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; hristina 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.
Arch Pathol Lab Med. 2018 Oct;142(10):1242-1253. doi: 10.5858/arpa.2018-0901-SA. 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 the American Society of Clinical Oncology 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 preanalytical variables, analytical validity, interpretation and reporting, and clinical validity and utility.
RESULTS.—: The literature search identified 1338 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.
CONCLUSIONS.—: 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 or clinical utility to suggest that ctDNA assays are useful for cancer screening, outside of a clinical trial. Given the rapid pace of research, reevaluation of the literature will shortly be required, along with the development of tools and guidance for clinical practice.
临床分析检测用于评估循环肿瘤 DNA（ctDNA）中的基因组变异的应用正在增加。美国临床肿瘤学会和美国病理学家学院的联合审查总结了目前关于临床 ctDNA 检测的信息，并为未来的研究提供了框架。
专家小组对用于实体瘤的 ctDNA 检测进行了文献综述，包括分析前变量、分析有效性、解释和报告以及临床有效性和实用性。
文献检索确定了 1338 篇参考文献。其中，390 篇加上专家小组提供的 31 篇参考文献进行了全文审查。共选择了 77 篇文章进行纳入。
证据表明，在细胞稳定或 EDTA 管中收集的血浆中进行 ctDNA 检测最佳，EDTA 管应在采集后 6 小时内处理。一些 ctDNA 检测已证明在某些类型的晚期癌症中具有临床有效性和实用性；然而，大多数 ctDNA 检测在晚期癌症中的临床有效性和实用性的证据不足。证据表明 ctDNA 检测与肿瘤标本的基因分型结果存在不一致，并支持对肿瘤组织进行基因分型以确认 ctDNA 检测中未检测到的结果。在早期癌症、治疗监测或残留疾病检测中，ctDNA 检测既没有临床实用性的证据，也没有临床有效性的证据。没有证据表明 ctDNA 检测在癌症筛查方面具有临床有效性或临床实用性，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，同时还需要开发用于临床实践的工具和指南。
