 20.6 (11.4-NR) and 27.1 (18.7-34.2) months, respectively (p = 0.57).No difference in efficacy was observed in non-squamous aNSCLC patients treated with first-line pembrolizumab immunotherapy whether they presented a KRAS G12C, non KRAS G12C or wild-type KRAS genotype.

Few real-world data are available in patients with advanced metastatic non-small cell lung cancer (NSCLC) treated with first-line immunotherapy, particularly in those with brain metastases at treatment initiation.This was a national, retrospective, multicenter study that consecutively included all patients with PD-L1-positive (tumor proportion score ≥ 50%) advanced NSCLC who initiated first-line treatment with pembrolizumab as a single agent between May 2017 (date of availability of pembrolizumab in this indication in France) to November 22, 2019 (approval of the pembrolizumab-chemotherapy combination). Data were collected from medical records with local response assessment.The cohort included 845 patients and 176 (20.8%) had brain metastases at diagnosis. There were no significant differences in outcomes for patients with and without brain metastases: 9.2 (95% CI 5.6-15) and 8 (95% CI 6.7-9.2, p = 0.3) months for median progression-free survival (PFS) and, 29.5 (95% CI 17.2-NA) and 22 (95% CI 17.8-27.1, p = 0.3) months for median overall survival (OS), respectively. Overall response rates were 47% and 45% in patients with and without cerebral metastases. In multivariate analysis, performance status 2-4 vs. 0-1 and neutrophil-to-lymphocyte ratio ≥ 4 vs. 4 were the main independent negative factors for OS; brain metastasis was not an independent factor for OS.In this large multicenter cohort, nearly 20% of patients initiating pembrolizumab therapy for advanced NSCLC had cerebral metastases. There was no significant difference in response rates, PFS and OS between patients with and without brain metastases.

Background Patient hospitalized for coronavirus disease 2019 (COVID-19) pulmonary infection can have sequelae such as impaired exercise capacity. We aimed to determine the frequency of long-term exercise capacity limitation in survivors of severe COVID-19 pulmonary infection and the factors associated with this limitation. Methods Patients with severe COVID-19 pulmonary infection were enrolled 3 months after hospital discharge in COVulnerability, a prospective cohort. They underwent cardiopulmonary exercise testing, pulmonary function test, echocardiography, and skeletal muscle mass evaluation. Results Among 105 patients included, 35% had a reduced exercise capacity (VO2peak CO (p = 0.015). Moreover, we uncovered a decrease of muscular mass index and grip test in the reduced exercise capacity group (p = 0.001 and p = 0.047 respectively), whilst 38.9% of patients with low exercise capacity had a sarcopenia, compared to 10.9% in those with normal exercise capacity (p = 0.001). Myocardial function was normal with similar systolic and diastolic parameters between groups whilst reduced exercise capacity was associated with a slightly shorter pulmonary acceleration time, despite no pulmonary hypertension. Conclusion Three months after a severe COVID-19 pulmonary infection, more than one third of patients had an impairment of exercise capacity which was associated with a reduced pulmonary function, a reduced skeletal muscle mass and function but without any significant impairment in cardiac function.

Background Previous studies have yielded inconsistent findings regarding the association between OSA and cancer in humans. Research Question Is there an association between indexes of sleep-disordered breathing severity and cancer incidence in patients investigated for suspected OSA? Study Design and Methods Data from a large multicenter cohort of cancer-free patients investigated for OSA were linked to health administrative data to identify new-onset cancer. Kaplan-Meier survival analysis and Cox proportional hazards models were used to evaluate the association of cancer incidence with OSA severity and nocturnal hypoxemia. Results After a median follow-up period of 5.8 years (interquartile range, 3.8-7.8), 718 of 8,748 patients (8.2%) had received a diagnosis of cancer. On unadjusted Kaplan-Meier survival analyses, cancer incidence was associated with increasing severity of OSA (log-rank test, P Interpretation Nocturnal hypoxemia was associated with all-cancer incidence in patients investigated for OSA. Whether OSA therapy might reduce the risk of cancer needs further evaluation.

