title: Choosing a Prescription Isodose in Stereotactic Radiosurgery for Brain Metastases: Implications for Local Control.
abstract: OBJECTIVE
  Stereotactic radiosurgery (SRS) achieves excellent local control (LC) with limited toxicity for most brain metastases. SRS dose prescription variables influence LC; therefore, we evaluated the impact of prescription isodose line (IDL) on LC after SRS.
  
  
  METHODS
  A retrospective analysis of patients with brain metastases treated on a Gamma Knife platform from 2004 to 2014 was conducted. Clinical, toxicity, radiographic, and dosimetric data were collected. Cox proportional hazards regression was used to determine progression-free survival (PFS) and competing risks analysis was used to determine predictive factors for LC.
  
  
  RESULTS
  A total of 134 patients with 374 brain metastases were identified with a median survival of 8.7 months (range, 0.2-64.8). The median tumor maximum dimension was 8 mm (range, 2-62 mm), median margin dose was 20 Gy (range, 5-24 Gy), and 12-month LC rate was 88.7%. On multivariate analysis, PFS improved with increasing IDL (P = 0.003) and decreased with non-non-small-cell lung cancer histology (P = 0.001). Margin dose, tumor size, conformality, and previous whole-brain irradiation failed to independently affect PFS. When adjusting for death as a competing risk, the cumulative likelihood of LC improved with higher IDL (P = 0.04). The rate of SRS-induced radiographic and clinical toxicity was low (16.6% and 1.5%, respectively), and neither was affected by IDL.
  
  
  CONCLUSIONS
  Our results confirm that SRS for brain metastases results in favorable LC, particularly for patients with smaller tumors. We noted that dose delivery to a higher prescription IDL is associated with small but measurable improvements in LC. This finding could be related to higher dose just beyond the radiographically apparent tumor.
authors.affiliation: Department of Radiation Oncology, University of Virginia, Charlottesville, Virginia, USA. Electronic address: kara.e.downs@gmail.com.
authors.forename: Kara D
authors.initials: KD
authors.lastname: Romano
authors.affiliation: Department of Radiation Oncology, University of Virginia, Charlottesville, Virginia, USA.
authors.forename: Daniel M
authors.initials: DM
authors.lastname: Trifiletti
authors.affiliation: Department of Radiation Oncology, University of Virginia, Charlottesville, Virginia, USA.
authors.forename: Allison
authors.initials: A
authors.lastname: Garda
authors.affiliation: Department of Neurological Surgery, University of Virginia, Charlottesville, Virginia, USA.
authors.forename: Zhiyuan
authors.initials: Z
authors.lastname: Xu
authors.affiliation: Department of Radiation Oncology, University of Virginia, Charlottesville, Virginia, USA; Department of Neurological Surgery, University of Virginia, Charlottesville, Virginia, USA.
authors.forename: David
authors.initials: D
authors.lastname: Schlesinger
authors.affiliation: Department of Radiation Oncology, University of Virginia, Charlottesville, Virginia, USA.
authors.forename: William T
authors.initials: WT
authors.lastname: Watkins
authors.affiliation: Department of Radiation Oncology, University of Virginia, Charlottesville, Virginia, USA.
authors.forename: Brian
authors.initials: B
authors.lastname: Neal
authors.affiliation: Department of Radiation Oncology, University of Virginia, Charlottesville, Virginia, USA.
authors.forename: James M
authors.initials: JM
authors.lastname: Larner
authors.affiliation: Department of Radiation Oncology, University of Virginia, Charlottesville, Virginia, USA; Department of Neurological Surgery, University of Virginia, Charlottesville, Virginia, USA.
authors.forename: Jason P
authors.initials: JP
authors.lastname: Sheehan
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D001932:Brain Neoplasms / Q000473:pathology / Q000532:radiotherapy* / Q000556:secondary; D005260:Female; D006801:Humans; D008279:Magnetic Resonance Imaging; D008297:Male; D008875:Middle Aged; D016634:Radiosurgery / Q000009:adverse effects / Q000379:methods*; D011879:Radiotherapy Dosage; D012189:Retrospective Studies; D016896:Treatment Outcome; D047368:Tumor Burden
keywords: Brain metastases; Isodose; Local control; Margin dose; Radiosurgery