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Delayed complications of cranial irradiation

Jorg Dietrich, MD, PhD
Vinai Gondi, MD
Minesh Mehta, MD
Section Editor
Lisa M DeAngelis, MD, FAAN, FANA
Deputy Editor
April F Eichler, MD, MPH


Cranial irradiation is used to treat patients with primary or metastatic brain tumors and as prophylaxis for selected patients at high risk of neoplastic involvement of the nervous system. A full understanding of the potential consequences associated with cranial irradiation is needed both to manage potential complications and to properly counsel patients and families prior to treatment.

The complications of radiation therapy are usually divided into acute effects that can occur during radiation or up to six weeks afterwards, early-delayed effects that appear up to six months after radiation, and late effects that can develop six months or more after the completion of radiation. Unlike acute and early-delayed reactions that are usually reversible, late reactions are generally irreversible.

The late complications of fractionated cranial irradiation will be reviewed here. Early complications of brain radiation therapy and complications of spinal cord and peripheral nerve irradiation are discussed elsewhere. (See "Acute complications of cranial irradiation" and "Complications of spinal cord irradiation" and "Brachial plexus syndromes", section on 'Neoplastic and radiation-induced brachial plexopathy' and "Lumbosacral plexus syndromes", section on 'Radiation plexopathy'.)


The effects of radiation can be divided into the effects on the vasculature of the brain as well as the direct effects on neuroglial cells and their precursors, including stem cells [1]. In addition, inflammation and blood-brain barrier disruption, induced by radiation, may also cause direct or indirect cellular damage [2].

In preclinical studies, endothelial damage occurs within the first 24 hours after a large single dose of radiation [3]. The exact mechanism is not known, but endothelial cell apoptosis appears to play a major role. Preclinical studies suggest that radiation may act directly on the plasma membrane of several cell types, activating acid sphingomyelinase and generating ceramide that initiates apoptosis [4]. Endothelial damage can lead to subsequent disruption of the blood-brain barrier and other late vascular effects, such as telangiectasias, microvascular dilatation, and thickening and hyalinization of the vessel wall. As a result, ischemic strokes or brain hemorrhage, such as microbleeds, may occur months to years after brain radiation. (See 'Cerebrovascular effects' below.)

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Literature review current through: Nov 2017. | This topic last updated: Oct 17, 2017.
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  1. Belka C, Budach W, Kortmann RD, Bamberg M. Radiation induced CNS toxicity--molecular and cellular mechanisms. Br J Cancer 2001; 85:1233.
  2. Rola R, Raber J, Rizk A, et al. Radiation-induced impairment of hippocampal neurogenesis is associated with cognitive deficits in young mice. Exp Neurol 2004; 188:316.
  3. Nordal RA, Wong CS. Molecular targets in radiation-induced blood-brain barrier disruption. Int J Radiat Oncol Biol Phys 2005; 62:279.
  4. Kolesnick R, Fuks Z. Radiation and ceramide-induced apoptosis. Oncogene 2003; 22:5897.
  5. Burger P, Boydo OB. Radiation injury to the nervous system. In: The pathology of central nervous system radiation injury, Raven Press, New York p.191.
  6. Burger PC, Mahley MS Jr, Dudka L, Vogel FS. The morphologic effects of radiation administered therapeutically for intracranial gliomas: a postmortem study of 25 cases. Cancer 1979; 44:1256.
  7. Monje M, Dietrich J. Cognitive side effects of cancer therapy demonstrate a functional role for adult neurogenesis. Behav Brain Res 2012; 227:376.
  8. Dietrich J, Monje M, Wefel J, Meyers C. Clinical patterns and biological correlates of cognitive dysfunction associated with cancer therapy. Oncologist 2008; 13:1285.
  9. Crossen JR, Garwood D, Glatstein E, Neuwelt EA. Neurobehavioral sequelae of cranial irradiation in adults: a review of radiation-induced encephalopathy. J Clin Oncol 1994; 12:627.
