(P038) Leukoencephalopathy Following Stereotactic Radiosurgery for Brain Metastases

April 30, 2015

Our results establish that WBRT + SRS produces leukoencephalopathy at a much higher rate than SRS alone. Surprisingly, an SRS integral dose of over only 3 J predicts for leukoencephalopathy in patients treated with SRS alone. Our data define a dosimetric threshold at which radiation-induced leukoencephalopathy is likely to occur following SRS. As the survival of patients with CNS metastases increases and as the neurotoxicity of chemotherapeutic and targeted agents becomes established, the threshold of 3 J may influence the therapeutic management of patients with multiple brain metastases.

Daniel M. Trifiletti, MD, Cheng-Chia Lee, MD, David Schlesinger, PhD, Jason P. Sheehan, MD, PhD, James M. Larner, MD;University of Virginia;National Yang-Ming University

PURPOSE/OBJECTIVE: The use of stereotactic radiosurgery (SRS) in the treatment of brain metastases has increased dramatically over the last decade in order to avoid the neurocognitive dysfunction that is induced by whole-brain radiotherapy (WBRT). Technical improvements in SRS delivery have greatly enhanced the SRS workflow and allowed for the treatment of numerous intracranial metastases in a single session. It is now common practice to treat up to 5–10 lesions with SRS in a single session, followed by subsequent SRS sessions based on surveillance imaging; however, the cumulative neurocognitive effect of numerous SRS sessions remains unknown. As leukoencephalopathy is a sensitive marker for radiation-induced central nervous system (CNS) damage, we investigated the dosimetric thresholds for SRS-induced leukoencephalopathy in patients treated with SRS alone, as well as SRS in combination with WBRT.

MATERIALS AND METHODS: All patients treated at our institution with at least two sessions of SRS for brain metastases between 2007 and 2013 were reviewed. Pre- and post-SRS fluid-attenuated inversion recovery and T1- and T2-weighted MRI sequences were reviewed and graded for white matter changes associated with radiation leukoencephalopathy using a previously validated scale. Patient characteristics and SRS dosimetric parameters were reviewed for factors that contributed to radiographic leukoencephalopathy using Cox proportional hazards modeling.

RESULTS: A total of 103 patients meeting the inclusion criteria were identified. The overall incidence of leukoencephalopathy was 53% at 3 years, and four factors predicted for radiation-induced leukoencephalopathy: the use of WBRT (P = .001), SRS integral cranial dose of > 3 J (P = .026), total number of tumors (P = .001), and total tumor volume (P = .009). The volumes receiving 8 Gy (V8), V10, V12, and V15 were not predictive.

CONCLUSIONS: Our results establish that WBRT + SRS produces leukoencephalopathy at a much higher rate than SRS alone. Surprisingly, an SRS integral dose of over only 3 J predicts for leukoencephalopathy in patients treated with SRS alone. Our data define a dosimetric threshold at which radiation-induced leukoencephalopathy is likely to occur following SRS. As the survival of patients with CNS metastases increases and as the neurotoxicity of chemotherapeutic and targeted agents becomes established, the threshold of 3 J may influence the therapeutic management of patients with multiple brain metastases.

Proceedings of the 97th Annual Meeting of the American Radium Society - americanradiumsociety.org