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Blood, 1 March 2007, Vol. 109, No. 5, pp. 1878-1886.
Prepublished online as a Blood First Edition Paper on November 21, 2006; DOI 10.1182/blood-2006-07-034405.
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Submitted July 12, 2006
Accepted October 4, 2006
Late cardiotoxicity after treatment for Hodgkin's lymphoma
Berthe M.P. Aleman, Alexandra W. van den Belt-Dusebout, Marie L. De Bruin, Mars B. van 't Veer, Margreet H.A. Baaijens, Jan Paul de Boer, Augustinus A.M. Hart, Willem J. Klokman, Marianne A. Kuenen, Gabey M. Ouwens, Harry Bartelink, and Flora E. van Leeuwen*
Dept of Radiotherapy, The Netherlands Cancer Institute, Amsterdam, Netherlands
Dept of Epidemiology, The Netherlands Cancer Institute, Amsterdam, Netherlands
Dept of Hematology, Dr Daniel den Hoed Cancer Center, Rotterdam, Netherlands
Dept of Radiotherapy, Dr Daniel den Hoed Cancer Center, Rotterdam, Netherlands
Dept of Medical Oncology, The Netherlands Cancer Institute, Amsterdam, Netherlands
* Corresponding author; email: f.v.leeuwen{at}nki.nl.
We assessed cardiovascular disease (CVD)-incidence in 1,474 Hodgkin's lymphoma (HL) survivors younger than 41 years at treatment (1965-1995). Multivariable Cox regression and competing risks analyses were used to quantify treatment-effects on CVD-risk. After a median follow-up of 18.7 years, risks of myocardial infarction (MI) and congestive heart failure (CHF) were strongly increased compared to the general population [Standardized Incidence Ratios (SIRs)=3.6 and 4.9, respectively], resulting in 35.7 excess cases of MI and 25.6 excess cases of CHF per 10,000 patients/year. SIRs of all CVDs combined remained increased for 25 years and were more strongly elevated in younger patients. Mediastinal radiotherapy significantly increased the risks of MI, angina pectoris, CHF and valvular disorders (2- to 7-fold). Anthracyclines significantly added to the elevated risks of CHF and valvular disorders from mediastinal RT (Hazard Ratios (HRs): 2.81 and 2.10, respectively). The 25-year cumulative incidence of CHF after mediastinal radiotherapy and anthracyclines in competing risk analyses was 7.9%. In conclusion, risks of several CVDs are 3- to 5-fold increased in HL-survivors compared to the general population, even after prolonged follow-up, leading to increasing absolute excess risks over time. Anthracyclines further increase the elevated risks of CHF and valvular disorders from mediastinal radiotherapy.

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