  10. Lai R, Abrey LE, Rosenblum MK, DeAngelis LM. Treatment-induced leukoencephalopathy in primary CNS lymphoma: a clinical and autopsy study. Neurology 2004; 62:451.
  11. Andreassen CN, Alsner J. Genetic variants and normal tissue toxicity after radiotherapy: a systematic review. Radiother Oncol 2009; 92:299.
  12. Hosking FJ, Feldman D, Bruchim R, et al. Search for inherited susceptibility to radiation-associated meningioma by genomewide SNP linkage disequilibrium mapping. Br J Cancer 2011; 104:1049.
  13. West CM, Barnett GC. Genetics and genomics of radiotherapy toxicity: towards prediction. Genome Med 2011; 3:52.
  14. Barnett GC, West CM, Dunning AM, et al. Normal tissue reactions to radiotherapy: towards tailoring treatment dose by genotype. Nat Rev Cancer 2009; 9:134.
  15. Rosenstein BS. Identification of SNPs associated with susceptibility for development of adverse reactions to radiotherapy. Pharmacogenomics 2011; 12:267.
  16. Miller RC, Lachance DH, Lucchinetti CF, et al. Multiple sclerosis, brain radiotherapy, and risk of neurotoxicity: the Mayo Clinic experience. Int J Radiat Oncol Biol Phys 2006; 66:1178.
  17. Strenger V, Lackner H, Mayer R, et al. Incidence and clinical course of radionecrosis in children with brain tumors. A 20-year longitudinal observational study. Strahlenther Onkol 2013; 189:759.
  18. Leibel S, Sheline G. Tolerance of the brain and spinal cord to conventional therapeutic irradiation. In: Radiation Injury to the Nervous System, Gutin P, Leibel S, Sheline G (Eds), Raven Press, New York 1991. p.239.
  19. Ruben JD, Dally M, Bailey M, et al. Cerebral radiation necrosis: incidence, outcomes, and risk factors with emphasis on radiation parameters and chemotherapy. Int J Radiat Oncol Biol Phys 2006; 65:499.
  20. Blonigen BJ, Steinmetz RD, Levin L, et al. Irradiated volume as a predictor of brain radionecrosis after linear accelerator stereotactic radiosurgery. Int J Radiat Oncol Biol Phys 2010; 77:996.
  21. Suh JH. Stereotactic radiosurgery for the management of brain metastases. N Engl J Med 2010; 362:1119.
  22. Chao ST, Ahluwalia MS, Barnett GH, et al. Challenges with the diagnosis and treatment of cerebral radiation necrosis. Int J Radiat Oncol Biol Phys 2013; 87:449.
  23. Chen J, Dassarath M, Yin Z, et al. Radiation induced temporal lobe necrosis in patients with nasopharyngeal carcinoma: a review of new avenues in its management. Radiat Oncol 2011; 6:128.
  24. Kano H, Kondziolka D, Lobato-Polo J, et al. T1/T2 matching to differentiate tumor growth from radiation effects after stereotactic radiosurgery. Neurosurgery 2010; 66:486.
  25. Leeman JE, Clump DA, Flickinger JC, et al. Extent of perilesional edema differentiates radionecrosis from tumor recurrence following stereotactic radiosurgery for brain metastases. Neuro Oncol 2013; 15:1732.
  26. Sugahara T, Korogi Y, Tomiguchi S, et al. Posttherapeutic intraaxial brain tumor: the value of perfusion-sensitive contrast-enhanced MR imaging for differentiating tumor recurrence from nonneoplastic contrast-enhancing tissue. AJNR Am J Neuroradiol 2000; 21:901.
  27. Mitsuya K, Nakasu Y, Horiguchi S, et al. Perfusion weighted magnetic resonance imaging to distinguish the recurrence of metastatic brain tumors from radiation necrosis after stereotactic radiosurgery. J Neurooncol 2010; 99:81.
  28. Asao C, Korogi Y, Kitajima M, et al. Diffusion-weighted imaging of radiation-induced brain injury for differentiation from tumor recurrence. AJNR Am J Neuroradiol 2005; 26:1455.
