Journal of the National Cancer Institute Advance Access published online on June 17, 2009
JNCI Journal of the National Cancer Institute, doi:10.1093/jnci/djp147
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© The Author 2009. Published by Oxford University Press.
ARTICLES |
Increased Risk of Stroke and Transient Ischemic Attack in 5-Year Survivors of Hodgkin Lymphoma
Affiliations of authors: Department of Epidemiology (MLDB, FEvL), Department of Neuro-Oncology (WB), and Department of Radiotherapy (BMPA), the Netherlands Cancer Institute, Amsterdam, the Netherlands; Donders Institute for Brain, Cognition and Behavior, Radboud University Nijmegen Medical Centre, Nijmegen, the Netherlands (LDAD, ACK); Department of Hematology, Erasmus MC, Daniel den Hoed Cancer Center, Rotterdam, the Netherlands (MBvV); Department of Radiotherapy, Leiden University Medical Center, Leiden, the Netherlands (ADGK); Department of Pediatric Oncology, Emma Children's Hospital/Academic Medical Center, University of Amsterdam, Amsterdam, the Netherlands (HJvdP)
Correspondence to: Flora E. van Leeuwen, PhD, Department of Epidemiology, the Netherlands Cancer Institute, Plesmanlaan 121, 1066 CX Amsterdam, the Netherlands (e-mail: f.v.leeuwen{at}nki.nl).
Background: Information on clinically verified stroke and transient ischemic attack (TIA) following Hodgkin lymphoma is scarce. We quantified the long-term risk of cerebrovascular disease associated with the use of radiotherapy and chemotherapy in survivors of Hodgkin lymphoma and explored potential pathogenic mechanisms.
Methods: We performed a retrospective cohort study among 2201 five-year survivors of Hodgkin lymphoma treated before age 51 between 1965 and 1995. We compared incidence rates of clinically verified stroke and TIA with those in the general population. We used multivariable Cox regression techniques to study treatment-related factors and other risk factors. All statistical tests were two-sided.
Results: After a median follow-up of 17.5 years, 96 patients developed cerebrovascular disease (55 strokes, 31 TIAs, and 10 with both TIA and stroke; median age = 52 years). Most ischemic events were from large-artery atherosclerosis (36%) or cardioembolisms (24%). The standardized incidence ratio for stroke was 2.2 (95% confidence interval [CI] = 1.7 to 2.8), and for TIA, it was 3.1 (95% CI = 2.2 to 4.2). The risks remained elevated, compared with those in the general population, after prolonged follow-up. The cumulative incidence of ischemic stroke or TIA 30 years after Hodgkin lymphoma treatment was 7% (95% CI = 5% to 8%). Radiation to the neck and mediastinum was an independent risk factor for ischemic cerebrovascular disease (hazard ratio = 2.5, 95% CI = 1.1 to 5.6 vs without radiotherapy). Treatment with chemotherapy was not associated with an increased risk. Hypertension, diabetes mellitus, and hypercholesterolemia were associated with the occurrence of ischemic cerebrovascular disease, whereas smoking and overweight were not.
Conclusions: Patients treated for Hodgkin lymphoma experience a substantially increased risk of stroke and TIA, associated with radiation to the neck and mediastinum. Physicians should consider appropriate risk-reducing strategies.
| CONTEXT AND CAVEATS Prior knowledge There have been few studies to date on the long-term influence of treatment for Hodgkin lymphoma on incidence of stroke and transient ischemic attack (TIA). Study design The authors studied incidence of stroke and TIA among 2201 five-year survivors of Hodgkin lymphoma in the Netherlands. Incidence was stratified by sex, age, treatment period, cerebrovascular risk factors, type of chemotherapy, and radiation field. Hazard ratios (HRs) were calculated on the basis of Cox regression analyses. Contribution After a median follow-up of 17.5 years, 96 patients developed cerebrovascular disease: 47 with ischemic strokes, eight with hemorrhagic or unknown strokes, 31 with TIAs, and 10 with ischemic strokes and TIAs. Incidence of stroke was 2.2, and of TIA, was 3.1 times the incidence in the general population. Radiation to the neck and mediastinum was associated with increased risk (HR = 2.5), whereas treatment with chemotherapy was not. Implications Most survivors of Hodgkin lymphoma are at increased risk for cerebrovascular events, and risk-reducing strategies should be considered. Limitations Precise information on radiation dosage was lacking in this study, and in some cases, the etiology of cerebrovascular events was unknown. From the Editors
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Manuscript received October 14, 2008; revised April 7, 2009; accepted April 29, 2009.
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J Natl Cancer Inst 2009 101: 901.
J Natl Cancer Inst 2009 101: 901.