Abstract 4788: Noninvasive longitudinal monitoring of residual disease in chemotherapy-treated colorectal cancer patients

Abstract Noninvasive monitoring of cancer shows great promise in assessing therapy response and improving patient outcomes. Recently, various groups have developed methods that detect circulating tumor DNA (ctDNA) in the plasma to measure minimal or molecular residual disease (MRD). Aberrant DNA methylation patterns are a hallmark of cancers, and robust signals can be detected by sensitive ctDNA assays. Here, we present a methylation-based approach for longitudinal monitoring of tumor burden that is tumor-naive, i. e. , with no reliance on prior characterization of tumor molecular characteristics. We assess the effectiveness of our approach in a cohort of colorectal cancer (CRC) patients receiving chemotherapy with or without additional targeted agents. Longitudinal blood samples were collected from patients (n = 57) while on therapy, which averaged 4. 9 months, for a total of 239 sample collection time points (median per patient = 5). Based on RECIST status, 16 patients were classified as complete responders (CR) at the end of treatment. We generated plasma cell free DNA-derived libraries for methylation sequencing targeting regions relevant to CRC. Next, we computed a disease burden score for each sample and related these scores to clinical response (CR vs. non-CR). We trained a classifier on an independent cohort of CRC and healthy donor plasma cfDNA samples, and used this classifier to check for residual disease at the end of treatment for each of our 57 patients. The classifier detected residual disease in only 3/16 CRs (19%) but 35/41 non-CRs (85%). Two of the non-CR patients were initially assessed as CRs at earlier time points. In both cases, our method successfully detected residual disease at or prior to the CR assessment and consistently showed residual disease in all follow up samples. This suggests improved sensitivity relative to RECIST and highlights the potential of using noninvasive blood tests for continuous monitoring of CRC patients receiving therapy. Citation Format: Alison D. Tang, Rebecca Gupte, Victoria Cheung, Tao Qing, Austin Cauwels, Emily Leff, Kimberly Walter, Ehsan Tabari, Alex Lovejoy, Jimmy C. Lin. Noninvasive longitudinal monitoring of residual disease in chemotherapy-treated colorectal cancer patients abstract. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts) ; 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84 (6Suppl): Abstract nr 4788.