Cognitive functioning and predictors thereof in patients with 1-10 brain metastases selected for stereotactic radiosurgery

Wietske C M Schimmel, Karin Gehring, Patrick E J Hanssens, Margriet M Sitskoorn, Wietske C M Schimmel, Karin Gehring, Patrick E J Hanssens, Margriet M Sitskoorn

Abstract

Purpose: Information on predictive factors of cognitive functioning in patients with (multiple) brain metastases (BM) selected for radiosurgery may allow for more individual care and may play a role in predicting cognitive outcome after radiosurgery. The aim of this study was to evaluate cognitive performance, and predictors thereof, in patients with 1-10 BM before radiosurgery.

Methods: Cognition was measured before radiosurgery using a standardized neuropsychological test battery in patients with 1-10 BM (expected survival > 3 months; KPS ≥ 70; no prior BM treatment). Regression formulae were constructed to calculate sociodemographically corrected z scores. Group and individual cognitive functioning was analyzed. Multivariable regression was used to explore potential predictors.

Results: Patients (N = 92) performed significantly worse than controls (N = 104) on all 11 test variables (medium-large effect sizes for 8 variables). Percentages of impairment were highest for information processing (55.3%), dexterity (43.2%) and cognitive flexibility (28.7%). 62% and 46% of patients had impairments in at least two, or three test variables, respectively. Models including combinations of clinical and psychological variables were predictive of verbal memory, psychomotor speed, information processing and dexterity. Neither number nor volume of metastases predicted patients' test performance.

Conclusions: Already before radiosurgery, almost half of the patients suffered from severe cognitive deficits in at least three test variables. At group and individual level, information processing, cognitive flexibility, and dexterity were most affected. These cognitive impairments may impair daily functioning and patients' ability to make (shared) treatment decisions. Both clinical (symptomatic BM; timing of BM diagnosis) and psychological (mental fatigue) characteristics influenced cognitive performance.

Clinical trial information: Cognition and Radiation Study A (CAR-Study A; ClinicalTrials.gov Identifier: NCT02953756; Medical Ethics Committee file number: NL53472.028.15/P1515).

Keywords: Brain metastases; Cognitive functioning; Gamma knife radiosurgery; Stereotactic radiosurgery.

Conflict of interest statement

The authors declare that they have no competing interests.

