Evidence map›Paper›PMID 41115959›Full record

Trial reportNature medicine2025

Circulating tumor DNA-guided adjuvant therapy in locally advanced colon cancer: the randomized phase 2/3 DYNAMIC-III trial.

Jeanne Tie, Yuxuan Wang, Jonathan M Loree, Joshua D Cohen, Rachel Wong, Timothy Price, Niall C Tebbutt, Val Gebski, David Espinoza, Matthew Burge and 21 more

Abstract readRandomized Controlled TrialClinical Trial, Phase IIIClinical Trial, Phase II
PubMed Publisher
In one paragraph

Trial report in Nature medicine, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 56 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
56citing papers in PubMed, 1 pooled it
–field-weighted citation impact
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

56 citing papers in PubMed, 1 synthesis or guideline pooled it.

  1. Pooled it
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  3. Tissue-Free Circulating Tumor DNA Assay and Patient Outcome in a Phase III Trial of FOLFOX-Based Adjuvant Chemotherapy (Alliance N0147).Journal of clinical oncology : official journal of the American Society of Clinical Oncology · 2026
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4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

31 authors.

Jeanne Tie *Department of Medical Oncology, Peter MacCallum Cancer Centre, Melbourne, Victoria, Australia. jeanne.tie@petermac.org.ORCID http://orcid.org/0000-0001-9244-2057
Yuxuan Wang *Ludwig Center for Cancer Genetics and Therapeutics, Johns Hopkins University School of Medicine, Baltimore, MD, USA.
Jonathan M LoreeDivision of Medical Oncology, BC Cancer, Vancouver, British Columbia, Canada.ORCID http://orcid.org/0000-0001-8189-2132
Joshua D CohenLudwig Center for Cancer Genetics and Therapeutics, Johns Hopkins University School of Medicine, Baltimore, MD, USA.
Rachel WongDepartment of Medical Oncology, Eastern Health, Melbourne, Victoria, Australia.ORCID http://orcid.org/0000-0002-4926-5689
Timothy PriceDepartment of Medical Oncology, The Queen Elizabeth and University of Adelaide, Adelaide, South Australia, Australia.
Niall C TebbuttWarringal Private Hospital, Melbourne, Victoria, Australia.
Val GebskiNHMRC Clinical Trials Centre, The University of Sydney, Sydney, New South Wales, Australia.
David EspinozaNHMRC Clinical Trials Centre, The University of Sydney, Sydney, New South Wales, Australia.
Matthew BurgeDepartment of Medical Oncology, Royal Brisbane and Women's Hospital, Brisbane, Queensland, Australia.
Sam HarrisDepartment of Medical Oncology, Bendigo Health, Bendigo, Victoria, Australia.
James LynamNewcastle Private Hospital, Newcastle, New South Wales, Australia.ORCID http://orcid.org/0000-0002-6742-820X
Belinda LeeDepartment of Medical Oncology, Peter MacCallum Cancer Centre, Melbourne, Victoria, Australia.ORCID http://orcid.org/0000-0002-0947-9834
Margaret M LeeDepartment of Medical Oncology, Eastern Health, Melbourne, Victoria, Australia.
Daniel BreadnerVerspeeten Family Cancer Centre at the Schulich School of Medicine and Dentistry, London, Ontario, Canada.
Marlyse DebrincatDivision of Personalised Oncology, Walter and Eliza Hall Institute of Medical Research, Melbourne, Victoria, Australia.
Siavash ForoughiDivision of Personalised Oncology, Walter and Eliza Hall Institute of Medical Research, Melbourne, Victoria, Australia.ORCID http://orcid.org/0000-0001-6916-8424
Lorraine ChantrillDepartment of Medical Oncology, Wollongong Hospital, Wollongong, New South Wales, Australia.ORCID http://orcid.org/0000-0002-5790-0208
Stephanie H LimMacarthur Cancer Therapy Centre, Campbelltown Hospital, Sydney, New South Wales, Australia.
Sharlene GillDivision of Medical Oncology, BC Cancer, Vancouver, British Columbia, Canada.ORCID http://orcid.org/0000-0003-3306-3617
Chris O'CallaghanCanadian Cancer Trials Group, Kingston, Ontario, Canada.
Janine PtakLudwig Center for Cancer Genetics and Therapeutics, Johns Hopkins University School of Medicine, Baltimore, MD, USA.
Natalie SillimanLudwig Center for Cancer Genetics and Therapeutics, Johns Hopkins University School of Medicine, Baltimore, MD, USA.
Lisa DobbynLudwig Center for Cancer Genetics and Therapeutics, Johns Hopkins University School of Medicine, Baltimore, MD, USA.
Maria PopoliLudwig Center for Cancer Genetics and Therapeutics, Johns Hopkins University School of Medicine, Baltimore, MD, USA.
Chetan BettegowdaLudwig Center for Cancer Genetics and Therapeutics, Johns Hopkins University School of Medicine, Baltimore, MD, USA.ORCID http://orcid.org/0000-0001-9991-7123
Nicholas PapadopoulosLudwig Center for Cancer Genetics and Therapeutics, Johns Hopkins University School of Medicine, Baltimore, MD, USA.ORCID http://orcid.org/0000-0001-7135-7451
Kenneth W KinzlerLudwig Center for Cancer Genetics and Therapeutics, Johns Hopkins University School of Medicine, Baltimore, MD, USA.ORCID http://orcid.org/0000-0001-5591-1176
Bert Vogelstein *Ludwig Center for Cancer Genetics and Therapeutics, Johns Hopkins University School of Medicine, Baltimore, MD, USA.ORCID http://orcid.org/0000-0003-0766-3854
Peter Gibbs *Division of Personalised Oncology, Walter and Eliza Hall Institute of Medical Research, Melbourne, Victoria, Australia.
AGITG DYNAMIC-III Study Group (Intergroup Study of the Australasian Gastro-Intestinal Trials Group and Canadian Cancer Trials Group)

