Smarter Decisions,
Better Care

UpToDate synthesizes the most recent medical information into evidence-based practical recommendations clinicians trust to make the right point-of-care decisions.

  • Rigorous editorial process: Evidence-based treatment recommendations
  • World-Renowned physician authors: over 5,100 physician authors and editors around the globe
  • Innovative technology: integrates into the workflow; access from EMRs

Choose from the list below to learn more about subscriptions for a:


Subscribers log in here


Related articles

Complications of cranial irradiation

INTRODUCTION

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/or families prior to treatment.

The primary factors influencing the likelihood of developing complications include the volume of normal brain tissue treated, the total radiation dose, and the fractionation schedule. The likelihood of brain damage also increases in the young (ie, <5 years old) and the elderly. Furthermore, the use of concurrent or sequential chemotherapy can significantly affect the incidence and severity of radiation-induced toxicity. In addition, the underlying tumor often can impair neurologic function, making it difficult to assess accurately the separate effect of radiation. Finally, genetic factors may make certain individuals more susceptible to otherwise safe doses of radiation. For example, a study of 15 families with radiation-induced meningiomas after treatment for tinea capitis identified several genes as potential risk factors [1]. Other genetic markers have been found to enhance susceptibility when specific organs are irradiated [2].

The complications of radiation therapy (RT) are usually divided into acute effects that can occur during the course of radiation, early-delayed effects that appear two to four months after radiation, and late effects that can develop more than 90 days after the initiation of RT. The Radiation Therapy Oncology Group (RTOG) has established specific grading criteria for acute and delayed toxicities (table 1 and table 2) [3].

Complications that might occur many months or even years following cranial irradiation are generally not important as a consideration for patients with brain metastases or grade IV primary brain tumors, where a median survival in the range of 6 to 15 months is expected. Late effects are a more important consideration for patients with a much longer life expectancy (eg, low-grade glioma and primary CNS lymphoma patients or pediatric patients with acute lymphocytic leukemia) [4,5]. The distinction between early and late complications is also important since acute and early-delayed complications are usually reversible while late reactions often are not.

Both the acute and late complications of fractionated cranial irradiation will be reviewed here. Complications of spinal cord and peripheral nerve irradiation and complications of single-fraction cranial radiosurgery are discussed elsewhere. (See "Complications of spinal cord irradiation" and "Complications of peripheral nerve irradiation" and "Complications of cranial stereotactic radiosurgery".)

                                               

