Role of Cardiology in Cancer Treatment: Cardio-Oncology

Introduction Welcome back to another exciting episode of The Oncology Brothers. I'm Rohit Gosain and along with my brother Rahul Gosain. Today we have fascinating discussion planned out for you, which is around cardio oncology. Though we have seen improvement in oral survival when it comes to cancer with our newer cancer treatment options, whether that's targeted therapy, antibody drug conjugates or immune checkpoint inhibitors, This comes at a cost. Certainly part of it is financial toxicity, but rather also side effects that these newer agents have. Speaker 2 Rohit, I have to agree. It's not just good enough for us to stop by saying that our patients have better survival or are living longer. It is important for us to acknowledge that some of these agents have lifelong side effects and these treatment modalities are not benign. And it's not just Adriamycin or trastizumab as you pointed out, some of our newer agents can also have this long lasting cardiac side effects. So to focus on our patients receiving optimal cancer care while keeping their cardiac health in track, it is very important for us to keep this as a whole for our patients. To help us explore this topic of cardio oncology, we're thrilled to have Doctor Susan Dent, a medical oncologist and President of the International Cardio Oncology Society, join us today. Susan, thank you so much for joining us today. But personally, I'm also looking forward for you to be joining us here in person at the Beaumont Cancer Center in Rochester, NY. Speaker 3 Thank you for inviting me. You know, I think this is such an important topic and really excited to discuss it today, especially after just coming back from ASCO and hearing about all the new therapies that we have that are really improving the clinical care of our patients. Speaker 1 Indeed, Susan, this is certainly very, very important topic to address. So just to get started, let's start off with the basics. What is cardio oncology and why has it become such an important discipline? What exactly is cardio oncology and why has it become such an important discipline? It's a. Speaker 3 Very good question. I think even today when I mentioned cardio oncology to individuals, even those in the healthcare profession, they think this is focused on cardiac tumors or tumors of the heart and that's not at all what cardio oncology is all about. Cardio oncology really looks at the intersection between cardiology and oncology. 2 professions that come together to look after the entire individual with cancer right from the beginning when they start their cancer treatment through the entire treatment into after completion of their cancer therapy. And I can't stress that enough. It's the whole journey and really it's dedicated to ensure that our patients with cancer get the best possible cancer therapy without having a negative impact on their cardiovascular health. And that's so important as we see patients aging, we're seeing older people develop cancer, they may have pre-existing cardiovascular disease. How do we treat both? How do we get them through their cancer treatment without worsening their cardiovascular health? And so it's that working together, I call it more of a person centric approach then a disease centric approach where we want to treat the whole person, not just a cancer. Speaker 2 Indeed, Susan, thank you for laying that foundation. And you know, we all talk about survivorship, particularly we often state that we want our patients to thrive, not to survive. But let's be honest, that is not going to happen if their cardiovascular system is compromised. And you set this perfectly. Let's cure cancer and save hearts. So, Susan, let's start off with a broad topic and then we can start to narrow down a little. Cardiotoxicity and Cardiotoxicity in Oncology Can you highlight some of the key cardiovascular risks and toxicities that I need to be aware of as an oncologist? Speaker 3 No. We've known about anthracyclines for a long time and anthracyclines are still part of our treatment regimens that we use in breast and many other cancers. And we've known for many years that if we give a certain amount of lifetime exposure to anthracyclines, that can potentially lead to heart failure. A few things that are new about that topic. Actually, we understand now that the dose, the total lifetime dose of anthracyclines is much lower than what used to think. So anything over 250 milligrams per meter squared, you really do have to start worrying about cardio toxicity, which usually presents as drops in LVEF or heart failure in some cases. So that's something that's new. And then trestuzumab or her two target therapies came along a number of years ago and when they were introduced for the treatment of early stage her two positive breast cancer, it really changed the landscape of how we approach that disease and it led to significant gains in disease free and overall survival. But we know that her two target therapies can also affect the heart and can cause drops in LVEF. And as we're being asked to do these echocardiograms both in academic and community centers and we were seeing drops in the left ventricular ejection fraction and quit. Honestly, I don't think as oncologists, we really knew what to do with that. So the LVS would drop to the below 50% and then we would say, well, we better hold the therapy because that's what we're told to do. So that was really where my interest in this whole field began is I felt that this was a therapy that really improved the clinical outcomes for our patients. Cardiotoxicity in cancer therapy And OK, we've seen that they've had some form of cardio toxicity. Can't we do something about this? What can we do so that our patients complete their therapy? And that's where I think cardio oncology was really born with this idea that we need to be able to provide the best cancer therapy for our patients, even in the setting of some compromised cardiovascular toxicity. And there's a new term for that, by the way. We call it permissive cardio toxicity, meaning you can accept a little bit of toxicity if it's in the context of providing life care sustaining or life caring therapy. Speaker 2 Susan, thank you so much for touching on that. You've mentioned anti her two therapy and breast