Cell-free DNA can help detect measurable residual disease in children with medulloblastoma



Scientists from the Children’s Research Hospital St. Jude showed that cell-free DNA from cerebrospinal fluid (CSF) can be used to detect measurable residual disease (MRD) in children treated for medulloblastoma brain tumor. The researchers developed a test to detect MRD and thus the risk of recurrence earlier than a recurrent tumor will be identified using traditional imaging. The findings were published today in Cancer cell.

Medulloblastoma is one of the most common malignant childhood brain tumors. The image at the end of therapy is useful for assessing the absence of volume disease, but to date there is no definitive test to declare a patient free of disease. As such, clinicians do not know who is cured or who will recur, but they know that up to a third of patients may relapse.

MRD refers to tumor cells that are present during or after cancer treatment. Detection of these tumor cells or their markers, such as cell-free DNA, is vital for recognizing the early risk of recurrence and potentially preventing it before it is identified.

We often scan patients in the first few years when they leave therapy, but unfortunately, when we see a recurrence on scan, there are already many diseases. Recurrent medulloblastoma has an incredibly poor prognosis and for many people it is too late to cure. As a result, we looked for a better way to determine if a child was indeed cleared of the disease at the time of leaving therapy.

Giles Robinson, MD, Co-senior author, Department of Oncology of St. Jude

“With this test, we now know that if there is cell-free medulloblastoma DNA in the CSF at the end of therapy, then that patient is very likely to recur,” Robinson said. “It gives us something we can work on, an opportunity to really eradicate the disease before it has a chance of recurrence or recurrence.”

The right test to answer the right question

As part of standard treatment for medulloblastoma, children undergo serial spinal taps to check for disease. This is specific to the treatment of pediatric brain tumors, which are more likely to spread through CSF. Cell-free DNA is not bound to the cell membrane and is instead floating in plasma or CSF. The researchers used CSF samples from patients treated for medulloblastoma in the SJMB03 study to look for cell-free DNA that showed the presence of MRD. Samples were collected as part of the necessary care.

“There is a lot of interest in the concept of liquid biopsy for cancer, but the technology is not optimized for pediatric brain tumors,” said co-author Dr. Paul Norcott, of the Department of St. Jude ”for Neurobiology Development. “Through careful scientific trial and error and laboratory bench optimization, we have found a protocol that can reliably identify the genomic variations characteristic of medulloblastoma.”

Northcott and his team rely on a methodology called low-coverage genome sequencing, which summarizes variation in the number of copies throughout the genome (changes in the genetic code). Most medulloblastoma genomes carry these changes, which can be easily detected with this approach.

The results show that this method of detecting MRD can alert clinicians to the risk of recurrence earlier. However, before it can be included in future clinical trials, a certified clinical laboratory will need to accept the test (not a research laboratory).

Source:

St. Jude Children’s Research Hospital

Reference in the magazine:

Liu, A., and others. (2021) Serial assessment of measurable residual disease in liquid biopsies of medulloblastoma. Cancer cell. doi.org/10.1016/j.ccell.2021.09.012.



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