Abstract 1159P
Background
The feasibility of DNA methylation-based assays in detecting minimal residual disease (MRD) and postoperative cancer surveillance remains unestablished. Our prospective study investigated the dynamic characteristics of cancer-related methylation signals and the feasibility of methylation-based MRD detection in surgical lung cancer patients.
Methods
Matched tumor, tumor-adjacent tissues, and longitudinal blood samples collected from 114 patients (MEDAL cohort) with stage I-IIIA non-small cell lung cancer were analyzed by both ultra-deep targeted sequencing and bisulfite sequencing. A tumor-informed methylation-based MRD (timMRD) model was employed to evaluate the methylation status of each blood sample. Survival analysis was performed in the MEDAL cohort and validated in the independent DYNAMIC cohort.
Results
Baseline timMRD-score was positively correlated with tumor burden and invasiveness reflected as tumor area, pathological stage, and solid nodules. TimMRD-score was significantly correlated with the existence and the abundance of somatic mutations in baseline blood samples. TimMRD-score revealed significant dynamic changes at perioperative periods and was significantly higher among the relapsed patients. Patients with higher timMRD-scores at the first follow-up demonstrated significantly shorter disease-free survival in both the MEDAL cohort (HR:5.02, 95%CI:1.17-21.51; P=0.007) and DYNAMIC cohort (HR: 2.36, 95%CI: 1.06-5.23; P=0.025). TimMRD-score identified all the relapsed patients during follow-up regardless of mutation status in the MEDAL cohort. Integrating methylation and mutation status identified recurrence in 0% (0/34) of the low-risk group, 22.2% (8/36) of the medium-risk group, and 100% (3/3) of the high-risk group at the first follow-up.
Conclusions
The dynamic analysis of the methylation status in peripheral blood provides a promising strategy for postoperative cancer surveillance.
Clinical trial identification
MEDAL Study: NCT03634826; 08/05/2018.
Editorial acknowledgement
Legal entity responsible for the study
The authors.
Funding
National Natural Science Funds (grant No. 82072566).
Disclosure
All authors have declared no conflicts of interest.