Mutational Profile from Targeted NGS Predicts Survival in LDCT Screening-Detected Lung Cancers

BACKGROUND: The issue of overdiagnosis in low-dose computed tomography (LDCT) screening trials could be addressed by the development of complementary bio-markers able to improve detection of aggressive disease. The mutation profile of LDCT screening–detected lung tumors is currently unknown. METHODS: Targeted next-generation sequencing was performed on 94 LDCT screening–detected lung tumors. Associations with clinicopathologic features, survival, and the risk profile of a plasma microRNA signature classifier were analyzed. RESULTS: The mutational spectrum and frequency observed in screening series was similar to that reported in public data sets, although a larger number of tumors without mutations in driver genes was detected. The 5-year overall survival (OS) rates of patients with and without mutations in the tumors were 66% and 100%, respectively (p = 0.015). By combining the mutational status with the microRNA signature classifier risk profile, patients were stratified into three groups with 5-year OS rates ranging from 42% to 97% (p < 0.0001) and the prognostic value was significant after controlling for stage (p = 0.02). CONCLUSION: Tumor mutational status along with a microRNA-based liquid biopsy can provide additional information in planning clinical follow-up in lung cancer LDCT screening programs.