Volume-staged radiosurgery for large arteriovenous malformations: an evolving paradigm

Abstract

abbreviatioNs ARE = adverse radiation effect; AVM = arteriovenous malformation; CI = confidence interval; CTCAE V4.0 = Common Terminology Criteria for Adverse Events version 4.0; HR = hazard ratio; mRBAS = modified radiosurgery-based AVM score; SM = Spetzler-Martin; SRS = stereotactic radiosurgery; VRAS = Virginia Radiosurgery AVM Scale; VS = volume staged. submitted July 17, 2014. accepted December 9, 2014. iNclude wheN citiNg Published online July 3, 2015; DOI: 10.3171/2014.12.JNS141308. disclosure The authors report no conflict of interest concerning the materials or methods used in this study or the findings specified in this paper. Dr. Dowd adjudicated the FRED Trial (MicroVention). * Drs. Seymour and Sneed contributed equally to this work. obJective Large arteriovenous malformations (AVMs) remain difficult to treat, and ideal treatment parameters for volume-staged stereotactic radiosurgery (VS-SRS) are still unknown. The object of this study was to compare VS-SRS treatment outcomes for AVMs larger than 10 ml during 2 eras; Era 1 was 1992-March 2004, and Era 2 was May 2004-2008. In Era 2 the authors prospectively decreased the AVM treatment volume, increased the radiation dose per stage, and shortened the interval between stages. methods All cases of VS-SRS treatment for AVM performed at a single institution were retrospectively reviewed. results Of 69 patients intended for VS-SRS, 63 completed all stages. The median patient age at the first stage of VS-SRS was 34 years (range 9-68 years). The median modified radiosurgery-based AVM score (mRBAS), total AVM volume, and volume per stage in Era 1 versus Era 2 were 3.6 versus 2.7, 27.3 ml versus 18.9 ml, and 15.0 ml versus 6.8 ml, respectively. The median radiation dose per stage was 15.5 Gy in Era 1 and 17.0 Gy in Era 2, and the median clinical follow-up period in living patients was 8.6 years in Era 1 and 4.8 years in Era 2. All outcomes were measured from the first stage of VS-SRS. Near or complete obliteration was more common in Era 2 (log-rank test, p = 0.0003), with 3- and 5-year probabilities of 5% and 21%, respectively, in Era 1 compared with 24% and 68% in Era 2. Radiosurgical dose, AVM volume per stage, total AVM volume, era, compact nidus, Spetzler-Martin grade, and mRBAS were significantly associated with near or complete obliteration on univariate analysis. Dose was a strong predictor of response (Cox proportional hazards, p < 0.001, HR 6.99), with 3- and 5-year probabilities of near or complete obliteration of 5% and 16%, respectively, at a dose < 17 Gy versus 23% and 74% at a dose ≥ 17 Gy. Dose per stage, compact nidus, and total AVM volume remained significant predictors of near or complete obliteration on multivariate analysis. Seventeen patients (25%) had salvage surgery, SRS, and/or embolization. Allowing for salvage therapy, the probability of cure was more common in Era 2 (log-rank test, p = 0.0007) with 5-year probabilities of 0% in Era 1 versus 41% in Era 2. The strong trend toward improved cure in Era 2 persisted on multivariate analysis...

Results of volume-staged fractionated Gamma Knife radiosurgery for large complex arteriovenous malformations: obliteration rates and clinical outcomes of an evolving treatment paradigm

“…19 A few studies have shown promising results in terms of obliteration rates and adverse events following volume-staged SRS for large cerebral AVMs. Our obliteration rate of 42% is in line with results previously reported by others, 2,3,6,11,13,23,26,27 which range from 10% to 62% for series describing more than 10 patients. A significant proportion of our patients had a nidus characterized by diffuse morphology and features of perinidal angiogenesis and high nidal flow; these features are associated with a lower rate of postradiosurgical obliteration.…”

“…Many options are theoretically available within the armamentarium of the treating neurosurgeon. Resection of an AVM previously reduced by GKRS can be an effective option, as reported by Seymour et al 26 Repeating a radiosurgical procedure can also be an effective option, so long as it is technically feasible according to the previously irradiated volumes and dosimetry plan, and adverse event risks are carefully weighed.…”

“…1,[8][9][10]22,28 In previously reported series of volume-staged GKRS treatment for AVMs, the postradiosurgical hemorrhage rate ranged from 14.2% up to 27.7%. 2,3,6,11,13,23,26,27 In addition, Huang et al 11 , Sirin et al 31 , and Kano et al 13 detailed neurological outcomes for patients who suffered a postradiosurgical bleeding episode: 8/19 (42%) deaths were reported overall. In our series, none of the patients who presented acutely with intracerebral hemorrhage experienced a rebleeding episode, and we discovered only 2 (10%) patients who suffered from a bleeding episode after radiosurgery.…”

“…A few series report promising results using volume-staged radiosurgery for large cerebral AVMs. 2,3,6,11,13,23,26,27 We think volume-staged radiosurgery should be considered the first line of treatment for these formidable cerebral vascular malformations, and here we report the results of our experience with such a treatment paradigm. Our aim was to analyze the outcome of volume-staged radiosurgery on large AVMs, and our results show how this strategy carries a significant lesion volume reduction and reasonably low complication rates.…”

Spatiotemporal Fractionation Schemes for Irradiating Large Cerebral Arteriovenous Malformations

“…Volume-staged radiosurgery [7,8,9]: In this approach, the AVM is divided into several regions (typically 2–4). Each region is treated separately with a high single fraction dose.…”