M. Huncharek et al., K-ras oncogene mutation as a prognostic marker in non-small cell lung cancer: a combined analysis of 881 cases, CARCINOGENE, 20(8), 1999, pp. 1507-1510
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.