# Highly Accurate Detection of Circulating Tumor DNA for Monitoring Minimal Residual Disease in Solid Tumors: Analytical and Clinical Validation of the Haystack MRD Assay

Source: https://onco.cc/key-papers/paper-clark-haystack-mrd-validation-j-mol-diagn-2026/  
OnCo record `paper-clark-haystack-mrd-validation-j-mol-diagn-2026` (Key paper). Data CC BY-NC 4.0, attribute "Data from OnCo (onco.cc)"; commercial use needs a licence.

## TL;DR

The validation of Quest's Haystack blood test for leftover cancer, which reports results as a count of tumour DNA molecules per millilitre of plasma.

## Summary

Haystack MRD tracks patient-specific somatic mutations with background noise suppression. Analytical validation used reference materials and clinical specimens across 23 tumour types, followed by clinical validation in stage II to III colorectal cancer and real-world evaluation across 27 cancer types. The 95 per cent limit of detection was 0.063 mean ctDNA molecules per mL, with an analytical measurement range of 0.25 to 1,000; concordance with expected residual disease status was 99 per cent (95% CI 94.2 to 99.9), and quantitative measurements agreed with an orthogonal method (R2 = 0.9998). In early colorectal cancer, post-treatment status gave 100 per cent sensitivity and specificity for recurrence at three years, and 83.3 per cent sensitivity and 100 per cent specificity at five years.

## Fields

- Kind: Key paper
- Last checked: 2026-11-04
- Journal: Journal of Molecular Diagnostics
- Year: 2026
- DOI: 10.1016/j.jmoldx.2026.07.006
- Authors: Clark M, Prathapam R, Bramlett KS, et al.
- Findings: LOD95 0.063 mean ctDNA molecules/mL.; 99% agreement with expected MRD status.; Colorectal cancer: 100% sensitivity and specificity at 3 years; 83.3% sensitivity at 5 years.
- What it means: At these levels the honest unit is a count of molecules, not an allele fraction, which is the counting limit behind attributing residual disease to a clone.
- Caveats: A limit in molecules per mL cannot be converted to parts per million without each sample's cell-free DNA concentration.

## Sources

- Clark et al., J Mol Diagn 2026: https://doi.org/10.1016/j.jmoldx.2026.07.006
- PubMed: https://pubmed.ncbi.nlm.nih.gov/42624249/

## Connected records

- cancers: [Colorectal cancer](https://onco.cc/cancers/colorectal/)
- fronts: [Diagnostics & Biomarkers](https://onco.cc/fronts/diagnostics/)
- technologies: [MRD / molecular residual disease testing](https://onco.cc/technologies/mrd-testing/)
- drugs: [Haystack MRD](https://onco.cc/drugs/haystack-mrd/)
- companies: [Haystack Oncology](https://onco.cc/companies/haystack-oncology/), [Quest Diagnostics](https://onco.cc/companies/quest-diagnostics/)
- terms: [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/)
- bottlenecks: [Naming which clone or phenotype is left after treatment](https://onco.cc/bottlenecks/b-subclone-attribution-residual-disease/)

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