{"entity":{"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","aka":[],"tldr":"Traces of tumour DNA in blood after a colon cancer operation identified the patients who would relapse with a hazard ratio of 18. It is the observation the whole ctDNA field is built on.","summary":"Tie, Wang, Tomasetti and colleagues used massively parallel sequencing-based assays to evaluate the ability of circulating tumour DNA to detect minimal residual disease in 1,046 plasma samples from a prospective cohort of 230 patients with resected stage II colon cancer.\n\nIn patients who were not given adjuvant chemotherapy, postoperative circulating tumour DNA identified a group whose recurrence risk was an order of magnitude higher than everyone else's; in patients who were treated, detectable circulating tumour DNA after chemotherapy carried the same meaning.","asOf":"2026-09-24","links":[{"label":"Sci Transl Med 2016","url":"https://doi.org/10.1126/scitranslmed.aaf6219"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/27384348/"},{"label":"Europe PMC full text (PMC5346159)","url":"https://europepmc.org/article/MED/27384348"}],"tags":["colorectal-evidence"],"related":["ctdna-tests","paper-tie-dynamic-ctdna-guided-adjuvant-stage-ii-colon-nejm-2022"],"cancers":["colorectal","colon-cancer"],"sections":["diagnostics"],"technologies":["mrd-testing","liquid-biopsy","ngs","signatera"],"targets":[],"drugs":[],"companies":[],"institutions":["wehi","peter-mac","johns-hopkins"],"pathways":[],"terms":["ctdna","mrd"],"trials":[],"people":["jeanne-tie","bert-vogelstein","kenneth-kinzler"],"bottlenecks":["b-dormancy-mrd","b-biomarker-validation"],"keyPapers":[],"journals":["science-translational-medicine"],"dependsOn":[],"notes":[],"journal":"Science Translational Medicine","year":2016,"doi":"10.1126/scitranslmed.aaf6219","pmid":"27384348","authors":"Tie J, Wang Y, Tomasetti C, et al.","paperType":"translational","findings":["Circulating tumour DNA was detected postoperatively in 14 of 178 (7.9 percent) untreated patients, 11 (79 percent) of whom had recurred at a median 27 months.","Recurrence occurred in 16 of 164 (9.8 percent) patients with negative circulating tumour DNA: hazard ratio 18 (95 percent CI 7.9 to 40, p<0.001).","In chemotherapy-treated patients, circulating tumour DNA after completion of chemotherapy also predicted inferior recurrence-free survival (hazard ratio 11, 1.8 to 68, p=0.001)."],"whatItMeans":"Minimal residual disease became measurable in solid tumours, and the DYNAMIC and CIRCULATE trials that followed turned the measurement into a treatment decision.","caveats":["Observational: it shows prognosis, not that acting on the result helps.","Tumour-informed assay requiring tissue sequencing first, with a turnaround that constrains how soon after surgery it can be used.","Only 14 patients were positive, so the positive predictive estimate rests on a small number."],"changedPractice":true,"participants":230},"route":"/key-papers/paper-tie-ctdna-minimal-residual-disease-stage-ii-colon-sci-transl-med-2016/","neighbours":{"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/"}],"paper":[{"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)","route":"/key-papers/paper-tie-dynamic-ctdna-guided-adjuvant-stage-ii-colon-nejm-2022/"}],"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":"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/"}],"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":"ngs","kind":"term","name":"Next-generation sequencing (NGS)","route":"/terms/ngs/"}],"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/"}],"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-biomarker-validation","kind":"bottleneck","name":"Biomarkers are not validated or standardised","route":"/bottlenecks/b-biomarker-validation/"},{"id":"b-dormancy-mrd","kind":"bottleneck","name":"Dormant cells and minimal residual disease","route":"/bottlenecks/b-dormancy-mrd/"}],"journal":[{"id":"science-translational-medicine","kind":"journal","name":"Science Translational Medicine","route":"/journals/science-translational-medicine/"}],"idea":[{"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/"}]}}