Microscopic residual disease (MRD) monitoring and time to disease recurrence across gastrointestinal (GI) malignancies: A single-institution, real-world study

e15518 Background: Circulating tumor DNA (ctDNA) is a powerful tool that can detect early evidence of cancer relapse, or MRD. While most GI MRD studies to date are in colorectal adenocarcinoma (AC), a limited but growing body of evidence supports its use in other GI cancers. We describe the outcomes of patients (pts) with various GI cancers who underwent real-world MRD testing at our institution. Methods: In this retrospective analysis, we identified GI cancer pts with at least 1 tumor-informed ctDNA test (Natera, Inc) ordered between June 2020-August 2022. Descriptive statistics were used to characterize clinicopathologic factors, clinical contexts of ctDNA testing, rates of ctDNA positivity (ctDNA+), and relapse rates. Median relapse-free survival (mRFS) and overall survival (mOS) were calculated using Kaplan-Meier methods, comparison between groups by log-rank test, and hazard ratios (HR) by Cox proportional hazard models. Results: In total, 228 GI cancer pts underwent ctDNA testing for MRD monitoring. Pts had stage I (20.6%), 2 (32.0%), 3 (38.2%), and 4 (9.2%) disease at diagnosis. Testing started after an initial curative therapy attempt in 82% of pts and after a repeat curative attempt for disease recurrence in 18% of pts. The median follow-up time was 15.0 months (mo). ctDNA testing was successful in 222 pts (97.4%). The cancer subtypes, ctDNA, and clinical outcomes are reported (table). Collectively, 61/222 of pts had at least 1 ctDNA+ test, and 59.0% of these pts had relapse on their next scan performed after a median interval of 40 days (IQR 22-70) from the first positive test. Of the 62/222 pts who relapsed, ctDNA detected relapse before imaging in 43 pts (69.4%) with a median lead time of 57 days (IQR 29-128). The relapse rates were 82.0% vs. 7.5%, mRFS 10.8 mo vs. not reached (NR) (HR 18.6; 95% CI 9.8-35.3), and mOS 43.1 mo vs. NR (HR 5.0; 95% CI 1.8-13.9) in anytime-ctDNA+ pts compared to never-ctDNA+ pts. Similar trends were observed in the colon, rectal, and pancreas AC subgroups. Conclusions: ctDNA was utilized successfully across GI cancers and detected relapse before imaging in most pts. Anytime-ctDNA+ status predicted worse outcomes. About 40% of pts had a ctDNA+ test with no evidence of disease on an immediate subsequent scan, highlighting a prevalent “new stage” of high-risk pts that may benefit from novel treatments. [Table: see text]