title: International multicenter cohort study of pediatric brain arteriovenous malformations. Part 2: Outcomes after stereotactic radiosurgery.
abstract: OBJECTIVE Pediatric patients (age < 18 years) harboring brain arteriovenous malformations (AVMs) are burdened with a considerably higher cumulative lifetime risk of hemorrhage than adults. Additionally, the pediatric population was excluded from recent prospective comparisons of intervention versus conservative management for unruptured AVMs. The aims of this multicenter, retrospective cohort study are to analyze the outcomes after stereotactic radiosurgery for unruptured and ruptured pediatric AVMs. METHODS We analyzed and pooled AVM radiosurgery data from 7 participating in the International Gamma Knife Research Foundation. Patients younger than 18 years of age who had at least 12 months of follow-up were included in the study cohort. Favorable outcome was defined as AVM obliteration, no post-radiosurgical hemorrhage, and no permanently symptomatic radiation-induced changes (RIC). The post-radiosurgery outcomes of unruptured versus ruptured pediatric AVMs were compared, and statistical analyses were performed to identify predictive factors. RESULTS The overall pediatric AVM cohort comprised 357 patients with a mean age of 12.6 years (range 2.8-17.9 years). AVMs were previously treated with embolization, resection, and fractionated external beam radiation therapy in 22%, 6%, and 13% of patients, respectively. The mean nidus volume was 3.5 cm3, 77% of AVMs were located in eloquent brain areas, and the Spetzler-Martin grade was III or higher in 59%. The mean radiosurgical margin dose was 21 Gy (range 5-35 Gy), and the mean follow-up was 92 months (range 12-266 months). AVM obliteration was achieved in 63%. During a cumulative latency period of 2748 years, the annual post-radiosurgery hemorrhage rate was 1.4%. Symptomatic and permanent radiation-induced changes occurred in 8% and 3%, respectively. Favorable outcome was achieved in 59%. In the multivariate logistic regression analysis, the absence of prior AVM embolization (p = 0.001) and higher margin dose (p < 0.001) were found to be independent predictors of a favorable outcome. The rates of favorable outcome for patients treated with a margin dose ≥ 22 Gy vs < 22 Gy were 78% (110/141 patients) and 47% (101/216 patients), respectively. A margin dose ≥ 22 Gy yielded a significantly higher probability of a favorable outcome (p < 0.001). The unruptured and ruptured pediatric AVM cohorts included 112 and 245 patients, respectively. Ruptured AVMs had significantly higher rates of obliteration (68% vs 53%, p = 0.005) and favorable outcome (63% vs 51%, p = 0.033), with a trend toward a higher incidence of post-radiosurgery hemorrhage (10% vs 4%, p = 0.07). The annual post-radiosurgery hemorrhage rates were 0.8% for unruptured and 1.6% for ruptured AVMs. CONCLUSIONS Radiosurgery is a reasonable treatment option for pediatric AVMs. Obliteration and favorable outcomes are achieved in the majority of patients. The annual rate of latency period hemorrhage after radiosurgery for both ruptured and unruptured pediatric AVM patients conveys a significant risk until the nidus is obliterated.
authors.affiliation: University of Miami, Department of Neurological Surgery, Miami, Florida.
authors.forename: Robert M
authors.initials: RM
authors.lastname: Starke
authors.affiliation: University of Virginia, Department of Neurosurgery, Charlottesville, Virginia.
authors.forename: Dale
authors.initials: D
authors.lastname: Ding
authors.affiliation: University of Pittsburgh, Department of Neurological Surgery, Pittsburgh, Pennsylvania.
authors.forename: Hideyuki
authors.initials: H
authors.lastname: Kano
authors.affiliation: University of Sherbrooke, Division of Neurosurgery, Sherbrooke, Quebec, Canada; and.
authors.forename: David
authors.initials: D
authors.lastname: Mathieu
authors.affiliation: New York University Langone Medical Center, Department of Neurosurgery, New York, New York.
authors.forename: Paul P
authors.initials: PP
authors.lastname: Huang
authors.affiliation: University of Puerto Rico, Section of Neurological Surgery, San Juan, Puerto Rico.
authors.forename: Caleb
authors.initials: C
authors.lastname: Feliciano
authors.affiliation: University of Puerto Rico, Section of Neurological Surgery, San Juan, Puerto Rico.
authors.forename: Rafael
authors.initials: R
authors.lastname: Rodriguez-Mercado
authors.affiliation: University of Puerto Rico, Section of Neurological Surgery, San Juan, Puerto Rico.
authors.forename: Luis
authors.initials: L
authors.lastname: Almodovar
authors.affiliation: Beaumont Health System, Department of Radiation Oncology, Royal Oak, Michigan.
authors.forename: Inga S
authors.initials: IS
authors.lastname: Grills
authors.affiliation: Cleveland Clinic Foundation, Department of Neurosurgery, Cleveland, Ohio.
authors.forename: Danilo
authors.initials: D
authors.lastname: Silva
authors.affiliation: Cleveland Clinic Foundation, Department of Neurosurgery, Cleveland, Ohio.
authors.forename: Mahmoud
authors.initials: M
authors.lastname: Abbassy
authors.affiliation: Cleveland Clinic Foundation, Department of Neurosurgery, Cleveland, Ohio.
authors.forename: Symeon
authors.initials: S
authors.lastname: Missios
authors.affiliation: New York University Langone Medical Center, Department of Neurosurgery, New York, New York.
authors.forename: Douglas
authors.initials: D
authors.lastname: Kondziolka
authors.affiliation: Cleveland Clinic Foundation, Department of Neurosurgery, Cleveland, Ohio.
authors.forename: Gene H
authors.initials: GH
authors.lastname: Barnett
authors.affiliation: University of Pittsburgh, Department of Neurological Surgery, Pittsburgh, Pennsylvania.
authors.forename: L
authors.initials: L
authors.lastname: Dade Lunsford
authors.affiliation: University of Virginia, Department of Neurosurgery, Charlottesville, Virginia.
authors.forename: Jason P
authors.initials: JP
authors.lastname: Sheehan
mesh_terms: D000293:Adolescent; D002648:Child; D002675:Child, Preschool; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D038622:Internationality; D002538:Intracranial Arteriovenous Malformations / Q000453:epidemiology* / Q000601:surgery*; D053208:Kaplan-Meier Estimate; D016015:Logistic Models; D008297:Male; D015999:Multivariate Analysis; D019106:Postoperative Hemorrhage / Q000453:epidemiology; D011379:Prognosis; D016016:Proportional Hazards Models; D016634:Radiosurgery / Q000009:adverse effects; D011879:Radiotherapy Dosage; D012189:Retrospective Studies; D012307:Risk Factors; D012737:Sex Factors; D016896:Treatment Outcome
keywords: ARUBA = A Randomized Trial of Unruptured Brain AVMs; AVM = arteriovenous malformation; EBRT = fractionated external beam radiation therapy; Gamma Knife; ICH = intracranial hemorrhage; IGKRF = International Gamma Knife Research Foundation; KOSCHI = King Outcome Scale for Childhood Head Injury; RBAS = radiosurgery-based AVM score; RIC = radiation-induced changes; RIN = radiation-induced neoplasia; SAIVM = Scottish Audit of Intracranial Vascular Malformations; VRAS = Virginia Radiosurgery AVM Scale; intracranial arteriovenous malformation; intracranial hemorrhages; pediatric; stereotactic radiosurgery; stroke; vascular disorders; vascular malformations