K-ras oncogene mutation as a prognostic marker in non-small cell lung cancer: a combined analysis of 881 cases

The treatment of non-small cell lung cancer (NSCLC) remains unsatisfactory, with most patients succumbing to metastatic disease within 5 years of diag nosis. Improved selection of patients for aggressive adjuvant therapy may c ontribute to improved survival. Mutation of the k-ras oncogene is considere d a potentially clinically useful prognostic biomarker for this purpose. Th is report presents the results of a meta-analysis performed to determine wh ether the existing data support such a role for k-ras mutations in NSCLC. T wo year survival data derived from 881 NSCLC patients in eight published st udies were analyzed using a general variance-based meta-analytical method e mploying confidence intervals. The outcome of interest was a summary relati ve risk (RI,) reflecting the risk of death at 2 years associated with k-ras mutation-positive versus k-ras mutation-negative disease. Prior to calcula tion of RR,, analysis for heterogeneity showed Q to equal 15.52 (7 df, P = 0.03). This indicated heterogeneity across the analyzed studies in terms of their estimate of effect. Possible sources of heterogeneity were identifie d and included selection bias and various other sources of uncontrolled con founding. Although a RR, of 2.35 (95 % CI = 1.61-3.22) was found when all e ight studies were combined (favoring a negative prognostic role for k-ras m utation), it is unclear whether the magnitude of the RR, would persist afte r adjusting for other well-established prognostic indicators (e.g. stage). The existing data suggest that k-ras mutation may be associated with shorte ned survival in NSCLC, although this finding awaits confirmation in well-de signed multivariate analyses which adjust for the effect of known prognosti c indicators.