# Validation of a methylation-based, tissue-free MRD assay in colorectal cancer patients from the GALAXY study

## TL;DR

A new methylation-based test for detecting cancer recurrence in colorectal cancer patients shows strong results in predicting outcomes and treatment benefits.

## Contribution

A tissue-free methylation-based MRD assay is validated for robust prognostic and predictive capabilities in CRC.

## Key findings

- ctDNA-positivity correlates with significantly worse disease-free survival in CRC patients.
- The assay detects relapse with high sensitivity and specificity, providing a median lead time of 4.6 months.
- ctDNA-positive patients benefit from adjuvant chemotherapy, unlike ctDNA-negative patients.

## Abstract

This study validates a methylation-based, tissue-free assay (LatitudeTM assay) for detecting molecular residual disease (MRD) in colorectal cancer (CRC), analyzing data from 195 patients (1230 timepoints) from the observational GALAXY study. The assay demonstrated that ctDNA-positivity correlated with significantly worse disease-free survival (DFS) in both the MRD (HR = 10.0, P < 0.001) and post-definitive treatment surveillance windows (HR = 31.9, P < 0.001). In the MRD window, the assay demonstrated a sensitivity of 58.5% (38/65), while the specificity in patients who did not receive adjuvant chemotherapy (ACT) was 100% (63/63). Longitudinally, relapse was detected with a sensitivity of 84.4% (54/64), with high specificity at the patient (92.1%; 116/126) and sample (97.2%; 619/637) levels. Median lead time from first circulating tumor DNA (ctDNA)-positive result to relapse was 4.6 months. For high-risk stage II and III CRC, ctDNA-positive patients benefited from ACT (adj.HR = 0.014, P < 0.0001), unlike ctDNA-negative patients. These findings highlight the robust prognostic and predictive capabilities of this tissue-free MRD assay in CRC patients.