Researchers at U of T and SickKids may spark a major shift in treating children with certain brain cancers (Bigstock photo)

Treating brain cancer in children

Study finds important differences between tumours

An international collaboration led by a team from the University of Toronto and The Hospital for Sick Kids (SickKids) may spark a major shift in treating children with certain brain cancers.

“This is exciting but also daunting,” says Dr. Eric Bouffet, 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.”

The most common malignant brain tumour in children, medulloblastoma affects 30 to 40 children in Canada each year. And with four different types of medulloblastoma, each case is even rarer – making it difficult for doctors to determine the best treatments for individual patients.

But that may change, thanks to Medulloblastoma Advanced Genomics International Consortium (MAGIC), which brought together scientists and physicians from 46 institutions across the globe to study more than 1,000 medulloblastoma tumours - an unprecedented number of samples.

Their findings are published in the July 25 advance online edition of Nature.

“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 Taylor, Associate Professor in the Departments of Surgery and Laboratory Medicine and Pathobiology at the University of Toronto.

Today, 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, the effects of such treatments on the developing brain mean children are often left with significant neurological, intellectual and physical disabilities.

“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, 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.

In the new study, researchers identified several clinical and genetic differences in each group which suggests that each group may require separate therapeutic strategies.

For example, the research suggests radiation may not be necessary in some medulloblastomas that arise in teenagers, says Bouffet, 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.

“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,” Bouffet says. “We will need to lead this change with new innovative clinical strategies.”

Analysis of these tumours also revealed 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; the Canadian Cancer Society; 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.

 

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