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.
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.
Schellong
Günther
G
Department of Pediatric Hematology and Oncology, University Hospital Münster, Münster, Germany. schellon@uni-muenster.de
Riepenhausen
Marianne
M
Bruch
Christian
C
Kotthoff
Stefan
S
Vogt
Johannes
J
Bölling
Tobias
T
Dieckmann
Karin
K
Pötter
Richard
R
Heinecke
Achim
A
Brämswig
Jürgen
J
Dörffel
Wolfgang
W
D000293:Adolescent; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D002648:Child; D002675:Child, Preschool; D003131:Combined Modality Therapy; D003520:Cyclophosphamide / Q000008:administration & dosage; D004317:Doxorubicin / Q000008:administration & dosage; D005260:Female; D005500:Follow-Up Studies; D006331:Heart Diseases / Q000175:diagnosis / Q000209:etiology*; D006349:Heart Valve Diseases / Q000175:diagnosis / Q000209:etiology*; D006689:Hodgkin Disease / Q000150:complications / Q000188:drug therapy / Q000532:radiotherapy*; D006801:Humans; D008137:Longitudinal Studies; D008297:Male; D008479:Mediastinal Neoplasms / Q000150:complications / Q000188:drug therapy / Q000532:radiotherapy*; D011241:Prednisone / Q000008:administration & dosage; D011344:Procarbazine / Q000008:administration & dosage; D011879:Radiotherapy Dosage; D015996:Survival Rate; D016896:Treatment Outcome; D014750:Vincristine / Q000008:administration & dosage
D011344:Procarbazine; D014750:Vincristine; D004317:Doxorubicin; D003520:Cyclophosphamide; D011241:Prednisone