title: Patterns of distant brain recurrences after radiosurgery alone for newly diagnosed brain metastases: implications for salvage therapy.
abstract: BACKGROUND
  Single modality radiosurgery (RS) is an established treatment option for patients with brain metastases (BM) with the aim of achieving optimal local control while avoiding toxicity from whole brain radiotherapy (WBRT). Published studies generally lack detailed data on distant brain recurrence (DBR) rates and characteristics. This study describes the patterns of DBR and consequences for salvage treatment in a group of patients treated with RS alone for 1-3 BM.
  
  
  METHODS
  Between 2002 and 2012, 443 patients were treated with RS alone in doses ranging 15-24 Gy in 1-3 fractions. Patient selection for RS was performed using triple dose gadolinium-enhanced MRI scans, obtained with slice distance of 2mm (until 2008), 1.5 mm (2008-2012), and of 1 mm (from 2012). During follow-up, a DBR was observed in 147 patients, but in 20 of these patients (14%) these "new lesions" could retrospectively be seen on the planning MRI scan. These missed metastases had a median size of 2mm, and in order to study real DBR patterns, these patients were excluded from analysis.
  
  
  RESULTS
  Actuarial DBR rates at 6, 12 and 24 months in the remaining 423 patients were 21%, 41% and 54%, respectively, with a median time to DBR of 5.6 months. In 42% of DBR, a single new lesion was seen, in 70% there were ⩽3 new lesions. Median diameter of the DBR was 6mm; 97% of lesions were ⩽30 mm. Salvage therapy was delivered in 82% of DBR patients, consisting of WBRT (46%), repeated RS (27%), or systemic treatment (9%). A RPA classification system (DBR-RPA), based on WHO performance status and interval between initial RS and diagnosis of DBR, was developed to estimate life expectancy after the development of DBR, which can be used to guide salvage therapy.
  
  
  CONCLUSIONS
  In this study of patients treated with RS alone, only 25% of treated patients needed salvage treatment for DBR, and ultimately only 18% of all patients underwent WBRT at any time during follow-up. A three-monthly MRI follow-up scheme identifies DBR at an early stage with respect to size and number of lesions, and most patients were asymptomatic at radiological diagnosis.
authors.affiliation: Department of Radiation Oncology, VU University Medical Center, Amsterdam, The Netherlands.
authors.forename: Jaap D
authors.initials: JD
authors.lastname: Zindler
authors.affiliation: Department of Radiation Oncology, VU University Medical Center, Amsterdam, The Netherlands.
authors.forename: Ben J
authors.initials: BJ
authors.lastname: Slotman
authors.affiliation: Department of Radiation Oncology, VU University Medical Center, Amsterdam, The Netherlands. Electronic address: FJ.Lagerwaard@vumc.nl.
authors.forename: Frank J
authors.initials: FJ
authors.lastname: Lagerwaard
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D001932:Brain Neoplasms / Q000473:pathology / Q000556:secondary* / Q000601:surgery*; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D009364:Neoplasm Recurrence, Local / Q000473:pathology*; D018579:Patient Selection; D016634:Radiosurgery / Q000379:methods*; D016032:Randomized Controlled Trials as Topic; D012189:Retrospective Studies; D016879:Salvage Therapy / Q000379:methods*; D055815:Young Adult
keywords: Brain metastases; Outfield; Radiosurgery; Radiotherapy; Recurrence; Stereotactic