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A Critical Review of the Clinical Effects of Therapeutic Irradiation Damage to the Brain: The Roots of Controversy

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Abstract

We critically examined the damaging affects of therapeutic irradiation by comparing results from cross-disciplinary studies of early- and late-delayed radiotherapy effects. Focus is attained by concentrating on clinical treatment issues (volume of brain, dose, timing of effects, age, modality types, and stereotactic treatment techniques), rather than on methodological means or problems, which is necessary to understand the mechanisms and characteristics of radiotherapy-induced behavioral dysfunction including cognition. We make observations and hypotheses about the actual risks from radiotherapy that could be informative in the treatment decision process, and which may lessen the concerns of some patients and their families about the risks they take when receiving radiation. Conditions that predispose to radiation injury are reviewed: (1) higher doses even to part of the brain versus lower doses to the whole brain, (2) combined treatment modalities, (3) malignancy itself, (4) radiation early during postnatal brain development, and (5) late-delayed effects (more than 3 years posttreatment). Current neurocognitive frameworks for understanding cognitive change over time in children and adults are summarized, along with the literature on effects of brain tumors and treatment on depression. No studies have as yet identified candidate brain regions that are more sensitive to radiotherapy. Two studies have provided early, preliminary evidence for a specific vulnerability of visual attention/memory to the early stage of late radiation damage. Furthermore, radiation effects appear severe only in a minority of patients. Risk is related to direct and indirect effects of cancer type, concurrent clinical factors, and premorbid risk factors.

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REFERENCES

  • Ahles, T. A., Silberfarb, P. M., Herndon, J., Maurer, L. H., Kornblith, A. B., Aisner, J., et al. (1998). Psychological and neuropsychologic functioning of patients with limited small-cell lung cancer treated with chemotherapy and radiation therapy with or without warfarin: A study by the Cancer and Leukemia Group C. J. Clin. Oncol. 16: 1954-1960.

    Google Scholar 

  • Al-Amro, A., and Schultz, H. (1995). Moyamoya vasculopathy after cranial irradiation-A case Report. Acta Oncol. 34: 261-263.

    Google Scholar 

  • Appleton, R. E., Farrell, K., and Rogers, P. (1990). Decline in head growth and congnitive impairment in survivors of acute lymphoblastic leukaemia. Arch. Dis. Child. 65: 530-534.

    Google Scholar 

  • Archibald, Y. M., Lunn, D., Ruttan, L. A., MacDonald, D. R., Del Maestro, R. F., Barr, H. W., et al. (1994). Cognitive functioning in long-term survivors of high-grade glioma. J. Neurosurg. 80: 247-253.

    Google Scholar 

  • Armstrong, C. L., Corn, B. W., Ruffer, J. E., Pruitt, A. A., Mollman, J. E., and Phillips, P. C. (2000). Radiotherapeutic effects on brain function: Double dissociation of memory systems. Neuropsychiatry Neuropsychol. Behav. Neurol. 13: 101-111.

    Google Scholar 

  • Armstrong, C. L., Goldstein, B., Cohen, B., Jo, M.-Y., and Tallent, E. M. (2002a). Clinical predictors of depression in patients with low-grade brain tumors: Consideration of a neurologic versus a psychogenic model. J. Clin. Psychol. Med. Settings 9(2): 97-107.

    Google Scholar 

  • Armstrong, C. L., Goldstein, B., Shera, D., Ledakis, G. E., and Tallent, E. M. (2003). The predictive value of longitudinal nuropsychologic assessment in the early detection of brain tumor recurrence. Cancer 97: 649-656.

    Google Scholar 

  • Armstrong, C. L., Guglielmi, L., Seiler, C. (2004). Early-delayed radiotherapy damage affects widespread semantic memory networks [Abstract]. J. Int. Neuropsychol. Soc., in press.

  • Armstrong, C. L., Hampstead, B., and Guglielmi, L. (2004). Hippocampal response to neuro-oncological stressors [Abstract]. J. Int. Neuropsychol. Soc.

  • Armstrong, C. L., Hunter, J. V., Hackney, D., Ledakis, G. E., Shabbout, M., Lustig, R., et al. (2004). MRI changes during the early-delayed phase of radiotherapy-induced damaging effects. Manuscript submitted for publication.

  • Armstrong, C. L., Hunter, J. V., Ledakis, G. E., Cohen, B., Tallent, E. M., Goldstein, B. H., et al. (2002b). Late cognitive and radiographic changes related to radiotherapy: Initial prospective findings. Neurology 59: 40-48.

    Google Scholar 

  • Armstrong, C. L., Mollman, J. E., Corn, B. W., Alavi, J., and Grossman, M. (1993). Effects of radiation therapy on adult brain behavior: Evidence for a rebound phenomenon in a phase 1 trial. Neurology 43: 1961-1965.

    Google Scholar 

  • Armstrong, C. L., Ruffer, J. E., Corn, B. W., De Vries, K., and Mollman, J. E. (1995). Biphasic patterns of memory deficits following moderate dose/partial brain irradiation: Neuropsychologic outcome and proposed mechanisms. J. Clin. Oncol. 13: 2263-2271.

    Google Scholar 

  • Armstrong, C. L., Stern, C. H., Ruffer, J., and Corn, B. (2001). Memory performance used to detect radiation effects on cognitive functioning. Appl. Neuropsychol. 8: 129-139.

    Google Scholar 

  • Assessment: Neuropsychological testing of adults. Considerations for neurologists. Report of the Therapeutics and Technology Assessment Subcommittee of the American Academy of Neurology (1996). Neurology 47: 592-599.

