Dynamic analysis of predictive biomarkers for radiation therapy efficacy in non-small cell lung cancer patients by next-generation sequencing based on blood specimens.

ABSTRACT

PURPOSE: Radiotherapy plays an important role in the treatment of non-small cell lung cancer, and the aim of this study was to explore the potential association of single gene mutation or pathway mutations with radiotherapy response using targeted next-generation sequencing (NGS) testing of peripheral blood specimens. MATERIAL AND METHODS: We performed NGS containing 425 genes on peripheral blood specimens from 13 NSCLC patients pre- and post-radiotherapy or post-radiotherapy. Patients whose tumors were in complete response or partial response within 1 month after radiotherapy were classified as a radiotherapy-sensitive group; otherwise, they were categorized as a radiotherapy-resistant group. The relationship between single gene mutations, signaling pathway mutations, dynamic fluctuations in circulating tumor DNA （ctDNA）, and radiotherapy response was investigated. RESULTS: Of these 13 patients，6 patients were categorized as a radiotherapy-sensitive group (46.2%), and 7 patients were categorized as a radiotherapy-resistant group (53.8%). No correlation between single gene mutations and response to radiotherapy. Mutations in the SWI/SNF complex were more likely to occur in the radiotherapy-sensitive group than in the other group (p = 0.07). Among all patients，9 patients underwent NGS tests pre- and post-radiotherapy. Dynamic analysis based on ctDNA before and after treatment revealed that a decrease in ctDNA abundance was observed in all patients in the radiotherapy-sensitive group. CONCLUSIONS: SWI/SNF complex mutations may be potential predictive biomarkers of radiotherapy response. Decreased ctDNA abundance after radiotherapy correlates with better efficacy of radiotherapy.