title: Gamma knife radiosurgery for brain metastasis of nonsmall cell lung cancer: is there a difference in outcome between morning and afternoon treatment?
abstract: BACKGROUND
  Circadian cell-cycle progression causes fluctuating radiosensitivity in many tissues, which could affect clinical outcomes. The purpose of this study was to determine whether outcomes of single-session gamma knife radiosurgery (GKRS) for metastatic nonsmall cell lung cancer (NSCLC) differ based on treatment time.
  
  
  METHODS
  Fifty-eight patients received GKRS between 10:00 am and 12:30 pm and 39 patients received GKRS between 12:30 pm and 3:00 pm. The mean peripheral dose was 18.6 Gy. The mean tumor size was 7.3 cm³. Magnetic resonance imaging was used to score local control at 3 months. Cause of death (COD) was categorized as central nervous system (CNS)-related or systemic.
  
  
  RESULTS
  Demographic and disease characteristics of the 2 groups were similar. Local control at 3 months was achieved in 97% (35/36) of patients who underwent GKRS early in the day versus 67% (8/12) of patients who underwent GKRS later in the day (chi-square, P = .014). Early GKRS was associated with better survival (median 9.5 months) than late GKRS (median 5 months) (Kaplan-Meier log-rank test, P = .025). Factors contributing to better survival in a Cox regression model included early treatment time (P = .004) and recursive partition analysis class (P < .001). Cause of death in the early treatment group was CNS-related in 6% (3/47) of patients versus 24% (8/34) of patients in the late treatment group (chi-square test, P = .026).
  
  
  CONCLUSIONS
  GKRS for metastatic NSCLC had better local control, better survival, and a lower rate of CNS-related cause of death when given earlier in the day versus later in the day. These retrospective data should encourage future study in brain radiosurgery and non-CNS stereotactic body radiotherapy series.
authors.affiliation: Department of Radiation Oncology, University of Virginia Health Sciences Center, Charlottesville, Virginia 22908, USA.
authors.forename: Douglas A
authors.initials: DA
authors.lastname: Rahn
authors.forename: Dibyendu K
authors.initials: DK
authors.lastname: Ray
authors.forename: David J
authors.initials: DJ
authors.lastname: Schlesinger
authors.forename: Ladislau
authors.initials: L
authors.lastname: Steiner
authors.forename: Jason P
authors.initials: JP
authors.lastname: Sheehan
authors.forename: John M
authors.initials: JM
authors.lastname: O'Quigley
authors.forename: Tyvin
authors.initials: T
authors.lastname: Rich
mesh_terms: D001932:Brain Neoplasms / Q000401:mortality / Q000473:pathology / Q000556:secondary* / Q000601:surgery*; D002289:Carcinoma, Non-Small-Cell Lung / Q000473:pathology*; D002940:Circadian Rhythm; D005260:Female; D006801:Humans; D008175:Lung Neoplasms / Q000473:pathology*; D008279:Magnetic Resonance Imaging; D008297:Male; D008875:Middle Aged; D016634:Radiosurgery / Q000379:methods*; D012189:Retrospective Studies; D016896:Treatment Outcome