Perioperative ctDNA-based Molecular Residual Disease Detection for Non-Small Cell Lung Cancer: A Prospective Multicenter Cohort Study (LUNGCA-1)
Abstract
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…
How strong is the evidence?
Evidence Hub reads this as a cohort study, done in people. Its evidence level is 3 of 5 (Moderate · trial / cohort / secondary analysis). Trials without a large randomized design, cohorts and secondary analyses give moderate evidence.
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