@Article{or.2026.080218,
AUTHOR = {William C. Cho, Yingyu Wang, Qianqian Yao, Tam Berntsen, George Yeung, Paul Tang, Tobias Wittkop, Li Weng, Lui Ng, Dominic C. C. Foo},
TITLE = {Monitoring Molecular Residual Disease in Colorectal Cancer Using Tumor-Informed ctDNA Analysis},
JOURNAL = {Oncology Research},
VOLUME = {},
YEAR = {},
NUMBER = {},
PAGES = {{pages}},
URL = {http://www.techscience.com/or/online/detail/28000},
ISSN = {1555-3906},
ABSTRACT = {<b>Background:</b> 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. <b>Methods:</b> 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. <b>Results:</b> 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 (<i>n</i> = 13) and 85.7% (95% CI: 42.1–99.6%) for the combined cohort (FFPE- and/or FF-guided analysis (<i>n</i> = 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 (<i>p</i> &lt; 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. <b>Conclusions:</b> 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.},
DOI = {10.32604/or.2026.080218}
}