Radiation dose-volume effects on growth hormone secretion

Area of Science:

• Pediatric Oncology
• Radiation Oncology
• Endocrinology

Background:

• Central nervous system irradiation can lead to growth hormone (GH) deficiency.
• The precise relationship between hypothalamic radiation dose and the timing of GH deficiency is not well understood.
• Conformal radiotherapy (CRT) allows for more accurate hypothalamic dosimetry.

Purpose of the Study:

• To correlate hypothalamic dosimetry with peak GH values in children undergoing CRT for brain tumors.
• To investigate the time course of GH deficiency following CRT.
• To develop a predictive model for GH decline based on radiation dose and volume to the hypothalamus.

Main Methods:

• 25 children treated with CRT for brain tumors underwent GH testing (arginine tolerance/L-dopa) at baseline, 6, and 12 months.
• Peak GH levels were modeled as a function of time post-CRT and the irradiated volume of the hypothalamus at specific dose intervals (0-20 Gy, 20-40 Gy, 40-60 Gy).
• A linear model was used to sum the effects of irradiation dose distribution on GH levels over time.

Main Results:

• Peak GH levels significantly declined within 12 months post-CRT (p < 0.0001).
• GH deficiency developed in 20 of 25 children by 12 months.
• A predictive equation was derived, demonstrating that higher irradiated hypothalamic volumes at higher doses (40-60 Gy) had the greatest impact on GH decline. Hydrocephalus and tumor location also influenced the rate of decline.

Conclusions:

• Post-CRT GH response within 12 months is dependent on hypothalamic dose-volume effects.
• A linear model effectively predicts GH decline based on the distribution of radiation dose to the hypothalamus.
• These findings can inform radiotherapy planning to minimize and manage GH deficiency in pediatric patients.