  29. Rock JP, Scarpace L, Hearshen D, et al. Associations among magnetic resonance spectroscopy, apparent diffusion coefficients, and image-guided histopathology with special attention to radiation necrosis. Neurosurgery 2004; 54:1111.
  30. Quan D, Hackney DB, Pruitt AA, et al. Transient MRI enhancement in a patient with seizures and previously resected glioma: use of MRS. Neurology 1999; 53:211.
  31. Davidson A, Tait DM, Payne GS, et al. Magnetic resonance spectroscopy in the evaluation of neurotoxicity following cranial irradiation for childhood cancer. Br J Radiol 2000; 73:421.
  32. Henry RG, Vigneron DB, Fischbein NJ, et al. Comparison of relative cerebral blood volume and proton spectroscopy in patients with treated gliomas. AJNR Am J Neuroradiol 2000; 21:357.
  33. Lin A, Bluml S, Mamelak AN. Efficacy of proton magnetic resonance spectroscopy in clinical decision making for patients with suspected malignant brain tumors. J Neurooncol 1999; 45:69.
  34. Kimura T, Sako K, Tanaka K, et al. Evaluation of the response of metastatic brain tumors to stereotactic radiosurgery by proton magnetic resonance spectroscopy, 201TlCl single-photon emission computerized tomography, and gadolinium-enhanced magnetic resonance imaging. J Neurosurg 2004; 100:835.
  35. Valk PE, Budinger TF, Levin VA, et al. PET of malignant cerebral tumors after interstitial brachytherapy. Demonstration of metabolic activity and correlation with clinical outcome. J Neurosurg 1988; 69:830.
  36. Thiel A, Pietrzyk U, Sturm V, et al. Enhanced accuracy in differential diagnosis of radiation necrosis by positron emission tomography-magnetic resonance imaging coregistration: technical case report. Neurosurgery 2000; 46:232.
  37. Barker FG 2nd, Chang SM, Valk PE, et al. 18-Fluorodeoxyglucose uptake and survival of patients with suspected recurrent malignant glioma. Cancer 1997; 79:115.
  38. Doyle WK, Budinger TF, Valk PE, et al. Differentiation of cerebral radiation necrosis from tumor recurrence by [18F]FDG and 82Rb positron emission tomography. J Comput Assist Tomogr 1987; 11:563.
  39. Janus TJ, Kim EE, Tilbury R, et al. Use of [18F]fluorodeoxyglucose positron emission tomography in patients with primary malignant brain tumors. Ann Neurol 1993; 33:540.
  40. Glantz MJ, Hoffman JM, Coleman RE, et al. Identification of early recurrence of primary central nervous system tumors by [18F]fluorodeoxyglucose positron emission tomography. Ann Neurol 1991; 29:347.
  41. Ross DA, Sandler HM, Balter JM, et al. Imaging changes after stereotactic radiosurgery of primary and secondary malignant brain tumors. J Neurooncol 2002; 56:175.
  42. Schwartz RB, Holman BL, Polak JF, et al. Dual-isotope single-photon emission computerized tomography scanning in patients with glioblastoma multiforme: association with patient survival and histopathological characteristics of tumor after high-dose radiotherapy. J Neurosurg 1998; 89:60.
  43. Eisele SC, Dietrich J. Cerebral radiation necrosis: diagnostic challenge and clinical management. Rev Neurol 2015; 61:225.
  44. Gonzalez J, Kumar AJ, Conrad CA, Levin VA. Effect of bevacizumab on radiation necrosis of the brain. Int J Radiat Oncol Biol Phys 2007; 67:323.
  45. Torcuator R, Zuniga R, Mohan YS, et al. Initial experience with bevacizumab treatment for biopsy confirmed cerebral radiation necrosis. J Neurooncol 2009; 94:63.
  46. Liu AK, Macy ME, Foreman NK. Bevacizumab as therapy for radiation necrosis in four children with pontine gliomas. Int J Radiat Oncol Biol Phys 2009; 75:1148.
