Abstract 3774: Detection of post-surgical minimal residual disease (MRD) in colorectal cancer; preliminary results from the VICTORI study
Authors: Emma Titmuss, Joao Paulo Solar Vasconcelos, Fabio C. Navarro, Neeraja Ravi, Charles Abbott, Brendan Chia, James T. Topham, Gale Ladua, Daniela Hegebarth, Sophie C. Chuang, Howard J. Lim, Karamjit Gill, Sharlene Gill, Carl J. Brown, Amandeep Ghuman, Adam Meneghetti, David F. Schaeffer, Richard O. Chen, Sean M. Boyle, Jonathan M. Loree
Journal: Cancer Research (2025)

Abstract Background: Circulating tumor (ctDNA) for detection of minimal residual disease (MRD) in colorectal cancers is prognostic, however, many cancers are not detected prior to clinical recurrence. Chemotherapy and surgery may limit detection of ctDNA due to increased shedding of DNA. We are exploring the use of an ultra-sensitive MRD assay (NeXT Personal®) in a prospective study of colorectal cancers (VICTORI) undergoing resection, with the aim to determine the optimal timepoint post-surgery to detect MRD. Methods: Patients enrolled undergo whole genome sequencing on tissue samples to generate a personalized panel of up to ∼1800 somatic variants for MRD detection, enabling detection of ctDNA down to ∼1 part per million (PPM). Blood draws are taken prior to surgery, within the MRD landmark window (weeks 2, 4, 6 and 8), and on follow-up thereafter every 3 months for 3 years. Results: We present preliminary results on 474 samples from the first 68 patients (N=40 rectal [59%], N=28 colon [41%]; N= 51 stage I-III [75%], N=17 stage IV [25%]) with a median follow up of 387 days. Pre-surgery positivity in treatment-naïve patients was 93.8% (n=30/32; negative are both stage I), and 72.4% in patients that received neoadjuvant therapy (n=21/29). Sixty-seven patients were evaluable for clinical outcomes, of which 23 had a recurrence. Of these, all evaluable patients were ctDNA-positive prior to recurrence (100%, 21/21; 2 patients were excluded due to lack of plasma samples prior to recurrence). ctDNA detection preceded clinical relapse determined by standard of care imaging by a median of 194 days (range 1-416 days). Most recurrences had ctDNA detected in the MRD landmark window (86%, 18/21). Of the three detected after the landmark window, one (stage IV) had neoadjuvant therapy prior to surgery, and was detected at the first follow-up timepoint (month 3). Another (stage III) was detected at month 6, and the third (stage II) at month 9. The median level of detection for the first post-surgical MRD positive sample was 54.9 PPM (range 2.45-111,120 PPM), and the ctDNA level at the first detection was correlated with disease-free survival (r=-0.47, p=0.05, Spearman). Detection of MRD at each individual timepoint in the MRD landmark window was associated with reduced disease-free survival (week 2 HR 4.75 [95% CI:1.63-13.84], p=0.0043; week 4 HR 11.72 [3.87-35.47], p=1.33x10-5; week 6 HR 7.73 [2.79-21.41], p=8.4x10-5; week 8 HR 16.70 [4.85-57.49], p=8.08x10-6). Conclusions: The VICTORI study is an ongoing study to understand the prognostic value of ultra-sensitive ctDNA detection and determine the optimal timepoint for detecting MRD post-surgery. Preliminary results indicate NeXT Personal detects MRD at ultra-low levels and is prognostic as early as two weeks post-surgery for recurrences. Citation Format: Emma Titmuss, Joao Paulo Solar Vasconcelos, Fabio C. Navarro, Neeraja Ravi, Charles Abbott, Brendan Chia, James T. Topham, Gale Ladua, Daniela Hegebarth, Sophie C. Chuang, Howard J. Lim, Karamjit Gill, Sharlene Gill, Carl J. Brown, Amandeep Ghuman, Adam Meneghetti, David F. Schaeffer, Richard O. Chen, Sean M. Boyle, Jonathan M. Loree. Detection of post-surgical minimal residual disease (MRD) in colorectal cancer; preliminary results from the VICTORI study [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2025; Part 1 (Regular Abstracts); 2025 Apr 25-30; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2025;85(8_Suppl_1):Abstract nr 3774.