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Current Neurology and Neuroscience Reports
Published in: Current Neurology and Neuroscience Reports 3/2010

01-05-2010

Neurocognitive Function in Brain Tumors

Author: Denise D. Correa

Published in: Current Neurology and Neuroscience Reports | Issue 3/2010

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Abstract

Cognitive dysfunction associated with both the disease and the adverse effects of radiotherapy (RT) and chemotherapy is a significant problem among brain tumor patients. Currently, it is considered the most frequent complication among long-term survivors. A review of the literature indicates that whole-brain RT alone or in combination with chemotherapy results in cognitive dysfunction more pronounced than from either partial RT or chemotherapy alone. The cognitive domains sensitive to treatment adverse effects include attention, executive functions, memory, and graphomotor speed. An increasing number of studies and clinical trials have incorporated cognitive outcome measures and have provided relevant information about therapy-related neurotoxicity and the incidence of cognitive dysfunction. Recent studies have begun to elucidate the pathophysiologic mechanisms that may underlie RT and chemotherapy injury to the brain. Although there are no established preventive or therapeutic interventions for treatment-induced cognitive dysfunction, this is an area of growing interest, and several approaches are currently under investigation.
Literature
1.
Behin A, Delattre, J-Y: Neurologic sequelae of radiotherapy on the nervous system. In Cancer Neurology in Clinical Practice. Edited by Schiff D, Wen PY. Totowa, NJ: Humana Press Inc.; 2003:173–191.
2.
Correa DD, DeAngelis LM, Shi W, et al.: Cognitive functions in survivors of primary central nervous system lymphoma. Neurology 2004; 62:548–555.PubMed
3.
Harder H, Holtel H, Bromberg JEC, et al.: Cognitive status and quality of life after treatment for primary CNS lymphoma. Neurology 2004, 62:544–547.PubMed
4.
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; 21:3557–3558.CrossRefPubMed
5.
Nordal RA, Wong CS: Molecular targets in radiation-induced blood-brain barrier disruption. Int J Radiat Oncol Biol Phys 2005, 62:279–287.CrossRefPubMed
6.
•• Dietrich J, Han R, Yang Y, et al.: CNS progenitor cells and oligodendrocytes are targets of chemotherapeutic agents in vitro and vivo. J Biol 2006, 5:1–23. This is an excellent paper describing in vitro and in vivo (mice) studies demonstrating that common chemotherapy agents caused increased cell death and decreased cell division in the subventricular zone and in the dentate gyrus of the hippocampus (regions involved in neurogenesis). These effects were seen in doses that were not effective in causing cell death in tumor cell lines. CrossRef
7.
•• Gehring K, Sitskoorn MM, Aaronson NK, et al.: Interventions for cognitive deficits in adults with brain tumours. Lancet Neurol 2008, 7:548–560. This article provides a comprehensive review of empiric studies using pharmacologic interventions to treat and prevent cognitive impairment in brain tumor patients; studies using cognitive rehabilitation techniques also are reviewed. CrossRefPubMed
8.
Wefel JS, Kayl AE, Meyers CA: Neuropsychological dysfunction associated with cancer and cancer therapies: a conceptual review of an emerging target. Br J Cancer 2004, 90:1691–1696.PubMed
9.
• Meyers CA, Brown PD: Role and relevance of neurocognitive assessments in clinical trials of patients with CNS tumors. J Clin Oncol 2006, 24:1305–1309. This study outlines the rationale for performing prospective neuropsychological evaluations at diagnosis and following treatment in patients with brain tumors. A brief test battery including standardized cognitive tests and quality-of-life questionnaires is suggested for use in neuro-oncology trials. CrossRefPubMed
