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

Variability and Action Mechanism of a Family of Anticomplement Proteins in Ixodes ricinus

Background: Ticks are blood feeding arachnids that characteristically take a long blood meal. They must therefore counteract host defence mechanisms such as hemostasis, inflammation and the immune response. This is achieved by expressing batteries of salivary proteins coded by multigene families. Methodology/Principal Findings: We report the in-depth analysis of a tick multigene family and describe five new anticomplement proteins in ixodes ricinus. Compared to previously described Ixodes anticomplement proteins, these segregated into a new phylogenetic group or subfamily. These proteins have a novel action mechanism as they specifically bind to properdin, leading to the inhibition of C3 convertase and the alternative complement pathway. An excess of non-synonymous over synonymous changes indicated that coding sequences had undergone diversifying selection. Diversification was not associated with structural, biochemical o, functional diversity, adaptation to host species or stage specificity but rather to differences in antigenicity. Conclusion/Significance: Anticomplement proteins from I. ricinus are the first inhibitors that specifically target a positive regulator of complement, properdin. They may provide new tools for the investigation of role of properdin in physiological and pathophysiological mechanisms. They may also be useful in disorders affecting the alternative complement pathway, Looking for and detecting the different selection pressures involved will help in understanding the evolution of multigene families and hematophagy in arthropods. © 2008 Couveur et al.Journal ArticleResearch Support, Non-U.S. Gov'tSCOPUS: ar.jinfo:eu-repo/semantics/publishe

Les recommandations médicales (application à la prescription de l'albumine, des anti 5 HT3 et des G-CSF à l'Hôpital Tenon)

PARIS-BIUP (751062107) / SudocSudocFranceF

Valeur pronostique de la tomographie par émission de positons au FDG-(18F) lors du bilan initial des cancers bronchiques non à petites cellules de stade I et II

Introduction : L'intensité de fixation du FDG-(18F), mesurée sous forme de standardized uptake value (SUV) lors d'une tomographie par émission de positons (TEP), est corrélée au métabolisme tumoral. L'objectif de ce travail a été d'évaluer la valeur pronostique de cet indice (SUV), lors du diagnostic initial et avant tout traitement, dans le cancer bronchique non à petites cellules (CBNPC) de stade I et II. Patients et méthodes : Ont été étudiés, en rétrospectif à partir d'un fichier prospectif, tous les patients ayant présenté, du 01/01/2000 au 31/12/2003, un CBNPC de stade I ou II, opérable, et évalué par TEP lors du bilan d'extension initial. La valeur maximale du SUV de la tumeur primitive a été testée en terme de survie globale et de survie sans récidive, selon une valeur seuil établie par courbe ROC. Résultats : La médiane de suivi des 62 patients retenus est de 25 mois. En analyse univariée, un SUV maximum supérieur à 10,9 est associé à une diminution de la survie globale (p=0,0085) et de la survie sans récidive (p=0,0071). En analyse multivariée, un SUV maximum supérieur à 10,9 multiplie le risque de récidive par 2,3 (p=0,0224) indépendamment du stade tumoral. Ce risque est multiplié par 4,6 pour un CBNPC de stade II par comparaison à un stade I (p=0,0001). La valeur pronostique péjorative d'un SUV maximum élevé lors du diagnostic est bien démontrée dans les stades II (p=0,0182). Elle doit être confirmée dans les stades I. Conclusion : Dans les CBNPC de stades I et II, un SUV maximum élevé en préthérapeutique est prédictif de récidive, après exérèse chirurgicale, indépendamment du stade TNMIntroduction: FDG-(18F) uptake, represented by standardized uptake value (SUV) and determined by positron emission tomography (PET), is correlated with tumor metabolism. This review aimed at determining if the SUV, measured at diagnosis and before treatment, was a prognostic factor in early stage non-small cell lung cancer (NSCLC). Patients and Methods :This was a retrospective review of a prospective database. All patients with a stage I or II NSCLC who underwent PET at diagnosis and who were surgically treated between 01/01/2000 and 31/12/2003 were included. The cutoff point of maximum SUV for the primary tumor was calculated by using receiver operating characteristics curves. Overall survival and disease-free survival were analyzed. Results: Sixty two patients were included and the median follow-up was 25 months. In univariate analysis, a maximum SUV higher than 10,9 was correlated with a poorer overall survival (p=0,0085) and a poorer disease-free survival (p=0,0071). In multivariate analysis, a maximum SUV higher than 10,9 and the TNM stage were significant and independent predictive factors of recurrence (p=0,0224 and p=0,0001 respectively). The prognosis value of maximum SUV for disease-free survival was demonstrated in stage II (p=0,0182) but not in stage I. Conclusion: A high maximum SUV at diagnosis, measured by FDG-(18F) PET is predictive of recurrence in patients with surgically resected in early stage NSCLC, independently of TNM stagePARIS12-CRETEIL BU Médecine (940282101) / SudocPARIS-BIUM (751062103) / SudocSudocFranceF

Le cancer bronchique.

Editorialinfo:eu-repo/semantics/publishe

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

Impact of guidelines implemented in a paris university hospital: application to the use of antiemetics by cancer patients

AIMS: To assess the impact with time of guidelines on antiemetic use in an 850-bed Paris university hospital with a high proportion of cancer patients. METHODS: Guidelines on the use of antiemetics available in cancer chemotherapy were drafted according to the Delphi technique. Their implementation was based upon a patient-specific antiemetic prescription form. To assess the impact of guideline implementation over time, discrepancies between current practice and the guidelines were compared before guideline implementation (between March and August 1995) and after implementation (between March and August 1997, and March and August 1998). RESULTS: Before the Delphi panel’s guidelines were implemented, 5-HT(3) antagonists were inappropriately administered in 70% of cases. After guideline implementation, this proportion dropped significantly (P <0.0001, Fisher’s exact test) to 22% between March and August 1997 and 28% between March and August 1998. CONCLUSIONS: Implementation of guidelines seems to have resulted in significant changes with time, although a causal relationship has not been demonstrated. The development of guidelines by our hospital’s multidisciplinary working group helped the various consultants to adjust medical practices to take account of these changes

Cancer bronchique non à petites cellules localement évolué: place de la chimioradiothérapie exclusive

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