Regression After Whole-Brain Radiation Therapy for Brain Metastases Correlates With Survival and Improved Neurocognitive Function

Brain metastasis (BM) is a major cause of suffering and health costs in cancer patients. Whole-brain radiation therapy (WBRT) offers tumor shrinking and palliation in many cases, but it has been speculated that these benefits may be outweighed by adverse effects on neurocognitive function (NCF). Two...

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Published inJournal of clinical oncology Vol. 25; no. 10; pp. 1260 - 1266
Main Authors Li, Jing, Bentzen, Soren M., Renschler, Markus, Mehta, Minesh P.
Format Journal Article
LanguageEnglish
Published Baltimore, MD American Society of Clinical Oncology 01.04.2007
Lippincott Williams & Wilkins
Subjects
Online AccessGet full text
ISSN0732-183X
1527-7755
1527-7755
DOI10.1200/JCO.2006.09.2536

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Abstract Brain metastasis (BM) is a major cause of suffering and health costs in cancer patients. Whole-brain radiation therapy (WBRT) offers tumor shrinking and palliation in many cases, but it has been speculated that these benefits may be outweighed by adverse effects on neurocognitive function (NCF). Two hundred eight BM patients from the WBRT arm of phase III trial PCI-P120-9801 evaluating motexafin gadolinium were analyzed. NCF, assessed by tests of memory, executive function, and fine motor coordination, was correlated to magnetic resonance imaging-measured BM volume. NCF and survival were compared in 135 patients assessable at 2 months with tumor shrinkage below (poor responders) and above (good responders) the population median (45%). Mean NCF scores and BM volume at 4 and 15 months were compared. Good responders experienced a significantly improved survival (unidirectional P = .03). For all tests, the median time to NCF deterioration was longer in good compared with poor responders, with statistical significance seen for Trailmaking B (executive function), and two Pegboard tests (fine motor). In long-term survivors, tumor shrinkage significantly correlated with preservation of executive function and fine motor coordination (r = 0.68 to 0.88). During the early follow-up period, the population mean NCF scores were dominated by patients with progressive disease. A small subset of 15-month survivors had stable or improving scores, and greater mean BM reduction. WBRT-induced tumor shrinkage correlates with better survival and NCF preservation. NCF is stable or improved in long-term survivors. Tumor progression adversely affects NCF more than WBRT does, thus making enhancement of radiation response a worthwhile aim in this patient population.
AbstractList Brain metastasis (BM) is a major cause of suffering and health costs in cancer patients. Whole-brain radiation therapy (WBRT) offers tumor shrinking and palliation in many cases, but it has been speculated that these benefits may be outweighed by adverse effects on neurocognitive function (NCF). Two hundred eight BM patients from the WBRT arm of phase III trial PCI-P120-9801 evaluating motexafin gadolinium were analyzed. NCF, assessed by tests of memory, executive function, and fine motor coordination, was correlated to magnetic resonance imaging-measured BM volume. NCF and survival were compared in 135 patients assessable at 2 months with tumor shrinkage below (poor responders) and above (good responders) the population median (45%). Mean NCF scores and BM volume at 4 and 15 months were compared. Good responders experienced a significantly improved survival (unidirectional P = .03). For all tests, the median time to NCF deterioration was longer in good compared with poor responders, with statistical significance seen for Trailmaking B (executive function), and two Pegboard tests (fine motor). In long-term survivors, tumor shrinkage significantly correlated with preservation of executive function and fine motor coordination (r = 0.68 to 0.88). During the early follow-up period, the population mean NCF scores were dominated by patients with progressive disease. A small subset of 15-month survivors had stable or improving scores, and greater mean BM reduction. WBRT-induced tumor shrinkage correlates with better survival and NCF preservation. NCF is stable or improved in long-term survivors. Tumor progression adversely affects NCF more than WBRT does, thus making enhancement of radiation response a worthwhile aim in this patient population.
Brain metastasis (BM) is a major cause of suffering and health costs in cancer patients. Whole-brain radiation therapy (WBRT) offers tumor shrinking and palliation in many cases, but it has been speculated that these benefits may be outweighed by adverse effects on neurocognitive function (NCF).PURPOSEBrain metastasis (BM) is a major cause of suffering and health costs in cancer patients. Whole-brain radiation therapy (WBRT) offers tumor shrinking and palliation in many cases, but it has been speculated that these benefits may be outweighed by adverse effects on neurocognitive function (NCF).Two hundred eight BM patients from the WBRT arm of phase III trial PCI-P120-9801 evaluating motexafin gadolinium were analyzed. NCF, assessed by tests of memory, executive function, and fine motor coordination, was correlated to