The prognostic value of Kirsten rat sarcoma viral oncogene homolog mutations in resected lung adenocarcinoma differs according to clinical features

Abstract

Background: The ninth edition of lung cancer staging system recommends that specific driver mutations should be considered as prognostic factors in survival models. This study comprehensively investigated the prognostic value of Kirsten rat sarcoma viral oncogene homolog (KRAS) mutation in patients with resected lung adenocarcinomas according to different clinicopathologic and radiologic characteristics.

Methods: In total, 1464 patients with completely resected primary lung adenocarcinomas were examined for KRAS mutations from November 2008 to March 2015. Age, sex, smoking status, performance status, tumor-node-metastasis stage, radiologic features, and histologic subtypes were collected. Competing risk model was used to estimate the cumulative incidence rate of recurrence. Cox regression multivariable analyses on recurrence-free survival (RFS) and overall survival (OS) were performed.

Results: KRAS mutations were more frequent in male subjects (P < .001), current/former smokers (P < .001), invasive mucinous adenocarcinoma (P < .001), and solid tumors (P < .001). In general, KRAS-mutated patients had greater cumulative recurrence rate (hazard ratio [HR], 1.95; 95% confidence interval [CI], 1.23-3.08; P < .001) and worse overall survival (OS; HR, 1.88; 95% CI, 1.23-2.87; P < .001) than KRAS wild-type patients. The OS (P < .001) of patients harboring KRAS-G12C/V mutations was shorter than that of other KRAS-mutated patients. Cox multivariable analyses demonstrated that KRAS mutations were independently associated with worse RFS (HR, 5.34; 95% CI, 2.53-11.89; P = .001) and OS (HR, 2.63; 95% CI, 1.03-6.76; P = .044) in part-solid lung adenocarcinomas. For stage I patients, Cox multivariable analyses revealed that KRAS mutation was an independent risk factor for RFS (HR, 2.05; 95% CI, 1.19-3.56; P = .010) and OS (HR, 2.38; 95% CI, 1.29-4.40; P = .005).

Conclusions: In this study, we revealed that KRAS mutations was an independent prognostic factor in part-solid tumors and in stage I lung adenocarcinomas. These findings may contribute to the ninth edition of lung cancer staging project.

Keywords: KRAS mutation; TNM stage I; lung adenocarcinoma; part-solid nodule; prognosis.