cancer. That field is also shifting fast 'cause now it's not only breast cancer that I have to worry about. When it comes to anti her two agents. We have a bucket approval for something like Trastism Abdurex T can. So this field is not just between breast medical oncologists or cardio oncology, but as a community who's giving TDXD, this should be on our radar. Drugs like osimertinib that we tend to use in lung cancer, they have cardiac side effects. So all this is very important for us to keep in mind when treating our patients. Speaker 3 You're right, originally it was very focused on, on breast cancer, but now as you can see from here that there are many, many cardiovascular toxicities associated with different classes of drugs. Cardiovascular Toxicities of Cancer Drugs So you know, we, we've seen tyrosine kinase inhibitors and, and their impact in terms of hypertension. We see some of our drugs lead to increased risk of thrombosis. We have PR3 kinase inhibitors that can cause a metabolic syndrome that can be detrimental. And we can't forget about things like radiation. So when you introduce radiation into the field, they can also cause cardiovascular toxicity. So most people think of chest radiation or left sided radiation and the impact of it on the structures of the heart, which can appear years down the road in terms of coronary artery disease or valvular heart disease. But even if you have radiation to other parts of your body in the in the abdominal area, you're affecting the vascular system and that can lead to potentially hypertension. So many different mechanisms of toxicity in across many classes of drugs. And as we're moving away from traditional chemotherapy drugs and more target drugs, each one of those new target drugs seems to carry with it a unique cardiovascular toxicity. Speaker 1 Right. Can't stress the importance of that, especially when in the past as you stressed that we only had to worry about trastuzumab and anthracycline. So we still have to worry about that today. But along with that, a very common class that we tend to rely on in a lot of cases is immune checkpoint inhibitor. As a community oncologist, we very well need to be educated from this aspect. Now, have you seen less cases of cardiac toxicity with this? Wonder if that is partly because we don't know how to diagnose the cardiac toxicity being contributed from immune checkpoint inhibitor. But we have seen cases like myocarditis, which leads to mortality, which is very concerning. Susan, to me, it seems collaboration between oncology and cardiology is critical. Collaboration between oncology and cardiology Can you build on this a little? I'm curious to see how. And basically, as a community oncologist, I should be collaborating with my cardiac colleagues so we can provide better care to our patients. Speaker 3 Right. That's very true. And I think there are different time points where that collaboration is very important. So I would say, you know, we need to think about collaborating with our cardiology colleagues right at the very beginning when patients are starting their cancer therapy. And I would advocate that as oncologists, we need to think about risk assessment right at the beginning. So you have a patient coming to you who might be exposed to immune checkpoint inhibitor. What are their underlying risk factors and can we determine are they at low, moderate or very high risk of experiencing cardiovascular toxicity? So we're very fortunate that the European Society of Cardiology, she came out with these cardio oncology guidelines in 2022. And it really speaks to trying to think about how we can determine risk. And as you can see here, and they have endorsed these performa that are used in several different classes of drugs that help us determine what that risk is. And then of course, during the course of their therapy, patients may run into issues such as hypertension or drops in EF. And that's another twine point where it's important to collaborate and then willing to survivorship. So I think that collaboration, it really needs to start at the very beginning. And not that you need to refer every single patient to a cardio oncologist, but for instance, if you have someone who's at high or very high risk of experiencing cardiovascular toxicity, that is a person, probably you want to speak to a cardio oncologist earlier rather than later. The low risk people can go ahead and you know you treat them only if something develops down the line. Should you then, I think, entertain reaching out to your colleagues. Speaker 1 From community oncology standpoint, would you say that one needs cardiac clearance before we start in any immunotherapy or chemotherapy? Cardiovascular clearance and immunotherapy And also if one is on immunotherapy, would you say getting serial troponin or getting troponins beforehand or anything from practical aspect of it? Speaker 3 Yeah, there are. I would say that, you know, I would refer you to the these guidelines which actually outlines exactly what they recommend as baseline tests for immune checkpoint inhibitors. Now as you alluded to things such as myocarditis, it does happen, it's not common. It happens in about 1 to 2% of patients with cancer. It's more common in cancer patients who are getting dual immune checkpoint inhibitors. So for instance in renal cell. So we're not, we don't see it as commonly in in things like breast cancer where we're just being one, but in this guideline actually outlines what they recommend in terms of baseline investigations and importantly, how you can follow those patients while they're on therapy. And you know, as you can see on this diagram, I want to point out that there are some level one recommendations around how we manage people, how we assess them for risk. But a lot of this is based on expert opinion because we still don't have the data. We still need to do clinical research and we need to understand better how to manage these. But for now, this is the best information that we have. So this is my one plug for research in this area. I think we need to have we need to have a better understanding of how to manage well, actually, you know, determine who's at risk and how to manage. And another area that's very interesting in the space is we're now looking at prevention strategy energies. Preventive