  • Becker, G., Duffner, F., Kortmann, R., Weinmann, M., Grote, E. H., and Bamberg, M. (1999). Radiosurgery for the treatment of brain metastases in renal cell carcinoma. Anticancer Res. 19: 1611-1618.

    Google Scholar 

  • Berg, R. A., Ch'ien, L. T., Lancaster, W., Williams, S., and Cummins, J. (1983). Neuropsychological sequelae of postradiation somnolence syndrome. J. Dev. Behav. Pediatr. 4: 103-107.

    Google Scholar 

  • Bleyer, A., Geyer, J., Taylor, E., and Hubbard, B. (1989). The susceptibility of the cerebral subependymal zone (SEZ) to chemotherapy (CT) and radiotherapy (RT): Mechanism of clincal neurotoxicity caused by CT and RT [Abstract] Proc. Am. Soc. Clin. Oncol. 8: 84.

    Google Scholar 

  • Bleyer, W. A., and Griffin, T. W. (1980). White matter necrosis, mineralizing microangiopathy and intellectual abilities in survivors of childhood leukemia: Associations with central nervous system irradiation and methotrexate therapy. In: Gilbert, H. A., and Kagan, A. R. (eds.), Radiation Damage to the Nervous System, Raven Press, New York, pp. 155-174.

    Google Scholar 

  • Blonder, L. X., Hodes, J. E., Ranseen, J. D., and Schmitt, F. A. (1999). Short-term neuropsychological outcome following gamma knife radiosurgery for arteriovenous malformations: A preliminary report. Appl. Neuropsychol. 6: 181-186.

    Google Scholar 

  • Brandes, A. A., Rigon, A., and Monfardini, S. (2000). Contra. Current controversies in cancer. Eur. J. Cancer 36: 443-452.

    Google Scholar 

  • Brouwers, P., Riccardi, R., Fedio, P., and Poplack, D. G. (1985). Long-term neuropsychologic sequelae of childhood leukemia: Correlation with CT brain scan abnormalities. J. Pediatr. 106: 723-728.

    Google Scholar 

  • Brown, P. D., Buckner, J. C., O'Fallon, J. R., Iturria, N. L., Brown, C. A., O'Neill, B. P., et al. (2003). Effects of radiotherapy on cognitive function in patients with low-grade glioma measured by the Folstein Mini-Mental State Examination. J. Clin. Oncol. 21: 2519-2524.

    Google Scholar 

  • Bruehlmeier, M., Roelcke, U., Amsler, B., Schubert, K. H., Hausmann, O., von Ammon, K., et al. (1999). Effect of radiotherapy on brain glucose metabolism in patients operated on for low grade astrocytoma. J. Neurol. Neurosurg. Psychiatry 66: 648-653.

    Google Scholar 

  • Burger, P. C., Mahaley, M. S., Dudka, L., and Vogel, F. S. (1979). The morphologic effects of radiation administered therapeutically for intracranial gliomas: A postmortem study of 25 cases. Cancer 44: 1256-1272.

    Google Scholar 

  • Butler, R. W., Hill, J. M., Steinherz, P. G., Meyers, P. A., and Finaly, J. L. (1994). Neuropsychologic effects of cranial irradiation, intrathecal methotrexate, and systemic methotrexate in childhood cancer. J. Clin. Oncol. 12: 2621-2629.

    Google Scholar 

  • Butler, R. W., Kerr, M., and Marchand, A. (1999). Attention and executive functions following cranial irradiation in children [Abstract]. J. Int. Neuropsychol. Soc. 5: 108.

    Google Scholar 

  • Cairncross, J. G., Ueki, K., Zlatescu, M. C., Lisle, D. K., Finkelstein, D. M., Hammond, R. R., et al. (1998). Specific genetic predictors of chemotherapeutic response and survival in patients with anaplastic oligodendroglomas. J. Nat. Cancer Inst. 90(19): 1473-1479.

    Google Scholar 

  • Calvo, W., Hopewell, J., Reinhold, H., and Yeung, T. (1988). Time and dose-related changes in the white matter of the rat brain after single doses of X-rays. Br. J. Radiol. 61: 183-190.

    Google Scholar 

  • Catane, R., Schwade, J. G., Yarr, I., Lichter, A. S., Tepper, J. E., Dunnick, N. R., et al. (1981). Follow-up neurological evaluation in patients with small cell lung carcinoma treated with prophylactic cranial irradiation and chemotherapy. Int. J. Radiat. Oncol. Biol. Phys. 7: 105-109.

    Google Scholar 

  • Copeland, D. R., Fletcher, J. M., Pfefferbaum-Levine, B., Jaffe, N., Ried, H., and Maor, M. (1985). Neuropsychological sequelae of childhood cancer in long-term survivors. Pediatrics 75: 745-753.

    Google Scholar 

  • Corn, B. W., Yousem, D. M., Scott, C. B., Rotman, M., Asbell, S. O., Nelson, D. F., et al. (1994). White matter changes are correlated significantly with radiation dose. Cancer 74: 2828-2835.

    Google Scholar 

  • Corry, J., Smith, J. G., Wirth, A., Quong, G., and Liew, K. H. (1998). Primary central nervous system lymphoma: Age and performance status are more important than treatment modality. Int. J. Radiat. Oncol. Biol. Phys. 41(3): 615-620.

    Google Scholar 

  • Cousens, P., Ungerer, J. A., Crawford, J. A., and Stevens, M. M. (1991). Cognitive effects of childhood leukemia therapy: A case for four specific deficits. J. Pediatr. Psychol. 16: 475-488.

