Clinical and prognostic implications of ALK and ROS1 rearrangements in never-smokers with surgically resected lung adenocarcinoma

Abstract Objectives The aim of this study is to evaluate the prevalence and prognostic significance of anaplastic lymphoma kinase ( ALK ) and c-ros oncogene 1 ( ROS1 ) rearrangement in never-smokers with surgically resected lung adenocarcinoma. Methods We retrospectively analyzed 162 consecutive never-smokers who underwent curative resection for stage IB to IIIA lung adenocarcinoma at a single institution. We concurrently analyzed mutations in the epidermal growth factor receptor ( EGFR ) and v-Ki-ras2 Kirsten rat sarcoma viral oncogene homolog ( KRAS ) genes, and investigated ALK rearrangements by fluorescence in situ hybridization assay. ROS1 rearrangement was also determined in all triple ( EGFR/KRAS/ALK )-negative tumors. Results Of 162 never smokers with lung adenocarcinoma, 14 (8.6%) and 5 (3.1%) had ALK and ROS1 rearrangements, respectively. Nineteen of the 74 (25.7%) EGFR and KRAS mutation-negative patients were fusion-positive ( ALK or ROS1 fusion). Fusion-positive patients tended to have shorter median disease-free survival (DFS) than fusion-negative patients (28.0 vs. 33.9 months; p = 0.128). In multivariate analysis, fusion-positive patients had significantly poorer DFS than fusion-negative patients after adjustment for age, sex, T stage, N stage, and adjuvant chemotherapy use ( p = 0.022; hazard ratio, 2.11; 95% confidence interval, 1.19–4.30). The first recurrence sites were not significantly different between fusion-positive and fusion-negative patients in this study. Conclusion This study shows significantly poorer DFS of ALK or ROS1 fusion-positive lung adenocarcinoma in never-smokers after curative surgery.