title: Local control after stereotactic radiosurgery for brain metastases in patients with melanoma with and without BRAF mutation and treatment.
abstract: OBJECTIVE
  BRAF inhibitors improve progression-free and overall survival in patients with metastatic melanoma. Brain metastases are common, and stereotactic radiosurgery (SRS) has been used, resulting in excellent local control. Because BRAF inhibitors are associated with intracranial responses, the authors hypothesized that BRAF inhibitors would improve local control in patients with melanoma who are receiving SRS for brain metastases.
  
  
  METHODS
  The authors retrospectively identified patients with metastatic melanoma who had been tested for BRAF mutation and treated with SRS for brain metastases. Patients with previous resection, multiple brain metastases, or multiple courses of SRS were eligible. SRS was delivered in a single fraction to a median dose of 2000 cGy. Patients with a BRAF mutation were treated with a BRAF inhibitor on the basis of physician preference.
  
  
  RESULTS
  The authors identified 52 patients who were treated in 82 treatment sessions for 185 brain metastases and 13 tumor beds. At a median follow-up of 10.5 months, the 1-year local control rate was 69.2%. At 1 year, the local control rate for brain metastases in patients with BRAF mutation with BRAF treatment was 85.0%, and the local control rate for brain metastases in those without BRAF treatment was 51.5% (p = 0.0077). The rates of distant brain failure, freedom from whole-brain radiation, and overall survival were not different on the basis of BRAF mutation status or inhibitor therapy. The number of new intratumoral hemorrhages after SRS was increased significantly in patients with BRAF treatment.
  
  
  CONCLUSIONS
  Treatment with BRAF inhibitors was associated with improved local control after SRS in patients with melanoma and brain metastases. An increased number of intratumoral hemorrhages was associated with BRAF inhibitor therapy.
authors.affiliation: Department of Radiation Oncology and.
authors.forename: David
authors.initials: D
authors.lastname: Ly
authors.affiliation: Department of Radiation Oncology and.
authors.forename: Hilary P
authors.initials: HP
authors.lastname: Bagshaw
authors.affiliation: Division of Radiation Oncology, University of Vermont Cancer Center, Burlington, Vermont.
authors.forename: Christopher J
authors.initials: CJ
authors.lastname: Anker
authors.affiliation: Department of Radiation Oncology and.
authors.forename: Jonathan D
authors.initials: JD
authors.lastname: Tward
authors.affiliation: Division of Oncology, Huntsman Cancer Hospital, and.
authors.forename: Kenneth F
authors.initials: KF
authors.lastname: Grossmann
authors.affiliation: Department of Neurosurgery, University of Utah, Salt Lake City, Utah; and.
authors.forename: Randy L
authors.initials: RL
authors.lastname: Jensen
authors.affiliation: Department of Radiation Oncology and.
authors.forename: Dennis C
authors.initials: DC
authors.lastname: Shrieve
mesh_terms: D000328:Adult; D000970:Antineoplastic Agents / Q000627:therapeutic use; D001921:Brain / Q000473:pathology / Q000601:surgery*; D001932:Brain Neoplasms / Q000188:drug therapy / Q000401:mortality / Q000556:secondary / Q000601:surgery*; D005260:Female; D006801:Humans; D007093:Imidazoles / Q000627:therapeutic use; D007211:Indoles / Q000627:therapeutic use; D008297:Male; D008545:Melanoma / Q000188:drug therapy / Q000401:mortality / Q000556:secondary / Q000601:surgery*; D008875:Middle Aged; D009154:Mutation; D010091:Oximes / Q000627:therapeutic use; D011379:Prognosis; D048493:Proto-Oncogene Proteins B-raf / Q000037:antagonists & inhibitors* / Q000235:genetics; D016634:Radiosurgery; D012189:Retrospective Studies; D013449:Sulfonamides / Q000627:therapeutic use; D016019:Survival Analysis; D016896:Treatment Outcome; D000077484:Vemurafenib; D055815:Young Adult
chemical_list: D000970:Antineoplastic Agents; D007093:Imidazoles; D007211:Indoles; D010091:Oximes; D013449:Sulfonamides; D000077484:Vemurafenib; C482119:BRAF protein, human; D048493:Proto-Oncogene Proteins B-raf; C561627:dabrafenib
keywords: BRAF; BRAF inhibitor; CI = confidence interval; HR = hazard ratio; SRS = stereotactic radiosurgery; brain metastases; melanoma; stereotactic radiosurgery