title: Secondary analysis of RTOG 9508, a phase 3 randomized trial of whole-brain radiation therapy versus WBRT plus stereotactic radiosurgery in patients with 1-3 brain metastases; poststratified by the graded prognostic assessment (GPA).
abstract: OBJECTIVE
  Radiation Therapy Oncology Group (RTOG) 9508 showed a survival advantage for patients with 1 but not 2 or 3 brain metastasis (BM) treated with whole-brain radiation therapy (WBRT) and stereotactic radiosurgery (SRS) versus WBRT alone. An improved prognostic index, the graded prognostic assessment (GPA) has been developed. Our hypothesis was that if the data from RTOG 9508 were poststratified by the GPA, the conclusions may vary.
  
  
  METHODS
  In this analysis, 252 of the 331 patients were evaluable by GPA. Of those, 211 had lung cancer. Breast cancer patients were excluded because the components of the breast GPA are not in the RTOG database. Multiple Cox regression was used to compare survival between treatment groups, adjusting for GPA. Treatment comparisons within subgroups were performed with the log-rank test. A free online tool (brainmetgpa.com) simplified GPA use.
  
  
  RESULTS
  The fundamental conclusions of the primary analysis were confirmed in that there was no survival benefit overall for patients with 1 to 3 metastases; however, there was a benefit for the subset of patients with GPA 3.5 to 4.0 (median survival time [MST] for WBRT + SRS vs WBRT alone was 21.0 versus 10.3 months, P=.05) regardless of the number of metastases. Among patients with GPA 3.5 to 4.0 treated with WBRT and SRS, the MST for patients with 1 versus 2 to 3 metastases was 21 and 14.1 months, respectively.
  
  
  CONCLUSIONS
  This secondary analysis of predominantly lung cancer patients, consistent with the original analysis, shows no survival advantage for the group overall when treated with WBRT and SRS; however, in patients with high GPA (3.5-4), there is a survival advantage regardless of whether they have 1, 2, or 3 BM. This benefit did not extend to patients with lower GPA. Prospective validation of this survival benefit for patients with multiple BM and high GPA when treated with WBRT and SRS is warranted.
authors.affiliation: Metro-Minnesota CCOP and Minneapolis Radiation Oncology, Minneapolis, Minnesota. Electronic address: psperduto@mropa.com.
authors.forename: Paul W
authors.initials: PW
authors.lastname: Sperduto
authors.affiliation: Masonic Cancer Center, University of Minnesota, Minneapolis, Minnesota.
authors.forename: Ryan
authors.initials: R
authors.lastname: Shanley
authors.affiliation: Masonic Cancer Center, University of Minnesota, Minneapolis, Minnesota; Division of Biostatistics, School of Public Health, University of Minnesota, Minneapolis, Minnesota.
authors.forename: Xianghua
authors.initials: X
authors.lastname: Luo
authors.affiliation: Thomas Jefferson University, Department of NeuroOncology, Philadelphia, Pennsylvania.
authors.forename: David
authors.initials: D
authors.lastname: Andrews
authors.affiliation: Thomas Jefferson University, Department of Radiation Oncology, Philadelphia, Pennsylvania.
authors.forename: Maria
authors.initials: M
authors.lastname: Werner-Wasik
authors.affiliation: UC Davis Medical Center, Department of Radiation Oncology, Sacramento, California.
authors.forename: Richard
authors.initials: R
authors.lastname: Valicenti
authors.affiliation: CHUM Hospital Notre Dame, Quebec, Canada.
authors.forename: Jean-Paul
authors.initials: JP
authors.lastname: Bahary
authors.affiliation: McGill University, Montreal, Quebec, Canada.
authors.forename: Luis
authors.initials: L
authors.lastname: Souhami
authors.affiliation: NRG Oncology Statistics and Data Management Center, Philadelphia, Pennsylvania.
authors.forename: Minhee
authors.initials: M
authors.lastname: Won
authors.affiliation: University of Maryland Medical System, Baltimore, Maryland.
authors.forename: Minesh
authors.initials: M
authors.lastname: Mehta
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D001932:Brain Neoplasms / Q000401:mortality* / Q000532:radiotherapy / Q000556:secondary* / Q000601:surgery; D001943:Breast Neoplasms / Q000473:pathology; D003131:Combined Modality Therapy / Q000379:methods / Q000401:mortality; D016371:Cranial Irradiation / Q000379:methods / Q000401:mortality*; D005260:Female; D006801:Humans; D007680:Kidney Neoplasms / Q000473:pathology; D008175:Lung Neoplasms / Q000473:pathology; D008297:Male; D008545:Melanoma / Q000556:secondary; D008875:Middle Aged; D011379:Prognosis; D016634:Radiosurgery / Q000379:methods / Q000401:mortality*; D012044:Regression Analysis; D055815:Young Adult