Subscribers log in here

To continue reading this article, you must log in with your personal, hospital, or group practice subscription. For more information or to purchase a personal subscription, click below on the option that best describes you:
Literature review current through: Aug 2014. | This topic last updated: Oct 14, 2013.
The content on the UpToDate website is not intended nor recommended as a substitute for medical advice, diagnosis, or treatment. Always seek the advice of your own physician or other qualified health care professional regarding any medical questions or conditions. The use of this website is governed by the UpToDate Terms of Use ©2014 UpToDate, Inc.
References
Top
  1. 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.
  2. Rosenstein BS. Identification of SNPs associated with susceptibility for development of adverse reactions to radiotherapy. Pharmacogenomics 2011; 12:267.
  3. RTOG Acute Radiation Morbidity Scoring Criteria www.rtog.org/members/toxicity/acute.html (Accessed on June 08, 2011).
  4. Borgelt B, Gelber R, Kramer S, et al. The palliation of brain metastases: final results of the first two studies by the Radiation Therapy Oncology Group. Int J Radiat Oncol Biol Phys 1980; 6:1.
  5. Simpson JR, Horton J, Scott C, et al. Influence of location and extent of surgical resection on survival of patients with glioblastoma multiforme: results of three consecutive Radiation Therapy Oncology Group (RTOG) clinical trials. Int J Radiat Oncol Biol Phys 1993; 26:239.
  6. Belka C, Budach W, Kortmann RD, Bamberg M. Radiation induced CNS toxicity--molecular and cellular mechanisms. Br J Cancer 2001; 85:1233.
  7. 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.
  8. Nordal RA, Wong CS. Molecular targets in radiation-induced blood-brain barrier disruption. Int J Radiat Oncol Biol Phys 2005; 62:279.
  9. Humpl T, Brühl K, Bohl J, et al. Cerebral haemorrhage in long-term survivors of childhood acute lymphoblastic leukaemia. Eur J Pediatr 1997; 156:367.
  10. Kurita H, Kawahara N, Asai A, et al. Radiation-induced apoptosis of oligodendrocytes in the adult rat brain. Neurol Res 2001; 23:869.
  11. Hellström NA, Björk-Eriksson T, Blomgren K, Kuhn HG. Differential recovery of neural stem cells in the subventricular zone and dentate gyrus after ionizing radiation. Stem Cells 2009; 27:634.
  12. Jaganathan A, Tiwari M, Phansekar R, et al. Intensity-modulated radiation to spare neural stem cells in brain tumors: a computational platform for evaluation of physical and biological dose metrics. J Cancer Res Ther 2011; 7:58.
  13. Lawrence YR, Li XA, el Naqa I, et al. Radiation dose-volume effects in the brain. Int J Radiat Oncol Biol Phys 2010; 76:S20.
  14. Young DF, Posner JB, Chu F, Nisce L. Rapid-course radiation therapy of cerebral metastases: results and complications. Cancer 1974; 34:1069.
  15. Hindo WA, DeTrana FA 3rd, Lee MS, Hendrickson FR. Large dose increment irradiation in treatment of cerebral metastases. Cancer 1970; 26:138.
  16. Phillips P, Delattre JY, Berger C. Early and progressive increases in regional brain capillary permeability following single and fractionated dose cranial radiation in the rat. Neurology1987; 37:301 (Abstract).
  17. Evans ML, Graham MM, Mahler PA, Rasey JS. Use of steroids to suppress vascular response to radiation. Int J Radiat Oncol Biol Phys 1987; 13:563.
  18. DeAngelis LM, Posner JB. Neurologic Complications of Cancer, 2nd, Oxford University Press, 2008. p.163.
  19. Powell C, Guerrero D, Sardell S, et al. Somnolence syndrome in patients receiving radical radiotherapy for primary brain tumours: a prospective study. Radiother Oncol 2011; 100:131.
  20. Breitbart W, Alici Y. Psychostimulants for cancer-related fatigue. J Natl Compr Canc Netw 2010; 8:933.
  21. Lawenda BD, Gagne HM, Gierga DP, et al. Permanent alopecia after cranial irradiation: dose-response relationship. Int J Radiat Oncol Biol Phys 2004; 60:879.
  22. Aguiar D, Pazo R, Durán I, et al. Toxic epidermal necrolysis in patients receiving anticonvulsants and cranial irradiation: a risk to consider. J Neurooncol 2004; 66:345.
  23. Jereczek-Fossa BA, Zarowski A, Milani F, Orecchia R. Radiotherapy-induced ear toxicity. Cancer Treat Rev 2003; 29:417.
  24. Cairncross JG, Salmon J, Kim JH, Posner JB. Acute parotitis and hyperamylasemia following whole-brain radiation therapy. Ann Neurol 1980; 7:385.
  25. Ryan J. Radiation somnolence syndrome. J Pediatr Oncol Nurs 2000; 17:50.
  26. Freeman JE, Johnston PG, Voke JM. Somnolence after prophylactic cranial irradiation in children with acute lymphoblastic leukaemia. Br Med J 1973; 4:523.
  27. Berg RA, Ch'ien LT, Lancaster W, et al. Neuropsychological sequelae of postradiation somnolence syndrome. J Dev Behav Pediatr 1983; 4:103.
