title: Novel risk stratification score for predicting early distant brain failure and salvage whole-brain radiotherapy after stereotactic radiosurgery for brain metastases.
abstract: BACKGROUND
  The purpose of this study was to evaluate predictors of early distant brain failure (DBF) and salvage whole-brain radiotherapy (WBRT) after treatment with stereotactic radiosurgery (SRS) for brain metastases and create a clinically relevant risk score to stratify patients' risk for these events.
  
  
  METHODS
  The records of 270 patients with brain metastases who were treated with SRS between 2003 and 2012 were reviewed. Pretreatment patient and tumor characteristics were analyzed with univariate and multivariate analyses. The cumulative incidences of first DBF and salvage WBRT were calculated. Significant factors were used to create a score for stratifying early (6-month) DBF risk.
  
  
  RESULTS
  No prior WBRT, a total lesion volume < 1.3 cm(3), primary breast cancer or malignant melanoma histology, and multiple metastases (≥2) were found to be significant predictors of early DBF. Each factor was ascribed 1 point because of similar hazard ratios. Scores of 0 to 1, 2, and 3 to 4 were considered to indicate low, intermediate, and high risk, respectively. This correlated with 6-month cumulative incidences of DBF of 16.6%, 28.8%, and 54.4%, respectively (P < .001). For patients without prior WBRT, the 6-month cumulative incidence of salvage WBRT was 2%, 17.7%, and 25.7%, respectively (P < .001).
  
  
  CONCLUSIONS
  Early DBF after SRS requiring salvage WBRT remains a significant clinical problem. Patient stratification for early DBF can better inform the decision for the initial treatment strategy for brain metastases. The provided risk score may help to predict early DBF and subsequent salvage WBRT if SRS is initially used. External validation is needed before clinical implementation.
authors.affiliation: Department of Radiation Oncology, Emory University, Atlanta, Georgia.|Winship Cancer Institute, Emory University, Atlanta, Georgia.
authors.forename: Robert H
authors.initials: RH
authors.lastname: Press
authors.affiliation: Southeast Radiation Oncology Group, Levine Cancer Institute, Carolinas Healthcare System, Charlotte, North Carolina.
authors.forename: Roshan S
authors.initials: RS
authors.lastname: Prabhu
authors.affiliation: Biostatistics and Bioinformatics, Rollins School of Public Health, Emory University, Atlanta, Georgia.
authors.forename: Dana C
authors.initials: DC
authors.lastname: Nickleach
authors.affiliation: Biostatistics and Bioinformatics, Rollins School of Public Health, Emory University, Atlanta, Georgia.
authors.forename: Yuan
authors.initials: Y
authors.lastname: Liu
authors.affiliation: Department of Radiation Oncology, Emory University, Atlanta, Georgia.|Winship Cancer Institute, Emory University, Atlanta, Georgia.
authors.forename: Hui-Kuo G
authors.initials: HK
authors.lastname: Shu
authors.affiliation: Department of Radiation Oncology, Emory University, Atlanta, Georgia.|Winship Cancer Institute, Emory University, Atlanta, Georgia.
authors.forename: Shravan
authors.initials: S
authors.lastname: Kandula
authors.affiliation: Department of Radiation Oncology, Emory University, Atlanta, Georgia.|Winship Cancer Institute, Emory University, Atlanta, Georgia.
authors.forename: Kirtesh R
authors.initials: KR
authors.lastname: Patel
authors.affiliation: Department of Radiation Oncology, Emory University, Atlanta, Georgia.|Winship Cancer Institute, Emory University, Atlanta, Georgia.
authors.forename: Walter J
authors.initials: WJ
authors.lastname: Curran
authors.affiliation: Department of Radiation Oncology, Emory University, Atlanta, Georgia.|Winship Cancer Institute, Emory University, Atlanta, Georgia.
authors.forename: Ian
authors.initials: I
authors.lastname: Crocker
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D001921:Brain / Q000187:drug effects / Q000528:radiation effects / Q000601:surgery; D001926:Brain Death; D001932:Brain Neoplasms / Q000556:secondary* / Q000628:therapy*; D003131:Combined Modality Therapy; D018450:Disease Progression; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D008297:Male; D008875:Middle Aged; D011237:Predictive Value of Tests; D016634:Radiosurgery / Q000379:methods*; D011878:Radiotherapy / Q000379:methods*; D012189:Retrospective Studies; D018570:Risk Assessment; D016879:Salvage Therapy / Q000379:methods*; D016896:Treatment Outcome; D055815:Young Adult
keywords: brain metastases; distant brain failure; predictive modeling; salvage whole-brain radiation therapy; stereotactic radiosurgery