    Google Scholar 

  • Crosley, C. J., Rorke, L. B., Evans, A., and Nigro, M. (1978). Central nervous system lesions in childhood leukemia. Neurology 28: 678-685.

    Google Scholar 

  • Crossen, J. R., Garwood, D., Glatstein, E., and Neuwelt, E. A. (1994). Neurobehavioral sequelae of cranial irradiation in adults: A review of radiation-induced encephalopathy. J. Clin. Oncol. 12: 627-642.

    Google Scholar 

  • Curnes, J., Laster, D. W., Ball, M., Moody, D. M, and Witcofski, R. L. (1986). MRI. of radiation injury to the brain. AJR: Am. J. Roentgenol. 147: 119-124.

    Google Scholar 

  • Curran, W., Hecht-Leavitt, C., Schut, L., Zimmerman, R. A., and Nelson, D. F. (1987). Magnetic resonance imaging of cranial radiation lesions. Int. J. Radiat. Oncol. Biol. Phys. 13: 1093-1098.

    Google Scholar 

  • Daum, I., and Ackermann, H. (1995). Cerebellar contributions to cognition. Behav. Brain Res. 67: 201-210.

    Google Scholar 

  • DeAngelis, L. M., Delattre, J. V., and Posner, J. B. (1989). Radiation-induced dementia in patients cured of brain metastases. Neurology 39: 789-796.

    Google Scholar 

  • Dowell, R. E., Copeland, D. R., Francis, D. J., Fletcher, J. M., and Stovall, M. (1991). Absence of synergistic effects of CNS treatments on neuropsychological test performance among children. J. Clin. Oncol. 9: 1029-1026.

    Google Scholar 

  • Duffner, P. K., Cohen, M. E., Myers, M. H., and Heise, H. W. (1986). Survival of children with brain tumors: SEER Program, 1973-1980. Neurology 36: 597-601.

    Google Scholar 

  • Duffner, P. K., Horowitz, M. E., Krischer, J. P., Friedman, H. S., Burger, P. C., Cohen, M. E., et al. (1993). Postoperative chemotherapy and delayed radiation radiation in children less than three years of age with malignant brain tumors. N. Engl. J. Med. 328: 1725-1731.

    Google Scholar 

  • Dunbar, S. F., and Loeffler, J. S. (1994). Stereotactic radiation therapy. In: Mauch, P. M., and Leoffler, J. S. (eds.), Radiation Oncology: Technology and Biology, W. B. Saunders, Philadelphia, pp. 237-251.

    Google Scholar 

  • Ellenberg, L., McComb, J. G., Siegel, S. E., and Stowe, S. (1987). Factors afecting intellectual outcome in pediatric brain tumor patients. Neurosurgery 21: 638-644.

    Google Scholar 

  • Fischer, A., and Holfelder, H. (1930). Lokales amyloid im gehirn. Deutsche Zeitschrift für Chirurgie 227: 475-483.

    Google Scholar 

  • Flickinger, J. C., Kondziolka, D., Pollock, B. E., Maitz, A. H., and Lunsford, L. D. (1997). Complications from arteriovenous malformation radiosurgery: Multivariate analysis and risk modeling. Int. J. Radiat. Oncol. Biol. Phys. 38: 485-490.

    Google Scholar 

  • Fouladi, M., Wallace, D., Langston, J. W., Mulhern, R., Rose, S. R., Gajjar, A., et al. (2003). Survival and functional outcome of children with hypothalamic/chiasmatic tumors. Cancer 97: 1084-1092.

    Google Scholar 

  • Frytak, S., Earnest, F., O'Neil, B. P., Lee, R. E., Creagan, E. T., and Trautmann, J. C. (1985). Magnetic resonance imaging for neurotoxicity in long-term survivors of carcinoma. Mayo Clin. Proc. 60: 803-812.

    Google Scholar 

  • Fuss, M., Poljanc, K., and Hug, E. G. (2000). Full Scale IQ (FSIQ) changes in children treated with whole brain and partial brain irradiation: A review and analysis. Strahlenther Onkol. 176: 573-581.

    Google Scholar 

  • Giovagnoli, A. R., Tamburini, M., and Boiardi, A. (1996). Quality of life in brain tumor patients. J. Neuro-Oncol. 30: 71-80.

    Google Scholar 

  • Goldsmith, B. J., Wara, W. M., Wilson, C. B., and Larson, D. A. (1994). Postoperative irradiation for subtotally resected meningiomas: A retrospective analysis of 140 patients treated from 1967 to 1990. J. Neurosurg. 80: 195-201.

    Google Scholar 

  • Goldstein, B., Armstrong, C. L., Modetino, E., Ledakis, G. E., John, C., and Hunter, J. V. (2004). Picture and word recognition memory in adult intracranial tumor patients. Brain Cogn. 54: 1-6.

    Google Scholar 

  • Hampstead, B. M., Guglielmi, L., and Armstrong, C. L. (2003). Early delay hippocampal MTR change in patients with low grade primary brain tumors [Abstract]. Arch. Clin. Neuropsychol. 18: 770-771.

    Google Scholar 

  • Hochberg, F. H., and Slotnick, B. (1980). Neuropsychologic impairment in astrocytoma survivors. Neurology 30: 172-177.

    Google Scholar 

  • Hoffman, W. F., Levin, V. A., and Wilson, C. B. (1979). Evaluation of malignant glioma patients during the postirradiation period. J. Neurosurg. 50: 624-628.

    Google Scholar 

  • Hopewell, J. W. (1998). Radiation injury to the central nervous system. Med. Pediatr. Oncol. 1(Suppl.): 1-9.

