Growth Hormone Secretion After Conformal Radiation Therapy in Pediatric Patients With Localized Brain Tumors

Abstract

A B S T R A C T PurposeGrowth hormone deficiency (GHD) after radiation therapy negatively affects growth and development and quality of life in children with brain tumors. Between 1997 and 2008, 192 pediatric patients with localized primary brain tumors (ependymoma, n ϭ 88; low-grade glioma, n ϭ 51; craniopharyngioma, n ϭ 28; high-grade glioma, n ϭ 23; and other tumor types, n ϭ 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. Patients and Materials ResultsBaseline 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 ). ConclusionGH 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.

Long-term Cardiovascular Toxicity in Children, Adolescents, and Young Adults Who Receive Cancer Therapy: Pathophysiology, Course, Monitoring, Management, Prevention, and Research Directions

“…453 A few studies have considered the incidence and importance of cardiac arrhythmias long after chemotherapy by guest on http://circ.ahajournals.org/ Downloaded from during childhood. Although some have reported occasional instances of sudden death 177 that may be related to repolarization abnormalities (QT prolongation and abnormal QT dispersion) in association with ventricular dysfunction, 455 others have described only infrequent and clinically unimportant arrhythmias. 456 Other studies of pediatric cancer survivors have described ventricular arrhythmias in association with late ventricular dysfunction, 457 but in general, these studies have been small and were not systematic evaluations of the population at risk.…”

“…175 Radiation to the neck can damage the carotid arteries, increasing the risk of stroke, even without hormonal changes, as discussed further under the sections below entitled "Treatment of Radiation-Associated CVD Risk Factors" and "Cardiometabolic Risk Factors for Premature Atherosclerosis." 29,176,177 In addition, spinal radiation used to treat brain malignancies may include the heart in the treatment field. Jakacki et al 178 reported in 1993 that subclinical cardiac dysfunction and conduction abnormalities were greater in survivors who received such therapy than in those who received flank radiation, in which the heart was not in the treatment field.…”

BRAF Mutation and CDKN2A Deletion Define a Clinically Distinct Subgroup of Childhood Secondary High-Grade Glioma

“…Radiation therapy is thought to play a role in malignant transformation of PLGG, 5 particularly in the context of cancer predisposition. 6,7 Before the genomic era, Broniscer et al 3 were the first to describe several genetic events that occur in these cancers. Recent next-generation sequencing efforts have uncovered somatic mutations in TP53, ATRX, and IDH1/2, among other alterations that are present in adult…”

Childhood Cancer Treatments and Associated Endocrine Late Effects: A Concise Guide for the Pediatric Endocrinologist

“…Skeletal growth, bone health, body composition, and metabolic homeostasis may be impaired as a consequence of radiation-induced endocrine deficits or because of direct radiation-related toxicity. The effect of radiotherapy on the various endocrine organs is dictated primarily by the total dose received and the duration since treatment such that the risk increases with increasing doses and greater elapsed time between exposure and follow-up [5-7]. Additional considerations include fraction size and number [8] and the method of delivery of the radiation [9-11].…”

“…The most common childhood CNS tumors treated with radiotherapy include medulloblastoma, craniopharyngioma, ependymoma, high-grade glioma, and low-grade glioma [5, 14]. Other childhood malignancies that may require cranial radiotherapy include acute lymphoblastic leukemia (ALL), previously for prophylaxis and currently for treatment of CNS disease [15], and malignant non-brain solid tumors of the head or neck (e.g., nasopharyngeal carcinoma, retinoblastoma, and rhabdomyosarcoma) [16].…”