Circulating tumor DNA analysis guiding adjuvant therapy in stage II colon cancer: 5-year outcomes of the randomized DYNAMIC trial
Document Type
Journal Article
Publication Title
Nature Medicine
Publisher
Nature
School
School of Medical and Health Sciences
RAS ID
78482
Funders
Australian National Health and Medical Research Council / Marcus Foundation / Virginia and D.K. Ludwig Fund for Cancer Research / Oncology Core CA06973 / Lustgarten Foundation / The Conrad N. Hilton Foundation / Commonwealth Fund / The Sol Goldman Charitable Trust / John Templeton Foundation / National Institutes of Health (CA62924, CA009071, GM136577, CA06973, U01CA230691) / Benjamin Baker Endowment / The V Foundation for Cancer Research / Eastern Health Research Foundation
Abstract
Early data from the DYNAMIC study of circulating tumor DNA (ctDNA)-guided adjuvant chemotherapy (ACT) versus standard approach met its primary outcome demonstrating reduced ACT use without compromising 2-year recurrence-free survival (RFS) for stage II colon cancer. We report here other prespecified analyses of overall survival, ctDNA clearance and ctDNA level. At a median follow-up of 59.7 months, 5-year RFS was 88% and 87% with ctDNA-guided and standard management, respectively (difference 1.1%, 95% confidence interval −5.8% to 8.0%), and 5-year overall survival is similar (93.8% versus 93.3%, hazard ratio (HR) 1.05; P = 0.887). For treated ctDNA-positive patients, ctDNA clearance was observed at the end of ACT (EOT) in 35 out of 40 patients (87.5%). A higher than median postoperative tumor-derived mutant molecules per milliliter plasma was associated with worse 5-year RFS (HR 10.62; P = 0.005). For treated ctDNA-positive patients, post hoc analysis of ctDNA clearance at EOT assessed by a new assay that evaluated an average of 29 tumor-derived mutations per patient predicted for a favorable 5-year recurrence-free probability of 97% versus 0% for ctDNA persistence (P < 0.001). Mature DYNAMIC outcome data support a ctDNA-guided approach to ACT for stage II colon cancer, with potential to further risk stratify ctDNA-positive patients based on ctDNA burden and EOT results. Australian New Zealand Clinical Trials Registry Identifier: ACTRN12615000381583.
DOI
10.1038/s41591-025-03579-w
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Tie, J., Wang, Y., Lo, S. N., Lahouel, K., Cohen, J. D., Wong, R., Shapiro, J. D., Harris, S. J., Khattak, A., Burge, M. E., Lee, M., Harris, M., McLachlan, S., Horvath, L., Karapetis, C., Shannon, J., Singh, M., Yip, D., Ananda, S., . . . Gibbs, P. (2025). Circulating tumor DNA analysis guiding adjuvant therapy in stage II colon cancer: 5-year outcomes of the randomized DYNAMIC trial. Nature Medicine, 31, 1509-1518. https://doi.org/10.1038/s41591-025-03579-w