Medulloblastoma is a primary central nervous system (CNS) tumor and can occur in both children and adults, but is more common in children. As with other brain tumors, imaging studies are the key component in diagnosing a medulloblastoma. Magnetic resonance imaging (MRI) and computerized tomography (CT) scans produce detailed images of the brain and spine and allow doctors to detect the presence of a tumor. Now, scientists at St. Jude Children’s Research Hospital have shown that cell-free DNA (cfDNA) from cerebrospinal fluid (CSF) can be used to detect measurable residual disease (MRD) in children treated for medulloblastoma. The researchers developed a test to detect MRD, and thus the risk of relapse, earlier than a recurrent tumor would be identified using a traditional imaging scan.
Their findings were published in the journal Cancer Cell in a paper titled, “Serial assessment of measurable residual disease in medulloblastoma liquid biopsies.”
“Nearly one-third of children with medulloblastoma, a malignant embryonal tumor of the cerebellum, succumb to their disease,” the researchers wrote. “Conventional response monitoring by imaging and CSF cytology remains challenging, and a marker for MRD is lacking. Here, we show the clinical utility of CSF-derived cfDNA as a biomarker of MRD in serial samples collected from children with medulloblastoma (123 patients, 476 samples) enrolled on a prospective trial.”
MRD are tumor cells that are present during or after cancer treatment has concluded. Detecting these tumor cells is critical for recognizing early risk of relapse.
“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 co-senior author Giles Robinson, MD, associate faculty member, department of oncology at St. Jude. “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,” Robinson added. “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 researchers used CSF samples from patients treated for medulloblastoma to look for cell-free DNA that would indicate the presence of MRD. The trial samples were collected as part of necessary care.
“There’s a lot of interest in the concept of liquid biopsy for cancer, but the technology hadn’t been optimized for pediatric brain tumors,” said corresponding and co-senior author Paul Northcott, PhD, associate faculty member, department of developmental neurobiology at St. Jude. “Through careful scientific trial and error and optimization at the lab bench, we found a protocol that can reliably identify the genomic variations characteristic of medulloblastoma.”
“Using low-coverage whole-genome sequencing, tumor-associated copy-number variations in CSF-derived cfDNA are investigated as an MRD surrogate. MRD is detected at baseline in 85% and 54% of patients with metastatic and localized disease, respectively,” noted the researchers.
The researchers found that this method of detecting MRD can alert clinicians to the risk of relapse earlier. “Our findings advocate for the prospective assessment of CSF-derived liquid biopsies in future trials for medulloblastoma,” concluded the researchers.