title: Impact of time of day on outcomes after stereotactic radiosurgery for non-small cell lung cancer brain metastases.
abstract: BACKGROUND
  This study tested the hypothesis that time of day of treatment with stereotactic radiosurgery (SRS) has an effect on local control (LC) and overall survival (OS) in a large cohort of patients with non-small cell lung cancer (NSCLC) brain metastases.
  
  
  METHODS
  At Washington University in St. Louis, 437 patients with NSCLC were treated with SRS for NSCLC brain metastases. Receiver operating characteristics analysis was used to identify an optimal cut-point for OS relative to time of day. Kaplan-Meier log-rank statistics, and Cox regression univariate and multivariate analysis were employed to isolate any independent effect of treatment time on OS and LC. Matched-pair analysis was performed to isolate any independent effect of time on OS and LC of day while controlling for confounding variables.
  
  
  RESULTS
  Receiver operating characteristics analysis identified a cut-point of 11:41 AM as providing the highest predictive value for OS. On univariate analysis, late SRS was associated with decreased OS, as was age, Karnofsky performance status, risk-stratification schemes, extracranial disease status, and overall burden of brain metastases. On univariate analysis for LC, late SRS was associated with decreased LC, as was burden of brain metastases. On multivariate analysis, only Graded Prognostic Assessment remained predictive of OS, and total number of targets and total tumor volume remained predictive of LC. Matched-pair analysis demonstrated no significant effect of time of day on LC or OS.
  
  
  CONCLUSIONS
  Although earlier treatment appears to be associated with improved LC and OS, treatment time fails to remain significant when accounting for confounding variables.
authors.affiliation: Department of Radiation Oncology Mallinckrodt Institute of Radiology, Washington University in St. Louis, St. Louis, Missouri.
authors.forename: Shahed N
authors.initials: SN
authors.lastname: Badiyan
authors.forename: Daniel J
authors.initials: DJ
authors.lastname: Ferraro
authors.forename: Sridhar
authors.initials: S
authors.lastname: Yaddanapudi
authors.forename: Robert E
authors.initials: RE
authors.lastname: Drzymala
authors.forename: Andrew Y
authors.initials: AY
authors.lastname: Lee
authors.forename: Shawgi A
authors.initials: SA
authors.lastname: Silver
authors.forename: Pawel
authors.initials: P
authors.lastname: Dyk
authors.forename: Todd
authors.initials: T
authors.lastname: DeWees
authors.forename: Joseph R
authors.initials: JR
authors.lastname: Simpson
authors.forename: Keith M
authors.initials: KM
authors.lastname: Rich
authors.forename: Clifford G
authors.initials: CG
authors.lastname: Robinson
mesh_terms: D001932:Brain Neoplasms / Q000556:secondary* / Q000601:surgery*; D002289:Carcinoma, Non-Small-Cell Lung / Q000556:secondary* / Q000601:surgery*; D002909:Chronobiology Phenomena; D002940:Circadian Rhythm; D015331:Cohort Studies; D005260:Female; D006801:Humans; D053208:Kaplan-Meier Estimate; D008175:Lung Neoplasms / Q000473:pathology* / Q000601:surgery*; D008297:Male; D008875:Middle Aged; D011379:Prognosis; D016634:Radiosurgery / Q000379:methods; D016019:Survival Analysis; D016896:Treatment Outcome
keywords: Gamma Knife; brain metastases; chronobiology; circadian rhythm; local control; non-small cell lung cancer; radiosurgery; survival; time of day