Detecting genetic mutations in circulating
cell-free DNA (
cfDNA) is a promising approach of liquid biopsy. Between June 2014 and May 2015, 168 plasma samples were collected monthly from 20 patients with metastatic
lung adenocarcinoma with
epidermal growth factor receptor (EGFR) mutation receiving
gefitinib therapy. Clinically relevant EGFR mutations, including exon 19 deletion, L858R and T790M, were quantified using droplet digital polymerase chain reaction. In baseline samples, 19 (95.0%) patients had the same mutation with the matched
tumors, and pretreatment T790M mutations were also detected in 3 (15.0%) patients. The dynamics of EGFR mutations were generally associated with treatment response for patients with or without measurable disease. For patients with immeasurable
tumor deposits, monitoring disease evolution using
cfDNA-based mutation quantification appeared to be more reliable compared with measuring the diameters of target
tumor lesions. In addition, molecular progressive disease, defined as a ≥20% increase of EGFR mutation concentration compared with the lowest concentration recorded during treatment, was tracked up to 8 months prior to objective progression. In survival analysis, sex (P=0.005), pretreatment T790M mutation status (P=0.006), T790M mutation status at the
disease progression (P=0.043) and growth rate of EGFR mutations (P=0.023), had a significant impact on median progression-free survival. In conclusion, dynamic monitoring of EGFR mutations in
cfDNA is feasible and appears to be useful in early prediction of drug resistance for patients with
lung cancer receiving EGFR
tyrosine kinase inhibitors.