A gene expression platform to predict benefit from adjuvant external beam radiation in resected non-small cell lung cancer

ABSTRACT Background We hypothesized that the radiosensitivity index (RSI), would classify non-small cell lung cancer (NSCLC) patients into radioresistant (RR) or radiosensitive (RS). Methods We identified resected pathologic stage III NSCLC. For the radiation group (RT) group, at least 45 Gy of external beam radiation was required. mRNA was extracted from primary tumor. The predefined cut-point was the median RSI with a primary endpoint of local control. Similar criteria were then applied to two extramural datasets (E1; E2) with progression free survival as the primary endpoint. Results Median follow-up from diagnosis was 23.5 months (range: 4.8-169.6 months). RSI was associated with time to local failure in the RT group with a two-year rate of local control of 80% and 56% between RS and RR groups, respectively p=0.02. RSI was the only variable found to be significant on Cox local control analysis (HR 2.9; 95% CI: 1.2-8.2; p=0.02). There was no significance of RSI in predicting local control in patients not receiving RT, p=0.48. A cox regression model between receipt of radiotherapy and RSI combining E1 and E2 showed that the interaction term was significant for PFS (3.7; 95% CI 1.4-10; p=0.009). A summary measure combining E1 and E2 showed statistical significance for PFS between RR and RS patients treated with radiotherapy (HR 2.7l; 95% CI 1.3-5.6; p=0.007) but not in patients not treated with radiotherapy (HR 0.94; 95% CI 0.5-1.78; p=0.86). Conclusions RSI appears to be predictive for benefit from adjuvant radiation. Prospective validation is required.