Anju Nohria, MD, explains how the Cardio-Oncology Program originated and some of the challenges clinicians face in identifying high-risk patients and monitoring cardiovascular risks.
Anju Nohria, MD
In recognition of the growing numbers of cancer survivors who may experience cardiotoxicities as a result of their treatment, several major cancer centers in the United States have created interdisciplinary cardio-oncology programs that focus on preventing and managing such risks.
Research indicates that late cardiac effects of therapy fall into three major categories: (1) vascular conditions such as atherosclerosis, thrombosis, and hypertension; (2) structural problems such as valvular degeneration; and (3) myocardial dysfunction and heart failure.1 These effects can stem from radiation therapy, anthracyclines, antiangiogenic therapies, and the HER2-targeting agent trastuzumab.1
Anju Nohria, MD, is an assistant professor at Harvard Medical School and a member of the Cardio-Oncology Program, a collaboration between Brigham and Women’s Hospital and Dana-Farber Cancer Institute. A cardiologist by training, her area of subspecialty is heart failure and transplantation.
Nohria spoke to OncLive about how the Cardio-Oncology Program originated and some of the challenges clinicians face in identifying high-risk patients and monitoring cardiovascular risks.
Q: Can you provide a brief history of the launching of the Cardio-Oncology Program?
Dr Lawrence Shulman, chief of staff at Dana-Farber Cancer Institute, and Dr Kenneth Baughman, who was the head of the cardiovascular Shapiro Center at Brigham, recognized the unmet need and together decided to develop a collaborative program. It was primarily initiated as a survivorship program, looking at late cardiotoxicities in people who had previously been treated with anthracyclines and radiation; during the course of the program, though, we recognized the cardiotoxic effects of novel chemotherapy agents as well. So it evolved into a program that looks at survivorship, cardiotoxic effects of novel agents during treatment, and taking care of patients with concomitant heart disease and cancer.
The cardiotoxic effects of anthracyclines have been known for a while; additionally, patients treated with radiation in the late 1980s or earlier were known to present with late cardiac effects. So they decided that being a big cancer center and cardiology center, we needed a program that evaluates this. It was more of an administrative decision. We were not the first in the nation, though, to monitor cardiac effects of oncology treatment. Memorial Sloan Kettering and MD Anderson have had [cardio-oncology] programs for a while.
Q: What is known about the newer oncology agents and their effect on the cardiovascular system?
Several tyrosine kinase inhibitors, especially the ones that inhibit vascular endothelial growth factor, have been shown to cause hypertension. So we manage a lot of patients with concomitant hypertension while they are undergoing chemotherapy with those agents. Some of these agents, for example, sunitinib, used to treat renal cell carcinoma, have been shown in some instances to cause cardiomyopathy and heart failure. Some of the newer agents used in the treatment of chronic myelogenous leukemia have been shown to cause acute vascular events, and we are involved in the care of those patients as well.
With several of the newer agents, we still don’t have enough information to predict their cardiovascular effects. A few have targets that are expressed in cardiac as well as cancer cells, which may result in unwanted adverse events.
Q: What is the demographic of the patients who participate in the program?
Older persons or those with preexisting heart conditions or cardiac disease tend to be more susceptible.
This is true for late cardiotoxicity as well as for acute cardiotoxicity. For example, a 65-to- 70-year-old patient with coronary artery disease will be at a greater risk of developing heart failure.
Similarly, very young children, whose organs are still developing, tend to be more susceptible to the cardiotoxic effects of these treatments.
Q: When does the cardiologist become a part of the care team of a cancer patient?
I get involved when there is a problem. I don’t see all cancer patients. I only see high-risk cancer patients or those who develop an issue following treatment.
Patient management then becomes a collaborative process. I’d start the patient on cardiac medication, consult with the oncologist on whether their oncology treatment needs to continue or needs to be held till their cardiac function improves. We’d also discuss whether there’s a need to alter their oncology regimen, although the final decision is made by the oncologist. I see the patient as often as is needed. It’s a collaborative decision, because for a patient with a high-grade disease, if they are not going to be alive without the chemotherapy, you have to weigh how bad their cardiac condition is and whether it can be managed medically. It’s a conversation that depends on who the patient is.
Q: Are medical organizations like the American College of Cardiology (ACC) or the American Society of Clinical Oncology raising awareness of cardio-oncology?
Several major meetings now include sessions on cardio-oncology; at the recent ACC meeting I was part of a half-day session that was devoted to cardio-oncology. The American Society of Echocardiography has developed independent guidelines on how to monitor patients who have been treated with anthracyclines and trastuzumab.
So although it’s still a relatively data-free zone, various organizations are working to raise awareness around this issue. What we are still lacking is a mutually acceptable set of guidelines collectively developed by cardiologists and oncologists to prospectively monitor these patients, and this is primarily because of the lack of sufficient data in the field.
Q: How aware is the pharmaceutical industry about this issue, and what steps do they implement to manage these drug toxicities?
Drug developers are quite aware of the toxicities of chemotherapeutic agents, and they include cardiac event side effects in their adverse event reporting.
Several cancer drugs have a rapid approval process because progression-free survival is an acceptable endpoint. In cancer the criteria for approval of oncologic drugs are different, and sometimes it’s about the risk-to-benefit ratio. We have to understand it’s a different equation, because you have competing risks from two lethal diseases and you have to decide whether the benefit from chemotherapy will outweigh the risk of a concurrent cardiotoxic effect of the drug, which could be manageable.
There are several novel oncology regimens being developed that could affect various organs, including the heart. Going forward, the more vigilant we are, the better we can manage these patients so we do not necessarily deprive them of essential cancer therapy.