Data from Perioperative ctDNA-Based Molecular Residual Disease Detection for Non–Small Cell Lung Cancer: A Prospective Multicenter Cohort Study (LUNGCA-1)
التفاصيل البيبلوغرافية
العنوان:
Data from Perioperative ctDNA-Based Molecular Residual Disease Detection for Non–Small Cell Lung Cancer: A Prospective Multicenter Cohort Study (LUNGCA-1)
American Association for Cancer Research (AACR), 2023.
سنة النشر:
2023
الوصف:
Purpose:We assessed whether perioperative circulating tumor DNA (ctDNA) could be a biomarker for early detection of molecular residual disease (MRD) and prediction of postoperative relapse in resected non–small cell lung cancer (NSCLC).Experimental Design:Based on our prospective, multicenter cohort on dynamic monitoring of ctDNA in lung cancer surgery patients (LUNGCA), we enrolled 950 plasma samples obtained at three perioperative time points (before surgery, 3 days and 1 month after surgery) of 330 stage I–III NSCLC patients (LUNGCA-1), as a part of the LUNGCA cohort. Using a customized 769-gene panel, somatic mutations in tumor tissues and plasma samples were identified with next-generation sequencing and utilized for ctDNA-based MRD analysis.Results:Preoperative ctDNA positivity was associated with lower recurrence-free survival (RFS; HR = 4.2; P < 0.001). The presence of MRD (ctDNA positivity at postoperative 3 days and/or 1 month) was a strong predictor for disease relapse (HR = 11.1; P < 0.001). ctDNA-based MRD had a higher relative contribution to RFS prediction than all clinicopathologic variables such as the TNM stage. Furthermore, MRD-positive patients who received adjuvant therapies had improved RFS over those not receiving adjuvant therapy (HR = 0.3; P = 0.008), whereas MRD-negative patients receiving adjuvant therapies had lower RFS than their counterparts without adjuvant therapy (HR = 3.1; P < 0.001). After adjusting for clinicopathologic variables, whether receiving adjuvant therapies remained an independent factor for RFS in the MRD-positive population (P = 0.002) but not in the MRD-negative population (P = 0.283).Conclusions:Perioperative ctDNA analysis is effective in early detection of MRD and relapse risk stratification of NSCLC, and hence could benefit NSCLC patient management.