magnetic resonance imaging-measured BM volume. NCF and survival were compared in 135 patients assessable at 2 months with tumor shrinkage below (poor responders) and above (good responders) the population median (45%). Mean NCF scores and BM volume at 4 and 15 months were compared.PATIENTS AND METHODSTwo hundred eight BM patients from the WBRT arm of phase III trial PCI-P120-9801 evaluating motexafin gadolinium were analyzed. NCF, assessed by tests of memory, executive function, and fine motor coordination, was correlated to magnetic resonance imaging-measured BM volume. NCF and survival were compared in 135 patients assessable at 2 months with tumor shrinkage below (poor responders) and above (good responders) the population median (45%). Mean NCF scores and BM volume at 4 and 15 months were compared.Good responders experienced a significantly improved survival (unidirectional P = .03). For all tests, the median time to NCF deterioration was longer in good compared with poor responders, with statistical significance seen for Trailmaking B (executive function), and two Pegboard tests (fine motor). In long-term survivors, tumor shrinkage significantly correlated with preservation of executive function and fine motor coordination (r = 0.68 to 0.88). During the early follow-up period, the population mean NCF scores were dominated by patients with progressive disease. A small subset of 15-month survivors had stable or improving scores, and greater mean BM reduction.RESULTSGood responders experienced a significantly improved survival (unidirectional P = .03). For all tests, the median time to NCF deterioration was longer in good compared with poor responders, with statistical significance seen for Trailmaking B (executive function), and two Pegboard tests (fine motor). In long-term survivors, tumor shrinkage significantly correlated with preservation of executive function and fine motor coordination (r = 0.68 to 0.88). During the early follow-up period, the population mean NCF scores were dominated by patients with progressive disease. A small subset of 15-month survivors had stable or improving scores, and greater mean BM reduction.WBRT-induced tumor shrinkage correlates with better survival and NCF preservation. NCF is stable or improved in long-term survivors. Tumor progression adversely affects NCF more than WBRT does, thus making enhancement of radiation response a worthwhile aim in this patient population.CONCLUSIONWBRT-induced tumor shrinkage correlates with better survival and NCF preservation. NCF is stable or improved in long-term survivors. Tumor progression adversely affects NCF more than WBRT does, thus making enhancement of radiation response a worthwhile aim in this patient population.
Author Markus Renschler
Jing Li
Soren M. Bentzen
Minesh P. Mehta
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  surname: Li
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– sequence: 2
  givenname: Soren M.
  surname: Bentzen
  fullname: Bentzen, Soren M.
  organization: From the Department of Human Oncology, University of Wisconsin Comprehensive Cancer Center, Madison, WI; and Oncology Clinical Development, Pharmacyclics, Sunnyvale, CA
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  givenname: Markus
  surname: Renschler
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  organization: From the Department of Human Oncology, University of Wisconsin Comprehensive Cancer Center, Madison, WI; and Oncology Clinical Development, Pharmacyclics, Sunnyvale, CA
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  givenname: Minesh P.
  surname: Mehta
  fullname: Mehta, Minesh P.
  organization: From the Department of Human Oncology, University of Wisconsin Comprehensive Cancer Center, Madison, WI; and Oncology Clinical Development, Pharmacyclics, Sunnyvale, CA
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Issue 10
Keywords Nervous system diseases
Cancerology
Treatment
Brain cancer
Central nervous system disease
Regression
Malignant tumor
Radiotherapy
Cerebral metastasis
Survival
Cerebral disorder
Language English
License CC BY 4.0
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PublicationTitle Journal of clinical oncology
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Lippincott Williams & Wilkins
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17761992 - J Clin Oncol. 2007 Sep 1;25(25):4023; author reply 4024-5
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Snippet Brain metastasis (BM) is a major cause of suffering and health costs in cancer patients. Whole-brain radiation therapy (WBRT) offers tumor shrinking and...
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SubjectTerms Adult
Biological and medical sciences
Brain - physiopathology
Brain Neoplasms - mortality
Brain Neoplasms - psychology
Brain Neoplasms - radiotherapy
Brain Neoplasms - secondary
Cognition
Cranial Irradiation
Humans
Medical sciences
Neurology
Prospective Studies
Quality of Life
Tumors
Tumors of the nervous system. Phacomatoses
Title Regression After Whole-Brain Radiation Therapy for Brain Metastases Correlates With Survival and Improved Neurocognitive Function
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https://www.ncbi.nlm.nih.gov/pubmed/17401015
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