Circulating Tumor DNA Analysis Guiding Adjuvant Therapy in Stage II Colon Cancer
- Study type
- Clinical trial
- Study name
- DYNAMIC
- Phase
- Phase 2
- Design
- Multicentre randomised trial (2:1 randomisation) comparing ctDNA-guided management with standard clinicopathological management; registration: ACTRN12615000381583
- Sample size
- 455 patients (302 ctDNA-guided management, 153 standard management)
- Source
- N Engl J Med · 2022
In plain words
After surgery for stage 2 bowel cancer, it is not always clear who really needs chemotherapy. In this study, a simple blood test was used to look for traces of tumour DNA (ctDNA) in the blood. Patients without these traces did not get chemotherapy and did just as well; as a result, about half as many patients received chemotherapy, without a higher chance of the cancer coming back. This means the test can spare many patients the side effects of an unnecessary treatment.
Key results
Treatment arms and regimens
ctDNA testing at weeks 4 and 7 after surgery (personalised Safe-SeqS assay based on tumour mutations). If ctDNA was positive at either time point: adjuvant chemotherapy with single-agent fluoropyrimidine or an oxaliplatin-based regimen at the physician's choice; ctDNA-negative patients did not receive chemotherapy.
Permitted regimens in both groups (ANZCTR trial registration; duration 3 to 6 months):
- Modified de Gramont every 2 weeks: leucovorin 50 mg IV, fluorouracil 400 mg/m² IV, then 2400 mg/m² continuous IV infusion by pump over 46 hours.
- Modified QUASAR weekly: leucovorin 50 mg IV and fluorouracil 375 to 450 mg/m² IV (per centre standard).
- Modified Roswell Park weekly (6 weeks then 2 weeks' rest): leucovorin 50 mg IV and fluorouracil 500 mg/m² IV.
- Capecitabine: orally on days 1 to 14 every 21 days (dose per centre standard).
- mFOLFOX6 every 2 weeks: oxaliplatin 85 mg/m² IV, leucovorin 50 mg IV, fluorouracil 400 mg/m² IV and 2400 mg/m² continuous infusion over 46 hours.
- XELOX/CAPOX every 3 weeks: oxaliplatin 130 mg/m² and capecitabine 1000 mg/m² twice daily orally on days 1 to 14 every 21 days.
Dose modification was per each centre's standard. Of the 45 treated patients, 28 (62%) received an oxaliplatin-based doublet and 17 (38%) single-agent fluoropyrimidine; median time from surgery to start of chemotherapy was 83 days and median treatment duration 24 weeks.
Decision on adjuvant chemotherapy based on clinical and pathological criteria at the physician's discretion, with the same permitted regimens and doses (listed in the ctDNA group). Of the 41 treated patients, 4 (10%) received an oxaliplatin-based regimen and 37 (90%) single-agent fluoropyrimidine; median time from surgery to start of treatment was 53 days and median treatment duration 24 weeks.
Source of the regimen details: Permitted regimens and their doses: ANZCTR trial registration (ACTRN12615000381583, intervention description section); regimen received and treatment duration: Table 2 of the full text (PMC9701133)
Doses are given for the information of specialists, as in this study’s protocol, and are not a prescription. Every drug must be prescribed by the treating physician for the individual patient.
Study population
Patients with stage II (T3 or T4, N0, M0) colon or rectal adenocarcinoma resected with negative margins, ECOG performance status 0 to 2 and able to receive adjuvant chemotherapy. Patients who had preoperative chemoradiotherapy were not enrolled. Median age 64 years; 15% had T4 tumours.
Endpoints
Primary efficacy endpoint: recurrence-free survival (RFS) at 2 years (non-inferiority test with a margin of −8.5 percentage points).
Key secondary endpoint: use of adjuvant chemotherapy.
Safety and side effects
Because only standard treatments were used, adverse events were not systematically recorded in this trial; the main safety advantage was the reduction in the number of patients exposed to chemotherapy (and its adverse effects) (15% versus 28%).
Clinical significance and place in guidelines
DYNAMIC was the first randomised trial to show that ctDNA-guided decisions on adjuvant chemotherapy in stage II colon cancer are feasible and reduce chemotherapy use. This is a phase 2 trial, and ctDNA testing has not yet replaced standard clinicopathological criteria in all guidelines; the 5-year follow-up results (DYNAMIC, Nat Med 2025) confirmed these findings.
Limitations
Phase 2 trial with a relatively small sample size; relatively wide non-inferiority margin (8.5 percentage points); the chemotherapy regimen was the physician's choice and most ctDNA-positive patients received an oxaliplatin-based regimen; adverse events were not recorded; time to start of treatment in the ctDNA group was longer because of waiting for the test result (median 83 versus 53 days).
This summary was prepared by the editorial team from the published paper; the original paper is the final reference. Read the original abstract on PubMed.