Neurocognitive function assessment for cancer patients with brain metastases following whole brain radiation therapy
A SINGLE INSTITUTIONAL OBSERVATIONAL STUDY FROM A TERTIARY CARE HOSPITAL
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Abstract
ABSTRACT BACKGROUND: Whole Brain Radiation Therapy (WBRT) has been effective in the management of brain metastases, giving good local control but has shown to have potential neurocognitive effects. Assessing its effect on neurocognitive function is decisive assessing quality of life and therapeutic decision-making. METHOD: This is an observational study at R. G. Kar Medical College and Hospital from May 2022 to April 2023 involving 60 biopsy proven carcinoma patients with brain metastases fulfilling inclusion and exclusion criteria. All received 30Gray (Gy)/10# WBRT over 2 weeks. Neurocognitive function assessment using Mini Mental State Examination (MMSE) were conducted before and at 2nd, 3rd, and 6th months post WBRT. RESULTS: The study, encompassing a median age of 58, revealed 43.3% had lung primary and 35% breast primary. Mean MMSE score was 27 pre radiation. Following WBRT, a more than equals to 3-point MMSE decrease occurred in 6.6%, 11.6%, and 18.3% at 2nd, 3rd, and 6th months post radiation respectively. Neurocognitive decline was 36% for those above 50 years and 64% for those below 50 years by the 6th month. At 2nd months 88.3% patients had controlled disease having a decrease in MMSE score by 1.6, while 11.6% with uncontrolled disease showed 3.1 MMSE change and the same trend continued at 3rd and 6th month observations. CONCLUSION: WBRT is crucial for local control of brain metastases, but neurocognitive decline, especially under 50, is of major concern. Study results offers awareness for pre-treatment counseling on WBRT benefits, risks and consideration for Hippocampal Avoidance WBRT or WBRT with memantine, and requires further extensive research.
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[2] Gianluca Ferini, Viola A, Valenti V, Tripoli A, Molino L, Marchese V, et al. Whole Brain Irradiation or Stereotactic RadioSurgery for five or more brain metastases (WHOBI-STER): A prospective comparative study of neurocognitive outcomes, level of autonomy in daily activities and quality of life. 2021 Dec 1;32:52–8.
[3] Tallet AV, Azria D, Barlesi F, Spano JP, Carpentier AF, Gonçalves A, et al. Neurocognitive function impairment after whole brain radiotherapy for brain metastases: actual assessment. Radiation Oncology. 2012 May 28;7(1).
[4] Li J, Bentzen SM, Renschler M, Mehta MP. Regression After Whole-Brain Radiation Therapy for Brain Metastases Correlates With Survival and Improved Neurocognitive Function. Journal of Clinical Oncology. 2007 Apr 1;25(10):1260–6.
[5] Brown PD, Jaeckle K, Ballman KV, Farace E, Cerhan JH, Anderson SK, et al. Effect of Radiosurgery Alone vs Radiosurgery With Whole Brain Radiation Therapy on Cognitive Function in Patients With 1 to 3 Brain Metastases: A Randomized Clinical Trial. JAMA [Internet]. 2016;316(4):401–9. Available from: https://www.ncbi.nlm.nih.gov/pubmed/27458945
[6] Chang EL, Wefel JS, Hess KR, Allen PK, Lang FF, Kornguth DG, Arbuckle RB, Swint JM, Shiu AS, Maor MH, 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(11):1037–44.
[7] Prabhu RS, Won M, Shaw EG, Hu C, Brachman DG, Buckner JC, et al. Effect of the Addition of Chemotherapy to Radiotherapy on Cognitive Function in Patients With Low-Grade Glioma: Secondary Analysis of RTOG 98-02. Journal of Clinical Oncology [Internet]. 2014 Feb 20;32(6):535–41. Available from: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3918537/
[8] Regine WF, Scott C, Murray K, Curran W. Neurocognitive outcome in brain metastases patients treated with accelerated-fractionation vs. accelerated-hyper-fractionated radiotherapy: an analysis from Radiation Therapy Oncology Group Study 91-04. International Journal of Radiation Oncology*Biology*Physics [Internet]. 2001 Nov 1 [cited 2023 Jan 6];51(3):711–7. Available from: https://www.sciencedirect.com/science/article/pii/S0360301601016765
[9] Gavrilovic IT, Posner JB. Brain metastases: epidemiology and pathophysiology. J Neurooncol. (2005) 75:5–14. 10.1007/s11060-004-8093-6
[10] Armstrong C, Ruffer J, Corn B, DeVries K, Mollman J. Biphasic patterns of memory deficits following moderate-dose partial brain irradiation: neuropsychologic outcomes and proposed mechanisms. J Clin Oncol. 1995;13:2263–71.
