Approximately 14,000 new cases of cancer in childhood and adolescence are found each year in the US, and 84% will be alive 5 years later. It is estimated that over 500,000 childhood cancer survivors live to adulthood. The cure of cancer sometimes comes at a cost with late psychosocial effects on social interaction, education, careers, chronic fatigue, depression, and PTSD, as well as physical effects such as growth, fertility, cognitive and cardio-pulmonary changes.
In the St. Jude Lifetime Cohort Study of 1,713 adult survivors, it was found that by the age of 45, 95% of survivors will have more than one chronic condition, with over 80% being a serious disabling or life-threatening chronic condition. In addition, survivors have increased mortality from second cancer, pulmonary fibrosis, and cardiovascular disease.
Over half of childhood cancer survivors (CCS) are estimated to have received treatment with known cardiotoxic agents such as anthracycline chemotherapy or chest radiation, and they are at increased risk of adverse cardiac outcomes, with cardiomyopathy being the most prevalent. CCS have an 11% cumulative incidence of heart failure over the 40 years following treatment and are at seven times higher risk of cardiovascular mortality compared to age- and sex-adjusted controls. Young adults cancer survivors (age 15-39) in particular are at a 1.4 fold increase in cardiovascular death compared to the general population. Vulnerable groups like survivors of Hodgkin’s lymphoma and brain cancer require careful follow-up care of cardiovascular conditions.
What Are the Cardiovascular Complications Seen in Childhood Cancer Survivors?
Coronary artery disease is the second most common manifestation and depends on the radiation dose and the age at which it was administered. The St. Jude lifetime cohort detected coronary artery disease in 3.8% of survivors. However, the incidence of symptomatic coronary artery disease at 50 years old was found in 20% of males exposed to >35 Gy of radiation. A CT study in patients with Hodgkin lymphoma who received chest radiation found the coronary lesions to be more proximal and tended to place more heart muscle at risk.
Finally, chest radiation can sometimes affect the pericardium and present as constrictive pericarditis or affect the aortic or mitral valves and present as stenosis or narrowing of the valves.
How Can We Predict Cardiac Complications in Childhood Cancer Survivors?
Different risk prediction models have been studied for heart failure as well as ischemic heart disease in cancer survivors. In general, female sex, younger age at cancer diagnosis, anthracycline dose, and chest radiation have been related to heart failure risk. For cardiovascular mortality: male sex, non-white, age at cancer diagnosis, lymphoma treatment, and any radiation.
There is a large inter-individual variation in the susceptibility to adriamycin toxicity and genetic predisposition is being studied.
In patients at higher risk for complications, the administration of chemotherapy and radiation treatment has been modified to mitigate these risks without compromising its effect on the eradication of cancer. The use of dexrazoxane and liposomal anthracycline as well as prolonging the infusion duration of anthracycline can reduce cardiac toxicity, but there are very few studies in children.
The most important risk factors driving cardiovascular morbidity and mortality in cancer survivors are very similar to the general population. Hypertension was the most prevalent risk and present in 40% of survivors >50 years of age vs 26% of their siblings. It was the only risk factor associated with a reduced heart function in the St. Jude cohort. Metabolic syndrome was present in 32% of survivors in the St. Jude cohort study and 9% of French survivors of childhood leukemia.
Children’s Oncology Group (COG) guidelines are a great resource for providers on when and what to screen based on the age of treatment, chemotype, and radiation.
Also, the Childhood Cancer Survivorship Study cardiovascular risk calculator can be found at https://ccss.stjude.org/tools-documents/calculators-other-tools/ccss-cardiovascular-risk-calculator.html.
How Can We Prevent Heart Disease in Childhood Cancer Survivors?
Management of cardiovascular risk factors is essential in all childhood cancer survivors, particularly in those at increased risk of cardiac disease. A healthy lifestyle that includes abstinence from smoking, five days per week of physical activity, a healthy diet that excludes processed food, and less than moderate alcohol consumption may benefit cardiovascular health.
Several studies have shown that aerobic exercise was positively related to cardiopulmonary fitness in childhood cancer survivors.
Survivors identified at a higher risk of cardiovascular disease may benefit from more aggressive surveillance with an echocardiogram that includes 3D echo and global longitudinal strain, CT calcium score, and even cardiac MRI. This, combined with early intervention on risk factors, may reduce cardiovascular morbidity and mortality in childhood cancer survivors.