Leukoencephalopathy after whole-brain radiation therapy plus radiosurgery versus radiosurgery alone for metastatic lung cancer

Background: As systemic therapies improve and patients live longer, concerns mount about the toxicity of whole-brain radiation therapy (WBRT) for treatment of brain metastases. Development of delayed white matter abnormalities indicative of leukoencephalopathy have been correlated with cognitive dysfunction. This study assesses the risk of imaging-defined leukoencephalopathy in patients whose management included WBRT in addition to stereotactic radiosurgery (SRS). This risk is compared to patients who only underwent SRS. Methods: We retrospectively compared 37 patients with non-small cell lung cancer who underwent WBRT plus SRS to 31 patients who underwent only SRS. All patients survived at least 1 year after treatment. We graded the development of delayed white matter changes on magnetic resonance imaging using a scale to evaluate T₂/FLAIR (fluid attenuated image recovery) images: grade 1 = little or no white matter hyperintensity; grade 2 = limited periventricular hyperintensity; and grade 3 = diffuse white matter hyperintensity. Results: Patients treated with WBRT and SRS had a significantly greater incidence of delayed white matter leukoencephalopathy compared to patients who underwent SRS alone (P <.001). On final imaging, 36 of 37 patients (97.3%) treated by WBRT developed leukoencephalopathy (25% with grade 2; 70.8% with grade 3). Only 1 patient treated with SRS alone developed leukoencephalopathy. Conclusions: Risk of leukoencephalopathy in patients treated with SRS alone for brain metastases was significantly lower than that for patients treated with WBRT plus SRS. A prospective study is necessary to correlate these findings with neurocognition and quality of life. These data supplement existing reports regarding the differential effects of WBRT and SRS on normal brain structure and function. Cancer 2013.