Surviving Cancer, But at a Cost: Radiation & Chemo-induced Cardiovascular Diseases

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 - Drip

Wars leave damage in their wake, and the war on cancer may be no exception. Radiation therapy and chemotherapy have greatly improved survivorship in some cancers, but they also may leave the heart and cardiovascular system battle scarred. In the absence of clinical trials, cardio-oncologists are building a case for the need to monitor survivors at risk of developing radiation- and chemo-induced cardiovascular diseases, but how and how often remains unclear.

Changing landscape

In the mid to late 1970s, the five-year survival rate for a child diagnosed with cancer was 58 percent and for a woman with invasive breast cancer it was 75 percent, according to the National Cancer Institute. Until then, the heart was thought to be safe from the damaging effects of two mainstay cancer treatments, radiation therapy and anthracyclines, a belief that was turned on its head with evidence of treatment-induced cardiomyopathy and heart failure. That prompted changes in protocol, including lowering doses, shielding the heart during radiation and measuring left ventricular ejection fraction (LVEF) at baseline and follow-up to identify at-risk patients and modify treatments if needed.

Patient with Radiation-induced Valvular Heart Disease
RadCardDisease.jpg - Patient with Radiation-induced Valvular Heart Disease
This echocardiogram shows extensive calcification of the aortic and mitral valves (arrows) and of the left ventricle. There is significant aortic stenosis and regurgitation.
Source: This figure originally appeared in the European Heart Journal - Cardiovascular Imaging, 2013 Aug;14(8):721-740, in the report "Expert consensus for multi-modality imaging evaluation of cardiovascular complications of radiotherapy in adults: a report from the European Association of Cardiovascular Imaging and the American Society of Echocardiography." Used with permission of EACVI.

Those five-year survival figures changed dramatically over the decades, jumping to 82 percent for pediatric cancers and 91 percent for breast cancer by the mid-2000s. Today, almost 59,000 childhood cancer survivors and 3 million breast cancer survivors live in the U.S. That has been a victory on the cancer front, but as survivors live longer, they face another life-threatening specter: the possibility that over time cardiovascular injury from anticancer treatments may manifest into a host of diseases.     

“You have children now who are survivors who are living into their 30s and they are starting to experience cardiovascular events,” says W. Gregory Hundley, MD, a cardiologist at Wake Forest Baptist Medical Center in Winston-Salem, N.C. “For breast cancer patients, it is a very similar story. Twenty to 30 years ago, there was a relatively high morbidity and mortality. … But women who survive beyond five years from treatment of their cancer are now beginning to experience cardiovascular events.”

One assessment of 1,713 adult childhood cancer survivors treated between 1962 and 2001 found that 56 percent who had been exposed to cardiotoxic therapies had cardiac abnormalities, and most of these abnormalities were revealed during the study evaluation (JAMA 2013;309[22]:2371-2381). In a scientific statement on long-term cardiovascular toxicity, the American Heart Association (AHA) reported that cardiovascular disease in childhood cancer survivors is now second only to cancer as a cause of death (Circulation online Sept. 30, 2013). Cardiovascular disease also ranks as the second leading cause of morbidity and mortality in women who have lived five years or more after a breast cancer diagnosis.

Some of those patients were treated in an era of high-dose anthracycline treatments, though. To better assess the early effect of the current low-dose protocol, Hundley and his colleagues evaluated 53 cancer survivors who received low to moderate doses of anthracycline chemotherapy (JACC Cardiovasc Imaging 2013:6[8]:877-885).  Using cardiac magnetic resonance (CMR) imaging and biomarker tests at baseline and at one, three and six months, they found LVEF diminished and aortic stiffening increased over six months.

“Are the early changes meaningful? Do they indicate down that road that someone may or may not be at risk? Or are they transient and we don’t need to necessarily react to them? We don’t know,” Hundley says.

Navigating unknowns

Another study that looked at the risk of ischemic heart disease in women irradiated for cancer in Sweden and Denmark between 1958 and 2001 found the rate of MI, coronary revascularization and death from ischemic heart disease increased