TORONTO – Luana Locke was eight months pregnant with her first child when she was diagnosed with breast cancer. Soon after, Locke learned that she had Li-Fraumeni syndrome, a cancer predisposition syndrome that put her at high risk of developing the disease. Having lost several family members to cancer, Locke later had her two children tested and found out they had also inherited the abnormal gene that causes Li-Fraumeni syndrome.
New research led by The Hospital for Sick Children (SickKids) indicates that children and adults with inherited cancer susceptibility, like the Locke family, can benefit from a new cancer surveillance protocol that helps detect tumours early and improves overall survival. The study is published in the May 20 advance online edition of The Lancet Oncology.
The study supports the use of genetic testing in at-risk individuals. It shows that close monitoring of patients who test positive for a genetic mutation can lead to early tumour detection. This detection can occur even before symptoms arise, allowing oncologists to remove tumours when they are very small and in some cases eliminate the need for aggressive cancer therapy.
Researchers focused on families with Li-Fraumeni syndrome and found that survival was 100 per cent in the surveillance group and only 21 per cent for those who did not undergo surveillance.
“This surveillance protocol was implemented for families with Li-Fraumeni syndrome because of their high lifetime risk of developing cancer,” says Dr. David Malkin, Principal Investigator for the study, Director of the Cancer Genetics Program and Senior Staff Oncologist at SickKids. “However, the concept of a comprehensive surveillance protocol may be applicable to some of the more common cancer susceptibility disorders.”
People with Li-Fraumeni syndrome typically have a mutation of the TP53 tumour suppressor gene that predisposes them to cancer. Their lifetime risk of developing cancer is estimated at 73 per cent in male carriers and 93 per cent in female carriers.
“This important study illustrates the power of genetics to identify children and young adults at high risk of developing cancer so that they can be carefully monitored,” says Dr. Christine Williams, Director of Research, Canadian Cancer Society Research Institute, which co-funded the study. “Then, if they do develop cancer, it will be detected early and their chance of surviving and thriving is much better.”
The study followed 33 confirmed TP53 carriers; 18 underwent surveillance and 16 did not (one patient started surveillance after tumour diagnosis and is therefore included in both groups). The clinical surveillance protocol identified 10 tumours in seven patients from the surveillance group. These tumours were detected and removed prior to symptoms and all seven patients survived after an average of 47 months of follow-up. The group that did not undergo surveillance had a different outcome. Twelve tumours presented symptomatically in 10 of the patients. By the end of the 24-month follow-up, only two had survived.
“Previously, genetic testing in children has been controversial and considered unjustified,” says Malkin, who is also Senior Scientist at SickKids. “The argument was ‘what’s the benefit in knowing that your child is at risk of cancer if there’s nothing you can do to prevent it?’ From other cancer scenarios, we know that early detection may translate into improved survival outcomes and in the cases of at-risk patients, genetic screening and frequent monitoring may enable early detection and thus survival.”
The number of tumours per group was similar and the number of patients who developed tumours was similar, but the survival benefit shown in patients who underwent surveillance demonstrates the impact of the protocol, now being dubbed the ‘Toronto protocol’.
The buzz has been spreading around the world and institutions in the United States (such as Los Angeles, Philadelphia, Utah and Vermont), Brazil, England, Israel and France are establishing similar surveillance programs adapted from the ‘Toronto protocol’.
It’s important to understand that the tests involved in the protocol are available at virtually every hospital, explains Malkin. Patients return every three to four months for a combination of tests, including blood work, ultrasound of the abdomen and pelvis and MRIs of the whole body and brain.
“This study validates our decision to have our children tested,” says Locke. “This approach gives people who have a predisposition to cancer a tool to be able to do something proactive for themselves. It gives us hope.”
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 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.
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The Hospital for Sick Children
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