title: Neuropsychological testing and biomarkers in the management of brain metastases.
abstract: Prognosis for patients with brain metastasis remains poor. Whole brain radiation therapy is the conventional treatment option; it can improve neurological symptoms, prevent and improve tumor associated neurocognitive decline, and prevents death from neurologic causes. In addition to whole brain radiation therapy, stereotactic radiosurgery, neurosurgery and chemotherapy also are used in the management of brain metastases. Radiosensitizers are now currently being investigated as potential treatment options. All of these treatment modalities carry a risk of central nervous system (CNS) toxicity that can lead to neurocognitive impairment in long term survivors. Neuropsychological testing and biomarkers are potential ways of measuring and better understanding CNS toxicity. These tools may help optimize current therapies and develop new treatments for these patients. This article will review the current management of brain metastases, summarize the data on the CNS effects associated with brain metastases and whole brain radiation therapy in these patients, discuss the use of neuropsychological tests as outcome measures in clinical trials evaluating treatments for brain metastases, and give an overview of the potential of biomarker development in brain metastases research.
authors.affiliation: Radiation Oncology Branch, National Cancer Institute, National Institutes of Health, 9000 Rockville Pike, Building 10-CRC, Room B2-3561, Bethesda, Maryland, 20892, USA. amb26@buffalo.edu
authors.forename: Andrew
authors.initials: A
authors.lastname: Baschnagel
authors.forename: Pamela L
authors.initials: PL
authors.lastname: Wolters
authors.forename: Kevin
authors.initials: K
authors.lastname: Camphausen
mesh_terms: D000368:Aged; D014408:Biomarkers, Tumor / Q000378:metabolism*; D001932:Brain Neoplasms / Q000150:complications / Q000175:diagnosis* / Q000378:metabolism / Q000523:psychology*; D002490:Central Nervous System / Q000187:drug effects / Q000473:pathology; D002986:Clinical Trials as Topic; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D009362:Neoplasm Metastasis; D009483:Neuropsychological Tests; D011379:Prognosis; D016634:Radiosurgery; D012107:Research Design; D016896:Treatment Outcome
chemical_list: D014408:Biomarkers, Tumor
references.citation: Cancer. 1981 Jul 15;48(2):384-94
references.pmid: 7237407
references.citation: Clin Chim Acta. 1989 Jul 31;183(1):13-31
references.pmid: 2548772
references.citation: J Neurooncol. 1994;19(2):149-54
references.pmid: 7964990
references.citation: Int J Radiat Oncol Biol Phys. 2001 Oct 1;51(2):426-34
references.pmid: 11567817
references.citation: Cancer. 1965 Mar;18:298-306
references.pmid: 14264031
references.citation: J Clin Oncol. 2004 Jan 1;22(1):157-65
references.pmid: 14701778
references.citation: Strahlenther Onkol. 1994 Mar;170(3):155-61
references.pmid: 8160096
references.citation: J Psychiatr Res. 1975 Nov;12(3):189-98
references.pmid: 1202204
references.citation: Int J Radiat Oncol Biol Phys. 2008 May 1;71(1):64-70
references.pmid: 18406884
references.citation: N Engl J Med. 1990 Feb 22;322(8):494-500
references.pmid: 2405271
references.citation: Md State Med J. 1965 Feb;14:61-5
references.pmid: 14258950
references.citation: Int J Radiat Oncol Biol Phys. 1999 Mar 1;43(4):795-803
references.pmid: 10098435
references.citation: Int J Radiat Oncol Biol Phys. 1995 Oct 15;33(3):619-26
references.pmid: 7558951
