Prognostic impact and characteristics of ROS1 fusion in patients with surgically resected lung adenocarcinoma.

Objective: We aimed to investigate the prognostic significance of ROS1 fusion in surgically resected lung adenocarcinoma (LUAD).

Materials And Methods: Consecutive patients who underwent complete resection and ROS1 testing between 2015 and 2020 were included. Propensity score matching (1:2) was applied to balance baseline characteristics. Disease-free survival (DFS), overall survival (OS), and cumulative incidence of recurrence (CIR) were compared overall and by TNM stage. Recurrence patterns and post-recurrence survival (PRS) in ROS1 fusion-positive patients were also analyzed.

Results: Overall, 16,779 patients met the inclusion criteria (216 ROS1 fusion-positive and 16,563 ROS1 fusion-negative). After matching, 216 ROS1 fusion-positive and 432 ROS1 fusion-negative patients were included in survival analysis. In the overall cohort, the ROS1 fusion-positive group had similar DFS (5-year: 72.7 % vs. 66.4 %; p = 0.074) and OS (5-year: 87.6 % vs. 80.7 %; p = 0.055) compared with theROS1fusion-negative group. Subgroup analysis showed that ROS1 fusion was associated with better DFS (hazard ratio [HR], 0.609; 95 % confidence interval [CI], 0.376-0.986; p = 0.043) and OS (HR, 0.481; 95 % CI, 0.242-0.958; p = 0.037) in stage I, with similar outcomes in stages II-III. In addition, recurrence patterns and CIR analyses were consistent with these findings. Among patients who experienced recurrence, ROS1 tyrosine kinase inhibitors (TKIs) significantly improved PRS (median PRS: 65 vs. 20 months; p < 0.001). In multivariate Cox regression analysis, ROS1-TKI therapy remained an independent protective factor for PRS (HR = 0.259; 95 % CI, 0.103-0.647; p = 0.004).

Conclusion: ROS1 fusion was associated with better prognosis in stage I LUAD, and ROS1-TKI therapy conferred a survival advantage after recurrence.