Consider Cardioncology: Individualized Patient Care
Reinaldo José Lopes | 19-04-2017
Hospital Sírio-Libanês, in São Paulo, Brazil, employs cutting-edge technology and clinical expertise to help patients in both oncology and cardiovascular conditions. Read how of one of the most respected health centers in Latin America tend to shape the field of cardioncology for a better understanding of the interactions between cancer therapy and heart conditions.
Photos: Luiz Maximiano
Physicians have long known that cancer treatment can affect the cardiovascular system in undesirable ways. With a rising average life expectancy for cancer patients and a constant stream of new drugs, whose adverse effects are not yet fully known, cardioncology is becoming an increasingly important subspecialty. In São Paulo, Brazil, Hospital Sírio-Libanês, one of the most respected health centers in Latin America, is at the forefront of the efforts to raise awareness about the need to better understand the interactions between cancer therapy and heart conditions and to apply this knowledge in a clinical setting.
“In the last decade, we led the effort to establish the first Brazilian guidelines on cardioncology, focusing particularly on prevention,” says Roberto Kalil Filho, MD, General Director of Sírio’s Cardiology Center. Since then, the hospital, located a few blocks away from the city’s vibrant Paulista Avenue, has intensified the interaction between cardiologists and oncologists and is poised to become the Latin American branch of ICOS (International Cardioncology Society). According to Kalil, a partnership between Sírio-Libanês, Incor (the University of São Paulo’s Heart Institute) and Icesp (the São Paulo State Cancer Institute) to establish a joint cardioncology center is also in the works.
Paulo Marcelo Hoff, MD, Head of the Oncology Center at Sírio, says it’s not easy to pinpoint exactly when and how the need arose to see cardioncology as a subfield in its own right. “From my perspective, it was more like a gradual process than a rupture.” For Hoff, one factor was the increase in the diversity of cancer drugs, especially those with a clear molecular target – somewhat unexpectedly, this new generation of medicines also affected the cardiovascular system, particularly the heart. “We must always bear in mind that tumors are just repurposing and ‘retrofitting’ molecular tools already present in healthy cells for their own ends, so it makes sense that the drugs used to fight them will also hit unexpected targets throughout the patient’s organism,” he explains. “Back in the 1990’s, when I started my career as an oncologist, we had a few dozen cancer drugs. Now there are more than a hundred, and hundreds more being tested around the world, so at least some of them are bound to have cardiovascular side effects.”
There are some significant examples of this pattern in clinical use nowadays, says Hoff. One of them is Trastuzumab, which was designed to interact with the HER2 receptor in breast cancer. “We didn’t expect its effects on the myocardium, but it turned out that some young cells in the heart have the same receptor. It is something we can manage, of course, with proper support from cardiologists.” The same goes for Bevacizumab – its antiangiogenic properties can also be responsible for a decrease in vasodilation in small blood vessels, which leads to higher blood pressure in a subset of patients.
“I can say there is genuine and growing interest among Brazilian cardiologists in all these variables. When it comes to the patients themselves, there is very little awareness, but that is probably because cancer is still very much a taboo,” he says.
Treating people, not the disease
The interaction between tumors and cardiovascular disease tend to be complex and have to be considered in a patient-by-patient manner, argues Pedro Alves Lemos Neto, MD, Coordinator of the Hemodynamics and Interventionist Cardiology Service at Sírio-Libanês. “I’m afraid I’ll have to use a cliché here: we don’t treat diseases, we treat people,” says Lemos. “We need to take into account the detailed circumstances of each patient, from their age and personal history to what kind of tumor and cardiovascular conditions each of them are facing.” According to him, the situation can become a kind of Catch-22, especially if the patient already had a heart condition before the cancer diagnosis: it is crucial to do something about the tumor, of course, but in order to do that the patient’s cardiovascular health needs to improve. “You have to strike a delicate balance.”