[11] Sheline G, Wara WM, Smith V. Therapeutic irradiation and brain injury. Int J Radiat Oncol Biol Phys. 1980;6:1215–28. doi: 10.1016/0360-3016(80)90175-3.
[12] Butler JM, Rapp SR, Shaw EG. Managing the cognitive effects of brain tumor radiation therapy. Curr Treat Options Oncol. 2006;7(6):517–23.
[13] DeAngelis LM, Posner JB. In: Side effects of radiation therapy. 2. DeAngelis LM, Posner JB, editor. Oxford University Press, New York; 2009. pp. 551–555.
[14] Aoyama H. Radiation therapy for brain metastases in breast cancer patients. Breast Cancer. 2011;18(4):244–51.
[15] Abe E, Aoyama H. The Role of Whole Brain Radiation Therapy for the Management of Brain Metastases in the Era of Stereotactic Radiosurgery. Curr Oncol Rep. 2012;14(1):79–84. doi: 10.1007/s11912-011-0201-0.
[16] Aoyama H, Tago M, Kato N, Toyoda T, Kenjyo M, Hirota S. et al. Neurocognitive function of patients with brain metastasis who received either whole brain radiotherapy plus stereotactic radiosurgery or radiosurgery alone. Int J Radiat Oncol Biol Phys. 2007;68(5):1388–95.
[17] Mehta MP, Rodrigus P, Terhaard CH, Rao A, Suh J, Souhami L. et al. Survival and neurologic outcomes in a randomized trial of motexafin gadolinium and whole-brain radiation therapy in brain metastases. J Clin Oncol. 2003;21(13):2529–36.
[18] Li J, Bentzen SM, Renschler M, Mehta MP. Regression after whole-brain radiation therapy for brain metastases correlates with survival improved neurocognitive function. J Clin Oncol. 2007;25(10):1260–66.
[19] Meyers CA, Smith JA, Bezjak A, Mehta MP, Liebmann J, Illidge T. 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(1):157–65.
[20] Regine WF, Huhn JL, Patchell RA, St Clair WH, Strottmann J, Meigooni A. et al. Risk of symptomatic brain tumor recurrence and neurologic deficit after radiosurgery alone in patients with newly diagnosed brain metastases: Results and implications. Int J Radiat Oncol Biol Phys. 2002;52:333–8.
[21] Rosenman J, Choi NC. Improved quality of life of patients with small-cell carcinoma of the lung by elective irradiation of the brain. Int J Radiat Oncol Biol Phys. 1982;8(6):1041–3.
[22] Regine WF, Scott C, Murray KJ, Curran W. Neurocognitive outcome in brain metastases patients treated with accelerated-fractionation vs. accelerated-hyperfractionated radiotherapy: an analysis from Radiation therapy Oncology Group study 91–04. Int J Radiat Oncol Biol Phys. 2001;51(3):711–17.
[2] Gianluca Ferini, Viola A, Valenti V, Tripoli A, Molino L, Marchese V, et al. Whole Brain Irradiation or Stereotactic RadioSurgery for five or more brain metastases (WHOBI-STER): A prospective comparative study of neurocognitive outcomes, level of autonomy in daily activities and quality of life. 2021 Dec 1;32:52–8.
[3] Tallet AV, Azria D, Barlesi F, Spano JP, Carpentier AF, Gonçalves A, et al. Neurocognitive function impairment after whole brain radiotherapy for brain metastases: actual assessment. Radiation Oncology. 2012 May 28;7(1).
[4] Li J, Bentzen SM, Renschler M, Mehta MP. Regression After Whole-Brain Radiation Therapy for Brain Metastases Correlates With Survival and Improved Neurocognitive Function. Journal of Clinical Oncology. 2007 Apr 1;25(10):1260–6.
[5] Brown PD, Jaeckle K, Ballman KV, Farace E, Cerhan JH, Anderson SK, et al. Effect of Radiosurgery Alone vs Radiosurgery With Whole Brain Radiation Therapy on Cognitive Function in Patients With 1 to 3 Brain Metastases: A Randomized Clinical Trial. JAMA [Internet]. 2016;316(4):401–9. Available from: https://www.ncbi.nlm.nih.gov/pubmed/27458945
[6] Chang EL, Wefel JS, Hess KR, Allen PK, Lang FF, Kornguth DG, Arbuckle RB, Swint JM, Shiu AS, Maor MH, 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(11):1037–44.
