A systems pathology model for predicting overall survival in patients with refractory, advanced non-small-cell lung cancer treated with gefitinib

Purpose: To identify clinical and biometric features associated with overall survival of patients with advanced refractory non-small-cell lung cancer (NSCLC) treated with gefitinib. Experimental design: 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. (C) 2009 Elsevier Ltd. All rights reserved.