基因融合和 MET 改变很少见，并且很难在血浆样本中检测到。基于循环肿瘤 DNA (ctDNA) 的分子残留病 (MRD) 对携带这些突变的非小细胞肺癌 (NSCLC) 患者的临床检测效果仍不清楚。这项前瞻性、非干预性研究招募了 49 名可手术 NSCLC 患者，这些患者具有可操作的基因融合（ALK、ROS1、RET 和 FGFR1）、MET 外显子 14 跳跃或从头 MET 扩增。我们分别使用 1021 和 338 基因组分析了 43 个肿瘤组织和 111 个连续围手术期血浆样本。可检测到的 MRD 与显着较高的复发率相关 (P < 0.001)，在里程碑和纵向时间点的阳性预测值分别为 100% 和 90.9%，阴性预测值分别为 82.4% 和 86.4%。与未检测到 MRD 的患者相比，可检测到 MRD 的患者无病生存期 (DFS) 较低 (P < 0.001)。与那些没有 MRD 改变的患者相比，那些 MRD 发生组织衍生融合/MET 改变的患者的 DFS 降低（P = 0.05）。据我们所知，这是第一个针对基因融合和 MET 改变的可手术 NSCLC 患者的 ctDNA-MRD 临床检测效果的综合研究。术后 MRD 中可检测到组织源性融合/MET 改变的患者临床结果较差。© 2024。高等教育出版社。

Gene fusions and MET alterations are rare and difficult to detect in plasma samples. The clinical detection efficacy of molecular residual disease (MRD) based on circulating tumor DNA (ctDNA) in patients with non-small cell lung cancer (NSCLC) with these mutations remains unknown. This prospective, non-intervention study recruited 49 patients with operable NSCLC with actionable gene fusions (ALK, ROS1, RET, and FGFR1), MET exon 14 skipping or de novo MET amplification. We analyzed 43 tumor tissues and 111 serial perioperative plasma samples using 1021- and 338-gene panels, respectively. Detectable MRD correlated with a significantly higher recurrence rate (P < 0.001), yielding positive predictive values of 100% and 90.9%, and negative predictive values of 82.4% and 86.4% at landmark and longitudinal time points, respectively. Patients with detectable MRD showed reduced disease-free survival (DFS) compared to those with undetectable MRD (P < 0.001). Patients who harbored tissue-derived fusion/MET alterations in their MRD had reduced DFS compared to those who did not (P = 0.05). To our knowledge, this is the first comprehensive study on ctDNA-MRD clinical detection efficacy in operable NSCLC patients with gene fusions and MET alterations. Patients with detectable tissue-derived fusion/MET alterations in postoperative MRD had worse clinical outcomes.© 2024. Higher Education Press.