title: Phenotypic heterogeneity of potentially curable non-small-cell lung cancer: cohort study with cluster analysis.
abstract: BACKGROUND
  Significant differences in outcome are observed among lung cancer patients belonging to the same tumor node metastasis stage, suggesting phenotypic heterogeneity beyond this staging algorithm. We used a cluster analysis approach to classify patients into distinct phenotypes, and we attempted to validate the clinical relevance of these phenotypes by comparing outcome.
  
  
  METHODS
  We formed a cohort of all stage I to III non-small-cell lung cancer patients seen between January 2004 and October 2010 in a cancer center and followed until death or last follow-up appointment, with prospectively collected data on clinical and tumor characteristics. Multiple correspondence analysis was followed by hierarchical clustering to form homogenous clusters of patients. Overall survival and disease-free survival estimates were compared among clusters.
  
  
  RESULTS
  The cohort included 367 patients (mean follow-up of 2.5 years), 173 of whom died during that period (191 deaths per 1000 person-years). A four-cluster model was identified, revealing distinct phenotypes with respect to baseline characteristics. Hazard ratios for mortality were 8.1, 5.0, and 3.7 (all statistically significant) for clusters 2, 1, and 3, respectively, when compared with cluster 4-with the most favorable outcome.
  
  
  CONCLUSIONS
  Staging of patients with non-small-cell lung cancer for prognostic purposes may be improved by considering phenotypes that exhibit significant differences in clinical course and outcome.
authors.affiliation: Division of Pulmonary Diseases, Department of Medicine, Jewish General Hospital, McGill University, Quebec, Canada. Electronic address: lama.sakr@mail.mcgill.ca.
authors.forename: Lama
authors.initials: L
authors.lastname: Sakr
authors.affiliation: Division of Pulmonary Diseases, Department of Medicine, Jewish General Hospital, McGill University, Quebec, Canada.
authors.forename: David
authors.initials: D
authors.lastname: Small
authors.affiliation: Peter Brojde Lung Cancer Centre, Jewish General Hospital, Montreal, Quebec, Canada.
authors.forename: Goulnar
authors.initials: G
authors.lastname: Kasymjanova
authors.affiliation: Department of Epidemiology and Biostatistics, McGill University, Quebec, Canada; Center for Clinical Epidemiology, Lady Davis Institute, Jewish General Hospital, McGill University, Montreal, Quebec, Canada.
authors.forename: Samy
authors.initials: S
authors.lastname: Suissa
authors.affiliation: Division of Pulmonary Diseases, Department of Medicine, Jewish General Hospital, McGill University, Quebec, Canada; Department of Epidemiology and Biostatistics, McGill University, Quebec, Canada; Center for Clinical Epidemiology, Lady Davis Institute, Jewish General Hospital, McGill University, Montreal, Quebec, Canada.
authors.forename: Pierre
authors.initials: P
authors.lastname: Ernst
mesh_terms: D000230:Adenocarcinoma / Q000737:chemistry / Q000473:pathology*; D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D002289:Carcinoma, Non-Small-Cell Lung / Q000145:classification / Q000401:mortality / Q000473:pathology*; D002294:Carcinoma, Squamous Cell / Q000473:pathology*; D002648:Child; D002675:Child, Preschool; D016000:Cluster Analysis; D015331:Cohort Studies; D018572:Disease-Free Survival; D005260:Female; D005500:Follow-Up Studies; D006304:Health Status; D006801:Humans; D007223:Infant; D007231:Infant, Newborn; D008175:Lung Neoplasms / Q000145:classification / Q000401:mortality / Q000473:pathology*; D008297:Male; D008875:Middle Aged; D015233:Models, Statistical; D009367:Neoplasm Staging; D009687:Nuclear Proteins / Q000032:analysis; D010641:Phenotype; D012737:Sex Factors; D012907:Smoking; D015996:Survival Rate; D000074482:Thyroid Nuclear Factor 1; D014157:Transcription Factors / Q000032:analysis; D016896:Treatment Outcome; D015431:Weight Loss; D055815:Young Adult
chemical_list: D009687:Nuclear Proteins; D000074482:Thyroid Nuclear Factor 1; D014157:Transcription Factors