  47. Levin VA, Bidaut L, Hou P, et al. Randomized double-blind placebo-controlled trial of bevacizumab therapy for radiation necrosis of the central nervous system. Int J Radiat Oncol Biol Phys 2011; 79:1487.
  48. Deibert CP, Ahluwalia MS, Sheehan JP, et al. Bevacizumab for refractory adverse radiation effects after stereotactic radiosurgery. J Neurooncol 2013; 115:217.
  49. Boothe D, Young R, Yamada Y, et al. Bevacizumab as a treatment for radiation necrosis of brain metastases post stereotactic radiosurgery. Neuro Oncol 2013; 15:1257.
  50. Sadraei NH, Dahiya S, Chao ST, et al. Treatment of cerebral radiation necrosis with bevacizumab: the Cleveland clinic experience. Am J Clin Oncol 2015; 38:304.
  51. Jeyaretna DS, Curry WT Jr, Batchelor TT, et al. Exacerbation of cerebral radiation necrosis by bevacizumab. J Clin Oncol 2011; 29:e159.
  52. Furuse M, Kawabata S, Kuroiwa T, Miyatake S. Repeated treatments with bevacizumab for recurrent radiation necrosis in patients with malignant brain tumors: a report of 2 cases. J Neurooncol 2011; 102:471.
  53. McPherson CM, Warnick RE. Results of contemporary surgical management of radiation necrosis using frameless stereotaxis and intraoperative magnetic resonance imaging. J Neurooncol 2004; 68:41.
  54. Rao MS, Hargreaves EL, Khan AJ, et al. Magnetic resonance-guided laser ablation improves local control for postradiosurgery recurrence and/or radiation necrosis. Neurosurgery 2014; 74:658.
  55. Glantz MJ, Burger PC, Friedman AH, et al. Treatment of radiation-induced nervous system injury with heparin and warfarin. Neurology 1994; 44:2020.
  56. Chuba PJ, Aronin P, Bhambhani K, et al. Hyperbaric oxygen therapy for radiation-induced brain injury in children. Cancer 1997; 80:2005.
  57. Cihan YB, Uzun G, Yildiz S, Dönmez H. Hyperbaric oxygen therapy for radiation-induced brain necrosis in a patient with primary central nervous system lymphoma. J Surg Oncol 2009; 100:732.
  58. Chang EL, Wefel JS, Hess KR, et al. Neurocognition in patients with brain metastases treated with radiosurgery or radiosurgery plus whole-brain irradiation: a randomised controlled trial. Lancet Oncol 2009; 10:1037.
  59. Sun A, Bae K, Gore EM, et al. Phase III trial of prophylactic cranial irradiation compared with observation in patients with locally advanced non-small-cell lung cancer: neurocognitive and quality-of-life analysis. J Clin Oncol 2011; 29:279.
  60. Li J, Bentzen SM, Renschler M, Mehta MP. Regression after whole-brain radiation therapy for brain metastases correlates with survival and improved neurocognitive function. J Clin Oncol 2007; 25:1260.
  61. 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. JAMA 2016; 316:401.
  62. Soffietti R, Kocher M, Abacioglu UM, et al. A European Organisation for Research and Treatment of Cancer phase III trial of adjuvant whole-brain radiotherapy versus observation in patients with one to three brain metastases from solid tumors after surgical resection or radiosurgery: quality-of-life results. J Clin Oncol 2013; 31:65.
  63. Gondi V, Paulus R, Bruner DW, et al. Decline in tested and self-reported cognitive functioning after prophylactic cranial irradiation for lung cancer: pooled secondary analysis of Radiation Therapy Oncology Group randomized trials 0212 and 0214. Int J Radiat Oncol Biol Phys 2013; 86:656.
  64. Monaco EA 3rd, Faraji AH, Berkowitz O, et al. Leukoencephalopathy after whole-brain radiation therapy plus radiosurgery versus radiosurgery alone for metastatic lung cancer. Cancer 2013; 119:226.
