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Matters of the Heart in Hematologic Cancers

Neff Newitt, Valerie

doi: 10.1097/01.COT.0000553144.65191.55
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Michael Fradley, MD; cardio-oncology
Michael Fradley, MD; cardio-oncology:
“The last thing we want is for cardiovascular disease to become a barrier to patients receiving cancer treatments that may potentially cure them,” stressed Michael Fradley, MD, Director of the Cardio-Oncology Program at Moffitt Cancer Center. photos courtesy USF Health

Cardio-oncology has seen explosive growth during the last 7 years. The hybrid field is a collaborative effort between cardiology and oncology to address relationships—both long-recognized and newly discovered—between cancer, cancer treatments, and heart health.

Michael Fradley, MD, Director of the Cardio-Oncology Program and Associate Professor of Medicine in the Department of Cardiovascular Sciences at University of South Florida and Moffitt Cancer Center, co-chaired the 2018 Global Cardio-Oncology Summit in Tampa that attracted some 370 oncologists and cardiologists from 25 countries to explore all aspects cardio-oncology.

“The field developed from the 1970s-era recognition that anthracyclines, like doxorubicin, can lead to the development of heart failure and weakening of the heart muscle,” Fradley told HemOnc Times. “Eventually it became clear that trastuzumab, a breast cancer drug, also could weaken the heart muscle and cause heart failure. Those two drugs laid the foundation for what would become cardio-oncology.”

Had such associations been limited to just two drugs, cardio-oncology might have started and ended there. But that was not the case. Instead, oncology has forged brave new pathways of treatment, heroic in their ability to fight cancer, yet sometimes indicted by their propensity to wreak cardiovascular (CV) havoc.

“The paradigm has shifted substantially in the world of oncology as we have now moved into targeted therapies and immunotherapies,” explained Fradley. “We've come to recognize a variety of cardiovascular complications that can occur from this new world of cancer treatments. It ranges from heart failure, to heart attacks, strokes, arrhythmias, and inflammatory conditions like myocarditis. It runs the gamut of CV diseases.”

He explained that novel cancer therapeutics can damage the cardiovascular system in ways traditional chemotherapies did not. “Newer agents are based on an improved understanding of cancer biology, and yet they have off-target affects that can damage the cardiovascular system. For example, while you are harvesting the immune system to attack cancer cells, they can also damage normal tissues including the heart.”

Cardiovascular Risks

While the field was originally focused on anthracyclines in the setting of breast cancer, it now impacts all cancer specialties and a wide range of cancer therapeutics.

“In my own practice at Moffitt Cancer Center, my highest volume of patients is referred from either malignant hematology or stem cell transplant programs,” revealed Fradley. “This is due in part to the continued use of anthracyclines in the treatment of leukemias and lymphomas. But many novel treatments can also cause problems. For example, in multiple myeloma the proteasome inhibitor carfilzomib can lead to heart failure, cardiomyopathy, arrhythmias, and accelerated hypertension.”

Another drug, ibrutinib, an oral tyrosine kinase inhibitor, is increasingly utilized to treat chronic lymphocytic leukemia, mantle cell lymphoma, and chronic graft-versus-host disease in stem cell transplant patients. “A very high rate of atrial fibrillation has been observed with this particular drug, leading to significant management challenges in order for patients to continue receiving it,” Fradley said.

In addition to the specific drug toxicities, some patients have pre-existing cardiovascular disease and risk factors that must be taken into account. “Aggressive management of underlying hypertension, diabetes, and high cholesterol may reduce the likelihood of developing toxicities and potentially improve outcomes,” enumerated Fradley.

Understanding the Nexus

Cardio-oncology is roughly defined as the management of cardiovascular disease and risk factors in cancer patients and cancer survivors, with a goal to prevent cardiovascular disease from affecting delivery of optimal cancer care. “At its core, the field is multidisciplinary,” added Fradley. “We are proud to be breaking down the barriers and silos that often exist between different specialties.”

While the majority of clinicians in cardio-oncology are trained cardiologists, there are a significant number of oncologists championing the field as well. “The cardiologist works with the oncologist to clear the CV path for treatment, and shepherd patients through their treatments safely from a CV standpoint. We want to mitigate risk to the cardiovascular system so that patients can be offered a therapy that may actually save their lives.” Further making the point that the field must avoid needlessly implicating drugs or causing a medication to get a bad reputation, Fradley added, “These drugs have been developed because they have fantastic effect on cancers that may have no other treatment options.”

