Callesen Louise B, Takacova Tana, Hamfjord Julian, Würschmidt Florian, Oldhafer Karl J, Brüning Roland, Arnold Dirk, Spindler Karen-Lise G
Department of Experimental Clinical Oncology, Aarhus University Hospital, Palle Juul-Jensens Boulevard 99, Aarhus N 8200, Denmark.
Institute of Clinical Medicine, Aarhus University, Aarhus, Denmark.
Ther Adv Med Oncol. 2022 Nov 2;14:17588359221133171. doi: 10.1177/17588359221133171. eCollection 2022.
Loco-regional treatment strategies of colorectal cancer (CRC) metastases are evolving, but biological markers that can benefit patients and assist physicians in clinical decisions are lacking. The primary objective of this systematic review and meta-analysis is to investigate the current knowledge on circulating DNA and its clinical utility in predicting outcomes in patients undergoing loco-regional treatment of CRC metastases.
A systematic search of PubMed, Embase, and Cochrane Central Register of Controlled Trials was conducted on March 22, 2022. We included studies on patients undergoing loco-regional treatment of CRC metastases reporting the predictive or prognostic value of circulating DNA in the blood. Hazard ratios (HR) were pooled in separate random-effects meta-analyses to investigate if pre- or post-ablation measurements of circulating DNA were associated with survival. The risk of bias was assessed according to the Quality in Prognosis Studies tool.
Twenty-eight studies with 2868 patients were included, of which 16 studies were eligible for meta-analyses. As expected in this new research field, a majority of included studies ( = 21/28) had a high risk of bias in at least one domain. Circulating DNA above the cutoff in a plasma sample taken before loco-regional treatment was associated with a short recurrence-free survival [pooled HR = 2.8, 95% confidence interval (CI) 1.4-5.7, = 162] and overall survival (pooled HR = 4.7, 95% CI 1.1-20.6, = 105). Circulating DNA above the cutoff in a plasma sample taken after loco-regional treatment was associated with a short recurrence-free survival (pooled HR = 4.5, 95% CI 3.4-6.1, = 569) and overall survival (pooled HR = 7.5, 95% CI 2.0-27.3, = 161). There was limited data on the association between dynamics in circulating DNA and outcome.
Measurements of circulating DNA can be valuable when selecting and monitoring patients undergoing loco-regional treatment of CRC metastases. Studies designed to investigate the true clinical utility of circulating DNA in the context of various ablation modalities are warranted.The review has been registered at PROSPERO (ID: CRD42022320032).
结直肠癌（CRC）转移灶的局部区域治疗策略不断发展，但缺乏能使患者受益并协助医生进行临床决策的生物标志物。本系统评价和荟萃分析的主要目的是研究关于循环DNA的现有知识及其在预测接受CRC转移灶局部区域治疗患者预后方面的临床应用价值。
于2022年3月22日对PubMed、Embase和Cochrane对照试验中央注册库进行了系统检索。我们纳入了关于接受CRC转移灶局部区域治疗患者的研究，这些研究报告了血液中循环DNA的预测或预后价值。在单独的随机效应荟萃分析中汇总风险比（HR），以研究消融前或消融后循环DNA测量值是否与生存相关。根据预后研究质量工具评估偏倚风险。
纳入了28项研究，共2868例患者，其中16项研究符合荟萃分析的条件。正如在这个新研究领域中所预期的，大多数纳入研究（21/28）在至少一个领域存在高偏倚风险。局部区域治疗前采集的血浆样本中循环DNA高于临界值与无复发生存期缩短相关[汇总HR = 2.8，95%置信区间（CI）1.4 - 5.7，n = 162]和总生存期缩短相关[汇总HR = 4.7，95% CI 1.1 - 20.6，n = 105]。局部区域治疗后采集的血浆样本中循环DNA高于临界值与无复发生存期缩短相关（汇总HR = 4.5，95% CI 3.4 - 6.1，n = 569）和总生存期缩短相关（汇总HR = 7.5，95% CI 2.0 - 27.3，n = 161）。关于循环DNA动态变化与预后之间关联的数据有限。
在选择和监测接受CRC转移灶局部区域治疗的患者时，循环DNA测量可能具有重要价值。有必要开展旨在研究在各种消融方式背景下循环DNA真正临床应用价值的研究。本综述已在PROSPERO注册（注册号：CRD42022320032）。
