Ntzifa Aliki, Lianidou Evi
Analysis of Circulating Tumor Cells Lab, Lab of Analytical Chemistry, Department of Chemistry, National and Kapodistrian University of Athens, Athens, Greece.
Crit Rev Clin Lab Sci. 2023 Dec;60(8):573-594. doi: 10.1080/10408363.2023.2230290. Epub 2023 Jul 30.
Over the last decade, great advancements have been made in the field of liquid biopsy through extensive research and the development of new technologies that facilitate the use of liquid biopsy for cancer patients. This is shown by the numerous liquid biopsy tests that gained clearance by the US Food and Drug Administration (FDA) in recent years. Liquid biopsy has significantly altered cancer treatment by providing clinicians with powerful and immediate information about therapeutic decisions. However, the clinical integration of liquid biopsy is still challenging and there are many critical factors to consider prior to its implementation into routine clinical practice. Lack of standardization due to technical challenges and the definition of the clinical utility of specific assays further complicates the establishment of Standard Operating Procedures (SOPs) in liquid biopsy. Harmonization of laboratories to established guidelines is of major importance to overcome inter-lab variabilities observed. Quality control assessment in diagnostic laboratories that offer liquid biopsy testing will ensure that clinicians can base their therapeutic decisions on robust results. The regular participation of laboratories in external quality assessment schemes for liquid biopsy testing aims to promptly pinpoint deficiencies and efficiently educate laboratories to improve their quality of services. Accreditation of liquid biopsy diagnostic laboratories based on the ISO15189 standard in Europe or by CLIA/CAP accreditation procedures in the US is the best way to achieve the adaptation of liquid biopsy into the clinical setting by assuring reliable results for the clinicians and their cancer patients. Nowadays, various organizations from academia, industry, and regulatory agencies collaborate to set a framework that will include all procedures from the pre-analytical phase and the analytical process to the final interpretation of results. In this review, we underline several challenges in the analysis of circulating tumor DNA (ctDNA) and circulating tumor cells (CTCs) concerning standardization of protocols, quality control assessment, harmonization of laboratories, and compliance to specific guidelines that need to be thoroughly considered before liquid biopsy enters the clinic.
在过去十年中，通过广泛的研究以及新技术的开发，液体活检领域取得了巨大进展，这些新技术推动了液体活检在癌症患者中的应用。近年来，众多液体活检检测获得了美国食品药品监督管理局（FDA）的批准，这证明了这一点。液体活检通过为临床医生提供有关治疗决策的有力且即时的信息，显著改变了癌症治疗方式。然而，液体活检的临床整合仍具有挑战性，在将其应用于常规临床实践之前，有许多关键因素需要考虑。由于技术挑战导致的缺乏标准化以及特定检测临床效用的定义，进一步使液体活检标准操作程序（SOP）的建立变得复杂。使实验室符合既定指南对于克服所观察到的实验室间差异至关重要。提供液体活检检测的诊断实验室的质量控制评估将确保临床医生能够基于可靠的结果做出治疗决策。实验室定期参与液体活检检测的外部质量评估计划旨在迅速找出不足之处，并有效地培训实验室以提高其服务质量。在欧洲，基于ISO15189标准对液体活检诊断实验室进行认可，或在美国通过CLIA/CAP认可程序进行认可，是通过确保为临床医生及其癌症患者提供可靠结果，从而使液体活检适应临床环境的最佳方式。如今，来自学术界、产业界和监管机构的各种组织合作建立一个框架，该框架将涵盖从分析前阶段、分析过程到结果最终解读的所有程序。在本综述中，我们强调了在循环肿瘤DNA（ctDNA）和循环肿瘤细胞（CTC）分析方面的几个挑战，这些挑战涉及方案标准化、质量控制评估、实验室协调以及在液体活检进入临床之前需要全面考虑的遵守特定指南的问题。
