• Hang Cao, Wangyang Zhu, Huatao Tang, Chaoqiang Deng, Fangqiu Fu, Yuan Li, Yang Zhang, and Haiquan Chen.
• Department of Thoracic Surgery and State Key Laboratory of Genetic Engineering, Fudan University Shanghai Cancer Center, Shanghai, China; Institute of Thoracic Oncology, Fudan University, Shanghai, China; Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, China.
• J. Thorac. Cardiovasc. Surg. 2024 Sep 20.

ObjectivesThe ALINA trial introduced anaplastic lymphoma kinase (ALK) inhibitors in an early-stage context, generating notable interest. This study aims to investigate the characteristics and prognostic implications of ALK rearrangement in patients with resected lung adenocarcinoma (LUAD).MethodsWe retrospectively evaluated resected LUAD cases with documented ALK status from 2008 to 2020. The association between ALK positivity and clinicopathologic characteristics, molecular profiles, and outcomes was explored.ResultsAmong 4944 cases, 238 (4.8%) were ALK-positive, correlating with younger age and nonsmokers. ALK positivity was also significantly associated with pure-solid nodules, spread through air spaces, and solid-predominant adenocarcinoma. ALK-positive tumors exhibited an overall low frequency of co-mutations (eg, TP53, STK11). ALK positivity was associated with inferior recurrence-free survival (RFS) in patients with stage I who did not receive adjuvant chemotherapy whereas it was associated with prolonged RFS in patients with stage II and III who received adjuvant chemotherapy. Notably, 6 patients treated with adjuvant ALK inhibitors experienced no recurrence or metastasis during the follow-up period. In addition, the administration of ALK inhibitors significantly improved postrecurrence survival in patients positive for ALK.ConclusionsALK positivity was associated with specific aggressive pathologic features and inferior RFS in stage I LUAD. Patients positive for ALK seemed to benefit more from adjuvant chemotherapy. Active treatment with ALK inhibitors or chemotherapy should be considered for patients with ALK-positive LUAD, although further evidence is warranted to expand their utility in early-stage disease management.Copyright © 2024 The American Association for Thoracic Surgery. Published by Elsevier Inc. All rights reserved.

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