title: Impact of systemic targeted agents on the clinical outcomes of patients with brain metastases.
abstract: BACKGROUND
  To determine the clinical benefits of systemic targeted agents across multiple histologies after stereotactic radiosurgery (SRS) for brain metastases.
  
  
  METHODS
  Between 2000 and 2013, 737 patients underwent upfront SRS for brain metastases. Patients were stratified by whether or not they received targeted agents with SRS. 167 (23%) received targeted agents compared to 570 (77%) that received other available treatment options. Time to event data were summarized using Kaplan-Meier plots, and the log rank test was used to determine statistical differences between groups.
  
  
  RESULTS
  Patients who received SRS with targeted agents vs those that did not had improved overall survival (65% vs. 30% at 12 months, p < 0.0001), improved freedom from local failure (94% vs 90% at 12 months, p = 0.06), improved distant failure-free survival (32% vs. 18% at 12 months, p = 0.0001) and improved freedom from whole brain radiation (88% vs. 77% at 12 months, p = 0.03). Improvement in freedom from local failure was driven by improvements seen in breast cancer (100% vs 92% at 12 months, p < 0.01), and renal cell cancer (100% vs 88%, p = 0.04). Multivariate analysis revealed that use of targeted agents improved all cause mortality (HR = 0.6, p < 0.0001).
  
  
  CONCLUSIONS
  Targeted agent use with SRS appears to improve survival and intracranial outcomes.
authors.affiliation: Department of Radiation Oncology, Wake Forest School of Medicine, Winston-Salem, NC, USA.
authors.forename: Adam G
authors.initials: AG
authors.lastname: Johnson
authors.affiliation: Department of Medicine, Section on Hematology and Oncology, Wake Forest School of Medicine, Winston-Salem, NC, USA.|W.G. (Bill) Hefner Veteran Administration Medical Center, Cancer Center, Salisbury, NC, USA.
authors.forename: Jimmy
authors.initials: J
authors.lastname: Ruiz
authors.affiliation: Department of Radiation Oncology, Wake Forest School of Medicine, Winston-Salem, NC, USA.
authors.forename: Ryan
authors.initials: R
authors.lastname: Hughes
authors.affiliation: Department of Radiation Oncology, Wake Forest School of Medicine, Winston-Salem, NC, USA.
authors.forename: Brandi R
authors.initials: BR
authors.lastname: Page
authors.affiliation: Department of Biostatistical Sciences, Wake Forest School of Medicine, Winston-Salem, NC, USA.
authors.forename: Scott
authors.initials: S
authors.lastname: Isom
authors.affiliation: Department of Radiation Oncology, Wake Forest School of Medicine, Winston-Salem, NC, USA.
authors.forename: John T
authors.initials: JT
authors.lastname: Lucas
authors.affiliation: Department of Radiation Oncology, Wake Forest School of Medicine, Winston-Salem, NC, USA.
authors.forename: Emory R
authors.initials: ER
authors.lastname: McTyre
authors.affiliation: Department of Radiation Oncology, Wake Forest School of Medicine, Winston-Salem, NC, USA.
authors.forename: Kristin W
authors.initials: KW
authors.lastname: Houseknecht
authors.affiliation: Department of Radiation Oncology, Wake Forest School of Medicine, Winston-Salem, NC, USA.
authors.forename: Diandra N
authors.initials: DN
authors.lastname: Ayala-Peacock
authors.affiliation: Department of Radiation Oncology, Wake Forest School of Medicine, Winston-Salem, NC, USA.
authors.forename: Daniel J
authors.initials: DJ
authors.lastname: Bourland
authors.affiliation: Department of Radiation Oncology, Wake Forest School of Medicine, Winston-Salem, NC, USA.
authors.forename: William H
authors.initials: WH
authors.lastname: Hinson
authors.affiliation: Department of Neurosurgery, Wake Forest School of Medicine, Winston-Salem, NC, USA.
authors.forename: Adrian W
authors.initials: AW
authors.lastname: Laxton
authors.affiliation: Department of Neurosurgery, Wake Forest School of Medicine, Winston-Salem, NC, USA.
authors.forename: Stephen B
authors.initials: SB
authors.lastname: Tatter
authors.affiliation: Brain Tumor Center of Excellence, Wake Forest School of Medicine, Winston-Salem, NC, USA.
authors.forename: Waldemar
authors.initials: W
authors.lastname: Debinski
authors.affiliation: Department of Cancer Biology, Wake Forest School of Medicine, Winston-Salem, NC, USA.
authors.forename: Kounosuke
authors.initials: K
authors.lastname: Watabe
authors.affiliation: Department of Radiation Oncology, Wake Forest School of Medicine, Winston-Salem, NC, USA.
authors.forename: Michael D
authors.initials: MD
authors.lastname: Chan
mesh_terms: D001932:Brain Neoplasms / Q000188:drug therapy / Q000556:secondary* / Q000601:surgery / Q000628:therapy*; D015331:Cohort Studies; D003131:Combined Modality Therapy; D018572:Disease-Free Survival; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D058990:Molecular Targeted Therapy; D009362:Neoplasm Metastasis; D016634:Radiosurgery / Q000379:methods*; D012189:Retrospective Studies; D016019:Survival Analysis; D016896:Treatment Outcome
keywords: brain metastases; chemotherapy; stereotactic radiosurgery; targeted agents