    Google Scholar 

  • Hoppe-Hirsch, E., Brunet, L., Laroussinie, F., Cinalli, G., Pierre-Kahn, A., Renier, D., et al. (1995). Intellectual outcome in children with malignant tumors of the posterior fossa: Influence of the field of irradiation and quality of surgery. Childs Nerv. Syst. 11: 340-346.

    Google Scholar 

  • Hoppe-Hirsch, E., Renier, D., Lellouch-Tubiana, A., Sainte-Rose, C., Pierre-Kahn, A., and Hirsch, J. F. (1990). Medulloblastoma in childhood: Progressive intellectual deterioration. Childs Nerv. Syst. 6: 60-65.

    Google Scholar 

  • Irle, E., Peper, M., Wowra, B., and Kunze, S. (1994). Mood changes after surgery for tumors of the cerebral cortex. Arch. Neurol. 51: 164-174.

    Google Scholar 

  • Johnson, B., Becker, B., Goff, W., Petronas, N., Krehbiel, M. A., Makuch, R. W., et al. (1985). Neurologic, neuropsychologic, and computed cranial tomography scan abnormalities in 2-to 10-year survivors of small-cell lung cancer. J. Clin. Oncol. 3: 1659-1667.

    Google Scholar 

  • Johnson, B., Patronas, N., Hayes, W., Grayson, J., Becker, B., Gnepp, D., et al. (1990). Neurologic, computed cranial tomographic, and magnetic resonance imaging abnormalities in patients with small cell lung cancer: Further follow-up of 6-to 13-year survivors. J. Clin. Oncol. 8: 48-56.

    Google Scholar 

  • Keime-Guibert, F., Napolitano, M., and Delattre, J. Y. (1998). Neurological complications of radiotherapy and chemotherapy. J. Neurol. 245: 695-709.

    Google Scholar 

  • Klein, M., Heimans, J. J., Aaronson, N. K., van der Ploeg, H. M., Grit, J., Muller, M., et al. (2002). Effect of radiotherapy and other treatment-related factors on mid-term to long-term cognitive sequelae in low-grade gliomas: A comparative study. Lancet 360: 1361-1368.

    Google Scholar 

  • Klein, M., Taphoorn, M. J. B., Heimans, J. J., van der Ploeg, H. M., Vandertop, W. P., Smit, E. F., et al. (2001). Neurobehavioral status and health-related quality of life in newly diagnosed high-grade glioma patients. J. Clin. Oncol. 19: 4037-4047.

    Google Scholar 

  • Kleinschmidt-DeMasters, B. K. (1995). Necrotizing brainstem leukoencephalopathy six weeks following radiotherapy. Clin. Neuropathol. 14(20): 63-68.

    Google Scholar 

  • Kramer, J., and Moore, I. M. (1989). Late effects of cancer treatment on the central nervous system. Semin. Oncol. Nurs. 5: 22-28.

    Google Scholar 

  • Laukkanen, E., Klonoff, H., Allan, B., Graeb, D., and Murray, N. (1988). The role of prophylactic brain irradiation in limited stage small cell lung cancer: Clinical, neuropsychologic, and CT sequelae. J. Radiat. Oncol. Biol. Phys. 14: 1109-1117.

    Google Scholar 

  • Lavey, R. S., Johnston, A. K., Taylor, J. M. G., and McBride, W. H. (1992). The effect of hyperfractionation on spinal cord response to radiation. Int. J. Radiat. Oncol. Biol. Phys. 24: 681-686.

    Google Scholar 

  • LeBaron, S., Zeltzer, P. M., Zeltzer, L. K., Scott, S. E., and Marlin, A. E. (1988). Assessment of quality of survival in children with medulloblastoma and cerebellar astrocytoma. Cancer 62: 1215-1222.

    Google Scholar 

  • Lee, P. W., Hung, B. K., Woo, E. K., Tai, P. T., and Choi, D. T. (1989). Effects of radiation therapy on neuropsychological functioning in patients with nasopharyngeal carcinoma. J. Neurol. Neurosurg. Psychiatry 52: 488-492.

    Google Scholar 

  • Lee, Y. Y., Nauert, C., and Glass, P. (1986). Treatment-related white matter changes in cancer patients. Cancer 57: 1473-1482.

    Google Scholar 

  • Lezak, M. D. (1995). Neuropsychological Assessment, 3rd edn., Oxford University Press, New York.

    Google Scholar 

  • Llanes, S., Torres, I. J., Roeske, A., Mundt, S., Keedy, S., Zakowski, S. (in press). Temporal lobe radiation and memory in adult brain tumor patients. J. Int. Neuropsychol. Soc.

  • Longeway, K., Mulhern, R., Crisco, J., Kun, L., Lauer, S., Casper, J., et al. (1990). Treatment of meningeal relapse in childhood acute lymphoblastic leukemia: II. A prospective study of intellectual loss specific to CNS relapse and therapy. Am. J. Pediatr. Hematol. Oncol. 12: 45-50.

    Google Scholar 

  • Maguire, P. D., Clough, R., Friedman, A. H., and Halperin, E. C. (1999). Fractionated external-beam radiation therapy for meningiomas of the cavernous sinus. Int. J. Radiat. Oncol. Biol. Phys. 44: 75-79.

    Google Scholar 

  • Maire, J. P., Coudin, B., Guerin, J., and Caudry, M. (1987). Neuropsychologic impairment in adults with brain tumors. Am. J. Clin. Oncol. 10: 156-162.

