Routine molecular profiling of cancer: results of a one-year nationwide program of the French Cooperative Thoracic Intergroup (IFCT) for advanced non-small cell lung cancer (NSCLC) patients.

International audienceBackground: The molecular profiling of patients with advanced non-small-cell lung cancer (NSCLC) for known oncogenic drivers is recommended during routine care. Nationally, however, the feasibility and effects on outcomes of this policy are unknown. We aimed to assess the characteristics, molecular profiles, and clinical outcomes of patients who were screened during a 1-year period by a nationwide programme funded by the French National Cancer Institute. Methods This study included patients with advanced NSCLC, who were routinely screened for EGFR mutations, ALK rearrangements, as well as HER2 (ERBB2), KRAS, BRAF, and PIK3CA mutations by 28 certified regional genetics centres in France. Patients were assessed consecutively during a 1-year period from April, 2012, to April, 2013. We measured the frequency of molecular alterations in the six routinely screened genes, the turnaround time in obtaining molecular results, and patients' clinical outcomes. This study is registered with ClinicalTrials.gov, number NCT01700582. Findings 18 679 molecular analyses of 17 664 patients with NSCLC were done (of patients with known data, median age was 64·5 years [range 18–98], 65% were men, 81% were smokers or former smokers, and 76% had adenocarcinoma). The median interval between the initiation of analysis and provision of the written report was 11 days (IQR 7–16). A genetic alteration was recorded in about 50% of the analyses; EGFR mutations were reported in 1947 (11%) of 17 706 analyses for which data were available, HER2 mutations in 98 (1%) of 11 723, KRAS mutations in 4894 (29%) of 17 001, BRAF mutations in 262 (2%) of 13 906, and PIK3CA mutations in 252 (2%) of 10 678; ALK rearrangements were reported in 388 (5%) of 8134 analyses. The median duration of follow-up at the time of analysis was 24·9 months (95% CI 24·8–25·0). The presence of a genetic alteration affected first-line treatment for 4176 (51%) of 8147 patients and was associated with a significant improvement in the proportion of patients achieving an overall response in first-line treatment (37% [95% CI 34·7–38·2] for presence of a genetic alteration vs 33% [29·5–35·6] for absence of a genetic alteration; p=0·03) and in second-line treatment (17% [15·0–18·8] vs 9% [6·7–11·9]; p<0·0001). Presence of a genetic alteration was also associated with improved first-line progression-free survival (10·0 months [95% CI 9·2–10·7] vs 7·1 months [6·1–7·9]; p<0·0001) and overall survival (16·5 months [15·0–18·3] vs 11·8 months [10·1–13·5]; p<0·0001) compared with absence of a genetic alteration. Interpretation Routine nationwide molecular profiling of patients with advanced NSCLC is feasible. The frequency of genetic alterations, acceptable turnaround times in obtaining analysis results, and the clinical advantage provided by detection of a genetic alteration suggest that this policy provides a clinical benefit

Admission of advanced lung cancer patients to intensive care unit: A retrospective study of 76 patients

<p>Abstract</p> <p>Background</p> <p>Criteria for admitting patients with incurable diseases to the medical intensive care unit (MICU) remain unclear and have ethical implications.</p> <p>Methods</p> <p>We retrospectively evaluated MICU outcomes and identified risk factors for MICU mortality in consecutive patients with advanced lung cancer admitted to two university-hospital MICUs in France between 1996 and 2006.</p> <p>Results</p> <p>Of 76 included patients, 49 had non-small cell lung cancer (stage IIIB n = 20; stage IV n = 29). In 60 patients, MICU admission was directly related to the lung cancer (complication of cancer management, n = 30; cancer progression, n = 14; and lung-cancer-induced diseases, n = 17). Mechanical ventilation was required during the MICU stay in 57 patients. Thirty-six (47.4%) patients died in the MICU. Three factors were independently associated with MICU mortality: use of vasoactive agents (odds ratio [OR] 6.81 95% confidence interval [95%CI] [1.77-26.26], p = 0.005), mechanical ventilation (OR 6.61 95%CI [1.44-30.5], p = 0.015) and thrombocytopenia (OR 5.13; 95%CI [1.17-22.5], p = 0.030). In contrast, mortality was lower in patients admitted for a complication of cancer management (OR 0.206; 95%CI [0.058-0.738], p = 0.015). Of the 27 patients who returned home, four received specific lung cancer treatment after the MICU stay.</p> <p>Conclusions</p> <p>Patients with acute complications of treatment for advanced lung cancer may benefit from MCIU admission. Further studies are necessary to assess outcomes such as quality of life after MICU discharge.</p

