title: Prospective screening for ALK: clinical features and outcome according to ALK status.
abstract: The aim of this study was to analyse the clinico-pathological characteristics and outcomes of a cohort of French patients who were prospectively screened for Anaplastic Lymphoma Kinase (ALK) rearrangement. One hundred and sixteen consecutive patients screened for ALK rearrangement to be recruited into a crizotinib registration trial were included from eight French centres. ALK rearrangement was detected by fluorescence in situ hybridization. Seventeen patients (14.6%) were positive for ALK. ALK+ patients were younger (p = 0.049) and more likely to be males (p=0.032), non- or light-smokers (p = 0.048) and without underlying respiratory disease (p=0.025) compared to ALK- patients. Thyroid-transcription factor-1 expression was present in all ALK+ tumours. ALK+ tumours tended to have lymph node and brain metastases. In multivariate analyses, gender, smoking history and N stage were independently associated with ALK status. Median overall survival (OS) was not reached for ALK+ patients and was significantly longer than for ALK- patients (hazard ratio for death for ALK- patients 2.98; 95% CI [1.29-6.90], p=0.01). French ALK+ patients present a specific phenotype. ALK rearrangement should be determined to improve OS with an effective targeted therapy.
authors.affiliation: GRC-04-Theranoscan, Université Pierre et Marie Curie, Paris, France; Service de Pneumologie, Hôpital Tenon APHP, Paris, France.
authors.forename: Vincent
authors.initials: V
authors.lastname: Fallet
authors.affiliation: GRC-04-Theranoscan, Université Pierre et Marie Curie, Paris, France; Service de Pneumologie, Hôpital Tenon APHP, Paris, France.
authors.forename: Jacques
authors.initials: J
authors.lastname: Cadranel
authors.affiliation: Service de Pneumologie, Hôpital Foch, Suresnes, France.
authors.forename: Hélène
authors.initials: H
authors.lastname: Doubre
authors.affiliation: Service de Pneumologie, Hôpital Tenon APHP, Paris, France.
authors.forename: Cécile
authors.initials: C
authors.lastname: Toper
authors.affiliation: Service de Pneumologie et Pathologie Professionnelle, Centre Hospitalier Intercommunal de Créteil, Créteil, France.
authors.forename: Isabelle
authors.initials: I
authors.lastname: Monnet
authors.affiliation: Service de Pneumologie, Hôpital Ambroise Paré APHP, Boulogne-Billancourt, France.
authors.forename: Thierry
authors.initials: T
authors.lastname: Chinet
authors.affiliation: Service de Pneumologie, Centre Hospitalier de Longjumeau, Longjumeau, France.
authors.forename: Gérard
authors.initials: G
authors.lastname: Oliviero
authors.affiliation: Service de Pneumologie, Hôpital Max Fourestier, Nanterre, France.
authors.forename: Guillaume
authors.initials: G
authors.lastname: Foulon
authors.affiliation: Service de Pneumologie, Centre Hospitalier d'Argenteuil, Argenteuil, France.
authors.forename: Hubert
authors.initials: H
authors.lastname: De Cremoux
authors.affiliation: GRC-04-Theranoscan, Université Pierre et Marie Curie, Paris, France.
authors.forename: Thibault
authors.initials: T
authors.lastname: Vieira
authors.affiliation: GRC-04-Theranoscan, Université Pierre et Marie Curie, Paris, France; Service d'Anatomo-Pathologie, Hôpital Tenon APHP, Paris, France.
authors.forename: Martine
authors.initials: M
authors.lastname: Antoine
authors.affiliation: GRC-04-Theranoscan, Université Pierre et Marie Curie, Paris, France; Service de Pneumologie, Hôpital Tenon APHP, Paris, France. Electronic address: marie.wislez@tnn.aphp.fr.
authors.forename: Marie
authors.initials: M
authors.lastname: Wislez
mesh_terms: D000230:Adenocarcinoma / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D000328:Adult; D000368:Aged; D000704:Analysis of Variance; D000077548:Anaplastic Lymphoma Kinase; D000970:Antineoplastic Agents / Q000627:therapeutic use; D002289:Carcinoma, Non-Small-Cell Lung / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D000077547:Crizotinib; D018572:Disease-Free Survival; D005260:Female; D015321:Gene Rearrangement; D006801:Humans; D008175:Lung Neoplasms / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D008297:Male; D008875:Middle Aged; D015999:Multivariate Analysis; D009687:Nuclear Proteins / Q000378:metabolism; D011446:Prospective Studies; D047428:Protein Kinase Inhibitors / Q000627:therapeutic use; D011720:Pyrazoles / Q000627:therapeutic use; D011725:Pyridines / Q000627:therapeutic use; D020794:Receptor Protein-Tyrosine Kinases / Q000235:genetics*; D012307:Risk Factors; D012737:Sex Factors; D012907:Smoking / Q000009:adverse effects; D000074482:Thyroid Nuclear Factor 1; D014157:Transcription Factors / Q000378:metabolism
chemical_list: D000970:Antineoplastic Agents; C000614412:NKX2-1 protein, human; D009687:Nuclear Proteins; D047428:Protein Kinase Inhibitors; D011720:Pyrazoles; D011725:Pyridines; D000074482:Thyroid Nuclear Factor 1; D014157:Transcription Factors; D000077547:Crizotinib; C000626173:ALK protein, human; D000077548:Anaplastic Lymphoma Kinase; D020794:Receptor Protein-Tyrosine Kinases
keywords: Adenocarcinoma; Crizotinib; EML4-ALK fusion protein; Lung neoplasms; Non-small-cell lung; Survival analysis