Endocrine Deficiency As a Function of Radiation Dose to the Hypothalamus and Pituitary in Pediatric and Young Adult Patients With Brain Tumors

• Published in: Journal of clinical oncology Vol. 36; no. 28; pp. 2854 - 2862
• Main Authors: Vatner, Ralph E, Niemierko, Andrzej, Misra, Madhusmita, Weyman, Elizabeth A, Goebel, Claire P, Ebb, David H, Jones, Robin M, Huang, Mary S, Mahajan, Anita, Grosshans, David R, Paulino, Arnold C, Stanley, Takara, MacDonald, Shannon M, Tarbell, Nancy J, Yock, Torunn I
• Format: Journal Article
• Language: English
• Published: United States American Society of Clinical Oncology 01-10-2018
• Subjects: Adolescent; Brain Neoplasms - radiotherapy; Child; Child, Preschool; Clinical Trials, Phase II as Topic; Cranial Irradiation - adverse effects; Cranial Irradiation - methods; Endocrine System Diseases - epidemiology; Endocrine System Diseases - etiology; Female; Humans; Hypothalamus - radiation effects; Male; ORIGINAL REPORTS; Pituitary Gland - radiation effects; Proton Therapy - adverse effects; Radiation Injuries - epidemiology; Young Adult
• ISSN: 0732-183X; 1527-7755
• DOI: 10.1200/JCO.2018.78.1492

There are sparse data defining the dose response of radiation therapy (RT) to the hypothalamus and pituitary in pediatric and young adult patients with brain tumors. We examined the correlation between RT dose to these structures and development of endocrine dysfunction in this population.
Dosimetric and clinical data were collected from children and young adults (< 26 years of age) with brain tumors treated with proton RT on three prospective studies (2003 to 2016). Deficiencies of growth hormone (GH), thyroid hormone, adrenocorticotropic hormone, and gonadotropins were determined clinically and serologically. Incidence of deficiency was estimated using the Kaplan-Meier method. Multivariate models were constructed accounting for radiation dose and age.
Of 222 patients in the study, 189 were evaluable by actuarial analysis, with a median follow-up of 4.4 years (range, 0.1 to 13.3 years), with 31 patients (14%) excluded from actuarial analysis for having baseline hormone deficiency and two patients (0.9%) because of lack of follow-up. One hundred thirty patients (68.8%) with medulloblastoma were treated with craniospinal irradiation (CSI) and boost; most of the remaining patients (n = 56) received involved field RT, most commonly for ependymoma (13.8%; n = 26) and low-grade glioma (7.4%; n = 14). The 4-year actuarial rate of any hormone deficiency, growth hormone, thyroid hormone, adrenocorticotropic hormone, and gonadotropin deficiencies were 48.8%, 37.4%, 20.5%, 6.9%, and 4.1%, respectively. Age at start of RT, time interval since treatment, and median dose to the combined hypothalamus and pituitary were correlated with increased incidence of deficiency.
Median hypothalamic and pituitary radiation dose, younger age, and longer follow-up time were associated with increased rates of endocrinopathy in children and young adults treated with radiotherapy for brain tumors.