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

Publication Unique Identifier

10.1038/s41591-025-03579-w

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

Comments

Tie, J., Wang, Y., Lo, S. N., Lahouel, K., Cohen, J. D., Wong, R., ... & 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

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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