Dissecting the clinicopathological, genomic, and prognostic significance of ALK rearrangement in resected lung adenocarcinoma.

in The Journal of thoracic and cardiovascular surgery by Hang Cao, Wangyang Zhu, Huatao Tang, Chaoqiang Deng, Fangqiu Fu, Yuan Li, Yang Zhang, Haiquan Chen

TLDR

  • ALK positivity in lung cancer is linked to younger age, not smoking, aggressive features, and worse outcomes in early-stage patients without chemotherapy. Treatment with ALK inhibitors or chemotherapy may improve outcomes for ALK-positive patients. More research is needed to determine the best approach for managing early-stage lung cancer with ALK rearrangements.

Abstract

The 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). We retrospectively evaluated resected LUAD cases with documented ALK status from 2008 to 2020. The association between ALK positivity and clinicopathological characteristics, molecular profiles, and outcomes was explored. Among 4944 cases, 238 (4.8%) were ALK-positive, correlating with younger age and non-smokers. 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 (e.g., TP53, STK11). ALK positivity was associated with inferior recurrence-free survival (RFS) in stage I patients who did not receive adjuvant chemotherapy while with prolonged RFS in stage II and III patients who received adjuvant chemotherapy. Notably, six patients treated with adjuvant ALK inhibitors experienced no recurrence or metastasis during the follow-up period. Additionally, the administration of ALK inhibitors significantly improved post-recurrence survival in ALK-positive patients. ALK positivity was associated with specific aggressive pathological features and inferior RFS in stage I LUAD. ALK-positive patients seemed to benefit more from adjuvant chemotherapy. Active treatment with ALK inhibitors or chemotherapy should be considered for ALK-positive LUAD, although further evidence is warranted to expand their utility in early-stage disease management.

Overview

  • The 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).
  • The study retrospectively evaluated resected LUAD cases with documented ALK status from 2008 to 2020. The association between ALK positivity and clinicopathological characteristics, molecular profiles, and outcomes was explored.

Comparative Analysis & Findings

  • ALK positivity was significantly associated with younger age and non-smokers. ALK-positive tumors exhibited an overall low frequency of co-mutations (e.g., TP53, STK11). ALK positivity was associated with inferior recurrence-free survival (RFS) in stage I patients who did not receive adjuvant chemotherapy while with prolonged RFS in stage II and III patients who received adjuvant chemotherapy. Notably, six patients treated with adjuvant ALK inhibitors experienced no recurrence or metastasis during the follow-up period. Additionally, the administration of ALK inhibitors significantly improved post-recurrence survival in ALK-positive patients.

Implications and Future Directions

  • ALK positivity was associated with specific aggressive pathological features and inferior RFS in stage I LUAD. ALK-positive patients seemed to benefit more from adjuvant chemotherapy. Active treatment with ALK inhibitors or chemotherapy should be considered for ALK-positive LUAD, although further evidence is warranted to expand their utility in early-stage disease management.
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