Association of Oncogene Driver Mutations with Recurrence and Survival in Stage I Nonsmall Cell Lung Cancer

Abstract

Background: Stage I nonsmall cell lung cancer (NSCLC) is primarily treated with surgical resection and has a favorable prognosis with an expected recurrence rate of 30%. New methods to risk stratify patients with stage I NSCLC are needed to help select those that might benefit from more active surveillance or adjuvant therapy.

Methods: We analyzed clinical data from 1330 patients (1469 tumors) with NSCLC and correlated it with next-generation sequencing (NGS). To reduce the potential confounding variables of stage and treatment, this analysis only included patients with stage I NSCLC in whom surgical resection was the primary treatment.

Results: In 570 patients (600 tumors), 75 (12.5%) developed recurrence. Recurrence occurred in 37.5% of patients with KRAS G12V mutation versus 11.1% of patients without this mutation (P < .001). A lower chance of recurrence was associated with "any EGFR" mutation (6.74% vs. 14.9%, P = .006). A history of coronary artery disease (CAD) increased the chance of recurrence: OR 2.7 (1.57-4.89, P < .001). Shorter survival was predicted by KRAS G12V (P = .009) and "other TP53" mutation (P = .025). KRAS G12V, KRAS G13D, MET E168D, PTEN, and "other TP53" were oncogene mutations associated with reduced survival in stage I NSCLC. CAD, type 2 diabetes (DM2), and "other cancer" were medical comorbidities associated with reduced survival in stage I NSCLC.

Conclusions: Oncogene mutations such as KRAS G12V and EGFR may have implications for cancer surveillance strategies and inform future treatment trials of stage I NSCLC.

Keywords: Driver Mutations; Stage I Non-small cell lung cancer.