DYNAMIC Trial 5-Year Data Validate ctDNA-Guided Adjuvant Chemotherapy De-Escalation in Stage II Colon Cancer
At 5-year follow-up, the randomised DYNAMIC trial confirmed that ctDNA-guided management of stage II colon cancer reduced adjuvant chemotherapy use without compromising recurrence-free or overall survival compared with standard clinicopathological staging. Among ctDNA-positive patients receiving chemotherapy, a multi-mutation assay detected ctDNA clearance at end of treatment with striking prognostic value: 97% recurrence-free probability with clearance versus 0% with persistence. These mature data provide the strongest evidence yet for ctDNA-directed treatment decisions in early-stage colorectal cancer.
The original study
Circulating tumor DNA analysis guiding adjuvant therapy in stage II colon cancer: 5-year outcomes of the randomized DYNAMIC trial.
- Authors
- Tie J, Wang Y, Lo SN, Lahouel K, Cohen JD, Wong R, et al.
- Journal
- Nature medicine
- Type
- Journal Article, Randomized Controlled Trial
- PMID
- 40055522
Original 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 .