{"entity":{"id":"paper-tie-dynamic-ctdna-guided-adjuvant-stage-ii-colon-nejm-2022","kind":"paper","name":"Circulating tumor DNA analysis guiding adjuvant therapy in stage II colon cancer (DYNAMIC)","aka":[],"tldr":"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.\n\nOf 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.","asOf":"2026-09-24","links":[{"label":"N Engl J Med 2022","url":"https://doi.org/10.1056/NEJMoa2200075"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/35657320/"},{"label":"Europe PMC full text (PMC9701133)","url":"https://europepmc.org/article/MED/35657320"}],"tags":["colorectal-evidence"],"related":["idea-ctdna-guided-adjuvant-crc","paper-tie-ctdna-minimal-residual-disease-stage-ii-colon-sci-transl-med-2016","paper-kotani-galaxy-molecular-residual-disease-nat-med-2023"],"cancers":["colorectal","colon-cancer"],"sections":["diagnostics","chemotherapy"],"technologies":["mrd-testing","liquid-biopsy","signatera"],"targets":[],"drugs":[],"companies":[],"institutions":["wehi","peter-mac"],"pathways":[],"terms":["ctdna","mrd","neoadjuvant-adjuvant"],"trials":["dynamic"],"people":["jeanne-tie","bert-vogelstein","kenneth-kinzler"],"bottlenecks":["b-dormancy-mrd","b-toxicity-qol"],"keyPapers":[],"journals":["nejm"],"dependsOn":[],"notes":[],"journal":"New England Journal of Medicine","year":2022,"doi":"10.1056/NEJMoa2200075","pmid":"35657320","authors":"Tie J, Cohen JD, Lahouel K, et al.","paperType":"rct","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."],"whatItMeans":"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."],"changedPractice":true,"participants":455},"route":"/key-papers/paper-tie-dynamic-ctdna-guided-adjuvant-stage-ii-colon-nejm-2022/","neighbours":{"idea":[{"id":"idea-ctdna-guided-adjuvant-crc","kind":"idea","name":"ctDNA-guided adjuvant therapy as the default in stage II-III colon cancer","route":"/ideas/idea-ctdna-guided-adjuvant-crc/"},{"id":"idea-crc-ctdna-de-escalation-beyond-stage-ii","kind":"idea","name":"Take ctDNA-guided de-escalation beyond stage II, and stop escalating on a positive result until a trial says it helps","route":"/ideas/idea-crc-ctdna-de-escalation-beyond-stage-ii/"}],"paper":[{"id":"paper-quasar-adjuvant-chemotherapy-vs-observation-lancet-2007","kind":"paper","name":"Adjuvant chemotherapy versus observation in patients with colorectal cancer: a randomised study (QUASAR)","route":"/key-papers/paper-quasar-adjuvant-chemotherapy-vs-observation-lancet-2007/"},{"id":"paper-tie-ctdna-minimal-residual-disease-stage-ii-colon-sci-transl-med-2016","kind":"paper","name":"Circulating tumor DNA analysis detects minimal residual disease and predicts recurrence in patients with stage II colon cancer","route":"/key-papers/paper-tie-ctdna-minimal-residual-disease-stage-ii-colon-sci-transl-med-2016/"},{"id":"paper-kotani-galaxy-molecular-residual-disease-nat-med-2023","kind":"paper","name":"Molecular residual disease and efficacy of adjuvant chemotherapy in patients with colorectal cancer (GALAXY, CIRCULATE-Japan)","route":"/key-papers/paper-kotani-galaxy-molecular-residual-disease-nat-med-2023/"}],"cancer":[{"id":"colon-cancer","kind":"cancer","name":"Colon cancer (adenocarcinoma of the colon)","route":"/cancers/colon-cancer/"},{"id":"colorectal","kind":"cancer","name":"Colorectal cancer","route":"/cancers/colorectal/"}],"section":[{"id":"chemotherapy","kind":"section","name":"Chemotherapy","route":"/fronts/chemotherapy/"},{"id":"diagnostics","kind":"section","name":"Diagnostics & Biomarkers","route":"/fronts/diagnostics/"}],"technology":[{"id":"liquid-biopsy","kind":"technology","name":"Liquid biopsy (ctDNA)","route":"/technologies/liquid-biopsy/"},{"id":"mrd-testing","kind":"technology","name":"MRD / molecular residual disease testing","route":"/technologies/mrd-testing/"}],"drug":[{"id":"signatera","kind":"drug","name":"Signatera","route":"/drugs/signatera/"}],"institution":[{"id":"peter-mac","kind":"institution","name":"Peter MacCallum Cancer Centre","route":"/institutions/peter-mac/"},{"id":"wehi","kind":"institution","name":"Walter and Eliza Hall Institute of Medical Research","route":"/institutions/wehi/"}],"term":[{"id":"ctdna","kind":"term","name":"Circulating tumour DNA (ctDNA)","route":"/terms/ctdna/"},{"id":"mrd","kind":"term","name":"Minimal / molecular residual disease (MRD)","route":"/terms/mrd/"},{"id":"neoadjuvant-adjuvant","kind":"term","name":"Neoadjuvant / adjuvant / perioperative","route":"/terms/neoadjuvant-adjuvant/"}],"trial":[{"id":"dynamic","kind":"trial","name":"DYNAMIC","route":"/trials/dynamic/"}],"person":[{"id":"bert-vogelstein","kind":"person","name":"Bert Vogelstein","route":"/people/bert-vogelstein/"},{"id":"jeanne-tie","kind":"person","name":"Jeanne Tie","route":"/people/jeanne-tie/"},{"id":"kenneth-kinzler","kind":"person","name":"Kenneth W. Kinzler","route":"/people/kenneth-kinzler/"}],"bottleneck":[{"id":"b-dormancy-mrd","kind":"bottleneck","name":"Dormant cells and minimal residual disease","route":"/bottlenecks/b-dormancy-mrd/"},{"id":"b-toxicity-qol","kind":"bottleneck","name":"Toxicity and quality of life are undervalued","route":"/bottlenecks/b-toxicity-qol/"}],"journal":[{"id":"nejm","kind":"journal","name":"New England Journal of Medicine","route":"/journals/nejm/"}],"roadmap":[{"id":"colorectal-roadmap","kind":"roadmap","name":"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","route":"/roadmaps/colorectal-roadmap/"}]}}