Division of Hematology and Oncology, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, PA, USA.
Marlene and Stewart Greenebaum Comprehensive Cancer Center, University of Maryland School of Medicine, Balitmore, MD, USA.
Nat Rev Clin Oncol. 2021 Jan;18(1):56-62. doi: 10.1038/s41571-020-0423-x. Epub 2020 Sep 11.
Upfront tumour genotyping is now considered an essential step in guiding treatment decision-making in the management of patients with advanced-stage non-small-cell lung cancer (NSCLC) in light of the ever-expanding toolbox of targeted therapies and immune-checkpoint inhibitors. However, genotyping of tumour biopsy samples is not feasible for all patients and, therefore, genomic analysis of circulating tumour DNA (ctDNA) has emerged as a compelling non-invasive option. Current guidelines universally recommend genotyping and support the use of ctDNA testing in certain settings, although they often omit the detail necessary for integrating these tests into clinical care on an individual basis. In this Perspective, we describe the rationale, promise and challenges associated with ctDNA-based NSCLC genotyping and suggest a framework for the implementation of these assays into routine clinical practice. We also offer considerations for the interpretation of ctDNA genotyping results, which, particularly when using next-generation sequencing panels, can be nuanced. Through the addition of this new approach to clinical practice, we propose that oncologists might finally be able to utilize effective genotyping in nearly all patients with advanced-stage NSCLC.
鉴于靶向治疗和免疫检查点抑制剂的工具不断扩展，目前对晚期非小细胞肺癌（NSCLC）患者的治疗决策进行指导时，肿瘤基因分型已被认为是一个重要步骤。然而，并非所有患者都可行肿瘤活检样本基因分型，因此，循环肿瘤 DNA（ctDNA）的基因组分析已成为一种极具吸引力的非侵入性选择。目前的指南普遍建议进行基因分型，并支持在某些情况下使用 ctDNA 检测，但它们通常省略了将这些检测纳入个体化临床护理的必要细节。在本观点文章中，我们描述了基于 ctDNA 的 NSCLC 基因分型的原理、前景和挑战，并提出了将这些检测纳入常规临床实践的框架。我们还提供了 ctDNA 基因分型结果解读的注意事项，特别是在使用下一代测序面板时，结果解读可能较为复杂。通过将这种新方法添加到临床实践中，我们提出肿瘤学家最终可能能够在几乎所有晚期 NSCLC 患者中使用有效的基因分型。
