The prognostic implications of EGFR mutation and ALK rearrangement for the long-term outcomes of patients with resected lung adenocarcinomas

Thorac Cancer. 2019 Jul;10(7):1619-1627. doi: 10.1111/1759-7714.13128. Epub 2019 Jun 18.

Abstract

Background: To investigate the prognostic impact of epidermal growth factor receptor (EGFR) mutation and anaplastic lymphoma kinase (ALK) rearrangement for the overall survival (OS) of patients with surgically treated lung adenocarcinomas.

Methods: A total of 689 patients with stage I-III lung adenocarcinomas (male:female = 334:355; median age, 64 years) underwent complete surgical resection between 2007 and 2013. The prognostic impact of EGFR mutation and ALK rearrangement on OS was analyzed using Cox regression analysis. Certain clinicopathological prognostic factors (i.e., age, sex, smoking status, nodule type, solid portion size, pathologic stage, adenocarcinoma subtype, and history of adjuvant chemotherapy) were included for adjustments of the hazard ratio (HR).

Results: EGFR mutation was observed in 438 patients (64%) and ALK rearrangement was seen in 28 patients (4%). Multivariable-adjusted Cox regression demonstrated that the prognostic effect of EGFR mutation on OS differed by age (HR, exp.[-5.199 + 0.064* age]). The adjusted HR for EGFR mutation was 0.14 (95% CI: 0.05-0.36; P < 0.001) at 50 years, 0.26 (95% CI: 0.15-0.46; P < 0.001) at 60 years, and 0.50 (95% CI: 0.31-0.81; P = 0.005) at 70 years. However, the effect of ALK rearrangement on OS was without statistical significance (P > 0.05).

Conclusions: EGFR mutation was independently prognostic of the long-term outcomes of patients with surgically treated lung adenocarcinomas. A more favorable prognostic effect was seen in younger than in older patients. ALK rearrangement was not associated with OS.

Keywords: Adenocarcinoma; anaplastic lymphoma kinase; epidermal growth factor receptor; prognosis; survival analysis.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adenocarcinoma of Lung / genetics
  • Adenocarcinoma of Lung / pathology
  • Adenocarcinoma of Lung / surgery*
  • Age Factors
  • Aged
  • Anaplastic Lymphoma Kinase / genetics*
  • Biomarkers, Tumor
  • ErbB Receptors / genetics
  • Female
  • Gene Rearrangement*
  • Humans
  • Lung Neoplasms / genetics
  • Lung Neoplasms / pathology
  • Lung Neoplasms / surgery*
  • Male
  • Middle Aged
  • Mutation*
  • Neoplasm Staging
  • Prognosis
  • Regression Analysis
  • Retrospective Studies
  • Survival Analysis
  • Treatment Outcome

Substances

  • Biomarkers, Tumor
  • ALK protein, human
  • Anaplastic Lymphoma Kinase
  • EGFR protein, human
  • ErbB Receptors