references.citation: Radiat Res. 2000 Apr;153(4):357-70
references.pmid: 10798963
references.citation: Cancer Res. 2003 Jul 15;63(14):4021-7
references.pmid: 12874001
references.citation: Neurosurgery. 2007 Feb;60(2):277-83; discussion 283-4
references.pmid: 17290178
references.citation: Ment Retard Dev Disabil Res Rev. 2006;12(3):184-91
references.pmid: 17061287
references.citation: J Clin Oncol. 2005 Dec 1;23(34):8870-6
references.pmid: 16314647
references.citation: J Am Acad Dermatol. 1999 Dec;41(6):962-9
references.pmid: 10570381
references.citation: Br J Cancer. 2004 May 4;90(9):1691-6
references.pmid: 15150608
references.citation: Ann Neurol. 1980 Jun;7(6):529-41
references.pmid: 7436358
references.citation: Cancer Res. 1996 Jan 1;56(1):172-81
references.pmid: 8548760
references.citation: Br J Cancer. 1997;76(8):1041-5
references.pmid: 9376264
references.citation: JAMA. 2006 Jun 7;295(21):2483-91
references.pmid: 16757720
references.citation: Lancet. 2004 May 22;363(9422):1665-72
references.pmid: 15158627
references.citation: J Clin Oncol. 2006 Mar 20;24(9):1415-20
references.pmid: 16549835
references.citation: J Clin Oncol. 2004 Feb 1;22(3):499-506
references.pmid: 14752073
references.citation: Strahlenther Onkol. 1986 Mar;162(3):157-61
references.pmid: 3515602
references.citation: Cancer. 2005 Aug 15;104(4):817-24
references.pmid: 15971200
references.citation: Int J Radiat Oncol Biol Phys. 1981 Dec;7(12):1633-8
references.pmid: 6174490
references.citation: Int J Radiat Oncol Biol Phys. 1991 Jan;20(1):53-8
references.pmid: 1993631
references.citation: Int J Radiat Oncol Biol Phys. 2008 Feb 1;70(2):510-4
references.pmid: 17931798
references.citation: J Clin Oncol. 2000 Apr;18(7):1423-31
references.pmid: 10735889
references.citation: Technol Cancer Res Treat. 2003 Apr;2(2):111-5
references.pmid: 12680791
references.citation: J Clin Oncol. 2002 Sep 1;20(17):3644-50
references.pmid: 12202665
references.citation: Int J Radiat Oncol Biol Phys. 1980 Jan;6(1):1-9
references.pmid: 6154024
references.citation: J Clin Oncol. 2000 Feb;18(3):646-50
references.pmid: 10653880
references.citation: J Neurosurg. 2002 Dec;97(5 Suppl):499-506
references.pmid: 12507085
references.citation: Int J Radiat Oncol Biol Phys. 1997 Mar 1;37(4):745-51
references.pmid: 9128946
references.citation: J Clin Oncol. 2003 Jul 1;21(13):2519-24
references.pmid: 12829670
references.citation: Stroke. 2000 Oct;31(10):2325-9
references.pmid: 11022058
references.citation: Cancer. 1996 Oct 1;78(7):1470-6
references.pmid: 8839553
references.citation: Lancet. 1997 Jan 11;349(9045):79-83
references.pmid: 8996418
references.citation: J Clin Oncol. 2004 Jun 1;22(11):2233-9
references.pmid: 15169812
references.citation: Int J Radiat Oncol Biol Phys. 2004 Apr 1;58(5):1346-52
references.pmid: 15050309
references.citation: J Clin Oncol. 2004 Feb 15;22(4):706-13
references.pmid: 14966095
references.citation: Cancer. 1995 Mar 1;75(5):1151-61
references.pmid: 7850714
references.citation: Lancet. 2002 Nov 2;360(9343):1361-8
references.pmid: 12423981
references.citation: Int J Radiat Oncol Biol Phys. 1981 Jul;7(7):891-5
references.pmid: 6171553
references.citation: J Neurooncol. 1984;2(4):325-30
references.pmid: 6397578
references.citation: Int J Radiat Oncol Biol Phys. 1977 Nov-Dec;2(11-12):1091-4
references.pmid: 74375
references.citation: Stroke. 2001 May;32(5):1154-61
references.pmid: 11340225
references.citation: J Clin Oncol. 1998 Jul;16(7):2522-7
references.pmid: 9667273
references.citation: J Clin Oncol. 2003 Jun 15;21(12):2364-71
