Increasing Heart RT Raises Risk of Heart Disease in Hodgkin Survivors

An increased risk for coronary heart disease (CHD) was found with increasing mean heart dose of radiation in survivors of Hodgkin lymphoma, according to the results of a case-control study published in the Journal of Clinical Oncology.

“To our knowledge, we are the first to show a linear radiation dose-response relationship for CHD in Hodgkin lymphoma survivors,” wrote Frederika A. van Nimwegen, MSc, of the Netherlands Cancer Institute in Amsterdam, and colleagues. “This knowledge may help clinicians to predict the risk of CHD in Hodgkin lymphoma patients treated today, as well as in survivors, and will assist in defining appropriate follow-up care for Hodgkin lymphoma survivors.”

Improved treatment of Hodgkin lymphoma has led to survival rates of greater than 80%; however, as survivors live longer, treatment with radiation and chemotherapy has led to increased cardiac-related morbidity and mortality.

Therefore, in this study, van Nimwegen and colleagues wanted to assess if there was a dose-response relationship between cardiac radiation dose and risk for CHD. They looked at 2,617 survivors of Hodgkin lymphoma who were treated for their disease between 1965 and 1995. They collected information from 325 cases in which patients were diagnosed with CHD as their first cardiovascular event after Hodgkin lymphoma, and 1,204 matched controls.

The median time between Hodgkin lymphoma and diagnosis of CHD was 19 years. The researchers found that the risk for heart disease increased linearly with an increasing mean heart dose of radiation, with an excess relative risk (ERR) of 7.4% per Gy.

According to the researchers, patients who received a mean heart dose of 20 Gy from mediastinal radiotherapy had a 2.5-fold increased risk for heart disease compared with patients who did not have mediastinal radiotherapy.

“Excess relative risks seemed to be highest in the lowest tertile of age at Hodgkin lymphoma diagnosis (ERR_{< 27.5 years}, 20.0%/Gy [95% confidence interval (CI), 5.4%–70.5%]) and decreased for the middle (ERR_{27.5–36.4 years}, 8.8%/Gy [95% CI, 2.6%–22.9%]) and third tertile (ERR_{36.5–50.9 years}^, 4.2%/Gy [95% CI, 0.6%–11.1%]), although this difference was not statistically significant,” the researchers wrote.

The researchers also looked at patient-related risk factors for heart disease. One in four cases had at least one cardiovascular risk factor prior to diagnosis with heart disease. Hypertension (relative risk [RR], 1.85) was associated with an increased risk for CHD. The researchers also found that smoking within 5 years (RR, 1.56) and obesity at the time of diagnosis (RR, 1.64) were both associated with an increased risk for heart disease.

Finally, the researchers found that the cases that had completed more than 3 hours per week of physical activity at follow-up had a reduced risk for developing heart disease compared with cases with less than 1 hour per week (RR, 0.52).

“Our findings regarding both exercise and cardiac risk factors, in combination with previous evidence regarding cardiac risk factors, underline the importance of risk factor control and maintenance or adoption of a healthy lifestyle after Hodgkin lymphoma treatment,” the researchers wrote.