Perioperative ctDNA-based Molecular Residual Disease Detection for Non-Small Cell Lung Cancer: A Prospective Multicenter Cohort Study (LUNGCA-1)

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Clin Cancer Res. 2021 Nov 29:clincanres.3044.2021. doi: 10.1158/1078-0432.CCR-21-3044. Online ahead of print.


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-day and 1-month after surgery) of 330 stage I-III NSCLC patients (LUNGCA-1), as a part of 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-day 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 clinicopathological 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 clinicopathological 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.

PMID:34844976 | DOI:10.1158/1078-0432.CCR-21-3044