10.
• Correa DD, Maron L, Harder H, et al.: Cognitive functions in primary central nervous system lymphoma: literature review and assessment guidelines. Ann Oncol 2007, 18:1145–1151. This article provides a comprehensive review of cognitive studies in PCNSL patients. It also proposes the use of a standardized cognitive test battery in future collaborative studies. CrossRefPubMed
11.
12.
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 2004, 58:1346–1352.CrossRef
13.
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, 22:157–165.CrossRefPubMed
14.
Klein M, Helmans 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, 360:1361–1368.CrossRefPubMed
15.
Correa DD, Rocco-Donovan M, DeAngelis LM, et al.: Prospective cognitive follow-up in primary CNS lymphoma patients treated with chemotherapy and reduced-dose radiotherapy. J Neurooncol 2009, 91:315–321.CrossRefPubMed
16.
Kayl AE, Meyers CA: Does brain tumor histology influence cognitive function? Neuro Oncol 2003, 5:255–260.CrossRefPubMed
17.
Hahn CA, Dunn RH, Logue PE, et al.: Prospective study of neuropsychologic testing and quality-of-life assessment of adults with primary malignant brain tumors. Int J Radiat Oncol Biol Phys 2003, 55:992–999.PubMed
18.
Lupien SJ, Gillin CJ, Hauger RL: Working memory is more sensitive than declarative memory to the acute effects of corticosteroids: a dose-response study in humans. Behav Neurosci 1999, 113:420–430.CrossRefPubMed
19.
• van Breemen MSM, Wilms EB, Vecht CJ: Epilepsy in patients with brain tumors: epidemiology, mechanisms, and management. Lancet Neurol 2007, 6:421–430. This article discusses the role of antiepileptic drugs in the management of seizures in brain tumor patients. Prophylactic use was not suggested, and interactions with chemotherapeutic agents and cognitive side effects are among the issues to consider in decision making. CrossRefPubMed
20.
• Bosma I, Vos MJ, Heimans JJ, et al.: The course of neurocognitive functioning in high grade glioma patients. Neuro Oncol 2007, 9:53–62. This study describes the results of longitudinal cognitive follow-up before and after treatment with RT in high-grade gliomas. Tumor progression and antiepileptic agents were associated with neurocognitive decline. CrossRefPubMed
21.
DeAngelis LM, Posner JB: Side effects of radiation therapy. In Neurologic Complications of Cancer, edn 2. Edited by DeAngelis LM, Posner JB. New York: Oxford University Press; 2009:551–555.
22.
Nagesh V, Tsien CI, Chenevert TL, et al.: Radiation-induced changes in normal appearing white matter in patients with cerebral tumors: a diffusion tensor imaging study. Int J Radiat Oncol Biol Phys 2008, 70:1002–1010.PubMed
23.
Hahn CA, Zhou SM, Raynor R, et al.: Dose-dependent effects of radiation therapy on cerebral blood flow, metabolism, and neurocognitive dysfunction. Int J Radiat Oncol Biol Phys 2009, 73:1082–1087.PubMed
24.
Bosma I, Douw L, Bartolomei F, et al.: Synchronized brain activity and neurocognitive function in patients with low-grade glioma: a magnetoencephalography study. Neuro Oncol 2008, 10:734–744.CrossRefPubMed
25.
Tofilon PJ, Fike JR: The radioresponse of the central nervous system: a dynamic process. Radiat Res 2000, 153:357–370.CrossRefPubMed
26.
Noble M, Dietrich J: Intersections between neurobiology and oncology: tumor origin, treatment and repair of treatment-associated damage. Trends Neurosci 2002, 25:103–107.CrossRefPubMed
27.
Kim JH, Brown SL, Jenrow KA: Mechanisms of radiation-induced brain toxicity and implications for future trials. J Neurooncol 2008, 87:279–286.CrossRefPubMed
28.
Fishel ML, Vasko MR, Kelley MR: DNA repair in neurons: so if they don’t divide what’s to repair. Mutat Res 2007, 614:24–36.PubMed