  65. Wara WM, Bauman GS, Sneed PK, et al. Brain, brain stem and cerebellum. In: Principles and Practice of Radiation Oncology, 3rd ed, Perez E, Brady LW (Eds), Lippincott-Raven, Philadelphia 1997. p.799.
  66. Sabsevitz DS, Bovi JA, Leo PD, et al. The role of pre-treatment white matter abnormalities in developing white matter changes following whole brain radiation: a volumetric study. J Neurooncol 2013; 114:291.
  67. Constine LS, Konski A, Ekholm S, et al. Adverse effects of brain irradiation correlated with MR and CT imaging. Int J Radiat Oncol Biol Phys 1988; 15:319.
  68. DeAngelis LM, Delattre JY, Posner JB. Radiation-induced dementia in patients cured of brain metastases. Neurology 1989; 39:789.
  69. Tekkök IH, Carter DA, Robinson MG, Brinker R. Reversal of CNS-prophylaxis-related leukoencephalopathy after CSF shunting: case histories of identical twins. Childs Nerv Syst 1996; 12:309.
  70. Perrini P, Scollato A, Cioffi F, et al. Radiation leukoencephalopathy associated with moderate hydrocephalus: intracranial pressure monitoring and results of ventriculoperitoneal shunting. Neurol Sci 2002; 23:237.
  71. Dietrich J, Klein JP. Imaging of cancer therapy-induced central nervous system toxicity. Neurol Clin 2014; 32:147.
  72. Correa DD, DeAngelis LM, Shi W, et al. Cognitive functions in low-grade gliomas: disease and treatment effects. J Neurooncol 2007; 81:175.
  73. Kiehna EN, Mulhern RK, Li C, et al. Changes in attentional performance of children and young adults with localized primary brain tumors after conformal radiation therapy. J Clin Oncol 2006; 24:5283.
  74. Jalali R, Gupta T, Goda JS, et al. Efficacy of Stereotactic Conformal Radiotherapy vs Conventional Radiotherapy on Benign and Low-Grade Brain Tumors: A Randomized Clinical Trial. JAMA Oncol 2017; 3:1368.
  75. Prust MJ, Jafari-Khouzani K, Kalpathy-Cramer J, et al. Standard chemoradiation for glioblastoma results in progressive brain volume loss. Neurology 2015; 85:683.
  76. Karunamuni R, Bartsch H, White NS, et al. Dose-Dependent Cortical Thinning After Partial Brain Irradiation in High-Grade Glioma. Int J Radiat Oncol Biol Phys 2016; 94:297.
  77. Klein M, Heimans JJ, Aaronson NK, et al. Effect of radiotherapy and other treatment-related factors on mid-term to long-term cognitive sequelae in low-grade gliomas: a comparative study. Lancet 2002; 360:1361.
  78. Douw L, Klein M, Fagel SS, et al. Cognitive and radiological effects of radiotherapy in patients with low-grade glioma: long-term follow-up. Lancet Neurol 2009; 8:810.
  79. Brown PD, Buckner JC, O'Fallon JR, et al. Effects of radiotherapy on cognitive function in patients with low-grade glioma measured by the folstein mini-mental state examination. J Clin Oncol 2003; 21:2519.
  80. Meyers CA, Wefel JS. The use of the mini-mental state examination to assess cognitive functioning in cancer trials: no ifs, ands, buts, or sensitivity. J Clin Oncol 2003; 21:3557.
  81. Prabhu RS, Won M, Shaw EG, et al. Effect of the addition of chemotherapy to radiotherapy on cognitive function in patients with low-grade glioma: secondary analysis of RTOG 98-02. J Clin Oncol 2014; 32:535.
  82. Meyers CA, Weitzner MA, Valentine AD, Levin VA. Methylphenidate therapy improves cognition, mood, and function of brain tumor patients. J Clin Oncol 1998; 16:2522.
