title: Results of volume-staged fractionated Gamma Knife radiosurgery for large complex arteriovenous malformations: obliteration rates and clinical outcomes of an evolving treatment paradigm.
abstract: OBJECTIVE There are few reported series regarding volume-staged Gamma Knife radiosurgery (GKRS) for the treatment of large, complex, cerebral arteriovenous malformations (AVMs). The object of this study was to report the results of using volume-staged Gamma Knife radiosurgery for patients affected by large and complex AVMs. METHODS Data from 20 patients with large AVMs were prospectively included in the authors' AVM database between 2004 and 2012. A staging strategy was used when treating lesion volumes larger than 10 cm3. Hemorrhage and seizures were the presenting clinical feature for 6 (30%) and 8 (40%) patients, respectively. The median AVM volume was 15.9 cm3(range 10.1-34.3 cm3). The mean interval between stages (± standard deviation) was 15 months (± 9 months). The median margin dose for each stage was 20 Gy (range 18-25 Gy). RESULTS Obliteration was confirmed in 8 (42%) patients after a mean follow-up of 45 months (range 19-87 months). A significant reduction (> 75%) of the original nidal volume was achieved in 4 (20%) patients. Engel Class I-II seizure status was reported by 75% of patients presenting with seizures (50% Engel Class I and 25% Engel Class II) after radiosurgery. After radiosurgery, 71.5% (5/7) of patients who had presented with a worsening neurological deficit reported a complete resolution or amelioration. None of the patients who presented acutely because of hemorrhage experienced a new bleeding episode during follow-up. One (5%) patient developed radionecrosis that caused sensorimotor hemisyndrome. Two (10%) patients sustained a bleeding episode after GKRS, although only 1 (5%) was symptomatic. High nidal flow rate and a time interval between stages of less than 11.7 months were factors significantly associated with AVM obliteration (p = 0.021 and p = 0.041, respectively). Patient age younger than 44 years was significantly associated with a greater than 75% reduction in AVM volume but not with AVM obliteration (p = 0.024). CONCLUSIONS According to the results of this study, volume-staged GKRS is an effective and safe treatment strategy for large, complex, cerebral AVMs for which microsurgery or endovascular approaches could carry substantially higher risks to the patient. Radiation doses up to 20 Gy can be safely administered. The time interval between stages should be shorter than 11.7 months to increase the chance of obliteration. High nidal flow and a patient age younger than 44 years were factors associated with nidus obliteration and significant nidus reduction, respectively.
authors.affiliation: Departments of 1 Neurosurgery and Radiosurgery, and.
authors.forename: Alberto
authors.initials: A
authors.lastname: Franzin
authors.affiliation: Departments of 1 Neurosurgery and Radiosurgery, and.
authors.forename: Pietro
authors.initials: P
authors.lastname: Panni
authors.affiliation: Departments of 1 Neurosurgery and Radiosurgery, and.
authors.forename: Giorgio
authors.initials: G
authors.lastname: Spatola
authors.affiliation: Medical Physics, IRCCS San Raffaele Scientific Institute, Milan, Italy.
authors.forename: Antonella
authors.initials: A
authors.lastname: Del Vecchio
authors.affiliation: Departments of 1 Neurosurgery and Radiosurgery, and.
authors.forename: Alberto L
authors.initials: AL
authors.lastname: Gallotti
authors.affiliation: Medical Physics, IRCCS San Raffaele Scientific Institute, Milan, Italy.
authors.forename: Carmen R
authors.initials: CR
authors.lastname: Gigliotti
authors.affiliation: Departments of 1 Neurosurgery and Radiosurgery, and.
authors.forename: Andrea
authors.initials: A
authors.lastname: Cavalli
authors.affiliation: Departments of 1 Neurosurgery and Radiosurgery, and.
authors.forename: Carmine A
authors.initials: CA
authors.lastname: Donofrio
authors.affiliation: Departments of 1 Neurosurgery and Radiosurgery, and.
authors.forename: Pietro
authors.initials: P
authors.lastname: Mortini
mesh_terms: D000293:Adolescent; D000328:Adult; D005260:Female; D006801:Humans; D002538:Intracranial Arteriovenous Malformations / Q000473:pathology / Q000532:radiotherapy*; D008297:Male; D008875:Middle Aged; D016634:Radiosurgery / Q000295:instrumentation / Q000379:methods*; D012189:Retrospective Studies; D016896:Treatment Outcome; D055815:Young Adult
keywords: AED = antiepileptic drug; AUC = area under the curve; AVM = arteriovenous malformation; DSA = digital subtraction angiography; GKRS = Gamma Knife radiosurgery; Gamma Knife; ROC = receiver operating characteristic; SM = Spetzler-Martin; arteriovenous malformations; clinical outcome; hemorrhage; stereotactic radiosurgery; vascular disorders; volume