Minimal residual disease (MRD) testing identifies the presence of tiny numbers of cancer cells that may remain in the body after treatment. Some MRD tests detect DNA fragments released by cancer cells into the bloodstream. These DNA fragments, known as circulating tumor DNA (ctDNA), are identified by sequencing the DNA in a blood sample. 

This information can be used for the following purposes:

• To help determine a patient’s risk of recurrence in the absence of additional treatment
• To help identify patients who are more likely to benefit from additional treatment
• To help monitor a patient’s disease while on treatment
• To help identify patients with disease recurrence following definitive treatment

MRD testing can detect residual, recurrent, or resistant cancer cells earlier than traditional detection methods. Earlier detection enables treatment decisions to be made when the tumor burden is low, increasing the chances for successful treatment.

Searching for and analyzing ctDNA is a minimally-invasive way to test for residual disease. A liquid (blood-based) biopsy can detect the presence of tumor cells significantly earlier than imaging, increasing the likelihood that a therapeutic intervention will be successful.

Haystack MRD is a liquid biopsy (blood) test that uses a tumor-informed approach for exceptional sensitivity and specificity for detecting circulating tumor DNA (ctDNA) detection. Haystack MRD testing begins with whole-exome sequencing (WES) of a patient’s tumor tissue and a matched normal blood sample to identify patient-specific somatic mutations. A personalized mutation panel is then designed for each patient, and a next-generation sequencing (NGS)-based assay is performed to detect and monitor ctDNA in plasma to identify the presence of residual, recurrent, or resistant disease.

Haystack MRD was specifically built with the sensitivity to accurately detect MRD in patients with early-stage disease. Haystack MRD detects ultralow levels of ctDNA to provide insights at critical moments for important treatment decisions, to accurately monitor treatment response and disease clearance, and to detect the early stages of disease relapse. Importantly, Haystack MRD’s exceptional performance delivers confidence in results and enables an early window of opportunity when clinical management decisions can have the greatest impact on patient outcomes.

Haystack MRD can accelerate clinical development by enriching for number of patients with residual disease than traditional test methods can. By providing highly accurate ctDNA results, Haystack MRD is capable of identifying a larger pool of MRD-positive patients, which can impact enrollment and time to trial completion. In addition, Haystack MRD can be used for monitoring treatment response for clinical investigations, facilitating early determination of treatment efficacy.

Haystack MRD is broadly available, as patient samples can be provided to any of the more than 2,000 Quest Diagnostics Patient Service Centers across the US.

These key features differentiate Haystack MRD from other tests.

• Superb accuracy for detection of MRD, therapeutic response monitoring, and surveillance for cancer recurrence—Haystack MRD can detect 95% of cases at 0.0006% tumor fraction¹ and, with zero false-positive results, boasts an analytical specificity of 100%.² With enhanced analytical sensitivity and specificity, you can trust that the results reflect biological reality, not technical artifacts
• Tumor-informed, personalized assay—A personalized assay is developed based on “ground-truth” mutations that are identified via whole-exome sequencing (WES) in the original tumor sample
• Built on decades of ctDNA clinical technology development—Haystack MRD was built from the ground up by pioneers in liquid biopsy technology to overcome the unique challenges of ctDNA detection in the MRD setting
• Ultradeep sequencing and error correction technology—Haystack MRD detects ctDNA in blood using proprietary technology that reads each molecule up to 1 million times and double-checks each variant to eliminate sequencing noise. This ensures that whether ctDNA is detected or not, you can trust the results to help you more fully understand your patient’s disease status
• Demonstrated clinical utility—With ctDNA detection technology backed by 2 NEJM-published studies—one using an earlier version and one using our current technology—Haystack MRD demonstrates both clinical impact and credibility.⁴ Click here to learn more

Haystack MRD is based on the first method to generate interventional data supporting the clinical utility of using ctDNA MRD testing to guide adjuvant therapy decisions (see “What is the DYNAMIC study?” below).³
Also, in a landmark immunotherapy study, Haystack MRD served as a real-time method to track how patients responded to treatment, identifying response to therapy earlier than traditional imaging methods.

