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A Liquid Biopsy Approach for Predicting Likely Relapse Following Treatment of Medulloblastoma in Children

By LabMedica International staff writers
Posted on 02 Nov 2021
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Image: Example of gene duplication that has created a copy number variation. The chromosome now has two copies of this section of DNA, rather than one (Photo courtesy of Wikimedia Commons)
Image: Example of gene duplication that has created a copy number variation. The chromosome now has two copies of this section of DNA, rather than one (Photo courtesy of Wikimedia Commons)
A liquid biopsy technique that determines the level of cell-free DNA in cerebrospinal fluid (CSF) can be used to detect measurable residual disease (MRD) in children being treated for the malignant brain tumor medulloblastoma.

Nearly one-third of children with medulloblastoma die from the disease. Conventional drug response monitoring by imaging and CSF cytology remains challenging, while a biomarker for MRD has not been found. MRD, which is the major cause of disease relapse, is the label for the small number of cancer cells that remain in the patient during treatment, or after treatment when the patient is in remission.

Investigators at St. Jude Children’s Research Hospital (Memphis, TN, USA) recently reported that they had identified a biomarker for medulloblastoma MDR. To do this, they used a liquid biopsy technique to acquire samples of cell-free DNA from the patients’ CSF combined with low-coverage whole-genome sequencing, which characterized the type of mutation called genome-wide copy number variation.

For this study, they analyzed serial CSF samples collected from children with medulloblastoma (123 patients, 476 samples) enrolled in a prospective trial. Results revealed that MRD was detected at baseline in 85% and 54% of patients with metastatic and localized disease, respectively. The number of MRD-positive patients declined with therapy, yet those with persistent MRD had significantly higher risk of progression. Importantly, MRD detection by the liquid biopsy method preceded radiographic progression in half the patients who relapsed.

“We scan patients frequently for the first couple of years when they come off therapy, but unfortunately, by the time we see a recurrence on a scan there is already a lot of disease,” said senior author Dr. Giles Robinson, a neuro-oncologist at St. Jude Children’s Research Hospital. “Relapsed medulloblastoma harbors an incredibly poor prognosis and for many it is too late to cure. As a result, we sought a better way to determine whether a child is truly clear of disease at the time they come off therapy. With this test, we now know that if there is medulloblastoma cell-free DNA in the CSF at the end of therapy, then that patient is very likely to relapse. That gives us something we can act on, an opportunity to truly eradicate the disease before it has had a chance to relapse or re-emerge.”

The medulloblastoma MRD study was published in the October 21, 2021, online edition of the journal Cancer Cell.

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