Early stage NSCLC - challenges to implementing ctDNA-based screening and MRD detection
Early stage NSCLC - challenges to implementing ctDNA-based screening and MRD detection
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DOI：
10.1038/s41571-018-0058-3
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发表时间：
2018-09-01
影响因子：
78.8
通讯作者：
Swanton, Charles
中科院分区：
文献类型：
--
作者：
Abbosh, Christopher;Birkbak, Nicolai J.;Swanton, Charles
循环肿瘤DNA（ctDNA）是指患者血液中来源于肿瘤的无细胞DNA部分。DNA测序技术的进步和我们对肿瘤分子生物学的理解，使人们越来越有兴趣利用ctDNA作为一种工具，以促进早期检测癌症，从而改善治疗结果，使早期干预。ctDNA分析还可以在辅助治疗环境中具有实用性，其通过使得能够基于手术后最小（或分子）残留疾病（MRD）的检测来鉴定处于疾病复发的高风险的患者。这种方法可以提供在辅助治疗环境中适应临床试验的能力，以优化风险分层，我们认为，这一目标是可以实现的与当前的技术。在此，我们评估了当代新一代测序（NGS）方法来检测ctDNA，重点是非小细胞肺癌。我们解释了使用基于NGS的ctDNA分析进行低频突变检测的技术和分析挑战，并评估了ctDNA分析在筛查和MRD评估背景下的可行性。
Circulating tumour DNA (ctDNA) refers to the fraction of cell-free DNA in a patient's blood that originates from a tumour. Advances in DNA sequencing technologies and our understanding of the molecular biology of tumours have resulted in increased interest in exploiting ctDNA as a tool to facilitate earlier detection of cancer and thereby improve therapeutic outcomes by enabling early intervention. ctDNA analysis might also have utility in the adjuvant therapeutic setting by enabling the identification of patients at a high risk of disease recurrence on the basis of the detection of post-surgical minimal (or molecular) residual disease (MRD). This approach could provide the capability to adapt clinical trials in the adjuvant setting in order to optimize risk stratification, and we argue that this objective is achievable with current technologies. Herein, we evaluate contemporary next-generation sequencing (NGS) approaches to ctDNA detection with a focus on non-small-cell lung cancer. We explain the technical and analytical challenges to low-frequency mutation detection using NGS-based ctDNA profiling and evaluate the feasibility of ctDNA profiling in both screening and MRD assessment contexts.