We assessed cardiovascular disease (CVD) incidence in 1474 survivors of Hodgkin lymphoma (HL) younger than 41 years at treatment . Multivariable Cox regression and competing risk 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 with 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 at least 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] were 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 conclu IntroductionOver the past decades, survival of patients treated for Hodgkin lymphoma (HL) has improved dramatically, as a result of the development of multiagent chemotherapy (CT), more accurate radiotherapy (RT), and enhanced possibilities to reduce treatment complications. 1 Unfortunately, the improved prognosis of HL has been accompanied by long-term toxicity, such as elevated risks of second primary malignancies, 2-9 cardiovascular disease (CVD), 2,3,[8][9][10] and infections. 2,8,9 Increased mortality of cardiac disease after mediastinal radiotherapy for HL has been reported in several studies. 2,3,[8][9][10] Dose-dependent anthracycline-induced cardiotoxicity has been observed in survivors of malignancies other than HL, who were usually treated with higher anthracycline doses. 11,12 It is not known, therefore, whether anthracyclines add to the increased risk of CVD from mediastinal RT for survivors of HL. This is an important clinical question because most patients with HL now receive anthracycline-containing chemotherapy. Although a few studies reported on nonfatal cardiac events, comparisons with the general population were usually not made, because in most countries CVD incidence rates are not available. [13][14][15][16][17][18] The purpose of our study was to assess the long-term risk of various CVDs in a cohort of 1474 five-year survivors of HL treated between 1965 and 1995.Unique features of this study include long and near complete follow-up and the availability of complete treatment data, including radiation fields and chemotherapeutic agents. In addition, we compared the incidence of various CVDs with population-based reference rates from the general population, we accounted for competing risk of death from any cause, and we incorporated cardiac risk factors in the analyses. Patients and methods Data collection proceduresWe included all 5-year survivors of HL diagnosed before age 41 years (n ϭ 148...
The main cause of death among HD patients was lymphoma, but after 20 years, HD mortality was negligible. The RRs and AERs of death from second primary cancers (SCs) and CVDs continued to increase after 10 years. Even more than 30 years after diagnosis, HD patients experienced elevated risk of death from all causes other than HD. Increased risk of death from SCs and CVDs was found especially in patients treated before age 21, but these risks seemed to abate with age.
Radiotherapy and chemotherapy increased the risk of developing SMN or CVD to a similar extent as smoking. Subdiaphragmatic radiotherapy strongly increases the risk of SMNs but not of CVD, whereas chemotherapy increases the risks of both SMNs and CVDs. Prolonged follow-up after chemotherapy is needed to reliably compare the late complications of radiotherapy and chemotherapy after 20 years.
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