# 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-stage-ii-colon-sci-transl-med-2016/  
OnCo record `paper-tie-ctdna-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

In 230 people whose stage II colon cancer had been removed, finding a trace of tumour DNA in the blood afterwards meant a four in five chance of the cancer coming back, against one in ten if the blood was clear.

## Summary

Massively parallel sequencing assays were used 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 not treated with adjuvant chemotherapy, ctDNA was detected postoperatively in 14 of 178 (7.9%), and 11 of those 14 (79%) had recurred at a median follow-up of 27 months; recurrence occurred in only 16 of 164 (9.8%) with negative ctDNA, giving a hazard ratio of 18. In patients treated with chemotherapy, the presence of ctDNA after completion of chemotherapy was also associated with inferior recurrence-free survival (hazard ratio 11).

## Fields

- Kind: Key paper
- Last checked: 2026-09-24
- Journal: Science Translational Medicine
- Year: 2016
- DOI: 10.1126/scitranslmed.aaf6219
- Authors: Tie J, Wang Y, Tomasetti C, et al.
- Findings: Postoperative ctDNA in 14 of 178 untreated patients (7.9%); 11 of 14 (79%) recurred.; Recurrence in 16 of 164 ctDNA-negative patients (9.8%); hazard ratio 18.; Post-chemotherapy ctDNA also predicted recurrence (hazard ratio 11).
- What it means: It is the founding observation of tumour-informed residual disease testing in solid tumours, and it led directly to DYNAMIC, the randomised trial that made the test change treatment.
- Caveats: Observational; the 9.8% recurrence among ctDNA-negative patients is the false-negative problem.; A bespoke Safe-SeqS assay on tumour-specific mutations rather than a commercial test.; Stage II colon cancer only.

## Sources

- Tie et al., Sci Transl Med 2016: ctDNA detects minimal residual disease after stage II colon cancer resection (230 patients): https://doi.org/10.1126/scitranslmed.aaf6219
- PubMed: https://pubmed.ncbi.nlm.nih.gov/27384348/

## Connected records

- biomarkers: [ctDNA MRD positivity (molecular residual disease after curative treatment)](https://onco.cc/biomarkers/ctdna-mrd-positive/)
- cancers: [Colorectal cancer](https://onco.cc/cancers/colorectal/)
- technologies: [Liquid biopsy (ctDNA)](https://onco.cc/technologies/liquid-biopsy/), [MRD / molecular residual disease testing](https://onco.cc/technologies/mrd-testing/)
- 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/)
- terms: [Cell-free DNA (cfDNA)](https://onco.cc/terms/cfdna/), [Circulating tumour DNA (ctDNA)](https://onco.cc/terms/ctdna/), [Minimal / molecular residual disease (MRD)](https://onco.cc/terms/mrd/), [Tumour-informed versus tumour-naive ctDNA assays](https://onco.cc/terms/tumour-informed-assay/)
- trials: [DYNAMIC](https://onco.cc/trials/dynamic/)
- 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/)
- journals: [Science Translational Medicine](https://onco.cc/journals/science-translational-medicine/)

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