    Google Scholar 

  • Matsuo, T., Shibata, S., Yasunaga, A., Iwanaga, M., Mori, K., Shimizu, T., et al. (1999). Dose optimization and indication of LINAC radiosurgery for brain metastases. Int. J. Radiat. Oncol. Biol. Phys. 45: 931-939.

    Google Scholar 

  • Mettler, F. A., and Upton, A. C. (1995). Medical Effects of Ionizing Radiation, 2nd edn., W. B. Saunders, Philadelphia.

    Google Scholar 

  • Meyers, C. A., Geara, F., Wong, P. F., and Morrison, W. H. (2000). Neurocognitive effects of therapeutic irradiation for base of skull tumors. Int. J. Radiat. Oncol. Biol. Phys. 46: 51-55.

    Google Scholar 

  • Meyers, C. A., and Hess, K. R. (2003). Multifaceted end points in brain tumor clinical trials: Cognitive deterioration precedes MRI progression. Neuro-Oncology 5(2): 89-95.

    Google Scholar 

  • Meyers, C. A., Hess, K. R., Yung, W. K. A., and Levin, V. A. (2000). Cognitive function as a predictor of survival in patients with recurrent malignant glioma. J. Clin. Oncol. 18: 646-650.

    Google Scholar 

  • Monje, M. L., Mizumatsu, S., Fike, J. R., and Palmer, T. D. (2002). Irradiation induces neural precursor-cell dysfunction. Nat. Med. 8(9): 955-962.

    Google Scholar 

  • Monje, M. L., and Palmer, T. (2003). Radiation injury and neurogenesis. Curr. Opin. Neurol. 16: 129-134.

    Google Scholar 

  • Moore, B. D., Ater, J. L., and Copeland, D. R. (1992a). Improved neuropsychological outcome in children with brain tumors diagnosed during infancy and treated without cranial irradiation. J. Child Neurol. 7: 281-290.

    Google Scholar 

  • Moore, B. D., Copeland, D. R., Ried, H., and Levy, B. (1992b). Neurophysiological bases of cognitive deficits in long-term survivors of childhood cancer. Arch. Neurol. 49: 809-817.

    Google Scholar 

  • Mori, Y., Kondziolka, D., Flickinger, J. C., Kirkwood, J. M., Agarwale, S., and Lunsford, L. D. (1998). Stereotactic radiosurgery for cerebral metastatic melanoma: Factors affecting local disease control and survival. Int. J. Radiat. Oncol. Biol. Phys. 42: 581-589.

    Google Scholar 

  • Mulhern, R. K., Crisco, J. J., and Kun, L.E. (1983). Neuropsychological sequelae of childhood brain tumors: A review. J. Clin. Child Psychol. 12: 66-73.

    Google Scholar 

  • Mulhern, R. K., Fairclough, D., and Ochs, D. (1991). A prospective comparison of neuropsychlogical performance of children surviving leukemia who received 18-Gy, 24-Gy, or no cranial irradiation. J. Clin. Oncol. 9: 1348-1356.

    Google Scholar 

  • Mulhern, R. K., Hancock, J., Fairclough, D., and Kun, L. E. (1992). Neuropsychological status of children treated for brain tumors: A critical review and integrative analysis. Med. Pediatr. Oncol. 20: 181-191.

    Google Scholar 

  • Mulhern, R. K., Kepner, J. L., Thomas, P. R., Armstrong, F. D., Friedman, H. S., and Kun, L. E. (1998). Neuropsychologic functioning of survivors of childhood medulloblastoma randomized to receive conventional or reduced-dose craniospinal irradiation: A Pediatric Oncology Group study. J. Clin. Oncol. 16: 1723-1728.

    Google Scholar 

  • Mulhern, R. K., Palmer, S. L., Reddick, W. E., Glass, J. O., Kun, L. E., Taylor, J., et al. (2001). Risks of young age for selected neurocognitive deficits in medulloblastoma are associated with white matter loss. J. Clin. Oncol. 19: 472-479.

    Google Scholar 

  • Mulhern, R. K., Reddick, W. E., Palmer, S. L., Glass, J. O., Elkin, T. D., Kun, L. E., et al. (1999). Neurocognitive deficits in medulloblastoma survivors and white matter loss. Ann. Neurol. 46: 834-841.

    Google Scholar 

  • Mulhern, R. K., Wasserman, A. L., Fairclough, D., and Ochs, J. (1988). Memory function in disease-free survivors of childhood acute lymphocytic leukemia given CNS prophylaxis with or without 1,800 cGy cranial irradiation. J. Clin. Oncol. 6: 315-320.

    Google Scholar 

  • Murros, K., and Toole, J. (1989). The effect of radiation on carotid arteries: A review article. Arch. Neurol. 46: 449-455.

    Google Scholar 

  • National Cancer Institute (1995). Physician Data Query: Childhood brain tumor: General information. Retrieved from cancernet.nci.nih.gov (updated July 1995).

  • Neuwelt, E. A., Goldman, D. L., Dahlborg, S. A., Crossen, J., Ramsey, F., Roman-Goldstein, S., et al. (1991). Primary CNS lymphoma treated with osmotic blood-brain barrier disruption: Prolonged survival and preservation of cognitive function. J. Clin. Oncol. 9: 1580-90.

    Google Scholar 

  • Ochs, J., Mulhern, R., Fairclough, D., Parvey, L., Whitaker, J., Ch'ien, L., et al. (1991). Comparison of neuropsychologic functioning and clinical indicators of neurotoxicity in long-term survivors of childhood leukemia given cranial radiation or parenteral methotrexate: A prospective study. J. Clin. Oncol. 9: 145-151.

