Pai H H, Thornton A, Katznelson L, Finkelstein D M, Adams J A, Fullerton B C, Loeffler J S, Leibsch N J, Klibanski A, Munzenrider J E
Department of Radiation Oncology, Massachusetts General Hospital-Harvard Medical School, Boston, MA, USA.
Int J Radiat Oncol Biol Phys. 2001 Mar 15;49(4):1079-92. doi: 10.1016/s0360-3016(00)01387-0.
To evaluate the incidence and pattern of hypopituitarism from hypothalamic (HT) and pituitary gland (PG) damage following high-dose conformal fractionated proton-photon beam radiotherapy (PPRT) to the base of skull (BOS) region in adults. The relationship between dose, volume, and PG function is explored.
Between May 1982 to October 1997, 107 adults with non-PG and non-HT neoplasms (predominantly chordoma and chondrosarcomas) of the BOS were treated with PPRT after subtotal resection(s). The median age was 41.2 years (range, 17-75) with 58 males and 49 females. Median prescribed target dose was 68.4 cobalt gray equivalent (CGE) (range, 55.8-79 CGE) at 1.80-1.92 CGE per fraction per day (where CGE = proton Gy x 1.1). The HT and PG were outlined on planning CT scans to allow dose-volume histograms (DVH) analysis. All patients had baseline and follow-up clinical testing of anterior and posterior pituitary function including biochemical assessment of thyroid, adrenal, and gonadal function, and prolactin secretion.
The 10-year actuarial overall survival rate was 87%, with median endocrine follow-up time of 5.5 years, thus the majority of patients were available for long-term follow-up. Five-year actuarial rates of endocrinopathy were as follows: 72% for hyperprolactinemia, 30% for hypothyroidism, 29% for hypogonadism, and 19% for hypoadrenalism. The respective 10-year endocrinopathy rates were 84%, 63%, 36%, and 28%. No patient developed diabetes insipidus (vasopressin deficiency). Growth hormone deficiency was not routinely followed in this study. Minimum target dose (Dmin) to the PG was found to be predictive of endocrinopathy: patients receiving 50 CGE or greater at Dmin to the PG experiencing a higher incidence and severity (defined as the number of endocrinopathies occurring per patient) of endocrine dysfunction. Dmax of 70 CGE or greater to the PG and Dmax of 50 CGE or greater to the HT were also predictive of higher rates of endocrine dysfunction.
Radiation-induced damage to the HT & PG occurs frequently after high-dose PPRT to the BOS and is manifested by anterior pituitary gland dysfunction. Hyperprolactinemia was detected in the majority of patients. Posterior pituitary dysfunction, represented by vasopressin activity with diabetes insipidus, was not observed in this dose range. Limiting the dose to the HT and PG when feasible should reduce the risk of developing clinical hypopituitarism.
评估成人高剂量适形分割质子 - 光子束放疗（PPRT）至颅底（BOS）区域后，下丘脑（HT）和垂体腺（PG）损伤导致垂体功能减退的发生率和模式。探讨剂量、体积与垂体腺功能之间的关系。
1982年5月至1997年10月期间，107例患有BOS非垂体腺和非下丘脑肿瘤（主要为脊索瘤和软骨肉瘤）的成人在次全切除术后接受了PPRT治疗。中位年龄为41.2岁（范围17 - 75岁），其中男性58例，女性49例。中位处方靶剂量为68.4钴灰当量（CGE）（范围55.8 - 79 CGE），每天每分次剂量为1.80 - 1.92 CGE（其中CGE = 质子戈瑞×1.1）。在计划CT扫描上勾勒出HT和PG，以进行剂量 - 体积直方图（DVH）分析。所有患者均进行了垂体前叶和后叶功能的基线及随访临床检测，包括甲状腺、肾上腺和性腺功能的生化评估以及催乳素分泌检测。
10年精算总生存率为87%，内分泌中位随访时间为5.5年，因此大多数患者可进行长期随访。内分泌病的5年精算发生率如下：高催乳素血症为72%，甲状腺功能减退为30%，性腺功能减退为29%，肾上腺功能减退为19%。相应的10年内分泌病发生率分别为84%、63%、36%和28%。无患者发生尿崩症（血管加压素缺乏）。本研究未常规随访生长激素缺乏情况。发现PG的最小靶剂量（Dmin）可预测内分泌病：PG的Dmin接受50 CGE或更高剂量的患者，内分泌功能障碍的发生率和严重程度（定义为每位患者发生的内分泌病数量）更高。PG的Dmax为70 CGE或更高以及HT的Dmax为50 CGE或更高也可预测更高的内分泌功能障碍发生率。
高剂量PPRT至BOS后，HT和PG的放射性损伤频繁发生，表现为垂体前叶功能障碍。大多数患者检测到高催乳素血症。在该剂量范围内未观察到以尿崩症的血管加压素活性为代表的垂体后叶功能障碍。在可行时限制对HT和PG的剂量应可降低发生临床垂体功能减退的风险。
