Correlation Between Circulating Tumor DNA Levels and Response to Tyrosine Kinase Inhibitors (TKI) Treatment in Non-Small Cell Lung Cancer

BACKGROUND: Clinical monitoring of EGFR-positive NSCLC patients is important to gauge treatment response. The current study addresses the usage of circulating tumor DNA (ctDNA) as a prognostic marker during treatment of first-generation TKIs. MATERIAL/METHODS: Serial samplings of peripheral blood from 200 EGFR-positive NSCLC patients were taken. Baseline ctDNA quantification was conducted by digital droplet PCR before TKI treatment was administered and compared to primary biopsies. Thereafter blood sampling at different treatment cycles were measured and assessed for its prognostic and predictive value. RESULTS: ctDNA was successfully detected in a number of patients and overall concordance rate was 84%. Importantly, we observed a strong correlation to ctDNA increase with disease progression using radiographic scans. In addition to survival analysis, we noted patients with the largest ctDNA variations had worst outcome. A significant number of EGFR patients during treatment developed a secondary mutation T790M and this cohort had worst survival outcome as well. CONCLUSIONS: Our study demonstrated a highly associative relation of ctDNA to NSCLC patients during treatment that can be utilized to gauge treatment response. CtDNA is an attractive means compared with conventional core needle biopsies and presents new methods for accurately profiling NSCLC disease progression.