References

    1. Loeffler JS (2019) Overview of the treatment of brain metastases. Wen PY, ed. UpToDate. Waltham, MA: UpToDate Inc.. Accessed June 14 2019
    1. Witgert ME, Meyers CA. Neurocognitive and quality of life measures in patients with metastatic brain disease. Neurosurg Clin N Am. 2011;22(1):79–85.
    1. Li J, Bentzen SM, Li J, Renschler M, Mehta MP. Relationship between neurocognitive function and quality of life after whole-brain radiotherapy in patients with brain metastasis. Int J Radiat Oncol Biol Phys. 2008;71(1):64–70.
    1. Wefel JS, Parsons MW, Gondi V, Brown PD. Neurocognitive aspects of brain metastasis. Handb Clin Neurol. 2018;149:155–165.
    1. Schimmel WCM, Gehring K, Eekers DBP, Hanssens PEJ, Sitskoorn MM. Cognitive effects of stereotactic radiosurgery in adult patients with brain metastases: a systematic review. Adv Radiat Oncol. 2018;3(4):568–581.
    1. Chang EL, Wefel JS, Maor MH, Hassenbusch SJ, Mahajan A, Lang FF, 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(2):277–283.
    1. Chang EL, Wefel JS, Hess KR, Allen PK, Lang FF, Kornguth DG, 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):1037–1044.
    1. Onodera S, Aoyama H, Tha KK, Hashimoto N, Toyomaki A, Terae S, et al. The value of 4-month neurocognitive function as an endpoint in brain metastases trials. J Neurooncol. 2014;120(2):311–319.
    1. 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. JAMA. 2016;316(4):401–409.
    1. Habets EJJ, Dirven L, Wiggenraad RG, Verbeek-de Kanter A, Lycklama A, Nijeholt GJ, Zwinkels H, et al. Neurocognitive functioning and health-related quality of life in patients treated with stereotactic radiotherapy for brain metastases: a prospective study. Neuro-oncology. 2016;18(3):435–444.
    1. Mehta MP, Shapiro WR, Glantz MJ, Patchell RA, Weitzner MA, Meyers CA, et al. Lead-in phase to randomized trial of motexafin gadolinium and whole-brain radiation for patients with brain metastases: centralized assessment of magnetic resonance imaging, neurocognitive, and neurologic end points. J Clin Oncol. 2002;20(16):3445–3453.
    1. Brown PD, Ballman KV, Cerhan JH, Anderson SK, Carrero XW, Whitton AC, et al. Postoperative stereotactic radiosurgery compared with whole brain radiotherapy for resected metastatic brain disease (NCCTG N107C/CEC·3): a multicentre, randomised, controlled, phase 3 trial. Lancet Oncol. 2017;18(8):1049–1060.
    1. Berger A, Strauss I, Moshe SB, Corn BW, Limon D, Shtraus N, et al. Neurocognitive evaluation of brain metastases patients treated with post-resection stereotactic radiosurgery: a prospective single arm clinical trial. J Neurooncol. 2018;140(2):307–315.
    1. Welzel G, Fleckenstein K, Schaefer J, Hermann B, Kraus-Tiefenbacher U, Mai SK, et al. Memory function before and after whole brain radiotherapy in patients with and without brain metastases. Int J Radiat Oncol Biol Phys. 2008;72(5):1311–1318.
    1. 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):157–165.
    1. Hunter GK, Suh JH, Reuther AM, Vogelbaum MA, Barnett GH, Angelov L, et al. Treatment of five or more brain metastases with stereotactic radiosurgery. Int J Radiat Oncol Biol Phys. 2012;83(5):1394–1398.
    1. Limon D, McSherry F, Herndon J, Sampson J, Fecci P, Adamson J, et al. Single fraction stereotactic radiosurgery for multiple brain metastases. Adv Radiat Oncol. 2017;2(4):555–563.
    1. Lam T-C, Sahgal A, Chang EL, Lo SS. Stereotactic radiosurgery for multiple brain metastases. Expert Rev Anticancer Ther. 2014;14(10):1153–1172.
    1. Baschnagel AM, Meyer KD, Chen PY, Krauss DJ, Olson RE, Pieper DR, et al. Tumor volume as a predictor of survival and local control in patients with brain metastases treated with Gamma Knife surgery. J Neurosurg. 2013;119(5):1139–1144.
    1. Emery A, Trifiletti DM, Romano KD, Patel N, Smolkin ME, Sheehan JP. More than just the number of brain metastases: evaluating the impact of brain metastasis location and relative volume on overall survival after stereotactic radiosurgery. World Neurosurg. 2017;99:111–117.
    1. Kotecha R, Miller JA, Chao ST, Mohammadi AM, Murphy ES, Suh JH, et al. What drives patient outcomes in brain metastases: number, volume, or biology? J Clin Oncol Am Soc Clin Oncol. 2017;35(15_suppl):2071.
    1. Sharma M, Jia X, Ahluwalia M, Barnett GH, Vogelbaum MA, Chao ST, et al. Cumulative intracranial tumor volume and number of brain metastasis as predictors of developing new lesions after stereotactic radiosurgery for brain metastasis. World Neurosurg. 2017;106:666–675.
    1. Sperduto PW, Kased N, Roberge D, Xu Z, Shanley R, Luo X, et al. Summary report on the graded prognostic assessment: an accurate and facile diagnosis-specific tool to estimate survival for patients with brain metastases. J Clin Oncol. 2012;30(4):419–425.
    1. Pulenzas N, Khan L, Tsao M, Zhang L, Lechner B, Thavarajah N, et al. Fatigue scores in patients with brain metastases receiving whole brain radiotherapy. Support Care Cancer. 2014;22(7):1757–1763.
