脑部放疗引起认知功能障碍的预防和治疗

doi:10.3760/cma.j.cn371439-20200810-00010

摘要/Abstract

摘要：

放射性脑损伤是恶性肿瘤放疗后的严重不良反应,在放疗后期常出现认知功能障碍,严重影响患者的生命质量。尽管放疗引起的认知功能障碍的机制尚不完全明确,但随着人们对认知功能障碍的关注,越来越多的预防策略应用于临床,包括海马回避的全脑放疗、立体定向放射外科在多发性脑转移患者中的应用以及使用神经保护药物美金刚、多奈哌齐等。为脑瘤患者选择合适的放疗管理模式,规律进行认知测试,并在适当的时机提供治疗措施对改善患者的生命质量至关重要。

关键词: 放射性脑损伤, 认知功能障碍, 生活质量

Abstract:

Radiation-induced brain injury is a serious untoward effect of radiotherapy for malignant tumors. Patients received radiotherapy frequently occur cognitive dysfunction which seriously affects the quality of life. Although the exact mechanisms regarding radiation-induced cognitive dysfunction remain unclear, prevention strategies targeting cognitive dysfunction are increasingly applied to clinical intervention, including whole brain radiotherapy with hippocampus avoidance, stereotactic radiosurgery in patients with multiple brain metastases, and pretreatment with neuroprotective drugs such as memantine and donepezil. In addition, measures including appropriate radiotherapy management models, regular cognitive tests, and therapeutic measures at the appropriate time are critical to improve the quality of life for brain tumor patients.

Key words: Radiation-induced brain injury, Cognitive dysfunction, Quality of life

彭雯硕, 陈乃耀, 胡霞, 张靖宜. 脑部放疗引起认知功能障碍的预防和治疗[J]. 国际肿瘤学杂志, 2021, 48(1): 52-56.

Peng Wenshuo, Chen Naiyao, Hu Xia, Zhang Jingyi. Prevention and treatment of cognitive dysfunction caused by radiotherapy to the brain[J]. Journal of International Oncology, 2021, 48(1): 52-56.

