title: Leukoencephalopathy After Stereotactic Radiosurgery for Brain Metastases.
abstract: OBJECTIVE
  Although the use of stereotactic radiosurgery (SRS) in the treatment of multiple brain metastases has increased dramatically during the past decade to avoid the neurocognitive dysfunction induced by whole brain radiation therapy (WBRT), the cumulative neurocognitive effect of numerous SRS sessions remains unknown. Because leukoencephalopathy is a sensitive marker for radiation-induced central nervous system damage, we studied the clinical and dosimetric predictors of SRS-induced leukoencephalopathy.
  
  
  METHODS
  Patients treated at our institution with at least 2 sessions of SRS for brain metastases from 2007 to 2013 were reviewed. The pre- and post-SRS magnetic resonance imaging 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 leukoencephalopathy using Cox proportional hazards modeling.
  
  
  RESULTS
  A total of 103 patients meeting the inclusion criteria were identified. The overall incidence of leukoencephalopathy was 29% at year 1, 38% at year 2, and 53% at year 3. Three factors were associated with radiation-induced leukoencephalopathy: (1) the use of WBRT (P=.019); (2) a higher SRS integral dose to the cranium (P=.036); and (3) the total number of intracranial metastases (P=.003).
  
  
  CONCLUSIONS
  Our results have established that WBRT plus SRS produces leukoencephalopathy at a much higher rate than SRS alone. In addition, for patients who did not undergo WBRT before SRS, the integral dose was associated with the development of leukoencephalopathy. As the survival of patients with central nervous system metastases increases and as the neurotoxicity of chemotherapeutic and targeted agents becomes established, these 3 potential risk factors will be important to consider.
authors.affiliation: Department of Radiation Oncology, University of Virginia Health System, Charlottesville, Virginia. Electronic address: daniel.trifiletti@gmail.com.
authors.forename: Daniel M
authors.initials: DM
authors.lastname: Trifiletti
authors.affiliation: Department of Neurosurgery, National Yang-Ming University School of Medicine, Taipei, Taiwan.
authors.forename: Cheng-Chia
authors.initials: CC
authors.lastname: Lee
authors.affiliation: Department of Radiation Oncology, University of Virginia Health System, Charlottesville, Virginia; Department of Neurological Surgery, University of Virginia Health System, Charlottesville, Virginia.
authors.forename: David
authors.initials: D
authors.lastname: Schlesinger
authors.affiliation: Department of Radiation Oncology, University of Virginia Health System, Charlottesville, Virginia.
authors.forename: James M
authors.initials: JM
authors.lastname: Larner
authors.affiliation: Department of Neurological Surgery, University of Virginia Health System, Charlottesville, Virginia.
authors.forename: Zhiyuan
authors.initials: Z
authors.lastname: Xu
authors.affiliation: Department of Radiation Oncology, University of Virginia Health System, Charlottesville, Virginia; Department of Neurological Surgery, University of Virginia Health System, Charlottesville, Virginia.
authors.forename: Jason P
authors.initials: JP
authors.lastname: Sheehan
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000704:Analysis of Variance; D001932:Brain Neoplasms / Q000473:pathology / Q000532:radiotherapy / Q000556:secondary* / Q000601:surgery*; D016371:Cranial Irradiation / Q000009:adverse effects; D005260:Female; D006801:Humans; D015994:Incidence; D056784:Leukoencephalopathies / Q000453:epidemiology* / Q000209:etiology*; D008297:Male; D008875:Middle Aged; D016016:Proportional Hazards Models; D011832:Radiation Injuries / Q000150:complications*; D016634:Radiosurgery / Q000009:adverse effects*; D011879:Radiotherapy Dosage; D012189:Retrospective Studies; D012307:Risk Factors