# Leukoencephalopathy following stereotactic radiosurgery for breast cancer brain metastases: a single-center analysis of 1,077 lesions

## TL;DR

This study found that combining whole-brain radiation with stereotactic radiosurgery increases the risk of brain-related side effects in breast cancer patients.

## Contribution

The study identifies prior whole-brain radiation as a major risk factor for high-grade leukoencephalopathy after radiosurgery for brain metastases.

## Key findings

- 23.4% of patients who had whole-brain radiation plus radiosurgery developed high-grade leukoencephalopathy by year 3.
- Prior whole-brain radiation was a significant predictor of high-grade leukoencephalopathy in both univariate and multivariate analyses.
- Radiation dose and number of brain lesions also influenced leukoencephalopathy risk.

## Abstract

Leukoencephalopathy is the most prevalent and delayed adverse radiation effect (ARE) after intracranial radiotherapy (RT). Patients with leukoencephalopathy experience some levels of cognitive and neurological dysfunction. This investigation assessed the frequency and clinical outcomes of leukoencephalopathy following stereotactic radiosurgery (SRS) alone or SRS following whole-brain radiation therapy (WBRT) in breast cancer brain metastasis.

We retrospectively evaluated the data of brain metastases from breast cancer individuals who underwent SRS between 2007 and 2022. MRI sequences were examined to assess white matter changes and tumor control.

Among 125 patients with 1,077 brain metastases, 58 (46.4%) patients received WBRT prior to SRS. By year 3, 23.4% of WBRT + SRS patients developed high-grade leukoencephalopathy (grades 2–3) compared to 5.7% in the SRS-only group (p < 0.001). In univariate analyses, significant predictors of high-grade leukoencephalopathy included prior WBRT (HR: 18.4, p = 0.005), cumulative integral dose > 3 J (HR: 4.17, p = 0.029), and the total number of lesions (HR: 1.22, p < 0.001). In multivariate analyses, prior WBRT (HR: 11.1, p = 0.022) and total lesions (HR: 1.14, p = 0.037) remained significant predictors.

Our findings demonstrated that WBRT plus SRS is associated with higher leukoencephalopathy rates than SRS alone. This underscores the importance of carefully weighing the benefits and risks of different ionizing radiation approaches in the management of brain metastasis from breast cancer.