Many Childhood Cancer Survivors Have Silent Cardiac Conditions

Adult survivors of childhood cancer are inevitably at higher risk of developing many chronic conditions compared with the general population, but a new study has found that heart problems, including coronary artery disease, are not uncommon among those previously treated with cardiotoxic therapies, although they are often asymptomatic and overlooked.

Take Home: Many Childhood Cancer Survivors Have Silent Cardiac Conditions

Now in their thirties and forties, “these are people who, if they came into a primary care setting, wouldn’t typically be screened for coronary artery disease or valve disease,” study author Daniel A. Mulrooney, MD, MS, of St. Jude Children’s Research Hospital (Memphis, TN), told TCTMD.

His team conducted a series of follow-up screenings and tests on 1,853 survivors—diagnosed with cancer at a median age of 8 years—who had received cardiotoxic therapies at their institution at least 10 years prior. The median age of study participants was 31 years, 52.3% were men, and almost two-thirds had been treated at least 20 years earlier.

Cardiotoxic exposures included anthracycline in 82% of patients (20.8% received cumulative doses of at least 250 mg/m2) and cardiac radiation in less than half (22.2% had a dose of more than 1,500 cGy).

The conditions identified in the cohort were cardiomyopathy (7.4%), CAD (3.8%), conduction/rhythm disorder (4.4%), and functional valve findings (28.0%), with 4.7%, 2.2%, 1.4%, and 24.8%, respectively, newly identified. Most cases of valve regurgitation and stenosis were mild and located in the tricuspid or pulmonary valves, though a few cases of mitral and aortic valve issues were noted.

Cardiac complications seemed to increase with age, ranging from 3% to 24% among survivors in their thirties and from 10% to 37% among those in their forties and older.

Exposure to anthracycline (OR 2.7; 95% CI 1.1-6.9) and cardiac radiation (OR 1.9; 95% CI 1.1-3.7) were independent predictors of cardiomyopathy on multivariable analysis. Also, exposures of 250 mg/m2 and 1,500 cGy or higher, respectively, seemed to result in overall more frequent complications.

Best Level of Screening a ‘Matter of Controversy’

All of the previous studies of this nature have been based on mostly self-reported data, Mulrooney said. “This is the first time we’ve ever had the opportunity to clinically evaluate a group of survivors and do an extensive study like this,” he observed. “We were surprised to find that many of these survivors really were asymptomatic and had subclinical disease which puts them not only at high risk already but [also at] high risk for progression in later cardiac disease.”

In an interview with TCTMD, cancer outcomes researcher David C. Hodgson, MD, MPH, of Princess Margaret Cancer Centre (Toronto, Canada), said because so many patients lacked symptoms, a key question for the future will be to “figure out which of these patients is actually at serious risk to progress to having serious heart disease and in which of these is this just an asymptomatic incidental finding that’s not necessarily going to be a big problem.”

Contemporary Hodgkin lymphoma trials treat children with less than 250 mg/m2 of anthracycline and a mean cardiac radiation dose of about 1,000 cGy, Hodgson reported. This is “good news,” he commented, as “we can expect much lower risks of [future] heart disease … because the doses of radiation and anthracycline used are much lower than they have been in the past.”

But for the current generation of survivors, the challenge is to determine who exactly needs special screening and how often. The extent to which patients with minimal exposures need routine echocardiograms or lipid profiles is “a matter of controversy,” according to Hodgson. “My own personal view is that [many] don’t need a lot of sophisticated screening, whereas [people] who were getting high doses of chemotherapy and radiation who start to accumulate other risk factors need to be followed with echocardiography or maybe even… cardiac MRI.”

Lifestyle factors are becoming even more important, he added, because “elevated cholesterol, poor control of blood sugar, and obesity [are] starting to increase in the general population of young adults, so it’s going to be a real focus of attention in managing these issues in the survivors who already start out in life with a couple of knocks against them.”

Encouraging Follow-Up by Communicating

Another issue, Mulrooney said, is that though most children are monitored during and immediately after their cancer therapy, “what often happens, especially for childhood cancer survivors, is they age out of pediatric care…. They often leave the institution. They are cured of their disease, and don’t necessarily have the opportunity or feel the need for clinical follow-up.”

Hodgson also commented on the importance of communication between primary care providers and oncologists. Many larger hospitals, he explained, have developed relationships with cardiologists who appreciate the added risk in the survivor population, but “one of the biggest challenges going forward will be to understand how exactly to manage these treatment related complications” and whether or not the treatments that are offered to the general population for, say, cardiomyopathy are as effective in cancer survivors.

“That’s a complete unknown,” Hodgson continued. “We don’t really know much about if you have coronary artery disease caused by radiotherapy [and] you have a stent placed, [if it is] as effective as it is in an elderly person who has CAD.”

Mulrooney said his team plans to continue following this cohort of survivors and invite them back periodically for further screening. “We need to learn more about CAD. We need to do further work on the valvular disease, especially since it was so high in this study,” he said. “Nobody has ever had this many EKGs on cancer survivors, so we’ve analyzed those data and have them under review for publication.”

Mulrooney DA, Armstrong GT, Huang S, et al. Cardiac outcomes in adult survivors of childhood cancer exposed to cardiotoxic therapy: a cross-sectional study. Ann Intern Med. 2016;Epub ahead of print.

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  • The study was funded by the American Lebanese Syrian Associated Charities and the National Cancer Institute.
  • Mulrooney and Hodgson report no relevant conflicts of interest.