title: Stereotactic radiosurgery for patients with multiple brain metastases: a case-matched study comparing treatment results for patients with 2-9 versus 10 or more tumors.
abstract: OBJECTIVE
  Although stereotactic radiosurgery (SRS) alone is not a standard treatment for patients with 4-5 tumors or more, a recent trend has been for patients with 5 or more, or even 10 or more, tumors to undergo SRS alone. The aim of this study was to reappraise whether the treatment results for SRS alone for patients with 10 or more tumors differ from those for patients with 2-9 tumors.
  
  
  METHODS
  This was an institutional review board-approved, retrospective cohort study that gathered data from the Katsuta Hospital Mito GammaHouse prospectively accumulated database. Data were collected for 2553 patients who consecutively had undergone Gamma Knife SRS alone, without whole-brain radiotherapy (WBRT), for newly diagnosed (mostly) or recurrent (uncommonly) brain metastases during 1998-2011. Of these 2553 patients, 739 (28.9%) with a single tumor were excluded, leaving 1814 with multiple metastases in the study. These 1814 patients were divided into 2 groups: those with 2-9 tumors (Group A, 1254 patients) and those with 10 or more tumors (Group B, 560 patients). Because of considerable bias in pre-SRS clinical factors between groups A and B, a case-matched study, which used the propensity score matching method, was conducted for clinical factors (i.e., age, sex, primary tumor state, extracerebral metastases, Karnofsky Performance Status, neurological symptoms, prior procedures [surgery and WBRT], volume of the largest tumor, and peripheral doses). Ultimately, 720 patients (360 in each group) were selected. The standard Kaplan-Meier method was used to determine post-SRS survival times and post-SRS neurological death-free survival times. Competing risk analysis was applied to estimate cumulative incidence for local recurrence, repeat SRS for new lesions, neurological deterioration, and SRS-induced complications.
  
  
  RESULTS
  Post-SRS median survival times did not differ significantly between the 2 groups (6.8 months for Group A vs 6.0 months for Group B; hazard ratio [HR] 1.133, 95% CI 0.974-1.319, p = 0.10). Furthermore, rates of neurological death were very similar: 10.0% for group A and 9.4% for group B (p = 0.89); neurological death-free survival times did not differ significantly between the 2 groups (HR 1.073, 95% CI 0.649-1.771, p = 0.78). The cumulative incidence of local recurrence (HR 0.425, 95% CI 0.0.181-0.990, p = 0.04) and repeat SRS for new lesions (HR 0.732, 95% CI 0.554-0.870, p = 0.03) were significantly lower for Group B than for Group A patients. No significant differences between the groups were found for cumulative incidence for neurological deterioration (HR 0.994, 95% CI 0.607-1.469, p = 0.80) or SRS-related complications (HR 0.541, 95% CI 0.138-2.112, p = 0.38).
  
  
  CONCLUSIONS
  Post-SRS treatment results (i.e., median survival time; neurological death-free survival times; and cumulative incidence for local recurrence, repeat SRS for new lesions, neurological deterioration, and SRS-related complications) were not inferior (neither less effective nor less safe) for patients in Group B than for those in Group A. We conclude that carefully selected patients with 10 or more tumors are not unfavorable candidates for SRS alone. A randomized controlled trial should be conducted to test this hypothesis.
authors.affiliation: Katsuta Hospital Mito GammaHouse, Hitachinaka;
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: Shinya
authors.initials: S
authors.lastname: Watanabe
authors.forename: Hidetoshi
authors.initials: H
authors.lastname: Kasuya
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D001932:Brain Neoplasms / Q000401:mortality / Q000556:secondary* / Q000601:surgery*; D016022:Case-Control Studies; D016208:Databases, Factual; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D015994:Incidence; D017567:Karnofsky Performance Status; D008297:Male; D008875:Middle Aged; D009364:Neoplasm Recurrence, Local / Q000401:mortality; D016634:Radiosurgery / Q000379:methods* / Q000401:mortality; D012189:Retrospective Studies; D012720:Severity of Illness Index; D015996:Survival Rate
keywords: Gamma Knife; HR = hazard ratio; KPS = Karnofsky Performance Status; RPA = recursive partitioning analysis; SRS = stereotactic radiosurgery; WBRT = whole-brain radiation therapy; brain metastases; radiation therapy; radiosurgery; stereotactic radiosurgery; tumor number