Monitoring Molecular Residual Disease in Colorectal Cancer Using Tumor-Informed ctDNA Analysis
- 1Department of Clinical Oncology, Queen Elizabeth Hospital, Hong Kong SAR, China
- 2Department of Research and Development, AccuraGen Inc., San Jose, CA, USA
- 3Department of Surgery, University of Hong Kong, Hong Kong SAR, China
Abstract
Background: The early detection of molecular residual disease (MRD) is critical for predicting recurrence and guiding management in colorectal cancer (CRC). We aimed to evaluate the performance of tumor-informed circulating tumor DNA (ctDNA) analysis in monitoring MRD after curative-intent surgery. Methods: In this cohort study of 28 resected CRC patients, tumor-informed variants were identified from formalin-fixed paraffin-embedded (FFPE) or fresh-frozen (FF) tissues using whole-genome sequencing. Post-operative plasma ctDNA was analyzed with the next-generation sequencing-based AccuScan platform at landmark (2–6 weeks) and longitudinal time points. Results: ctDNA-based MRD detection achieved 100% specificity (95% CI: 78.2–100%) and positive predictive value for recurrence in this cohort of 28 patients, which included 13 recurrence events with a median follow-up of 36.2 months. Sensitivity was 83.3% (95% CI: 35.9–99.6%) for patients with FFPE-guided analysis (n = 13) and 85.7% (95% CI: 42.1–99.6%) for the combined cohort (FFPE- and/or FF-guided analysis (n = 20) at the landmark time point, improving to 88.9% and 92.3%, respectively, with longitudinal monitoring. MRD-positive status was associated with significantly reduced disease-free survival (p < 0.0001) in unadjusted analyses. Although FFPE-derived sequencing introduced more artifacts, bioinformatic filtering preserved assay accuracy, and the concurrent use of both reference types in a subset of patients highlighted the potential to improve overall detection sensitivity. Conclusions: These findings suggest that tumor-informed ctDNA analysis provides a promising approach for post-operative MRD surveillance and recurrence risk stratification in CRC. However, the small sample size, lack of external validation, and absence of neoadjuvant-treated patients preclude definitive conclusions. Independent prospective validation is required.
Related
- Consensus and controversy of liquid biopsy using circulating tumour DNA (ctDNA) for molecular residual disease detection in colorectal cancer
- Targeting minimal residual disease (MRD) in colorectal cancer: Therapeutic strategies, clinical trials, and the path toward molecular cure
- Risk stratification by circulating tumor DNA-based pretreatment genomic profile and post-operative molecular residual disease detection in resectable colorectal oligometastases: PRECISION, a prospective multicenter study
- Circulating Tumor DNA (ctDNA) for Minimal Residual Disease (MRD) Detection in Colorectal Cancer (CRC): Current Evidence, Clinical Applications, and Future Directions.
- Measurable Residual Disease (MRD) Monitoring in Myeloproliferative Neoplasms
BibTeX
@article{cho2026monitoring,
title = {{Monitoring Molecular Residual Disease in Colorectal Cancer Using Tumor-Informed ctDNA Analysis}},
author = {William C. Cho and Yingyu Wang and Qianqian Yao and Tam Berntsen and George Yeung and Paul Tang and Tobias Wittkop and Li Weng and Lui Ng and Dominic C. C. Foo},
journal = {Oncology Research},
year = {2026},
month = oct,
doi = {10.32604/or.2026.080218},
url = {https://doi.org/10.32604/or.2026.080218},
note = {CC BY 4.0},
}
RIS
TY - JOUR
TI - Monitoring Molecular Residual Disease in Colorectal Cancer Using Tumor-Informed ctDNA Analysis
AU - William C. Cho
AU - Yingyu Wang
AU - Qianqian Yao
AU - Tam Berntsen
AU - George Yeung
AU - Paul Tang
AU - Tobias Wittkop
AU - Li Weng
AU - Lui Ng
AU - Dominic C. C. Foo
PY - 2026
DA - 2026/10/28
JO - Oncology Research
DO - 10.32604/or.2026.080218
UR - https://doi.org/10.32604/or.2026.080218
AB - Background: The early detection of molecular residual disease (MRD) is critical for predicting recurrence and guiding management in colorectal cancer (CRC). We aimed to evaluate the performance of tumor-informed circulating tumor DNA (ctDNA) analysis in monitoring MRD after curative-intent surgery. Methods: In this cohort study of 28 resected CRC patients, tumor-informed variants were identified from formalin-fixed paraffin-embedded (FFPE) or fresh-frozen (FF) tissues using whole-genome sequencing. Post-operative plasma ctDNA was analyzed with the next-generation sequencing-based AccuScan platform at landmark (2–6 weeks) and longitudinal time points. Results: ctDNA-based MRD detection achieved 100% specificity (95% CI: 78.2–100%) and positive predictive value for recurrence in this cohort of 28 patients, which included 13 recurrence events with a median follow-up of 36.2 months. Sensitivity was 83.3% (95% CI: 35.9–99.6%) for patients with FFPE-guided analysis (n = 13) and 85.7% (95% CI: 42.1–99.6%) for the combined cohort (FFPE- and/or FF-guided analysis (n = 20) at the landmark time point, improving to 88.9% and 92.3%, respectively, with longitudinal monitoring. MRD-positive status was associated with significantly reduced disease-free survival (p < 0.0001) in unadjusted analyses. Although FFPE-derived sequencing introduced more artifacts, bioinformatic filtering preserved assay accuracy, and the concurrent use of both reference types in a subset of patients highlighted the potential to improve overall detection sensitivity. Conclusions: These findings suggest that tumor-informed ctDNA analysis provides a promising approach for post-operative MRD surveillance and recurrence risk stratification in CRC. However, the small sample size, lack of external validation, and absence of neoadjuvant-treated patients preclude definitive conclusions. Independent prospective validation is required.
SN - 0965-0407
SN - 1555-3906
ER -