Multimodal cerebral arteriovenous malformation treatment: a 12-year experience and comparison of key outcomes to ARUBA

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  • 1 Department of Radiology, Massachusetts General Hospital, Harvard Medical School;
  • 2 Department of Neurosurgery, Massachusetts General Hospital, Harvard Medical School;
  • 3 Neurosurgical Service, Beth Israel Deaconess Medical Center; and
  • 4 Department of Neurology, Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts
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OBJECTIVE

Curative treatment of unruptured brain arteriovenous malformations (AVMs) remains controversial after the only randomized controlled trial, A Randomized Trial of Unruptured Brain Arteriovenous Malformations (ARUBA), was halted prematurely because interim analysis revealed superiority of the medical management group. In contrast, meta-analyses of retrospective cohorts suggest that intervention is much safer than was found in ARUBA.

METHODS

The authors retrospectively analyzed 318 consecutive adult patients with brain AVMs treated at their institution with embolization, surgery, and/or proton beam radiosurgery. Analysis was performed in 142 ARUBA-eligible patients (baseline modified Rankin Scale [mRS] score 0–1, no history of hemorrhage), and results were compared to primary and secondary outcomes from ARUBA, as well as to natural history cohorts.

RESULTS

The annualized stroke rate (hemorrhagic or ischemic) in this cohort was 1.8%, 4.9% in the first 12 months and 0.8% after the first 12 months, which was lower than in natural history studies and the ARUBA medical management arm (p = 0.001). The primary ARUBA endpoint of symptomatic stroke was reached in 13 patients (9.2%), which compares favorably to the ARUBA intervention arm (39.6%, p = 0.0001) and is similar to the ARUBA medical management arm (9.2%, p = 1.0). The secondary ARUBA endpoint (mRS score ≥ 2 at 5 years of follow-up) was reached in 14.3% of patients, compared to 40.5% in the ARUBA intervention arm (p = 0.002) and 16.7% in the ARUBA medical management arm (p = 0.6).

CONCLUSIONS

This multimodal approach to the selection and treatment of patients with brain AVMs yields good clinical outcomes with key safety endpoints (stroke, death, and mRS score 0–1) better than the ARUBA intervention arm and similar to the ARUBA medical arm at 5 years of follow-up. Results compare favorably to natural history cohorts at longer follow-up times. This suggests that tertiary care centers with integrated programs, expertise in patient selection, and individualized treatment approaches may allow for better clinical outcomes than reported in ARUBA. It supports current registry studies and merits consideration of future randomized controlled trials in patients with brain AVMs.

ABBREVIATIONS ARUBA = A Randomized Trial of Unruptured Brain Arteriovenous Malformations; cAVM = cerebral arteriovenous malformation; mRS = modified Rankin Scale; NASSAU = New Assessment of Cerebral Arteriovenous Malformations yet Unruptured; RCT = randomized controlled trial; SM = Spetzler-Martin; UCSF = University of California, San Francisco.

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Contributor Notes

Correspondence James D. Rabinov: Massachusetts General Hospital, Boston, MA. jrabinov@mgh.harvard.edu.

INCLUDE WHEN CITING Published online November 1, 2019; DOI: 10.3171/2019.8.JNS19998.

Disclosures Dr. Hirsch is a consultant for Medtronic. He is also a Data Monitoring Committee member for Relievent, a Data and Safety Monitoring Board member for Cerenovus, and a grant holder with Neiman Health Policy Institute. Dr. Patel is a consultant for Medtronic, Penumbra, and MicroVention.

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