As the survival rate of cancer patients increases, many long-term adverse effects of treatment are leading straight to the heart. According to the Surveillance, Epidemiology, and End Results (SEER) Program from the National Cancer Institute, US deaths from cancer rose from 195.4 per 100,000 in 1950 to 206.9 in 1980—but, 30 years later, dropped to 171.8 per 100,000 in 2010. A statistic to be cheered and improved upon; it's a double-edged sword, though, leaving in its wake a new set of patients for cardiologists. What's needed now is a partnership between specialties. Joerg Herrmann, MD, assistant professor of medicine, Mayo Graduate School of Medicine, discusses cardio-oncology with CardioSource WorldNews executive editor Rick McGuire.

Rick McGuire: Oncology meets cardiology: some of the new drugs that have propelled real successes in oncology are creating problems on the cardiology side. First off, what's the issue?

Joerg Herrmann, MD: The good news is that the cancer survivor rate has really improved over the past decade, particularly for breast cancer and lymphomas, leukemias, childhood cancers, and it's to a point that collateral damage related to that improved therapy truly starts to matter. In the past, the paradigm in cancer was to hit hard and hit strong, and then essentially run away and leave whatever is left to the cardiologist if it came to it. Nowadays, the oncologists and hematologists have turned this into a chronic disease process with survivor rates of 90–95% at 5 years plus. So we have to really start thinking about these issues, such as side effects of drugs and radiation therapy, from a cardiovascular standpoint.

A few years ago at an ACC meeting, investigators reported on early heart failure in survivors of breast cancer. Are we seeing more attention paid to this issue?

Initially, as you can imagine, it started in cancer centers—like MD Anderson and Sloan Kettering—with their cardiologists working more closely with their oncologists. Since then, we've seen some momentum with cardio-oncology clinics; most on the east coast, a few in the center of the country, and Cedars-Sinai on the west coast. In Canada they have the Cardio-Oncology Initiative Working Group and in Italy it's the International Group of Cardio-Oncology. So worldwide, it's gaining momentum.

How hard is it for these two groups to come together and work together?

Very hard indeed—that's the short answer. For instance, the European Society of Cardiology came out with a position paper about 2 years ago devoted to this topic. They invited four or five oncologists to join and, as I understand it, a few accepted the invitation; but in the end, I don't think even one showed up. At our institution, we try to foster these efforts—and really feel the need for it—to have these two groups together for consensus papers, position papers, or any type of review, because we are totally seeing it from a different spectrum. It's so important to see both sides.

I imagine, like many things, you need one leader on each side to start talking to each other.

That's correct; otherwise, it doesn't have the fuel to really move forward.

It serves the patients and it should serve the departments, too, because patients are receiving better care, right?

Absolutely. It goes back to the idea of a multidisciplinary approach. The patients are very open to this and are very much appreciative of it. We've had a couple of examples of relatively young patients who were devastated by the fact that they now had heart failure. These patients received anthracylines and trastuzumab and, almost like a classic scenario, developed heart failure. It's bad enough if you have a heart failure patient to begin with, but someone with cancer facing heart failure? That's taking it to another level emotionally and psychologically.

Both the National Cancer Institute and National Heart, Lung and Blood Institute are also recognizing this. In March 2013, they had a 2-day workshop specifically devoted to this. We're seeing support gather for it at the institutional level and hopefully on a national level, too.

Will the effort make a difference?

Although a lot of it is retrospective, there are some really good data that early recognition and treatment, particularly for anthracycline-induced cardiotoxicity, is key to restoring and maintaining cardiac function.

If you miss this window of opportunity and time is passing by, you're fighting a pretty rough battle. This is not just trying to find a new niche—I believe this will really impact outcomes of patients. If they are cured of their cancer, it would be such a pity if they fall victim to heart failure.

At your center, when do you and the oncologist come together? There has been some evidence that the time for heart care is upfront, as patients are getting their cardiotoxic drugs, when you can keep an eye on left ventricular ejection fraction and other things.

