International multicenter cohort study of pediatric brain arteriovenous malformations. Part 2: Outcomes after stereotactic radiosurgery
Authors: Starke Robert M. , Ding Dale , Kano Hideyuki , Mathieu David , Huang Paul P. , Feliciano Caleb , Rodriguez-Mercado Rafael , Almodovar Luis , Grills Inga S. , Silva Danilo , Abbassy Mahmoud , Missios Symeon , Kondziolka Douglas , Barnett Gene H. , Dade Lunsford L. , Sheehan Jason P. 
Published: December 2016

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.