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

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.

Research Progress on Postoperative Minimal/Molecular Residual Disease Detection in Lung Cancer

Lung cancer is the leading cause of cancer-related deaths worldwide.Approximately 10%-50%of patients experience relapse after radical surgery,which may be attributed to the persistence of minimal/molecular residual disease(MRD).Circulating tumor DNA(ctDNA),a common liquid biopsy approach,has been demonstrated to have significant clinical merit.In this study,we review the evidence supporting the use of ctDNA for MRD detection and discuss the potential clinical applications of postoperative MRD detection,including monitoring recurrence,guiding adjuvant treatment,and driving clinical trials in lung cancer.We will also discuss the problems that prevent the routine application of ctDNA MRD detection.Multi-analyte methods and identification of specific genetic and molecular alterations,especially methylation,are effective detection strategies and show considerable prospects for future development.Interventional prospective studies based on ctDNA detection are needed to determine whether the application of postoperative MRD detection can improve the clinical outcomes of lung cancer patients,and the accuracy,sensitivity,specificity,and robustness of different detection methods still require optimization and refinement.