Radiation dose associated with increased heart disease in Hodgkin lymphoma survivors

1. In a retrospective review of over 1500 Hodgkin lymphoma (HL) survivors, the risk of coronary heart disease (CHD) was significantly associated with radiation doses to the heart in a linear, dose-dependent manner.

Evidence Rating Level: 3 (Average)

Study Rundown: Improvements in the management of HL have led to an increased number of long-term survivors. However, there is a paucity of data on the long-term health outcomes of this patient population. Previous studies of breast cancer survivors have found a dose-dependent relationship between radiation exposure to the heart and risk for CHD. The purpose of this nested case-control study was to evaluate the dose-response curve for cardiac radiation and CHD among HL survivors.

The trial retrospectively reviewed the 5-year outcomes of over 1500 HL survivors for incident cases of CHD and calculated their relevant radiation exposure. At the conclusion of the trial, there was a significant linear dose-response relationship between cardiac radiation dose and risk for CHD. This translated into a 2.5-fold increase in risk per 20 Gray (Gy) of mediastinal radiation exposure. Additionally, traditional risk factors such as hypertension, obesity, and smoking were also independent risk factors for CHD in this patient population. Although the study is limited by the calculation of cardiac radiation dose based on cardiac volume rather than specific dosimetry to the coronary arteries, this was the first study to describe the linear dose-response relationship of radiation exposure to CHD. Furthermore, it highlights the need for further information about the long-term cardiovascular morbidities in this population and re-emphasizes the key role in lifestyle modifications to reduce cardiovascular risk.

Click to read the study in JCO

Relevant Reading: Risk of ischemic heart disease in women after radiotherapy for breast cancer

In-Depth [retrospective cohort]: This was a nested case-control study of 5-year HL survivors who developed CHD. The patient population was obtained from a large registry of HL survivors treated in the Netherlands between 1965 and 1995. Cases (n = 325) were patients who developed CHD, defined as symptomatic myocardial infarction or angina pectoris requiring intervention. Each case was matched with four controls (n = 1204) from the cohort matched for sex, age at HL diagnosis, and date of HL diagnosis. Radiation exposure was determined via mean heart dose (MHD). The outcome of interest was the calculated odds ratios for CHD and estimated the dose-response relationship between cardiac radiation exposure and CHD. At the conclusion of the trial, mediastinal radiation therapy was associated with 2.63-fold increased risk of CHD (95% CI, 1.74 – 3.99; p < 0.001). A linear dose-response relationship was observed, with a 2.48-fold increased risk at MHD at 20 Gy exposure (95% CI: 1.66 – 3.96; p < 0.001). Additionally, 25% of cases had at least one known CHD risk factor, such as family history (RR, 2.87; 95% CI: 1.41 – 5.88), hypertension (RR: 1.85; 95% CI: 1.28 – 2.66), obesity at the time of CHD diagnosis (RR: 1.64; 95% CI: 1.24 – 2.16), or smoking within 5 years before their diagnosis of CHD (RR: 1.56; 95% CI: 1.13 – 2.15).

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