About Sickkids
About SickKids
print        

March 22, 2010

SickKids discovery changes the recommended standard of care for children with rare brain tumour

Choroid plexus carcinoma patients with a specific genetic mutation may now be able to avoid aggressive radiation therapy

TORONTO – For many patients, one of the most difficult aspects of cancer treatment is undergoing radiation therapy. New research led by The Hospital for Sick Children (SickKids) and funded in part by the Canadian Cancer Society, indicates that patients suffering from a rare form of paediatric brain cancer may now be spared from the debilitating effects of radiation.

A team of scientists from SickKids, the University of Toronto and The Children’s Hospital of Los Angeles have identified a genetic mutation that plays a major role in the outcome of a paediatric brain cancer called choroid plexus carcinoma. The study also sheds light on why some choroid plexus tumours are more aggressive and reoccur more frequently, and may also provide insight into the treatment of other cancers. The study is published in the March 22 advance online issue of the Journal of Clinical Oncology.

The disease occurs most commonly in the first year of life and accounts for four per cent of all childhood brain tumours. It is usually treated with radiation, chemotherapy and surgeries, with a success rate of only 25 per cent. Patients undergoing radiation often have to cope with long-term side-effects, such as neurocognitive delay and severe growth impairment. For very young patients, the lifelong impact of these radiation-induced toxicities can be even more serious.

"Unfortunately, children with this type of cancer have a very poor survival rate,” says Dr. David Malkin, principal investigator of the study, Associate Chief of Clinical Research, Co-Director of the Cancer Genetics Program, Senior Staff Oncologist and Senior Scientist at SickKids. “They also often have an inherited condition called Li-Fraumeni syndrome, which predisposes them to develop a spectrum of early-onset malignancies. The aim of our study was to determine how these diseases were related, and to identify ways of improving survival for patients with choroid plexus tumours," adds Malkin, who is also a Professor in the Department of Paediatrics at the University of Toronto.

The researchers examined the DNA of 64 patients with choroid plexus tumours and correlated genetic findings to disease outcomes and family histories. They found that most of the tumours had either a mutated tumour suppressor gene called TP53, or mutations in other genes that modify TP53 activity. Patients without a family history of cancer or Li-Fraumeni syndrome were less likely to have TP53 alterations in DNA.    

The scientists concluded that the presence of the TP53 mutation determined the expected prognosis. Patients with normal TP53 genes in their tumours had better outcomes, even without aggressive radiation treatment. This suggests these patients can be successfully treated with chemotherapy and surgery in the future, without suffering from the additional effects of radiation.

"This is good news for these very young patients and their families,” says Dr. Christine Williams, director of research at the Canadian Cancer Society. “Probably the most significant finding is that radiation is not necessary for some of these children, and so they will no longer have to endure what can be devastating side-effects.”

"A big challenge facing physicians and medical specialists is knowing which patients will respond favourably to treatments and which will not," says Dr. Uri Tabori, co-lead author of the study, Staff Oncologist and Scientist at SickKids and Assistant Professor in the Department of Paediatrics at the University of Toronto. "This is promising news.”

As a result of their findings, Malkin and his team are recommending a new approach to managing choroid plexus tumours, and strongly suggest that the TP53 status be determined in patients as well as in their family members. This information would then be used to select the most appropriate therapy for the patient. In the absence of TP53 testing, however, the study recommends that doctors examine the patient's family and clinical history to determine if Li-Fraumeni syndrome may be a factor.

"Ideally, we would want to screen all patients for their TP53 status, but this is not always practical or possible,” says Tabori. “By taking a careful family and clinical history, we can still make a reasonable prediction about the patient’s status, and the potential status of other family members, based on an unusually high occurrence of certain types of cancer.”

These findings are expected to have a significant impact on patients and their families who are dealing with choroid plexus tumours. The study is also relevant to members of the paediatric oncology community and to scientists who study TP53, as this research may hold important clues for treating other types of cancer.

Malkin and his team are continuing their research by validating their TP53 findings in a larger subset of patients, as well as identifying the other genes that may be disrupted in choroid plexus tumours. “We know that TP53  is not the only gene involved, so we are applying the latest microarray technology to identify other mutations that may also play a more complex role in these tumours,” says Adam Shlien, co-first author and a graduate student in Malkin's laboratory. “Understanding the genetic and biological determinants of choroid plexus tumours will have a direct implication for modifying therapy. We intend to see if these findings extend to other forms of cancer as well.”  

This research was funded by the Canadian Cancer Society, the Canadian Institutes of Health Research 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 Peter Gilgan Centre for Research and Learning 
The Peter Gilgan 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 Architects Inc. and HDR Inc. with a goal to achieve LEED® Gold Certification for sustainable design, the Gilgan Centre will create an architectural landmark as the eastern gateway to Toronto’s Discovery District. The Peter Gilgan 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.

About the Canadian Cancer Society
The Canadian Cancer Society fights cancer by doing everything we can to prevent cancer, save lives and support people living with cancer. Last year, we invested $48.5 million in research to outsmart cancer. Visit fightback.ca to find out how you can join the fight. When you want to know more about cancer, visit our website at cancer.ca or call our toll-free bilingual Cancer Information Service at 1-888-939-3333.

For more information, please contact:

Matet Nebres
The Hospital for Sick Children
416-813-6380
matet.nebres@sickkids.ca

Suzanne Gold
The Hospital for Sick Children
416-813-7654 ext. 2059
suzanne.gold@sickkids.ca

Alexa Giorgi
Canadian Cancer Society
416-934-5650
agiorgi@cancer.ca