title: Stereotactic radiosurgery for brain metastases: analysis of outcome and risk of brain radionecrosis.
abstract: OBJECTIVE
  to investigate the factors affecting survival and toxicity in patients treated with stereotactic radiosurgery (SRS), with special attention to volumes of brain receiving a specific dose (V10 - V16 Gy) as predictors for brain radionecrosis.
  
  
  METHODS
  Two hundred six consecutive patients with 310 cerebral metastases less than 3.5 cm were treated with SRS as primary treatment and followed prospectively at University of Rome La Sapienza Sant'Andrea Hospital. Overall survival, brain control, and local control were estimated using the Kaplan-Meier method calculated from the time of SRS. Univariate and multivariate analysis using a Cox proportional hazards regression model were performed to determine the predictive value of prognostic factors for treatment outcome and SRS-related complications.
  
  
  RESULTS
  Median overall survival and brain control were 14.1 months and 10 months, respectively. The 1-year and 2-year survival rates were 58% and 24%, and respective brain control were 43% and 22%. Sixteen patients recurred locally after SRS, with 1-year and 2-year local control rates of 92% and 84%, respectively. On multivariate analysis, stable extracranial disease and KPS >70 were associated with the most significant survival benefit. Neurological complications were recorded in 27 (13%) patients. Severe neurological complications (RTOG Grade 3 and 4) occurred in 5.8% of patients. Brain radionecrosis occurred in 24% of treated lesions, being symptomatic in 10% and asymptomatic in 14%. On multivariate analysis, V10 through V16 Gy were independent risk factors for radionecrosis, with V10 Gy and V12 Gy being the most predictive (p = 0.0001). For V10 Gy >12.6 cm3 and V12 Gy >10.9 cm3 the risk of radionecrosis was 47%.
  
  
  CONCLUSIONS
  SRS alone represents a feasible option as initial treatment for patients with brain metastases, however a significant subset of patients may develop neurological complications. Lesions with V12 Gy >8.5 cm3 carries a risk of radionecrosis >10% and should be considered for hypofractionated stereotactic radiotherapy especially when located in/near eloquent areas.
authors.affiliation: Department of Radiation Oncology, Sant'Andrea Hospital, University La Sapienza, Rome, Italy. gminniti@ospedalesantandrea.it
authors.forename: Giuseppe
authors.initials: G
authors.lastname: Minniti
authors.forename: Enrico
authors.initials: E
authors.lastname: Clarke
authors.forename: Gaetano
authors.initials: G
authors.lastname: Lanzetta
authors.forename: Mattia Falchetto
authors.initials: MF
authors.lastname: Osti
authors.forename: Guido
authors.initials: G
authors.lastname: Trasimeni
authors.forename: Alessandro
authors.initials: A
authors.lastname: Bozzao
authors.forename: Andrea
authors.initials: A
authors.lastname: Romano
authors.forename: Riccardo Maurizi
authors.initials: RM
authors.lastname: Enrici
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D001921:Brain / Q000528:radiation effects; D001932:Brain Neoplasms / Q000150:complications* / Q000532:radiotherapy*; D019583:Dose Fractionation, Radiation; D004307:Dose-Response Relationship, Radiation; D005260:Female; D006801:Humans; D008279:Magnetic Resonance Imaging / Q000379:methods; D008297:Male; D008875:Middle Aged; D009336:Necrosis / Q000175:diagnosis* / Q000209:etiology; D009362:Neoplasm Metastasis; D011832:Radiation Injuries / Q000175:diagnosis* / Q000209:etiology; D016634:Radiosurgery / Q000009:adverse effects*; D012306:Risk; D016896:Treatment Outcome