title: A case-matched study of stereotactic radiosurgery for patients with multiple brain metastases: comparing treatment results for 1-4 vs ≥ 5 tumors: clinical article.
abstract: OBJECTIVE
  Although stereotactic radiosurgery (SRS) alone for patients with 4-5 or more tumors is not a standard treatment, a trend for patients with 5 or more tumors to undergo SRS alone is already apparent. The authors' aim in the present study was to reappraise whether SRS results for ≥ 5 tumors differ from those for 1-4 tumors.
  
  
  METHODS
  This institutional review board-approved retrospective cohort study used the authors' database of prospectively accumulated data that included 2553 consecutive patients who underwent SRS, not in combination with concurrent whole-brain radiotherapy, for brain metastases (METs) between 1998 and 2011. These 2553 patients were divided into 2 groups: 1553 with tumor numbers of 1-4 (Group A) and 1000 with ≥ 5 tumors (Group B). Because there was considerable bias in pre-SRS clinical factors between Groups A and B, a case-matched study was conducted. Ultimately, 1096 patients (548 each in Groups A and B) were selected. The standard Kaplan-Meier method was used to determine post-SRS survival and the post-SRS neurological death-free survival times. Competing risk analysis was applied to estimate cumulative incidences of local recurrence, repeat SRS for new lesions, neurological deterioration, and SRS-induced complications.
  
  
  RESULTS
  The post-SRS median survival time was significantly longer in the 548 Group A patients (7.9 months, 95% CI 7.0-8.9 months) than in the 548 Group B patients (7.0 months 95% [CI 6.2-7.8 months], HR 1.176 [95% CI 1.039-1.331], p = 0.01). However, incidences of neurological death were very similar: 10.6% in Group A and 8.2% in Group B (p = 0.21). There was no significant difference between the groups in neurological death-free survival intervals (HR 0.945, 95% CI 0.636-1.394, p = 0.77). Furthermore, competing risk analyses showed that there were no significant differences between the groups in cumulative incidences of local recurrence (HR 0.577, 95% CI 0.312-1.069, p = 0.08), repeat SRS (HR 1.133, 95% CI 0.910-1.409, p = 0.26), neurological deterioration (HR 1.868, 95% CI 0.608-1.240, p = 0.44), and major SRS-related complications (HR 1.105, 95% CI 0.490-2.496, p = 0.81). In the authors' cohort, age ≤ 65 years, female sex, a Karnofsky Performance Scale score ≥ 80%, cumulative tumor volume ≤ 10 cm(3), controlled primary cancer, no extracerebral METs, and neurologically asymptomatic status were significant factors favoring longer survival equally in both groups.
  
  
  CONCLUSIONS
  This retrospective study suggests that increased tumor number is an unfavorable factor for longer survival. However, the post-SRS median survival time difference, 0.9 months, between the two groups is not clinically meaningful. Furthermore, patients with 5 or more METs have noninferior results compared to patients with 1-4 tumors, in terms of neurological death, local recurrence, repeat SRS, maintenance of good neurological state, and SRS-related complications. A randomized controlled trial should be conducted to test this hypothesis.
authors.affiliation: Katsuta Hospital Mito GammaHouse, Ibaraki, Japan. BCD06275@nifty.com
authors.forename: Masaaki
authors.initials: M
authors.lastname: Yamamoto
authors.forename: Takuya
authors.initials: T
authors.lastname: Kawabe
authors.forename: Yasunori
authors.initials: Y
authors.lastname: Sato
authors.forename: Yoshinori
authors.initials: Y
authors.lastname: Higuchi
authors.forename: Tadashi
authors.initials: T
authors.lastname: Nariai
authors.forename: Bierta E
authors.initials: BE
authors.lastname: Barfod
authors.forename: Hidetoshi
authors.initials: H
authors.lastname: Kasuya
authors.forename: Yoichi
authors.initials: Y
authors.lastname: Urakawa
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D001932:Brain Neoplasms / Q000401:mortality / Q000556:secondary* / Q000601:surgery*; D001943:Breast Neoplasms / Q000473:pathology; D016022:Case-Control Studies; D015331:Cohort Studies; D005260:Female; D005770:Gastrointestinal Neoplasms / Q000473:pathology; D006801:Humans; D053208:Kaplan-Meier Estimate; D008175:Lung Neoplasms / Q000473:pathology; D008297:Male; D008875:Middle Aged; D016634:Radiosurgery; D012189:Retrospective Studies; D016896:Treatment Outcome