The clinical value of circulating tumor DNA detection in advanced non-small cell lung cancer

Xiao Lin, Wentao Dong, Xiaojing Lai, Wei Feng, Xiaofu Yu, Qing Gu, Chunyang Wang, Wen Xiao, Xiao Zheng


Background: Circulating tumor DNA (ctDNA) is a kind of cell-free DNA which comes from tumor cells and effectively reflects the molecular characteristics of tumors, which providing us a novel method to explore its clinical therapeutic value in advanced lung cancer.
Methods: A total of 36 patients with advanced non-small cell lung cancer (NSCLC) were enrolled in this study, including 28 cases of adenocarcinoma and 8 cases of squamous cell carcinoma. Next-generation sequencing based ctDNA detection, tissue DNA (tDNA) detection, corresponding survival analysis, and retrospective statistics were performed to explore the feasibility of clinical practice directed by molecular characteristics in NSCLC.
Results: Epidermal growth factor receptor mutation (EGFR mutation) took over the highest mutation frequency (36.11%) in 36 samples, and the subsequent genes were PIK3CA, BRAF, KRAS, NRAS, MAP2K1, and GNAQ; 11 patients were detected with multiple gene mutations, including 8 cases with double gene mutations, 1 case with three gene mutations, and 2 cases with four gene mutations, and the subsequent 12-month survival observation revealed that patients with less mutations also had a longer OS (10.37±0.74 vs. 7.08±1.43 months, P=0.034). Twenty-one patients with EGFR mutation and subsequently treated with EGFR-tyrosine kinase inhibitor (TKI) combined chemotherapy, had significantly longer PFS than those with EGFR wild type and treated with chemotherapy in next 5-year monitoring test (18.00±4.41 vs. 7.33±1.58 months, P=0.024).
Conclusions: Gene mutation in advanced lung cancer is complex, and ctDNA detection has important guiding significance in clinical treatment of advanced NSCLC.