  28. Mandell LR, Walker RW, Steinherz P, Fuks Z. Reduced incidence of the somnolence syndrome in leukemic children with steroid coverage during prophylactic cranial radiation therapy. Results of a pilot study. Cancer 1989; 63:1975.
  29. Uzal D, Ozyar E, Hayran M, et al. Reduced incidence of the somnolence syndrome after prophylactic cranial irradiation in children with acute lymphoblastic leukemia. Radiother Oncol 1998; 48:29.
  30. Schultheiss TE, Kun LE, Ang KK, Stephens LC. Radiation response of the central nervous system. Int J Radiat Oncol Biol Phys 1995; 31:1093.
  31. Xu JL, Li YL, Lian JM, et al. Distinction between postoperative recurrent glioma and radiation injury using MR diffusion tensor imaging. Neuroradiology 2010; 52:1193.
  32. Armstrong C, Ruffer J, Corn B, et al. Biphasic patterns of memory deficits following moderate-dose partial-brain irradiation: neuropsychologic outcome and proposed mechanisms. J Clin Oncol 1995; 13:2263.
  33. Armstrong CL, Corn BW, Ruffer JE, et al. Radiotherapeutic effects on brain function: double dissociation of memory systems. Neuropsychiatry Neuropsychol Behav Neurol 2000; 13:101.
  34. RTOG Late Radiation Morbidity Scoring Schema www.rtog.org/members/toxicity/late.html (Accessed on June 08, 2011).
  35. 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.
  36. 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.
  37. 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.
  38. Emami B, Lyman J, Brown A, et al. Tolerance of normal tissue to therapeutic irradiation. Int J Radiat Oncol Biol Phys 1991; 21:109.
  39. 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.
  40. 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.
  41. Wara WM, Bauman GS, Sneed PK, et al. Brain, brain stem and cerebellum. In: Principles and Practice of Radiation Oncology, 3rd, Perez E, Brady LW (Eds), Lippincott-Raven, Philadelphia 1997. p.799.
  42. 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.
  43. 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.
  44. 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.
  45. 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.
  46. 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.
  47. 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.
  48. 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.
  49. 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.
  50. 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.
  51. 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.
  52. 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.
  53. 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.
  54. 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.
  55. 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.
  56. 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.
  57. Glantz MJ, Burger PC, Friedman AH, et al. Treatment of radiation-induced nervous system injury with heparin and warfarin. Neurology 1994; 44:2020.
  58. Chuba PJ, Aronin P, Bhambhani K, et al. Hyperbaric oxygen therapy for radiation-induced brain injury in children. Cancer 1997; 80:2005.
  59. 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.
  60. 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.
  61. 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.
  62. Torcuator R, Zuniga R, Mohan YS, et al. Initial experience with bevacizumab treatment for biopsy confirmed cerebral radiation necrosis. J Neurooncol 2009; 94:63.
  63. 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.
  64. 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.
  65. Deibert CP, Ahluwalia MS, Sheehan JP, et al. Bevacizumab for refractory adverse radiation effects after stereotactic radiosurgery. J Neurooncol 2013; 115:217.
  66. 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.
  67. Jeyaretna DS, Curry WT Jr, Batchelor TT, et al. Exacerbation of cerebral radiation necrosis by bevacizumab. J Clin Oncol 2011; 29:e159.
  68. 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.
  69. 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.
  70. Price RA, Jamieson PA. The central nervous system in childhood leukemia. II. Subacute leukoencephalopathy. Cancer 1975; 35:306.
  71. Doyle DM, Einhorn LH. Delayed effects of whole brain radiotherapy in germ cell tumor patients with central nervous system metastases. Int J Radiat Oncol Biol Phys 2008; 70:1361.
  72. Frytak S, Shaw JN, O'Neill BP, et al. Leukoencephalopathy in small cell lung cancer patients receiving prophylactic cranial irradiation. Am J Clin Oncol 1989; 12:27.
  73. 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.
  74. 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.
  75. 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.
  76. 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.
