通过对实体瘤循环肿瘤DNA进行下一代测序进行全面基因组分析：一所学术机构的经验
Comprehensive genome profiling by next generation sequencing of circulating tumor DNA in solid tumors: a single academic institution experience.
作者信息
Caputo Vincenza, De Falco Vincenzo, Ventriglia Anna, Famiglietti Vincenzo, Martinelli Erika, Morgillo Floriana, Martini Giulia, Corte Carminia Maria Della, Ciardiello Davide, Poliero Luca, De Vita Ferdinando, Orditura Michele, Fasano Morena, Franco Renato, Caraglia Michele, Avitabile Arianna, Scalamogna Roberto, Marchi Beatrice, Ciardiello Fortunato, Troiani Teresa, Napolitano Stefania
机构信息
Medical Oncology, Department of Precision Medicine, Università degli Studi della Campania 'Luigi Vanvitelli', Napoli, Italy.
Pathology Unit, Department of Mental and Physical Health and Preventive Medicine, Università degli Studi della Campania 'Luigi Vanvitelli', Napoli, Italy.
出版信息
Ther Adv Med Oncol. 2022 May 7;14:17588359221096878. doi: 10.1177/17588359221096878. eCollection 2022.
BACKGROUND
Recently, new evidence of the next-generation sequencing (NGS) liquid biopsy utility in clinical practice has been developed. This assay is emerging as a new promising tool to use as a noninvasive biomarker for cancer mutation profiling. Additional data supporting the clinical validity of cell free DNA (cfDNA) based testing is necessary to inform optimal use of these assays in the clinic.
MATERIALS AND METHODS
A total of 398 cancer patients were analyzed by FoundationOne Liquid Analysis (F1LA), a genomic profiling assay and by standard NGS diagnostic ThermoFisher platform. The association between diagnostic technique was evaluated using a Poisson regression model. FoundationOne Liquid (F1L) and FoundationOne Liquid CDx (F1LCDx) detect 70 and 324 cancer-related genes alterations, respectively, including genomic signatures tumor fraction, blood tumor mutational burden (only for the 324 genes version), and microsatellite instability high status. Both assays used a single DNA extraction method to obtain cfDNA. The real-life clinical impact and feasibility of F1L and F1LCDx were evaluated across different solid tumors in our department.
RESULTS
Between 1 January 2019 and 28 February 2021, 398 samples of different tumor types from 398 patients were analyzed (overall success rate: 92%, in FoundationOne Liquid CDx Analysis success rate: 97%). Most frequent molecular alterations were (74), (40), (39), (23). The comprehensive clinical impact of F1LA compared with standard diagnostic was 64.7% 22.1% [risk ratio (RR) = 2.94; < 0.001] and the potential clinical impact was 58.6% 11.0% (RR = 5.32; < 0.001), respectively. Furthermore, some clinical cases were selected, in which F1LA detected actionable alterations offering an unexpected therapeutic choice.
CONCLUSIONS
Although additional studies are needed to better select patients and setting, NGS F1LA is a useful, noninvasive, and repeatable assay to guide therapeutic choice in oncology. It provides a snapshot of cancer heterogeneity profile that could be incorporated in routinely clinical practice.
背景
最近，下一代测序（NGS）液体活检在临床实践中的应用有了新证据。该检测正成为一种新的有前景的工具，用作癌症突变谱分析的非侵入性生物标志物。需要更多支持基于游离DNA（cfDNA）检测临床有效性的数据，以便在临床中优化这些检测的使用。
材料与方法
共有398例癌症患者接受了FoundationOne液体分析（F1LA），这是一种基因组分析检测，并通过标准的NGS诊断ThermoFisher平台进行检测。使用泊松回归模型评估诊断技术之间的关联。FoundationOne液体检测（F1L）和FoundationOne液体CDx检测（F1LCDx）分别检测70个和324个癌症相关基因改变，包括基因组特征肿瘤分数、血液肿瘤突变负担（仅适用于324个基因版本）和微卫星高度不稳定状态。两种检测均使用单一DNA提取方法获取cfDNA。在我们科室，对F1L和F1LCDx在不同实体瘤中的实际临床影响和可行性进行了评估。
结果
在2019年1月1日至2021年2月28日期间，对398例患者的398份不同肿瘤类型样本进行了分析（总体成功率：92%，在FoundationOne液体CDx分析中成功率：97%）。最常见的分子改变为（74）、（40）、（39）、（23）。与标准诊断相比，F1LA的综合临床影响为64.7% 22.1%[风险比（RR） = 2.94； < 0.001]，潜在临床影响为58.6% 11.0%（RR = 5.32； < 0.001）。此外，还选择了一些临床病例，其中F1LA检测到可采取行动的改变，提供了意想不到的治疗选择。
结论
尽管需要更多研究以更好地选择患者和确定应用场景，但NGS F1LA是一种有用的、非侵入性且可重复的检测，可指导肿瘤学中的治疗选择。它提供了癌症异质性谱的概况，可纳入常规临床实践。
Zotero 插件