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Matthew C. Hull, MD; Christopher G. Morris, MS; Carl J. Pepine, MD; Nancy Price Mendenhall, MD

JAMA. 2003;290:2831-2837.

Context  The majority of patients with Hodgkin lymphoma are young and highly curable. This necessitates concern for prevention, diagnosis, and optimal management of potential treatment-related complications.

Objective  To identify and quantify the incidence of and factors contributing to long-term cardiac and vascular complications after radiation therapy for Hodgkin lymphoma.

Design and Setting  Retrospective study comparing patients treated from 1962 to 1998 at a university–based referral center with a matched general population.

Patients  Four hundred fifteen consecutive patients who fulfilled the inclusion criteria of a minimum 2-year follow-up (median, 11.2 years) and whose radiation fields included the heart or carotid or subclavian arteries.

Main Outcome Measures  Multivariable analyses of potential risk factors and observed-to-expected ratios for cardiac valve surgery, coronary artery bypass graft surgery, percutaneous coronary intervention, or both based on Surveillance, Epidemiology, and End Results (SEER) and National Hospital Discharge Survey (NHDS) data.

Results  Forty-two patients (10.4%) developed coronary artery disease at a median of 9 years after treatment, 30 patients (7.4%) developed carotid and/or subclavian artery disease at a median of 17 years after treatment, and 25 patients (6.2%) developed clinically significant valvular dysfunction at a median of 22 years. The most common valve lesion was aortic stenosis, which occurred in 14 valves. The observed-to-expected ratio for valve surgery was 8.42 (95% confidence interval [CI], 3.20-13.65) and the observed-to-expected ratio for coronary artery bypass graft surgery or percutaneous coronary intervention was 1.63 (95% CI, 0.98-2.28). At least 1 cardiac risk factor was present in all patients who developed coronary artery disease. The only treatment-related factor associated with the development of coronary artery disease was utilization of a radiation technique that resulted in a higher total dose to a portion of the heart (relative risk, 7.8; 95% CI, 1.1-53.2; P = .04) . No specific treatment-related factor was associated with carotid or subclavian artery disease or valvular dysfunction. Freedom from any cardiovascular morbidity was 88% at 15 years and 84% at 20 years.

Conclusions  Among patients treated with radiation therapy for Hodgkin lymphoma, there are statistically higher than expected rates of valve surgery and coronary revascularization procedures over the next 10 to 20 years. Coronary vascular disease is associated with higher radiation doses and traditional coronary heart disease risk factors. Noncoronary vascular disease and clinically important valvular dysfunction are less well understood complications at 15 to 20 years after radiation, requiring surveillance and further study.

Author Affiliations: Departments of Radiation Oncology (Drs Hull and Mendenhall and Mr Morris) and Medicine (Dr Pepine), University of Florida College of Medicine, Gainesville.

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