Research has shown that survivors of childhood cancers are more likely to have heart problems later in life compared with their peers who have not had cancer. There's further evidence that increased cardiovascular disease risk is largely attributable to cancer treatments survivors were exposed to. But what research has not yet revealed is how better to lower risk of these problems and how best to screen survivors of childhood cancer.
So says Saro H. Armenian, DO, MPH, a pediatric hematologist/oncologist and Associate Professor in the Departments of Pediatrics and Population Sciences at City of Hope, Duarte, Calif., in a new review paper (J Clin Oncol 2018; doi.org/10.1200/JCO.2017.76.3920).
"We've known through large cohort studies and epidemiologic studies that the magnitude of risk is greater than you would expect in the general population, and it continues to increase with time," Armenian told Oncology Times. "This paper was to really highlight what are some of the directions that we're going to be headed in as we think about ways to improve the lives of our survivors as well as patients are going through treatment today."
So what are some of those directions that need to be explored to solve the problem? Here's what Armenian, who is also Director of both the Childhood Cancer Survivorship Clinic and the Division of Outcomes Research in the Department of Population Sciences at City of Hope, explained to Oncology Times.
1 What are the key paradigms in how cardiovascular disease affects survivors of childhood cancer?
"The paper breaks it down into specific areas. The first area had to do with the scientific community getting a better sense [of] what the mechanisms are for cardiovascular disease in these individuals and how best to study these mechanisms. Because if we understand the mechanism of premature cardiovascular disease, then we can think about more targeted and precise approaches to disease prevention.
"We then grapple the issue of how do you best identify individuals who are at risk. So right now we're in a world of precision medicine, specifically precision oncology. And we think about the tumor makeup as what drives our treatment decisions. And we believe that we can use this same precision medicine approach to identify who is going to be at risk for developing cardiovascular disease. And in turn, think about more targeted approaches for prevention.
"So it might be understanding the treatments [survivors] received in more detail or thinking about the individual's own genetic makeup, and how that may potentially put them at risk for subsequent cardiovascular disease.
"The next area we wanted to focus on was specifically on what are the emerging therapies that are going to be used in the treatment of childhood cancer over the next few decades-and what are the potential long-term side effects that we might be able to anticipate (if we are more active in how we start studying individuals who are being treated with these new drugs).
"We really don't have a good sense to what the long-term side effects are. But we can use paradigms of research that have been successful from previous drugs.
"And then finally we talk about sort of novel paradigms of early detection and screening-and clinical trials that are necessary to help prevent cardiovascular disease."
2 What are the biggest questions that need to be answered to really move the needle in terms of this problem?
"Overall we understand what the disease burden is in this population. What we have not done enough of is developing studies to help prevent these conditions from happening in our patients.
"We are now thinking about new paradigms of disease prevention that combine information obtained from population-based studies about who is at risk with more granular information about individual genetic differences as modifiers of this risk. This precision medicine approach can facilitate the implementation of innovative approaches to disease prevention.
"We are in a position to really launch the next wave of prevention studies so that these severe and life-threatening conditions-like heart failure, stroke, and heart attack-are no longer an issue for our growing number of survivors of childhood cancers."
3 What would you say all practicing oncologists should know about this area of childhood cancer survivorship?
"We in the community who are entrenched in this research can get very stuck in the weeds of it. But from a general oncology practice standpoint, when the patient walks into our office-let's say they're a long-term survivor of a specific cancer-having basic information about their treatment and where that puts them in the spectrum of risk is really important because that drives the kind of monitoring, screening, and conversations that you're going to be having with that patient.
"There are established guidelines for how we define individuals at high risk. Practitioners need to think not just about the conversation they're going to have about heart-healthy lifestyle behaviors, but also about early screening strategies for individuals at highest risk.
"And at the primary care level, it may just be as straightforward as lowering that threshold for that young person who's going to walk in with symptoms that would not cross your mind that would be associated with cardiovascular disease due to their age or due to their health profile. Because they're a survivor of cancer and have been treated with certain drugs or have had certain exposures, they're at an exponentially higher risk. So really lowering that threshold for which you start thinking about doing additional diagnostic studies and not dismissing certain symptoms."