strategies for cardiovascular toxicity So once you've identified that person who's at high or very high risk, can you prevent them from developing cardiovascular toxicity? And so now there are some studies that are ongoing looking at different agents, the traditional beta blockers, ACE inhibitors and Arbs, but importantly statins, there's a lot of interest in that and SGLT 2 inhibitors, really promising data looking at the potential benefit even in non diabetics of preventing cardiovascular toxicity. So it's a real exciting area. We don't know the a lot of the answers yet, but I believe that we should be more proactive in trying to prevent these things rather than reactive as oncologists and waiting till they get into trouble and then consulting our cardiology colleagues. Speaker 2 In the future looks exciting, but bringing it back to my clinic. So I have a patient, I'm hyper vigilant. These patients are going for their screening echocardiogram. The way the EF is being reported, the modalities are also changing. So a patient in front of me, stable EF, but the cardiologist also reported GLS. What to do if a patient with stable EF but a GLS increase is reported What am I making out of that? So let's say if the EF is preserved but the GLS continues to go up and down in my clinical settings, do I need to change my practice based on that? Any opinion on day in day out what I need to worry about in my clinic with this? Speaker 1 And so sorry Susan, before you search, if you could define GLS for our audience as well, please. Speaker 3 Of course, fair question. So GLS stands for Global Longitudinal Strain, and essentially it is thought to be a more sensitive indicator of LV dysfunction. So GLS really looks at the difference between diastole and systole and the heart, and you get a number, let's say a number of -18 so -18 meaning the difference between those two, the diastole and systole. And So what happens is as the left ventricular becomes more dysfunctional, that number drops because you're not getting the same difference, You're not getting the same pumping action. So you, however, you should never make a clinical decision based on GLS changes alone. This is an early indicator that your patient might be getting into trouble. And so my feeling is if you see a difference or a change of about 15% of the current standard, that's an early sign for you that maybe you should contact your cardiologist or cardiologist, the oncologist that this patient might be getting in trouble. So often you see the GLS drop, but then the before the LVEF. So I have reached out to my sort of cardiology oncology colleagues and I've advocated that I would like them to put a line in that echo report saying if this, then this to help, you know, oncologist because I don't expect them to understand what that means, but it's actually being advocated for all the echoes that are being done now. Speaker 2 I really appreciate that because day in, day out, like I said, this is something we see in our clinic very frequently. Speaker 1 Susan, looking ahead, any particular major research priorities and initiatives happening in cardio oncology that we should have it on our radar? Research priorities and initiatives in cardio oncology Yeah, thank you for asking that. So this is my my sort of thoughts around how we should approach cancer patients and their care in 2024. I think it's no longer adequate just to see a patient and say you should get, you know, drug X or you should be treated with this radiation that we need to think about the whole person. So what I would say for oncologist both in the community and academic centers, look at your whole patient, assess them at the beginning, look at their risk factors, try and see if you can determine whether they're at low or high risk. Then they can start their therapy hopefully in good shape. If they develop problems, reach out early to a cardio oncologist. And importantly, we have to also think about lifestyle as our patients are going through the treatment. So advocate for exercise, smoking, sensation, lowering of their BMI. Where research is really going in this area, as I alluded to earlier, is looking at what we call primary prevention strategies. They of course are looking at better drugs to try and deal with cardiovascular toxicity. And then the third area that's really been under researched is after completion of your cancer therapy into survivorship. You know, we discharge these people from our practices and then we hear five years down the road that they've developed heart failure. We need to find a way to actively monitor these patients that are high risk and intervene much earlier. So it's that whole once you know, once you're diagnosed with cancer, you're automatically a cancer survivor. We have to put as much intensity and interest in not just treating their cancer, but what happens to them after they finish that into survivorship. Speaker 1 This has been incredibly insightful. Conclusion Thank you so much, Susan, for going over this very important topic. And it is important for our listeners to know, as you stress that we need to treat the person as a whole. As a result, please, please, please tie in the cardiac colleagues much sooner before it gets too late. As you cited, that preventative measure is more important than reactive. Thank you so much for joining us for this podcast. Speaker 3 Oh, you're most welcome. Speaker 2 Today we had a chance to discuss the important topic of cardio oncology with Doctor Susan Dent, a president of the International Cardio Oncology Society and a medical oncologist at Duke University. Not only do anthrocyclines or anti her two therapies have cardiac side effects, but we have to be mindful of this with immune checkpoint inhibitors, anti EGFR and the newer class antibody drug conjugates. Speaker 1 Being proactive in your approach in collaborating with your cardiology colleagues is critical so that our patients are not only surviving but also thriving. Monitoring their cardiac function with echocardiogram and keeping newer tools such as global longitudinal strain is extremely important. As Doctor Dent stated previously, let's make sure that we are curing cancers but also saving hearts. Thank you for joining us. Stay tuned for more practice changing and informing discussions. We are the oncology brothers.