We've started to define the algorithms and come together before any cancer therapy is given. Because once a patient is set on a certain pathway, on a certain therapy, the doctors want to finish it. Otherwise, it's like, "Why do we start in the first place?"

We're trying to develop a risk score that will stratify each patient, because there are some factors that you know even before starting chemotherapy that mean a particular individual will be at higher risk. If we were to come up with a certain risk score algorithm to define this, it would help the oncologists and hematologists to say, "In this case, we better take this particular combination." There's also work to do during and after therapy; it's no longer just 10 or 20 years after cancer therapy, we're seeing cardiovascular complications much earlier.

What happens when patients return home from a specialty center? A home that may be clear across the country?

That's obviously a concern. As a tertiary referral center, Mayo has some problems as far as giving recommendations and then seeing patients go elsewhere in this country and other countries. What we do links back to the survivorship program: we give an outline at the first follow-up with the patient as to what should be followed up upon and when, so they have a full template, including cardiovascular. The outline has annual visits and screenings, and then an echo at 5 years—particularly given certain parameters, such as radiation therapy at a certain dose, greater than 30 Gy, although that might be changing, or anthracycline more than 240 mcg/m².

If these patients move into that kind of higher-risk category, based on some of those parameters, then they should be looked after by a cardiologist at 5 years, and every 5 years from there on. When you look, for instance, at radiation-induced disease, where there's coronary artery disease, we do see the incidence of MIs going up after 15 years. It is stenotic occlusive disease, so starting at year 10, we feel clinicians should maybe do a stress test, and repeat it at year 15 post-therapy completion. Our survivorship programs now outline these kinds of protocols: specific landmarks and steps along the road at different years.

You mentioned 30 Gy may be changing: Higher? Lower?

Lower. The old thought was that there is an exponential relationship between dose and effect. But that may not be the case, it might be more linear. For instance, a Nordic study on women was just published in the New England Journal of Medicine. They were well below the 30 Gy–dose spectrum but there was a linear relationship between coronary artery disease and related events and the radiation exposure.

When very careful dose calculation was done they found it was the LAD that received most of the dose. So, mid-LAD is the classic location for stenosis induced by radiation in breast cancer. Now, in Hodgkin's disease it's different, because of the mantle field. You actually get the left main and the right coronary, and in that population there is a 15-fold higher risk of MI, even in asymptomatic people. So, the location may relate to the type of dose, the radiation field, the volume, different parameters. We've become sophisticated with radiation therapy, but it might not be that simple.

What happens when you tell the patient, "You've won your battle against cancer, now let's talk about preventing heart disease"? Do they run out the door or are they girded for battle?

They really are girded for battle. They've already been through a tough battle and they don't want to lose it now in the last round. Once aware of the risk, patients are truly motivated as far as testing and adhering to healthy living.

What are the financial issues here? Are there oncologists and cardiologists trying to figure out who gets paid for what?

Not at all, particularly not at Mayo, as it's not really private practice in that sense. We all have our own individual private practice groups, and that's how it should be. As for cost effectiveness, I think the tests are reasonable and cost effective—it's not like we're running an MRI on everyone. For the initial stratification, what our institution does routinely is an echo before anthracycline-based chemotherapy, and that's reimbursed. Most do an echo once the patient develops heart failure symptoms; we would argue to do it even earlier. I think what will be recommended by the American Society of Echocardiography on screening in these patients. We've now seen one from the European community and this will help insurers I don't think this would be much of an issue as long as they can see the value and the merit of this screening.

It's working at the Mayo Clinic and at some other major centers. Are you optimistic that smaller institutions will be able to develop a cooperation level between cardiologists and oncologists?

Once you see the rationale, yes. All of us want to help the patient and as long as we continue to show we're making a difference, I think this will be picked up. I cannot see any other response to it honestly.