参考文献 36

[1]	McTyre E, Scott J, Chinnaiyan P. Whole brain radiotherapy for brain metastasis[J]. Surg Neurol Int, 2013,4(4):S236-S244. DOI: 10.4103/2152-7806.
[2]	Tallet AV, Azria D, Barlesi F, et al. Neurocognitive function impairment after whole brain radiotherapy for brain metastases: actual assessment[J]. Radiat Oncol, 2012,7:77. DOI: 10.1186/1748-717X-7-77. doi: 10.1186/1748-717X-7-77 pmid: 22640600
[3]	Brown PD, Jaeckle K, Ballman KV, et al. Effect of radiosurgery alone vs radiosurgery with whole brain radiation therapy on cognitive function in patients with 1 to 3 brain metastases: a randomized clinical trial[J]. JAMA, 2016,316(4):401-409. DOI: 10.1001/jama.2016.9839. pmid: 27458945
[4]	Makale MT, McDonald CR, Hattangadi-Gluth JA, et al. Mechanisms of radiotherapy-associated cognitive disability in patients with brain tumours[J]. Nat Rev Neurol, 2017,13(1):52-64. DOI: 10.1038/nrneurol.2016.185. doi: 10.1038/nrneurol.2016.185 pmid: 27982041
[5]	Lin NU, Wefel JS, Lee EQ, et al. Challenges relating to solid tumour brain metastases in clinical trials, part 2: neurocognitive, neurological, and quality-of-life outcomes. A report from the RANO group[J]. Lancet Oncol, 2013,14(10):e407-e416. DOI: 10.1038/nrneurol.2016.185. pmid: 23993385
[6]	Cramer CK, Cummings TL, Andrews RN, et al. Treatment of radiation-induced cognitive decline in adult brain tumor patients[J]. Curr Treat Options Oncol, 2019,20(5):42. DOI: 10.1007/s11864-019-0641-6. pmid: 30963289
[7]	Parihar VK, Limoli CL. Cranial irradiation compromises neuronal architecture in the hippocampus[J]. Proc Natl Acad Sci U S A, 2013,110(31):12822-12827. DOI: 10.1073/pnas.1307301110. pmid: 23858442
[8]	Tang FR, Loke WK, Khoo BC. Postnatal irradiation-induced hip-pocampal neuropathology, cognitive impairment and aging[J]. Brain Dev, 2017,39(4):277-293. DOI: 10.1016/j.braindev.2016.11.001. pmid: 27876394
[9]	Yahyapour R, Motevaseli E, Rezaeyan A, et al. Reduction-oxidation (redox) system in radiation-induced normal tissue injury: molecular mechanisms and implications in radiation therapeutics[J]. Clin Transl Oncol, 2018,20(8):975-988. DOI: 10.1007/s12094-017-1828-6. doi: 10.1007/s12094-017-1828-6
[10]	Lumniczky K, Szatmári T, Sáfrány G. Ionizing radiation-induced immune and inflammatory reactions in the brain[J]. Front Immunol, 2017,5(8):517. DOI: 10.3389/fimmu.2017.00517.
[11]	Gondi V, Hermann BP, Mehta MP, et al. Hippocampal dosimetry predicts neurocognitive function impairment after fractionated ste-reotactic radiotherapy for benign or low-grade adult brain tumors[J]. Int J Radiat Oncol Biol Phys, 2012,83(4):e487-e493. DOI: 10.1016/j.ijrobp.2011.10.021. doi: 10.1016/j.ijrobp.2011.10.021 pmid: 22209148
[12]	Gondi V, Tolakanahalli R, Mehta MP, et al. Hippocampal-sparing whole-brain radiotherapy: a "how-to" technique using helical tomotherapy and linear accelerator-based intensity-modulated radiotherapy[J]. Int J Radiat Oncol Biol Phys, 2010,78(4):1244-1252. DOI: 10.1016/j.ijrobp.2010.01.039. pmid: 20598457
[13]	Gondi V, Pugh SL, Tome WA, et al. Preservation of memory with conformal avoidance of the hippocampal neural stem-cell compartment during whole-brain radiotherapy for brain metastases (RTOG 0933): a phase Ⅱ multi-institutional trial[J]. J Clin Oncol, 2014,32(34):3810-3816. DOI: 10.1200/JCO.2014.57.2909.
[14]	Brown PD, Gondi V, Pugh S, et al. Hippocampal avoidance during whole-brain radiotherapy plus memantine for patients with brain metastases: phase Ⅲ trial NRG Oncology CC001[J]. J Clin Oncol, 2020,38(10):1019-1029. DOI: 10.1200/JCO.19.02767. pmid: 32058845
[15]	Kazda T, Jancalek R, Pospisil P, et al. Why and how to spare the hippocampus during brain radiotherapy: the developing role of hip-pocampal avoidance in cranial radiotherapy[J]. Radiat Oncol, 2014,9:139. DOI: 10.1186/1748-717X-9-139. doi: 10.1186/1748-717X-9-139
[16]	Brown PD, Ballman KV, Cerhan JH, et al. Postoperative stereotactic radiosurgery compared with whole brain radiotherapy for resected metastatic brain disease (NCCTG N107C/CEC·3): a multicentre, randomised, controlled, phase 3 trial[J]. Lancet Oncol, 2017,18(8):1049-1060. DOI: 10.1016/S1470-2045(17)30441-2. doi: 10.1016/S1470-2045(17)30441-2 pmid: 28687377
[17]	Kraft J, Zindler J, Minniti G, et al. Stereotactic radiosurgery for multiple brain metastases[J]. Curr Treat Options Neurol, 2019,21(2):6. DOI: 10.1007/s11940-019-0548-3. doi: 10.1007/s11940-019-0548-3 pmid: 30758726
[18]	Robin TP, Camidge DR, Stuhr K, et al. Excellent outcomes with radiosurgery for multiple brain metastases in ALK and EGFR driven non-small cell lung cancer[J]. J Thorac Oncol, 2018,13(5):715-720. DOI: 10.1016/j.jtho.2017.12.006. doi: 10.1016/j.jtho.2017.12.006 pmid: 29269007
