title: Competing Risk Analysis of Neurologic versus Nonneurologic Death in Patients Undergoing Radiosurgical Salvage After Whole-Brain Radiation Therapy Failure: Who Actually Dies of Their Brain Metastases?
abstract: OBJECTIVE
  To estimate the hazard for neurologic (central nervous system, CNS) and nonneurologic (non-CNS) death associated with patient, treatment, and systemic disease status in patients receiving stereotactic radiosurgery after whole-brain radiation therapy (WBRT) failure, using a competing risk model.
  
  
  METHODS
  Of 757 patients, 293 experienced recurrence or new metastasis following WBRT. Univariate Cox proportional hazards regression identified covariates for consideration in the multivariate model. Competing risks multivariable regression was performed to estimate the adjusted hazard ratio (aHR) and 95% confidence interval (CI) for both CNS and non-CNS death after adjusting for patient, disease, and treatment factors. The resultant model was converted into an online calculator for ease of clinical use.
  
  
  RESULTS
  The cumulative incidence of CNS and non-CNS death at 6 and 12 months was 20.6% and 21.6%, and 34.4% and 35%, respectively. Patients with melanoma histology (relative to breast) (aHR 2.7, 95% CI 1.5-5.0), brainstem location (aHR 2.1, 95% CI 1.3-3.5), and number of metastases (aHR 1.09, 95% CI 1.04-1.2) had increased aHR for CNS death. Progressive systemic disease (aHR 0.55, 95% CI 0.4-0.8) and increasing lowest margin dose (aHR 0.97, 95% CI 0.9-0.99) were protective against CNS death. Patients with lung histology (aHR 1.3, 95% CI 1.1-1.9) and progressive systemic disease (aHR 2.14, 95% CI 1.5-3.0) had increased aHR for non-CNS death.
  
  
  CONCLUSIONS
  Our nomogram provides individual estimates of neurologic death after salvage stereotactic radiosurgery for patients who have failed prior WBRT, based on histology, neuroanatomical location, age, lowest margin dose, and number of metastases after adjusting for their competing risk of death from other causes.
authors.affiliation: Department of Radiation Oncology, Wake Forest School of Medicine, Winston-Salem, North Carolina. Electronic address: jolucas@wakehealth.edu.
authors.forename: John T
authors.initials: JT
authors.lastname: Lucas
authors.affiliation: Wake Forest School of Medicine, Winston-Salem, North Carolina.
authors.forename: Hentry G
authors.initials: HG
authors.lastname: Colmer
authors.affiliation: Wake Forest School of Medicine, Winston-Salem, North Carolina.
authors.forename: Lance
authors.initials: L
authors.lastname: White
authors.affiliation: Department of Biostatistical Sciences, Wake Forest School of Medicine, Winston-Salem, North Carolina.
authors.forename: Nora
authors.initials: N
authors.lastname: Fitzgerald
authors.affiliation: Department of Biostatistical Sciences, Wake Forest School of Medicine, Winston-Salem, North Carolina.
authors.forename: Scott
authors.initials: S
authors.lastname: Isom
authors.affiliation: Department of Radiation Oncology, Wake Forest Baptist Medical Center, Winston-Salem, North Carolina.
authors.forename: John D
authors.initials: JD
authors.lastname: Bourland
authors.affiliation: Department of Neurosurgery, Wake Forest Baptist Medical Center, Winston-Salem, North Carolina.
authors.forename: Adrian W
authors.initials: AW
authors.lastname: Laxton
authors.affiliation: Department of Neurosurgery, Wake Forest School of Medicine, Winston-Salem, North Carolina.
authors.forename: Stephen B
authors.initials: SB
authors.lastname: Tatter
authors.affiliation: Department of Radiation Oncology, Wake Forest School of Medicine, Winston-Salem, North Carolina.
authors.forename: Michael D
authors.initials: MD
authors.lastname: Chan
mesh_terms: D001932:Brain Neoplasms / Q000401:mortality* / Q000532:radiotherapy / Q000556:secondary* / Q000601:surgery; D001943:Breast Neoplasms; D002423:Cause of Death; D002493:Central Nervous System Diseases / Q000401:mortality*; D016371:Cranial Irradiation / Q000009:adverse effects; D005260:Female; D006801:Humans; D015994:Incidence; D008175:Lung Neoplasms; D008297:Male; D008545:Melanoma / Q000401:mortality / Q000532:radiotherapy / Q000556:secondary / Q000601:surgery; D008875:Middle Aged; D009364:Neoplasm Recurrence, Local / Q000401:mortality* / Q000601:surgery; D049451:Nomograms; D016016:Proportional Hazards Models; D016634:Radiosurgery / Q000009:adverse effects; D016879:Salvage Therapy / Q000379:methods / Q000401:mortality*; D017211:Treatment Failure