A recurrence occurs when cancer comes back after treatment. This can happen weeks, months, or even years after the primary or original cancer was treated. It is impossible to know for sure if the cancer will recur and timely detection of recurrence, as well as identification of patients at high risk of recurrence after surgery, can be challenging.  Postsurgical circulating tumor DNA (ctDNA) analysis is a promising tool for the identification of patients with minimal residual disease. Now researchers at Massachusetts General Hospital (MGH) report they have evaluated the first test that detects cancer DNA circulating in the blood of patients following treatment without knowing the particular mutations that were present in the patient’s tumor.

Their new study is published in the journal Clinical Cancer Research in a paper titled, “Minimal Residual Disease Detection using a Plasma-Only Circulating Tumor DNA Assay in Colorectal Cancer Patients.”

The new test is called Guardant Reveal and was developed by precision oncology company Guardant Health.

“The use of ctDNA, which is a type of ‘liquid biopsy,’ is a powerful prognostic tool to detect residual disease, and many prospective trials are underway in the United States, Europe, Asia, and Australia to use ctDNA to guide treatment decision-making,” explained lead author Aparna R. Parikh, MD, an investigator in the division of hematology and oncology at MGH and an assistant professor of medicine at Harvard Medical School. “Most studies have used a tumor-informed ctDNA approach that requires testing of the tumor and knowledge of tumor-specific alterations, which can’t be used when a patient has insufficient tumor tissue for analysis.”

Most ctDNA MRD assays require tumor sequencing to identify tumor-derived mutations to facilitate ctDNA detection, requiring tumor and blood. The researchers at MGH and Guardant Health evaluated a plasma-only ctDNA assay integrating genomic and epigenomic cancer signatures to enable tumor-uninformed MRD detection.

The researchers analyzed 252 prospective serial plasma specimens from 103 colorectal cancer patients undergoing curative intent surgery. Of 103 patients, 84 had evaluable plasma drawn post-completion of definitive therapy.

“This is one of the first studies to report on a plasma-only approach. There are advantages and disadvantages to each of the approaches,” said Parikh. Ongoing studies will provide additional information on the performance of this assay for detecting residual cancer cells and for guiding treatment decisions.

“Plasma-only MRD detection demonstrated favorable sensitivity and specificity for recurrence, comparable to tumor-informed approaches. Integrating analysis of epigenomic and genomic alterations enhanced sensitivity. These findings support the potential clinical utility of plasma-only ctDNA MRD detection,” concluded the researchers.

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