Background Liquid biopsies are emerging as valuable clinical biomarkers for cancer monitoring. Although International Organization for Standards (ISO) and Technical Specifications from the European Committee for Standardization (CEN/TS) standardized workflows exist, their implementation in clinical practice is underdeveloped. We aimed to assess the applicability of ISO and CEN/TS standards in a real-world clinical setting, with a particular focus on evaluating the impact of preanalytical parameters and hemolysis on liquid biopsy analysis. Methods We evaluated 659 peripheral blood samples from advanced prostate cancer patients against ISO and CEN/TS standards and documented all essential criteria, including tube draw order, filling level, temperature, and time tracking from blood draw to storage. We assessed hemolysis and its effect on circulating tumor DNA (ctDNA) and circulating tumor cell (CTC) analysis. Results Our results demonstrated a high compliance rate, with 96.2% (634/659) of samples meeting essential ISO and CEN/TS criteria. We did not observe a significant impact on ctDNA or CTC detection rates between hemolytic and nonhemolytic samples. Hemolysis was identified in 12.9% (40/311) of plasma samples from our advanced prostate cancer cohort, and within the draw order of 5 blood collection tubes, hemolysis did not significantly increase from tube 1 to 5. In total, 83.8% (552/659) of blood collection tubes had high fill levels above 80% of nominal filling level. Conclusions Our study demonstrates the feasibility and benefits of adhering to ISO and CEN/TS standards in a clinical liquid biopsy study. The standards revealed that hemolysis occurred frequently but did not impair downstream ctDNA and CTC analysis in our cohort of advanced prostate cancer patients.

中文翻译：

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液体活检 ISO 和 CEN/TS 标准的临床应用 — 每个人都想要但没有人愿意付费的信息


背景 液体活检正在成为癌症监测的有价值的临床生物标志物。尽管存在国际标准化组织 （ISO） 和欧洲标准化委员会 （CEN/TS） 的技术规范标准化工作流程，但它们在临床实践中的实施尚不成熟。我们旨在评估 ISO 和 CEN/TS 标准在真实临床环境中的适用性，特别侧重于评估分析前参数和溶血对液体活检分析的影响。方法 我们根据 ISO 和 CEN/TS 标准评估了来自晚期前列腺癌患者的 659 份外周血样本，并记录了所有基本标准，包括抽管顺序、填充水平、温度和从抽血到储存的时间跟踪。我们评估了溶血及其对循环肿瘤 DNA （ctDNA） 和循环肿瘤细胞 （CTC） 分析的影响。结果 我们的结果表明，依从率很高，96.2% （634/659） 的样品符合基本的 ISO 和 CEN/TS 标准。我们没有观察到溶血性和非溶血性样本之间对 ctDNA 或 CTC 检测率的显著影响。在我们晚期前列腺癌队列的 12.9% （40/311） 血浆样本中发现了溶血，并且在 5 根采血管的抽吸顺序中，溶血从试管 1 到 5 没有显着增加。总共 83.8% （552/659） 的采血管填充水平高于标称填充水平的 80%。结论 我们的研究表明了在临床液体活检研究中遵守 ISO 和 CEN/TS 标准的可行性和益处。标准显示，在我们的晚期前列腺癌患者队列中，溶血频繁发生，但并未影响下游 ctDNA 和 CTC 分析。