Tan Aaron C, Lai Gillianne G Y, Saw Stephanie P L, Chua Kevin L M, Takano Angela, Ong Boon-Hean, Koh Tina P T, Jain Amit, Tan Wan Ling, Ng Quan Sing, Kanesvaran Ravindran, Rajasekaran Tanujaa, Kalashnikova Ekaterina, Renner Derrick, Sudhaman Sumedha, Malhotra Meenakshi, Sethi Himanshu, Liu Minetta C, Aleshin Alexey, Lim Wan-Teck, Tan Eng-Huat, Skanderup Anders J, Ang Mei-Kim, Tan Daniel S W
Division of Medical Oncology, National Cancer Centre Singapore, Singapore, Singapore.
Duke-NUS Medical School, National University of Singapore, Singapore, Singapore.
Cancer. 2024 May 15;130(10):1758-1765. doi: 10.1002/cncr.35263. Epub 2024 Feb 29.
In early-stage non-small cell lung cancer (NSCLC), recurrence is frequently observed. Circulating tumor DNA (ctDNA) has emerged as a noninvasive tool to risk stratify patients for recurrence after curative intent therapy. This study aimed to risk stratify patients with early-stage NSCLC via a personalized, tumor-informed multiplex polymerase chain reaction (mPCR) next-generation sequencing assay.
This retrospective cohort study included patients with stage I-III NSCLC. Recruited patients received standard-of-care management (surgical resection with or without adjuvant chemotherapy, followed by surveillance). Whole-exome sequencing of NSCLC resected tissue and matched germline DNA was used to design patient-specific mPCR assays (Signatera, Natera, Inc) to track up to 16 single-nucleotide variants in plasma samples.
The overall cohort with analyzed plasma samples consisted of 57 patients. Stage distribution was 68% for stage I and 16% each for stages II and III. Presurgery (i.e., at baseline), ctDNA was detected in 15 of 57 patients (26%). ctDNA detection presurgery was significantly associated with shorter recurrence-free survival (RFS; hazard ratio [HR], 3.54; 95% confidence interval [CI], 1.00-12.62; p = .009). In the postsurgery setting, ctDNA was detected in seven patients, of whom 100% experienced radiological recurrence. ctDNA positivity preceded radiological findings by a median lead time of 2.8 months (range, 0-12.9 months). Longitudinally, ctDNA detection at any time point was associated with shorter RFS (HR, 16.1; 95% CI, 1.63-158.9; p < .0001).
ctDNA detection before surgical resection was strongly associated with a high risk of relapse in early-stage NSCLC in a large unique Asian cohort. Prospective studies are needed to assess the clinical utility of ctDNA status in this setting.
在早期非小细胞肺癌（NSCLC）中，复发较为常见。循环肿瘤DNA（ctDNA）已成为一种用于对接受根治性治疗后的患者复发风险进行分层的非侵入性工具。本研究旨在通过个性化的、基于肿瘤信息的多重聚合酶链反应（mPCR）下一代测序检测对早期NSCLC患者进行复发风险分层。
这项回顾性队列研究纳入了I - III期NSCLC患者。入选患者接受标准治疗管理（手术切除，伴或不伴辅助化疗，随后进行监测）。对NSCLC切除组织和匹配的种系DNA进行全外显子测序，以设计患者特异性的mPCR检测（Signatera，Natera公司），用于追踪血浆样本中多达16个单核苷酸变异。
分析血浆样本的整个队列由57名患者组成。分期分布为I期占68%，II期和III期各占16%。术前（即基线时），57名患者中有15名（26%）检测到ctDNA。术前ctDNA检测与无复发生存期（RFS）较短显著相关（风险比[HR]，3.54；95%置信区间[CI]，1.00 - 12.62；p = 0.009）。在术后阶段，7名患者检测到ctDNA，其中100%出现影像学复发。ctDNA阳性比影像学发现提前出现，中位提前时间为2.8个月（范围，0 - 12.9个月）。纵向来看，在任何时间点检测到ctDNA都与较短的RFS相关（HR，16.1；95% CI，1.63 - 158.9；p < 0.0001）。
在一个大型独特的亚洲队列中，手术切除前ctDNA检测与早期NSCLC的高复发风险密切相关。需要进行前瞻性研究来评估在此情况下ctDNA状态的临床效用。
