title: Hypofractionated stereotactic radiotherapy of limited brain metastases: a single-centre individualized treatment approach.
abstract: BACKGROUND
  We retrospectively report treatment results of our single-centre experience with hypofractionated stereotactic radiotherapy (hfSRT) of limited brain metastases in primary and recurrence disease situations. Our aim was to find the most effective and safe dose concept.
  
  
  METHODS
  From 04/2006 to 12/2010, 75 patients, with 108 intracranial metastases, were treated with hfSRT. 52 newly diagnosed metastases (48%), without up-front whole brain radiotherapy (WBRT), received hfSRT as a primary treatment. 56 metastases (52%) received a prior WBRT and were treated in this study in a recurrence situation. Main fractionation concepts used for primary hfSRT were 6-7x5 Gy (61.5%) and 5x6 Gy (19.2%), for recurrent hfSRT 7-10x4 Gy (33.9%) and 5-6x5 Gy (33.9%).
  
  
  RESULTS
  Median overall survival (OS) of all patients summed up to 9.1 months, actuarial 6-and 12-month-OS was 59% and 35%, respectively. Median local brain control (LC) was 11.9 months, median distant brain control (DC) 3.9 months and intracranial control (IC) 3.4 months, respectively. Variables with significant influence on OS were Gross Tumour Volume (GTV) (p = 0.019), the biological eqivalent dose (calculated on a 2 Gy single dose, EQD2, α/β = 10) < and ≥ median of 39 Gy (p = 0.012), extracerebral activity of the primary tumour (p < 0.001) and the steroid uptake during hfSRT (p = 0.03). LC was significantly influenced by the EQD2, ≤ and > 35 Gy (p = 0.004) in both uni- and multivariate Cox regression analysis. Median LC was 14.9 months for EQD2 >35 Gy and 3.4 months for doses ≤35 Gy, respectively. Early treatment related side effects were usually mild. Nevertheless, patients with a EQD2 >35 Gy had higher rates of toxicity (31%) than ≤35 Gy (8.3%, p=0.026).
  
  
  CONCLUSIONS
  Comparing different dose concepts in hfSRT, a cumulative EQD2 of ≥35 Gy seems to be the most effective concept in patients with primary or recurrent limited brain metastases. Despite higher rates of only mild toxicity, this concept represents a safe treatment option.
authors.affiliation: Radiation Oncology, Medical School Hannover, Carl-Neuberg-Str, 1, Hannover, 30625, Germany.
authors.forename: Bettina
authors.initials: B
authors.lastname: Märtens
authors.forename: Stefan
authors.initials: S
authors.lastname: Janssen
authors.forename: Martin
authors.initials: M
authors.lastname: Werner
authors.forename: Jörg
authors.initials: J
authors.lastname: Frühauf
authors.forename: Hans
authors.initials: H
authors.lastname: Christiansen
authors.forename: Michael
authors.initials: M
authors.lastname: Bremer
authors.forename: Diana
authors.initials: D
authors.lastname: Steinmann
mesh_terms: D000328:Adult; D000368:Aged; D001932:Brain Neoplasms / Q000532:radiotherapy* / Q000556:secondary*; D016371:Cranial Irradiation / Q000379:methods; D019583:Dose Fractionation, Radiation; D004307:Dose-Response Relationship, Radiation; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D008297:Male; D008875:Middle Aged; D057285:Precision Medicine / Q000379:methods*; D011879:Radiotherapy Dosage; D012189:Retrospective Studies; D013256:Steroids / Q000008:administration & dosage; D015996:Survival Rate
chemical_list: D013256:Steroids