TWIST1 a New Determinant of Epithelial to Mesenchymal Transition in EGFR Mutated Lung Adenocarcinoma

Metastasis is a multistep process and the main cause of mortality in lung cancer patients. We previously showed that EGFR mutations were associated with a copy number gain at a locus encompassing the TWIST1 gene on chromosome 7. TWIST1 is a highly conserved developmental gene involved in embryogenesis that may be reactivated in cancers promoting both malignant conversion and cancer progression through an epithelial to mesenchymal transition (EMT). The aim of this study was to investigate the possible implication of TWIST1 reactivation on the acquisition of a mesenchymal phenotype in EGFR mutated lung cancer. We studied a series of consecutive lung adenocarcinoma from Caucasian non-smokers for which surgical frozen samples were available (n = 33) and showed that TWIST1 expression was linked to EGFR mutations (P<0.001), to low CDH1 expression (P<0.05) and low disease free survival (P = 0.044). To validate that TWIST1 is a driver of EMT in EGFR mutated lung cancer, we used five human lung cancer cell lines and demonstrated that EMT and the associated cell mobility were dependent upon TWIST1 expression in cells with EGFR mutation. Moreover a decrease of EGFR pathway stimulation through EGF retrieval or an inhibition of TWIST1 expression by small RNA technology reversed the phenomenon. Collectively, our in vivo and in vitro findings support that TWIST1 collaborates with the EGF pathway in promoting EMT in EGFR mutated lung adenocarcinoma and that large series of EGFR mutated lung cancer patients are needed to further define the prognostic role of TWIST1 reactivation in this subgroup

Relation entre état nutritionnel et dose-intensité de chimiothérapie chez les patients atteints de cancer

L objectif de cette étude était de rechercher une association entre état nutritionnel et dose-intensité de chimiothérapie (DI). Il s agit d une étude rétrospective de patients (pts) traités par une association gemcitabine oxaliplatine (GEMOX), ou paclitaxel et carboplatine (CP) de 2006 à 2010. La dénutrition était définie par un IMC 10% ou une albuminémie <35g/L. Groupe CP (N=45) : La médiane d âge était de 62 ans [35,1-84,0], 54% avaient un PS <=1, 38% avaient une maladie localement avancée, 40% étaient dénutris. La DI médiane était de 0,88 [0,17-1,03]. Il n y avait pas d association significative entre la DI et les autres paramètres.Groupe GEMOX (N=165) : La médiane d âge était de 61ans [29.0-84.3], 71% avaient un PS <=1, 52% étaient dénutris. La DI médiane était de 0,90 [0,17-1,04]. La DI et la perte de poids durant le traitement étaient négativement corrélées (r=-0,24 ; p=0,016). Le PS, la CRP et l albuminémie étaient plus élevé (p=0,0098), plus élevée (p=0,027) et plus basse (p=0,027) chez les patients ayant reçu moins de 2 cycles de chimiothérapie.La dénutrition contribue à l altération du PS et elle est associée à une réduction de DI. Des études interventionnelles évaluant une prise en charge nutritionnelle précoce et ciblée sont nécessaires afin d améliorer la faisabilité de la chimiothérapie anticancéreuse chez les patients atteints de cancer.PARIS6-Bibl.Pitié-Salpêtrie (751132101) / SudocSudocFranceF

How did we take care of our older cancer patients during the first COVID-19 wave? The French experience

International audienceBACKGROUND: The management of older cancer patients has been highly challenging for clinicians in a health-care system operating at maximum capacity during the COVID-19 pandemic. PATIENTS AND METHODS: We analyzed data from 9 different institutions. The primary endpoint was to assess the prevalence of adapted patient care during the pandemic for elderly cancer patients. The secondary endpoint was to assess the incidence of hospitalization and mortality due to COVID-19. All patients were older than 65years of age. RESULTS: We analyzed data from 332 outpatients’ case files between 9th of March and 30th of April 2020. The median age was 75years (range: 65-101) and 53% were male. Because of the COVID-19 pandemic, more than half of the outpatients received modified patient care, defined as postponement or cancellation of surgery, irradiation scheme adapted, systemic treatment or the use of telemedicine. Among patients with localized cancer, 60% had a change in management strategy due to the pandemic. Changes in management strategy were made for 53% of patients at the metastatic stage. GCSF was used , in 83% of patients, increasing considerably in the context of the pandemic. Sixty-nine percent of physicians used telemedicine. In the final analysis, only one patient was hospitalized for COVID-19 infection. No deaths due to COVID-19 were reported in elderly cancer patients during this time period. CONCLUSION: Our study is the first to assess modification of patient care in elderly cancer outpatients during an epidemic. With this unprecedented crisis, our objective is to protect our patients from infection via protective barrier measures and social distancing, but also to guarantee the continuity of cancer care without overexposing this fragile population. Physicians were able to adapt their practice and used new forms of management, like telemedicine