‘Toronto protocol’ dramatically improves survival rates in children at risk of cancer

Study’s five-year follow-up shows surveillance approach to detecting tumours early yields remarkable results   

TORONTO – A cancer surveillance system is being touted as the next best thing to finding a cure to an inherited cancer disorder called Li-Fraumeni syndrome. Patients with Li-Fraumeni carry a substantially higher lifetime risk of developing cancers such as bone cancer, leukemia and breast cancer.

Research led by The Hospital for Sick Children (SickKids) shows that children and adults with this inherited cancer susceptibility can benefit significantly from a cancer surveillance protocol that helps detect tumours early, enables quicker treatment and improves overall survival. The study is published in the August 5 online edition of The Lancet Oncology.   

This study builds on work published five years ago which suggested that a cancer surveillance protocol, dubbed the ‘Toronto Protocol’, increased survival rates for patients with Li-Fraumeni syndrome. The new research, which included patients at SickKids, the Huntsman Cancer Institute at the University of Utah and Children’s Hospital Los Angeles, observed more patients over a longer period of time and yielded remarkable results: the five-year overall survival rate was 89 per cent for people who underwent surveillance compared to only 60 per cent for those who did not undergo surveillance.

“Patients have told me in the absence of a cure, this protocol gives them something to fight back with,” says Dr. David Malkin, Principal Investigator for the study, Director of the Cancer Genetics Program and Senior Staff Oncologist at SickKids. “Not only does this data support the use of genetic testing in at-risk individuals, it also raises the awareness of the importance and value of surveillance strategies for early tumour detection, not only in the context of patients with Li-Fraumeni syndrome, but also for those with other cancer-susceptibility syndromes.”

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 at least 93 per cent in female carriers. The principle behind the protocol is to detect tumours even before symptoms arise, allowing oncologists to treat the cancers before they grow larger and more aggressive, and in some cases prevent the need for intensive cancer therapy.

The Toronto Protocol involves a combination of tests which are available at virtually every hospital, including blood work, ultrasound of the abdomen and pelvis every three to four months, and annual MRIs of the whole body and brain. The protocol has been adopted internationally in centres across North and South America, Australia, Europe, Japan and the Middle East. Malkin hopes to see the protocol adopted into standard clinical practice even more broadly and says this research provides the evidence to support health policy changes.

“This research is valuable because it demonstrates that the effect we saw with our first analysis is sustainable, both in terms of compliance with the surveillance protocol and survival benefit,” says Dr. Anita Villani, lead author of the study and Senior Fellow in the Division of Haematology and Oncology at SickKids. “Early tumour detection is critically important, particularly for paediatric patients with Li-Fraumeni syndrome, who have the greatest potential life-years gained from improved cancer outcomes. Beyond this, our aim is to minimize their exposure to toxic therapies, not only because their baseline risk for getting additional cancers is high, but also because the burden of late effects related to aggressive therapy is significant.”

According to the researchers, the next step will be to determine how the surveillance protocol can benefit more patients with cancer. They are currently looking at other cancer predisposition syndromes to see how the protocol can be adopted.  

Study Findings

• The study followed 89 confirmed TP53 carriers; of these, 59 patients underwent surveillance and 30 did not;
• Initially 40 people agreed to surveillance and 49 did not. During the study, 19 patients crossed over from non-surveillance to surveillance groups;
• Forty tumours were detected in 19 of the 59 patients (32 per cent), before symptoms arose;
• Following false negatives, two additional cancers were diagnosed between surveillance assessments;
• Two identified and biopsied lesions were not actually tumours (false positives);
• Among the 49 patients who initially declined surveillance, 61 symptomatic tumours were diagnosed in 43 patients (88 per cent);
• The five-year overall survival rate was 89 per cent in surveillance group and 60 per cent in non-surveillance group.

Malkin is also Professor in the Departments of Paediatrics and Medical Biophysics, School of Graduate Studies at the University of Toronto.

The study was supported by the Canadian Institutes of Health Research, Canadian Cancer Society, Terry Fox Research Institute, Soccer for Hope Foundation and SickKids Foundation.

This paper is an example of how SickKids is contributing to making Ontario Healthier, Wealthier and Smarter.