title: Single-fraction proton beam stereotactic radiosurgery for cerebral arteriovenous malformations.
abstract: OBJECTIVE
  To evaluate the obliteration rate and potential adverse effects of single-fraction proton beam stereotactic radiosurgery (PSRS) in patients with cerebral arteriovenous malformations (AVMs).
  
  
  METHODS
  From 1991 to 2010, 248 consecutive patients with 254 cerebral AVMs received single-fraction PSRS at our institution. The median AVM nidus volume was 3.5 cc (range, 0.1-28.1 cc), 23% of AVMs were in critical/deep locations (basal ganglia, thalamus, or brainstem), and the most common prescription dose was 15 Gy(relative biological effectiveness [RBE]). Univariable and multivariable analyses were performed to assess factors associated with obliteration and hemorrhage.
  
  
  RESULTS
  At a median follow-up time of 35 months (range, 6-198 months), 64.6% of AVMs were obliterated. The median time to total obliteration was 31 months (range, 6-127 months), and the 5-year and 10-year cumulative incidence of total obliteration was 70% and 91%, respectively. On univariable analysis, smaller target volume (hazard ratio [HR] 0.78, 95% confidence interval [CI] 0.86-0.93, P<.0001), smaller treatment volume (HR 0.93, 95% CI 0.90-0.96, P<.0001), higher prescription dose (HR 1.16, 95% CI 1.07-1.26, P=.001), and higher maximum dose (HR 1.14, 95% CI 1.05-1.23, P=.002) were associated with total obliteration. Deep/critical location was also associated with decreased likelihood of obliteration (HR 0.68, 95% CI 0.47-0.98, P=.04). On multivariable analysis, critical location (adjusted HR [AHR] 0.42, 95% CI 0.27-0.65, P<.001) and smaller target volume (AHR 0.81, 95% CI 0.68-0.97, P=.02) remained associated with total obliteration. Posttreatment hemorrhage occurred in 13 cases (5-year cumulative incidence of 7%), all among patients with less than total obliteration, and 3 of these events were fatal. The most common complication was seizure, controlled with medications, both acutely (8%) and in the long term (9.1%).
  
  
  CONCLUSIONS
  The current series is the largest modern series of PSRS for cerebral AVMs. PSRS can achieve a high obliteration rate with minimal morbidity. Post-treatment hemorrhage remains a potentially fatal risk among patients who have not yet responded to treatment.
authors.affiliation: Department of Radiation Medicine and Applied Sciences, University of California San Diego, San Diego, California.
authors.forename: Jona A
authors.initials: JA
authors.lastname: Hattangadi-Gluth
authors.affiliation: Department of Neurosurgery, Massachusetts General Hospital, Boston, Massachusetts.
authors.forename: Paul H
authors.initials: PH
authors.lastname: Chapman
authors.affiliation: Department of Radiation Oncology, Massachusetts General Hospital, Boston, Massachusetts.
authors.forename: Daniel
authors.initials: D
authors.lastname: Kim
authors.affiliation: Department of Radiation Oncology, Massachusetts General Hospital, Boston, Massachusetts.
authors.forename: Andrzej
authors.initials: A
authors.lastname: Niemierko
authors.affiliation: Department of Radiation Oncology, Massachusetts General Hospital, Boston, Massachusetts.
authors.forename: Marc R
authors.initials: MR
authors.lastname: Bussière
authors.affiliation: Department of Radiation Oncology, Massachusetts General Hospital, Boston, Massachusetts.
authors.forename: Alison
authors.initials: A
authors.lastname: Stringham
authors.affiliation: Department of Radiation Oncology, Massachusetts General Hospital, Boston, Massachusetts.
authors.forename: Juliane
authors.initials: J
authors.lastname: Daartz
authors.affiliation: Department of Neurosurgery, Beth Israel Deaconess Medical Center, Boston, Massachusetts.
authors.forename: Christopher
authors.initials: C
authors.lastname: Ogilvy
authors.affiliation: Department of Radiation Oncology, Massachusetts General Hospital, Boston, Massachusetts.
authors.forename: Jay S
authors.initials: JS
authors.lastname: Loeffler
authors.affiliation: Department of Radiation Oncology, Massachusetts General Hospital, Boston, Massachusetts. Electronic address: hshih@partners.org.
authors.forename: Helen A
authors.initials: HA
authors.lastname: Shih
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000704:Analysis of Variance; D002543:Cerebral Hemorrhage / Q000209:etiology / Q000401:mortality; D002648:Child; D002675:Child, Preschool; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D002538:Intracranial Arteriovenous Malformations / Q000150:complications / Q000000981:diagnostic imaging / Q000601:surgery*; D008297:Male; D008875:Middle Aged; D061766:Proton Therapy / Q000009:adverse effects / Q000379:methods*; D011859:Radiography; D016634:Radiosurgery / Q000009:adverse effects / Q000379:methods*; D011879:Radiotherapy Dosage; D012062:Relative Biological Effectiveness; D012189:Retrospective Studies; D012640:Seizures / Q000209:etiology; D055815:Young Adult