Jason D. Merker and Maximilian Diehn, Stanford University School of Medicine; Stanford, CA; Geoffrey R. Oxnard, Dana Farber Cancer Institute and Harvard Medical School; Neal Lindeman, Brigham and Women's Hospital and Harvard Medical School, Boston, MA; Carolyn Compton, Arizona State University, Tempe, AZ; Patricia Hurley, Richard L. Schilsky, Thomas K. Oliver, and Suanna S. Bruinooge, American Society of Clinical Oncology, Alexandria, VA; Alexander J. Lazar and Apostolia M. Tsimberidou, The University of Texas MD Anderson Cancer Center, Houston, TX; Christina M. Lockwood, University of Washington, Seattle, WA; Alex J. Rai, Columbia University Medical Center, New York, NY; Patricia Vasalos and Brooke L. Billman, College of American Pathologists, Northfield, IL; Daniel F. Hayes, University of Michigan Comprehensive Cancer Center, Ann Arbor, MI; and Nicholas C. Turner, Royal Marsden Hospital and Institute of Cancer Research, London, United Kingdom.
J Clin Oncol. 2018 Jun 1;36(16):1631-1641. doi: 10.1200/JCO.2017.76.8671. Epub 2018 Mar 5.
Purpose Clinical use of analytical tests to assess genomic variants in circulating tumor DNA (ctDNA) is increasing. This joint review from ASCO and the College of American Pathologists summarizes current information about clinical ctDNA assays and provides a framework for future research. Methods An Expert Panel conducted a literature review on the use of ctDNA assays for solid tumors, including pre-analytical variables, analytical validity, interpretation and reporting, and clinical validity and utility. Results The literature search identified 1,338 references. Of those, 390, plus 31 references supplied by the Expert Panel, were selected for full-text review. There were 77 articles selected for inclusion. Conclusion The evidence indicates that testing for ctDNA is optimally performed on plasma collected in cell stabilization or EDTA tubes, with EDTA tubes processed within 6 hours of collection. Some ctDNA assays have demonstrated clinical validity and utility with certain types of advanced cancer; however, there is insufficient evidence of clinical validity and utility for the majority of ctDNA assays in advanced cancer. Evidence shows discordance between the results of ctDNA assays and genotyping tumor specimens and supports tumor tissue genotyping to confirm undetected results from ctDNA tests. There is no evidence of clinical utility and little evidence of clinical validity of ctDNA assays in early-stage cancer, treatment monitoring, or residual disease detection. There is no evidence of clinical validity and clinical utility to suggest that ctDNA assays are useful for cancer screening, outside of a clinical trial. Given the rapid pace of research, re-evaluation of the literature will shortly be required, along with the development of tools and guidance for clinical practice.
临床应用分析检测方法评估循环肿瘤 DNA（ctDNA）中的基因组变异正在增加。美国临床肿瘤学会（ASCO）和美国病理学家学院（College of American Pathologists）联合发布的这份综述总结了当前关于临床 ctDNA 检测的信息，并为未来的研究提供了框架。
专家组对用于实体瘤的 ctDNA 检测的应用进行了文献回顾，包括分析前变量、分析有效性、解读和报告以及临床有效性和实用性。
文献检索共识别出 1338 篇参考文献。其中，390 篇加上专家组提供的 31 篇参考文献被选为全文审查。共选择了 77 篇文章进行纳入。
证据表明，ctDNA 检测最佳的检测标本是在细胞稳定或 EDTA 管中采集的血浆，EDTA 管应在采集后 6 小时内处理。某些 ctDNA 检测方法已经在某些类型的晚期癌症中显示出临床有效性和实用性；然而，大多数在晚期癌症中应用的 ctDNA 检测方法缺乏临床有效性和实用性的证据。证据表明 ctDNA 检测结果与肿瘤组织基因分型之间存在不一致性，并支持使用肿瘤组织基因分型来确认 ctDNA 检测未检出的结果。ctDNA 检测在早期癌症、治疗监测或残留疾病检测中的临床实用性和有效性证据有限。没有证据表明 ctDNA 检测具有临床有效性和实用性，可用于癌症筛查，除非在临床试验之外。鉴于研究进展迅速，需要对文献进行重新评估，并制定用于临床实践的工具和指南。
