Peng Rongxue, Zhang Rui, Li Jinming
National Center for Clinical Laboratories, Institute of Geriatric Medicine, Chinese Academy of Medical Sciences, Beijing Hospital/National Center of Gerontology, Beijing, China.
Clin Chem. 2022 Jul 3;68(7):940-952. doi: 10.1093/clinchem/hvac055.
Since circulating tumor DNA (ctDNA) sequencing is increasingly being applied in clinical management of patients with cancer, its testing accuracy has become a matter of serious concern. To address this issue, a long-term ctDNA analysis proficiency testing (PT) scheme for next-generation sequencing (NGS) was launched in China in 2018, serving as an educational tool for assessing and improving the testing quality of NGS-based ctDNA detection.
Feedback from participating laboratories across 23 different PT samples containing different variants with varying variant allele frequency was collected between 2018 and 2021. To further show the landscape of changing conditions in accuracy and reliability of NGS-based ctDNA testing, performance was analyzed by evaluating the cfDNA extraction kits, testing panels, target enrichment strategies, and sequencing platforms.
During the 4 years, 2745 results reported from 504 laboratories were evaluated. Only 66.3% of results from laboratories were entirely in concordance with the expected results. Nonetheless, along with an increasing number of participating laboratories, the number of errors occurring in laboratories, and the proportion of laboratories that experienced errors both showed a significant downward trend. No obvious differences in the error rates were found regarding the kit manufacturers or sequencing platform. Moreover, the individual performances of the laboratories improved when they participated in more PT scheme rounds.
These data demonstrated that the performance of individual Chinese laboratories for NGS-based ctDNA analysis continuously improved over time with participation in PT schemes. However, further care must also be taken in standardized operations and validations.
由于循环肿瘤DNA（ctDNA）测序在癌症患者的临床管理中应用越来越广泛，其检测准确性已成为一个备受关注的问题。为解决这一问题，2018年中国启动了一项针对下一代测序（NGS）的长期ctDNA分析能力验证（PT）计划，作为评估和提高基于NGS的ctDNA检测质量的教育工具。
收集了2018年至2021年间来自23个不同PT样本的参与实验室的反馈，这些样本包含不同变异等位基因频率的不同变异。为了进一步展示基于NGS的ctDNA检测准确性和可靠性变化情况，通过评估cfDNA提取试剂盒、检测面板、目标富集策略和测序平台来分析性能。
在这4年中，对504个实验室报告的2745个结果进行了评估。只有66.3%的实验室结果与预期结果完全一致。尽管如此，随着参与实验室数量的增加，实验室出现错误的数量以及出现错误的实验室比例均呈显著下降趋势。在试剂盒制造商或测序平台方面，未发现错误率有明显差异。此外，实验室参与更多轮PT计划时，其个体表现有所改善。
这些数据表明，随着参与PT计划，中国各实验室基于NGS的ctDNA分析性能随时间不断提高。然而，在标准化操作和验证方面仍需进一步谨慎对待。
