Cardiotoxicity After Cancer Treatment

It all began as a typical afternoon when I was in my office, working as a medical transcriptionist at a local neurology practice. I was organizing a few patient charts that had just been brought in by the last few neurologists as they headed out for the day. What I was doing was not physically taxing in any way, and I was not feeling particularly stressed. But in that moment, I became unaccountably aware of my heart — it suddenly seemed to be racing uncontrollably, pounding and galloping in my chest. I immediately sat down, breathed deeply, and waited for the sensation to stop. Fortunately, it quickly did, and I pushed the experience out of my mind.

But only a day or so later, as I was walking on my treadmill at home, I realized that strangely enough, my left arm was repeatedly, and of its own volition, rising toward the ceiling. Just as I was wondering, “What on earth am I doing?” I felt a heavy, crushing sensation in my chest. I quickly stepped off the treadmill, and the feeling went away almost immediately. Even then, I was not ready to acknowledge that something was terribly wrong. Yet later that same night, there was simply no denying it: as I was resting in bed, the crushing sensation returned, and I began to feel inexplicably, frighteningly short of breath, and it finally clicked that I needed help.

While speaking with my primary care provider’s office the next morning, I was told they had an opening in a few weeks. I almost accepted that … but at that very moment, a long-buried memory came roaring back, loudly insisting, “Tell them about your radiation and chemotherapy — do it now.” So I cleared my throat and told them I should probably be seen much sooner than that. I haltingly explained that I had received radiation to the chest and chemotherapy that had included Adriamycin (doxorubicin, a chemotherapy drug that can cause heart muscle damage) about 16 years before, and I was worried that my symptoms could be due to cardiotoxicity from my previous cancer treatment. When I hung up the phone a few moments later, I did so with an appointment scheduled for that day.

The memory that spoke to me so clearly was a brief discussion I’d had many years before with my new radiologist shortly after I had been diagnosed with stage III Hodgkin lymphoma. I was just 22 at the time, trying to cope with my new reality as a young adult with a serious cancer — by taking every moment and making every decision while in the midst of what I now see as a self-protective daze. My oncologist had referred me to the radiologist, explaining that because I had several unfavorable prognostic factors, we needed to consider treatment that included not solely chemotherapy and not solely radiation, but both.

I had extremely “bulky” disease — meaning that the lymphoma was greater than or equal to 10 centimeters or greater than 33 percent of my chest diameter on chest x-ray.¹ In addition to having stage III disease, I had also experienced “B symptoms,” including severe night sweats and weight loss, the presence of which serve as a marker for more advanced disease with systemic rather than solely localized involvement.

Thus, on that afternoon long ago, my new radiologist was explaining his recommendation for extended-field radiation to the mantle field and periaortal region, and he was reviewing with me the lengthy list of potential adverse effects associated with such treatment. His words describing these possibilities seemed to be flying around me, with none landing, until two words managed to break through my daze and push all the others aside. I asked, “Did you just say ‘heart damage’?” He had.

Compared with our current understanding, less was known at the time about cardiotoxicity due to radiation. Yet my radiologist did emphasize that, yes, it was possible for patients to manifest what he simply called cardiac damage many years following their radiation treatment. What wasn’t known then was that the higher the dose of the radiation, the higher was the risk of developing radiation- induced heart disease.²

Because my lymphoma was so bulky, the biggest fear was the very real chance of relapse which, should it occur, would leave me with far fewer and less effective treatment options. At that time (the 1980s), in such cases, six weeks of high-dose and extended-field radiation was typical following chemotherapy to reduce the risk of relapse as much as possible. Fortunately, in recent years, there have been ongoing efforts to reduce the extent of radiation treatment for both field size and dose without compromising benefit.

