Thymic cancer, a rare type of cancer that has brought patients to Indiana University Health in recent years for treatment, has become the subject of further study between investigators from the Krannert Cardiovascular Research Center and the Indiana University Melvin and Bren Simon Comprehensive Cancer Center at Indiana University School of Medicine, and collaborators at Regenstrief Institute.
“Everyone is born with a thymus; it serves as one of the bases for the immunologic center to fight off infections,” said Abhishek Khemka, MD, associate professor of clinical medicine and an affiliate member of the Krannert Cardiovascular Research Center at IU School of Medicine, of the thymus, which is located behind the lungs below the breastbone. “For most adults, it will disappear, it will envelop and go away; for some people, it stays there. And for an unfortunate few, it will become a tumor and can keep growing.”
Khemka explains the reason he and his colleagues were interested in studying thymic cancer is because IU Health is a referral center nationally and internationally. There is a relatively higher prevalence of thymic cancer in Japan and many patients from that region come to IU Health for a second or third opinion, he said.
“We would see some thymic cancer patients in the hospital with cardiac issues, and we were curious about the cardiac effects that they are dealing with,” Khemka said. “Our question was, how often is the heart a variable in these kinds of patients and should they be worried about downstream effects after their cancer is in remission…Most people with thymic cancer are going to survive the cancer once they’re treated.”
Results of their 17-year retroactive study were published in Frontiers last fall. Investigators compared 296 patients with pathology-confirmed confirmed thymic cancer patients to 2,960 noncancer controls. Researchers concluded that prior to cancer diagnosis, thymic cancer patients (TCPs) had a lower prevalence of hypertension, diabetes mellitus and dyslipidemia, and similar rates of obesity, tobacco uses and pre-existing cardiovascular disease compared to the controls. They were able to stratify patients into low and high risk categories for cardiovascular complications.
Researchers found that after the thymic cancer diagnosis, high-risk TCPs had an increased risk for cardiac events and patients with multiple cardiovascular risk factors receiving radiotherapy or chemotherapy had higher incidents of cardiac events.
“If you are somebody who does not have baseline risk factors, and I mean, you don’t have a history of tobacco use, high blood pressure, high cholesterol, diabetes, or you don’t have a prior history of heart disease, in terms of a heart attack, stroke or heart failure, and so forth, then your risk of having some sort of cardiac event is fairly low,” Khemka said. “If you have one or two of these risk factors, your risk goes up a little bit. But then if you’re somebody who has more than two risk factors at baseline when you’re diagnosed with thymic cancer, your risk is much higher for cardiac complications, especially when receiving radiotherapy or chemotherapy.”
Khemka said that patients with those higher risk factors are more at risk of mortality and said those are the patients they would advocate to get a baseline screening, such as an echocardiogram, and then follow them to see if they have any cardiac issues. Cardiooncologists typically consult with the oncologist about their treatment plan and take into consideration any medications that may be cardiotoxic. 
“If the person has a severely reduced heart function, their ejection fraction is really low, or they have other concerning findings, we may say this person is high-risk. Therefore, maybe we don’t treat them with the standard agent and instead work with the oncologists on the best cancer therapy with the least cardiac risk,” Khemka said.
A secondary objective of their study was to see if patients who experienced loss of muscle function, called paraneoplastic syndrome, would also show an increased incidence of cardiovascular disease, and in their study, they did not, Khemka said.
With the support of Regenstrief Institute in this study, researchers were able to analyze patient outcome data of patients in Indiana and neighboring states via the Indiana Network for Patient Care. It represents the largest health information exchange nationally with more than 100 healthcare entities providing data, including hospitals, health networks and insurance providers.
“The Indiana Network for Patient Care offers a fairly comprehensive view of the health history of patients in Indiana — and is thus a great basis to conduct this type of study,” said Titus K. Schleyer, DMD, MBA, PhD, a research scientist at the Center for Biomedical Informatics at the Regenstrief Institute, professor of medicine at IU School of Medicine and Khemka’s collaborator. “Being able to put health records together from many healthcare facilities and analyze them in detail enables cutting-edge research that benefits people in Indiana and beyond.”
Other co-authors of the study included Suparna C. Clasen, MD, Patrick J. Loehrer, MD, Anna R. Roberts, Lilian Golzarri-Arroyo, Sunil S. Badve, MD, Subha V. Raman, MD and Siu L. Hui, PhD.
