August 15, 2011
Scientists identify two distinct subgroups in common childhood brain cancer
Discovery may impact aggressiveness of current treatments for some infants and children with posterior fossa ependymoma
TORONTO – When Alexandra McLeod was almost eight years old, she came home from horseback riding, took a shower and suddenly fainted. Weeks later she was diagnosed with the third most common brain tumour in children: posterior fossa (PF) ependymoma.
Under the microscope, ependymoma tumours look similar, but in a new study by The Hospital for Sick Children (SickKids) and University Hospital Heidelberg in Germany, researchers found they are very different. They identified two molecularly and clinically distinct groups of posterior fossa ependymomas and markers to differentiate them. The significance of the findings is underlined by the fact that in one group of patients, almost everyone survives, while in the other group, the majority of patients die from their brain tumour. The study is published in the August 16 advance online edition of Cancer Cell.
Ependymomas can occur in the brain and spinal cord. The main symptom is pressure within the skull resulting in headaches, neck pain and vomiting. PF ependymomas are more common in infants and children. Up to 40 per cent of affected children will die of their disease, and many survivors will be left with serious disabilities secondary to the effects of both the disease and its treatment on the developing brain.
The current study suggests that PF ependymoma be treated as two distinct tumours identified as Groups A and B. Group A patients are younger (median age is two and a half), have tumours located on the sides of the brain and are more likely to experience tumour recurrence and death. Group B patients are typically older (median age is 20) and their tumours are much less likely to recur, resulting in more positive outcomes.
“Typically, PF ependymomas have been treated the same. This finding will help develop targeted, subgroup-specific therapies that treat the patient and not just the disease,” says Dr. Michael D. Taylor, Principal Investigator of the study, Scientist and Neurosurgeon in Developmental & Stem Cell Biology and The Arthur and Sonia Labatt Brain Tumour Research Centre at SickKids. “If we know that Group B tumours have better outcomes then we may be able to reduce the dose of radiation that some children receive, and thus reduce potential damage to the developing brains of these patients.”
Current treatment for patients with PF ependymoma includes surgical removal of the tumour followed by radiation therapy. In almost all other brain tumour types, chemotherapy is used and is believed to be of some benefit. For ependymoma patients, chemotherapy does not generally work and consequently, it is not commonly used. The lack of effective chemotherapy strategies has proven a major barrier to providing effective treatments for patients with ependymoma. Taylor adds that this is particularly poignant in babies with ependymoma, as their developing brains will not tolerate radiation therapy, leaving the treating physicians and their families few options for treatment and a high mortality rate.
Like most ependymoma patients, Alexandra did not receive any chemotherapy as prior attempts have shown that it is rarely effective in ependymoma. “Determining that PF ependymomas are comprised of two different diseases has allowed us to identify the biological pathways that are specifically activated in each subgroup,” says Stephen Mack, PhD student in the Department of Laboratory Medicine and Pathobiology at the University of Toronto, and lead author on the study. “Understanding these pathways may reveal targets for future effective chemotherapies.”
While radiation therapy kills the cancer cells, it also damages healthy cells which can lead to early or late side effects like memory loss or even a second cancer caused by exposure to radiation. When treating cancer patients, like Alexandra, physicians carefully weigh the known risks of treatment against the potential benefits for each patient. This is especially important for children with cancer as their brains are still developing.
“Thinking back to when I was diagnosed in 2000, this research could have affected the course of my treatment,” says Alexandra, who is now 19 years old and is currently in her third-year of university. “I have not experienced major developmental side effects, but this research may provide a better idea of which patient needs what treatment in the future. It’s great that ongoing research continues to provide better tools to make the tough decisions about treatment.”
In this study scientists used a human ependymoma tissue microarray (gene-chip techonology) to analyze 583 ependymomas, making it the largest group of these tumours studied to date. The study also identified immunohistochemical markers, which are antibodies used to detect specific proteins in tissue that indicate the differences in the tumours and help with diagnosis. These markers, LAMA2 and NELL2, validate the finding that PF ependymoma are two distinct diseases.
Dr. Michael D. Taylor is also Associate Professor in the Departments of Surgery, Laboratory Medicine and Pathobiology at the University of Toronto.
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 for Healthier Children. A Better World. For more information, please visit www.sickkids.ca.
About SickKids Research & Learning Tower
SickKids Research & Learning Tower 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 Tower 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 Tower will create an architectural landmark as the eastern gateway to Toronto’s Discovery District. SickKids Research & Learning Tower is funded by a grant from the Canada Foundation for Innovation and community support for the ongoing fundraising campaign. For more information, please visit www.buildsickkids.com.
The Hospital for Sick Children
Phone: 416-813-7654 ext. 2059
The Hospital for Sick Children
Phone: 416-813-7654 ext. 1436