Late Cardiac Effects of Cancer Treatment

A Conversation With Daniel J. Lenihan, MD


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There is so much that can be done to avoid the late and long-term effects of cancer treatment such as complex cardiovascular disease. Oncologists, cardiologists, and primary care physicians all have to work together to improve the long-term health of cancer survivors and ensure a higher-quality life after cancer.
— Daniel J. Lenihan, MD

The combination of more precise diagnostic tools and advances in surgery, chemotherapy, radiation therapy, and targeted therapy in the treatment of cancer has led to unprecedented numbers of cancer survivors in the United States—more than 15.5 million, according to the latest figures from the American Cancer Society.1 However, many of those survivors may have a shortened life span due to the late effects of cardiovascular disease from their cancer and its treatment. According to a recent study in the Journal of Clinical Oncology,2 survivors of certain cancers, including multiple myeloma, non-Hodgkin lymphoma, breast, kidney, lung/bronchus, or ovarian cancers, may have as much as a 70% higher risk of developing cardiovascular disease as a result of their treatment compared with someone who has not been diagnosed with cancer. 

At the 2016 Cancer Survivorship Symposium: Advancing Care and Research, Daniel J. Lenihan, MD, Professor in the Division of Cardiovascular Medicine and Director of Clinical Research at Vanderbilt University Medical Center in Nashville, spoke about the late cardiac effects of cancer treatment and the profound impact they can have on cancer survivors. Although cancer therapies—especially anthracycline agents such as doxorubicin, epirubicin, or mitoxantrone; HER2-receptor antagonists like trastuzumab (Herceptin); and radiation therapy—can potentially affect many aspects of the cardiovascular system, the most common conditions can be grouped into three main categories, according to Dr. Lenihan. They include vascular conditions such as atherosclerosis, thrombosis, and hypertension; cardiac structural problems, especially heart valve degeneration; and cardiac dysfunction and heart failure. 

Because of these potential late effects from cancer treatment, anticancer therapies should be considered a specific cardiovascular risk factor. More research is needed, said Dr. Lenihan, in the early detection, monitoring, and prevention of cardiovascular toxicity resulting from cancer therapies to improve the long-term outcomes of cancer survivors.

The ASCO Post talked with Dr. ­Lenihan about the cardiovascular risks many survivors face after a cancer diagnosis—in adult patients, the incidence can be as high as 50%3 depending on the type of cardiac condition—and how oncologists, cardiologists, and primary care physicians can collaborate to monitor their long-term care.

Cancer and the Heart

Please explain how cancer and its treatment affect the heart.

The type of cardiac toxicities a survivor may experience depends on the treatment, specifically chemotherapy or radiation. Of course, patients who have both are at the highest risk of cardiovascular disease. 

The cardiac risk from radiation is the most profound. Any vascular location that is in the field of radiation is at high risk for early and complex atherosclerosis, and radiation to the mediastinum is a major risk factor for the development of coronary artery disease. If a patient has comorbidities such as high cholesterol or high blood pressure, the risk for late cardiac effects becomes even greater. There are techniques for reducing this risk—for example, by having patients hold their breath for 10 seconds while they are being irradiated, which pulls the heart out of the field of radiation.

The clinical approach for patients with cancer should include a comprehensive assessment of their cardiovascular risk at baseline, before treatment begins, so cardiac risk can be mitigated or reduced. Currently, it is understandable that this assessment usually doesn’t happen, since the focus is on curing the cancer. 

All medical disciplines, including oncology, cardiology, and primary care, should be included in the care of patients with cancer, but in real-world practice, it typically doesn’t happen that way.

Anthracyclines and Androgen Deprivation

What is the cardiac risk from anthracycline chemotherapies and androgen-deprivation therapy in the treatment of prostate cancer?

In prostate cancer, androgen-deprivation therapy clearly changes patients’ metabolic profile, which over time increases their cardiovascular risk but not as dramatically as, say, someone receiving six cycles of an anthracycline agent. In that example, even if a patient has no evidence of heart disease when treatment is completed, a serious stressful event 5 years later, for example, can result in profound heart failure that can be traced back to the anticancer therapy.