References

1. Data on file. Haystack Oncology; 2024-2025.
2. Prathapam R, Champion K, Blakely K, et al. J Mol Diagn. 2024;26(11):S100. doi:10.1016/S1525-1578(24)00232-0
3. Tie J, Cohen JD, Lahouel K, et al. Circulating tumor DNA analysis guiding adjuvant therapy in stage II colon cancer. N Engl J Med. 2022;386(24):2261-2272. doi:10.1056/NEJMoa2200075
4. Cercek A, Foote MB, Rousseau B, et al. Nonoperative management of mismatch repair-deficient tumors. N Engl J Med. doi:10.1056/nejmoa2404512

Haystack MRD’s chemistry is a highly optimized version of Safe-SeqS chemistry, which was employed in the DYNAMIC study.

Through patented error-correction technology, Haystack MRD confirms that variants are detected on both DNA strands, effectively double-checking variants to set a higher standard for diagnostic accuracy so clinicians can act on results with confidence.

While we work with the Centers for Medicare & Medicaid Services (CMS) and private insurance companies to acquire favorable coverage, we have a robust patient access program to ensure Haystack MRD is available and affordable for all who need it.

Yes, our platform can be used to help stratify patients for enrollment in neoadjuvant and adjuvant settings, as well as second-line therapy trials. It can also be used to monitor therapeutic efficacy. All of which may provide significant time and cost savings.

To design the initial, personalized assay, Haystack MRD requires a formalin-fixed, paraffin-embedded tumor sample (or in some cases, a biopsy sample) and a blood draw. For monitoring MRD status at all future time points, a blood draw is required.

To build the personalized MRD panel, a tissue sample of at least 25 mm² of surface area and 50 µm of depth is required. Biopsies are accepted, but they may have a higher failure rate if they yield fewer non-necrotic tumor cells. See the table below for details.

The tumor sample is obtained surgically (typically when a tumor is removed surgically from the body with curative intent) and should be formalin-fixed and paraffin-embedded. When Haystack MRD is ordered, we will work with the pathology lab to obtain the tumor tissue.

Results for an initial order can take up to 4 weeks, which includes time to build a personalized test for new patients. Any subsequent test results will be provided within 5–7 days after the sample is received.

Our proprietary technology decreases the background signal so that the optimal number of mutations can be included in each patient’s test panel. Haystack MRD tracks up to 50 mutations, prioritizing truncal somatic mutations.

Yes, all Haystack MRD testing is done in a CLIA-certified lab.

A whole-exome sequencing report will not be available. The data from WES will be fed into Haystack MRD’s mutation-selecting algorithm to create a personalized MRD test.

If an additional paraffin block from the patient’s tumor is available, we can attempt to rescue failed tumor whole-exome sequencing (WES). To reduce the risk of failures, we ask that the block with the highest tumor cellularity and lowest amount of necrotic tissue is provided.

Cell-free DNA (cfDNA) is released into the bloodstream from various cells in the body, especially those of the hematopoietic system. If a tumor is present in the body, cells from the tumor may also release DNA into the bloodstream. This circulating tumor DNA (ctDNA) typically makes up a small proportion of the total cfDNA in the bloodstream.

The DYNAMIC study, reported at the 2022 American Society of Clinical Oncology (ASCO) meeting and published in the New England Journal of Medicine, is the first prospective, interventional, randomized trial to demonstrate the clinical utility of a ctDNA-guided treatment strategy. The study evaluated the potential of ctDNA-based MRD testing to guide adjuvant therapy decisions in stage II colorectal cancer patients who had undergone curative-intent surgery. The results of the study showed that a ctDNA-guided treatment strategy led to 50% fewer patients receiving chemotherapy as compared to patients treated based on standard-of-care clinicopathological risk factors, with no reduction in 2-year recurrence-free survival. Read more about the DYNAMIC study here.