Impact of Circulating Tumor DNA-Based Detection of Molecular Residual Disease on the Conduct and Design of Clinical Trials for Solid Tumors.
Impact of Circulating Tumor DNA-Based Detection of Molecular Residual Disease on the Conduct and Design of Clinical Trials for Solid Tumors.
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DOI：
10.1200/po.21.00181
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发表时间：
2022-03
影响因子：
4.6
通讯作者：
Kopetz S
中科院分区：
文献类型：
--
作者：
Kasi PM;Fehringer G;Taniguchi H;Starling N;Nakamura Y;Kotani D;Powles T;Li BT;Pusztai L;Aushev VN;Kalashnikova E;Sharma S;Malhotra M;Demko ZP;Aleshin A;Rodriguez A;Billings PR;Grothey A;Taieb J;Cunningham D;Yoshino T;Kopetz S
使用循环肿瘤DNA（ctDNA）检测分子残留病（MRD）来早期检测癌症复发具有显著影响癌症管理的潜力。我们回顾了支持使用ctDNA作为检测MRD的生物标志物的证据，并强调了ctDNA检测可能对临床试验的进行产生的潜在影响。我们使用MEDLINE（通过PubMed）检索了2000年1月1日以来的文献，重点是评估ctDNA作为癌症复发预测因子的研究。还对ctDNA和癌症进行了广泛集中的检索，以提供额外的背景信息。搜索www.clinialtrials.gov以识别包含ctDNA测试的试验。对不同癌症类型的大量研究表明，基于ctDNA的MRD检测预测复发具有高灵敏度和特异性，并且在标准成像之前的提前时间长达12个月。最近，ctDNA检测已开始用于将具有高复发风险的MRD阳性患者纳入试验，有望获得统计功效，从而可以用较小的队列证明临床实用性。基于ctDNA检测的MRD检测用于将患者分为低风险或高风险类别以进行治疗分配的试验也在进行中。此外，越来越多的证据支持使用ctDNA动力学或清除率作为替代终点，这可以显著缩短试验持续时间。在许多癌症中，基于ctDNA的试验富集似乎越来越普遍，以减少成本和时间。试验效率也可以从使用ctDNA作为替代终点中受益，从而加速新疗法的批准。使用基于ctDNA的MRD检测来分配治疗的试验的疗效的明确证明可以改变临床实践。
Earlier detection of cancer recurrence using circulating tumor DNA (ctDNA) to detect molecular residual disease (MRD) has the potential to dramatically affect cancer management. We review evidence supporting the use of ctDNA as a biomarker for detection of MRD and highlight the potential impact that ctDNA testing could have on the conduct of clinical trials. We searched the literature using MEDLINE (via PubMed) for articles from January 1, 2000, focusing on studies that assessed ctDNA as a predictor of cancer recurrence. Broadly focused searches on ctDNA and cancer were also performed to provide additional background information. www.clinialtrials.gov was searched to identify trials that incorporate ctDNA testing. Numerous studies across different cancer types indicate that ctDNA-based MRD detection predicts recurrence with high sensitivity and specificity, and with lead times that precede standard imaging by up to 12 months. Recently, ctDNA testing has started being used to enroll MRD-positive patients at high risk of recurrence into trials, promising gains in statistical power that allow clinical utility to be demonstrated with smaller cohorts. Trials where ctDNA testing based-MRD detection is used to stratify patients into low or high-risk categories for treatment assignment are also ongoing. In addition, there is increasing evidence supporting the use of ctDNA dynamics or clearance as a surrogate end point, which could significantly reduce trial duration. ctDNA-based trial enrichment across many cancers seems likely to become increasingly common for cost- and time-reduction benefits. Trial efficiency could also benefit from using ctDNA as a surrogate end point, leading to accelerated approval of new therapeutics. A clear demonstration of efficacy from trials that use ctDNA-based MRD detection to assign treatment could transform clinical practice.