Radiosurgery for Cerebral Arteriovenous Malformations in A Randomized Trial of Unruptured Brain Arteriovenous Malformations (ARUBA)-Eligible Patients

Cerebral arteriovenous malformations (AVMs) are rare vascular lesions detected at an annual incidence of ≈1 in 100 000. The natural history of unruptured AVMs is more benign than ruptured ones, primarily because of their lower hemorrhage risk. The only currently available strategy for AVM management that provides durable relief from the risk of hemorrhage is complete obliteration of the nidus. Management of unruptured AVMs, whether by microsurgery, radiosurgery, or embolization alone or in combination, may be associated with treatment-related morbidity. A Randomized Trial of Unruptured Brain AVMs (ARUBA) was a multicenter, randomized controlled trial of intervention versus medical management for patients with unruptured AVMs. The analysis that suggested that patients have a significantly higher rate of neurological morbidity and mortality after intervention. Criticisms of ARUBA included Background and Purpose—The benefit of intervention for patients with unruptured cerebral arteriovenous malformations (AVMs) was challenged by results demonstrating superior clinical outcomes with conservative management from A Randomized Trial of Unruptured Brain AVMs (ARUBA). The aim of this multicenter, retrospective cohort study is to analyze the outcomes of stereotactic radiosurgery for ARUBA-eligible patients. Methods—We combined AVM radiosurgery outcome data from 7 institutions participating in the International Gamma Knife Research Foundation. Patients with ≥12 months of follow-up were screened for ARUBA eligibility criteria. Favorable outcome was defined as AVM obliteration, no postradiosurgery hemorrhage, and no permanently symptomatic radiation– induced changes. Adverse neurological outcome was defined as any new or worsening neurological symptoms or death. Results—The ARUBA-eligible cohort comprised 509 patients (mean age, 40 years). The Spetzler–Martin grade was I to II in 46% and III to IV in 54%. The mean radiosurgical margin dose was 22 Gy and follow-up was 86 months. AVM obliteration was achieved in 75%. The postradiosurgery hemorrhage rate during the latency period was 0.9% per year. Symptomatic and permanent radiation–induced changes occurred in 11% and 3%, respectively. The rates of favorable outcome, adverse neurological outcome, permanent neurological morbidity, and mortality were 70%, 13%, 5%, and 4%, respectively. Conclusions—Radiosurgery may provide durable clinical benefit in some ARUBA-eligible patients. On the basis of the natural history of untreated, unruptured AVMs in the medical arm of ARUBA, we estimate that a follow-up duration of 15 to 20 years is necessary to realize a potential benefit of radiosurgical intervention for conservative management in unruptured patients with AVM. (Stroke. 2016;47:00-00. DOI: 10.1161/STROKEAHA.115.011400.)