Diagnostic and therapeutic methods that are both less invasive and more precise are making a huge difference in the way cardioncology patients are treated nowadays, he says. “Of course, when it comes to dealing with patients that have a tumor and a cardiovascular condition at the same time, reducing invasiveness is key, because these patients’ health condition can be especially delicate,” argues Lemos. “Thanks to more precise echocardiograms and CT, major surgery is no longer needed for much of the things we need to do here. You can use catheters in a very precise way to remove blockages from vessels or to close cavities that shouldn’t be there, you can take cameras inside coronaries and do measurements on the order of micrometers inside them, or you can correct arrhythmia by ‘ablating’ the exact point where it is being generated.” That is only possible because current methods allow physicians to visualize the tridimensional properties of the heart and also take into account its constant movement as it beats.
Through its IEP (Portuguese acronym for the Institute of Teaching and Research), Sírio-Libanês not only trains its physicians in the use of innovative technologies but stimulates them to turn the hospital into an engine of medical science.
“I need to stress that research and teaching are not just optional here: both activities are integral parts of Sírio’s institutional mission, besides our commitment to medical excellence,” explains Luiz Fernando Lima Reis, PhD, a biochemist as well as Research Superintendent and Head of the Graduate Program (both Master and PhD) at IEP. “There is nothing wrong, of course, when a great hospital chooses to focus on offering its patients the best possible treatment. However, in the end, the only way to maintain excellence is to keep attracting the most talented physicians to your clinical staff. How do you do that? By teaching. But you can only teach what you have mastered, and the best way to master any field is to be able to create new knowledge in that field – hence research.”
According to Reis, that is why the close partnership with Siemens Healthineers is crucial for Sírio-Libanês, since it gives their physicians the opportunity to learn how to use new technologies as they are being developed. “When this new technology reaches the market, I don’t have to train my staff – after all, they have helped to develop it and we will have been able to influence the way innovative medical care is going.”
Two recent projects, both spearheaded by Luiz Francisco Rodrigues de Ávila, MD, show how such commitment is bearing fruit. In one of them, Sírio’s team compared the accuracy and clinical usefulness of angiotomography (an eminently non-invasive method) to diagnose an acute myocardial infarction with the current gold standard, catheterism – which is considerably more invasive. “What we saw is that they perform very similarly,” says Ávila.
In a separate project, Ávila and his collaborators developed a novel and much simpler way to detect hemochromatosis in the heart and liver with the help of a Siemens ultrasound machine. “It’s pretty simple to do, but you have to be able to set the machine up yourself with a specific sequence of pulses,” he explains. “Without our method, it takes 45 minutes to diagnose the problem. With our method, you only need two minutes and, what’s more, patients don’t need to hold their breath, which is a limiting factor when you do the exam in the traditional way. It means that, even if one is conservative, it is possible to examine 20 patients per hour easily.” Iron overload in cardiac and hepatic tissue is not a very common problem in Brazil, but some countries around the world, such as India, have a high prevalence of the disorder and could benefit from the group’s findings.
Both Reis and Ávila say they are thrilled by the clinical and research possibilities of functional imaging. “We are about to leave behind the old paradigm of imaging technologies that were basically designed to provide you with a static portrait of organs or tissues,” Reis argues. “Instead, what we need now are molecular markers that could tell us about the metabolism of a given lesion, so we can infer what is happening inside it in real time.” Ávila agrees: “We’ve been constantly pushing the limits of what we can do in terms of detection. We used to be able to find 2-cm-wide lesions; now it is possible to see lesions that are half a centimeter across or less. If you keep finding things that are smaller and smaller, it does not mean this data will necessarily be more useful for the patients, unless you have a very detailed idea of what is going on there functionally. Once you do that, then you’ll be able to use drugs that have a specific affinity to the tumor, for example, or to activate them with magnetic resonance or ultrasound in a very precise manner.”
A leap forward in functional imaging would even help to face emerging diseases that are threatening both developing and developed countries, such as the Zika virus epidemic that has been strongly linked to a surge in microcephaly among Brazilian babies, says Reis. “In many of those cases, anomalies in the fetus were not apparent in the ultrasound images until the very last months of pregnancy. Anatomically, nothing seemed to be wrong. What if we could detect the cytopathic effects of the virus in their first stages? The same goes for cancer, and we know that, in general, early diagnosis is your best shot for a good prognosis.”
About the Author
Reinaldo José Lopes is a science and health writer at Folha de S. Paulo, Brazil's leading daily newspaper, and author of four books.
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