Asunto(s)
Carcinoma de Pulmón de Células no Pequeñas/tratamiento farmacológico , Carcinoma de Pulmón de Células no Pequeñas/genética , Receptores ErbB/genética , Exones , Neoplasias Pulmonares/tratamiento farmacológico , Neoplasias Pulmonares/genética , Mutación , Inhibidores de Proteínas Quinasas/uso terapéutico , Receptores ErbB/antagonistas & inhibidores , Femenino , Humanos , Masculino , Persona de Mediana Edad , Terapia Molecular DirigidaRESUMEN
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.
Asunto(s)
Adenocarcinoma/genética , Carcinoma de Pulmón de Células no Pequeñas/genética , Reordenamiento Génico , Neoplasias Pulmonares/genética , Proteínas Tirosina Quinasas Receptoras/genética , Adenocarcinoma/metabolismo , Adenocarcinoma/patología , Adulto , Anciano , Análisis de Varianza , Quinasa de Linfoma Anaplásico , Antineoplásicos/uso terapéutico , Carcinoma de Pulmón de Células no Pequeñas/metabolismo , Carcinoma de Pulmón de Células no Pequeñas/patología , Crizotinib , Supervivencia sin Enfermedad , Femenino , Humanos , Neoplasias Pulmonares/metabolismo , Neoplasias Pulmonares/patología , Masculino , Persona de Mediana Edad , Análisis Multivariante , Proteínas Nucleares/metabolismo , Estudios Prospectivos , Inhibidores de Proteínas Quinasas/uso terapéutico , Pirazoles/uso terapéutico , Piridinas/uso terapéutico , Factores de Riesgo , Factores Sexuales , Fumar/efectos adversos , Factor Nuclear Tiroideo 1 , Factores de Transcripción/metabolismoRESUMEN
The majority of bronchial and interstitial diseases of the adult are accompanied by bronchiolar inflammation, but over time the use of the term "bronchiolitis" has been limited to a few specific affections. Bronchiolitis with predominantly alveolar involvement Some "bronchiolites" emphasize the problem of an interstitial pneumopathy, since the disease predominantly involves the alveolar spaces. Only a few bronchiolites are severely damaging: bronchiolitis obliterans with organizing pneumonia and interstitial pneumopathy with respiratory bronchiolitis. These predominantly alveolar affections reveal the clinical (crepitant rales), radiographic (multiple or even diffuse opacities), and functional aspects (restrictive ventilation problems). Brochiolitis with obstructive airway problems In this case the disease predominantly involves the bronchioles and spares the alveolar tissue. The term "bronchiolitis" is in this case perfectly justified. The clinical picture is evocative with obstructed airway and a clear pulmonary parenchyma on the thoracic x-ray. These affections belong to the obstructive broncho-pneumopathy group. The prototype is brochiolitis obliterans, the anatomic correlation of which is generally constrictive bronchiolitis obliterans. Occasionally primitive, it frequently complicates the progression of many morbid states (transplants, collagenosis, inhaled or ingested toxic substances.). Diffuse panbronchiolitis Other "bronchiolites" deviate from this framework and are accompanied by marked lesions of other respiratory tracts (membrane bronchioles, cartilage bronchi, mucosa, ear nose and throat). The prototype is panbronchiolitis, described in the Far East. It is exceptional in Europe, where similar but nosologically different clinical aspects are observed during various diseases: cystic fibrosis, Young's syndrome, hypogammaglobulinemia, bone marrow transplant, context of HIV or haemorrhagic recto-colitis.