August 23, 2010

Late valvular and other cardiac diseases after different doses of mediastinal radiotherapy for hodgkin disease in children and adolescents: Report from the longitudinal GPOH follow-up project of the German-Austrian DAL-HD studies

GSG. SchellongUniwersytecki Szpital Dziecięcy MRMarianne RiepenhausenUniversity of Münster CBChristian BruchGESIS - Leibniz-Institute for the Social Sciences

Structured PICO

Does the dose of mediastinal radiotherapy affect the incidence of late cardiac diseases in long-term survivors of pediatric Hodgkin disease?

Population

1,132 long-term survivors of pediatric Hodgkin disease treated before 18 years of age, maintaining remission without secondary malignancy for 3.1-29.4 years. All received a uniform cumulative doxorubicin dose of 160 mg/m2.

Intervention

Mediastinal radiotherapy at varying doses (36, 30, 25, or 20 Gy)

Comparator

No mediastinal radiotherapy (0 Gy) or lower radiation doses

Outcome

Incidence of cardiac diseases (including valvular defects, coronary artery diseases, cardiomyopathies, conduction disorders, and pericardial abnormalities) and cardiac disease-free survivalcomposite

Higher doses of mediastinal radiotherapy significantly increase the long-term risk of late cardiac diseases in survivors of pediatric Hodgkin disease, supporting the use of lower radiation doses to reduce cardiotoxicity.

Abstract

BACKGROUND: To analyze the impact of mediastinal irradiation on the incidence of cardiac late effects in long-term survivors of pediatric Hodgkin disease (HD). METHODS: The study cohort comprised 1,132 survivors of HD who received treatment before 18 years of age in consecutive trials between 1978 and 1995. They had maintained remission without secondary malignancy for 3.1-29.4 years. The cumulative doxorubicin dose was uniformly 160 mg/m(2), the mediastinal radiation dose (MedRD) was 36, 30, 25, 20, or 0 Gy. Follow-up questionnaires complemented by additional contacts served to collect information on late effects from patients and physicians. A central expert panel reviewed all reported cardiac abnormalities. RESULTS: By October 2008, cardiac diseases (CD) had been diagnosed in 50 of 1,132 patients aged 15.0-41.7 (median 32.2) years. The interval since HD therapy was 3.0-28.2 (median 19.5) years. Valvular defects were diagnosed most frequently, followed by coronary artery diseases, cardiomyopathies, conduction disorders, and pericardial abnormalities. The cumulative incidence of CD after 25 years was highest in the MedRD-36 group (21%) decreasing to 10%, 6%, 5%, and 3% in the lower MedRD groups (P < 0.001). Multivariate Cox analysis of several putative risk factors showed MedRD to be the only significant variable predicting for CD-free survival (P = 0.0025). CONCLUSIONS: Our results indicate that lower MedRDs are less cardiotoxic. Consequently, reduction of cardiac late effects may be expected with the lower radiation doses used in current HD protocols. Longer follow-up is needed to confirm the present results.

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