Laughton Stephen J, Merchant Thomas E, Sklar Charles A, Kun Larry E, Fouladi Maryam, Broniscer Alberto, Morris E Brannon, Sanders Robert P, Krasin Matthew J, Shelso John, Xiong Zang, Wallace Dana, Gajjar Amar
Division of Neuro-Oncology, Department of Oncology, Memorial Sloan-Kettering Cancer Center, New York, NY, USA.
J Clin Oncol. 2008 Mar 1;26(7):1112-8. doi: 10.1200/JCO.2008.13.5293.
To estimate the cumulative incidence of specific hormone deficiencies and the influence of hypothalamic-pituitary (HP) axis radiation dose in a cohort of children with embryonal brain tumors treated with risk-adapted craniospinal irradiation (CSI), conformal primary site irradiation, and high-dose chemotherapy.
Clinical data and HP axis radiation dosimetry data were obtained from 88 eligible children. All patients received regular endocrine follow-up that included screening tests of thyroid function and stimulation testing for growth hormone deficiency (GHD), and adrenocorticotropin hormone deficiency.
The cumulative incidence of GHD, thyroid-stimulating hormone (TSH) deficiency, adrenocorticotropic hormone deficiency, and primary hypothyroidism at 4 years from diagnosis was 93% +/- 4%, 23% +/- 8%, 38% +/- 6%, and 65% +/- 7%, respectively. Radiation dosimetry to the HP axis was associated only with the development of TSH deficiency; the 4-year cumulative incidence was 44% +/- 19% and 11% +/- 8% (P = .014) for those receiving more or less than the median dose to the hypothalamus (>or= 42 v < 42 Gy), respectively. The median dose of CSI for the average-risk (AR) patients was 23.4 and 39.6 Gy (36 to 40.5 Gy) for the high-risk patients. The estimated mean decline in height Z-score after radiation therapy was greater in high-risk patients (-0.65 units/yr) when compared with AR patients (-0.54 units/yr; P = .039).
Pediatric patients with CNS embryonal tumors are at high risk for treatment-related hormone deficiencies. GHD and primary hypothyroidism were diagnosed in a majority of subjects relatively soon after the completion of therapy. Radiation dose to the hypothalamus in excess of 42 Gy was associated with an increase in the risk of developing TSH deficiency.
评估接受风险适应性全脑全脊髓照射（CSI）、适形原发部位照射及大剂量化疗的胚胎性脑肿瘤患儿队列中特定激素缺乏的累积发生率以及下丘脑 - 垂体（HP）轴辐射剂量的影响。
从88例符合条件的儿童中获取临床数据和HP轴辐射剂量测定数据。所有患者均接受定期内分泌随访，包括甲状腺功能筛查试验以及生长激素缺乏（GHD）和促肾上腺皮质激素缺乏的刺激试验。
诊断后4年时，GHD、促甲状腺激素（TSH）缺乏、促肾上腺皮质激素缺乏和原发性甲状腺功能减退的累积发生率分别为93%±4%、23%±8%、38%±6%和65%±7%。HP轴的辐射剂量测定仅与TSH缺乏的发生有关；下丘脑接受剂量大于或等于中位数剂量（≥42 Gy）与小于中位数剂量（<42 Gy）的患者，4年累积发生率分别为44%±19%和11%±8%（P = 0.014）。平均风险（AR）患者的CSI中位数剂量为23.4 Gy，高危患者为39.6 Gy（36至40.5 Gy）。与AR患者（-0.54单位/年；P = 0.039）相比，高危患者放疗后身高Z评分的估计平均下降幅度更大（-0.65单位/年）。
中枢神经系统胚胎性肿瘤的儿科患者存在与治疗相关的激素缺乏的高风险。大多数受试者在治疗完成后相对较短时间内被诊断为GHD和原发性甲状腺功能减退。下丘脑辐射剂量超过42 Gy与TSH缺乏发生风险增加相关。
