Anaplastic lymphoma kinase rearrangement in surgically resected stage IA lung adenocarcinoma

Background: It has not been determined if adjuvant chemotherapy would be helpful for completely resected early-stage lung adenocarcinoma even with unfavorable genetic markers. As the positive anaplastic lymphoma kinase (ALK) rearrangement is associated with aggressive clinical feature in lung adenocarcinoma, we evaluated the treatment outcomes of completely resected stage IA lung adenocarcinoma according to initial ALK status. Methods: This is a retrospective cohort study including 309 patients with surgically resected stage IA lung adenocarcinoma from February 2010 to December 2013. Patients were screened for ALK rearrangement using immunohistochemistry. A positive ALK status was defined as an immunohistochemistry score of 2+ or more. Both disease-free survival (DFS) and the initial recurrence pattern were analyzed according to ALK status. Results: Twenty-three (7.4%) patients had ALK-positive adenocarcinoma. During the median follow-up of 35.8 months, recurrence developed in 34 (11.0%) patients. The patients with ALK-positive tumor had significantly lower 5-year DFS rate (62.4%) compared to those with ALK-negative tumor (86.5%; P=0.038). The multivariable analysis showed that ALK rearrangement was associated with a higher risk of disease recurrence (adjusted hazard ratio =2.64; 95% confidence interval, 1.08-6.44). In addition, patient with ALKpositive tumor showed more frequent recurrence in regional lymph nodes compared with those with ALKnegative tumor (83.3% vs. 28.6%; P=0.031). Conclusions: In patients with completely resected stage IA lung adenocarcinoma, ALK rearrangement was associated with unfavorable DFS and more frequent regional lymph node metastasis. Therefore, careful surveillance for recurrence should be performed in this subset of patients.