Evaluation of molecular residual disease in operable non-small cell lung cancer with gene fusions,MET exon skipping or de novo MET amplification  

作　　者：Rui Fu Yuanyuan Xiong Miao Cai Fang Li Rongrong Chen Yilong Wu Wenzhao Zhong 

机构地区：[1]School of Medicine,South China University of Technology,Guangzhou,510006,China [2]Guangdong Lung Cancer Institute,Guangdong Provincial Key Laboratory of Translational Medicine in Lung Cancer,Guangdong Provincial People’s Hospital(Guangdong Academy of Medical Sciences),Southern Medical University,Guangzhou,510080,China [3]Geneplus-Beijing,Beijing,102206,China

出　　处：《Frontiers of Medicine》2024年第4期735-743,共9页医学前沿（英文版）

基　　金：supported by funding from the National Natural Science Foundation of China Major Joint Project on Key Scientific Issues of Lung Cancer(No.82241235);the National Natural Science Foundation of China(No.81872510);Guangdong Provincial People’s Hospital Young Talent Project(No.GDPPHYTP201902);Guangdong Basic and Applied Basic Research Foundation(No.2019B1515130002);High-level Hospital Construction Project(No.DFJH201801);Guangdong Provincial Key Laboratory of Translational Medicine in Lung Cancer(No.2017B030314120).

摘　　要：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.

关 键 词：CTDNA molecular residual disease operable NSCLC gene fusion MET exon skipping MET amplification 

分 类 号：R734.2[医药卫生—肿瘤]