Staying healthy long after pediatric cancer treatment ends

Begin with the end in mind. It might seem counterintuitive to look well past the finish line when you have only just begun a treatment journey. However, for those treating children with cancer, it is imperative. Unlike adults diagnosed with cancer, children are still rapidly growing in both body and mind.

If treatments succeed, they will likely have decades of survivorship ahead. Protecting that future requires focus from the start: To minimize treatment exposures, encourage healthy lifestyle habits and monitor for negative health effects so physicians can intervene before problems arise.

A study published in The Lancet, authored by a team of St. Jude researchers, showed adult survivors of childhood cancer experience four times the risk of late mortality as the general population, even 40 years after diagnosis. However, researchers are also learning how to safeguard survivors’ health and improve their quality of life.

Tens of thousands of survivors of pediatric cancer have contributed health data to the Childhood Cancer Survivor Study (CCSS) and the St. Jude LIFE cohort. Their participation

over decades helps researchers characterize their needs and identify strategies to reduce the late effects of childhood cancer treatment.

Controlling chronic conditions

Researchers led by Nickhill Bhakta, MD, MPH, Department of Global Pediatric Medicine, analyzed data from over 3,000 patients from St. Jude LIFE to assess the cumulative burden of chronic disease. They found that, like the general population, almost all patients developed at least one chronic condition by age 50. However, the cumulative burden of disease, which reflects both the number and severity of conditions, was nearly two times higher in survivors than in the control group.

“If they have twice as many chronic conditions, that probably means more doctors’ appointments, more medications and more all-around health care–related costs,” said Matt Ehrhardt, MD, MS, Department of Oncology. “That gives us a clearer picture of what challenges survivors face beyond just suggesting that they experience an earlier onset of health conditions, which we have known to be true for quite some time now.”

Ehrhardt said the higher burden of chronic disease ties with early onset of aging-related disease among survivors, including breast and colorectal cancer, heart failure and stroke. That means survivors should start screenings and other preventative measures decades earlier than the general population. “If you’re a 30-year-old survivor and your doctor approaches your care as if you’re 50, they’re probably offering a more appropriate level of screenings,” said Ehrhardt.

Other recent findings from the cohort studies may help identify serious late effects sooner. For example, researchers used five-year survivors from the CCSS to develop a prediction model to identify survivors at risk of kidney failure, a rare but serious late effect.

Another study, published in the Journal of Clinical Oncology last year, found that the addition of two common cardiac biomarkers, global longitudinal strain (GLS) and N-terminal-pro-B-type natriuretic peptide (NT-proBNP), helped to identify survivors who are at elevated risk for cardiomyopathy despite a normal ejection fraction, which is the measure typically used to screen for this condition. This information may help physicians tailor the frequency of screenings for an individual patient rather than based on broad categories of treatment-related exposures, as is the current practice.

Research relating to risk prediction and screening needs has also helped inform treatment guidelines with an aim to reduce late effects. For example, current survivorship guidelines, such as those from the Children’s Oncology Group, state that the risk of cardiac dysfunction is lower with daunorubicin, an anthracycline agent, and higher with mitoxantrone compared with

doxorubicin. The guidelines also recommend further research into the use of dexrazoxane to protect against the risk of heart failure and other cardiovascular dysfunction.

Endocrine and metabolic effects

Adult growth hormone deficiency (aGHD) is a common late effect in survivors of suprasellar tumors and patients exposed to radiation in the hypothalamic-pituitary (HP) region. In childhood, the condition inhibits growth. In adults, it leads to symptoms such as decreased muscle mass, increased body fat and lower bone density.

These symptoms are treatable with growth hormone therapy, but uptake remains low. According to a study led by Tomoko Yoshida, MD, PhD, in the Department of Epidemiology & Cancer Control, only about 9% of survivors diagnosed with aGHD used growth hormone therapy, likely due to limited access, insurance coverage and education.

“There are medical indications for growth hormone replacement in both children and adults, but it may become harder for adults to obtain coverage, and the benefits may be less easily perceived after survivors have achieved their adult height,” said Stephanie Dixon, MD, MPH, a physician-scientist in the Department of Oncology and Department of Epidemiology & Cancer Control. Not surprisingly, the study found lower income and lack of health insurance were associated with lower growth hormone therapy use compared to higher income, insured survivors.

A recent study showed that a common solution in the general population, bariatric surgery, also seems to benefit pediatric cancer survivors with obesity. Future research is needed to determine whether treatments such as GLP-1 inhibitors may also be safe for survivors. For now, physicians weigh the benefits and risks when providing advice, Dixon said.

“For almost all of our patients, with the exception of those who are predisposed to a certain type of thyroid cancer, I say, ‘We have no evidence that this is higher risk for you than it is for the general population, and we have pretty strong evidence that obesity and cardiometabolic disease are detrimental to your health. I can’t tell you the exact risk as a cancer survivor, but I think the benefits are probably still there.’”

Beyond these interventions, a plant-rich diet and regular exercise are known to reduce chronic disease risk for almost everyone. For survivors of pediatric cancer, healthy lifestyle habits are essential medicine, even in young adulthood. A study published in The Lancet found survivors who maintained healthy lifestyles had a 20% lower mortality risk than those who did not.

Screening for chronic diseases earlier than in the general population, and addressing new conditions promptly, helps physicians, patients and their families balance longevity with quality of life. “There are cancers where we’ve reached a nice balance of the amount of treatment required for cure without causing additional long-term toxicity compared to their peers,” said Ehrhardt. “We’re not there for everybody, though. The goal for us is to get everyone to the point where they can expect their health to be similar to their peers despite having had childhood cancer.”