    Google Scholar 

  • Olson, J. D., Riedel, E., and DeAngelis, L. M. (2000). Long-term outcome of low-grade oligodendroglioma and mixed glioma. Neurology 54: 1442-1448.

    Google Scholar 

  • Omura, M., Aida, N., Sekido, K., Kakehi, M., and Matsubara, S. (1997). Large intracranial vessel occlusive vasculopathy after radiation therapy in children: Clinical features and usefulness of magnetic resonance imaging. Int. J. Radiat. Oncol. Biol. Phys. 38: 241-249.

    Google Scholar 

  • Packer, R. J., Sutton, L. N., Atkins, T. E., Radcliffe, J., Bunin, G. R., D'Angio, G., et al. (1989). A prospective study of cognitive function in children receiving whole-brain radiation and chemotherapy: 2-year results. J. Neurosurg. 70: 707-713.

    Google Scholar 

  • Palmer, S. L., Gajjar, A., Reddick, W. E., Glass, J. O., Kun, L. E., Wu, S., et al., (2003). Predicting intellectual outcome among children treated with 35-40 Gy craniospinal irradiation for medulloblastoma. Neuropsychology 17: 548-555.

    Google Scholar 

  • Peylan-Ramu, N., Poplack, D. G., Adornato, B. T., and DiChiro, G. (1978). Abnormal CT scans of the brain in asymptomatic children with acute lymphocytic leukemia after prophylactic treatment of the central nervous system with radiation and intrathecal chemotherapy. N. Engl. J. Med. 298: 815-818.

    Google Scholar 

  • Phillips, P. C., Delattre, J. Y., Berger, C. A., and Rottenberg, D. A. (1987). Early and progressive increase in regional brain capillary permeability following single and fractionated dose cranial irradiation in the rat [Abstract]. Neurology 37(Suppl. 1): 301.

    Google Scholar 

  • Postma, T. J., van Groeningen, C. J., Witjes, R. J. G. M., Weerts, J. G. E., Kralendonk, J. H., and Heimans, J. J. (1998). Neurotoxicity of combination chemotherapy with procarbazine, CCNU and vincristine (PCV) for recurrent glioma. J. Neuro-Oncol. 38: 69-75.

    Google Scholar 

  • Radcliffe, J., Bunin, G. R., Sutton, L. N., Goldwein, J. W., and Phillips, P. C. (1994). Cognitive deficits in long-term survivors of childhood medulloblastoma and other noncortical tumors: Age-dependent effects of whole brain radiation. Int. J. Dev. Neurosci. 12: 327-334.

    Google Scholar 

  • Radcliffe, J., Packer, R. J., Atkins, T. E., Bunin, G. R., Schut, L., Goldwein, J. W., et al. (1992). Three-and four-year cognitive outcome in children with noncortical brain tumors treated with whole-brain radiotherapy. Ann. Neurol. 2: 551-554.

    Google Scholar 

  • Reijneveld, J. C., Sitskoorn, M. M., Klein, M., Nuyen, J., and Taphoorn, M. J. B. (2001). Cognitive status and quality of life in patients with suspected versus proven low-grade gliomas. Neurology 56: 618-623.

    Google Scholar 

  • Ris, M. D., and Noll, R. B. (1994). Long-term neurobehavioral outcome in pediatric brain-tumor patients: Review and methodological critique. J. Clin. Exp. Neuropsychol. 16: 21-42.

    Google Scholar 

  • Riva, D., Pantaleoni, C., Devoti, M., Lindquist, C., Steiner, L., and Giorgi, C. (1997). Radiosurgery for cerebral AVMs in children and adolescents: The neurobehavioral outcome. J. Neurosurg. 86: 207-210.

    Google Scholar 

  • Riva, D., Pantaleoni, C., Milani, N., and Belani, F. F. (1989). Impairment of neuropsychological functions in children with medulloblastomas and astrocytomas in the posterior fossa. Childs Nerv. Syst. 5: 107-110.

    Google Scholar 

  • Roessmann, U. (1974). Weight ratio between the intratentorial and supratentorial portions of the central nervous system. J. Neuropathol. Exp. Neurol. 33: 164-170.

    Google Scholar 

  • Roman, D. D., and Sperduto, P. W. (1995). Neuropsychological effects of cranial radiation: Current knowledge and future directions. Int. J. Radiat. Oncol. Biol. Phys. 32: 983-998.

    Google Scholar 

  • Rottenberg, D. A. (1991). Acute and chronic effects of radiation therapy on the nervous system. In: Rottenberg, D. A. (ed.), Neurological Complications of Cancer Treatment, Butterworths Publishers, Boston, pp. 3-17.

    Google Scholar 

  • Rubenstein, C. L., Varni, J. W., and Katz, E. R. (1990). Cognitive functioning in long-term survivors of childhood leukemia: A prospective analysis. J. Dev. Behav. Pediatr. 11: 301-305.

    Google Scholar 

  • Sato, K., Kameyama, M., Kayama, T., Yoshimoto, T., Ishiwata, K., and Ito, M. (1995). Serial positron emission tomography imaging of changes in amino acid metabolism in low grade astrocytoma after radio-and chemotherapy. Neurol. Med. Chir. 35: 808-812.

    Google Scholar 

  • Scalliet, P., Landuyt, W., and van der Schueren, E. (1989). Repair kinetics as a determining factor for late tolerance of central nervous system to low dose rate irradiation. Radiother. Oncol. 14: 345-353.

    Google Scholar 

  • Schatz, J., Kramer, J. H., Ablin, A., and Matthay, K. K. (2000). Processing speed, working memory, and IQ: A developmental model of cognitive deficits following cranial radiation therapy. Neuropsychology 14(2): 189-200.