  77. Regine WF, Schmitt FA, Scott CB, et al. Feasibility of neurocognitive outcome evaluations in patients with brain metastases in a multi-institutional cooperative group setting: results of Radiation Therapy Oncology Group trial BR-0018. Int J Radiat Oncol Biol Phys 2004; 58:1346.
  78. Duffey P, Chari G, Cartlidge NE, Shaw PJ. Progressive deterioration of intellect and motor function occurring several decades after cranial irradiation. A new facet in the clinical spectrum of radiation encephalopathy. Arch Neurol 1996; 53:814.
  79. Meyers CA, Smith JA, Bezjak A, et al. Neurocognitive function and progression in patients with brain metastases treated with whole-brain radiation and motexafin gadolinium: results of a randomized phase III trial. J Clin Oncol 2004; 22:157.
  80. 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.
  81. Patchell RA, Tibbs PA, Regine WF, et al. Postoperative radiotherapy in the treatment of single metastases to the brain: a randomized trial. JAMA 1998; 280:1485.
  82. 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.
  83. National Institutes of Health Clinical Trials database. http://www.clinicaltrials.gov/ (Accessed on February 08, 2011).
  84. Correa DD, DeAngelis LM, Shi W, et al. Cognitive functions in low-grade gliomas: disease and treatment effects. J Neurooncol 2007; 81:175.
  85. Karim AB, Afra D, Cornu P, et al. Randomized trial on the efficacy of radiotherapy for cerebral low-grade glioma in the adult: European Organization for Research and Treatment of Cancer Study 22845 with the Medical Research Council study BRO4: an interim analysis. Int J Radiat Oncol Biol Phys 2002; 52:316.
  86. 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.
  87. 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.
  88. 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.
  89. 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.
  90. Stuschke M, Pöttgen C. Prophylactic cranial irradiation as a component of intensified initial treatment of locally advanced non-small cell lung cancer. Lung Cancer 2003; 42 Suppl 1:S53.
  91. Tai TH, Yu E, Dickof P, et al. Prophylactic cranial irradiation revisited: cost-effectiveness and quality of life in small-cell lung cancer. Int J Radiat Oncol Biol Phys 2002; 52:68.
  92. Kanard A, Frytak S, Jatoi A. Cognitive dysfunction in patients with small-cell lung cancer: incidence, causes, and suggestions on management. J Support Oncol 2004; 2:127.
  93. Hsiao KY, Yeh SA, Chang CC, et al. Cognitive function before and after intensity-modulated radiation therapy in patients with nasopharyngeal carcinoma: a prospective study. Int J Radiat Oncol Biol Phys 2010; 77:722.
  94. 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.
  95. 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.
  96. 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.
  97. 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.
  98. 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.
  99. Rapp SR, Case D, Peiffer A, et al. Phase III randomized, double-blind, placebo-controlled trial of donepezil in irradiated brain tumor survivors (abstract #2006). J Clin Oncol 2013.
  100. Aarsen FK, Paquier PF, Reddingius RE, et al. Functional outcome after low-grade astrocytoma treatment in childhood. Cancer 2006; 106:396.
  101. Fouladi M, Gilger E, Kocak M, et al. Intellectual and functional outcome of children 3 years old or younger who have CNS malignancies. J Clin Oncol 2005; 23:7152.
  102. Mulhern RK, Palmer SL, Merchant TE, et al. Neurocognitive consequences of risk-adapted therapy for childhood medulloblastoma. J Clin Oncol 2005; 23:5511.
  103. Mulhern RK, Kepner JL, Thomas PR, et al. Neuropsychologic functioning of survivors of childhood medulloblastoma randomized to receive conventional or reduced-dose craniospinal irradiation: a Pediatric Oncology Group study. J Clin Oncol 1998; 16:1723.
  104. Palmer SL, Armstrong C, Onar-Thomas A, et al. Processing speed, attention, and working memory after treatment for medulloblastoma: an international, prospective, and longitudinal study. J Clin Oncol 2013; 31:3494.
  105. Duffner PK, Horowitz ME, Krischer JP, et al. Postoperative chemotherapy and delayed radiation in children less than three years of age with malignant brain tumors. N Engl J Med 1993; 328:1725.
  106. Duffner PK, Cohen ME, Sanford RA, et al. Lack of efficacy of postoperative chemotherapy and delayed radiation in very young children with pineoblastoma. Pediatric Oncology Group. Med Pediatr Oncol 1995; 25:38.
  107. Landier W, Bhatia S, Eshelman DA, et al. Development of risk-based guidelines for pediatric cancer survivors: the Children's Oncology Group Long-Term Follow-Up Guidelines from the Children's Oncology Group Late Effects Committee and Nursing Discipline. J Clin Oncol 2004; 22:4979.
  108. 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.
