Patients with pretreatment leukoencephalopathy and older patients have more cognitive decline after whole brain radiothe
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RESEARCH
Patients with pretreatment leukoencephalopathy and older patients have more cognitive decline after whole brain radiotherapy Matthew Chan1,2, David Ferguson3, Elaine Ni Mhurchu3, Ren Yuan3, Lovedeep Gondara4, Michael McKenzie1,2, Robert Olson1,5, Brian Thiessen6, Nafisha Lalani1,2, Roy Ma1,2 and Alan Nichol1,2*
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 18 years with a non-hematologic malignancy. They had 1–10 brain metastases measuring less than 3 cm, Karnofsky Performance Score (KPS) ≥ 70, an estimated median survival of ≥ 6 months, and a baseline MoCA score ≥ 20. Patients with previous craniotomy or brainstem metastases were eligible if they had ≥ 1 unresected, non-brainstem metastasis. There were no patients with upfront leptomeningeal involvement. Radiation therapy
A T1-weighted three-dimensional gadolinium-enhanced MRI sequence and a computed tomography (CT) scan with intravenous contrast were performed for radiotherapy planning using a slice reconstruction every 1.00– 1.25 mm within a week of the planning CT. The Eclipse treatment planning system (Varian Medical Systems, Palo Alto, CA) was used to co-register the MRI and CT studies, and to segment the metastases and organs at risk. Both the segmented metastasis volumes and whole brain clinical target volumes were expanded by 2 mm to create planning target volumes (PTVs) [37]. The radiosurgery prescription for the brain metastasis PTVs was 38 Gy in 5 fractions. The whole brain PTV was covered by 95% of 20 Gy in 5 fractions. This WBRT prescription was chosen because it could be delivered concurrently with 5-fraction radiosurgery and because it provided equivalent overall survival to 40 Gy in 20 fractions in a randomized clinical trial [38]. Based on the equivalent dose in 2 Gy fractions (EQD2) formulation and assuming an alpha–beta ratio of 10 for brain metastases, we appreciated that 20 Gy in 5 fractions (EQD2 = 23.3 Gy) would offer less cancer cell kill than the more commonly used 30 Gy in 10 fractions (EQD2 = 32.5 Gy); however, the brain metastases were being treated with radiosurgery. We hypothesized that 20 Gy in 5 fractions would provide a similar EQD2 to 25 Gy in 1
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