29.
Monje ML, Vogel H, Masek M, et al.: Impaired human hippocampal neurogenesis after treatment for central nervous system malignancies. Ann Neurol 2007, 62:515–520.CrossRefPubMed
30.
•• Fike JR, Rosi SR, Limoli CL: Neural precursor cells and central nervous system radiation sensitivity. Sem Radiat Oncol 2009, 19:122–132. This article describes the current knowledge on potential mechanisms for radiation injury to the brain. CrossRef
31.
•• Dietrich J, Monje M, Wefel J, et al.: Clinical patterns and biological correlates of cognitive dysfunction associated with cancer therapy. Oncologist 2008, 13:1285–1295. The authors provide a review of cognitive, imaging, and biological changes associated with chemotherapy and RT in cancer patients. CrossRefPubMed
32.
• Winocur G, Vardy J, Binns MA, et al.: The effects of anti-cancer drugs, methotrexate and 5-fluorouracil, on cognitive function in mice. Pharmacol Biochem Behav 2006, 85:66–75. These investigators reported deficits in several tasks associated with learning and memory in mice administered methotrexate and 5-fluorouracil. CrossRefPubMed
33.
Meyers CA, Hess KR, Yung WK, Levin VA: Cognitive function as a predictor of survival in patients with recurrent malignant glioma. J Clin Oncol 2000, 18:646–650.PubMed
34.
Armstrong CL, Goldstein B, Shera D, et al.: The predictive value of longitudinal neuropsychologic assessment in the early detection of brain tumor recurrence. Cancer 2003, 97:649–656.CrossRefPubMed
35.
Meyers CA, Hess KR: Multifaceted end points in brain tumor clinical trials: cognitive deterioration precedes MRI progression. Neuro Oncol 2003, 5:89–95.CrossRefPubMed
36.
Brown PD, Jensen AW, Felten SJ, et al.: Detrimental effects of tumor progression on cognitive function of patients with high-grade glioma. J Clin Oncol 2006, 24:5427–5433.CrossRefPubMed
37.
Hilverda K, Bosma I, Heimans JJ: Cognitive functioning in glioblastoma patients during radiotherapy and temozolomide treatment: initial findings. J Neurooncol 2010, 97:89–94.CrossRefPubMed
38.
Corn BW, Wang M, Fox S, et al.: Health related quality of life and cognitive status in patients with glioblastoma multiforme receiving escalating doses of conformal three dimensional radiation on RTOG 98-03. J Neurooncol 2009, 95:247–257.CrossRefPubMed
39.
• Keime-Guibert F, Chinot O, Tailandier L, et al.: Radiotherapy for glioblastoma in the elderly. N Engl J Med 2007, 356:1527–1535. This article reports the findings of a randomized trial comparing focal RT with supportive care in elderly patients (70 years or older) with high-grade tumors. RT was associated with a modest improvement in survival without significant neurocognitive decline at a median follow-up of 21 weeks. CrossRefPubMed
40.
Herman MA, Tremont-Lukats I, Meyers CA, et al.: Neurocognitive and functional assessment of patients with brain metastases. Am J Clin Oncol 2003, 26:273–279.CrossRefPubMed
41.
• Platta CS, Khuntia D, Mehta MP, Suh JH: Current treatment strategies for brain metastasis and complications from therapeutic techniques. Am J Clin Oncol (doi:10.​1097/​COC.​0b013e318194f744​). This article provides an overview of the most widely used therapies for brain metastases and discusses strategies to maintain or improve cognitive functions in these patients.
42.
Chang EL, Wefel JS, Maor MH, et al.: A pilot study of neurocognitive function in patients with one to three new brain metastases initially treated with stereotactic radiosurgery alone. Neurosurgery 2007, 60:285–292.
43.
Welzel G, Fleckenstein K, Schaefer J, et al.: Memory function before and after whole brain radiotherapy in patients with and without brain metastasis. Int J Radiat Oncol Biol Phys 2008, 72:1311–1318.PubMed
44.
