Predictive and prognostic factors in patients with anaplastic lymphoma kinase rearranged early-stage lung adenocarcinoma

Eur J Cardiothorac Surg. 2024 Nov 4;66(5):ezae406. doi: 10.1093/ejcts/ezae406.

Abstract

Objectives: This study aimed to evaluate the predictive and prognostic factors in clinical stage I, anaplastic lymphoma kinase (ALK)-rearranged lung adenocarcinoma following radical surgery. Additionally, it sought to compare these factors with an external cohort of ALK wild-type patients.

Methods: A multicentric, retrospective, case-control analysis was conducted on patients with clinical T1-2 N0 ALK-rearranged lung adenocarcinoma who underwent anatomical resection and radical lymphadenectomy. Data were collected from 5 high-volume oncological centres. An external cohort of ALK wild-type patients was also analysed for comparison. Survival analyses were performed using the Kaplan-Meier method, and multivariable Cox regression analysis was used to identify prognostic factors.

Results: From January 2016 to December 2022, 63 patients with ALK-rearranged lung adenocarcinoma were included. High-grade tumours (G3) significantly associated with upstaging (odds ratio = 3.904, P = 0.04). Disease-free survival (DFS) and overall survival were significantly improved in upstaged patients receiving adjuvant treatment [hazard ratio (HR) = 0.18, P = 0.0042; HR = 0.24, P = 0.0004, respectively]. The solid or micropapillary histological subtypes were independently associated with worse DFS (HR = 3.41, P = 0.022). Comparison with 435 ALK wild-type patients showed worse DFS in the ALK-rearranged group (HR = 2.09, P = 0.0003). ALK-rearranged patients had higher rates of nodal upstaging, systemic and brain recurrences.

Conclusions: Clinical T1-2 N0 ALK-rearranged lung adenocarcinoma is an aggressive disease with a specific tropism for lymph nodes and the brain. High-grade tumours are predictive of nodal upstaging. Adjuvant treatment significantly improves DFS and overall survival in upstaged patients, highlighting the need for personalized preoperative staging and post-surgical management in this cohort.

Keywords: Anaplastic lymphoma kinase-rearranged; Early stage; Lung adenocarcinoma; Lung cancer; Non-small cell lung cancer.

Publication types

  • Multicenter Study

MeSH terms

  • Adenocarcinoma of Lung* / genetics
  • Adenocarcinoma of Lung* / mortality
  • Adenocarcinoma of Lung* / pathology
  • Adenocarcinoma of Lung* / surgery
  • Adult
  • Aged
  • Anaplastic Lymphoma Kinase* / genetics
  • Case-Control Studies
  • Female
  • Gene Rearrangement
  • Humans
  • Lung Neoplasms* / genetics
  • Lung Neoplasms* / mortality
  • Lung Neoplasms* / pathology
  • Lung Neoplasms* / surgery
  • Male
  • Middle Aged
  • Neoplasm Staging*
  • Prognosis
  • Retrospective Studies

Substances

  • Anaplastic Lymphoma Kinase
  • ALK protein, human