# Circulating tumor DNA analysis guiding adjuvant therapy in stage II colon cancer (DYNAMIC)

Source: https://onco.cc/key-papers/paper-tie-dynamic-ctdna-guided-adjuvant-stage-ii-colon-nejm-2022/  
OnCo record `paper-tie-dynamic-ctdna-guided-adjuvant-stage-ii-colon-nejm-2022` (Key paper). Data CC BY-NC 4.0, attribute "Data from OnCo (onco.cc)"; commercial use needs a licence.

## TL;DR

The first randomised trial to let a blood test decide who gets chemotherapy. It halved chemotherapy use in stage II colon cancer with no loss of recurrence-free survival.

## Summary

Tie, Cohen, Lahouel and colleagues randomly assigned patients with stage II colon cancer 2:1 to have treatment decisions guided by circulating tumour DNA results or by standard clinicopathological features. Under circulating tumour DNA-guided management, a positive result at four or seven weeks after surgery prompted oxaliplatin-based or fluoropyrimidine chemotherapy and negative patients were not treated. The primary efficacy end point was recurrence-free survival at two years, with adjuvant chemotherapy use as a key secondary end point.

Of 455 patients randomised, 302 were assigned to circulating tumour DNA-guided management and 153 to standard management, with a median follow-up of 37 months.

## Fields

- Kind: Key paper
- Last checked: 2026-09-24
- Tags: colorectal-evidence
- Journal: New England Journal of Medicine
- Year: 2022
- DOI: 10.1056/NEJMoa2200075
- Authors: Tie J, Cohen JD, Lahouel K, et al.
- Findings: Adjuvant chemotherapy given to 15 percent of the circulating tumour DNA-guided group against 28 percent of the standard-management group (relative risk 1.82, 95 percent CI 1.25 to 2.65).; Two-year recurrence-free survival 93.5 percent against 92.4 percent: absolute difference 1.1 percentage points (95 percent CI -4.1 to 6.2), non-inferior against a margin of -8.5 percentage points.; Three-year recurrence-free survival 86.4 percent among circulating tumour DNA-positive patients who received chemotherapy and 92.5 percent among negative patients who did not.
- What it means: De-escalation guided by a blood test is now proven in stage II colon cancer, and is the template for the stage III and rectal trials that follow; the unsolved half is what to do for the positives, whose recurrence-free survival remains the worst in the trial even after chemotherapy.
- Caveats: Non-inferiority design with a wide margin and two-year follow-up; late recurrences are not captured.; Stage II colon cancer only, where the absolute benefit of chemotherapy is small to begin with.; The escalation half of the strategy was not tested against anything: no trial has yet shown that treating a positive result changes its outcome.

## Sources

- N Engl J Med 2022: https://doi.org/10.1056/NEJMoa2200075
- PubMed: https://pubmed.ncbi.nlm.nih.gov/35657320/
- Europe PMC full text (PMC9701133): https://europepmc.org/article/MED/35657320

## Connected records

- ideas: [ctDNA-guided adjuvant therapy as the default in stage II-III colon cancer](https://onco.cc/ideas/idea-ctdna-guided-adjuvant-crc/), [Take ctDNA-guided de-escalation beyond stage II, and stop escalating on a positive result until a trial says it helps](https://onco.cc/ideas/idea-crc-ctdna-de-escalation-beyond-stage-ii/)
- key papers: [Adjuvant chemotherapy versus observation in patients with colorectal cancer: a randomised study (QUASAR)](https://onco.cc/key-papers/paper-quasar-adjuvant-chemotherapy-vs-observation-lancet-2007/), [Circulating tumor DNA analysis detects minimal residual disease and predicts recurrence in patients with stage II colon cancer](https://onco.cc/key-papers/paper-tie-ctdna-minimal-residual-disease-stage-ii-colon-sci-transl-med-2016/), [Molecular residual disease and efficacy of adjuvant chemotherapy in patients with colorectal cancer (GALAXY, CIRCULATE-Japan)](https://onco.cc/key-papers/paper-kotani-galaxy-molecular-residual-disease-nat-med-2023/)
- cancers: [Colon cancer (adenocarcinoma of the colon)](https://onco.cc/cancers/colon-cancer/), [Colorectal cancer](https://onco.cc/cancers/colorectal/)
- fronts: [Chemotherapy](https://onco.cc/fronts/chemotherapy/), [Diagnostics & Biomarkers](https://onco.cc/fronts/diagnostics/)
- technologies: [Liquid biopsy (ctDNA)](https://onco.cc/technologies/liquid-biopsy/), [MRD / molecular residual disease testing](https://onco.cc/technologies/mrd-testing/)
- drugs: [Signatera](https://onco.cc/drugs/signatera/)
- institutions: [Peter MacCallum Cancer Centre](https://onco.cc/institutions/peter-mac/), [Walter and Eliza Hall Institute of Medical Research](https://onco.cc/institutions/wehi/)
- terms: [Circulating tumour DNA (ctDNA)](https://onco.cc/terms/ctdna/), [Minimal / molecular residual disease (MRD)](https://onco.cc/terms/mrd/), [Neoadjuvant / adjuvant / perioperative](https://onco.cc/terms/neoadjuvant-adjuvant/)
- trials: [DYNAMIC](https://onco.cc/trials/dynamic/)
- people: [Bert Vogelstein](https://onco.cc/people/bert-vogelstein/), [Jeanne Tie](https://onco.cc/people/jeanne-tie/), [Kenneth W. Kinzler](https://onco.cc/people/kenneth-kinzler/)
- bottlenecks: [Dormant cells and minimal residual disease](https://onco.cc/bottlenecks/b-dormancy-mrd/), [Toxicity and quality of life are undervalued](https://onco.cc/bottlenecks/b-toxicity-qol/)
- journals: [New England Journal of Medicine](https://onco.cc/journals/nejm/)
- roadmaps: [Colorectal cancer roadmap: from the adenoma-carcinoma sequence and the first screening trials to total mesorectal excision, oxaliplatin, RAS testing, immunotherapy for mismatch repair-deficient disease, ctDNA-guided treatment and organ preservation](https://onco.cc/roadmaps/colorectal-roadmap/)

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