In addition, technological advances have enabled more accurate targeted radiation delivery, which minimizes exposure to the heart and other surrounding normal tissue,³ though it is not yet clear whether these techniques have lowered the risk of developing late radiation-induced complications overall or served to delay the time to onset of such complications. Therefore, lengthier follow-up is needed to determine the prevalence and pattern of radiation- induced complications with current techniques.^4,5

At that time, however, all this was far off in the future, and there was little choice other than to go ahead with the radiation treatment as prescribed. So I went into “repression mode,” figuratively cupping my hands around those two words (“heart damage”), throwing them back into the swarm that was flying around me, and gratefully returning to my self-protective haze.

Self-Advocacy to Ensure Treatment

I so successfully buried those words that I never thought of them again until they miraculously roared back into my consciousness at the very moment I needed them. Because from the moment that I called my PCP’s office and pushed for an earlier appointment, I realized that it was crucial for me to advocate for myself and that I needed others to do so as well on my behalf to survive this.During my visit to the PCP’s office, the advanced practice registered nurse (APRN) who was examining me began by giving me an electrocardiogram (EKG). I was surprised to learn that my EKG results were normal. But I was not relieved. I knew that a “normal” EKG does not necessarily mean that you do not have heart problems, and I was worried the EKG results would keep my healthcare providers from further pursuing my symptoms. So I carefully outlined my history to the APRN, explaining that although I was only in my 30s, I had concerns that my symptoms could be due to cardiotoxicity secondary to my radiation, the Adriamycin I’d received during my chemotherapy, or both.

She agreed that heart disease was very rare in women my age and that my cancer treatment needed to be taken into account. She thanked me for being candid and for providing specific details about my medical history and explained that she wanted to make a phone call to have me seen by a cardiologist right away.

Years later, my APRN told me about what occurred during that phone call. She explained that when she finally got a cardiologist on the phone, he listened to everything she had to say about my case and responded, “Why are you calling me about this patient? She’s far too young for her symptoms to be caused by coronary artery disease.” She then again went over my case from the beginning, stressing my history of high-dose radiation to the chest area in my early 20s, my specific chemotherapy regimen, and the nature of my symptoms, including severe chest pain and dyspnea at rest. He listened as she advocated for me, minutes after I’d advocated for myself.

A Second Opinion … or Several

So yes, my EKG was normal, but the test results from my new cardiologist confirmed my fears: severe radiation- induced coronary artery fibrosis (scarring), stenosis (narrowing), and 90% blockage. The worsening chest pain I’d been experiencing was due to reduced flow of oxygenated blood to my heart, caused by progressive narrowing of one of my coronary arteries.Due to the complexity of my case, my cardiologist quickly brought in a colleague, an interventional cardiologist. He explained that because of the specific location of my blockage, there was concern over whether the better course of action would be a coronary artery bypass graft (CABG) or an angioplasty.

When my husband and I met with this second cardiologist, his demeanor was extremely grave as he explained the severity of my blockage and the risks associated with each procedure. At one point, when he was showing us images of my heart and the coronary arteries, I asked him point blank, “Should I be getting my affairs in order?” He simply said, “Yes.”

I was blindsided by his response. Although I’d asked the question, I expected reassurance. When I heard instead his devastating reply, time instantly divided into before the “yes” and after, and that’s when the tears came. They didn’t stop during our long drive home, and they came harder when I thought about having to share this bad news with my parents. I simply couldn’t bear it, so I asked my husband to call them for me. He did so as soon as we arrived home, as I listened, still in tears.

My cardiologists, in turn, brought my case for review before a large team of cardiologists, including invasive, interventional, and surgical cardiologists due to the difficult location of the blockage and the distinct risk of having another coronary artery collapse during an angioplasty.

After conferring, their overall recommendation was to conduct an angioplasty with placement of a drug-eluting stent, which had been approved by the FDA just the month before. But they also stressed the need to have a team of cardiac surgeons on hand to perform a CABG should a second artery indeed collapse, leading to a risk of myocardial infarction (MI) during the procedure. Whether to go with angioplasty or directly to a CABG was 100% my choice, and it was one of the most agonizing decisions I have ever made.

