Treatment Outcome of Intensity-modulated Radiotherapy for 15 Patients with Giant Pituitary Adenoma
-
摘要:
目的 分析调强放射治疗技术治疗垂体巨大腺瘤的临床实践经验,以期为临床诊疗提供借鉴。 方法 回顾性分析2012年10月至2018年10月于北京协和医院放射治疗科接受直线加速器6 MV-X线调强放射治疗(56~60 Gy/28~30次,5次/周)的垂体巨大腺瘤患者资料,以肿瘤生长控制率、激素缓解率、放射治疗相关并发症为指标评价患者的治疗效果。 结果 共15例符合纳入标准的患者入选本研究,其中男性8例,女性7例;中位年龄为32岁。肿瘤生长控制率为93.3%(11例部分缓解,3例肿瘤稳定,1例发展为垂体癌);7例功能性垂体巨大腺瘤患者中,1例激素水平完全缓解,2例部分缓解。4例患者采用调强放射治疗联合替莫唑胺治疗,均达到肿瘤部分缓解(中位缓解时间为5个月),缓解率及缓解时间均优于未使用替莫唑胺者。放射治疗后随访期内,4例患者出现新发垂体功能受损,未出现新发或进一步加重的视力减退及视野受损。 结论 调强放射治疗是垂体巨大腺瘤患者有效的治疗方法,与替莫唑胺联合应用可加快肿瘤体积缩小、缓解占位效应。 Abstract:Objective To summarize the clinical experience of intensity-modulated radiotherapy(IMRT) for patients with giant pituitary adenoma, and to provide evidence for clinical treatment. Methods The data of patients with giant pituitary adenoma who received 6MV-X IMRT with linear accelerator (prescription dose of 56-60 Gy/28-30 fractions, 5 fractions per week) in the Department of Radiation Oncology of Peking Union Medical College Hospital from October 2012 to October 2018 were reviewed. Treatment outcomes were evaluated by the control rate of tumor growth, remission rate of endocrine hormone, and radiation-related complications. Results A total of 15 patients were included in this study. There were 8 males and 7 females with a median age of 32 years. The control rate of tumor growth was 93.3% (partial response in 11 cases, stable in 3 cases, and development of pituitary carcinoma in 1 case). Among the 7 patients with functional giant pituitary adenoma, 1 patient achieved complete remission of the level of endocrine hormone and 2 patients achieved partial remission. Four patients treated with radiotherapy plus temozolomide achieved partial remission (median remission time was 5 months), and the remission rate and remission time were better than those who did not receive temozolomide. During the follow-up period after radiotherapy, 4 patients were found having newly pituitary dysfunction. There were no new or aggravating visional impairment and visual field defects. Conclusion Intensity-modulated radiotherapy is an effective treatment for giant pituitary adenoma, which can reduce the tumor faster combined with temozolomide. 作者贡献:连欣负责研究设计、项目执行、病历资料收集、结果分析及论文初稿撰写;沈晶、孙显松、孙玉亮参与患者随访工作;杨波负责设计调强放射治疗计划;沈捷、张福泉负责指导论文写作及修订。利益冲突:所有作者均声明不存在利益冲突 -
图 1 7例功能性垂体巨大腺瘤患者放射治疗后的激素水平变化情况(以放射治疗前IGF-1或PRL激素水平为基线,显示随访中相应激素水平与基线的比值)
GH、PRL:同表 1;IGF-1:胰岛素样生长因子-1
表 1 患者临床资料及治疗效果
编号 性别 年龄(岁) 肿瘤类别 Ki-67指数(%) p53 手术方式及次数 肿瘤体积(mL) 肿瘤侵袭范围 药物治疗 肿瘤生长控制 内分泌缓解 随访时间(月) 1 男 13 GH 3 - TSS×1 27.8 鞍上 无 PR CR 38.4 2 男 67 NF 3 - 活检术后×1 449.7 咽旁,颞叶,鼻腔,外耳道 替莫唑胺 PR 24.4 3 男 34 GH 3 - TSS×1 62.9 眼眶,鼻腔 奥曲肽 SD SD 25.9 4 女 54 NF 1 - TSS×1 38.1 鼻腔 替莫唑胺 PR 23.6 5 女 28 PRL 25 + TSS×1 52.5 眼眶 替莫唑胺,卡麦角林 PD PR 55.7 6 女 21 NF 20 N TSS×1,TC×1 42.5 斜坡骨质 替莫唑胺 PR 30.5 7 女 52 NF 2 - TSS×3 45.8 斜坡骨质 无 SD 30.7 8 男 57 PRL 20 N TSS×2 90.5 脑干 溴隐亭,卡麦角林 SD SD 43.4 9 男 24 GH 15 + TSS ×1 48.3 斜坡骨质 无 PR PR 93.3 10 男 32 GH+PRL 3 N TSS×3 107.5 斜坡骨质,颈椎,鼻腔 卡麦角林 PR PR 53.8 11 女 28 GH 6 - TSS×4 35.2 颅底,颞叶 奥曲肽 PR SD 23.3 12 女 49 NF 1 - TSS×1 34.1 颞叶 无 PR 38.4 13 男 28 NF 1 - TSS×2,TC×1 38.5 颅底 无 PR 24.4 14 女 45 NF 1 - TSS×1 26 斜坡骨质,筛窦,蝶窦 无 PR 25.9 15 男 26 NF 2 - TSS×1,TC×1 31.4 侧脑室 无 PR 23.6 GH:垂体生长激素细胞腺瘤;NF:无功能性垂体腺瘤;PRL:垂体泌乳素细胞腺瘤;N:未测定;TSS:经蝶窦入路手术;TC:开颅手术;PR:部分缓解;CR:完全缓解;SD:肿瘤稳定;PD:肿瘤进展 -
