Efficacy comparison of targeted next-generation sequencing in the identification of somatic mutations in circulating tumor DNA from different stages of lung cancer

This study aims to assess the potential clinical application of targeted next generation sequencing (NGS)-based deep sequencing for the detection of clinically relevant mutations in circulating tumor DNA (ctDNA) obtained from non-small cell lung cancer (NSCLC) patients. Targeted deep sequencing was performed to identify High Confidence Somatic Variants (HCSVs) in matched tumor tissue DNA (tDNA) and ctDNA in 50 NSCLC patients. Our results demonstrated that NSCLC patients with Stage IV (61.5%) exhibited a higher concordance rate at the mutation level between plasma ctDNA and tDNA samples than patients with Stage I-III (14.5%). Moreover, it is noteworthy that the allele frequency of these detected HCSVs in ctDNA increased with the advance in tumor stage. Besides, using tDNA as a reference, the sensitivity of plasma ctDNA analyzed by deep NGS for actionable EGFR was much higher in patients with Stage IV (66.6%) than in patients with Stage I-III (7.7%). In conclusion, it appears that ctDNA NGS-based deep sequencing is a feasible approach to identify mutations in patients with Stage IV NSCLC. However, additional methods with higher sensitivity and specificity are needed to improve the successful application of this platform in the earlier stages of NSCLC.