{"entity":{"id":"paper-dynamic-nejm-2022","kind":"paper","name":"DYNAMIC: a blood test safely halved chemotherapy use after surgery for stage II colon cancer","aka":[],"tldr":"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.","summary":"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.\n\nAdjuvant 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%.\n\nIt was the first randomised evidence that ctDNA can safely de-escalate adjuvant treatment.","asOf":"2026-09-08","links":[{"label":"DOI","url":"https://doi.org/10.1056/NEJMoa2200075"},{"label":"ANZCTR ACTRN12615000381583","url":"https://www.anzctr.org.au/Trial/Registration/TrialReview.aspx?id=368271"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/35657320/"},{"label":"Europe PMC full text (PMC9701133)","url":"https://europepmc.org/article/MED/35657320"}],"tags":[],"related":["idea-ctdna-guided-adjuvant-crc","ctdna-mrd-to-adjuvant","ctdna-mrd-positive","paper-tie-ctdna-minimal-residual-disease-stage-ii-colon-sci-transl-med-2016","paper-galaxy-signatera-nat-med-2023"],"cancers":["colorectal","colon-cancer"],"sections":["diagnostics","chemotherapy"],"technologies":["mrd-testing","liquid-biopsy","signatera"],"targets":[],"drugs":[],"companies":[],"institutions":["peter-mac","johns-hopkins","wehi"],"pathways":[],"terms":["mrd","ctdna","neoadjuvant-adjuvant","tumour-informed-assay"],"trials":["dynamic"],"people":["bert-vogelstein","kenneth-kinzler","jeanne-tie"],"bottlenecks":["b-dormancy-mrd","b-toxicity-qol","b-trial-design"],"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 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"],"whatItMeans":"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.","caveats":["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"],"changedPractice":true,"participants":455},"route":"/key-papers/paper-dynamic-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/"}],"pairing":[{"id":"ctdna-mrd-to-adjuvant","kind":"pairing","name":"ctDNA MRD → adjuvant therapy decision","route":"/pairings/ctdna-mrd-to-adjuvant/"}],"biomarker":[{"id":"ctdna-mrd-positive","kind":"biomarker","name":"ctDNA MRD positivity (molecular residual disease after curative treatment)","route":"/biomarkers/ctdna-mrd-positive/"}],"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-galaxy-signatera-nat-med-2023","kind":"paper","name":"GALAXY: tumour DNA in blood four weeks after bowel cancer surgery predicts relapse tenfold","route":"/key-papers/paper-galaxy-signatera-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":"johns-hopkins","kind":"institution","name":"Johns Hopkins Hospital / Sidney Kimmel Comprehensive Cancer Center","route":"/institutions/johns-hopkins/"},{"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/"},{"id":"tumour-informed-assay","kind":"term","name":"Tumour-informed versus tumour-naive ctDNA assays","route":"/terms/tumour-informed-assay/"}],"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/"},{"id":"b-trial-design","kind":"bottleneck","name":"Trial design, endpoints and cost","route":"/bottlenecks/b-trial-design/"}],"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/"},{"id":"ctdna-tests","kind":"roadmap","name":"ctDNA tests roadmap: from a curiosity in plasma to blood tests that decide treatment","route":"/roadmaps/ctdna-tests/"}]}}