Research Profile - Cutting the cost of surviving childhood cancer
Dr. Paul Nathan
Actor and singer Michael Cuccione beat cancer twice before succumbing, at the age of 16, to respiratory failure caused by scarring of his lungs from treatment for his Hodgkin's lymphoma.
The Vancouver teenager is just one of the many childhood cancer patients who survive their disease, only to die as a result of the secondary effects of their treatment.
Depending on the cancer treatments they receive, the side effects can come in the form of damage to their heart, lungs or kidneys, hearing loss, susceptibility to blood clots, cognitive impairment, fertility or hormonal problems, or Graft-versus-host-disease, a chronic multi-system failure that can follow bone marrow transplants.
At a Glance
Who: Dr. Kirk Schultz, Director, Childhood Cancer and Blood Research, BC Children’s Hospital and the Child and Family Research Institute; Professor of Paediatrics, University of British Columbia.
Dr. Paul Nathan, Haematologist/Oncologist, Hospital for Sick Children; Associate Scientist, Hospital for Sick Children Research Institute; Assistant Professor of Paediatrics and Health Policy, Management & Evaluation, University of Toronto.
Issue: Although about 80% of children who contract cancer now survive their disease, many of them develop complications from treatment. Childhood cancer survivors are about 10 times more likely to die of heart disease, for example, than people the same age who have never had cancer.
Approach: In Vancouver, Dr. Schultz and his team are using biomarkers linked to complications such as hearing loss to test their ability to predict who is at highest risk of developing these problems. In Toronto, Dr. Nathan and another team are focusing on biomarkers to predict which patients are at greatest risk of cardiac complications.
Impact: Using biomarkers to identify the patients at greatest risk of particular complications will enable doctors to reduce risk by altering treatment plans, or to prevent complications or treat them earlier.
Now CIHR-funded researchers are seeking ways to identify what children are at greatest risk of these complications. They hope to use biomarkers – biological indicators, such as genes or proteins, that can be measured to detect or monitor changes in a person's health – to help prevent these complications, or diagnose and treat them earlier.
"We'd rather be dealing with a child who is alive at the age of 25 with the complications, than a child who's not," says Dr. Kirk Schultz, the director of Childhood Cancer and Blood Research at BC Children's Hospital in Vancouver. "But the ideal is to have a child who's alive at the age of 25 who doesn't have those complications."
Dr. Schultz and his colleagues have focused on biomarkers that have already been identified, such as ones that indicate hearing loss, or Graft-versus-host-disease. They will then use the biomarkers to identify children who would receive preventive, or prophylactic, treatments. For example, if they can predict which children are at highest risk of getting Graft-versus-host-disease, they plan to treat them with a drug called rituximab to prevent the disease from developing. Another medication may decrease the risk of hearing loss associated with a particular chemotherapy drug, if it is given to high-risk patients, says Dr. Schulz.
"The idea is that if we can get a group that has an 80% chance of getting it, and by doing some kind of prophylactic approach we can decrease that chance to 40%, it's a step in the right direction," he adds.
In Toronto, Dr. Paul Nathan, a pediatric oncologist, is working with cardiologists and other researchers to look for biomarkers that will point to heart disease in people who have been treated for childhood cancer. Childhood cancer survivors are about 10 times more likely to die of heart disease than people who were never treated for cancer, he says. The complications occur because anthracycline drugs used to treat some cancers destroy heart muscle, which is replaced by scar tissue as the children grow. Radiation therapy can also increase the risk of heart failure.
Currently, cardiologists use echocardiograms – an ultrasound of the heart – to detect damage in childhood cancer survivors. Over time, they find abnormalities in as many as half the patients who have been exposed to these drugs, says Dr. Nathan. But not all of those patients go on to have congestive heart failure or other clinical heart problems, and so far, the doctors have no accurate way of knowing which of the patients are at highest risk.
The problem is compounded because these complications may not show up for 20 to 40 years after the initial cancer treatment. But if doctors wait until patients have developed clinical symptoms of cardiac disease, standard heart failure medications are often ineffective, Dr. Nathan says. Developing more sensitive tests that rely on chemical biomarkers or imaging biomarkers to diagnose the problem earlier could save lives.
"If we could learn to predict who is at particular risk, we could then target interventions, such as changing lifestyle or putting them on specific drugs," says Dr. Nathan.
Currently, parents whose children are diagnosed with cancer face difficult choices.
"These chemotherapy agents are toxins – they are poisons, essentially," Dr. Nathan says. "The families need to know that although we think whatever combination you are using gives your child the best chance of surviving, ultimately, it also affects normal tissues."
The doctors let families know that the most immediate issue is beating the disease. But the children who are lucky enough to be cured may face a lifetime of repercussions.
The great promise of biomarkers is their ability to help doctors and families make less agonizing decisions, because the new tests will find ways to improve long-term outcomes. Just as survival rates of most types of childhood cancer have soared, so too, these experts hope, will survival from secondary complications.
"Hopefully, we'll put ourselves out of business," says Dr. Schultz.
"If we could learn to predict who is at particular risk, we could then target interventions, such as changing lifestyle or putting them on specific drugs."
- Dr. Paul Nathan, University of Toronto.