Foundation Medicine, Inc., Morrisville, NC.
Foundation Medicine, Inc., Cambridge, MA.
Clin Chem. 2021 Nov 1;67(11):1554-1566. doi: 10.1093/clinchem/hvab176.
The amounts of circulating cell-free DNA (cfDNA) and circulating-tumor DNA (ctDNA) present in peripheral blood liquid biopsies can vary due to preanalytic/analytic variables. In this study, we examined the impact of patient age, sex, stage, and tumor type on cfDNA yield, ctDNA fraction, and estimated ctDNA quantity from a large cohort of clinical liquid biopsy samples.
We performed a retrospective analysis of 12 139 consecutive samples received for liquid biopsy (FoundationOne® Liquid) clinical testing.
Significant differences in both cfDNA yield and estimated ctDNA quantity were observed based on the underlying tumor type that initiated the liquid biopsy analysis and the stage of the patient (P < 0.001). In addition, significant differences in ctDNA quantity were present based in both the patient age and sex (P < 0.001). Importantly, we saw a significantly higher success rate of issuing a clinically useful report in patients with higher levels of cfDNA yield and ctDNA quantity (P < 0.001).
In this study, we show that ctDNA quantity varied significantly based on patient age, sex, stage, and tumor type, which could offer an explanation as to why certain liquid biopsy specimens are more likely to fail sequencing or provide clinically meaningful results. In addition, this could affect future clinical decisions on the blood sample volumes required to allow successful liquid biopsy testing.
外周血液体活检中循环无细胞 DNA(cfDNA)和循环肿瘤 DNA(ctDNA)的含量因分析前/分析变量而异。在这项研究中,我们研究了患者年龄、性别、分期和肿瘤类型对大量临床液体活检样本中 cfDNA 产量、ctDNA 分数和估计 ctDNA 量的影响。
我们对 12139 例连续接受液体活检(FoundationOne®液体)临床检测的样本进行了回顾性分析。
根据启动液体活检分析的基础肿瘤类型和患者分期,cfDNA 产量和估计 ctDNA 量均存在显著差异(P<0.001)。此外,ctDNA 量也存在显著差异,且与患者年龄和性别有关(P<0.001)。重要的是,我们发现 cfDNA 产量和 ctDNA 量较高的患者发布临床有用报告的成功率显著更高(P<0.001)。
在这项研究中,我们表明 ctDNA 量根据患者年龄、性别、分期和肿瘤类型存在显著差异,这可以解释为什么某些液体活检标本更有可能测序失败或提供有临床意义的结果。此外,这可能会影响未来关于允许成功进行液体活检检测所需的血液样本量的临床决策。