Role of cancer treatment in long-term overall and cardiovascular mortality after childhood cancer.
OBJECTIVE
The purpose of this study was to assess the role of treatment in long-term overall and cardiovascular mortality after childhood cancer.


METHODS
We studied 4,122 5-year survivors of a childhood cancer diagnosed before 1986 in France and the United Kingdom. Information on chemotherapy was collected, and the radiation dose delivered to the heart was estimated for 2,870 patients who had received radiotherapy.


RESULTS
After 86,453 person-years of follow-up (average, 27 years), 603 deaths had occurred. The overall standardized mortality ratio (SMR) was 8.3-fold higher (95% CI, 7.6-fold to 9.0-fold higher) in relation to the general populations in France and the United Kingdom. Thirty-two patients had died as a result of cardiovascular diseases (ie, 5.0-fold [95% CI, 3.3-fold to 6.7-fold] more than expected). The risk of dying as a result of cardiac diseases (n = 21) was significantly higher in individuals who had received a cumulative anthracycline dose greater than 360 mg/m(2) (relative risk [RR], 4.4; 95% CI, 1.3 to 15.3) and in individuals who received an average radiation dose that exceeded 5 Gy (RR, 12.5 and 25.1 for 5 to 14.9 Gy and > 15 Gy, respectively) to the heart. A linear relationship was found between the average dose of radiation to the heart and the risk of cardiac mortality (estimated excess [corrected] RR at 1 Gy, 60%).


CONCLUSIONS
This study is the first, to our knowledge, to establish a relationship between the radiation dose received by the heart during radiotherapy for a childhood cancer and long-term cardiac mortality. This study also confirms a significant excess risk of cardiac mortality associated with a high cumulative dose of anthracyclines.
L'Institut National de la Santé et de la Recherche Médicale,Institut Gustave Roussy, 94805 Villejuif Cedex, France.
Markhaba
M
Tukenova
Catherine
C
Guibout
Odile
O
Oberlin
Françoise
F
Doyon
Abdeddahir
A
Mousannif
Nadia
N
Haddy
Sylvie
S
Guérin
Hélène
H
Pacquement
Albertine
A
Aouba
Mike
M
Hawkins
Dave
D
Winter
Jean
J
Bourhis
Dimitri
D
Lefkopoulos
Ibrahima
I
Diallo
Florent
F
de Vathaire
D000293:Adolescent; D000328:Adult; D018943:Anthracyclines / Q000008:administration & dosage / Q000009:adverse effects; D000970:Antineoplastic Agents / Q000009:adverse effects*; D002318:Cardiovascular Diseases / Q000209:etiology / Q000401:mortality*; D002423:Cause of Death; D002648:Child; D002675:Child, Preschool; D004305:Dose-Response Relationship, Drug; D004307:Dose-Response Relationship, Radiation; D005260:Female; D005500:Follow-Up Studies; D005602:France / Q000453:epidemiology; D006801:Humans; D008297:Male; D008875:Middle Aged; D009026:Mortality; D015999:Multivariate Analysis; D009369:Neoplasms / Q000188:drug therapy* / Q000532:radiotherapy*; D011878:Radiotherapy / Q000009:adverse effects; D017741:Survivors; D006113:United Kingdom / Q000453:epidemiology
D018943:Anthracyclines; D000970:Antineoplastic Agents