    Google Scholar 

  • Seaver, E., Geyer, R., Sulzbacher, S., Warner, M., Batzel, L., Milstein, J., et al. (1994). Psychosocial adjustment in long-term survivors of childhood medulloblastoma and ependymoma treated with craniospinal irradiation. Pediatr. Neurosurg. 20: 248-253.

    Google Scholar 

  • Sheline, G., Wara, W., and Smith, V. (1980). Therapeutic irradiation and brain injury. Int. J. Radiat. Oncol. Biol. Phys. 6: 1215-1228.

    Google Scholar 

  • Shepherd, P. C., Kean, D. M., and Ritchie, G. L. (1989). Early-delayed radiation injury to the brainstem after radiotherapy for lymphoma of the tongue and neck. Clin. Oncol. 1(2): 1101-114.

    Google Scholar 

  • Shishido, F., Uemura, K., Inugami, A., Tomura, N., Higano, S., Fujita, H., et al. (1990). Value of C-methionine and PET in the diagnosis of low grade gliomas. Kaku Igaku 27: 293-302.

    Google Scholar 

  • Silber, J. H., Radcliffe, J., Peckham, V., Perilongo, G., Kishnani, P., Fridman, M., et al. (1992). Whole-brain irradiation and decline in intelligence: The influence of dose and age on IQ score. J. Clin. Oncol. 10: 1390-1396.

    Google Scholar 

  • Silverman, C. L., Palkes, H., Talent, B., Kovanar, E., Clouse, J. W., and Thomas, P. R. (1984). Late effects of radiotherapy of patients with cerebellar medulloblastoma. Cancer 54: 825-829.

    Google Scholar 

  • Spreen, O., Risser, A. H., and Edgell, D. (1995). Developmental Neuropsychology, Oxford University Press, New York.

    Google Scholar 

  • Spunberg, J. J., Chang, C. H., Goldman, M., Auricchio, E., and Bell, J. J. (1981). Quality of long-term survival following irradiation for intracranial tumors in children under the age of two. J. Radiat. Oncol. Biol. Phys. 7: 727-736.

    Google Scholar 

  • Stylopopulos, L. A., George, A. E., de Leon, M. J., Miller, J. D., Foo, S. H., Hiesiger, E., et al. (1988). Longitudinal CT study of parenchymal brain changes in glioma survivors. AJNR Am. J. Neuroradiol. 9: 517-522.

    Google Scholar 

  • Subach, B. R., Lunsford, L. D., Kondziolka, D., Maitz, A. H., and Flickinger, J. C. (1998). Management of petroclival meningiomas by stereotactic radiosurgery. Neurosurgery 42: 437-445.

    Google Scholar 

  • Surma-aho, O., Niemelä, M., Vilkki, J., Kouri, M., Brander, A., Salonen, O., et al. (2001). Adverse long-term effects of brain radiotherapy in adult low-grade glioma patients. Neurology 56: 1285-1290.

    Google Scholar 

  • Taphoorn, M. J., Schiphorst, A. K., Snoek, F. J., Lindeboom, J., Wolbers, J. G., Karim, A. B., et al. (1994). Cognitive functions and quality of life in patients with low-grade gliomas: The impact of radiotherapy. Ann. Neurol. 36: 48-54.

    Google Scholar 

  • Thaker, U., McDonagh, A. M., Iwatsubo, T., Lendon, C. L., Pickering-Brown, S. M., and Mann, D. M. (2003). Tau load is associated with apolipoprotein E genotype and the amount of amyloid beta protein, Abeta40, in sporadic and familial Alzheimer's disease. Neuropathol. Appl. Neurobiol. 29(1): 35-44.

    Google Scholar 

  • Tiver, K. (1989). Treatment of CNS tumor with conventional radiotherapy: The importance of dose and volume factors in tumor control and CNS radiation tolerance. Australas. Radiol. 33: 15-22.

    Google Scholar 

  • Torres, I. J., Mundt, A. J., Sweeney, P. J., Llanes-Macy, S., Dunaway, L., Castillo, M., et al. (2003). A longitudinal neuropsychological study of partial brain radiation in adults with brain tumors. Neurology 60: 1113-1118.

    Google Scholar 

  • Tortosa, A., Viñolas, N., Villà, S., Verger, E., Gil, J. M., Brell, M., et al. (2003). Prognostic implication of clinical, radiologic, and pathologic features in patients with anaplastic gliomas. Cancer 97: 1063-1071.

    Google Scholar 

  • Tucha, O., Smely, C., Preier, M., and Lange, K. W. (2000). Cognitive deficits before treatment among patients with brain tumors. Neurosurgery 47(2): 324-334.

    Google Scholar 

  • Tucker, J., Prior, P. F., Green, C.R., Ede, G. M., Stevenson, J. F., Gawler, J., et al. (1989). Minimal neuropsychological sequelae following prophylactic treatment of the central nervous system in adult leukaemia and lymphoma. Br. J. Cancer 60: 775-780.

    Google Scholar 

  • Twijnstra, A., Boo, P. J., Lormans, A. C. M., and Ten Velde, G. P. M. (1987). Neurotoxicity of prophylactic cranial irradiation in patients with small cell carcinoma of the lung. Eur. J. Cancer Clin. Oncol. 23: 983-986.

    Google Scholar 

  • Van den Bent, M. J., Looijenga, L. H. J., Langenberg, K., Dinjens, W., Graveland, W., Uytdewilligen, L., et al. (2003). Chromosomal anomalies in oligodendroglial tumors are correlated with clinical features. Cancer 97: 1276-1284.

