title: Valvular dysfunction and carotid, subclavian, and coronary artery disease in survivors of hodgkin lymphoma treated with radiation therapy.
abstract: BACKGROUND
  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.
  
  
  METHODS
  Retrospective study comparing patients treated from 1962 to 1998 at a university-based referral center with a matched general population.
  
  
  METHODS
  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.
  
  
  METHODS
  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.
authors.affiliation: Department of Radiation Oncology, University of Florida College of Medicine, Gainesville 32610-0385, USA.
authors.forename: Matthew C
authors.initials: MC
authors.lastname: Hull
authors.forename: Christopher G
authors.initials: CG
authors.lastname: Morris
authors.forename: Carl J
authors.initials: CJ
authors.lastname: Pepine
authors.forename: Nancy Price
authors.initials: NP
authors.lastname: Mendenhall
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D016893:Carotid Stenosis / Q000453:epidemiology / Q000209:etiology; D002561:Cerebrovascular Disorders / Q000453:epidemiology / Q000209:etiology*; D002648:Child; D002675:Child, Preschool; D003324:Coronary Artery Disease / Q000453:epidemiology / Q000209:etiology*; D005260:Female; D006349:Heart Valve Diseases / Q000453:epidemiology / Q000209:etiology*; D006689:Hodgkin Disease / Q000532:radiotherapy*; D006801:Humans; D008297:Male; D008875:Middle Aged; D016016:Proportional Hazards Models; D011878:Radiotherapy / Q000009:adverse effects; D011879:Radiotherapy Dosage; D012189:Retrospective Studies; D013349:Subclavian Steal Syndrome / Q000453:epidemiology / Q000209:etiology; D017741:Survivors / Q000706:statistics & numerical data*; D013997:Time Factors