  109. Hall P, Adami HO, Trichopoulos D, et al. Effect of low doses of ionising radiation in infancy on cognitive function in adulthood: Swedish population based cohort study. BMJ 2004; 328:19.
  110. Campen CJ, Kranick SM, Kasner SE, et al. Cranial irradiation increases risk of stroke in pediatric brain tumor survivors. Stroke 2012; 43:3035.
  111. 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.
  112. Desai SS, Paulino AC, Mai WY, Teh BS. Radiation-induced moyamoya syndrome. Int J Radiat Oncol Biol Phys 2006; 65:1222.
  113. Ullrich NJ, Robertson R, Kinnamon DD, et al. Moyamoya following cranial irradiation for primary brain tumors in children. Neurology 2007; 68:932.
  114. 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.
  115. 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.
  116. Burn S, Gunny R, Phipps K, et al. Incidence of cavernoma development in children after radiotherapy for brain tumors. J Neurosurg 2007; 106:379.
  117. 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.
  118. Heckl S, Aschoff A, Kunze S. Radiation-induced cavernous hemangiomas of the brain: a late effect predominantly in children. Cancer 2002; 94:3285.
  119. 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.
  120. 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.
  121. Parsons JT, Bova FJ, Fitzgerald CR, et al. Radiation optic neuropathy after megavoltage external-beam irradiation: analysis of time-dose factors. Int J Radiat Oncol Biol Phys 1994; 30:755.
  122. Harris JR, Levene MB. Visual complications following irradiation for pituitary adenomas and craniopharyngiomas. Radiology 1976; 120:167.
  123. 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.
  124. Kelly PJ, Dinkin MJ, Drappatz J, et al. Unexpected late radiation neurotoxicity following bevacizumab use: a case series. J Neurooncol 2011; 102:485.
  125. Fishman ML, Bean SC, Cogan DG. Optic atrophy following prophylactic chemotherapy and cranial radiation for acute lymphocytic leukemia. Am J Ophthalmol 1976; 82:571.
  126. 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.
  127. 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.
  128. Bessell EM, Henk JM, Wright JE, Whitelocke RA. Orbital and conjunctival lymphoma treatment and prognosis. Radiother Oncol 1988; 13:237.
  129. 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.
  130. Pomeranz HD, Henson JW, Lessell S. Radiation-associated cerebral blindness. Am J Ophthalmol 1998; 126:609.
  131. Kahana A, Rowley HA, Weinstein JM. Cortical blindness: clinical and radiologic findings in reversible posterior leukoencephalopathy syndrome: case report and review of the literature. Ophthalmology 2005; 112:e7.
  132. Vázquez E, Lucaya J, Castellote A, et al. Neuroimaging in pediatric leukemia and lymphoma: differential diagnosis. Radiographics 2002; 22:1411.
  133. 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.
  134. 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.
  135. 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.
  136. 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.
  137. 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.
  138. 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.
  139. 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.
  140. 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.
  141. 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.
  142. Formanek M, Czerny C, Gstoettner W, Kornfehl J. Cochlear implantation as a successful rehabilitation for radiation-induced deafness. Eur Arch Otorhinolaryngol 1998; 255:175.
  143. 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.
  144. 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.
  145. 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.
  146. Constine LS, Woolf PD, Cann D, et al. Hypothalamic-pituitary dysfunction after radiation for brain tumors. N Engl J Med 1993; 328:87.
  147. 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.
  148. Clarson CL, Del Maestro RF. Growth failure after treatment of pediatric brain tumors. Pediatrics 1999; 103:E37.
  149. 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.
  150. 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.
  151. 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.
  152. 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.
  153. 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.
  154. Gurney JG, Ness KK, Sibley SD, et al. Metabolic syndrome and growth hormone deficiency in adult survivors of childhood acute lymphoblastic leukemia. Cancer 2006; 107:1303.
  155. Duffner PK, Krischer JP, Horowitz ME, et al. Second malignancies in young children with primary brain tumors following treatment with prolonged postoperative chemotherapy and delayed irradiation: a Pediatric Oncology Group study. Ann Neurol 1998; 44:313.