Michael Dewan, MD, MSCI, assistant professor of Neurological Surgery and surgical director of the Pediatric Neuro-Oncology Program at Monroe Carell Jr. Children’s Hospital at Vanderbilt, has received a grant from the Pediatric Brain Tumor Foundation (PBTF) to study why some low-grade gliomas, a type of non-cancerous brain or spine tumor, spread and behave like cancerous tumors.
The study is a collaboration between Vanderbilt University Medical Center and the Hospital for Sick Children (HSC) in Toronto, Canada.
“Low-grade glioma brain tumors are most often overlooked in the research arena despite being one of the most common forms of brain tumors in kids,” said Amy Weinstein, PBTF national director of research investments.
“Because they are considered ‘low grade’, many don’t realize the damage that results. On behalf of the thousands of children battling this disease, PBTF is grateful to Dr. Dewan and the investigators from Sick Children’s for prioritizing this disease as an area of discovery. More effective treatments for these children have the potential to change the trajectory of the patients’ lives.”
Gliomas are formed from glial cells — neuron support cells — in the central nervous system. There are four types of glial cells that function to maintain and protect neurons in the brain. But occasionally the cells can go wrong, growing into gliomas.
Once diagnosed, a glioma is graded based on how abnormal the cells appear and how quickly they are growing or dividing. Grade I or grade II gliomas are considered low-grade gliomas; III and IV, high grade. Low-grade gliomas are typically slow growing and less likely to disseminate (spread) but can cause many problems and need medical treatment.
“Low-grade gliomas rarely disseminate to other parts of the brain or other parts of the spine, unlike high grade gliomas that are faster growing and tend to be malignant,” said Dewan, who also serves as the associate vice chair of Global Surgery. “Low-grade gliomas are a noncancerous form of brain tumor, less bad acting, less scary and usually more treatable. But when they do (spread), they behave much more like their high-grade counterparts, and we know that the mortality rate becomes higher and more difficult to treat.”
Dewan said it is unknown why low-grade gliomas sometimes decide to spread. It’s suspected that there are molecular alterations or mutations present that might encourage the tumors to spread.
“We know that based on our knowledge of other tumors in the brain and elsewhere,” he said. “There are molecular alterations that occur in lung cancer, for example, that predispose them to metastasize to other parts of the body, and we wonder whether similar mutations or a genetic change at the cell level happens in low-grade gliomas, prompting the tumor, instead of being localized in one part of the brain, to begin to spread.”
Pinpointing the molecular alterations, or genetic fingerprints, could eventually lead to treatment.
“If we can find those molecular alterations … then in the future when we have a patient with a low-grade glioma, we can interrogate that tumor for the same molecular alterations,” Dewan said. “When we find one, we say, ‘time out.’ This has been identified as low grade, but we aren’t going to treat it as such. We are going to be more aggressive with it. We may image it more often or perhaps resect it more extensively to get ahead of it before it becomes a bad actor.”
In the study, VUMC and HSC, where Dewan completed a pediatric neurosurgery fellowship before coming to Vanderbilt, will collect tumor samples and molecular information from all over the world to study and identify what’s responsible for low-grade glioma spread and metastasis.
“We can’t just study 20 patients. In order to get enough data to make definitive conclusions we need more patients, and to get more patients we need more centers,” he said. “Disseminated low grade gliomas are rare — in a year I might see two or three, and that is true of other high-volume centers like Vanderbilt,” Dewan said. “We recognize that we need many centers to contribute sufficient patients to achieve the kind of statistical power needed to draw actionable conclusions.”
Tissue from the gliomas will be shipped to a lab in Toronto where tests will be run to better understand the molecular characteristics of the tumors. In some cases where the molecular data has already been obtained, the information can be submitted to a shared REDCap database.
Dewan said funding from the PBTF is crucial. “Partnering with the PBTF in this effort has changed what is possible. Not only can we recruit more centers, but we can take a much deeper dive into the molecular nuances of these tumors.
“This international collaboration demonstrates a rare, diverse symphony of investigators, neurosurgeons, oncologists, and pathologist. The work we do together will have a direct impact on children here and around the world.”