    Google Scholar 

  • Vigliani, M.-C., Duyckaerts, C., and Delattre, J.-Y. (1997). Radiation-induced cognitive dysfunction in adults. In: Vecht, C. J. (Vol. ed.), Handbook of Clinical Neurology: Vol. 23(67). Neuro-Oncology, Elsevier, New York, pp. 371-388.

    Google Scholar 

  • Vigliani, M.-C., Sichez, N., Poisson, M., and Delattre, J. Y. (1996). A prospective study of cognitive functions following conventional radiotherapy for supratentorial gliomas in young adults: 4-year results. Int. J. Radiat. Oncol. Biol. Phys. 35: 527-533.

    Google Scholar 

  • Villa, S., Vinolas, N., Verger, E., Yaya, R., Martinez, A., Gil, M., et al. (1998). Efficacy of radiotherapy for malignant gliomas in elderly patients. Int. J. Radiat. Oncol. Biol. Phys. 42(5): 977-980.

    Google Scholar 

  • Voges, J., Treuer, H., Lehrke, R., Kocher, M., Staar, S., Muller, R. P, et al. (1997). Risk analysis of LINAC radiosurgery in patients with arteriovenous malformation (AVM). Acta Neurochir. 68: 118-123.

    Google Scholar 

  • Walter, A. W., Mulhern, R. K., Grajjar, A., Heideman, R. L., Reardon, D., Sanford, R. A., et al. (1999). Survival and neurodevelopmental outcome of young children with medulloblastoma at St. Jude Children's Research Hospital. J. Clin. Oncol. 17: 3720-3728.

    Google Scholar 

  • Wang, G. J., Volkow, N. D., Lau, Y. H., Fowler, J. S., Meek, A. G., Park, T. L., et al. (1996). Glucose metabolic changes in nontumoral brain tissue of patients with brain tumor following radiotherapy: A preliminary study. J. Comput. Assist. Tomogr. 20: 709-714.

    Google Scholar 

  • Wassenberg, M. W. M., Bromberg, J. E. C., Witkamp, Th. D., Terhaard, C. H. J., and Taphoorn, M. J. B. (2001). White matter lesions and encephalopathy in patients treated for primary central nervous system lymphoma. J. Neuro-Oncol. 52: 73-80.

    Google Scholar 

  • Weitzner, M. A., Meyers, C. A., and Byrne, K. (1996). Psychosocial functioning and quality of life in patients with primary brain tumors. J. Neurosurg. 84: 29-34.

    Google Scholar 

  • Wellisch, D. K., Kaleita, T. A., Freeman, D., Cloughesy, T., and Goldman, J. (2002). Predicting major depression in brain tumor patients. Psycho-Oncology 11: 230-238.

    Google Scholar 

  • Wenz, F., Steinvorth, S., Wildermuth, S., Lohr, F., Fuss, M., Debus, J., et al. (1998). Assessment of neuropsychological changes in patients with arteriovenous malformation (AVM) after radiosurgery. Int. J. Radiat. Oncol. Biol. Phys. 42: 995-999.

    Google Scholar 

  • Werner-Wasik, M., Rudoler, S., Preston, P. E., Hauck, W. W., Downes, B. M., Leeper, D., et al. (1999). Immediate side effects of stereotactic radiotherapy and radiosurgery. Int. J. Radiat. Oncol. Biol. Phys. 43: 299-304.

    Google Scholar 

  • Williams, J. M., Ochs, J., Davis, K., and Daniel, M. (1986). The subacute effects of CNS prophylaxis for acute lymphoblastic leukemia on neuropsychologic performance. Arch. Clin. Neuropsychol. 1: 183-192.

    Google Scholar 

  • Willis, D. B., and Colburn, N. H. (2002). Molecular targets for cancer prevention: A meeting review of the Third American Cancer Society-Schilling Research Conference. Cancer Epidemiol. Biomarkers Prev. 11: 972-978.

    Google Scholar 

  • Woodburn, K. W., Fan, Q., Kessel, D., Luo, Y., and Young, S. W. (1998). Photodynamic therapy of B16F10 murine melanoma with lutetium texaphyrin. J. Invest. Dermatol. 110(5): 746-751.

    Google Scholar 

  • Young, R. F., Shumway-Cook, A., Vermeulen, S. S., Grimm, P., Blasko, J., Posewitz, A., et al. (1998). Gamma knife radiosurgery as a lesioning technique in movement disorder surgery. J. Neurosurg. 89: 183-193.

    Google Scholar 

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Authors and Affiliations

  1. Department of Neurology, University of Pennsylvania Medical School, Philadelphia, Pennsylvania

    Carol L. Armstrong

  2. Division of Neurology, Children's Hospital of Philadelphia, Philadelphia, Pennsylvania

    Carol L. Armstrong & Abdel W. Awadalla

  3. Division of Child and Adolescent Psychiatry, Schneider Children's Hospital, North Shore – Long Island Jewish Health System, New Hyde Park, New York

    Kunsang Gyato

  4. Department of Radiation Oncology, University of Pennsylvania Medical School, Philadelphia, Pennsylvania

    Robert Lustig & Zelig A Tochner

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Correspondence to Carol L. Armstrong.

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Armstrong, C.L., Gyato, K., Awadalla, A.W. et al. A Critical Review of the Clinical Effects of Therapeutic Irradiation Damage to the Brain: The Roots of Controversy. Neuropsychol Rev 14, 65–86 (2004). https://doi.org/10.1023/B:NERV.0000026649.68781.8e

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