Yonsei Cancer Center, Division of Medical Oncology, Department of Internal Medicine, Yonsei University College of Medicine, Seoul, Korea; Center for Lung Cancer, Research Institute and Hospital, National Cancer Center, Goyang, Korea.
Division of Medical Oncology, Department of Internal Medicine, Gangnam Severance Hospital, Yonsei University College of Medicine, Seoul, Korea.
Cancer Treat Res Commun. 2023;36:100715. doi: 10.1016/j.ctarc.2023.100715. Epub 2023 Jun 8.
Plasma-based comprehensive circulating cell-free DNA (cfDNA) next generation sequencing (NGS) has shown utility in advanced non-small cell lung cancer (aNSCLC). The aim of this study was to determine the feasibility of cfDNA-based NGS to identify actionable gene alterations in patients with aNSCLC.
This single-center non-interventional retrospective study evaluated Korean patients with biopsy-confirmed stage III/IV non-squamous aNSCLC. Tissue biopsy samples were collected at baseline, and/or at progression and analysed with Standard of Care (SOC) testing; cfDNA was analyzed by NGS in some patients concurrently.
aNSCLC patients with cfDNA test results (n = 405) were categorized into three groups: treatment naïve (n = 182), progressive aNSCLC after chemotherapy and/or immunotherapy (n = 157), and progressive aNSCLC after tyrosine kinase inhibitors (TKIs) (n = 66). Clinically informative driver mutations were identified for 63.5% of patients which were classified as OncoKB Tiers 1 (44.2%), 2 (3.4%), tier 3 (18.9%), and 4 (33.5%). Concordance between cfDNA NGS and tissue SOC methods for concurrently collected tissue samples (n = 221) with common EGFR mutations or ALK/ROS1 fusions was 96.9%. cfDNA analysis identified tumor genomic alterations in 13 patients that were unidentified with tissue testing, enabling initiation of targeted treatment.
In clinical practice, results of cfDNA NGS are highly concordant with those of tissue SOC testing in aNSCLC patients. Plasma analysis identified actionable alterations that were missed or not evaluated by tissue testing, enabling the initiation of targeted therapy. Results from this study add to the body of evidence in the support routine use of cfDNA NGS for patients with aNSCLC.
基于血浆的综合游离循环 DNA（cfDNA）下一代测序（NGS）已显示出在晚期非小细胞肺癌（aNSCLC）中的应用价值。本研究旨在确定基于 cfDNA 的 NGS 用于鉴定 aNSCLC 患者可操作基因改变的可行性。
这是一项单中心、非干预性、回顾性研究，评估了经组织活检证实为 III/IV 期非鳞状 aNSCLC 的韩国患者。基线时采集组织活检样本，和/或在进展时采集并进行标准护理（SOC）检测分析；一些患者同时进行 cfDNA 的 NGS 分析。
有 cfDNA 检测结果的 aNSCLC 患者（n=405）分为三组：治疗初治（n=182）、化疗和/或免疫治疗后进展的 aNSCLC（n=157）、以及酪氨酸激酶抑制剂（TKI）后进展的 aNSCLC（n=66）。鉴定出 63.5%的患者具有临床意义的驱动基因突变，这些突变被归类为 OncoKB 级别 1（44.2%）、2（3.4%）、3（18.9%）和 4（33.5%）。同时采集的组织样本（n=221）中 cfDNA NGS 与 SOC 方法检测常见 EGFR 突变或 ALK/ROS1 融合的一致性为 96.9%。cfDNA 分析在 13 名患者中发现了组织检测未识别的肿瘤基因组改变，从而能够开始靶向治疗。
在临床实践中，cfDNA NGS 的结果与 aNSCLC 患者组织 SOC 检测的结果高度一致。血浆分析发现了组织检测遗漏或未评估的可操作改变，从而能够开始靶向治疗。这项研究的结果为支持常规使用 cfDNA NGS 用于 aNSCLC 患者提供了更多证据。
