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Lancet Haematol. 2015 Nov;2(11):e492-502. doi: 10.1016/S2352-3026(15)00153-2. Epub 2015 Oct 22.

Cardiovascular disease after treatment for Hodgkin's lymphoma: an analysis of nine collaborative EORTC-LYSA trials.

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Department of Oncology, Rigshospitalet, Copenhagen, Denmark. Electronic address:
European Organisation of Research and Treatment of Cancer, Brussels, Belgium.
Department of Oncology, Rigshospitalet, Copenhagen, Denmark.
Department of Oncology, Rigshospitalet, Copenhagen, Denmark; Niels Bohr Institute, Department of Science, University of Copenhagen, Copenhagen, Denmark.
Department of Internal Medicine, VU University Medical Centre, Amsterdam, Netherlands.
National Cancer Institute, Cairo University, Cairo, Egypt.
Centre de Traitement des Données du Cancéropôle Nord-Ouest, Centre François Baclesse, Caen, France.
Department of Radiation Oncology, Netherlands Cancer Institute, Amsterdam, Netherlands.
Department of Hematology, Radboud University Medical Center, Nijmegen, Netherlands.
Department of Radiation Oncology, ZNA Middelheim and University of Antwerp, Antwerp, Belgium.
Department of Radiation Oncology, Champalimaud Cancer Centre, Lisbon, Portugal.
Department of Hematology, University Medical Centre Groningen, University of Groningen, Groningen, Netherlands.
Department of Hematology, CHU de Nancy Hôpital de Brabois, Nancy, France.
Department of Hematology, CHU de Dijon Complexe du Bocage, Dijon, France.
Department of Oncology, Rigshospitalet, Copenhagen, Denmark; Department of Hematology, Rigshospitalet, Copenhagen, Denmark.



Cardiovascular disease after treatment is an important concern in cancer survivors. However, knowledge of cardiotoxicity is limited by the retrospective nature of data, which often does not contain details of treatment exposure. To facilitate individual risk counselling of patients, we aimed to quantify the effect of anthracyclines, vinca-alkaloids, and radiotherapy on the risk of cardiovascular disease in patients treated for Hodgkin's lymphoma.


In 2009-10, a Life Situation Questionnaire (LSQ) was distributed to patients by mail to assess late-onset effects of Hodgkin's lymphoma treatment in patients who were included in nine successive European Organisation for Research and Treatment of Cancer (EORTC) and the Groupe d'Etude des Lymphomes de l'Adulte (GELA, now renamed LYSA) randomised trials between 1964 and 2004. We reconstructed the mean radiation doses to the heart and carotid arteries and the cumulative doses of anthracyclines and vinca-alkaloids for all patients. Incidence of cardiovascular disease was reported during follow-up and updated through the LSQ. We applied Cox proportional hazards regression analyses to quantify the effect of chemotherapy and radiation on the risk of a first cardiovascular disease event.


Information of primary treatment was complete for 6039 patients (median age at diagnosis 30 years [IQR 23-40]; median length of follow-up 9 years [6-14]). 1919 patients responded to the LSQ. 1238 first cardiovascular events were recorded in 703 patients, most were ischaemic heart disease (132 [19%]), congestive heart failure (85 [12%]), arrhythmia (110 [16%]), and valvular disease (77 [11%]). The mean heart radiation dose per 1 Gy increase (HR 1·015 [95% CI 1·006-1·024], p=0·0014) and the dose of anthracyclines per 50 mg/m(2) increase in cumulative dose (1·077 [1·021-1·137], p=0·0064) were significant predictors of cardiovascular disease. Cumulative dose of vinblastine (unadjusted model p=0·77), vincristine (p=0·36), and mean radiation dose to the left (p=0·41) or right (p=0·70) internal carotid artery did not predict for cardiovascular events.


Quantification of the increased cardiovascular risk with specific doses of radiation and anthracycline exposure will enable a quantitative assessment of the optimum combination of systemic therapy and radiation, which will help clinicians to balance the risks and benefits of different regimens for individual patients.


Rigshospitalet Research Committee, the EORTC Cancer Research Fund, and the Sally Snowman Survivorship Fellowship.

[Indexed for MEDLINE]

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