[1] Maiter D, Delgrange E. Therapy of endocrine disease: the challenges in managing giant prolactinomas[J]. Eur J Endocrinol, 2014, 170: R213-R227. doi: 10.1530/EJE-14-0013 [2] Iglesias P, Rodríguez Berrocal V, Díez JJ. Giant pituitary adenoma: histological types, clinical features and thera-peutic approaches[J]. Endocrine, 2018, 61: 407-421. doi: 10.1007/s12020-018-1645-x [3] Chabot JD, Chakraborty S, Imbarrato G, et al. Evaluation of Outcomes After Endoscopic Endonasal Surgery for Large and Giant Pituitary Macroadenoma: A Retrospective Review of 39 Consecutive Patients[J]. World Neurosurg, 2015, 84: 978-988. doi: 10.1016/j.wneu.2015.06.007 [4] Juraschka K, Khan OH, Godoy BL, et al. Endoscopic endonasal transsphenoidal approach to large and giant pituitary adenomas: institutional experience and predictors of extent of resection[J]. J Neurosurg, 2014, 121: 75-83. [5] Sinha S, Sharma BS. Giant pituitary adenomas--an enigma revisited. Microsurgical treatment strategies and outcome in a series of 250 patients[J]. Br J Neurosurg, 2010, 24: 31-39. doi: 10.3109/02688690903370305 [6] McCormack A, Dekkers OM, Petersenn S, et al. Treatment of aggressive pituitary tumours and carcinomas: results of a European Society of Endocrinology (ESE) survey 2016[J]. Eur J Endocrinol, 2018, 178: 265-276. doi: 10.1530/EJE-17-0933 [7] Minniti G, Flickinger J. The risk/benefit ratio of radiother-apy in pituitary tumors[J]. Best Pract Res Clin Endocrinol Metab, 2019, 33: 101269. doi: 10.1016/j.beem.2019.04.003 [8] Sakanaka K, Mizowaki T, Hiraoka M. Hiraoka. Dosime-tric advantage of intensity-modulated radiotherapy for whole ventricles in the treatment of localized intracranial germinoma[J]. Int J Radiat Oncol Biol Phys, 2012, 82: e273-e280. doi: 10.1016/j.ijrobp.2011.04.007 [9] Raggi E, Mosleh-Shirazi MA, Saran FH. An evaluation of conformal and intensity-modulated radiotherapy in whole ventricular radiotherapy for localised primary intracranial germinomas[J]. Clin Oncol (R Coll Radiol), 2008, 20: 253-260. doi: 10.1016/j.clon.2007.12.011 [10] Minniti G, Scaringi C, Poggi M, et al. Fractionated stereotactic radiotherapy for large and invasive non-functioning pituitary adenomas: long-term clinical outcomes and volumetric MRI assessment of tumor response[J]. Eur J Endocrinol, 2015, 172: 433-441. doi: 10.1530/EJE-14-0872 [11] Raverot G, Burman P, McCormack A, et al. European Society of Endocrinology Clinical Practice Guidelines for the management of aggressive pituitary tumours and carcinomas[J]. Eur J Endocrinol, 2018, 178: G1-G24. doi: 10.1530/EJE-17-0796 [12] Zhong C, Yin S, Zhou P, et al. Pituitary atypical adenoma or carcinoma sensitive to temozolomide combined with radiation therapy: a case report of early identification and management[J]. Turk Neurosurg, 2014, 24: 963-966. http://www.ncbi.nlm.nih.gov/pubmed/25448217 [13] Kamiya-Matsuoka C, Cachia D, Waguespack SG, et al. Radiotherapy with concurrent temozolomide for the management of extraneural metastases in pituitary carcinoma[J]. Pituitary, 2016, 19: 415-421. doi: 10.1007/s11102-016-0721-6 [14] Misir Krpan A, Dusek T, Rakusic Z, et al. A Rapid Biochemical and Radiological Response to the Concomitant Therapy with Temozolomide and Radiotherapy in an Aggressive ACTH Pituitary Adenoma[J]. Case Rep Endocrinol, 2017: 2419590. http://europepmc.org/articles/PMC5357528/ [15] Touma W, Hoostal S, Peterson RA, et al. Successful treatment of pituitary carcinoma with concurrent radiation, temozolomide, and bevacizumab after resection[J]. J Clin Neurosci, 2017, 41: 75-77. doi: 10.1016/j.jocn.2017.02.052 [16] Lian X, Shen J, Gu Z, et al. Intensity-modulated Radiotherapy for Pituitary Somatotroph Adenomas[J]. J Clin Endocrinol Metab, 2020, 105: dgaa651. doi: 10.1210/clinem/dgz199 [17] Zhao K, Liu XM, Liu D, et al. Fractionated Gamma Knife surgery for giant pituitary adenomas[J]. Clin Neurol Neurosurg, 2016, 150: 139-142. doi: 10.1016/j.clineuro.2016.09.009 [18] Shimon I, Jallad RS, Fleseriu M, et al. Giant GH-secreting pituitary adenomas: management of rare and aggressive pituitary tumors[J]. Eur J Endocrinol, 2015, 172: 707-713. doi: 10.1530/EJE-14-1117