Genetic effects of radiotherapy for childhood cancer: gonadal dose reconstruction.
OBJECTIVE
To estimate the doses of radiation to organs of interest during treatment of childhood cancer for use in an epidemiologic study of possible heritable diseases, including birth defects, chromosomal abnormalities, cancer, stillbirth, and neonatal and premature death.


METHODS
The study population was composed of more than 25,000 patients with cancer in Denmark and the United States who were survivors of childhood cancer and subsequently had nearly 6,500 children of their own. Radiation therapy records were sought for the survivors who parented offspring who had adverse pregnancy outcomes (>300 offspring), and for a sample of all survivors in a case-cohort design. The records were imaged and centrally abstracted. Water phantom measurements were made to estimate doses for a wide range of treatments. Mathematical phantoms were used to apply measured results to estimate doses to ovaries, uterus, testes, and pituitary for patients ranging in age from newborn to 25 years. Gonadal shielding, ovarian pinning (oophoropexy), and field blocking were taken into account.


RESULTS
Testicular radiation doses ranged from <1 to 700 cGy (median, 7 cGy) and ovarian doses from <1 to >2,500 cGy (median, 13 cGy). Ten percent of the records were incomplete, but sufficient data were available for broad characterizations of gonadal dose. More than 49% of the gonadal doses were >10 cGy and 16% were >100 cGy.


CONCLUSIONS
Sufficient radiation therapy data exist as far back as 1943 to enable computation of gonadal doses administered for curative therapy for childhood cancer. The range of gonadal doses is broad, and for many cancer survivors, is high and just below the threshold for infertility. Accordingly, the epidemiologic study has >90% power to detect a 1.3-fold risk of an adverse pregnancy outcome associated with radiation exposure to the gonads. This study should provide important information on the genetic consequences of radiation exposure to humans.
Stovall
Marilyn
M
Department of Radiation Physics, The University of Texas M. D. Anderson Cancer Center, Houston, TX, USA. MStovall@mdanderson.org
Donaldson
Sarah S
SS
Weathers
Rita E
RE
Robison
Leslie L
LL
Mertens
Ann C
AC
Winther
Jeanette Falck
JF
Olsen
Jorgen H
JH
Boice
John D
JD
D000293:Adolescent; D000328:Adult; D002648:Child; D002675:Child, Preschool; D002869:Chromosome Aberrations; D015331:Cohort Studies; D000013:Congenital Abnormalities / Q000209:etiology; D003718:Denmark; D005260:Female; D006801:Humans; D007223:Infant; D007226:Infant Mortality; D007231:Infant, Newborn; D008297:Male; D009369:Neoplasms / Q000209:etiology / Q000532:radiotherapy*; D010053:Ovary / Q000528:radiation effects*; D019047:Phantoms, Imaging; D010902:Pituitary Gland / Q000528:radiation effects; D011879:Radiotherapy Dosage; D017741:Survivors; D013737:Testis / Q000528:radiation effects*; D014481:United States; D014599:Uterus / Q000528:radiation effects