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Zachary A. Seymour, Penny K. Sneed, Nalin Gupta, Michael T. Lawton, Annette M. Molinaro, William Young, Christopher F. Dowd, Van V. Halbach, Randall T. Higashida, and Michael W. McDermott


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.


All cases of VS-SRS treatment for AVM performed at a single institution were retrospectively reviewed.


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 even when considering mRBAS (Cox proportional hazards, p = 0.055, HR 4.01, 95% CI 0.97–16.59). The complication rate was 29% in Era 1 compared with 13% in Era 2 (Cox proportional hazards, not significant).


VS-SRS is an option to obliterate or downsize large AVMs. Decreasing the AVM treatment volume per stage to ≤ 8 ml with this technique allowed a higher dose per fraction and decreased time to response, as well as improved rates of near obliteration and cure without increasing complications. Reducing the volume of these very large lesions can facilitate a surgical approach for cure.

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Matthew D. Smyth, Penny K. Sneed, Samuel F. Ciricillo, Michael S. Edwards, William M. Wara, David A. Larson, Michael T. Lawton, Philip H. Gutin, and Michael W. Mcdermott

Object. Stereotactic radiosurgery for arteriovenous malformations (AVMs) is an accepted treatment option, but few reports have been published on the results of this treatment in children. In this study the authors describe a series of pediatric patients with a minimum follow-up duration of 36 months.

Methods. From 1991 to 1997, 40 children (26 boys and 14 girls) with AVMs were treated with radiosurgery at the University of California at San Francisco (UCSF). Follow-up information was available for 31 children (20 boys and 11 girls) in whom the median age at initial treatment was 11.2 years (range 3.4–17.5 years). The median follow-up duration was 60 months (range 6–99 months). Sixteen percent of the AVMs were Spetzler—Martin Grade II; 68%, Grade III; 10%, Grade IV; and 6%, Grade V. The mean volume of the AVMs was 5.37 cm3 and the median volume was 1.6 cm3. The mean marginal dose of radiation was 16.7 Gy and the median dose was 18 Gy (range 12–19 Gy).

Angiography performed in 26 children confirmed obliteration of the AVM nidus in nine patients (35%), partial response in 16 patients (62%), and no response in one patient (4%). In five patients who refused angiography, magnetic resonance (MR) imaging revealed obliteration in two patients and partial response in three patients, bringing the overall obliteration rate associated with initial radiosurgery to 35%. Logistic regression analysis confirmed a significant correlation between marginal dose prescription and response (p = 0.025); in AVMs that received at least 18 Gy there was a 10-fold increase in the obliteration rate (63%) over AVMs that received a lower dose. Lesions smaller than 3 cm3 were associated with a sixfold increased obliteration rate (53%) over lesions larger than 3 cm3 (8%), but AVM volume was not a statistically significant predictor of response (p = 0.09). Twelve patients have since undergone repeated radiosurgery and are currently being followed up with serial MR imaging studies (in five cases, the AVM is now obliterated). During the follow-up period (1918 patient-months) there were eight hemorrhages in five patients, with a cumulative posttreatment hemorrhage rate of 3.2%/patient/year in the 1st year and a rate of 4.3%/patient/year over the first 3 years. There were two permanent neurological complications (6%) and no deaths in this study.

Conclusions. The lower overall obliteration rate reported in this series is most likely due to the larger mean AVM volumes treated at UCSF as well as conservative dose—volume prescriptions delivered to children. Significantly higher obliteration rates were observed when a marginal radiation dose of at least 18 Gy was delivered. The permanent complication rate is low and should encourage those treating children to use doses similar to those used in adults.

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Adib A. Abla, William Caleb Rutledge, Zachary A. Seymour, Diana Guo, Helen Kim, Nalin Gupta, Penny K. Sneed, Igor J. Barani, David Larson, Michael W. McDermott, and Michael T. Lawton


The surgical treatment of many large arteriovenous malformations (AVMs) is associated with substantial risks, and many are considered inoperable. Furthermore, AVMs larger than 3 cm in diameter are not usually treated with conventional single-session radiosurgery encompassing the entire AVM volume. Volume-staged stereotactic radiosurgery (VS-SRS) is an option for large AVMs, but it has mixed results. The authors report on a series of patients with high-grade AVMs who underwent multiple VS-SRS sessions with resultant downgrading of the AVMs, followed by resection.


