Dosimetry and growth hormone deficiency following cranial irradiation of childhood brain tumors.
BACKGROUND
Dosimetry of the hypothalamus-pituitary (HP) region could allow prediction of the risk of growth hormone deficiency (GHD) following cranial irradiation.


METHODS
Nineteen children (15 boys) with a median age of 6.3 years (range 1.7-16.5) at the time of irradiation of a brain tumor not involving the HP axis were followed for 1.2-6.3 years (median 3.4) from radiotherapy (RT). The dose to a standardized anatomical model including the HP region was calculated from dose-volume histograms of 10% to 100% in steps of 10% of the HP model based on data from a computer-based treatment planning system. If GHD was suspected from insulin-like growth factor-I, serum insulin-like growth factor binding protein-3, and/or height velocity measurements, an arginine stimulation test was performed. GHD was defined by a peak GH <15mU/liter.


RESULTS
Ten patients developed GHD 10-26 months from irradiation. Cox regression analysis identified the 90% dose-volume of the HP box as the strongest predictor of development of GHD (P = 0.03). The median dose to the 90% dose-volume of the HP region was 37.5 Gy (range 2. 3-55.3). The cumulated risk of GHD 2.5 years after radiotherapy for children receiving more than and less than 37.5 Gy to the HP region was 87% and 33%, respectively (P = 0.036).


CONCLUSIONS
Dosimetry of a defined HP volume provides the opportunity to 1) calculate the exact dose delivered to this region, 2) predict the risk of GHD and, 3) in the future revise the treatment planning and thus reduce the risk of endocrine adverse effects.
Schmiegelow
M
M
Department of Growth and Reproduction, Juliane Marie Centre, The National University Hospital, Rigshospitalet, Copenhagen, Denmark. RH04642@RH.DK
Lassen
S
S
Weber
L
L
Poulsen
H S
HS
Hertz
H
H
Müller
J
J
D000293:Adolescent; D001827:Body Height / Q000528:radiation effects; D001932:Brain Neoplasms / Q000097:blood / Q000532:radiotherapy*; D002648:Child; D002675:Child, Preschool; D016371:Cranial Irradiation / Q000009:adverse effects*; D004307:Dose-Response Relationship, Radiation; D005260:Female; D006128:Growth / Q000528:radiation effects; D006130:Growth Disorders / Q000097:blood / Q000209:etiology*; D019382:Human Growth Hormone / Q000172:deficiency*; D006801:Humans; D007031:Hypothalamus / Q000378:metabolism / Q000528:radiation effects; D007223:Infant; D018972:Insulin-Like Growth Factor Binding Protein 3 / Q000097:blood; D007334:Insulin-Like Growth Factor I / Q000378:metabolism; D008297:Male; D010902:Pituitary Gland / Q000378:metabolism / Q000528:radiation effects; D011874:Radiometry; D011880:Radiotherapy Planning, Computer-Assisted; D018570:Risk Assessment
D018972:Insulin-Like Growth Factor Binding Protein 3; D019382:Human Growth Hormone; D007334:Insulin-Like Growth Factor I