  83. Mulhern RK, Khan RB, Kaplan S, et al. Short-term efficacy of methylphenidate: a randomized, double-blind, placebo-controlled trial among survivors of childhood cancer. J Clin Oncol 2004; 22:4795.
  84. Butler JM Jr, Case LD, Atkins J, et al. A phase III, double-blind, placebo-controlled prospective randomized clinical trial of d-threo-methylphenidate HCl in brain tumor patients receiving radiation therapy. Int J Radiat Oncol Biol Phys 2007; 69:1496.
  85. Gehring K, Patwardhan SY, Collins R, et al. A randomized trial on the efficacy of methylphenidate and modafinil for improving cognitive functioning and symptoms in patients with a primary brain tumor. J Neurooncol 2012; 107:165.
  86. Page BR, Shaw EG, Lu L, et al. Phase II double-blind placebo-controlled randomized study of armodafinil for brain radiation-induced fatigue. Neuro Oncol 2015; 17:1393.
  87. Lee EQ, Muzikansky A, Drappatz J, et al. A randomized, placebo-controlled pilot trial of armodafinil for fatigue in patients with gliomas undergoing radiotherapy. Neuro Oncol 2016; 18:849.
  88. 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 Clin Oncol 2006; 24:1415.
  89. Rapp SR, Case LD, Peiffer A, et al. Donepezil for Irradiated Brain Tumor Survivors: A Phase III Randomized Placebo-Controlled Clinical Trial. J Clin Oncol 2015; 33:1653.
  90. Campen CJ, Kranick SM, Kasner SE, et al. Cranial irradiation increases risk of stroke in pediatric brain tumor survivors. Stroke 2012; 43:3035.
  91. Bowers DC, Liu Y, Leisenring W, et al. Late-occurring stroke among long-term survivors of childhood leukemia and brain tumors: a report from the Childhood Cancer Survivor Study. J Clin Oncol 2006; 24:5277.
  92. Murphy ES, Xie H, Merchant TE, et al. Review of cranial radiotherapy-induced vasculopathy. J Neurooncol 2015; 122:421.
  93. Desai SS, Paulino AC, Mai WY, Teh BS. Radiation-induced moyamoya syndrome. Int J Radiat Oncol Biol Phys 2006; 65:1222.
  94. Ullrich NJ, Robertson R, Kinnamon DD, et al. Moyamoya following cranial irradiation for primary brain tumors in children. Neurology 2007; 68:932.
  95. Aizer AA, Du R, Wen PY, Arvold ND. Radiotherapy and death from cerebrovascular disease in patients with primary brain tumors. J Neurooncol 2015; 124:291.
  96. El-Fayech C, Haddy N, Allodji RS, et al. Cerebrovascular Diseases in Childhood Cancer Survivors: Role of the Radiation Dose to Willis Circle Arteries. Int J Radiat Oncol Biol Phys 2017; 97:278.
  97. Kranick SM, Campen CJ, Kasner SE, et al. Headache as a risk factor for neurovascular events in pediatric brain tumor patients. Neurology 2013; 80:1452.
  98. Haddy N, Mousannif A, Tukenova M, et al. Relationship between the brain radiation dose for the treatment of childhood cancer and the risk of long-term cerebrovascular mortality. Brain 2011; 134:1362.
  99. Hooning MJ, Dorresteijn LD, Aleman BM, et al. Decreased risk of stroke among 10-year survivors of breast cancer. J Clin Oncol 2006; 24:5388.
  100. Strenger V, Sovinz P, Lackner H, et al. Intracerebral cavernous hemangioma after cranial irradiation in childhood. Incidence and risk factors. Strahlenther Onkol 2008; 184:276.
  101. Burn S, Gunny R, Phipps K, et al. Incidence of cavernoma development in children after radiotherapy for brain tumors. J Neurosurg 2007; 106:379.
  102. Lew SM, Morgan JN, Psaty E, et al. Cumulative incidence of radiation-induced cavernomas in long-term survivors of medulloblastoma. J Neurosurg 2006; 104:103.