[19]	Kodama T, Hasegawa M, Takanashi K, et al. Antitumor activity of the selective ALK inhibitor alectinib in models of intracranial metastases[J]. Cancer Chemother Pharmacol, 2014,74(5):1023-1028. DOI: 10.1007/s00280-014-2578-6. doi: 10.1007/s00280-014-2578-6 pmid: 25205428
[20]	Peters S, Camidge DR, Shaw AT. Alectinib versus crizotinib in untreated ALK-positive non-small-cell lung cancer[J]. N Engl J Med, 2017,377(9):829-838. DOI: 10.1056/NEJMoa1704795. doi: 10.1056/NEJMoa1704795 pmid: 28586279
[21]	Ballard P, Yates JW, Yang Z, et al. Preclinical comparison of osi-mertinib with other EGFR-TKIs in EGFR-mutant NSCLC brain metastases models, and early evidence of clinical brain metastases activity[J]. Clin Cancer Res, 2016,22(20):5130-5140. DOI: 10.1158/1078-0432.CCR-16-0399. doi: 10.1158/1078-0432.CCR-16-0399 pmid: 27435396
[22]	Wu YL, Ahn MJ, Garassino MC, et al. CNS efficacy of osimertinib in patients with T790M-positive advanced non-small-cell lung can-cer: data from a randomized phase Ⅲ trial (AURA3)[J]. J Clin Oncol, 2018,36(26):2702-2709. DOI: 10.1200/JCO.2018.77.9363. doi: 10.1200/JCO.2018.77.9363 pmid: 30059262
[23]	Ahluwalia MS, Becker K, Levy BP. Epidermal growth factor receptor tyrosine kinase inhibitors for central nervous system metastases from non-small cell lung cancer[J]. Oncologist, 2018,23(10):1199-1209. DOI: 10.1634/theoncologist.2017-0572. doi: 10.1634/theoncologist.2017-0572 pmid: 29650684
[24]	Lynch M. Preservation of cognitive function following whole brain radiotherapy in patients with brain metastases: complications, treatments, and the emerging role of memantine[J]. J Oncol Pharm Pract, 2019,25(3):657-662. DOI: 10.1177/10781552187-98176. doi: 10.1177/1078155218798176 pmid: 30200844
[25]	Duman JG, Dinh J, Zhou W, et al. Memantine prevents acute radiation-induced toxicities at hippocampal excitatory synapses[J]. Neuro Oncol, 2018,20(5):655-665. DOI: 10.1093/neuonc/nox203. doi: 10.1093/neuonc/nox203 pmid: 29112734
[26]	Brown PD, Pugh S, Laack NN, et al. Memantine for the prevention of cognitive dysfunction in patients receiving whole-brain radiotherapy: a randomized, double-blind, placebo-controlled trial[J]. Neuro Oncol, 2013,15(10):1429-1437. DOI: 10.1093/neuonc/not114. doi: 10.1093/neuonc/not114 pmid: 23956241
[27]	Doody RS, Cummings JL, Farlow MR. Reviewing the role of donepezil in the treatment of Alzheimer's disease[J]. Curr Alzheimer Res, 2012,9(7):773-781. DOI: 10.2174/156720512802455412.
[28]	Eskandary A, Moazedi AA, Najaph Zade H, et al. Effects of donepezil hydrochloride on neuronal response of pyramidal neurons of the CA1 hippocampus in rat model of Alzheimer's disease[J]. Basic Clin Neurosci, 2019,10(2):109-117. DOI: 10.32598/bcn.9.10.305. doi: 10.32598/bcn.9.10.305 pmid: 31031898
[29]	Shaw EG, Rosdhal R, D'Agostino RB Jr, et al. Phase Ⅱ study of donepezil in irradiated brain tumor patients: effect on cognitive function, mood, and quality of life[J]. J Clin Oncol, 2006,24(9):1415-1420. DOI: 10.1200/JCO.2005.03.3001. doi: 10.1200/JCO.2005.03.3001 pmid: 16549835
[30]	Rapp SR, Case LD, Peiffer A, et al. Donepezil for irradiated brain tumor survivors: a phase Ⅲ randomized placebo-controlled clinical trial[J]. J Clin Oncol, 2015,33(15):1653-1659. DOI: 10.1200/JCO.2014.58.4508. doi: 10.1200/JCO.2014.58.4508 pmid: 25897156
[31]	Pazzaglia S, Briganti G, Mancuso M, et al. Neurocognitive decline following radiotherapy: mechanisms and therapeutic implications[J]. Cancers (Basel), 2020,12(1):146. DOI: 10.3390/can-cers12010146. doi: 10.3390/cancers12010146
[32]	Attia A, Rapp SR, Case LD, et al. Phase Ⅱ study of Ginkgo biloba in irradiated brain tumor patients: effect on cognitive function, qua-lity of life, and mood[J]. J Neurooncol, 2012,109(2):357-363. DOI: 10.1007/s11060-012-0901-9. doi: 10.1007/s11060-012-0901-9 pmid: 22700031
[33]	Singh VK, Seed TM. The efficacy and safety of amifostine for the acute radiation syndrome[J]. Expert Opin Drug Saf, 2019,18(11):1077-1090. DOI: 10.1080/14740338.2019.1666104. doi: 10.1080/14740338.2019.1666104 pmid: 31526195
[34]	Lee TC, Greene-Schloesser D, Payne V. Chronic administration of the angiotensin-converting enzyme inhibitor, ramipril, prevents fractionated whole-brain irradiation-induced perirhinal cortex-dependent cognitive impairment[J]. Radiat Res, 2012,178(1):46-56. DOI: 10.1667/rr2731.1. doi: 10.1667/RR2731.1
[35]	Feng X, Liu S, Chen D, et al. Rescue of cognitive function following fractionated brain irradiation in a novel preclinical glioma model[J]. Elife, 2018,7:e38865. DOI: 10.7554/eLife.38865. doi: 10.7554/eLife.38865 pmid: 30421720
[36]	Soria B, Martin-Montalvo A, Aguilera Y, et al. Human mesenchymal stem cells prevent neurological complications of radiotherapy[J]. Front Cell Neurosci, 2019,13:204. DOI: 10.3389/fncel.2019.00204. doi: 10.3389/fncel.2019.00204 pmid: 31156392