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Cardiovascular diseases are increasingly recognized as late effects of Hodgkin lymphoma (HL) treatment. The purpose of this study was to identify the risk factors for coronary heart disease (CHD) and to quantify the effects of radiation dose to the heart, chemotherapy, and other cardiovascular risk factors.We conducted a nested case-control study in a cohort of 2,617 5-year HL survivors, treated between 1965 and 1995. Cases were patients diagnosed with CHD as their first cardiovascular event after HL. Detailed treatment information was collected from medical records of 325 cases and 1,204 matched controls. Radiation charts and simulation radiographs were used to estimate in-field heart volume and mean heart dose (MHD). A risk factor questionnaire was sent to patients still alive.The median interval between HL and CHD was 19.0 years. Risk of CHD increased linearly with increasing MHD (excess relative risk [ERR]) per Gray, 7.4%; 95% CI, 3.3% to 14.8%). This results in a 2.5-fold increased risk of CHD for patients receiving a MHD of 20 Gy from mediastinal radiotherapy, compared with patients not treated with mediastinal radiotherapy. ERRs seemed to decrease with each tertile of age at treatment (ERR/Gy(<27.5years), 20.0%; ERR/Gy(27.5-36.4years), 8.8%; ERR/Gy(36.5-50.9years), 4.2%; P(interaction) = .149). Having ≥ 1 classic CHD risk factor (diabetes mellitus, hypertension, or hypercholesterolemia) independently increased CHD risk (rate ratio, 1.5; 95% CI, 1.1 to 2.1). A high level of physical activity was associated with decreased CHD risk (rate ratio, 0.5; 95% CI, 0.3 to 0.8).The linear radiation dose-response relationship identified can be used to predict CHD risk for future HL patients and survivors. Appropriate early management of CHD risk factors and stimulation of physical activity may reduce CHD risk in HL survivors.

Original publication




Journal article


Journal of clinical oncology : official journal of the American Society of Clinical Oncology

Publication Date





235 - 243


Frederika A. van Nimwegen, Michael Schaapveld, Michael Hauptmann, Karen Kooijman, Berthe M.P. Aleman, and Flora E. van Leeuwen, Netherlands Cancer Institute, Amsterdam; Michael Schaapveld, Netherlands Comprehensive Cancer Organization; Judith Roesink, University Medical Center Utrecht, Utrecht; Cècile P.M. Janus, Erasmus MC Cancer Institute, Rotterdam; Augustinus D.G. Krol, Leiden University Medical Center, Leiden; Richard van der Maazen, Radboud University Medical Center, Nijmegen, Netherlands; David J. Cutter, and Sarah C. Darby, University of Oxford; and David J. Cutter, Oxford University Hospitals NHS Trust, Oxford, United Kingdom.


Heart, Humans, Hodgkin Disease, Coronary Disease, Radiation Injuries, Risk Factors, Case-Control Studies, Cohort Studies, Dose-Response Relationship, Radiation, Adult, Middle Aged, Survivors, Netherlands, Female, Male