A cohort of patients was retrieved from a single-institution AVM patient registry consisting of prospectively collected data. VS-SRS was performed as a planned intentional treatment. Surgery was considered as salvage therapy in select patients.


Sixteen AVMs underwent VS-SRS followed by surgery. Four AVMs presented with rupture. The mean patient age was 25.3 years (range 13–54 years). The average initial Spetzler-Martin grade before any treatment was 4, while the average supplemented Spetzler-Martin grade (Spetzler-Martin plus Lawton-Young) was 7.1. The average AVM size in maximum dimension was 5.9 cm (range 3.3–10 cm). All AVMs were supratentorial in location and all except one were in eloquent areas of the brain, with 7 involving primary motor cortex. The mean number of VS-SRS sessions was 2.7 (range 2–5 sessions). The mean interval between first VS-SRS session and resection was 5.7 years. There were 4 hemorrhages that occurred after VS-SRS. The average Spetzler-Martin grade was reduced to 2.5 (downgrade, −1.5) and the average supplemented Spetzler-Martin grade was reduced to 5.6 (downgrade, −1.5). The maximum AVM size was reduced to an average of 3.0 cm (downsize = −2.9 cm). The mean modified Rankin Scale (mRS) scores were 1.2, 2.3, and 2.2 before VS-SRS, before surgery, and at last follow-up, respectively (mean follow-up, 6.9 years). Fifteen AVMs were cured after surgery. Ten patients had good outcomes at last follow-up (7 with mRS Score 0 or 1, and 3 with mRS Score 2). There were 2 deaths (both mRS Score 1 before treatment) and 4 patients with mRS Score 3 outcome (from mRS Scores 0, 1, and 2 [n = 2]).


Volume-staged SRS can downgrade AVMs, transforming high-grade AVMs (initially considered inoperable) into operable AVMs with acceptable surgical risks. This treatment paradigm offers an alternative to conservative observation for young patients with unruptured AVMs and long life expectancy, where the risk of hemorrhage is substantial. Difficult AVMs were cured in 15 patients. Surgical morbidity associated with downgraded AVMs is reduced to that of postradiosurgical/preoperative supplemented Spetzler-Martin grades, not their initial AVM grades.

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Matthew B. Potts, Sunil A. Sheth, Jonathan Louie, Matthew D. Smyth, Penny K. Sneed, Michael W. McDermott, Michael T. Lawton, William L. Young, Steven W. Hetts, Heather J. Fullerton, and Nalin Gupta


Stereotactic radiosurgery (SRS) is an established treatment modality for brain arteriovenous malformations (AVMs) in children, but the optimal treatment parameters and associated treatment-related complications are not fully understood. The authors present their single-institution experience of using SRS, at a relatively low marginal dose, to treat AVMs in children for nearly 20 years; they report angiographic outcomes, posttreatment hemorrhage rates, adverse treatment-related events, and functional outcomes.


The authors conducted a retrospective review of 2 cohorts of children (18 years of age or younger) with AVMs treated from 1991 to 1998 and from 2000 to 2010.


A total of 80 patients with follow-up data after SRS were identified. Mean age at SRS was 12.7 years, and 56% of patients had hemorrhage at the time of presentation. Median target volume was 3.1 cm3 (range 0.09–62.3 cm3), and median prescription marginal dose used was 17.5 Gy (range 12–20 Gy). Angiograms acquired 3 years after treatment were available for 47% of patients; AVM obliteration was achieved in 52% of patients who received a dose of 18–20 Gy and in 16% who received less than 18 Gy. At 5 years after SRS, the cumulative incidence of hemorrhage was 25% (95% CI 16%–37%). No permanent neurological deficits occurred in patients who did not experience posttreatment hemorrhage. Overall, good functional outcomes (modified Rankin Scale Scores 0–2) were observed for 78% of patients; for 66% of patients, functional status improved or remained the same as before treatment.


A low marginal dose minimizes SRS-related neurological deficits but leads to low rates of obliteration and high rates of hemorrhage. To maximize AVM obliteration and minimize posttreatment hemorrhage, the authors recommend a prescription marginal dose of 18 Gy or more. In addition, SRS-related symptoms such as headache and seizures should be considered when discussing risks and benefits of SRS for treating AVMs in children.