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

J Thorac Oncol. 2017 Jun;12(6):922-931. doi: 10.1016/j.jtho.2017.03.001. Epub 2017 Mar 14.

Abstract

Background: The issue of overdiagnosis in low-dose computed tomography (LDCT) screening trials could be addressed by the development of complementary biomarkers 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.

Keywords: Low-dose computed tomography; Lung cancer; MicroRNA-based liquid biopsy; Mutational load; Next-generation sequencing.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adenocarcinoma / genetics
  • Adenocarcinoma / mortality*
  • Adenocarcinoma / pathology
  • Adult
  • Biomarkers, Tumor / genetics*
  • Carcinoma, Squamous Cell / genetics
  • Carcinoma, Squamous Cell / mortality*
  • Carcinoma, Squamous Cell / pathology
  • Early Detection of Cancer
  • Female
  • Follow-Up Studies
  • High-Throughput Nucleotide Sequencing / methods*
  • Humans
  • Lung Neoplasms / genetics
  • Lung Neoplasms / mortality*
  • Lung Neoplasms / pathology
  • Male
  • Middle Aged
  • Mutation*
  • Prognosis
  • Small Cell Lung Carcinoma / genetics
  • Small Cell Lung Carcinoma / mortality*
  • Small Cell Lung Carcinoma / pathology
  • Survival Rate
  • Tomography, X-Ray Computed / methods

Substances

  • Biomarkers, Tumor