Perioperative dynamic changes in circulating tumor DNA in lung cancer patients (DYNAMIC)

Purpose: No study have investigated the precise perioperative dynamic changes in circulating tumor DNA (ctDNA) in any early stage cancer patients. This study (DYNAMIC) investigated perioperative dynamic changes in ctDNA and determine the appropriate detection time of ctDNA-based surveillance for surgical lung cancer patients. Experimental Design: Consecutive patients who underwent curative-intent lung resections were enrolled prospectively (NCT02965391). Plasma samples were obtained at multiple pre-specified time points including before surgery (time A)，during surgery after tumor resection (time B-time D) and after surgery (time P1-time P3). Next-generation sequencing based detection platform was performed to calculate the plasma mutation allele frequency. The primary endpoint was ctDNA half-life after radical tumor resection. Results: Thirty-six patients showed detectable mutations in time A. The plasma ctDNA concentration showed a rapid decreasing trend after radical tumor resection, with the average mutant allele fraction at times A, B, C and D being 2.72%, 2.11%, 1.14% and 0.17%, respectively. The median ctDNA half-life was 35.0min. Patients with MRD detection had a significant slower ctDNA half-life than those with negative MRD (103.2 mins vs. 29.7 mins, P=0.001). The RFS of patients with detectable and undetectable ctDNA concentrations at time P1 were 528 days and 543 days, respectively (p=0.657), while at time P2 were 278 days and 637 days, respectively (p=0.002). Conclusion: ctDNA decays rapidly after radical tumor resection. The ctDNA detection on the 3rd day after R0 resection can be used as the baseline value for postoperative lung cancer surveillance.