[7] Prabhu RS, Won M, Shaw EG, Hu C, Brachman DG, Buckner JC, et al. Effect of the Addition of Chemotherapy to Radiotherapy on Cognitive Function in Patients With Low-Grade Glioma: Secondary Analysis of RTOG 98-02. Journal of Clinical Oncology [Internet]. 2014 Feb 20;32(6):535–41. Available from: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3918537/
[8] Regine WF, Scott C, Murray K, Curran W. Neurocognitive outcome in brain metastases patients treated with accelerated-fractionation vs. accelerated-hyper-fractionated radiotherapy: an analysis from Radiation Therapy Oncology Group Study 91-04. International Journal of Radiation Oncology*Biology*Physics [Internet]. 2001 Nov 1 [cited 2023 Jan 6];51(3):711–7. Available from: https://www.sciencedirect.com/science/article/pii/S0360301601016765
[9] Gavrilovic IT, Posner JB. Brain metastases: epidemiology and pathophysiology. J Neurooncol. (2005) 75:5–14. 10.1007/s11060-004-8093-6
[10] Armstrong C, Ruffer J, Corn B, DeVries K, Mollman J. Biphasic patterns of memory deficits following moderate-dose partial brain irradiation: neuropsychologic outcomes and proposed mechanisms. J Clin Oncol. 1995;13:2263–71.
[11] Sheline G, Wara WM, Smith V. Therapeutic irradiation and brain injury. Int J Radiat Oncol Biol Phys. 1980;6:1215–28. doi: 10.1016/0360-3016(80)90175-3.
[12] Butler JM, Rapp SR, Shaw EG. Managing the cognitive effects of brain tumor radiation therapy. Curr Treat Options Oncol. 2006;7(6):517–23.
[13] DeAngelis LM, Posner JB. In: Side effects of radiation therapy. 2. DeAngelis LM, Posner JB, editor. Oxford University Press, New York; 2009. pp. 551–555.
[14] Aoyama H. Radiation therapy for brain metastases in breast cancer patients. Breast Cancer. 2011;18(4):244–51.
[15] Abe E, Aoyama H. The Role of Whole Brain Radiation Therapy for the Management of Brain Metastases in the Era of Stereotactic Radiosurgery. Curr Oncol Rep. 2012;14(1):79–84. doi: 10.1007/s11912-011-0201-0.
[16] Aoyama H, Tago M, Kato N, Toyoda T, Kenjyo M, Hirota S. et al. Neurocognitive function of patients with brain metastasis who received either whole brain radiotherapy plus stereotactic radiosurgery or radiosurgery alone. Int J Radiat Oncol Biol Phys. 2007;68(5):1388–95.
[17] Mehta MP, Rodrigus P, Terhaard CH, Rao A, Suh J, Souhami L. et al. Survival and neurologic outcomes in a randomized trial of motexafin gadolinium and whole-brain radiation therapy in brain metastases. J Clin Oncol. 2003;21(13):2529–36.
[18] Li J, Bentzen SM, Renschler M, Mehta MP. Regression after whole-brain radiation therapy for brain metastases correlates with survival improved neurocognitive function. J Clin Oncol. 2007;25(10):1260–66.
[19] Meyers CA, Smith JA, Bezjak A, Mehta MP, Liebmann J, Illidge T. 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(1):157–65.
[20] Regine WF, Huhn JL, Patchell RA, St Clair WH, Strottmann J, Meigooni A. et al. Risk of symptomatic brain tumor recurrence and neurologic deficit after radiosurgery alone in patients with newly diagnosed brain metastases: Results and implications. Int J Radiat Oncol Biol Phys. 2002;52:333–8.
[21] Rosenman J, Choi NC. Improved quality of life of patients with small-cell carcinoma of the lung by elective irradiation of the brain. Int J Radiat Oncol Biol Phys. 1982;8(6):1041–3.
[22] Regine WF, Scott C, Murray KJ, Curran W. Neurocognitive outcome in brain metastases patients treated with accelerated-fractionation vs. accelerated-hyperfractionated radiotherapy: an analysis from Radiation therapy Oncology Group study 91–04. Int J Radiat Oncol Biol Phys. 2001;51(3):711–17.
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| Issue | Vol 15 No 3 (2023) | |
| Section | Original Articles | |
| Keywords | ||
| Cranial Irradiation Brain Neoplasms Radiotherapy Cognition. | ||
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How to Cite
1.
Chakrabarti A, DAS R. Neurocognitive function assessment for cancer patients with brain metastases following whole brain radiation therapy. Basic Clin Cancer Res. 2024;15(3):171-178.
