Clinical study of ctDNA-MRD monitoring to predict the risk of early recurrence and adjuvant therapy after NSCLC surgery

YE Hui; XU Tao; YANG Ying; JIN Zhongwen

doi:10.3969/j.issn.1009-0460.2025.03.005

Abstract：Objective To explore the efficacy of circulating tumor DNA(ctDNA)-minimal residual lesions(MRD)in predicting the risk of early recurrence after NSCLC and the efficacy of adjuvant chemotherapy.Methods One hundred and two patients with non-small cell lung cancer(NSCLC)who underwent surgery at Ningde Hospital affiliated to Ningde Normal University from January 2020 to December 2022 were collected as research subjects.Second generation sequencing(NGS)technology was used to detect ctDNA mutations before surgery,after surgery(within 4 weeks after surgery and before the start of adjuvant therapy),after adjuvant therapy,and during subsequent longitudinal monitoring(every 3 months).Patients were followed for recurrence-free survival(RFS).Results Somatic mutations were detected in tumor tissues of 92(90.20%)patients,of which 83.70%(77/92)mutations were detected in preoperative plasma samples.The median follow-up time of patients was 388 days(range:123 to 592 days),and the recurrence rate was 30.43%(28/92).The results of multivariate Cox hazard proportion regression model showed that postoperative ctDNA-MRD was an independent factor affecting postoperative RFS of NSCLC(P<0.05).Compared with postoperative ctDNA-MRD negative patients,postoperative ctDNA-MRD positive patients had higher recurrence rate and shorter median RFS(P<0.05).Kaplan-Meier results showed that the median time to RFS was significantly longer in ctDNA-MRD-positive patients receiving adjuvant therapy than in positive patients without adjuvant therapy(352 days vs.140 days,P=0.027).Of the 28 patients with radiographically confirmed recurrence,85.71%(24/28)had positive longitudinal ctDNA-MRD.ctDNA-MRD positivity preceded radiographic recurrence with a median lead time of 158 days.The median RFS time of longitudinal ctDNA-MRD positive patients was significantly shorter than that of negative patients(P<0.05).Conclusion the positive blood ctDNA-MRD is related to RFS in NSCLC.Patients with positive ctDNA-MRD after surgery are more likely to benefit after receiving adjuvant therapy.Blood ctDNA-MRD may serve as a useful biomarker for risk stratification of early postoperative recurrence in NSCLC as well as adjuvant treatment decision-making.