title: Fractionated stereotactic radiation therapy for brain metastases: a systematic review with tumour control probability modelling.
abstract: OBJECTIVE
  Fractionated stereotactic radiotherapy (FSRT) is a relatively new option for the treatment of brain metastases. We performed a quantitative systematic review to determine if local control (LC) following is affected by FSRT dosing regimen.
  
  
  METHODS
  We reviewed articles describing LC following FSRT for brain metastases. LC data from each study were extracted from actuarial survival curves and aggregated to form a single data set. LC curves were generated using the Kaplan-Meier method. Log-rank testing and Cox proportional hazards modelling were utilized to test for associations between the biologically effective dose (BED) and LC. Tumour control probability modelling was performed to illustrate the relationship between the BED and the likelihood of LC after FSRT.
  
  
  RESULTS
  10 studies (720 metastases) met inclusion criteria. Prescription doses ranged from 18 to 42 Gy, delivered in 3-12 fractions (BED range: 29-100 Gy10). 1- and 2-year actuarial LC rates were 80% and 69%, respectively. Increasing BED was associated with improved LC (HR = 0.77 per increase of 10 Gy10, p = 0.009). Tumour control probability models demonstrated that the BEDs of 40, 50 and 60 Gy10yield predicted 1-year LC rates of 73%, 78% and 84%, respectively. The BEDs of 40, 50 and 60 Gy10yield 2-year LC rates of 62%, 69% and 81%, respectively.
  
  
  CONCLUSIONS
  FSRT provides high rates of LC for patients with brain metastases. We found evidence for a dose-response relationship that should be explored in prospective trials. Advances in knowledge: This review identified a dose-response relationship for LC in patients treated with FSRT for brain metastases.
authors.affiliation: 1 Department of Radiation Oncology, Montefiore Medical Center, Albert Einstein College of Medicine, New York, NY, USA.
authors.forename: Sujith
authors.initials: S
authors.lastname: Baliga
authors.affiliation: 1 Department of Radiation Oncology, Montefiore Medical Center, Albert Einstein College of Medicine, New York, NY, USA.
authors.forename: Madhur K
authors.initials: MK
authors.lastname: Garg
authors.affiliation: 1 Department of Radiation Oncology, Montefiore Medical Center, Albert Einstein College of Medicine, New York, NY, USA.
authors.forename: Jana
authors.initials: J
authors.lastname: Fox
authors.affiliation: 1 Department of Radiation Oncology, Montefiore Medical Center, Albert Einstein College of Medicine, New York, NY, USA.
authors.forename: Shalom
authors.initials: S
authors.lastname: Kalnicki
authors.affiliation: 2 Department of Neurosurgery, Montefiore Medical Center, Albert Einstein College of Medicine, New York, NY, USA.
authors.forename: Patrick A
authors.initials: PA
authors.lastname: Lasala
authors.affiliation: 3 Department of Oncology, Montefiore Medical Center, Albert Einstein College of Medicine, New York, NY, USA.
authors.forename: Mary R
authors.initials: MR
authors.lastname: Welch
authors.affiliation: 1 Department of Radiation Oncology, Montefiore Medical Center, Albert Einstein College of Medicine, New York, NY, USA.
authors.forename: Wolfgang A
authors.initials: WA
authors.lastname: Tomé
authors.affiliation: 1 Department of Radiation Oncology, Montefiore Medical Center, Albert Einstein College of Medicine, New York, NY, USA.
authors.forename: Nitin
authors.initials: N
authors.lastname: Ohri
mesh_terms: D001932:Brain Neoplasms / Q000532:radiotherapy* / Q000556:secondary*; D019583:Dose Fractionation, Radiation; D006801:Humans; D053208:Kaplan-Meier Estimate; D015233:Models, Statistical; D011336:Probability; D016016:Proportional Hazards Models; D016634:Radiosurgery / Q000379:methods*; D016896:Treatment Outcome