title: Hypofractionated stereotactic radiotherapy as an alternative to radiosurgery for the treatment of patients with brain metastases.
abstract: OBJECTIVE
  Modeling studies have demonstrated a potential biologic advantage of fractionated stereotactic radiotherapy for malignant brain tumors as compared to radiosurgery (SRS), even when only a few fractions are utilized. We prospectively evaluated the feasibility, toxicity, efficacy and cost of hypofractionated stereotactic radiotherapy (HSRT) in the treatment of selected radiosurgery-eligible patients with brain metastases.
  
  
  METHODS
  Patients with a limited number of brain metastases not involving the brainstem or optic chiasm underwent linac-based HSRT delivered in 3 fractions using a relocatable stereotactic frame. Depth-helmet and reference point measurements were recorded to address treatment accuracy. All patients underwent whole brain radiotherapy to a dose of 30 Gy. Toxicity, response, and survival duration were recorded for each patient. Prognostic factors were assessed by Cox regression analysis. Cost comparisons with a cohort of SRS treated patients were performed.
  
  
  RESULTS
  Thirty-two patients with 57 brain metastases were treated with HSRT. Twenty-three and 9 patients underwent HSRT for upfront and salvage treatment, respectively. The median dose delivered was 27 Gy, given in 3 fractions of 9 Gy. From 3328 depth-helmet measurements, the absolute median setup deviation in AP, lateral, and vertical orientations was approximately 1.0 mm. No significant acute toxicity was seen. Late toxicities included seizures in four patients, and radionecrosis in two patients. The median survival duration from treatment was 12 months. KPS (p = 0.039) and RTOG-RPA class (p = 0.039) were identified as significant prognostic factors for survival. HSRT was $4119 less costly than SRS.
  
  
  CONCLUSIONS
  HSRT, as delivered in this study, is more comfortable for patients and less costly than SRS in the treatment of selected patients with brain metastases. Proper dose selection and radiobiologic/toxicity trade-offs with SRS await further study.
authors.affiliation: Department of Radiation Oncology, Medical College of Virginia Hospitals, Virginia Commonwealth University, Richmond, VA 23298-0058, USA.
authors.forename: M A
authors.initials: MA
authors.lastname: Manning
authors.forename: R M
authors.initials: RM
authors.lastname: Cardinale
authors.forename: S H
authors.initials: SH
authors.lastname: Benedict
authors.forename: B D
authors.initials: BD
authors.lastname: Kavanagh
authors.forename: R D
authors.initials: RD
authors.lastname: Zwicker
authors.forename: C
authors.initials: C
authors.lastname: Amir
authors.forename: W C
authors.initials: WC
authors.lastname: Broaddus
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D001932:Brain Neoplasms / Q000556:secondary / Q000601:surgery*; D002648:Child; D003365:Costs and Cost Analysis; D016371:Cranial Irradiation; D019583:Dose Fractionation, Radiation; D005240:Feasibility Studies; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D011446:Prospective Studies; D016634:Radiosurgery / Q000191:economics / Q000379:methods*; D016879:Salvage Therapy