Cardio-Oncology Programs Strive to Balance Cancer Care With Heart Health
For many diseases, therapeutic advances have improved patient survival, but with prolonged life comes an increased likelihood of experiencing long-term adverse effects of treatment. For cancer survivors, it may be years after completing chemotherapy or radiation before problems are detected, with the most worrisome being secondary cancers and cardiovascular damage. In light of the increased potential that a cancer survivor of today will become the heart disease patient of tomorrow, many hospitals and research groups are dedicating multidisciplinary programs and subspecialties focused on cardio-oncology, with the goal of balancing the benefits of cancer treatments against the risks of adverse cardiovascular effects.
“The concept of cancer drug cardiotoxicity is not new actually, but cardio-oncology has emerged as a new field for two simple reasons,” said Javid J. Moslehi, MD, an Assistant Professor of Medicine and the Director of the Cardio-Oncology Program at Vanderbilt School of Medicine in Nashville, TN. “First, there has been an explosion of new cancer therapies, some of which adversely affect the cardiovascular system, and second, survival of cancer patients makes cardiovascular issues relevant.”
The heart is especially vulnerable to cancer treatments because cardiac cells do not divide and have minimal ability to heal, despite being very active. They are also very responsive to stress and, because they rely heavily on cell-cell communication, disruptions can negatively impact the heart in a significant way. Some anticancer agents primarily affect cardiac function (including doxorubicin and trastuzumab); others indirectly contribute to cardiac decompensation by affecting fluid retention, blood pressure, or heart rate (such as bevacizumab, sunitinib, and carfilzomib); and still others can cause vascular disease (such as 5-cisplatin and 5-fluorouracil and newer agents including nilotinib and ponatinib).
Breakthroughs in cancer therapy have led to treatments that are more selective for malignant cells over normal ones; however, many of these treatments are still toxic to the heart. For example, the HER2/ErbB2 protein on certain breast cancer cells that is targeted by trastuzumab is also important in the myocardium. “In fact, it was the unexpected occurrence of severe cardiac side effects with trastuzumab that provided the final impetus for the cardio-oncology field and the recognition that maybe cardiologists should be more involved when certain cancer drugs are given to patients,” said Joerg Herrmann, MD, an Associate Professor of Medicine with a focus on cardio-oncology at the Mayo Clinic in Rochester, MN. Some of the newer targeted therapies may cause reversible rather than irreversible damage, which has led to the concept of type I (irreversible) and type II (reversible) chemotherapy-induced cardiotoxicity. “This may be equated to old chemotherapy and new chemotherapy cardiotoxicity, respectively, but this may not always be true and the very concept of type I and type II cardiotoxicity continues to be debated,” said Herrmann.
Regarding radiation therapy, damage can occur to the myocardium, pericardium, valves, and coronary arteries, as well as extracardiac structures such as the great vessels where accelerated atherosclerosis can occur. For many patients, these impacts will not be evident until a decade or more after treatment. “To prevent these effects, modern radiation techniques are more advanced and less toxic than older techniques,” said Herrmann. For example, various strategies have been developed to reduce the dose of radiation to the heart in patients with breast cancer. These include breath-hold techniques, prone positioning, intensity-modulated radiation therapy, accelerated partial breast irradiation, proton beam therapy, and 3-dimensional planning with less radiation dosage. Herrmann noted that because these techniques are relatively new, however, many cancer survivors seen in clinical practice today are developing complications from radiation received in the past. “It will take years until we see a change, and hopefully we will.”
When weighing the risks and benefits of different cancer treatment options, physicians and patients, especially those with compromised cardiovascular health or those with risk factors such as diabetes mellitus or hypertension, may not always be in full support of initiating highly curative therapies. Also, with numerous guidelines addressing different cancer types (with different recommendations for various subtypes and stages), it can be challenging for physicians to factor cardiovascular variables into the decision-making process when they recommend treatment regimens to patients. Furthermore, because of the frequent exclusion of patients who have cancer from cardiovascular clinical trials and patients with heart disease from oncology ones, many decisions must be based on limited evidence and in the context of evolving knowledge.
“The issue is further complicated by the presence of problems common in patients with cancer, including low platelet counts, hypercoagulability, dehydration, deconditioning, and other side effects of their cancer therapy that can further complicate the diagnosis and management of cardiovascular disease in this patient population,” said Tochi Okwuosa, DO, who is an Assistant Professor of Medicine and Cardiology and Director of Cardio-Oncology Services at Rush University Medical Center in Chicago. “Such challenges can limit the hematology-oncologist’s ability to give life-saving therapy for fear of an adverse cardiovascular outcome; and the same for the cardiologist who may not fully understand which aggressive measures are appropriate based on a patient’s cancer-related comorbidities and prognosis.” As a result, patients may be left without meaningful input from either specialty on ways to safely receive necessary therapies.
Cardio-oncology programs hope to provide some clarity and direction through collaboration of clinicians with a range of expertise, and through education, training, and mentoring across disciplines, as well, to nurture onco-cardiologists and cardio-oncologists. “In 2016, a first rate cardio-oncology program must have the infrastructure to tackle issues related to cancer and heart health at a deeper and mechanistic level since what we are essentially seeing is the evolution of cancer and chronicity of disease, much like type I diabetes 100 years ago and HIV 20 years ago,” said Moslehi.
Although certain cancer therapies may be off-limits to patients with serious heart issues, cardiologists with a thorough understanding of how different cancer drugs and radiation techniques affect the heart can recommend heart-protective interventions to allow most patients to undergo potentially curative treatments. “The onco-cardiologist makes it a point of duty to stay current on cancer therapies and their cardiotoxic effects, so that referrals based on any of these drugs are more specifically managed, creating a tailored approach to cardiac therapies for cancer patients,” said Okwuosa. Cardio-oncology programs also stress the importance of considering cardiovascular health as soon as possible after a cancer diagnosis. “It is not longer only about managing complications as they arise,” said Herrmann. “Rather, it is about assessing and mitigating the cardiovascular risk acutely and chronically and allowing cancer patients to receive the best possible cancer therapy at the lowest cardiovascular risk for the most optimal long-term outcome.”
- © 2016 American Heart Association, Inc.