Metha MP, Shapiro WR, Phan SC, et al.: Motexafin gadolinium combined with prompt whole brain radiotherapy prolongs time to neurologic progression in non-small-cell lung cancer patients with brain metastases: results of a phase III trial. Int J Radiat Oncol Biol Phys 2009, 73:1069–1076.
45.
• Brown PD, Asher AL, Farace E: Adjuvant whole brain radiotherapy: strong emotions decide but rational studies are needed. Int J Radiat Oncol Biol Phys 2008, 70:1305–1309. This article discusses recent studies involving patients with brain metastases treated with whole-brain RT with regard to treatment efficacy and neurocognitive side effects. It emphasizes the importance of including serial neurocognitive assessment in large clinical trials to further elucidate the risks and benefits of ongoing and newly developed therapies. PubMed
46.
Taphoorn MJB, Schiphorst AK, Snoek FJ, et al.: Cognitive functions and quality of life in patients with low-grade gliomas: the impact of radiotherapy. Ann Neurol 1994, 36:48–54.CrossRefPubMed
47.
Laack NN, Brown PD, Furth A, et al.: Neurocognitive function after radiotherapy (RT) for supratentorial low-grade gliomas (LGG): results of a North Central Cancer Treatment Group prospective study. Int J Radiat Oncol Biol Phys 2003, 57:S134.
48.
Torres IJ, Mundt AJ, Sweeney PJ, et al.: A longitudinal neuropsychological study of partial brain radiation in adults with brain tumors. Neurology 2003, 60:1113–1118.CrossRefPubMed
49.
•• Douw L, Klein M, Fagel SA, et al.: Cognitive and radiological effects of radiotherapy in patients with low-grade glioma: long-term follow-up. Lancet Neurol 2009, 8:810–818. This study reports the findings of longitudinal cognitive follow-up for 65 low-grade glioma patients who participated in a prior study. The authors reported a decline in cognitive functions, particularly in attention, in patients treated with RT. CrossRefPubMed
50.
Armstrong CL, Corn BW, Ruffer JE, et al.: Radiotherapeutic effects on brain function: double dissociation of memory systems. Neuropsychiatry Neuropsychol Behav Neurol 2000, 13:101–111.PubMed
51.
Armstrong CL, Stern CH, Corn BW: Memory performance used to detect radiation effects on cognitive functioning. Appl Neuropsychol 2001, 8:129–139.CrossRefPubMed
52.
Correa DD, DeAngelis LM, Shi W, et al.: Cognitive functions and APOE genotype in low grade glioma patients. Neuro Oncol 2007, 81:175–184.
53.
Correa DD, Shi W, Thaler HT, et al.: Longitudinal cognitive follow-up in low grade gliomas. J Neurooncol 2008, 86:321–327.CrossRefPubMed
54.
Abrey LE: Primary central nervous system lymphoma. Curr Opin Neurol 2009 Sep 5 (Epub ahead of print).
55.
• Ghia A, Tome WA, Thomas S, et al.: Distribution of brain metastases in relation to the hippocampus: implications for neurocognitive functional preservation. Int J Radiat Oncol 2007, 68: 971–977. This study explored the viability of developing a tomotherapy plan to deliver hippocampus-sparing whole brain radiation to patients with brain metastasis; this method could potentially reduce the neurocognitive deficits associated with RT. CrossRef
56.
Torcuator R, Zuniga R, Mohan YS, et al.: Initial experience with bevacizumab treatment for biopsy confirmed cerebral radiation necrosis. J Neurooncol 2009, 94:63–68.CrossRefPubMed
57.
Gehring K, Sitskoorn MM, Gundy CM, et al.: Cognitive rehabilitation in patients with gliomas: a randomized, controlled trial. J Clin Oncol 2009, 27:3712–3722.CrossRefPubMed
Metadata
Title
Neurocognitive Function in Brain Tumors
Author
Denise D. Correa
Publication date
01-05-2010
Publisher
Current Science Inc.
Published in
Current Neurology and Neuroscience Reports / Issue 3/2010
Print ISSN: 1528-4042
Electronic ISSN: 1534-6293
DOI
https://doi.org/10.1007/s11910-010-0108-4

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