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

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.