Department of Thoracic Surgery, Xuanwu Hospital Capital Medical University, Beijing, China.
Medical Center, Geneplus-Beijing, Beijing, China.
Thorac Cancer. 2024 Apr;15(10):797-807. doi: 10.1111/1759-7714.15251. Epub 2024 Feb 26.
Circulating tumor DNA (ctDNA) has emerged as a potential novel biomarker to predict molecular residual disease (MRD) in lung cancer after definitive treatment. Herein, we investigated the value of ctDNA in prognosing risk of relapse and monitoring the effect of adjuvant therapy in surgical non-small cell lung cancer (NSCLC).
We enrolled 58 NSCLC patients in a real-world setting, and 58 tumor tissues and 325 plasma samples were analyzed. Tumor tissues and plasma samples were subjected to targeted next-generation sequencing (NGS) of 1021 cancer-related and ultra-deep targeted NGS covering 338 genes, respectively.
ctDNA was detected in 31.0% of cases at the first postoperative time, which was associated with advanced tumor stage, T stage and KEAP1 or GRIN2A mutations in tissues. ctDNA positivity at landmark and longitudinal indicated the shorter disease-free survival. For patients with ctDNA positivity at the first postoperative time, regardless of adjuvant therapy, all patients who were persistently ctDNA positive during postoperative surveillance had disease recurrence. Among the patients who were ctDNA negative, only two patients (15.4%, 2/13) receiving adjuvant therapy relapsed, while one patient (50.0%, 1/2) without adjuvant therapy relapsed. For the first postoperative ctDNA negative patients, the recurrence rate of patients with adjuvant therapy was and higher than without adjuvant therapy (22.6% [7/31] vs. 11.1% [1/9]). The patients who became ctDNA positive may also benefit from intervention therapy.
Postoperative ctDNA is a prognostic marker, and ctDNA-detection may facilitate personalized adjuvant therapy, and applying adjuvant therapy to the patients with detectable ctDNA could bring clinical benefits for them.
循环肿瘤 DNA（ctDNA）已成为预测肺癌根治性治疗后分子残留疾病（MRD）的一种潜在新型生物标志物。在此，我们研究了 ctDNA 在预测复发风险和监测辅助治疗对手术非小细胞肺癌（NSCLC）疗效中的作用。
我们在真实环境中招募了 58 例 NSCLC 患者，分析了 58 例肿瘤组织和 325 例血浆样本。分别对肿瘤组织和血浆样本进行了靶向下一代测序（NGS），检测 1021 个与癌症相关的基因和超深度靶向 NGS 检测 338 个基因。
首次术后时，31.0%的病例检测到 ctDNA，与晚期肿瘤分期、T 分期以及组织中的 KEAP1 或 GRIN2A 突变相关。首次术后的 ctDNA 阳性与无病生存期缩短相关。对于首次术后 ctDNA 阳性的患者，无论是否接受辅助治疗，所有在术后监测中持续 ctDNA 阳性的患者均出现疾病复发。在 ctDNA 阴性的患者中，仅 2 例（15.4%，2/13）接受辅助治疗的患者复发，而 1 例（50.0%，1/2）未接受辅助治疗的患者复发。对于首次术后 ctDNA 阴性的患者，接受辅助治疗的患者复发率高于未接受辅助治疗的患者（22.6%[7/31] vs. 11.1%[1/9]）。首次术后 ctDNA 转为阳性的患者可能也从干预治疗中获益。
术后 ctDNA 是一种预后标志物，ctDNA 检测可能有助于辅助治疗的个体化选择，对可检测到 ctDNA 的患者应用辅助治疗可能为他们带来临床获益。
