Research Targets Long-Term Health of Childhood Cancer Survivors

New research from the University of Alberta offers the hope of better long-term outcomes for survivors of childhood cancer — and the path to those better outcomes is exercise.

Two undergraduate honors students in the Faculty of Nursing, Kaitlyn Weinkauf and Emma Fyfe, wanted to find out why childhood cancer survivors are more prone to developing cardiovascular problems later in life, and what could be done to mitigate the harmful effects of cancer treatments, such as anthracycline chemotherapy, that are behind the higher risk. They carried out their research under the mentorship of Stephen Foulkes, a postdoctoral fellow in the Faculty of Nursing, and Mark Haykowsky, professor of nursing and Research Chair in Aging and Quality of Life.

A diagnosis of pediatric cancer used to be a death sentence for the vast majority of young patients. Foulkes says the survivorship from cancer at five years is now about 85 per cent, but there is a tradeoff. 

Cancer treatment leads to cardiovascular risk

"Chemotherapy and radiation can both target the cancer cells but also cause incidental damage and aging of other body systems," he explains. "One of the body systems that can be affected by cancer treatment is the cardiovascular system." That can lead to premature heart failure.

"So when studies now follow earlier and more recent generations of cancer survivors who have been exposed to these cancer therapies, we find that their risk of conditions such as coronary artery disease — particularly heart failure — is much higher than that of their siblings or other kids of their generation," Foulkes says. "It might be a five- to eight-fold higher risk of heart failure, even by the time they reach 40 years old, whereas the typical heart failure patient isn't affected until they're 60 to 80 years old."

With all this mind, Weinkauf and Fyfe did a systematic review of studies comparing cardiorespiratory fitness in childhood cancer survivors with their cancer-free peers. They used 18 studies that looked at 796 cancer survivors with 1,379 healthy peers of the same sex and age. "There's tons of primary research," Fyfe says, "which makes it great for us to synthesize and make the impact more digestible, and put a number to it."

To be included in the analysis, studies had to measure peak oxygen uptake — the maximum amount of oxygen a person can use during exercise. It is the gold-standard measure of cardiorespiratory fitness and one of the strongest predictors for the risk of developing or dying from cardiovascular conditions like heart failure, Foulkes notes.

They found that the average cardiorespiratory fitness level among the childhood cancer survivors was significantly lower than that of their peers — the equivalent of about 15 years of accelerated cardiovascular aging.

The students concluded that peak oxygen uptake in childhood cancer survivors is markedly lower, which may explain their increased risk of heart failure and cardiovascular mortality. Weinkauf and Fyfe suggest including the measurement of peak oxygen uptake among childhood cancer survivors may make it easier to identify who is at risk of future cardiovascular problems and get them into a rehabilitation program. 

A prescription to close the fitness gap

Regular exercise is one of the best ways to improve fitness, and Foulkes suggests that the study findings highlight a critical need for exercise rehabilitation programs for cancer survivors to close the fitness gap between them and their peers. 

Rehabilitation programs might include cardio-style exercise like cycling, rowing, walking and jogging, but also making sure people lift weights two or three times per week at a moderate to challenging level. The students note that further research into the types and efficacy of interventions is necessary.

Foulkes presented the findings at the end of April at the European Society of Cardiology Preventive Cardiology Congress in Athens. He says the reception was enthusiastic. 

"There was a lot of interest specifically in the findings from this study because, as Emma put it nicely, this study was a good way of synthesizing a large body of research into a clear and simple message." 

The message came as a surprise to the audience, he adds. "A lot of the cardiologists in the audience who work with these patients were quite shocked to realize how big the difference was in fitness scores. Both groups otherwise look reasonably healthy based on their resting heart function and blood pressure results."

But as Foulkes points out, a strength of a metric such as cardiorespiratory fitness is that it measures how well the cardiovascular system works under stress, so it may help unmask subtle problems that aren't apparent when heart function or blood pressure are measured at rest.

Weinkauf and Fyfe's conference abstract presenting their preliminary findings was published in the European Journal of Preventive Cardiology, and the full paper has been submitted to JAMA Pediatrics.

"It's been really cool to have the opportunity from the Faculty of Nursing and through the honors program to bridge the gap between clinical work and research, and see how those two connect. There's so much to nursing and so much to health sciences, but seeing the research aspect has been such a privilege." 

She adds, "Kaitlin and I are so grateful for our supervisors (Foulkes and Haykowsky) and also the Faculty of Nursing for allowing us to have the opportunity to get our feet wet — doing research and connecting the dots between all the cardiac patients we see in the hospital and knowing that there is something we can do about it. But the research has to be done to create these exercise rehabilitation programs to see a difference in the clinical setting."

Foulkes says the U of A is doing a great job of promoting students' success and creating leaders in the process.

"It's refreshing to come to a university where student research is encouraged right from the undergraduate level. And it's great to have these mentoring opportunities to help students who might not necessarily be on the pure research track to still gain these skill sets that will help them in their clinical practice."

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