Institute of Thoracic Oncology and Department of Thoracic Surgery, West China Hospital, Sichuan University, Chengdu, China.
Western China Collaborative Innovation Center for Early Diagnosis and Multidisciplinary Therapy of Lung Cancer, Sichuan University, Chengdu, China.
Clin Cancer Res. 2022 Aug 2;28(15):3308-3317. doi: 10.1158/1078-0432.CCR-21-3044.
We assessed whether perioperative circulating tumor DNA (ctDNA) could be a biomarker for early detection of molecular residual disease (MRD) and prediction of postoperative relapse in resected non-small cell lung cancer (NSCLC).
Based on our prospective, multicenter cohort on dynamic monitoring of ctDNA in lung cancer surgery patients (LUNGCA), we enrolled 950 plasma samples obtained at three perioperative time points (before surgery, 3 days and 1 month after surgery) of 330 stage I-III NSCLC patients (LUNGCA-1), as a part of the LUNGCA cohort. Using a customized 769-gene panel, somatic mutations in tumor tissues and plasma samples were identified with next-generation sequencing and utilized for ctDNA-based MRD analysis.
Preoperative ctDNA positivity was associated with lower recurrence-free survival (RFS; HR = 4.2; P < 0.001). The presence of MRD (ctDNA positivity at postoperative 3 days and/or 1 month) was a strong predictor for disease relapse (HR = 11.1; P < 0.001). ctDNA-based MRD had a higher relative contribution to RFS prediction than all clinicopathologic variables such as the TNM stage. Furthermore, MRD-positive patients who received adjuvant therapies had improved RFS over those not receiving adjuvant therapy (HR = 0.3; P = 0.008), whereas MRD-negative patients receiving adjuvant therapies had lower RFS than their counterparts without adjuvant therapy (HR = 3.1; P < 0.001). After adjusting for clinicopathologic variables, whether receiving adjuvant therapies remained an independent factor for RFS in the MRD-positive population (P = 0.002) but not in the MRD-negative population (P = 0.283).
Perioperative ctDNA analysis is effective in early detection of MRD and relapse risk stratification of NSCLC, and hence could benefit NSCLC patient management.
我们评估了围手术期循环肿瘤 DNA（ctDNA）是否可作为检测非小细胞肺癌（NSCLC）分子残留疾病（MRD）和预测术后复发的生物标志物。
基于我们前瞻性、多中心的肺癌手术患者 ctDNA 动态监测研究（LUNGCA），我们纳入了 330 例 I-III 期 NSCLC 患者（LUNGCA-1）的 950 个血浆样本，这些样本是在三个围手术期时间点（术前、术后 3 天和 1 个月）采集的，这是 LUNGCA 队列的一部分。使用定制的 769 基因panel，通过下一代测序鉴定肿瘤组织和血浆样本中的体细胞突变，并用于基于 ctDNA 的 MRD 分析。
术前 ctDNA 阳性与较低的无复发生存率（RFS；HR=4.2；P<0.001）相关。术后 3 天和/或 1 个月时存在 MRD（ctDNA 阳性）是疾病复发的强烈预测因子（HR=11.1；P<0.001）。ctDNA 基于 MRD 对 RFS 预测的相对贡献高于所有临床病理变量，如 TNM 分期。此外，接受辅助治疗的 MRD 阳性患者的 RFS 优于未接受辅助治疗的患者（HR=0.3；P=0.008），而接受辅助治疗的 MRD 阴性患者的 RFS 低于未接受辅助治疗的患者（HR=3.1；P<0.001）。在校正临床病理变量后，是否接受辅助治疗仍然是 MRD 阳性人群 RFS 的独立因素（P=0.002），但不是 MRD 阴性人群的独立因素（P=0.283）。
围手术期 ctDNA 分析可有效检测 NSCLC 的 MRD 和复发风险分层，从而有利于 NSCLC 患者的管理。
