Predicting the Probability of Abnormal Stimulated Growth Hormone Response in Children After Radiotherapy for Brain Tumors

Abstract

Purpose To develop a mathematical model utilizing more readily available measures than stimulation tests that identifies brain tumor survivors with high likelihood of abnormal growth hormone secretion after radiotherapy (RT), to avoid late recognition and a consequent delay in growth hormone replacement therapy. Methods and Materials We analyzed 191 prospectively collected post-RT evaluations of peak growth hormone level (arginine tolerance/levodopa stimulation test), serum insulin-like growth factor 1 (IGF-1), IGF-binding protein 3, height, weight, growth velocity, and body mass index in 106 children and adolescents treated for ependymoma (n = 72), low-grade glioma (n = 28) or craniopharyngioma (n = 6), who had normal growth hormone levels before RT. Normal level in this study was defined as the peak growth hormone response to the stimulation test ≥7 ng/mL. Results Independent predictor variables identified by multivariate logistic regression with high statistical significance (p < 0.0001) included IGF-1 z score, weight z score, and hypothalamic dose. The developed predictive model demonstrated a strong discriminatory power with an area under the receiver operating characteristic curve of 0.883. At a potential cutoff point of probability of 0.3 the sensitivity was 80% and specificity 78%. Conclusions Without unpleasant and expensive frequent stimulation tests, our model provides a quantitative approach to closely follow the growth hormone secretory capacity of brain tumor survivors. It allows identification of high-risk children for subsequent confirmatory tests and in-depth workup for diagnosis of growth hormone deficiency.

Development of Multifaceted Risk Taking and the Relations to Sex Steroid Hormones: A Longitudinal Study

“…Finally, to examine whether higher pubertal production of sex hormones relates to more risk taking compared to same‐aged peers , z ‐scores were calculated within each sex to approximate age‐standardized hormone values for participants at 11, 12, 13, 14, and 15 years of age: where z refers to the standardized hormonal value for an 11‐year old girl, an 11‐year old boy, 12‐year old girl, etc. This method can particularly be informative when establishing reference values, and a similar procedure has been adopted for other hormones such as growth hormone (Hua, Wu, Chemaitilly, Lukose, & Merchant, ), insulin growth factor (Alberti et al., ), and testosterone (Holmboe et al., ).…”

“…where z refers to the standardized hormonal value for an 11-year old girl, an 11-year old boy, 12-year old girl, etc. This method can particularly be informative when establishing reference values, and a similar procedure has been adopted for other hormones such as growth hormone (Hua, Wu, Chemaitilly, Lukose, & Merchant, 2012), insulin growth factor (Alberti et al, 2011), and testosterone (Holmboe et al, 2015). Note.…”

Range modulation in proton therapy planning: a simple method for mitigating effects of increased relative biological effectiveness at the end-of-range of clinical proton beams

“…When looking at the OAR doses, the difference in plans is pronounced due to this difference. Data exist that suggest doses over 10 Gy are sufficient to ultimately cause hypothalamic dysfunction [ 19 ]. In the NRMPBT plan, the average dose is lower, but the peak dose posteriorly is close to the full prescription dose due to the goal of treating through the full brainstem.…”

Craniopharyngioma

“…The most conservative criteria require post-stimulation values less than 5e7 ng/mL (Merchant et al, 2011). Provocative testing protocols use multiple blood draws, which can be uncomfortable for children (Hua et al, 2012). As an alternative, many centers use the serum insulin-like growth factor-1 (IGF-1) and insulin-like growth factor binding protein-3 (IGFBP-3), though these screening tests are significantly less sensitive for the detection of RT-induced GHD than provocative testing (Sklar et al, 1993;Tillmann et al, 1998;Hua et al, 2012).…”

“…Provocative testing protocols use multiple blood draws, which can be uncomfortable for children (Hua et al, 2012). As an alternative, many centers use the serum insulin-like growth factor-1 (IGF-1) and insulin-like growth factor binding protein-3 (IGFBP-3), though these screening tests are significantly less sensitive for the detection of RT-induced GHD than provocative testing (Sklar et al, 1993;Tillmann et al, 1998;Hua et al, 2012). Both IGF-1 and IGFBP-3 are affected by age, gender, pubertal status, and obesity, which can lead to an overestimation of GHD (Sklar et al, 1993).…”