references.pmid: 12805339
references.citation: Int J Radiat Oncol Biol Phys. 1997 Oct 1;39(3):571-4
references.pmid: 9336134
references.citation: Lancet Neurol. 2008 Jun;7(6):548-60
references.pmid: 18485318
references.citation: Neurology. 1989 Jun;39(6):789-96
references.pmid: 2725874
references.citation: Med Clin North Am. 1963 Nov;47:1647-58
references.pmid: 14078168
references.citation: Int J Radiat Oncol Biol Phys. 2007 Aug 1;68(5):1388-95
references.pmid: 17674975
references.citation: Int J Radiat Oncol Biol Phys. 2000 Aug 1;48(1):59-64
references.pmid: 10924972
references.citation: Neuro Oncol. 2003 Apr;5(2):89-95
references.pmid: 12672280
references.citation: J Clin Oncol. 2007 Apr 1;25(10):1260-6
references.pmid: 17401015
references.citation: Int J Radiat Oncol Biol Phys. 2001 Mar 15;49(4):1015-21
references.pmid: 11240242
references.citation: J Clin Oncol. 2006 Jan 1;24(1):106-14
references.pmid: 16314619
references.citation: Cancer. 2003 Jun 1;97(11):2806-13
references.pmid: 12767094
references.citation: Clin Cancer Res. 2008 Feb 1;14(3):931-8
references.pmid: 18245557
references.citation: Stroke. 2002 Apr;33(4):982-7
references.pmid: 11935048
references.citation: Mol Pharmacol. 1989 Jul;36(1):106-12
references.pmid: 2568579
references.citation: Neurosurg Clin N Am. 1996 Jul;7(3):337-44
references.pmid: 8823767
references.citation: Br J Cancer. 2001 Apr 6;84(7):903-9
references.pmid: 11286469
references.citation: J Neurol Neurosurg Psychiatry. 2003 Mar;74(3):322-5
references.pmid: 12588916
references.citation: Am J Clin Oncol. 2003 Jun;26(3):273-9
references.pmid: 12796600
references.citation: Int J Radiat Oncol Biol Phys. 1995 Mar 30;31(5):1093-112
references.pmid: 7677836
references.citation: Int J Radiat Oncol Biol Phys. 2008 May 1;71(1):71-8
references.pmid: 18164829
references.citation: Int J Radiat Oncol Biol Phys. 2001 Nov 1;51(3):711-7
references.pmid: 11597813
references.citation: Int J Radiat Oncol Biol Phys. 1995 Sep 30;33(2):339-48
references.pmid: 7673021
references.citation: Int J Radiat Oncol Biol Phys. 2007 Nov 1;69(3):839-45
references.pmid: 17544592
references.citation: Int J Radiat Oncol Biol Phys. 2007 Oct 1;69(2):589-97
references.pmid: 17869672
references.citation: J Clin Oncol. 2003 Jul 1;21(13):2529-36
references.pmid: 12829672
references.citation: Int J Radiat Oncol Biol Phys. 2008 May 1;71(1):79-86
references.pmid: 18164847
references.citation: J Neurooncol. 1989 Sep;7(3):241-7
references.pmid: 2677257
references.citation: J Clin Oncol. 2003 Oct 1;21(19):3557-8
references.pmid: 12913103
references.citation: Int J Radiat Oncol Biol Phys. 1994 Jul 1;29(4):711-7
references.pmid: 8040016
references.citation: Stroke. 2005 Jul;36(7):1415-20
references.pmid: 15947272
references.citation: Radiother Oncol. 1993 Feb;26(2):111-6
references.pmid: 7681997
references.citation: JAMA. 1998 Nov 4;280(17):1485-9
references.pmid: 9809728
references.citation: Neurosurgery. 1989 Jun;24(6):798-805
references.pmid: 2473409
references.citation: J Neurooncol. 1996 Mar;27(3):269-77
references.pmid: 8847561
references.citation: Int J Radiat Oncol Biol Phys. 2007 Jan 1;67(1):240-3
references.pmid: 17056192
references.citation: Ann Neurol. 1993 Jun;33(6):583-90
references.pmid: 8498838
references.citation: J Neurol Sci. 2007 Jun 15;257(1-2):67-71
references.pmid: 17316691
references.citation: Cancer Res. 1992 Aug 15;52(16):4548-9
references.pmid: 1322794
references.citation: Cancer. 2004 Jan 15;100(2):398-404
references.pmid: 14716777