Previous studies have yielded inconsistent findings regarding the association between OSA and cancer in humans.Is there an association between indexes of sleep-disordered breathing severity and cancer incidence in patients investigated for suspected OSA?Data from a large multicenter cohort of cancer-free patients investigated for OSA were linked to health administrative data to identify new-onset cancer. Kaplan-Meier survival analysis and Cox proportional hazards models were used to evaluate the association of cancer incidence with OSA severity and nocturnal hypoxemia.After a median follow-up period of 5.8 years (interquartile range, 3.8-7.8), 718 of 8,748 patients (8.2%) had received a diagnosis of cancer. On unadjusted Kaplan-Meier survival analyses, cancer incidence was associated with increasing severity of OSA (log-rank test, P .0005) and nocturnal hypoxemia (log-rank test, P .0001 for both oxygen desaturation index and percent night time with oxygen saturation 90% [T90]). After adjustment for anthropomorphic data, smoking and alcohol consumption, comorbid cardiac, metabolic, and respiratory diseases, marital status, type of sleep study, and study site, only T90 was associated with cancer incidence (adjusted hazard ratio, 1.33; 95% CI, 1.05-1.68 for T90 ≥ 13% vs 0.01%; P = .02). On stratified analyses, the association between T90 and cancer appeared stronger in older patients with obesity and no adequate OSA therapy. Among the most frequent cancer sites, nocturnal hypoxemia was associated with lung and breast malignancies.Nocturnal hypoxemia was associated with all-cancer incidence in patients investigated for OSA. Whether OSA therapy might reduce the risk of cancer needs further evaluation.

Introduction Les etudes en population clinique ont montre des resultats heterogenes concernant l’association entre le syndrome d’apnee obstructive du sommeil (SAOS) et le cancer. Notre objectif est de determiner si l’incidence du cancer est associee a la severite du SAOS et aux indices d’hypoxemie nocturne. Methodes L’etude est realisee sur les donnees de la cohorte multicentrique sur le syndrome d’apnees obstructives du sommeil des Pays de la Loire, dont les patients ont ete enquetes pour suspicion de SAOS de 2007 a 2015, appariees aux donnees du programme de medicalisation des systemes d’information (PMSI). Le critere de jugement principal de l’etude correspond a « toutes les tumeurs malignes » codes de C00 a C97. L’estimation des courbes de survie avec la methode de Kaplan–Meier et des risques proportionnels de Cox ont ete utilises pour evaluer l’association entre l’incidence du cancer, les categories de severite du SAOS et les indices d’hypoxemie nocturne. Les valeurs manquantes ont ete imputees a l’aide d’une methode d’imputation multiple. Resultats Apres un suivi median [intervalle interquartile] de 5,8 [3,8 a 7,8] annees, 718 patients sur 8748 (8,2 %) ont recu un diagnostic de cancer apres inclusion dans la cohorte sommeil. Les tests du log-rank non-ajustes montrent une association entre l’incidence du cancer et l’augmentation de la gravite du SAOS (p Discussion/Conclusion En conclusion, la severite de l’hypoxie nocturne mesuree par T90 est independamment associee a l’incidence du cancer dans cette large cohorte multicentrique de patients etudies pour suspicion de SAOS.

Objectif Les donnees experimentales suggerent que l’hypoxemie intermittente resultant des apnees du sommeil pourrait contribuer au developpement et la progression du cancer. Cependant les resultats des etudes cliniques sont contradictoires. L’objectif de cette vaste etude etait de determiner si l’incidence du cancer est associee avec la severite du SAHOS et les indices d’hypoxemie nocturne (index de desaturations en oxygene [ODI] et temps de sommeil au-dessous de 90 % de SaO2 [T90]) apres ajustement sur les facteurs de risque de cancer. Methodes Les donnees de 8,748 patients de la cohorte sommeil des Pays de la Loire, sans antecedent carcinologique, investigues (PSG ou PV) pour suspicion de SAHOS, ont ete appariees a celles Systeme National d’Information Inter-Regimes de l’Assurance Maladie [SNIIRAM] pour detecter les cancer incidents selon un algorithme developpe par l’INCA. Resultats Apres un suivi median de 5,8 [3,8–7,8] ans, 718 patients (8,2 %) avaient recu un diagnostic de cancer. En analyse univariee (Log Rank Test) la severite du SAHOS, l’ODI et le T90 etaient lies a l’incidence du cancer. Cependant, apres justement (modele de Cox), seul le T90 predisait le risque de cancer (HR [95 % CI] 1,47 [1,17–1,86] si T90 > 13 % vs Conclusion Le T90 predit le risque de cancer chez les patients avec SAHOS.