title: Planned two-fraction proton beam stereotactic radiosurgery for high-risk inoperable cerebral arteriovenous malformations.
abstract: OBJECTIVE
  To evaluate patients with high-risk cerebral arteriovenous malformations (AVMs), based on eloquent brain location or large size, who underwent planned two-fraction proton stereotactic radiosurgery (PSRS).
  
  
  METHODS
  From 1991 to 2009, 59 patients with high-risk cerebral AVMs received two-fraction PSRS. Median nidus volume was 23 cc (range, 1.4-58.1 cc), 70% of cases had nidus volume ≥ 14 cc, and 34% were in critical locations (brainstem, basal ganglia). Median AVM score based on age, AVM size, and location was 3.19 (range, 0.9-6.9). Many patients had prior surgery or embolization (40%) or prior PSRS (12%). The most common prescription was 16 Gy radiobiologic equivalent (RBE) in two fractions, prescribed to the 90% isodose.
  
  
  RESULTS
  At a median follow-up of 56.1 months, 9 patients (15%) had total and 20 patients (34%) had partial obliteration. Patients with total obliteration received higher total dose than those with partial or no obliteration (mean dose, 17.6 vs. 15.5 Gy (RBE), p = 0.01). Median time to total obliteration was 62 months (range, 23-109 months), and 5-year actuarial rate of partial or total obliteration was 33%. Five-year actuarial rate of hemorrhage was 22% (95% confidence interval, 12.5%-36.8%) and 14% (n = 8) suffered fatal hemorrhage. Lesions with higher AVM scores were more likely to hemorrhage (p = 0.024) and less responsive to radiation (p = 0.026). The most common complication was Grade 1 headache acutely (14%) and long term (12%). One patient developed a Grade 2 generalized seizure disorder, and two had mild neurologic deficits.
  
  
  CONCLUSIONS
  High-risk AVMs can be safely treated with two-fraction PSRS, although total obliteration rate is low and patients remain at risk for future hemorrhage. Future studies should include higher doses or a multistaged PSRS approach for lesions more resistant to obliteration with radiation.
authors.affiliation: Harvard Radiation Oncology Program, Boston, MA, USA.
authors.forename: Jona A
authors.initials: JA
authors.lastname: Hattangadi
authors.forename: Paul H
authors.initials: PH
authors.lastname: Chapman
authors.forename: Marc R
authors.initials: MR
authors.lastname: Bussière
authors.forename: Andrzej
authors.initials: A
authors.lastname: Niemierko
authors.forename: Christopher S
authors.initials: CS
authors.lastname: Ogilvy
authors.forename: Alison
authors.initials: A
authors.lastname: Rowell
authors.forename: Juliane
authors.initials: J
authors.lastname: Daartz
authors.forename: Jay S
authors.initials: JS
authors.lastname: Loeffler
authors.forename: Helen A
authors.initials: HA
authors.lastname: Shih
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D001479:Basal Ganglia / Q000002:abnormalities / Q000098:blood supply; D001933:Brain Stem / Q000002:abnormalities / Q000098:blood supply; D002648:Child; D005260:Female; D005500:Follow-Up Studies; D051271:Headache Disorders, Secondary / Q000209:etiology; D006801:Humans; D002538:Intracranial Arteriovenous Malformations / Q000150:complications / Q000401:mortality / Q000473:pathology / Q000601:surgery*; D020300:Intracranial Hemorrhages / Q000209:etiology / Q000401:mortality; D008297:Male; D008875:Middle Aged; D061766:Proton Therapy; D016634:Radiosurgery / Q000009:adverse effects / Q000379:methods*; D011879:Radiotherapy Dosage; D012306:Risk; D012422:Rupture, Spontaneous / Q000150:complications / Q000401:mortality; D055815:Young Adult; D011522:Protons
chemical_list: D011522:Protons