By the time a patient has been diagnosed with medulloblastoma, the most common type of malignant paediatric brain tumour, there is a high probability the cancer has already spread (metastasized). It was assumed this spread occurred through the cerebrospinal fluid because tumours that have spread (metastatic) are most commonly found in the leptomeningeal space, which encases the brain and spinal cord and is filled with cerebrospinal fluid. Now, researchers from The Hospital for Sick Children (SickKids) are turning this thinking on its head.
In a new study published online in Cell on February 22, 2018, SickKids scientists have discovered medulloblastoma can spread the same way the vast majority of cancers spread: through the blood.
“The overwhelming majority of medulloblastoma research has focused on the initial tumour before the patient receives any therapy,” says Dr. Michael D. Taylor, Principal Investigator of the study, Neurosurgeon and Senior Scientist at SickKids. “But the most significant cause of death in patients with medulloblastoma is not the initial tumour. Rather, it’s most often the metastatic tumours that represent the greatest threat to these patients.”
Previously, clinicians thought medulloblastoma spread through the cerebrospinal fluid (CSF) but SickKids researchers have discovered the cancer spreads through the blood (hematologic dissemination), goes around the body and then back into the brain to develop new tumours.
The researchers examined samples of the primary tumour, metastatic tumours and blood from patients with metastasized medulloblastoma cases and found a correlation between the presence of metastatic tumours and circulating tumour cells in the blood. These circulating tumour cells were also more similar to cells in the metastatic tumours compared to the primary tumour, providing evidence that medulloblastoma cells can effectively travel from the brain, through the blood and back into the brain to develop secondary tumours. The scientists confirmed their findings by using a mouse model and observing that even medulloblastoma tumour cells originating in the blood can travel to the brain.
“Finding out that medulloblastoma can spread through the blood has major implications for disease diagnosis and monitoring therapy response,” says Livia Garzia, lead author of the study and former Research Fellow at SickKids. “In the future, we may be able to diagnose these tumours through blood samples and perhaps deliver targeted treatments that will prevent the spread of medulloblastoma.”
The researchers believe these findings could be the next step in stopping the lethal spread of medulloblastoma. Future work will focus on the reliability of detecting circulating tumour cells in blood samples and determining the mechanisms behind how cells from the primary tumour get into the blood and back into the brain.
Dr. Michael D. Taylor is also a Professor in the Departments of Surgery and Laboratory Medicine and Pathology at the University of Toronto.
This work was supported by the National Institutes of Health, The Pediatric Brain Tumour Foundation, The Terry Fox Research Institute, The Canadian Institutes of Health Research (CIHR), The Cure Search Foundation, b.r.a.i.n.child, Meagan’s Walk, Genome Canada, Genome B.C., the Ontario Institute for Cancer Research and SickKids Foundation. It is an example to how SickKids is contributing to making Ontario Healthier, Wealthier and Smarter. www.healthierwealthiersmarter.com
The Hospital for Sick Children (SickKids).