Department of Respiratory and Critical Care Medicine, Affiliated Qingyuan Hospital of Guangzhou Medical University, Qingyuan People's Hospital, Qingyuan, 511518, China.
Guangzhou Medical University, Guangzhou, 511436, China.
EBioMedicine. 2024 May;103:105109. doi: 10.1016/j.ebiom.2024.105109. Epub 2024 Apr 13.
Circulating tumour DNA (ctDNA)-based molecular residual disease (MRD) detection technology has been widely used for recurrence evaluation, but there is no agreement on the efficacy of assessing recurrence and overall survival (OS) prognosis, as well as the sensitivity and specificity of landmark detection and longitudinal detection.
We systematically searched Pubmed, Embase, Cochrane, and Scopus for prospective studies or randomized controlled trials that collected blood samples prospectively. The search period was from Jan 1, 2013, to Sept 10, 2023. We excluded retrospective studies. The primary endpoint was to assess the hazard ratio (HR) between circulating tumour DNA positive (ctDNA+) and negative (ctDNA-) for recurrence-free survival incidence (RFS), disease-free survival (DFS), progression-free survival (PFS), event-free survival (EFS), time to recurrence (TTR), distant metastasis-free survival (DMFS) or OS in patients with resectable cancers. We calculated the pooled HR of recurrence and OS and 95% confidence interval (CI) in patients with resected cancers using a random-effects model. Pooled sensitivity and specificity were estimated using the bivariate random effects model.
This systematic review and meta-analysis returned 7578 records, yielding 80 included studies after exclusion. We found that the HR of recurrence across all included cancers between patients with ctDNA+ and ctDNA- was 7.48 (95% CI 6.39-8.77), and the OS was 5.58 (95% CI 4.17-7.48). We also found that the sensitivity, area under the summary receiver operating characteristic curve (AUSROC) and diagnostic odds ratio (DOR) of longitudinal tests were higher than that of landmark tests between patients with ctDNA+ and ctDNA- (0.74, 95% CI 0.68-0.80 vs 0.50, 95% CI 0.46-0.55; 0.88 vs. 0.80; 25.70, 95% CI 13.20-45.40 vs. 9.90, 95% CI 7.77-12.40).
Postoperative ctDNA testing was a significant prognosis factor for recurrence and OS in patients with resectable cancers. However, the overall sensitivity of ctDNA-MRD detection could be better. Longitudinal monitoring can improve the sensitivity, AUSROC, and DOR.
Special fund project for clinical research of Qingyuan People's Hospital (QYRYCRC2023006), plan on enhancing scientific research in GMU (GZMU-SH-301).
循环肿瘤 DNA（ctDNA）为基础的分子残留疾病（MRD）检测技术已广泛应用于复发评估，但对于评估复发和总生存（OS）预后的疗效，以及对标志检测和纵向检测的灵敏度和特异性，尚无共识。
我们系统地检索了 Pubmed、Embase、Cochrane 和 Scopus，以收集前瞻性研究或随机对照试验中前瞻性采集的血液样本。检索时间为 2013 年 1 月 1 日至 2023 年 9 月 10 日。我们排除了回顾性研究。主要终点是评估循环肿瘤 DNA 阳性（ctDNA+）和阴性（ctDNA-）患者在可切除癌症患者中的无复发生存率（RFS）、无病生存率（DFS）、无进展生存率（PFS）、无事件生存率（EFS）、复发时间（TTR）、远处转移无生存率（DMFS）或 OS 之间的危险比（HR）。我们使用随机效应模型计算了可切除癌症患者的复发和 OS 的汇总 HR 和 95%置信区间（CI）。使用双变量随机效应模型估计了汇总敏感性和特异性。
这项系统评价和荟萃分析共返回 7578 条记录，排除后得到 80 项纳入研究。我们发现，所有纳入癌症患者的 ctDNA+与 ctDNA-之间的复发 HR 为 7.48（95%CI 6.39-8.77），OS 为 5.58（95%CI 4.17-7.48）。我们还发现，ctDNA+与 ctDNA-患者之间的纵向检测的敏感性、综合受试者工作特征曲线下面积（AUSROC）和诊断比值比（DOR）均高于标志检测（0.74，95%CI 0.68-0.80 vs 0.50，95%CI 0.46-0.55；0.88 vs. 0.80；25.70，95%CI 13.20-45.40 vs. 9.90，95%CI 7.77-12.40）。
术后 ctDNA 检测是可切除癌症患者复发和 OS 的重要预后因素。然而，ctDNA-MRD 检测的总体敏感性可能更好。纵向监测可以提高敏感性、AUSROC 和 DOR。
清远市人民医院临床研究专项基金（QYRYCRC2023006），广医-清医深化合作计划（GZMU-SH-301）。