Ultimately, I chose the angioplasty. And during the operation, my cardiologists’ and my own fears came true: a second coronary artery did in fact collapse during the procedure. But fortunately, a CABG was not the option chosen by my cardiologists. I later learned that because the drug-eluting stent they used during my first angioplasty was so newly FDA-approved, their quantities were extremely limited and the cardiologists therefore needed to lobby strongly for approval to place a second stent.

To my good fortune, their efforts were successful: the team was able to immediately do a second angioplasty and place the second stent. At the end of my successful procedure, both of my cardiologists were visibly relieved. I was profoundly grateful to them then, and remain grateful today and every day, for they both became advocates on my behalf as well, helping me to survive the most frightening moments of my life.

Continuing Need for Advocacy

I knew then and know now just how fortunate I was that my radiation-induced coronary blockage was diagnosed before my symptoms worsened even further. Overall, for Hodgkin patients who have been treated with radiation, cardiovascular disease is the most common cause of death after malignant disease, most frequently occurring decades after their treatment. These patients have an increased risk for coronary artery disease, congestive heart failure, valvular heart disease, and sudden cardiac death, with the risk particularly high in those who were treated before the age of 40. The relative risk of death from a fatal MI in patients who received mediastinal radiation therapy is increased from 1.5 to 3.0 times that of patients who have not received radiation.5Years following my angioplasties, during a routine follow- up visit, my cardiologist shared with me that I was the first patient he’d diagnosed and treated for radiation- induced coronary artery disease due to cancer treatment. And I know that his advocacy on behalf of patients has extended far beyond my original case.

For example, just months after my procedure, he told me he had emergently treated a young man who also had Hodgkin lymphoma and developed cardiac symptoms as a late effect of his cancer treatment. In addition, he has given grand rounds (an important teaching tool in medical education and patient care for doctors, residents, and medical students) on recognizing and treating radiation-induced cardiotoxicity in young adult cancer survivors.

Nevertheless, few PCPs, generalists and patients are sufficiently aware of the late effects that may develop often decades after cancer treatment, no matter the patient’s age. With so many cancer patients now surviving their disease and ultimately returning to their PCPs for their medical care, there is an urgent need for these physicians and their patients to develop a more specific understanding of long-term, late, and secondary adverse effects of particular cancer treatments, including cardiotoxicity and second cancers.

Debra Madden became an active cancer research advocate following her second cancer diagnosis at the age of 42. Nearly 20 years earlier, she was diagnosed with Hodgkin lymphoma and subsequently developed late treatment effects, including cardiotoxicity and breast cancer. Debra is currently a member of the ECOG/ ACRIN Cancer Research Group as well as the Patient-Centered Outcomes Research Institute’s Advisory Panel on the Assessment of Prevention, Diagnosis, and Treatment Options. She also serves on multiple grant review panels, including the Congressionally Directed Medical Research Program (CDMRP) for breast cancer. Debra blogs at Musings of a Cancer Research Advocate and you can follow her on Twitter at @AdvocateDebM.

References

1. National Cancer Institute. Adult Hodgkin Lymphoma Treatment — for health professionals (PDQ). Updated April 2, 2015. http://1.usa.gov/1IgG039. Accessed April 11, 2015.
2. Darby SC, Ewertz M, McGale P, et al. Risk of ischemic heart disease in women after radiotherapy for breast cancer. N Engl J Med. 2013;368(11):987-998.
3. Terezakis SA, Kasamon YL. Tailored strategies for radiation therapy in classical Hodgkin lymphoma. Crit Rev Oncol Hematol. 2012;84(1):71-84.
4. Jaworski C, Mariani J, Wheeler G, Kaye DM. Cardiac complications of thoracic irradiation. J Am Coll Cardiol. 2013;61(23):2319-2328.
5. Yusuf SW, Sami S, Daher IN. Radiation-induced heart disease: a clinical update. Cardiol Res Pract. 2011; doi: 10.4061/2011/317659.