While it is known as the most common malignant brain tumour in children, medulloblastoma is not a common disease, affecting 30 to 40 children in Canada each year. Previous research found four different types of medulloblastoma, which makes each case even rarer. As a result, studying large numbers of these tumours has historically been a challenge for researchers.
Scientists and physicians from 46 institutions across the globe, led by a team at The Hospital for Sick Children (SickKids), are working together to better understand and treat medulloblastoma. This group, called the Medulloblastoma Advanced Genomics International Consortium (MAGIC), studied over 1,000 medulloblastoma tumours, an unprecedented number of samples. The findings could lead to a major shift in the clinical management of this life-threatening disease. The study is published in the July 25 advance online edition of Nature.
While a previous SickKids study found that medulloblastoma is actually four different subtypes of the disease, each with its own molecular composition, past attempts to identify specific targets for therapy have been underpowered because of small sample sizes.
“By studying over 1,000 samples we now better understand the four groups and can therefore identify them faster and treat them more specifically,” says Dr. Michael D. Taylor, Principal Investigator of the study, SickKids Neurosurgeon, Scientist in Developmental & Stem Cell Biology at SickKids Research Institute and at The Arthur and Sonia Labatt Brain Tumour Research Centre.
Currently, the standard treatment for medulloblastoma is the same for each patient. It includes nonspecific therapies such as surgery, radiation and aggressive chemotherapy. While the five-year survival rate is 70 to 85 per cent, these children are often left with significant neurological, intellectual and physical disabilities secondary to the effects of these nonspecific therapies on the developing brain. “By learning more about each of the four types of medulloblastoma tumours, we’re moving into an era where we will be able to use targeted treatments that will hopefully kill the tumour and leave the normal developing brain unharmed,” says Taylor, who is also Associate Professor in the Departments of Surgery and Laboratory Medicine and Pathobiology at the University of Toronto.
In the new study, researchers identified several clinical and genetic differences in each group which suggests that each group may require separate therapeutic strategies. One of the things they found, for example, is radiation may not be necessary in some medulloblastomas that arises in teenagers.
“This is exciting but also daunting,” says Dr. Eric Bouffet, Neuro-oncologist, Director of the Paediatric Neuro-oncology program in the Division of Haematology/Oncology at SickKids, Senior Associate Scientist in Child Health Evaluative Sciences at SickKids Research Institute, and Professor in the Department of Paediatrics at the University of Toronto. “What we found suggests a huge shift in the way clinicians work and think about medulloblastoma. Radiation has been part of the standard treatment for years, so eliminating radiation in this group of patients is a decision that will not be taken lightly. We will need to lead this change with new innovative clinical strategies.”
Another finding that came out of the genetic analysis of these tumours is that in some cases the genetics of medulloblastoma are similar to some more common adult tumours, which means there may be potential “new” treatments already available. “There are drugs that are currently being used to treat the adult tumours that could potentially be used to treat a specific group of paediatric patients with medulloblastoma,” says Taylor. “Developing new drugs can take upwards of 10 years, but if a drug already exists this would reduce the time significantly and enable patients to access it sooner.”
Additionally, a gene known to play a role in an adult condition, Parkinson’s disease, has now also been shown to be important in childhood medulloblastoma. “If you have too little of this gene, you get Parkinson’s disease, if you have too much, you develop brain cancer (medulloblastoma),” explains Taylor. The link between Parkinson’s disease and childhood brain cancer had not previously been identified.
These are just three examples of the many discoveries that were possible through international collaboration and major advancements in technology. Future research and clinical changes will also require this kind of collaboration.
“It seems more and more that not all medulloblastoma groups need the same intensity of treatment,” says Bouffet. “We have a unique opportunity to change the odds and move away from traditional treatment. We hope that these findings will enable us to identify and categorize medulloblastoma very quickly and then allocate a specific treatment for each individual patient.”
The study was supported by the Pediatric Brain Tumor Foundation and the National Institutes of Health; Genome Canada, Genome BC; the Terry Fox Research Institute; the Ontario Institute for Cancer Research; the Pediatric Oncology Group of Ontario; funds from ‘The Family of Kathleen Lorette’ and the Clark H. Smith Brain Tumour Centre; the Montreal Children’s Hospital Foundation; the Sonia and Arthur Labatt Brain Tumour Research Centre, Chief of Research Fund, Cancer Genetics Program, Garron Family Cancer Centre, b.r.a.i.n.child at SickKids; the Canadian Institutes of Health Research; the McLaughlin Centre at the University of Toronto; CIHR Institute of Cancer Research and C17 through the Advancing Technology Innovation through Discovery competition; and SickKids Foundation.
About The Hospital for Sick Children
The Hospital for Sick Children (SickKids) is recognized as one of the world’s foremost paediatric health-care institutions and is Canada’s leading centre dedicated to advancing children’s health through the integration of patient care, research and education. Founded in 1875 and affiliated with the University of Toronto, SickKids is one of Canada’s most research-intensive hospitals and has generated discoveries that have helped children globally. Its mission is to provide the best in complex and specialized family-centred care; pioneer scientific and clinical advancements; share expertise; foster an academic environment that nurtures health-care professionals; and champion an accessible, comprehensive and sustainable child health system. SickKids is proud of its vision of Healthier Children. A Better World.™ For more information, please visit www.sickkids.ca.
About SickKids Centre for Research and Learning
The SickKids Centre for Research and Learning will bring together researchers from different scientific disciplines and a variety of clinical perspectives, to accelerate discoveries, new knowledge and their application to child health — a different concept from traditional research building designs. The facility will physically connect SickKids science, discovery and learning activities to its clinical operations. Designed by award-winning architects Diamond + Schmitt Inc. and HDR Inc. with a goal to achieve LEED® Gold Certification for sustainable design, the Centre will create an architectural landmark as the eastern gateway to Toronto’s Discovery District. The SickKids Centre for Research and Learning is funded by a grant from the Canada Foundation for Innovation, the Government of Ontario, philanthropist Peter Gilgan and community support for the ongoing fundraising campaign. For more information, please visit www.sickkidsfoundation.com/bepartofit.
For more information, please contact:
The Hospital for Sick Children
Phone: 416-813-7654 ext. 2059
The Hospital for Sick Children
Phone: 416-813-7654 ext. 1436