Perioperative Dynamic Changes in Circulating Tumor DNA in Patients with Lung Cancer (DYNAMIC)
Perioperative Dynamic Changes in Circulating Tumor DNA in Patients with Lung Cancer (DYNAMIC)
复制标题
肺癌患者围手术期循环肿瘤 DNA 的动态变化（动态）
DOI：
10.1158/1078-0432.ccr-19-1213
复制
发表时间：
2019-12-01
影响因子：
11.5
通讯作者：
Wang, Jun
中科院分区：
文献类型：
--
作者：
Chen, Kezhong;Zhao, Heng;Wang, Jun
目的：尚未有研究对任何早期肿瘤患者围手术期循环肿瘤DNA （ctDNA）的精确动态变化进行研究。本研究（DYNAMIC）研究了围手术期ctDNA的动态变化，并确定了ctDNA为基础的肺癌手术患者监测的合适检测时间。实验设计：前瞻性纳入接受治疗目的肺切除术的连续患者（NCT02965391）。在手术前（时间A）、手术中肿瘤切除后（时间b -时间D）、手术后（时间p1 -时间P3）等多个预定时间点采集血浆样本。利用新一代测序检测平台计算血浆突变等位基因频率。主要终点是肿瘤根治后的ctDNA半衰期。结果：36例患者在a时间出现可检测到的突变，肿瘤根治后血浆ctDNA浓度呈快速下降趋势，a、B、C、D时间的平均突变等位基因比例分别为2.72%、2.11%、1.14%、0.17%。中位ctDNA半衰期为35.0分钟。最小残留病（MRD）检测患者的ctDNA半衰期明显慢于MRD阴性患者（103.2分钟vs 29.7分钟，P = 0.001）。ctDNA浓度可检测和不可检测的患者在P1时间的无复发生存期分别为528天和543天（P = 0.657），而在P2时间分别为278天和637天（P = 0.002）。结论：ctDNA在肿瘤根治性切除后迅速衰减。R0切除后第3天ctDNA检测可作为术后肺癌监测的基线值。
Purpose: No study has investigated the precise perioperative dynamic changes in circulating tumor DNA (ctDNA) in any patients with early-stage cancer. This study ( DYNAMIC) investigated perioperative dynamic changes in ctDNA and determined the appropriate detection time of ctDNA-based surveillance for surgical patients with lung cancer.Experimental Design: Consecutive patients who underwent curative-intent lung resections were enrolled prospectively (NCT02965391). Plasma samples were obtained at multiple prespecified 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 35.0 minutes. Patients with minimal residual disease (MRD) detection had a significant slower ctDNA half-life than those with negative MRD (103.2 minutes vs. 29.7 minutes, P = 0.001). The recurrence-free survival of patients with detectable and undetectable ctDNA concentrations at time P1 was 528 days and 543 days, respectively (P = 0.657), whereas at time P2 was 278 days and 637 days, respectively (P = 0.002).Conclusions: ctDNA decays rapidly after radical tumor resection. The ctDNA detection on the third day after R0 resection can be used as the baseline value for postoperative lung cancer surveillance.