title: Long-term Outcomes With Planned Multistage Reduced Dose Repeat Stereotactic Radiosurgery for Treatment of Inoperable High-Grade Arteriovenous Malformations: An Observational Retrospective Cohort Study.
abstract: BACKGROUND
  There is no consensus regarding the optimal management of inoperable high-grade arteriovenous malformations (AVMs). This long-term study of 42 patients with high-grade AVMs reports obliteration and adverse event (AE) rates using planned multistage repeat stereotactic radiosurgery (SRS).
  
  
  OBJECTIVE
  To evaluate the efficacy and safety of multistage SRS with treatment of the entire AVM nidus at each treatment session to achieve complete obliteration of high-grade AVMs.
  
  
  METHODS
  Patients with high-grade Spetzler-Martin (S-M) III-V AVMs treated with at least 2 multistage SRS treatments from 1989 to 2013. Clinical outcomes of obliteration rate, minor/major AEs, and treatment characteristics were collected.
  
  
  RESULTS
  Forty-two patients met inclusion criteria (n = 26, S-M III; n = 13, S-M IV; n = 3, S-M V) with a median follow-up was 9.5 yr after first SRS. Median number of SRS treatment stages was 2, and median interval between stages was 3.5 yr. Twenty-two patients underwent pre-SRS embolization. Complete AVM obliteration rate was 38%, and the median time to obliteration was 9.7 yr. On multivariate analysis, higher S-M grade was significantly associated ( P = .04) failure to achieve obliteration. Twenty-seven post-SRS AEs were observed, and the post-SRS intracranial hemorrhage rate was 0.027 events per patient year.
  
  
  CONCLUSIONS
  Treatment of high-grade AVMs with multistage SRS achieves AVM obliteration in a meaningful proportion of patients with acceptable AE rates. Lower obliteration rates were associated with higher S-M grade and pre-SRS embolization. This approach should be considered with caution, as partial obliteration does not protect from hemorrhage.
authors.affiliation: Department of Radiation Oncology and Molecular Radiation Sciences, Johns Hopkins University School of Medicine, Baltimore, Maryland.
authors.forename: Ariel E
authors.initials: AE
authors.lastname: Marciscano
authors.affiliation: Department of Neurosurgery, Johns Hopkins University School of Medicine, Baltimore, Maryland.
authors.forename: Judy
authors.initials: J
authors.lastname: Huang
authors.affiliation: Department of Neurosurgery, Johns Hopkins University School of Medicine, Baltimore, Maryland.
authors.forename: Rafael J
authors.initials: RJ
authors.lastname: Tamargo
authors.affiliation: Department of Oncology, Division of Biostatistics and Bioinformatics, Johns Hopkins University School of Medicine, Baltimore, Maryland.
authors.forename: Chen
authors.initials: C
authors.lastname: Hu
authors.affiliation: Department of Radiation Oncology and Molecular Radiation Sciences, Johns Hopkins University School of Medicine, Baltimore, Maryland.
authors.forename: Mohamed H
authors.initials: MH
authors.lastname: Khattab
authors.affiliation: The George Washington University School of Medicine & Health Sciences, Washington, DC.
authors.forename: Sameer
authors.initials: S
authors.lastname: Aggarwal
authors.affiliation: Department of Neurosurgery, Johns Hopkins University School of Medicine, Baltimore, Maryland.
authors.forename: Michael
authors.initials: M
authors.lastname: Lim
authors.affiliation: Department of Radiation Oncology and Molecular Radiation Sciences, Johns Hopkins University School of Medicine, Baltimore, Maryland.
authors.forename: Kristin J
authors.initials: KJ
authors.lastname: Redmond
authors.affiliation: Department of Radiation Oncology and Molecular Radiation Sciences, Johns Hopkins University School of Medicine, Baltimore, Maryland.
authors.forename: Daniele
authors.initials: D
authors.lastname: Rigamonti
authors.affiliation: Department of Radiation Oncology and Molecular Radiation Sciences, Johns Hopkins University School of Medicine, Baltimore, Maryland.
authors.forename: Lawrence R
authors.initials: LR
authors.lastname: Kleinberg
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D002648:Child; D002985:Clinical Protocols; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D002538:Intracranial Arteriovenous Malformations / Q000532:radiotherapy*; D008297:Male; D008875:Middle Aged; D011829:Radiation Dosage; D016634:Radiosurgery; D012189:Retrospective Studies; D016896:Treatment Outcome; D055815:Young Adult
keywords: AVM; Cerebral arteriovenous malformation; Inoperable high-grade AVM; Multistage SRS; Stereotactic radiosurgery