Abstract 2599: Methylation-based circulating tumor DNA predicts recurrence in definitively treated non-small cell lung cancer (NSCLC)

Abstract Background: Circulating tumor DNA (ctDNA) is being utilized in detecting molecular residual disease (MRD) and predicting recurrence of non-small cell lung cancer (NSCLC). However, real-world implementation is yet to be reported. Methods: We retrospectively analyzed 240 longitudinal plasma samples from a real-world cohort of 78 NSCLC patients treated with curative intent, including select stage IV patients who underwent bilateral lung transplantation. MRD was assessed using a tissue-naïve, methylation-based assay (Guardant Reveal), and plasma-based genomic profiling was performed (Guardant360) at the time of MRD positivity. Recurrence-free survival (RFS) and overall survival (OS) were analyzed based on three MRD timepoints post-treatment: within 3 months (Subgroup A, n=42), within 6 months (Subgroup B, n=55), and at any time (Subgroup C, n=78). Recurrence date was determined by biopsy-proven recurrence date when available, otherwise, radiographic recurrence date was used. Results: 78 patients (median age at diagnosis 65; 33 stage I, 19 stage II, 19 stage III, 7 stage IV) received definitive treatment (surgery alone, n=37; surgery with perioperative therapy, n=33; definitive radiation, n=8). 56 were adenocarcinoma and 21 were squamous cell carcinoma, and 1 was adenosquamous. Targetable alterations (EGFR, ALK, etc.) were found in 31 patients. The median follow-up duration was 22.3 months (range: 2-80.6 months). Among 23 MRD(+) cases, 10 recurrences and 3 deaths occurred, whereas 55 MRD(-) cases showed 5 recurrences and no deaths. MRD(+) was associated with worse OS in all subgroups (p