MRD refers to tumor cells that are present during or after cancer treatment has concluded. Detecting these tumor cells, or markers of them, such as cell-free DNA, is vital for recognizing early risk of relapse and potentially heading this off before it has become established.
“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, M.D., St. Jude Department of Oncology. “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 said. “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 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 by the membrane of a cell and is instead found floating in plasma or CSF. Researchers used CSF samples from patients treated for medulloblastoma on the SJMB03 study 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, Ph.D., St. Jude Department of Developmental Neurobiology. “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.”
Northcott and his team relied on a methodology called low-coverage whole-genome sequencing that summarizes genome-wide copy number variation (changes in the genetic code). Most medulloblastoma genomes harbor these changes that can be readily detected with this approach.
The results showed that this method of detecting MRD can alert clinicians to the risk of relapse earlier. However, before it can be incorporated into prospective clinical trials, a certified clinical laboratory will need to adopt the test (rather than a research laboratory).
The study’s co-first authors are Anthony Liu, Kyle Smith and Rahul Kumar of St. Jude. The other co-senior author is Amar Gajjar, St. Jude Department of Pediatric Medicine chair. Additional authors are Kendra Maass and Kristian Pajtler of the German Cancer Research Center; Murali Chintagumpala and Jack Su, Texas Children’s Cancer Center; Eric Bouffet, The Hospital for Sick Children; Michael Fisher, Children’s Hospital of Philadelphia; Sridharan Gururangan, UF Health Shands Hospital; Richard Cohn, Sydney Children’s Hospital; Tim Hassall, Queensland Children’s Hospital; Jordan Hansford, The Royal Children’s Hospital; Julie Harreld, Dartmouth Geisel School of Medicine; Richard Gilbertson, Cancer Research UK Cambridge Institute; and Leena Paul, Laure Bihannic, Tong Lin, Paul Klimo Jr., Frederick Boop, Clinton Stewart, Thomas Merchant, Ruth Tatevossian, Geoffrey Neale, Matthew Lear, Jeffery Klco, Brent Orr, David Ellison and Arzu Onar Thomas, all of St. Jude.
The study was funded by the National Cancer Institute (R21CA256386, P30CA021765), the Carson Leslie Foundation Young Investigator Award, the Li Shu Pui Medical Foundation (Training Grant), the Lin Kin Pang-KHU Foundation Scholarship, the Pew-Stewart Scholar for Cancer Research Award, the Sontag Foundation (Distinguished Scientists Award), St. Baldrick’s Foundation (Robert J. Arceci Innovation Award) and ALSAC, the fundraising and awareness organization of St. Jude.
Read more here: Source link