CHICAGO — Heart disease-related death among patients with esophageal cancer who are treated with radiation may be detectable as early as 8 months from diagnosis, according to findings presented at the ASCO 2015 annual meeting.
“It is known that radiation can cause cardiac toxicity,” study investigator Shane Lloyd, MD, told Healio.com. “In the short term, patients can have pericarditis and, longer-term, patients can experience an increased risk of coronary artery disease after radiation therapy to the heart. Our study was done to clarify the risks of this particular cancer treatment, even if the benefits may outweigh those risks.”
Lloyd, an assistant professor of radiation oncology at the University of Utah School of Medicine and Huntsman Cancer Institute, and colleagues identified 40,778 patients with esophageal cancer from the SEER database and divided patients into two groups. The first group included patients with esophageal cancer who had been treated with radiation (n = 26,377); the second comprised patients with esophageal cancer who had not been treated with radiation (n = 14,401). They analyzed heart disease-specific survival in both groups.
Patients receiving radiation were determined to be at an increased risk for heart disease-related death compared with those who did not undergo radiation (P < .05). The absolute risk of heart disease-related death was 2.8%, 5.3% and 9.4% at 5, 10 and 20 years, respectively. Analysis of heart disease-specific survival via log rank test demonstrated the risk for heart disease-related death was evident as early as 8 months after diagnosis (P < .05).
“Sometimes we think of cardiac toxicity as a more long-term complication of radiation therapy, but this study shows that, even in the first year, it is an issue,” Lloyd said.
Andrew Ko, MD, professor in the department of medicine, division of hematology/oncology, at the University of California, San Francisco, called the evidence of this early toxicity “striking.” He says the finding can serve as a reminder for physicians to be vigilant about both acute and longer-term toxicities when recommending radiation to patients with esophageal cancer.
Lloyd and Ko both noted other factors of illness that may contribute to this increased risk.
“The esophagus is right in the mediastinum, which is where the heart is,” Ko said. As a result, “there’s not going to be a way to avoid” exposing the heart to radiation.
The course of esophageal cancer may also play a role, Lloyd told Healio.com.
“Patients with esophageal cancer generally have a lot of de-conditioning over the course of their illness,” he said. “They may be malnourished. Their heart may be introduced to stress that comes solely from the disease and not necessarily from the treatment. So that probably increases their risk, although our study wasn’t designed to detect that.”
Ko and Lloyd also both pointed to the natural process of aging.
“These are obviously patients who might be at heightened risk for heart disease anyway – they’re older [and] they may have certain medical comorbidities that increase their risk for heart disease,” Ko said.
Patients with cancer, including esophageal cancer, are “still at risk for all the problems of normal aging,” Lloyd said, which can include heart disease and “other causes of death in an elderly population.”
“Unfortunately, less than 10% of the patients in our study survived 10 years,” Lloyd said. “Those who did … do face the normal risks of aging. They would have been diagnosed with a variety of illnesses [that] are associated with old age, including coronary artery disease.”
Study implications, next steps
Lloyd compares the prognosis for esophageal cancer, and the use of radiation therapy for this disease, to that of breast cancer.
“[Esophageal cancer] is a disease that portends a poor prognosis compared with some other cancers,” he said. “In breast cancer, we do think about the dose of radiation going to the heart and we’re not willing to accept a very high dose … because we feel that we can cure patients with breast cancer without much riskto the heart. But with esophageal cancer … because the disease is generally more commonly fatal, we tend not to worry as much about the doses that we’re giving to the heart.”
As a result, Lloyd says the study may raise some questions in the future about whether the radiation doses used in esophageal cancer are too high, as well as the compromise between the doses needed for effective treatment and the potential damage to the heart.
Ko says the results of the study raise “an appropriate concern.”
“I don’t think it changes practice as far as the fact that we still should use radiation treatment whenever appropriate for esophageal cancer,” he said. “But it serves as a reminder in terms of being vigilant about the very real possibility of later toxicities, including cardiac issues.” – by Julia Ernst, MS
Frandsen JE, et al. Abstract 4025.
Presented at: ASCO Annual Meeting; May 29-June 2, 2015; Chicago.
Frandsen J, et al. J Gastrointest Oncol. 2015;doi:10.3978/j.issn.2078-6891.2015.040.
Disclosure: The researchers report no relevant financial disclosures.