Risk Reduction

What can be done to reduce the risk of heart disease in cancer survivors?

The best plan is prevention. It is really important to identify modifiable risk factors at the beginning of treatment, such as hypertension, smoking cessation, or weight loss, but frequently this is overlooked due to the seriousness of the cancer diagnosis. If an oncologist has a 45-year-old patient with breast cancer, unless she has had a history of high blood pressure or some other cardiovascular risk factor, chances are she will get all the appropriate tests for her cancer, but treatment will be started without a good baseline assessment of heart disease risk.

Who should do that baseline assessment: the oncologist, cardiologist, or primary care physician? It is hard to say, but it needs to be done.

Also, preventive measures can be employed to decrease cardiotoxicity risk, including altering the administration of chemotherapy to separate the timing of potentially toxic therapies. For example, you could separate anthracycline dosing and trastuzumab therapy by 90 days or more or allow a careful titration of cardioprotective medications such as angiotensin-converting enzyme inhibitors or angiotensin-receptor blockers in advance of a patient receiving combination chemotherapy.

Role of the Cardiologist

Ideally, is it best for the oncologist to refer the patient to a cardiologist for a baseline assessment of heart disease risk? 

Yes, especially if the treatment planned will include the therapies we’ve discussed: radiation therapy, anthracycline agents, or HER2-receptor antagonists. If a patient is getting fairly innocuous treatment and is young and otherwise healthy, it is probably not necessary for the patient to see a cardiologist for a baseline assessment; he or she could instead see a primary care physician. However, if multiple drugs with known cardiovascular effects have been prescribed over a long period of time, the patient should be seen by a cardiologist before treatment begins and then be periodically monitored by the cardiologist for signs of heart disease.

Essentially, are you talking about the oncologist and cardiologist co-managing patients’ care?

Yes, in most circumstances that is best because it leads to the best outcomes. For example, patients with multiple myeloma are usually older and at greater risk of experiencing cardiovascular events, such as thrombosis, atrial fibrillation, or bradycardia, either from the cancer or the drugs used to treat the disease. An effective strategy for treating these patients has to include a comprehensive way to prevent cardiovascular events from happening, which requires careful coordination between oncologists and cardiologists.

Survivorship Care Plans

Would providing every cancer survivor with a survivorship care plan help avoid some of the late cardiotoxicity effects associated with cancer treatment? 

Yes, absolutely, because it would provide patients with an ongoing schedule for how often their health should be monitored for cancer recurrence and alert them to potential late effects of their treatment. Survivorship care plans also give medical providers a detailed record of the patient’s past cancer treatment, so physicians can more accurately assess possible future health risks and help prevent them. 

But I have to admit, no cancer survivor I’ve ever treated has ever presented me with his or her survivorship care plan. Sadly, the patient’s medical record often does not even include a complete treatment history.

Providing every cancer survivor with a survivorship care plan is essential now because many cancers are becoming chronic diseases, not a death sentence, and survivors are living many years after their cancer diagnosis. There is so much that can be done to avoid the late and long-term effects of cancer treatment such as complex cardiovascular disease. Oncologists, cardiologists, and primary care physicians all have to work together to improve the long-term health of cancer survivors and ensure a higher-quality life after cancer. ■

Disclosure: Dr. Lenihan is a consultant for BMS, Roche, and Amgen and also receives research funds from Takeda, Inc.

References

1. American Cancer Society: Cancer Treatment & Survivorship Facts & Figures, 2016-2017. Available at www.cancer.org/acs/groups/content/@research/documents/document/acspc-048074.pdf. Accessed August 4, 2016.

2. Armenian SH, Xu L, Ky B, et al: Cardiovascular disease among survivors of adult-onset cancer: A community-based retrospective cohort study. J Clin Oncol 34:1122-1130, 2016.

3. Yeh ET, Bickford CL: Cardiovascular complications of cancer therapy: Incidence, pathogenesis, diagnosis, and management. J Am Coll Cardiol 53:2231-2247, 2009.



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