DYNAMIC: a blood test safely halved chemotherapy use after surgery for stage II colon cancer
Giving chemotherapy only to patients with tumour DNA in their blood after surgery cut chemotherapy use from 28% to 15% with no loss in recurrence-free survival at two years.
DYNAMIC randomised 455 patients with resected stage II colon cancer 2:1 to ctDNA-guided management or standard management. In the ctDNA arm, plasma taken at weeks 4 and 7 after surgery was tested with a tumour-informed assay; ctDNA-positive patients received oxaliplatin-based or fluoropyrimidine chemotherapy and ctDNA-negative patients were observed. The primary endpoint was recurrence-free survival at 2 years, tested for non-inferiority.
Adjuvant chemotherapy was given to 15% of ctDNA-guided patients versus 28% of standard-management patients. Two-year recurrence-free survival was 93.5% versus 92.4%, meeting non-inferiority. ctDNA-positive patients treated with chemotherapy had a 3-year RFS of 86.4%, and untreated ctDNA-negative patients 92.5%.
It was the first randomised evidence that ctDNA can safely de-escalate adjuvant treatment.
- Adjuvant chemotherapy use 15% vs 28% (relative risk 1.82 for standard management)
- Two-year recurrence-free survival 93.5% vs 92.4% (absolute difference 1.1 percentage points; 95% CI -4.1 to 6.2), non-inferior
- ctDNA-positive patients treated with chemotherapy: 3-year RFS 86.4%; ctDNA-negative untreated: 92.5%
- About 15% of patients were ctDNA-positive after surgery
For stage II colon cancer, where most patients are cured by surgery alone, a blood test can identify the minority who benefit from chemotherapy and spare everyone else its side effects. It does not yet prove that treating ctDNA-positive patients improves survival compared with not treating them.
- Non-inferiority margin of 8.5 percentage points was generous; the trial was not powered to detect small losses
- Stage II only; DYNAMIC-III in stage III showed that escalation for ctDNA-positive patients did not clearly improve outcomes
- Assay (Safe-SeqS on 15 tumour-specific mutations) is not the commercial assays used elsewhere
- Two-year follow-up is short for colon cancer recurrence
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