Late cardiotoxicity after treatment for Hodgkin lymphoma

Abstract

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...

Long‐term risk of cardiovascular disease in Hodgkin lymphoma survivors—Retrospective cohort analyses and a concept for prospective intervention

“…7,22,23 Two recent large cohort studies from the Netherlands and UK show an increased standardized mortality rate in CVD that is probably attributed to radiotherapy and adriamycin. 5,4 The UK study also found a significant relation to vincristin. 4 The Dutch study, which was a matched control study, found that there was a general increase in the risk for in patient care for CVD in patients treated for HL.…”

“…The risk is particularly high in patients treated before the age of 40 years. [4][5][6][7][8] If given high doses, radiotherapy (RT) damages the endothelial cells, causes fibrosis of the valves, and induces myocardial injury and cardiomyopathy. 9 Therapy with adriamycin is a known risk factors for the development of cardiomyopathy.…”

Cardiovascular effects of radiotherapy on the patient with cancer

“…16,21,23 CAD risk begins to increase during the first five years after irradiation and continues for at least 20 years. 21,22 There is no statistically significant difference between patients with or without risk factors for CAD at the time of radiotherapy. 22 The increase in CAD is directly proportional to the average dose of radiation and heart volume included in the RT field.…”

“…Incidental exposure of the heart to RT increases the incidence of accelerated or premature coronary artery disease (CAD), [20][21][22] commonly identified in young or relatively young patients with none of the major risk factors for atherogenesis, such as smoking, diabetes mellitus, dyslipidemia, hypertension and a family history of early atherosclerosis. 16,21,23 CAD risk begins to increase during the first five years after irradiation and continues for at least 20 years.…”

Anticancer chemotherapy in teenagers and young adults: managing long term side effects

“…In a study of Hodgkin's lymphoma survivors, the actuarial risk of congestive heart failure 25 years after diagnosis was 0.4% with non-anthracycline chemotherapy without mediastinal radiotherapy, 7.5% with non-anthracycline chemotherapy and concurrent mediastinal radiotherapy, and 10.7% with anthracyclines and mediastinal radiotherapy. 11 …”