Cancer treatments can result in damage to the heart both during treatment and years following completion of therapy. As many cancer survivors are now living longer into adulthood, we’re gaining a better understanding of some of the late effects of cancer treatments that we weren’t able to observe before. As a result, we’re continuing to adjust therapies where possible in order to mitigate, or limit, harmful exposure while still maintaining excellent cure rates.
Risk for cardiomyopathy reflects a combination of factors specific to each patient and to the type of cancer treatments they received. The most broadly applicable risk relates to treatment exposure. For example, the higher the total dose of anthracycline chemotherapy, the higher the risk for cardiomyopathy. We like to focus on three prevention and intervention strategies that patients, families and care teams can implement to minimize or eliminate the risk of heart disease.
The most common form of cardiac dysfunction in cancer survivors is called cardiomyopathy, a condition resulting from abnormally functioning heart muscles. Cardiomyopathy can potentially progress to heart failure, a condition that occurs when the heart cannot adequately pump blood throughout the body. When this happens, individuals may experience fatigue, shortness of breath and accumulation of fluid in the body.
The most common cancer treatments associated with cardiomyopathy are anthracycline chemotherapies, such as doxorubicin and daunorubicin, and radiation exposure to the heart. If childhood cancer survivors received treatments that potentially affected the heart, their oncologists likely periodically obtained echocardiograms, or ultrasounds of the heart during and shortly after treatment. Depending on specific exposures, a survivor may continue to undergo these screening studies through long-term follow-up.
Physicians take several steps to reduce risk during cancer treatment. The first is to monitor the rate of administration of potentially cardiotoxic chemotherapies. This is standardized, but important for patients and families to know that doctors and pharmacists take these standards into consideration when administering these drugs. There is also a growing use of the drug dexrazoxane, which has been approved to provide some protection against anthracycline-related heart damage in adult women with breast cancer. Although insufficient data are available for the U.S. Food and Drug Administration to approve its use for this purpose in children, many oncologists believe the potential benefits outweigh any perceived risk and may recommend it to their patients.
Primary prevention: Interventions implemented to mitigate causative risk factors. For example, reducing exposure to anthracyclines, either via dose reductions or by co-administration of dexrazoxane to reduce the adverse effects of the dose administered. The latter is important for diseases in which higher doses are necessary for cancer cure.
Secondary prevention: Interventions implemented after risk occurs and the disease is present, but before symptoms develop. This includes screening for asymptomatic disease. For example, we may identify subtly abnormal heart muscle function that is not causing symptoms but may improve with cardiac medications.
Tertiary prevention: Intervention for disease that is clinically evident. This, for example, involves treatment of cardiomyopathy to minimize symptoms and slow progression to severe heart failure.
By combining these strategies, we can ideally minimize risk, and in some cases eliminate it. When this is not possible, we maximize early disease detection and intervention to slow progression to potentially severe heart disease or heart failure. Early recognition of dysfunction may heighten awareness and convince patients to reduce other risk factors, such as physical inactivity, obesity or smoking.
With respect to radiation, radiation oncologists have continued to modify radiation fields in order to minimize exposure of heart tissue when nearby tissues are irradiated. In addition, new modalities, such as proton beam radiation, further enhance the doctor’s ability to minimize healthy tissue exposure when treating a specific cancer site in the body.
Most individuals will never experience abnormal cardiac function related to their cancer treatments. However, for those who do, it can significantly impact their health and well-being. Identifying it early before symptoms begin to develop allows us to intervene and potentially slow the progression to symptom onset or severe illness. Because of this, we are continuing to research ways to identify those at highest risk in the earliest stages of disease. For example, as we learn more about genetics, we are identifying genetic variants associated with higher probabilities for heart dysfunction, even at the same doses of anthracyclines. We currently screen individuals for cardiomyopathy based on broad categories of risk (for example, based on cumulative doses of specific treatment exposures). As genetic testing becomes more accessible and prediction models more refined, we will likely be able to use a more personalized approach to identifying an individual childhood cancer survivor’s risk and tailoring screening strategies to match this risk.
For survivors, we cannot change the treatment exposures necessary to cure their cancer. However, we can minimize or eliminate other risk factors, such as physical inactivity, obesity and uncontrolled high blood pressure, that can substantially add to this risk. This is why these factors are often emphasized during clinic visits with survivors. Ten or 20 years from now, I expect we will be able to predict a patient’s risk for heart failure or other late effects with much greater precision. By doing so, we hope to be able to better quantify the direct effect of interventions targeting specific risk factors in individual patients (for example, how weight loss may reduce an individual’s risk of heart failure). This level of information will help to prioritize which interventions are most impactful in each patient, hopefully leading to greater likelihood of reducing the overall risk.