Asked at what point in cancer care cardio-oncology should be pressed into action, Fradley answered, “... as early as possible. It should be offered to patients at the beginning stages of treatment when cardiovascular risks and side effects may be minimized.

“As a field, we must focus on the early identification of patients at higher risk of developing complications during treatment,” he stressed. “These patients need to be referred to cardio-oncology early in their treatment to optimize their cardiovascular health.”

To make this dual-field nexus work, oncologists must identify qualified cardio-oncology partners so that they do not feel compelled to shy away from certain therapies because of their own discomfort in managing or mitigating associated CV risks.

Michael Fradley, MD
Michael Fradley, MD:
Michael Fradley, MD

“When oncologists don't have a cardio-oncology program or partnership, they may choose an alternative treatment—not their preferred option—because of a cardiovascular concern,” Fradley declared. “Moreover, not every cardiologist is familiar with cancer drugs and their toxicities. So, cardiologists and oncologists—both sides of the clinical equation—need education about cardio-oncology.”

An Ongoing Expansion

Fortunate is the oncologist—and patient—who connects with an established program and cardiologists with refined knowledge about oncology. “Today a majority of academic centers have cardio-oncology programs, or at very least cardiology practitioners interested in seeing oncology patients,” Fradley said. He himself became interested in the just-emerging field of cardio-oncology in 2011 when he was doing training in electrophysiology specific to abnormal heart rhythms at Massachusetts General Hospital, Boston.

“I started to see a lot of cancer patients who were having abnormal heart rhythms during their therapies. It started to pique my interest. Why was I seeing seeing more patients with these problems?” he wondered.

At the same time, Fradley had his own experience with melanoma. “Because of these observations and my personal experiences with cancer, I wanted to develop a career that incorporated both cardiology and oncology,” he said, crediting a mentor at Boston's Brigham and Women's Hospital and Dana-Farber Cancer Institute, Javid Moslehi, MD, now at Vanderbilt University leading their cardio-oncology program, as the “individual who significantly helped me develop my own career path.”

When Fradley was first getting into cardio-oncology, he did it largely on his own, through reading, independent study, exposure, and immersion.

“But as the field has grown and become increasingly complex, the professional community recognizes the need to define metrics and develop evaluation processes for individuals interested in becoming cardio-oncologists,” he said.

This includes developing training requirements, and cardio-oncology fellowships where fellows spend a year exclusively taking care of CV issues in cancer patients while learning nuances and complexities of the field. There are only a handful of programs that offer such fellowships, one of them being at Moffitt Cancer Center and the University of South Florida where Fradley runs the training.

Fradley said that while fellowships are now geared to cardiologists, he foresees a time when there may also be a role for more advanced training for oncologists as the field continues to grow and as standards for cardio-oncology evolve.

“An inadequate understanding of cardio-oncology has been one of the challenges up until now,” said Fradley whose earlier training included medical school at Johns Hopkins University, Baltimore, and cardiology training at Harvard Medical School, Boston. His first faculty position took him to the University of South Florida and Moffitt Cancer Center in 2013. A year later, the center's cardio-oncology program opened. “Today I spend over 95 percent of my time, either clinically or academically, on cancer-associated work,” said Fradley.

Asked to pinpoint the biggest challenge associated with opening a cardio-oncology program, Fradley did not hesitate. “Time. It takes time for referrals to develop and for patient volume to increase,” he said earnestly. “A lot of legwork is needed from cardiologists to educate oncologists and to gain their trust. It takes persistence.”

For now, oncologists can best serve the field by educating their peers and patients, collaborating in their cardiovascular care, and participating in cardio-oncology research endeavors. The program at Moffitt has an oncology partner/co-director, Roohi Ismail-Khan, MD, who helps fellow oncologists recognize that the program is not just a cardiology specialty, but rather a collaborative approach.

“Cardio-oncology speaks to the concept of caring for the whole patient, not just focusing on the cancer,” declared Fradley. “We can't simply say, ‘You have cancer and the other things don't matter.’ They do and if you don't pay attention to them, they can have serious consequences for a patient's long-term health and safety.”

Cardio-oncology is, at its root, a collaborative discipline that requires cardiologists and oncologists to work together as a team to provide stellar care. “As survival rates continue to increase for cancer patients, it is essential to manage their CV risk and disease aggressively,” said Fradley. “The last thing we want is for CV disease to become a barrier to patients receiving cancer treatments that may potentially cure them.”

Valerie Neff Newitt is a contributing writer.

Wolters Kluwer Health, Inc. All rights reserved.
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