Meng Wei, Petry Russell, Galicia Norberto Pantoja, van den Hout Allison, Yu Jessie, Gong Siliang, Shah Dhara, Sun Daokun, Guo Cui, Bailey Shannon, Munafo Daniela, Woodhouse Ryan, Mansfield Elizabeth, Pattani Varun, Perrault Steven, Zhou Jun, Vietz Christine, Li Meijuan, Huang Richard S P
Foundation Medicine, Inc., Boston, Massachusetts, United States of America.
PLoS One. 2025 Aug 1;20(8):e0329392. doi: 10.1371/journal.pone.0329392. eCollection 2025.
Per regulatory and standard requirements (e.g., Clinical & Laboratory Standards Institute (CLSI) guidelines, United States Food and Drug Administration (FDA) correspondence), analytical validation (AV) for each companion diagnostic (CDx) biomarker should be repeated using a clinical sample set for each cancer type listed as an indication in labelling for a CDx. Using data from AV studies and Foundation Medicine (FMI)'s clinical database, we evaluated the hypothesis that analytical performance of the FoundationOne®Liquid CDx (F1LCDx) assay is not impacted by cancer type and that large sets of clinical, tumor-specific samples might not be necessary for analytical validation of specific CDx biomarkers. We retrospectively evaluated all liquid biopsy samples from F1LCDx assay AV studies that were executed between April 2019 and November 2021 and clinical samples processed by F1LCDx between September 2020 and October 2021. For the samples from AV studies, we evaluated the precision and concordance performance by F1LCDx between tumor types; and for the clinical samples, we performed analyses comparing the distribution of coverage between tumor types. A total of 31,247 F1LCDx clinical samples and 579 samples from F1LCDx AV studies with a total of 335 disease ontologies (DOs) were included in this study. For precision: the median absolute pairwise difference of mean reproducibility between any pairs of two tumor types is 0.94% [0.01%-2.63%] and the median absolute pairwise difference of mean repeatability between any pairs of two tumor types is 0.91% [0.03%-2.98%]. For concordance: the median absolute [Formula: see text] between any pairs of two tumor types is 1.39% [0.1%-4.1%] and the median absolute [Formula: see text] between any pairs of two tumor types is 0.05% [0%-1%]. For coverage, a similar distribution was observed between tumor types using F1LCDx clinical samples. Herein, the results based on the extensive cohort of 31,826 liquid biopsy samples sequenced by the F1LCDx assay demonstrated that both analytical assessment of precision and concordance and coverage are comparable among tumor types (i.e., deoxyribonucleic acid (DNA) is DNA). The tumor type that circulating tumor DNA (ctDNA) was derived from is therefore not a vital consideration for AV studies for F1LCDx assay.
根据法规和标准要求（例如，临床与实验室标准协会（CLSI）指南、美国食品药品监督管理局（FDA）信函），对于每种伴随诊断（CDx）生物标志物的分析验证（AV），应使用在CDx标签中列为适应症的每种癌症类型的临床样本集重复进行。利用AV研究的数据和Foundation Medicine（FMI）的临床数据库，我们评估了以下假设：FoundationOne®液体CDx（F1LCDx）检测的分析性能不受癌症类型影响，并且大量的临床、肿瘤特异性样本对于特定CDx生物标志物的分析验证可能不是必需的。我们回顾性评估了2019年4月至2021年11月期间进行的F1LCDx检测AV研究中的所有液体活检样本，以及2020年9月至2021年10月期间由F1LCDx处理的临床样本。对于AV研究的样本，我们评估了F1LCDx在不同肿瘤类型之间的精密度和一致性性能；对于临床样本，我们进行了分析，比较了不同肿瘤类型之间覆盖范围的分布。本研究共纳入了31,247份F1LCDx临床样本和579份来自F1LCDx AV研究的样本，共涉及335种疾病本体（DO）。对于精密度：任意两种肿瘤类型之间平均重现性的中位绝对成对差异为0.94%[0.01%-2.63%]，任意两种肿瘤类型之间平均重复性的中位绝对成对差异为0.91%[0.03%-2.98%]。对于一致性：任意两种肿瘤类型之间的中位绝对[公式：见原文]为1.39%[0.1%-4.1%]，任意两种肿瘤类型之间的中位绝对[公式：见原文]为0.05%[0%-1%]。对于覆盖范围，使用F1LCDx临床样本在不同肿瘤类型之间观察到类似的分布。在此，基于通过F1LCDx检测测序的31,826份液体活检样本的广泛队列的结果表明，精密度、一致性和覆盖范围的分析评估在不同肿瘤类型之间具有可比性（即，脱氧核糖核酸（DNA）就是DNA）。因此，循环肿瘤DNA（ctDNA）来源的肿瘤类型对于F1LCDx检测的AV研究不是一个至关重要的考虑因素。
