Exploration of tumor-informed ctDNA detection and dynamics in a real-world cohort of colorectal cancer patients from the MD Anderson Cancer Center.

Abstract

e15658 Background: Circulating tumor DNA (ctDNA) is a promising tool for the treatment of patients with cancer. In the colorectal cancer (CRC) setting, various MRD assays are gradually being adopted into routine care, to assist with risk stratification and recurrence monitoring. In real-world usage, this type of test offers a timely assessment of treatment response and monitoring, which is otherwise mostly dependent on imaging. This study aims to characterize the association between ctDNA status and clinical data, during treatment and disease monitoring in a curative intent setting, and explore reproducibility. Methods: Here we retrospectively applied the tumor informed RaDaR ST assay to plasma samples from an initial group of 83 patients with stage II-IV resectable colon or rectal cancer. Participants had plasma collected at up to 4 timepoints, over the course of 6 months from enrollment. Collection coincided with real-world clinical care, with no pre-defined collection schedule relative to treatment. ctDNA detection and quantity (estimated variant allele fraction, eVAF) are compared against matching clinical data, as it becomes available, as well as orthogonal results for a subset. Results: After excluding 5 samples that failed QC checks, 107 plasma samples from 80 patients were analyzed by RaDaR ST, with ctDNA detected in 29 (27%) at levels ranging from 0.00056% (5.6 parts per million) to 3.4% eVAF. ctDNA detection was compared against clinical data, revealing a correlation with treatment response and disease recurrence status in the initial 46 cases with available clinical records. Use cases included post-surgery, pre- and post-systemic therapy, and on therapy monitoring. Further associations between ctDNA detection and patient outcomes will be explored in the wider cohort. To determine the generalizability of these findings to alternative ctDNA testing approaches, results were compared against matching data generated using two alternative tumor-informed assays, for a subset of samples (n = 71 and 65). In both cases this demonstrated > 95% concordance in detection, and good correlation between ctDNA measurements in positive samples ( R > 0.96, P < 0.001) . Conclusions: This is an ongoing effort to define ctDNA dynamics and explore the benefits of various approaches, in the setting of stage II-IV CRC treated with curative intent. These preliminary findings add to growing data supporting the potential of ctDNA to be routinely utilized in the management of patients treated for CRC, particular in a clinical setting outside of an interventional clinical trial. The detection of ctDNA at levels as low as 5.6 parts per million, and orthogonal confirmations, shows the importance of using highly sensitive assays to accurately detect and quantify disease. Whilst promising, further data are needed to confirm how best to exploit ctDNA to guide patient care in this setting.