  103. Heckl S, Aschoff A, Kunze S. Radiation-induced cavernous hemangiomas of the brain: a late effect predominantly in children. Cancer 2002; 94:3285.
  104. Kerklaan JP, Lycklama á Nijeholt GJ, Wiggenraad RG, et al. SMART syndrome: a late reversible complication after radiation therapy for brain tumours. J Neurol 2011; 258:1098.
  105. Farid K, Meissner WG, Samier-Foubert A, et al. Normal cerebrovascular reactivity in Stroke-like Migraine Attacks after Radiation Therapy syndrome. Clin Nucl Med 2010; 35:583.
  106. van Kempen-Harteveld ML, Struikmans H, Kal HB, et al. Cataract after total body irradiation and bone marrow transplantation: degree of visual impairment. Int J Radiat Oncol Biol Phys 2002; 52:1375.
  107. Mayo C, Martel MK, Marks LB, et al. Radiation dose-volume effects of optic nerves and chiasm. Int J Radiat Oncol Biol Phys 2010; 76:S28.
  108. Harris JR, Levene MB. Visual complications following irradiation for pituitary adenomas and craniopharyngiomas. Radiology 1976; 120:167.
  109. Borruat FX, Schatz NJ, Glaser JS, et al. Visual recovery from radiation-induced optic neuropathy. The role of hyperbaric oxygen therapy. J Clin Neuroophthalmol 1993; 13:98.
  110. Kelly PJ, Dinkin MJ, Drappatz J, et al. Unexpected late radiation neurotoxicity following bevacizumab use: a case series. J Neurooncol 2011; 102:485.
  111. Fishman ML, Bean SC, Cogan DG. Optic atrophy following prophylactic chemotherapy and cranial radiation for acute lymphocytic leukemia. Am J Ophthalmol 1976; 82:571.
  112. De Cicco L, Cella L, Liuzzi R, et al. Radiation therapy in primary orbital lymphoma: a single institution retrospective analysis. Radiat Oncol 2009; 4:60.
  113. Kennerdell JS, Flores NE, Hartsock RJ. Low-dose radiotherapy for lymphoid lesions of the orbit and ocular adnexa. Ophthal Plast Reconstr Surg 1999; 15:129.
  114. Bessell EM, Henk JM, Wright JE, Whitelocke RA. Orbital and conjunctival lymphoma treatment and prognosis. Radiother Oncol 1988; 13:237.
  115. Parsons JT, Bova FJ, Fitzgerald CR, et al. Radiation retinopathy after external-beam irradiation: analysis of time-dose factors. Int J Radiat Oncol Biol Phys 1994; 30:765.
  116. Jereczek-Fossa BA, Zarowski A, Milani F, Orecchia R. Radiotherapy-induced ear toxicity. Cancer Treat Rev 2003; 29:417.
  117. Bhandare N, Antonelli PJ, Morris CG, et al. Ototoxicity after radiotherapy for head and neck tumors. Int J Radiat Oncol Biol Phys 2007; 67:469.
  118. Ho WK, Wei WI, Kwong DL, et al. Long-term sensorineural hearing deficit following radiotherapy in patients suffering from nasopharyngeal carcinoma: A prospective study. Head Neck 1999; 21:547.
  119. Herrmann F, Dörr W, Müller R, Herrmann T. A prospective study on radiation-induced changes in hearing function. Int J Radiat Oncol Biol Phys 2006; 65:1338.
  120. Pan CC, Eisbruch A, Lee JS, et al. Prospective study of inner ear radiation dose and hearing loss in head-and-neck cancer patients. Int J Radiat Oncol Biol Phys 2005; 61:1393.
  121. Hua C, Bass JK, Khan R, et al. Hearing loss after radiotherapy for pediatric brain tumors: effect of cochlear dose. Int J Radiat Oncol Biol Phys 2008; 72:892.
  122. Paulino AC, Lobo M, Teh BS, et al. Ototoxicity after intensity-modulated radiation therapy and cisplatin-based chemotherapy in children with medulloblastoma. Int J Radiat Oncol Biol Phys 2010; 78:1445.
