# Circulating tumor DNA analysis detects minimal residual disease and predicts recurrence in patients with stage II colon cancer

Source: https://onco.cc/key-papers/paper-tie-ctdna-minimal-residual-disease-stage-ii-colon-sci-transl-med-2016/  
OnCo record `paper-tie-ctdna-minimal-residual-disease-stage-ii-colon-sci-transl-med-2016` (Key paper). Data CC BY-NC 4.0, attribute "Data from OnCo (onco.cc)"; commercial use needs a licence.

## TL;DR

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.

In 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.

## Fields

- Kind: Key paper
- Last checked: 2026-09-24
- Tags: colorectal-evidence
- Journal: Science Translational Medicine
- Year: 2016
- DOI: 10.1126/scitranslmed.aaf6219
- Authors: Tie J, Wang Y, Tomasetti C, et al.
- 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).
- What it means: 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.

## Sources

- Sci Transl Med 2016: https://doi.org/10.1126/scitranslmed.aaf6219
- PubMed: https://pubmed.ncbi.nlm.nih.gov/27384348/
- Europe PMC full text (PMC5346159): https://europepmc.org/article/MED/27384348

## Connected records

- 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/), [ctDNA tests roadmap: from a curiosity in plasma to blood tests that decide treatment](https://onco.cc/roadmaps/ctdna-tests/)
- key papers: [Circulating tumor DNA analysis guiding adjuvant therapy in stage II colon cancer (DYNAMIC)](https://onco.cc/key-papers/paper-tie-dynamic-ctdna-guided-adjuvant-stage-ii-colon-nejm-2022/)
- cancers: [Colon cancer (adenocarcinoma of the colon)](https://onco.cc/cancers/colon-cancer/), [Colorectal cancer](https://onco.cc/cancers/colorectal/)
- fronts: [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/)
- terms: [Circulating tumour DNA (ctDNA)](https://onco.cc/terms/ctdna/), [Minimal / molecular residual disease (MRD)](https://onco.cc/terms/mrd/), [Next-generation sequencing (NGS)](https://onco.cc/terms/ngs/)
- drugs: [Signatera](https://onco.cc/drugs/signatera/)
- institutions: [Johns Hopkins Hospital / Sidney Kimmel Comprehensive Cancer Center](https://onco.cc/institutions/johns-hopkins/), [Peter MacCallum Cancer Centre](https://onco.cc/institutions/peter-mac/), [Walter and Eliza Hall Institute of Medical Research](https://onco.cc/institutions/wehi/)
- 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: [Biomarkers are not validated or standardised](https://onco.cc/bottlenecks/b-biomarker-validation/), [Dormant cells and minimal residual disease](https://onco.cc/bottlenecks/b-dormancy-mrd/)
- journals: [Science Translational Medicine](https://onco.cc/journals/science-translational-medicine/)
- ideas: [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/)

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