Features of anaplastic lymphoma kinase rearrangement in early-stage lung cancer: Analysis of a nationwide Japanese database

J Surg Oncol. 2023 Oct;128(5):916-924. doi: 10.1002/jso.27384. Epub 2023 Jul 5.

Abstract

Background and objectives: Anaplastic lymphoma kinase (ALK) rearrangement is a representative driver mutation in lung cancer. However, the biology of early-stage ALK-rearranged lung cancer remains unclear. We aimed to assess the clinicopathological features, prognostic implications, and influence of ALK rearrangement on the postoperative course in surgically resected lung cancer.

Methods: We retrospectively analyzed data from the Japanese Joint Committee of Lung Cancer Registry database. Of the 12 730 patients with lung adenocarcinoma, 794 (6.2%) were tested for ALK rearrangement and were included.

Results: ALK rearrangements were detected in 76 patients (10%). The 5-year overall survival (OS) rate was significantly higher in the ALK rearrangement-positive group than in the ALK rearrangement-negative group (p = 0.030). Multivariable analysis revealed that ALK rearrangement was an independent prognostic factor for improved OS (hazard ratio, 0.521; 95% confidence interval, 0.298-0.911; p = 0.022). Regarding the postrecurrence state, there was no difference in the initial recurrence sites between both groups. Administration of ALK-tyrosine kinase inhibitors (TKIs) improved postrecurrence survival in any treatment lines.

Conclusion: In one of the largest national surveys, ALK rearrangement was associated with improved long-term outcomes in surgically resected patients. ALK-TKIs may be an important treatment strategy for ALK rearrangement-positive lung adenocarcinoma in the postrecurrence state.

Keywords: anaplastic lymphoma kinase; epidermal growth factor receptor; lung cancer; surgery; tyrosine kinase inhibitor.

MeSH terms

  • Adenocarcinoma of Lung* / genetics
  • Adenocarcinoma of Lung* / surgery
  • Adenocarcinoma* / genetics
  • Adenocarcinoma* / pathology
  • Adenocarcinoma* / surgery
  • Anaplastic Lymphoma Kinase / genetics
  • East Asian People
  • ErbB Receptors / genetics
  • Gene Rearrangement
  • Humans
  • Lung Neoplasms* / genetics
  • Lung Neoplasms* / surgery
  • Mutation
  • Protein Kinase Inhibitors / therapeutic use
  • Receptor Protein-Tyrosine Kinases / genetics
  • Retrospective Studies

Substances

  • Anaplastic Lymphoma Kinase
  • Receptor Protein-Tyrosine Kinases
  • ErbB Receptors
  • Protein Kinase Inhibitors