title: Stereotactic Radiosurgery With or Without Whole-Brain Radiotherapy for Brain Metastases: Secondary Analysis of the JROSG 99-1 Randomized Clinical Trial.
abstract: OBJECTIVE
  It remains uncertain whether treatment with stereotactic radiosurgery (SRS) alone can be safely applied to all patient populations with 1 to 4 brain metastases (BMs) exhibiting heterogeneous prognoses.
  
  
  OBJECTIVE
  To investigate the feasibility of SRS alone for patients with different prognoses determined by the diagnosis-specific Graded Prognostic Assessment (DS-GPA).
  
  
  METHODS
  A secondary analysis (performed in September 2014) of the Japanese Radiation Oncology Study Group (JROSG) 99-1, a phase 3 randomized trial, comparing SRS alone and whole-brain radiotherapy (WBRT) + SRS conducted in 1999 to 2003. Among a total of 132 patients, 88 with non-small-cell lung cancer (NSCLC) and 1 to 4 BMs were included and poststratified by DS-GPA scores to avoid potential bias from BMs from different primary cancer types. The median follow-up time was 8.05 months.
  
  
  METHODS
  The WBRT schedule was 30 Gy in 10 fractions over 2 to 2.5 weeks. The mean SRS dose was 21.9 Gy in SRS alone and 16.6 Gy in WBRT + SRS.
  
  
  METHODS
  The primary end point was overall survival (OS), and the secondary end points included brain tumor recurrence (BTR), salvage treatment, and radiation toxic effects.
  
  
  RESULTS
  Forty-seven patients had a favorable prognosis, with DS-GPA scores of 2.5 to 4.0 (26 SRS-alone and 21 WBRT + SRS [DS-GPA 2.5-4.0 group]), and 41 had an unfavorable prognosis, with DS-GPA scores of 0.5 to 2.0 (19 SRS-alone and 22 WBRT + SRS [DS-GPA 0.5-2.0 group]). Significantly better OS was observed in the DS-GPA 2.5-4.0 group in WBRT + SRS vs the SRS alone, with a median survival time of 16.7 (95% CI, 7.5-72.9) months vs 10.6 (95% CI, 7.7-15.5) months (P = .04) (hazard ratio [HR], 1.92; 95% CI, 1.01-3.78). However, no such difference was observed in the DS-GPA 0.5-2.0 group (HR, 1.05; 95% CI, 0.55-1.99) (P = .86). This benefit could be explained by the differing BTR rates, in that the prevention against BTR by WBRT had a more significant impact in the DS-GPA 2.5-4.0 group (HR, 8.31; 95% CI, 3.05-29.13) (P < .001) vs the DS-GPA 0.5-2.0 group (HR, 3.57; 95% CI, 1.02-16.49) (P = .04).
  
  
  CONCLUSIONS
  Despite the current trend of using SRS alone, the important role of WBRT for patients with BMs from NSCLC with a favorable prognosis should be considered. Our findings should be validated through appropriately designed prospective studies.
  
  
  BACKGROUND
  umin.ac.jp/ctr Identifier: C000000412.
authors.affiliation: Department of Radiology, Niigata University Graduate School of Medical and Dental Sciences, Niigata, Japan.
authors.forename: Hidefumi
authors.initials: H
authors.lastname: Aoyama
authors.affiliation: Department of Radiology, Teikyo University Mizonokuchi Hospital, Kawasaki, Japan.
authors.forename: Masao
authors.initials: M
authors.lastname: Tago
authors.affiliation: Department of Radiation Medicine, Hokkaido University Graduate School of Medicine, Sapporo, Japan.
authors.forename: Hiroki
authors.initials: H
authors.lastname: Shirato
mesh_terms: D001932:Brain Neoplasms / Q000401:mortality / Q000556:secondary* / Q000628:therapy*; D002289:Carcinoma, Non-Small-Cell Lung / Q000401:mortality / Q000556:secondary* / Q000628:therapy*; D016371:Cranial Irradiation; D018450:Disease Progression; D018572:Disease-Free Survival; D019583:Dose Fractionation, Radiation; D005240:Feasibility Studies; D005260:Female; D006801:Humans; D007564:Japan; D053208:Kaplan-Meier Estimate; D008175:Lung Neoplasms / Q000401:mortality / Q000473:pathology*; D008297:Male; D008875:Middle Aged; D016016:Proportional Hazards Models; D016634:Radiosurgery / Q000009:adverse effects / Q000401:mortality; D018714:Radiotherapy, Adjuvant / Q000009:adverse effects / Q000401:mortality; D012307:Risk Factors; D016879:Salvage Therapy; D013997:Time Factors; D016896:Treatment Outcome