Causes of death after therapy for early stage Hodgkin's disease entered on EORTC protocols

Henry-Amar, Michel; Hayat, M.; Meerwaldt, J.H.; Burgers, Melanie C J; Carde, Patrice; Somers, R.; Noordijk, E.M.; Monconduit, M.; Thomas, José; Cosset, Jean‐Marc; Schueren, Emmanuel van der; Regnier, R; Bron, Dominique; Lutsman-Marechal, J.; Tanguy, Alain; Pauw, Ben de; Tubiana, M

doi:10.1016/0360-3016(90)90221-5

Cited by 95 publications

(31 citation statements)

References 8 publications

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“…9 Other investigators also found age at irradiation to be a major determinant of mortality from CVD. 10,29,30 The higher risks in the patients treated at a younger age may partly be explained by low P values for trends were as follows: for myocardial infarction, P ϭ .001 for age at start of treatment, P ϭ .17 for attained age, and P ϭ .65 for follow-up interval; for angina pectoris, P Ͻ .001 for age at start of treatment, P ϭ .43 for attained age, and P ϭ .001 for follow-up interval; and for congestive heart failure, P Ͻ .001 for age at start of treatment, P Ͻ .001 for attained age; and P ϭ .29 for follow-up interval.…”

Section: Org Frommentioning

confidence: 99%

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Late cardiotoxicity after treatment for Hodgkin lymphoma

Aleman

Belt-Dusebout

Bruin

et al. 2006

Blood

649

438

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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...

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Section: Org Frommentioning

confidence: 99%

“…Increased risks of death from radiation-associated CVD have been frequently described. [8][9][10][29][30][31][32][33][34][35][36] Radiation-induced CVD includes a wide spectrum of pathologies. 37,38 Damage of the vascular endothelium of arteries of different sizes is probably important in the explanation of radiation-induced heart disease.…”

Section: Org Frommentioning

confidence: 99%

Late cardiotoxicity after treatment for Hodgkin lymphoma

Aleman

Belt-Dusebout

Bruin

et al. 2006

Blood

649

438

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“…The combination of excess mortality from cancer or from treatment related complications makes patients treated for Hodgkin's disease die more frequently than matched controls over 20 years of follow-up [1,2]. By 15 years of follow-up, the majority of deaths are related to treatment related complications while deaths from Hodgkin's disease are unusual [1].…”

Section: Introductionmentioning

confidence: 99%

“…It has become apparent that a significant cause of death in patients treated for Hodgkin's disease is related to complications of therapy rather than the cancer itself [1,2]. The combination of excess mortality from cancer or from treatment related complications makes patients treated for Hodgkin's disease die more frequently than matched controls over 20 years of follow-up [1,2].…”

Section: Introductionmentioning

confidence: 99%

Long-term toxicity of the treatment of Hodgkin’s disease

Armitage¹

1998

Annals of Oncology

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SummaryAt the present time, the majority of patients who develop Hodgkin's disease can be cured with radiotherapy and/or chemotherapy. A long follow up of cured patients has shown that the cumulative toxicity from treatment related complications rivals the mortality from Hodgkin's disease. In addition to late fatal complications, delayed adverse effects of therapy on the thyroid, reproductive system, and bones are burdens many patients have to bear. Future treatment regimens for Hodgkin's disease will be designed attempting to minimize these complications. Follow up of those patients now in remission should focus on the prevention of morbidity and mortality by anticipating and preventing late complications.

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“…Several studies have examined excess mortality from major causes in large cohorts of patients with HL, [3][4][5]8,13 but few have analyzed excess mortality by detailed treatment categories. 12 However, Swerdlow et al failed to identify treatment categories (with detailed chemotherapy dose or dose and field of radiation used) linked to an excess risk of death from myocardial infarction.…”

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confidence: 99%

Survival after Hodgkin lymphoma

Favier

Heutte

Stamatoullas‐Bastard³

et al. 2009

Cancer

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BACKGROUND:The objective of this study was to analyze cause‐specific excess mortality in adult patients with Hodgkin lymphoma (HL) with respect to treatment modality.METHODS:The study population consisted of 4401 Belgian, Dutch, and French patients aged 15 to 69, in all stages of disease, who were treated between 1964 and 2000. Excess mortality was expressed by using a standardized mortality ratio (SMR) and calculating the absolute excess risk (AER). Relative survival was calculated and analyzed using a previously described regression model.RESULTS:At a median follow‐up of 7.8 years, 725 of 4401 patients (16.5%) had died, 51% of HL, 10% of treatment‐related toxicity, 18% of second cancer, 5% of cardiovascular diseases, 2% of infections, 8% of other causes, and 6% of an unspecified cause. Overall, the SMR was 7.4 (95% confidence limits [CL], 6.9‐8.0), and the AER was 182.8 (95% CL, 167.7‐198.8). These indicators were 3.8 (95% CL, 3.2‐4.5) and 27.9, respectively, for deaths from a second cancer and 4.0 (95% CL, 2.3‐6.7) and 3.3, respectively for deaths from infection. After 15 years, the observed survival rate was 75%, and the relative survival rate was 80%. In patients with early‐stage disease, the overall excess mortality was associated with age ≥40 years (P = .007), men (P < .001), unfavorable prognosis features (P < .001), and 2 treatments: combined nonstandard nonalkylating chemotherapy plus involved‐field radiotherapy (P = .002) and mantle‐field irradiation alone (P = .003). With follow‐up censored at the first recurrence, no treatment modalities were associated with excess mortality.CONCLUSIONS:Progressive disease remained the primary cause of death in patients with HL in the first decades after treatment. Excess mortality in patients with early‐stage disease was linked significantly to treatment modalities that were associated with poor treatment failure‐free survival. Cancer 2009. © 2009 American Cancer Society.

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Causes of death after therapy for early stage Hodgkin's disease entered on EORTC protocols

Cited by 95 publications

References 8 publications

Late cardiotoxicity after treatment for Hodgkin lymphoma

Late cardiotoxicity after treatment for Hodgkin lymphoma

Long-term toxicity of the treatment of Hodgkin’s disease

Survival after Hodgkin lymphoma

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