  123. Kretschmar CS, Warren MP, Lavally BL, et al. Ototoxicity of preradiation cisplatin for children with central nervous system tumors. J Clin Oncol 1990; 8:1191.
  124. Low WK, Toh ST, Wee J, et al. Sensorineural hearing loss after radiotherapy and chemoradiotherapy: a single, blinded, randomized study. J Clin Oncol 2006; 24:1904.
  125. Huang E, Teh BS, Strother DR, et al. Intensity-modulated radiation therapy for pediatric medulloblastoma: early report on the reduction of ototoxicity. Int J Radiat Oncol Biol Phys 2002; 52:599.
  126. Formanek M, Czerny C, Gstoettner W, Kornfehl J. Cochlear implantation as a successful rehabilitation for radiation-induced deafness. Eur Arch Otorhinolaryngol 1998; 255:175.
  127. Zuur CL, Simis YJ, Lansdaal PE, et al. Ototoxicity in a randomized phase III trial of intra-arterial compared with intravenous cisplatin chemoradiation in patients with locally advanced head and neck cancer. J Clin Oncol 2007; 25:3759.
  128. Zuur CL, Simis YJ, Lansdaal PE, et al. Risk factors of ototoxicity after cisplatin-based chemo-irradiation in patients with locally advanced head-and-neck cancer: a multivariate analysis. Int J Radiat Oncol Biol Phys 2007; 68:1320.
  129. Constine LS, Woolf PD, Cann D, et al. Hypothalamic-pituitary dysfunction after radiation for brain tumors. N Engl J Med 1993; 328:87.
  130. Taphoorn MJ, Heimans JJ, van der Veen EA, Karim AB. Endocrine functions in long-term survivors of low-grade supratentorial glioma treated with radiation therapy. J Neurooncol 1995; 25:97.
  131. Collet-Solberg PF, Sernyak H, Satin-Smith M, et al. Endocrine outcome in long-term survivors of low-grade hypothalamic/chiasmatic glioma. Clin Endocrinol (Oxf) 1997; 47:79.
  132. Arlt W, Hove U, Müller B, et al. Frequent and frequently overlooked: treatment-induced endocrine dysfunction in adult long-term survivors of primary brain tumors. Neurology 1997; 49:498.
  133. Lam KS, Tse VK, Wang C, et al. Effects of cranial irradiation on hypothalamic-pituitary function--a 5-year longitudinal study in patients with nasopharyngeal carcinoma. Q J Med 1991; 78:165.
  134. Pai HH, Thornton A, Katznelson L, et al. Hypothalamic/pituitary function following high-dose conformal radiotherapy to the base of skull: demonstration of a dose-effect relationship using dose-volume histogram analysis. Int J Radiat Oncol Biol Phys 2001; 49:1079.
  135. Minniti G, Jaffrain-Rea ML, Osti M, et al. The long-term efficacy of conventional radiotherapy in patients with GH-secreting pituitary adenomas. Clin Endocrinol (Oxf) 2005; 62:210.
  136. Appelman-Dijkstra NM, Kokshoorn NE, Dekkers OM, et al. Pituitary dysfunction in adult patients after cranial radiotherapy: systematic review and meta-analysis. J Clin Endocrinol Metab 2011; 96:2330.
  137. Wara W, Bauman G, Sneed P. Brain, brain stem, and cerebellum. In: Principles and Practice of Radiation Oncology, Perez C, Brady L (Eds), Lippincott-Raven, Philadelphia 1998. p.777.
  138. Balasubramaniam A, Shannon P, Hodaie M, et al. Glioblastoma multiforme after stereotactic radiotherapy for acoustic neuroma: case report and review of the literature. Neuro Oncol 2007; 9:447.
  139. Sheehan J, Yen CP, Steiner L. Gamma knife surgery-induced meningioma. Report of two cases and review of the literature. J Neurosurg 2006; 105:325.