Tissue-Free Monitoring, Head to Head: What a New Peer-Reviewed Study Shows About Northstar Response

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For oncologists, the question when monitoring a patient on therapy is simple: is the treatment working? Circulating tumor DNA (ctDNA) can answer it from a blood draw, often before imaging can. A longstanding assumption has been that the most reliable way to track ctDNA is to build the assay around the patient’s own tumor tissue.

A new study published in The Journal of Liquid Biopsy puts that assumption to the test. It is one of the first peer-reviewed head-to-head comparison of Northstar Response®, a tissue-free, methylation-based ctDNA assay, and a commercially available tumor-informed ctDNA assay in patients with advanced cancer undergoing treatment.

What the study looked at

This retrospective, real-world study evaluated 169 paired samples from 61 patients. Of those, 71 sequential intervals from 36 patients had concurrent draws for the two assays collected within seven days of each other, which allowed a direct comparison of how each assay tracked change in tumor burden over time.

Northstar Response uses patented single-molecule counting technology to measure the absolute number of ctDNA molecules. It reads cancer-associated methylation signals rather than a panel of variants selected from an earlier tissue sample.

What it found

• Quantitative agreement was close. Quantitative measurements were strongly correlated (R² = 0.79), with an even stronger association after accounting for patient-specific differences using a mixed-effects model (conditional R² = 0.97).
• The two approaches usually reached the same conclusion. Across evaluable sequential pairs, they agreed on the direction of change in tumor burden in 94% of cases (67 of 71).
• When the assays diverged, Northstar Response detected progression that the tumor-informed assay missed. In all of the divergent cases, Northstar Response trends were more consistent with available clinical and radiographic findings, including instances of disease progression not reflected by the tumor-informed assay.

The overall finding: Northstar Response tracked disease dynamics comparably to the tumor-informed assay and, in select cases, more closely reflected the clinical picture, without requiring tissue sequencing.

Why the discordant cases matter

The cases where the assays disagreed are the most instructive. In several, Northstar Response detected progression where the tumor had evolved since the original biopsy, including a case of hormone receptor conversion in advanced breast cancer.

That is the practical limitation of a tissue-based approach, as Allen Chen, MD, Vice President of Oncology Clinical Development and Medical Affairs at Northstar Oncology, explains, “Tumor-informed assays link your monitoring to biopsy-obtained tissue… The tumor changes its genomic characteristics over time, and that leads to a situation where what you’re basing your monitoring on is no longer valid.”

Tiffany Farmer, PhD,  Associate Director of Medical Affairs for Northstar Oncology and a study author, adds: “Cancers change over time, so what happens if one of those variants are no longer available to track? I really think that thinking about epigenetic modifications like methylation is the way to go.”

A tumor-agnostic, methylation-based approach does not depend on which variants were present at the time of biopsy. It can follow changes in disease biology that emerge under treatment pressure.

A simpler path to monitoring

Concordance is only part of the story. Because Northstar Response does not require tumor tissue at any stage, monitoring can start without waiting on tissue sequencing and custom panel design. That can accelerate the start of molecular monitoring, potentially by weeks, and it makes monitoring possible when tissue is unavailable, inadequate, or hard to obtain.

Farmer highlights who benefits most: “There have definitely been patients who have not been well served by the tumor-informed approach - like lung cancer patients who have very small amounts of tissue, or pancreatic cancer patients who are unable to get a good tissue biopsy… I love that there’s an opportunity to leverage circulating tumor DNA to find answers for these patients.”

Dr. Chen sums up the practical significance: “Treatment monitoring must be both reliable and practical for it to be effective in routine oncology care. These results show that clinicians do not need to compromise one for the other.”

What clinicians are saying

Vaia Florou, MD, MS, Associate Professor, Division of Oncology, Huntsman Cancer Institute at the University of Utah, put it this way: “These results showing that a standardized assay can deliver precise longitudinal monitoring without tissue dependency are incredibly relevant for those of us practicing on the frontlines of cancer care.”

Watch and learn more

Watch the video above to hear our team discuss the study, why methylation-based monitoring holds up as tumors evolve, and what tissue-free monitoring can mean for patients.

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Northstar Response may produce false-positive or false-negative results. Test results are not a guarantee of the presence or absence of disease or treatment response and should not be used as the sole basis for medical decision-making. Results should be interpreted in conjunction with the patient’s clinical presentation, radiographic findings, and other diagnostic information. Northstar Response is intended to complement, not replace, standard clinical and radiographic assessment of disease status. Northstar Response is a laboratory-developed test (LDT) performed in a CLIA-certified and CAP-accredited laboratory. The test has not been cleared or approved by the U.S. Food and Drug Administration (FDA). Test performance may vary based on factors including cancer type, disease burden, treatment, and specimen characteristics.

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