• Hideyuki Kano, Douglas Kondziolka, John C Flickinger, Kyung-Jae Park, Phillip V Parry, Huai-che Yang, Sait Sirin, Ajay Niranjan, Josef Novotny, and L Dade Lunsford.
• Department of Neurological Surgery, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania 15213, USA.
• J. Neurosurg. 2012 Jan 1;116(1):54-65.

ObjectThe object of this study was to define the long-term outcomes and risks of arteriovenous malformation (AVM) management using 2 or more stages of stereotactic radiosurgery (SRS) for symptomatic large-volume lesions unsuitable for surgery.MethodsIn 1992, the authors prospectively began to stage the treatment of anatomical components to deliver higher single doses to AVMs with a volume of more than 10 cm(3). Forty-seven patients with such AVMs underwent volume-staged SRS. In this series, 18 patients (38%) had a prior hemorrhage and 21 patients (45%) underwent prior embolization. The median interval between the first-stage SRS and the second-stage SRS was 4.9 months (range 2.8-13.8 months). The median target volume was 11.5 cm(3) (range 4.0-26 cm(3)) in the first-stage SRS and 9.5 cm(3) in the second-stage SRS. The median margin dose was 16 Gy (range 13-18 Gy) for both stages.ResultsIn 17 patients, AVM obliteration was confirmed after 2-4 SRS procedures at a median follow-up of 87 months (range 0.4-209 months). Five patients had near-total obliteration (volume reduction > 75% but residual AVM). The actuarial rates of total obliteration after 2-stage SRS were 7%, 20%, 28%, and 36% at 3, 4, 5, and 10 years, respectively. The 5-year total obliteration rate after the initial staged volumetric SRS with a margin dose of 17 Gy or more was 62% (p = 0.001). Sixteen patients underwent additional SRS at a median interval of 61 months (range 33-113 months) after the initial 2-stage SRS. The overall rates of total obliteration after staged and repeat SRS were 18%, 45%, and 56% at 5, 7, and 10 years, respectively. Ten patients sustained hemorrhage after staged SRS, and 5 of these patients died. Three of 16 patients who underwent repeat SRS sustained hemorrhage after the procedure and died. Based on Kaplan-Meier analysis (excluding the second hemorrhage in the patient who had 2 hemorrhages), the cumulative rates of AVM hemorrhage after SRS were 4.3%, 8.6%, 13.5%, and 36.0% at 1, 2, 5, and 10 years, respectively. This corresponded to annual hemorrhage risks of 4.3%, 2.3%, and 5.6% for Years 0-1, 1-5, and 5-10 after SRS. Multiple hemorrhages before SRS correlated with a significantly higher risk of hemorrhage after SRS. Symptomatic adverse radiation effects were detected in 13% of patients, but no patient died as a result of an adverse radiation effect. Delayed cyst formation did not occur in any patient after SRS.ConclusionsProspective volume-staged SRS for large AVMs unsuitable for surgery has potential benefit but often requires more than 2 procedures to complete the obliteration process. To have a reasonable chance of benefit, the minimum margin dose should be 17 Gy or greater, depending on the AVM location. In the future, prospective volume-staged SRS followed by embolization (to reduce flow, obliterate fistulas, and occlude associated aneurysms) may improve obliteration results and further reduce the risk of hemorrhage after SRS.

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