title: Tumor progression in patients receiving adjuvant whole-brain radiotherapy vs localized radiotherapy after surgical resection of brain metastases.
abstract: BACKGROUND
  Surgery followed by adjuvant radiotherapy is a well-established treatment paradigm for brain metastases.
  
  
  OBJECTIVE
  To examine the effect of postsurgical whole-brain radiotherapy (WBRT) or localized radiotherapy (LRT), including stereotactic radiosurgery and intraoperative radiotherapy, on the rate of recurrence both local and distal to the resection site in the treatment of brain metastases.
  
  
  METHODS
  We retrospectively identified patients who underwent surgery for brain metastasis at the Cleveland Clinic between 2004 and 2012. Institutional review board-approved chart review was conducted, and patients who had radiation before surgery, who had nonmetastatic lesions, or who lacked postadjuvant imaging were excluded.
  
  
  RESULTS
  The final analysis included 212 patients. One hundred fifty-six patients received WBRT, 37 received stereotactic radiosurgery only, and 19 received intraoperative radiotherapy. One hundred forty-six patients were deceased, of whom 60 (41%) died with no evidence of recurrence. Competing risks methodology was used to test the association between adjuvant modality and progression. Multivariable analysis revealed no significant difference in the rate of recurrence at the resection site (hazard ratio [HR] 1.46, P = .26) or of unresected, radiotherapy-treated lesions (HR 1.70, P = .41) for LRT vs WBRT. Patients treated with LRT had an increased hazard of the development of new lesions (HR 2.41, P < .001) and leptomeningeal disease (HR 2.45, P = .04). Median survival was 16.5 months and was not significantly different between groups.
  
  
  CONCLUSIONS
  LRT as adjuvant treatment to surgical resection of brain metastases is associated with an increased rate of development of new distant metastases and leptomeningeal disease compared with WBRT, but not with recurrence at the resection site or of unresected lesions treated with radiation.
authors.affiliation: *Cleveland Clinic Lerner College of Medicine of Case Western Reserve University, Cleveland, Ohio; ‡Quantitative Health Sciences, Cleveland Clinic, Cleveland, Ohio; §Department of Neurosurgery, Neurological Institute, Cleveland Clinic, Cleveland, Ohio; ¶Rose Ella Burkhardt Brain Tumor and Neuro-Oncology Center, Neurological Institute, Cleveland Clinic, Cleveland, Ohio; ‖Department of Cancer Biology, Lerner Research Institute, Cleveland Clinic, Cleveland, Ohio; #Department of Neurosurgery, Geisinger Health System, Danville, Pennsylvania.
authors.forename: Jason
authors.initials: J
authors.lastname: Hsieh
authors.forename: Paul
authors.initials: P
authors.lastname: Elson
authors.forename: Balint
authors.initials: B
authors.lastname: Otvos
authors.forename: Jonathan
authors.initials: J
authors.lastname: Rose
authors.forename: Christopher
authors.initials: C
authors.lastname: Loftus
authors.forename: Gazanfar
authors.initials: G
authors.lastname: Rahmathulla
authors.forename: Lilyana
authors.initials: L
authors.lastname: Angelov
authors.forename: Gene H
authors.initials: GH
authors.lastname: Barnett
authors.forename: Robert J
authors.initials: RJ
authors.lastname: Weil
authors.forename: Michael A
authors.initials: MA
authors.lastname: Vogelbaum
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D001932:Brain Neoplasms / Q000401:mortality / Q000532:radiotherapy* / Q000556:secondary / Q000601:surgery; D003131:Combined Modality Therapy; D018450:Disease Progression; D005260:Female; D006801:Humans; D015994:Incidence; D008297:Male; D008875:Middle Aged; D009364:Neoplasm Recurrence, Local / Q000453:epidemiology* / Q000601:surgery; D016634:Radiosurgery / Q000379:methods; D018714:Radiotherapy, Adjuvant / Q000379:methods; D012189:Retrospective Studies