Patients with pretreatment leukoencephalopathy and older patients have more cognitive decline after whole brain radiotherapy

Matthew Chan, David Ferguson, Elaine Ni Mhurchu, Ren Yuan, Lovedeep Gondara, Michael McKenzie, Robert Olson, Brian Thiessen, Nafisha Lalani, Roy Ma, Alan Nichol, Matthew Chan, David Ferguson, Elaine Ni Mhurchu, Ren Yuan, Lovedeep Gondara, Michael McKenzie, Robert Olson, Brian Thiessen, Nafisha Lalani, Roy Ma, Alan Nichol

Abstract

Purpose: To investigate predictors of cognitive decline after whole brain radiotherapy (WBRT) for brain metastases.

Methods: A secondary analysis of a phase 2 clinical trial was conducted in patients who received stereotactic radiosurgery for 1-10 brain metastases and WBRT (NCT01046123). The Montreal Cognitive Assessment (MoCA) was performed at baseline and every 3 months after WBRT. Baseline T2-weighted fluid attenuation inversion recovery magnetic resonance imaging was independently assessed by two neuroradiologists for the presence of white matter hyperintensities (WMH) using the Fazekas visual rating scale. WMH were also manually segmented for volumetric analysis. Univariable and multivariable logistic regression were used to test the association between baseline variables and MoCA score decline.

Results: Forty-six patients survived ≥ 3 months after treatment. Age (OR 1.12 (1.04-1.21), p < 0.01), baseline WMH volume (OR 1.20, 95% CI 1.06-1.52, p = 0.02) and baseline Fazekas score ≥ 3/6 (OR 6.4, 95% CI 1.7-24.7, p < 0.01) were predictive of MoCA score decline. In multivariable analysis, age was the only significant predictor of MoCA decline. However, all three patients with pre-treatment leukoencephalopathy (Fazekas score = 6/6) had notable adverse outcomes due to cognitive impairment: one required full-time home nursing support and two were institutionalized.

Conclusion: A greater decline in cognition after WBRT was observed in older patients and patients with a higher baseline WMH burden. Although this study is small and hypothesis-generating, we propose that radiation oncologists should exercise caution in prescribing WBRT if leukoencephalopathy is present on pre-treatment imaging.

Trial registration: clinicaltrials.gov identifier NCT01046123. First posted January 11, 2010. https://ichgcp.net/clinical-trials-registry/NCT01046123.

Keywords: Brain metastases; Cognition; Fazekas score; MRI; Montreal Cognitive Assessment; Radiotherapy; White matter hyperintensities.

Conflict of interest statement

AN reports grants from Varian Medical Systems, outside the submitted work.

Figures

Fig. 1
Fig. 1
Study methodology. WMH volumes were contoured and scored using the Fazekas visual rating scale on pre-treatment T2-weighted MRI sequences. Changes in MoCA score after whole brain radiotherapy were assessed for associations with age, WMH volume and Fazekas scores. MoCA Montreal Cognitive Assessment, FLAIR fluid attenuation inversion recovery, dWMH deep white matter hyperintensity, pvWMH periventricular white matter hyperintensity
Fig. 2
Fig. 2
Correlation between segmented WMH volume and Fazekas score. A strong and statistically significant association was seen between Fazekas scores and segmented WMH volumes. WMH white matter hyperintensity
Fig. 3
Fig. 3
Changes in MoCA score after whole brain radiotherapy. Plotted with age and a pretreatment WMH volume and b pretreatment Fazekas score. The diamond-shaped data points are those of patients with a baseline Fazekas score of 6. WMH white matter hyperintensity, MoCA Montreal Cognitive Assessment

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