Funding

Canadian Cancer Society Research Institute (Société Canadienne du Cancer) 707213Department of Health | National Health and Medical Research Council (NHMRC) APP1194970Gouvernement du Canada | Canadian Institutes of Health Research (Instituts de Recherche en Santé du Canada) 178140U.S. Department of Health & Human Services | NIH | NCI | Division of Cancer Epidemiology and Genetics, National Cancer Institute (National Cancer Institute Division of Cancer Epidemiology and Genetics) CA62924, CA009071, GM136577 and CA06973
6 · The paper itself

Abstract

Adjuvant chemotherapy in stage III colon cancer provides uncertain benefit at the individual level. Circulating tumor DNA (ctDNA) may help refine risk-adjusted treatment selection. In this multicenter, randomized, phase 2/3 trial, patients with stage III colon cancer underwent ctDNA testing 5-6 weeks after surgery and were assigned (1:1) to ctDNA-guided or standard management. In the ctDNA-guided arm, patients negative for ctDNA received de-escalated therapy, whereas ctDNA-positive patients received escalated therapy. Clinicians prespecified the standard regimen. Primary endpoints were 3-year recurrence-free survival (RFS) for ctDNA-negative patients and 2-year RFS for ctDNA-positive patients. Secondary endpoints included treatment-related hospitalization and ctDNA clearance. Among 968 evaluable patients, 702 (72.5%) were ctDNA negative. With a median follow-up of 47 months, ctDNA-negative patients experienced significantly fewer recurrences than ctDNA-positive patients (3-year RFS 87% versus 49%; P < 0.001). In ctDNA-negative patients, de-escalation reduced oxaliplatin use (34.8% versus 88.6%) and hospitalizations (8.5% versus 13.2%) but yielded slightly lower RFS than standard management (85.3% versus 88.1%), not meeting the non-inferiority margin. In ctDNA-positive patients, higher ctDNA burden correlated with recurrence risk (3-year RFS 77% to 23% across quartiles; P < 0.001). Escalated therapy did not improve outcomes over standard management (2-year RFS 51% versus 61%). There was no unexpected toxicity. Persistent ctDNA after treatment predicted markedly worse prognosis (3-year RFS 14% versus 79%). ctDNA is validated as a strong prognostic classifier. ctDNA-guided de-escalation reduced oxaliplatin exposure and adverse events with outcomes approaching standard of care, whereas exploratory chemotherapy intensification conferred no RFS benefit, suggesting a need for novel strategies in ctDNA-positive disease.Australian New Zealand Clinical Trials Registry Identifier: ACTRN12617001566325 .

Indexed as

Circulating Tumor DNAColonic NeoplasmsAdultAgedAged, 80 and overAntineoplastic Combined Chemotherapy ProtocolsBiomarkers, TumorChemotherapy, AdjuvantFemaleHumansMaleMiddle AgedNeoplasm Recurrence, LocalNeoplasm StagingOxaliplatinBiomarkers, TumorCirculating Tumor DNAOxaliplatin

Identifiers

PMID41115959

What OpenQuestion holds

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Registered trials

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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.