OCTOMUT, étude observationnelle évaluant les modalités diagnostiques, thérapeutiques, de suivi et d'évolution des patients âgés de 80 ans et plus porteurs d'un cancer bronchique non à petites cellules avec mutation activatrice du gène de l'EGFR

Introduction: Nous présentons une étude rétrospective sur les patients de 80 ans et plus porteurs d'un CBNPC avec mutation activatrice de l'EGFR. Nous analysons les données épidémiologiques et l'utilisation des EGFR-TKI. Patients et méthode: Les plateformes de biologie moléculaire de Brest, Caen, Rennes et Nantes nous ont fournis la liste des patients de 80 ans et plus dont la recherche de mutation de l'EGFR était positive entre janvier 2010 et juin 2012. Nous avons contacté leurs médecins qui ont rempli des questionnaires les concernant. Résultats: Nous avons récupéré 44 dossiers. Il y a 73% de femmes, 73% de non-fumeurs, d'âge médian 84 ans, autonomes au domicile (93%). Ils sont porteurs d'adénocarcinomes (93%) métastatiques (80%). Les mutations retrouvées sont la délétion de l'exon 19 (52%) et les substitutions de l'exon 21 (48%). 34 patients ont bénéficié d'EGFR-TKI avec un taux de réponse globale de 90%. La SSI est de 12 mois et la SG est de 16 mois. 71% ont présenté des effets secondaires. Conclusion: Les patients de 80 ans porteurs d'un cancer muté EGFR peuvent bénéficier d'EGFR-TKI avecune bonne efficacité, au prix d'effets secondaires non négligeables.Introduction: We presented a retrospective study on patients aged 80 years or older with NSCLC harboring an activated mutation of EGFR. We analyzed epidemiologic, effect and tolerance of EFGR-TKI. Patients and methods: Listing of older patients was determined by biologic platforms of Rennes, Nantes, Brest and Caen. Theirs patricians were contacted to fill the form. Results: Between January 2010 and June 2012, 44 patients were enrolled. The median age was 84 years. 73% of patients were women, 73% were never smoked, 93% were self-ruling and 93% had adenocarcinoma. The disease control rate was 90%. The median progression-free survival was 12 months and the median overall survival was 16 months. The adverse events occurred at 71%. Conclusion: This study verified safety and efficacy of treatment with TKI-EGFR in elderly patients having NSCLC with EGFR mutation.RENNES1-BU Santé (352382103) / SudocSudocFranceF

Impact de la durée de séjour en maternité sur l'allaitement maternel et le recours aux soins maternels et pédiatriques (étude prospective au CHRU de Tours du 31/10/2010 au 08/09/2011)

TOURS-BU Médecine (372612103) / SudocSudocFranceF

EFGR-mutant lung adenocarcinoma and Li-Fraumeni syndrome: Report of two cases and review of the literature.

International audienceWe report two cases of non-smoker patients diagnosed with EGFR-mutated lung adenocarcinoma and bearing germinal TP53 gene mutation, also known as Li-Fraumeni syndrome (LFS). We describe for the first time an EGFR-TKI resistance mutation in this population. Finally, we provide an analysis of discerning epidemiological data obtained from the IARC database and from all the published cases of EGFR-mutated lung cancer in TP53 germline mutation carriers

Brief Report on the Efficacy of Nivolumab in Patients With Previously Treated Advanced Large-Cell Neuroendocrine Cancer of the Lung

International audienceINTRODUCTION: The optimal management of large cell neuroendocrine cancer of the lung (LCNEC) is unclear, and data regarding anti-programmed cell death protein 1 (PD-1) antibodies are scarce. This study reports the clinical efficacy of a PD-1 inhibitor in patients with advanced LCNEC. METHODS: All patients with stage III to IV LCNEC treated with at least one previous cycle of chemotherapy between January 1, 2015 and December 31, 2018 were reviewed retrospectively. Patients were divided into two groups depending on their exposure to nivolumab as second-line treatment or beyond. The primary objective was to assess nivolumab’s efficacy. RESULTS: A total of 51 patients with advanced LCNEC from eight centers were analyzed, including 17 who received nivolumab. The PD-1 inhibitor was used as second-line treatment in 77% of cases, with a median number of eight doses (range: 1-62). After nivolumab treatment, the median overall survival was 12.1 months (95% confidence interval [CI]: 7.10-14.20). The objective response rate was 29.4% (95% CI: 10.3-56.0), and median progression-free survival was 3.9 months (95% CI: 1.68-7.17). The programmed death-ligand 1 status was unknown. There was no difference in the efficacy of first-line chemotherapy; the objective response rate was 23.5% (n = four of 17) in the nivolumab group versus 32.4% (n = 11 of 34) in the conventional treatment group, and progression-free survival was 3.5 months (95% CI: 1.7-4.4) versus 2.1 months (95% CI: 1.4-4.2), respectively. CONCLUSIONS: In a real-world setting, nivolumab seems to be an effective second-line treatment in patients with advanced LCNEC. Large prospective studies in this setting are still required

