# Analysis of plasma cell-free DNA by ultradeep sequencing in patients with stages I to III colorectal cancer

Source: https://onco.cc/key-papers/paper-reinert-ctdna-ultradeep-sequencing-colorectal-jama-oncol-2019/  
OnCo record `paper-reinert-ctdna-ultradeep-sequencing-colorectal-jama-oncol-2019` (Key paper). Data CC BY-NC 4.0, attribute "Data from OnCo (onco.cc)"; commercial use needs a licence.

## TL;DR

Testing the same patients again and again after surgery, and after chemotherapy, and during follow-up, showed the blood test gets more powerful the later you use it, and found relapses up to 16 months before a scan did.

## Summary

In a prospective, multicentre cohort study, circulating tumour DNA was quantified before and after surgery, during and after adjuvant chemotherapy and during surveillance in stage I to III colorectal cancer by personalised multiplex PCR-based next-generation sequencing. 130 patients were enrolled at three Danish hospitals from 2014 to 2017, with 829 plasma samples collected before surgery, at postoperative day 30 and every three months for up to three years; 125 were analysable. Preoperatively, ctDNA was detectable in 108 of 122 patients (88.5%). After definitive treatment, longitudinal analysis identified 14 of 16 relapses (87.5%). At postoperative day 30, ctDNA-positive patients were 7 times more likely to relapse (hazard ratio 7.2); shortly after adjuvant chemotherapy, 17 times (hazard ratio 17.5), and all 7 patients who were positive after chemotherapy relapsed. During surveillance, ctDNA-positive patients were more than 40 times more likely to recur (hazard ratio 43.5). ctDNA status was independently associated with relapse after adjustment for known risk factors, and serial analysis revealed recurrence up to 16.5 months ahead of standard imaging.

## Fields

- Kind: Key paper
- Last checked: 2026-09-24
- Journal: JAMA Oncology
- Year: 2019
- DOI: 10.1001/jamaoncol.2019.0528
- Authors: Reinert T, Henriksen TV, Christensen E, et al.
- Findings: Preoperative ctDNA detectable in 108 of 122 patients (88.5%).; Relapse hazard ratios 7.2 at day 30, 17.5 after adjuvant chemotherapy and 43.5 during surveillance.; Lead time over standard imaging of up to 16.5 months.
- What it means: It showed that serial rather than single testing is what makes residual disease detection work, and it set the sampling schedule most later studies have used.
- Caveats: 130 patients at three centres, with 16 relapses, so the confidence intervals are wide.; Tumour-informed assay requires tumour tissue and bespoke panel design.; Observational: no treatment decision was made on the result.

## Sources

- Reinert et al., JAMA Oncol 2019: ultradeep sequencing of plasma cell-free DNA in 130 stage I-III colorectal cancers: https://doi.org/10.1001/jamaoncol.2019.0528
- PubMed: https://pubmed.ncbi.nlm.nih.gov/31070691/

## 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: [Continuous and near-continuous ctDNA monitoring](https://onco.cc/technologies/continuous-ctdna-monitoring/), [Liquid biopsy (ctDNA)](https://onco.cc/technologies/liquid-biopsy/), [MRD / molecular residual disease testing](https://onco.cc/technologies/mrd-testing/)
- drugs: [Oncodetect](https://onco.cc/drugs/oncodetect/), [Signatera](https://onco.cc/drugs/signatera/)
- institutions: [Aarhus University Hospital](https://onco.cc/institutions/aarhus-university-hospital/)
- 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/)
- journals: [JAMA Oncology](https://onco.cc/journals/jama-oncology/)
- trials: [DYNAMIC](https://onco.cc/trials/dynamic/)

---
JSON: https://onco.cc/api/v1/entities/paper-reinert-ctdna-ultradeep-sequencing-colorectal-jama-oncol-2019.json