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Growth hormone secretion after conformal radiation therapy in pediatric patients with localized brain tumors
Thomas E Merchant1, Susan R Rose, Christina Bosley
1St Jude Children’s Research Hospital, Memphis, TN 38015-3678, USA. thomas.merchant@stjude.org
Insights
Pediatric brain tumor patients receiving radiation therapy may develop growth hormone deficiency (GHD). GHD risk after radiation depends on the radiation dose to the hypothalamus and time elapsed post-treatment.
Area of Science:
- Pediatric endocrinology
- Radiation oncology
- Pediatric neuro-oncology
Background:
- Radiation therapy for pediatric brain tumors can lead to growth hormone deficiency (GHD).
- GHD negatively impacts children's growth, development, and quality of life.
Purpose of the Study:
- To predict the risk of GHD after conformal radiation therapy (CRT) in pediatric brain tumor patients.
- To establish an objective radiation dose constraint for the hypothalamus.
Main Methods:
- 192 pediatric patients with brain tumors underwent growth hormone (GH) secretion testing before and up to 60 months after CRT.
- GH secretion was assessed using arginine and L-dopa secretogogues.
- GH secretion was modeled as a function of time after CRT and radiation dose to the hypothalamus.
Main Results:
- 22.9% of patients had pre-irradiation GHD.
- A model predicted GHD risk based on time after CRT and hypothalamic radiation dose.
- A dose of 16.1 Gy to the hypothalamus was associated with a 50% risk of GHD at 5 years (TD(50/5)).
Conclusions:
- GH secretion post-CRT in pediatric brain tumor patients can be predicted by radiation dose and time.
- These findings offer an objective radiation dose constraint for the hypothalamus to mitigate GHD risk.
Purpose:
Growth hormone deficiency (GHD) after radiation therapy negatively affects growth and development and quality of life in children with brain tumors.
Patients And Materials:
Between 1997 and 2008, 192 pediatric patients with localized primary brain tumors (ependymoma, n = 88; low-grade glioma, n = 51; craniopharyngioma, n = 28; high-grade glioma, n = 23; and other tumor types, n = 2) underwent provocative testing of GH secretion by using the secretogogues arginine and L-dopa before and after (6, 12, 36, and 60 months) conformal radiation therapy (CRT). A total of 664 arginine/l-dopa test procedures were performed.
Results:
Baseline testing revealed preirradiation GHD in 22.9% of tested patients. On the basis of data from 118 patients, peak GH was modeled as an exponential function of time after CRT and mean radiation dose to the hypothalamus. The average patient was predicted to develop GHD with the following combinations of the time after CRT and mean dose to the hypothalamus: 12 months and more than 60 Gy; 36 months and 25 to 30 Gy; and 60 months and 15 to 20 Gy. A cumulative dose of 16.1 Gy to the hypothalamus would be considered the mean radiation dose required to achieve a 50% risk of GHD at 5 years (TD(50/5)).
Conclusion:
GH secretion after CRT can be predicted on the basis of dose and time after irradiation in pediatric patients with localized brain tumors. These findings provide an objective radiation dose constraint for the hypothalamus.