    1. Pendergrass JC, Targum SD, Harrison JE. Cognitive impairment associated with cancer: a brief review. Innov Clin Neurosci. 2018;15(1-2):36–44.
    1. Thong MSY, Mols F, van de Poll-Franse LV, Sprangers MAG, van der Rijt CCD, Barsevick AM, et al. Identifying the subtypes of cancer-related fatigue: results from the population-based PROFILES registry. J Cancer Surviv. 2018;12(1):38–46.
    1. Verhaak E, Gehring K, Hanssens PEG, Sitskoorn MM. Health-related quality of life of patients with brain metastases selected for stereotactic radiosurgery. J Neurooncol. 2019;4(5):289.
    1. Wefel JS, Vardy J, Ahles T, Schagen SB. International Cognition and Cancer Task Force recommendations to harmonise studies of cognitive function in patients with cancer. Lancet Oncol. 2011;12(7):703–708.
    1. Zigmond AS, Snaith RP. The hospital anxiety and depression scale. Acta Psychiatr Scand. 1983;67(6):361–370.
    1. Smets EM, Garssen B, Cull A, De Haes JC. Application of the multidimensional fatigue inventory (MFI-20) in cancer patients receiving radiotherapy. Br J Cancer. 1996;73(2):241–245.
    1. Weitzner MA, Meyers CA, Gelke CK, Byrne KS, Cella DF, Levin VA. The Functional Assessment of Cancer Therapy (FACT) scale. Development of a brain subscale and revalidation of the general version (FACT-G) in patients with primary brain tumors. Cancer. 1996;75(5):1151–1161.
    1. Oosterhuis HEM, van der Ark LA, Sijtsma K. Sample size requirements for traditional and regression-based norms. Assessment. 2015;23(2):191–202.
    1. Glass GV, McGaw B, Smith ML. Meta-analysis in social research. Thousand Oaks: Sage Publications; 1981. p. 279.
    1. Cohen J (1988) Statistical power analysis for the behavioural sciences. Hillsdale.
    1. Benjamini Y, Hochberg Y, Sijtsma K. Controlling the False Discovery rate: a practical and powerful approach to multiple testing. J R Stat Soc Ser B. 2002;57(1):289–300.
    1. van der Meer PB, Habets EJJ, Wiggenraad RG, Verbeek-de Kanter A, Lycklama A, Nijeholt GJ, Zwinkels H, et al. Individual changes in neurocognitive functioning and health-related quality of life in patients with brain oligometastases treated with stereotactic radiotherapy. J Neurooncol. 2018;139(2):359–368.
    1. Gerstenecker A, Nabors LB, Meneses K, Fiveash JB, Marson DC, Cutter G, et al. Cognition in patients with newly diagnosed brain metastasis: profiles and implications. J Neurooncol. 2014;120(1):179–185.
    1. Low E, Crewther SG, Ong B, Perre D, Wijeratne T. Compromised motor dexterity confounds processing speed task outcomes in stroke patients. Front Neurol. 2017;8:484.
    1. Kesler SR, Blayney DW, Ong B, Perre D, Wijeratne T. Neurotoxic effects of anthracycline- vs nonanthracycline-based chemotherapy on cognition in breast cancer survivors. JAMA Oncol. 2017;2(2):185–192.
    1. Schagen SB, Muller MJ, Boogerd W, Mellenbergh GJ, van Dam FSAM. Change in cognitive function after chemotherapy: a prospective longitudinal study in breast cancer patients. J Natl Cancer Inst. 2006;98(23):1742–1745.
    1. Wefel JS, Kesler SR, Noll KR, Schagen SB. Clinical characteristics, pathophysiology, and management of noncentral nervous system cancer-related cognitive impairment in adults. CA Cancer J Clin. 2015;65(2):123–138.
    1. Stelzer KJ. Epidemiology and prognosis of brain metastases. Surg Neurol Int. 2013;4(Suppl 4):S192–202.
    1. Dwan TM, Ownsworth T, Chambers S, Walker DJ, Shum DHK. Neuropsychological assessment of individuals with brain tumor: comparison of approaches used in the classification of impairment. Front Oncol. 2015;5(6):56.
    1. Li J, Bentzen SM, Renschler M, Mehta MP. Regression after whole-brain radiation therapy for brain metastases correlates with survival and improved neurocognitive function. J Clin Oncol. 2007;25(10):1260–1266.
    1. Noll KR, Bradshaw ME, Weinberg JS, Wefel JS. Neurocognitive functioning is associated with functional independence in newly diagnosed patients with temporal lobe glioma. Neurooncol Pract. 2018;5(3):184–193.
    1. Zeng KL, Raman S, Sahgal A, Soliman H, Tsao M, Wendzicki C, et al. Patient preference for stereotactic radiosurgery plus or minus whole brain radiotherapy for the treatment of brain metastases. Ann Palliat Med. 2017;6(Suppl 2):S155–S160.
    1. Triebel KL, Gerstenecker A, Meneses K, Fiveash JB, Meyers CA, Cutter G, et al. Capacity of patients with brain metastases to make treatment decisions. Psychooncology. 2015;24(11):1448–1455.
    1. Gerstenecker A, Duff K, Meneses K, Fiveash JB, Nabors LB, Triebel KL. Cognitive predictors of reasoning through treatment decisions in patients with newly diagnosed brain metastases. J Int Neuropsychol Soc. 2015;21(6):412–418.
    1. Gerstenecker A, Meneses K, Duff K, Fiveash JB, Marson DC, Triebel KL. Cognitive predictors of understanding treatment decisions in patients with newly diagnosed brain metastasis. Cancer. 2015;121(12):2013–2019.
    1. Gehring K, Sitskoorn MM, Gundy CM, Sikkes SAM, Klein M, Postma TJ, et al. Cognitive rehabilitation in patients with gliomas: a randomized, controlled trial. J Clin Oncol. 2009;27(22):3712–3722.

Source: PubMed

3
Prenumerera