title: A systems pathology model for predicting overall survival in patients with refractory, advanced non-small-cell lung cancer treated with gefitinib.
abstract: OBJECTIVE
  To identify clinical and biometric features associated with overall survival of patients with advanced refractory non-small-cell lung cancer (NSCLC) treated with gefitinib.
  
  
  METHODS
  One hundred and nine diagnostic NSCLC samples were analysed for EGFR mutation status, EGFR immunohistochemistry, histologic morphometry and quantitative immunofluorescence of 15 markers. Support vector regression modelling using the concordance index was employed to predict overall survival.
  
  
  RESULTS
  Tumours from 4 of 87 patients (5%) contained EGFR tyrosine kinase domain mutations. A multivariate model identified ECOG performance status, and tumour morphometry, along with cyclin D1, caspase-3 activated, and phosphorylated KDR to be associated with overall survival, concordance index of 0.74 (hazard ratio (HR) 5.26, p-value 0.0002).
  
  
  CONCLUSIONS
  System-based models can be used to identify a set of baseline features that are associated with reduced overall survival in patients with NSCLC treated with gefitinib. This is a preliminary study, and further analyses are required to validate the model in a randomised, controlled treatment setting.
authors.affiliation: Aureon Laboratories, 28 Wells Avenue, Yonkers, NY 10701, USA.
authors.forename: Michael J
authors.initials: MJ
authors.lastname: Donovan
authors.forename: Angeliki
authors.initials: A
authors.lastname: Kotsianti
authors.forename: Valentina
authors.initials: V
authors.lastname: Bayer-Zubek
authors.forename: David
authors.initials: D
authors.lastname: Verbel
authors.forename: Mikhail
authors.initials: M
authors.lastname: Teverovskiy
authors.forename: Carlos
authors.initials: C
authors.lastname: Cordon-Cardo
authors.forename: Jose
authors.initials: J
authors.lastname: Costa
authors.forename: F Anthony
authors.initials: FA
authors.lastname: Greco
authors.forename: John D
authors.initials: JD
authors.lastname: Hainsworth
authors.forename: Dinah V
authors.initials: DV
authors.lastname: Parums
mesh_terms: D000368:Aged; D000970:Antineoplastic Agents / Q000627:therapeutic use*; D014408:Biomarkers, Tumor / Q000032:analysis; D002289:Carcinoma, Non-Small-Cell Lung / Q000188:drug therapy / Q000401:mortality / Q000473:pathology*; D053148:Caspase 3 / Q000032:analysis; D019938:Cyclin D1 / Q000032:analysis; D066246:ErbB Receptors / Q000032:analysis / Q000235:genetics; D005260:Female; D000077156:Gefitinib; D006801:Humans; D007150:Immunohistochemistry; D008175:Lung Neoplasms / Q000188:drug therapy / Q000401:mortality / Q000473:pathology*; D008297:Male; D008875:Middle Aged; D009154:Mutation; D011379:Prognosis; D016016:Proportional Hazards Models; D011799:Quinazolines / Q000627:therapeutic use*; D015996:Survival Rate
chemical_list: D000970:Antineoplastic Agents; D014408:Biomarkers, Tumor; D011799:Quinazolines; D019938:Cyclin D1; D066246:ErbB Receptors; D053148:Caspase 3; D000077156:Gefitinib