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Late Effects of Treatment for Childhood Cancer (PDQ®): Treatment - Health Professional Information [NCI] - Late Effects of the Endocrine System

Table 8. Anterior Pituitary Hormones and Major Hypothalamic Regulatory Factors continued...

Approximately 60% to 80% of irradiated pediatric brain tumor patients who have received doses greater than 30 Gy will have impaired serum growth hormone (GH) response to provocative stimulation, usually within 5 years of treatment. The dose-response relationship has a threshold of 18 Gy to 20 Gy; the higher the radiation dose, the earlier that GHD will occur after treatment. A study of conformal radiation therapy in children with central nervous system (CNS) tumors indicates that GH insufficiency can usually be demonstrated within 12 months of radiation therapy, depending on hypothalamic dose-volume effects.[26] In a recent report from the St. Jude Children's Research Hospital on data from 118 patients with localized brain tumors that were treated with radiation therapy, peak GH was modeled as an exponential function of time after conformal radiation therapy (CRT) and mean radiation dose to the hypothalamus. The average patient was predicted to develop GHD with the following combinations of time after CRT and mean dose to the hypothalamus: 12 months and more than 60 Gy; 36 months and 25 Gy to 30 Gy; and 60 months and 15 Gy 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 (TD50/5).[27]


cdr0000727434.jpg
Figure 5. Peak growth hormone (GH) according to hypothalamic mean dose and time after start of irradiation. According to equation 2, peak GH = exp{2.5947 + time × [0.0019 − (0.00079 × mean dose)]}. Thomas E. Merchant, Susan R. Rose, Christina Bosley, Shengjie Wu, Xiaoping Xiong, and Robert H. Lustig, Growth Hormone Secretion After Conformal Radiation Therapy in Pediatric Patients With Localized Brain Tumors, Journal of Clinical Oncology, volume 29, issue 36, pages 4776-4780. Reprinted with permission. © (2011) American Society of Clinical Oncology. All rights reserved.

Children treated with CNS irradiation for leukemia are also at increased risk of GHD. One study evaluated 127 patients with acute lymphocytic leukemia (ALL) treated with 24 Gy, 18 Gy, or no cranial irradiation. The change in height, compared with population norms expressed as the standard deviation score (SDS), was significant for all three groups with a dose-response of -0.49 ± 0.14 for the no radiation therapy group, -0.65 ± 0.15 for the 18 Gy radiation therapy group, and -1.38 ± 0.16 for the 24 Gy group.[28] Another study found similar results in 118 ALL survivors treated with 24 Gy cranial irradiation, in which 74% had SDS score of -1 or greater and the remainder had -2 or greater.[29] However, survivors of childhood ALL who are treated with chemotherapy alone are also at increased risk for adult short stature, though the risk is highest for those treated with cranial and craniospinal radiation therapy at a young age.[30] In this cross-sectional study, attained adult height was determined among 2,434 ALL survivors participating in the Childhood Cancer Survivor Study (CCSS). All survivor treatment exposure groups (chemotherapy alone and chemotherapy with cranial or craniospinal radiation therapy) had decreased adult height and an increased risk of adult short stature (height standard deviation score < -2) compared with siblings (P < .001). Compared with siblings, the risk of short stature for survivors treated with chemotherapy alone was elevated (odds ratio = 3.4; 95% confidence interval [CI], 1.9-6.0). Among survivors, significant risk factors for short stature included diagnosis of ALL before puberty, higher-dose cranial radiation therapy (≥20 Gy vs. <20 Gy), any radiation therapy to the spine, and female gender.

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Last Updated: February 25, 2014
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