Ralph E. Vatner, Andrzej Niemierko, Madhusmita Misra, Elizabeth A. Weyman, Claire P. Goebel, David H. Ebb, Robin M. Jones, Mary S. Huang, Takara Stanley, Shannon M. MacDonald, Nancy J. Tarbell, and Torunn I. Yock, Massachusetts General Hospital, Boston, MA; Ralph E. Vatner, University of Cincinnati College of Medicine and Cincinnati Children's Hospital Medical Center, Cincinnati, OH; Anita Mahajan, Mayo Clinic, Rochester, MN; and David R. Grosshans and Arnold C. Paulino, MD Anderson Cancer Center, Houston, TX.
J Clin Oncol. 2018 Oct 1;36(28):2854-2862. doi: 10.1200/JCO.2018.78.1492. Epub 2018 Aug 17.
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.
关于儿童和青少年脑瘤患者接受放射治疗（RT）对下丘脑和垂体的剂量反应，相关数据资料十分有限。本研究旨在探讨该人群中这些结构的放射剂量与内分泌功能障碍发展之间的相关性。
从 2003 年至 2016 年期间，对接受质子放射治疗的儿童和青年（<26 岁）脑瘤患者的剂量学和临床资料进行了收集。通过临床和血清学检测确定生长激素（GH）、甲状腺激素、促肾上腺皮质激素和促性腺激素缺乏的情况。使用 Kaplan-Meier 法估计缺乏的发生率。构建了考虑放射剂量和年龄的多变量模型。
在这项研究的 222 例患者中，有 189 例通过 actuarial 分析进行了评估，中位随访时间为 4.4 年（范围，0.1 至 13.3 年），31 例患者（14%）因基线激素缺乏而被排除在 actuarial 分析之外，2 例患者（0.9%）因缺乏随访而被排除。130 例（68.8%）髓母细胞瘤患者接受了颅脊髓照射（CSI）和加量照射；其余大多数患者（n=56）接受了累及野放疗，最常见的是室管膜瘤（13.8%；n=26）和低级别胶质瘤（7.4%；n=14）。任何激素缺乏、生长激素缺乏、甲状腺激素缺乏、促肾上腺皮质激素缺乏和促性腺激素缺乏的 4 年累积发生率分别为 48.8%、37.4%、20.5%、6.9%和 4.1%。放射治疗开始时的年龄、治疗后时间间隔和下丘脑-垂体联合部位的中位剂量与缺乏的发生率增加相关。
儿童和青少年脑瘤患者接受放射治疗后，中位下丘脑和垂体的放射剂量、年龄较小以及随访时间较长与内分泌疾病的发生率增加有关。