ING2 tumor suppressive protein translocates into mitochondria and is involved in cellular metabolism homeostasis

International audienceING2 (Inhibitor of Growth 2) is a tumor suppressor gene that has been implicated in critical biological functions (cell-cycle regulation, replicative senescence, DNA repair and DNA replication), most of which are recognized hallmarks of tumorigenesis occurring in the cell nucleus. As its close homolog ING1 has been recently observed in the mitochondrial compartment, we hypothesized that ING2 could also translocate into the mitochondria and be involved in new biological functions. In the present study, we demonstrate that ING2 is imported in the inner mitochondrial fraction in a redox-sensitive manner in human cells and that this mechanism is modulated by 14-3-3 eta protein expression. Remarkably, ING2 is necessary to maintain mitochondrial ultrastructure integrity without interfering with mitochondrial networks or polarization. We observed an interaction between ING2 and mtDNA under basal conditions. This interaction appears to be mediated by TFAM, a critical regulator of mtDNA integrity. The loss of mitochondrial ING2 does not impair mtDNA repair, replication or transcription but leads to a decrease in mitochondrial ROS production, suggesting a detrimental impact on OXPHOS activity. We finally show using multiple models that ING2 is involved in mitochondrial respiration and that its loss confers a protection against mitochondrial respiratory chain inhibition in vitro. Consequently, we propose a new tumor suppressor role for ING2 protein in the mitochondria as a metabolic shift gatekeeper during tumorigenesis

Long-term effectiveness and treatment sequences in patients with extensive stage small cell lung cancer receiving atezolizumab plus chemotherapy: Results of the IFCT-1905 CLINATEZO real-world study

International audienceBackground: Small cell lung cancer (SCLC) has a tendency towards recurrence and limited survival. Standard-of-care in 1st-line is platinum-etoposide chemotherapy plus atezolizumab or durvalumab, based on landmark clinical trials. Methods: IFCT-1905 CLINATEZO is a nationwide, non-interventional, retrospective study of patients with extensive-SCLC receiving atezolizumab plus chemotherapy as part of French Early Access Program. Objectives were to analyse effectiveness, safety and subsequent treatments. Results: The population analyzed included 518 patients who received atezolizumab in 65 participating centers. There were 66.2% male, mean age was 65.7 years; 89.1% had a performance status (PS) 0/1 and 26.6% brain metastases. Almost all (95.9%) were smokers. Fifty-five (10.6%) received at least 1 previous treatment. Median number of atezolizumab injections was 7.0 (range [1.0–48.0]) for a median duration of 4.9 months (95% CI 4.5–5.1). Atezolizumab was continued beyond progression in 122 patients (23.6%) for a median duration of 1.9 months (95% CI: [1.4–2.3]). Best objective response was complete and partial in 19 (3.9%) and 378 (77.1%) patients. Stable disease was observed in 50 patients (10.2%). Median follow-up was 30.8 months (95% CI: [29.9–31.5]). Median overall survival (OS), 12-, 24-month OS rates were 11.3 months (95% CI: [10.1–12.4]), 46.7% (95% CI [42.3–50.9]) and 21.2% (95% CI [17.7–24.8]). Median real-world progression-free survival, 6-, 12-month rates were 5.2 months (95% CI [5.0–5.4]), 37.5% (95% CI [33.3–41.7]) and 15.2% (95% CI [12.2–18.6]). For patients with PS 0/1, median OS was 12.2 months (95% CI [11.0–13.5]). For patients with previous treatment, median OS was 14.9 months (95% CI [10.1–21.5]). Three-hundred-and-twenty-six patients (66.4%) received subsequent treatment and 27 (5.2%) were still under atezolizumab at date of last news. Conclusions: IFCT-1905 CLINATEZO shows reproductibility, in real-life, of IMpower-133 survival outcomes, possibly attributed to selection of patients fit for this regimen, adoption of pragmatic approaches, including concurrent radiotherapy and treatment beyond progression