Detection of EGFR mutations using target capture sequencing in plasma of patients with non-small-cell lung cancer

Purpose Circulating tumour DNA (ctDNA) is a promising biomarker for detection of non-invasive epidermal growth factor receptor (EGFR ) mutations in patients with non-small-cell lung cancer (NSCLC). However, the existing methods have limitations in sensitivity or in availability. The aim was to evaluate the accuracy of capture target sequencing for detecting EGFR mutations in ctDNA. Methods A total of 79 patients with NSCLC and available plasma and matched tissue specimens were enrolled. Through capture target sequencing, mutations were searched in over 20 000 reads obtained from each exon region. Parameters corresponding to the limit of detection and limit of quantification were used as the thresholds for mutation detection. To evaluate the accuracy, detection of EGFR mutations in matched tissue samples was performed by target capture sequencing and the amplification refractory mutation system (ARMS). Results EGFR mutations were discovered in 32.9 % (26/79) of the patients with NSCLC, the overall rate of consistency for the 79 paired plasma and tissue samples was 86.1 % (68/79). The sensitivity and specificity of detecting EGFR mutations in the plasma were 72.7 % and 95.7 %. In terms of the EGFR mutations identified by ARMS, the overall consistency was 78.5 % (62/79) in three groups. Of 21 patients with EGFR sensitive mutation defined by next generation sequencing in ctDNA, 20 (95.2%) showed long-term disease control with epidermal growth factor receptor tyrosine kinase inhibitor (EGFR TKI) treatment; the median progression-free survival was 10.8 months (95% CI 9.1 to 16.8). Conclusions Target capture sequencing of ctDNA can be used for genotyping of EGFR in patients with NSCLC, which may enable a direct recommendation for EGFR TKI on the basis of positive results with plasma DNA.