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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.
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.
The blood test stratifies risk far better than stage or pathology. It supports treating ctDNA-positive patients and suggests ctDNA-negative patients gain little from chemotherapy, but because treatment was not randomised the de-escalation claim needs the randomised trials that are now under way.
Minimal residual disease became measurable in solid tumours, and the DYNAMIC and CIRCULATE trials that followed turned the measurement into a treatment decision.
The number every stage II conversation still uses. It is also the baseline against which ctDNA-guided de-escalation is judged: DYNAMIC halved chemotherapy use in exactly this group without losing recurrence-free survival.
Shares ctDNA MRD → adjuvant therapy decision, ctDNA-guided adjuvant therapy as the default in stage II-III colon cancer, GALAXY: tumour DNA in blood four weeks after bowel cancer surgery predicts relapse tenfold, DYNAMIC.
Shares ctDNA MRD → adjuvant therapy decision, Signatera, ctDNA tests roadmap: from a curiosity in plasma to blood tests that decide treatment, Dormant cells and minimal residual disease.
Shares ctDNA MRD → adjuvant therapy decision, Tumour-informed versus tumour-naive ctDNA assays, DYNAMIC, Signatera.
Shares Jeanne Tie, ctDNA-guided adjuvant therapy as the default in stage II-III colon cancer, Take ctDNA-guided de-escalation beyond stage II, and stop escalating on a positive result until a trial says it helps, GALAXY: tumour DNA in blood four weeks after bowel cancer surgery predicts relapse tenfold.
Shares Tumour-informed versus tumour-naive ctDNA assays, DYNAMIC, ctDNA MRD positivity (molecular residual disease after curative treatment), Signatera.
Shares Jeanne Tie, ctDNA MRD positivity (molecular residual disease after curative treatment), Signatera, Minimal / molecular residual disease (MRD).
Shares Tumour-informed versus tumour-naive ctDNA assays, ctDNA MRD positivity (molecular residual disease after curative treatment), Signatera, ctDNA tests roadmap: from a curiosity in plasma to blood tests that decide treatment.
Shares Tumour-informed versus tumour-naive ctDNA assays, ctDNA MRD positivity (molecular residual disease after curative treatment), Signatera, ctDNA tests roadmap: from a curiosity in plasma to blood tests that decide treatment.