Tumeur bénigne à cellules claires du poumon "tumeur sucre" (à propos d'un cas et revue de la littérature)

CAEN-BU Médecine pharmacie (141182102) / SudocPARIS-BIUM (751062103) / SudocSudocFranceF

Valeur pronostique du test de marche de six minutes dans le cancer bronchique non à petites cellules localement avancé ou métastatique

CAEN-BU Médecine pharmacie (141182102) / SudocSudocFranceF

Chemotherapy in elderly patients with advanced non-small cell lung cancer.

International audienceBecause of increasing life expectancy and of higher risk of cancer with ageing, lung cancer in elderly is a frequent disease. For a long time nihilism influenced treatment decisions in elderly patients with advanced non-small cell lung cancer. Since the beginning of the last decade single agent chemotherapy has been accepted as standard of care, vinorelbine and gemcitabine being the most frequently used drugs in Europe and US, docetaxel in Japan. Platinum-based doublets have been shown to be superior to monotherapy in young and fit patients with advanced non-small cell lung cancer. Although there were some indications from subgroup analyses of clinical trials not specifically dedicated to elderly patients that a platinum-based doublet might also benefit to older patients, there was no definitive proof of concept until ASCO meeting 2010. At this meeting results of a phase 3 trial showed that PS 0-2 patients, aged 70-89 years drove a significant benefit from a treatment with carboplatin associated to weekly paclitaxel compared to a monotherapy. Thus, the paradigm of treatment in elderly patients should perhaps be modified from a single agent to doublet chemotherapy. Whether other platinum-based doublets would provide the same benefit as the specific one studied remains to be evaluated

RASSF1A, puppeteer of cellular homeostasis, fights tumorigenesis and metastasis - An 1 updated review

CERVOXYInternational audienceThe Ras association domain family protein1 isoform A (RASSF1A) is a well-known tumor-suppressor protein frequently inactivated in various human cancers. Consistent with its function as a molecular scaffold protein, referred to in many studies, RASSF1A prevents initiation of tumorigenesis, growth, and dissemination through different biological functions, including cell cycle arrest, migration/metastasis inhibition, microtubular stabilization, and apoptosis promotion. As a regulator of key cancer pathways, namely Ras/Rho GTPases and Hippo signaling without ignoring strong interaction with microtubules, RASSF1A is indeed one of the guardians of cell homeostasis. To date, as we approach the two decade anniversary of RASSF1A's discovery, this review will summarize our current knowledge on the RASSF1A key interactions as a tumor suppressor and discuss their impact on cell fate during carcinogenesis. This could facilitate a deeper understanding of tumor development and provide us with new strategies in cancer treatment by targeting the RASSF1A pathway

Predictive biomarkers in patients with resected non-small cell lung cancer treated with perioperative chemotherapy

International audienceThe aim of this article is to summarise the published data on prognostic and predictive biomarkers for early-stage non-small cell lung cancer (NSCLC), and discuss how to integrate them into clinical trials. Large phase III trials have been published in resected NSCLC with biomarkers identifying subsets of patients benefitting from perioperative chemotherapy. Initial findings of predictive implications for the DNA repair protein, ERCC1, were not confirmed in a larger series of patients due to the versatility of the commercially available monoclonal ERCC1 antibody. Prediction of survival by RRM1 tumour expression was not confirmed in a prospective phase III trial in 275 patients with stage IV disease, precluding its use in early-stage NSCLC. BRCA1 mRNA tumour content also failed to predict platinum resistance in 287 stage IV NSCLC patients included in a phase II trial, and the results of a similar trial in early-stage patients are still pending. Of the several cDNA gene expression studies in early-stage NSCLC with non-overlapping prognostic signatures, few have been replicated in independent cohorts for prognostic value, and none received external validation for predictive value. Therefore, use of biomarkers predicting chemotherapy efficacy still needs additional validation before becoming routine practice in oncogene-driven pan-negative NSCLC patients