title: Gamma knife stereotactic radiosurgery as salvage therapy after failure of whole-brain radiotherapy in patients with small-cell lung cancer.
abstract: OBJECTIVE
  Radiosurgery has been successfully used in selected cases to avoid repeat whole-brain irradiation (WBI) in patients with multiple brain metastases of most solid tumor histological findings. Few data are available for the use of radiosurgery for small-cell lung cancer (SCLC).
  
  
  METHODS
  Between November 1999 and June 2009, 51 patients with SCLC and previous WBI and new brain metastases were treated with GammaKnife stereotactic radiosurgery (GKSRS). A median dose of 18 Gy (range, 10-24 Gy) was prescribed to the margin of each metastasis. Patients were followed with serial imaging. Patient electronic records were reviewed to determine disease-related factors and clinical outcomes after GKSRS. Local and distant brain failure rates, overall survival, and likelihood of neurologic death were determined based on imaging results. The Kaplan-Meier method was used to determine survival and local and distant brain control. Cox proportional hazard regression was performed to determine strength of association between disease-related factors and survival.
  
  
  RESULTS
  Median survival time for the entire cohort was 5.9 months. Local control rates at 1 and 2 years were 57% and 34%, respectively. Distant brain failure rates at 1 and 2 years were 58% and 75%, respectively. Fifty-three percent of patients ultimately died of neurologic death. On multivariate analysis, patients with stable (hazard ratio [HR] = 2.89) or progressive (HR = 6.98) extracranial disease (ECD) had worse overall survival than patients without evidence of ECD (p = 0.00002). Concurrent chemotherapy improved local control (HR = 89; p = 0.006).
  
  
  CONCLUSIONS
  GKSRS represents a feasible salvage option in patients with SCLC and brain metastases for whom previous WBI has failed. The status of patients' ECD is a dominant factor predictive of overall survival. Local control may be inferior to that seen with other cancer histological results, although the use of concurrent chemotherapy may help to improve this.
authors.affiliation: Department of Radiation Oncology, Wake Forest University, Winston-Salem, North Carolina, USA.
authors.forename: Sunit
authors.initials: S
authors.lastname: Harris
authors.forename: Michael D
authors.initials: MD
authors.lastname: Chan
authors.forename: James F
authors.initials: JF
authors.lastname: Lovato
authors.forename: Thomas L
authors.initials: TL
authors.lastname: Ellis
authors.forename: Stephen B
authors.initials: SB
authors.lastname: Tatter
authors.forename: J Daniel
authors.initials: JD
authors.lastname: Bourland
authors.forename: Michael T
authors.initials: MT
authors.lastname: Munley
authors.forename: Allan F
authors.initials: AF
authors.lastname: deGuzman
authors.forename: Edward G
authors.initials: EG
authors.lastname: Shaw
authors.forename: James J
authors.initials: JJ
authors.lastname: Urbanic
authors.forename: Kevin P
authors.initials: KP
authors.lastname: McMullen
mesh_terms: D000328:Adult; D000368:Aged; D001932:Brain Neoplasms / Q000401:mortality / Q000532:radiotherapy / Q000556:secondary* / Q000601:surgery*; D016371:Cranial Irradiation / Q000379:methods; D005260:Female; D006801:Humans; D008175:Lung Neoplasms; D008297:Male; D008875:Middle Aged; D016016:Proportional Hazards Models; D016634:Radiosurgery / Q000295:instrumentation / Q000379:methods*; D011879:Radiotherapy Dosage; D012189:Retrospective Studies; D016879:Salvage Therapy / Q000379:methods*; D055752:Small Cell Lung Carcinoma / Q000401:mortality / Q000532:radiotherapy / Q000556:secondary* / Q000601:surgery*; D016019:Survival Analysis; D017211:Treatment Failure