Arteriovenous Malformations Score Research Articles

CyberKnife based fractionated stereotactic radiotherapy as an upfront treatment for cerebral arteriovenous malformation

BackgroundTo explore the therapeutic outcomes of CyberKnife based fractionated stereotactic radiotherapy (CKFRT) for patients with cerebral arteriovenous malformations (AVM). MethodsBetween January 2008 and October 2020, 45 patients underwent CKFRT for cerebral AVMs as a first treatment. The delineation of AVM targets included AVM nidus. The mean target volume was 4.07 cm3, and 9 lesions (20%) were larger than 10.0 cm3. The mean marginal dose was 24 Gy (range, 20–35 Gy). CKFRT was delivered in median 3 fractions (range, 2 ∼ 5 fractions). AVM obliteration following CKFRT was confirmed by magnetic resonance imaging or angiography. ResultsDuring a median follow-up of 47 (5–148) months, complete obliteration and partial obliteration of AVM after CKFRT were obtained in 23 (51%) and 13 (29%) patients, respectively. Median time to complete obliteration was 39 (15–63) months. The cumulative probability of complete obliteration rate at 3 years was 47%. Complete obliteration rate of AVM was associated with Radiosurgery-based AVM score, which was consisted of AVM volume, patients age, and AVM location. One (2%) patient had hemorrhage during the follow-up period. ConclusionsCKFRT is an effective primary treatment for patients with cerebral AVMs with a low hemorrhage risk.

External validation of the R2eD AVM scoring system to assess rupture risk in pediatric AVM patients.

The assessment of hemorrhagic risk is of central importance in the management of pediatric brain arteriovenous malformations (AVMs). A recently published scoring system, the R2eD AVM (race, exclusive deep location or not, AVM size < 3 or ≥ 3, venous drainage exclusively deep or not, and monoarterial feeding or >1 arterial feeders) considers patient race and AVM location, size, venous drainage, and arterial supply and was successfully externally validated for use in adults to predict the risk of AVM hemorrhagic presentation. In this study the authors sought to externally validate the R2eD AVM score for prediction of hemorrhagic risk in the pediatric AVM population. A pediatric database at Boston Children's Hospital was retrospectively reviewed for all patients with a diagnosis of intracranial AVM. Exclusion criteria included age > 21 years, multiple AVMs, and incomplete clinical/radiographic data. Demographic data and R2eD AVM score calculations were collected for all patients. Univariate binary logistic regression and multivariate stepwise backward elimination models were used to determine factors associated with hemorrhagic presentation. A total of 212 AVMs were identified in 212 patients with vascular anomalies from 1995 to 2021, and 144 patients met the inclusion criteria (74 [51.4%] male, 111 [77.1%] White), of whom 87 (60.4%) patients presented with rupture and 122 (84.7%) underwent resection. The mean age at surgery was 12 years (range 3 months to 20 years). The R2eD AVM scoring system was applied to each patient. The score components of size < 3 cm and exclusive deep venous drainage were significantly associated with rupture risk (p < 0.05). The complete model for the R2eD AVM score had an area under the curve of 0.671 (95% CI 0.586-0.757). This study demonstrated poor external validity of the R2eD AVM score in predicting pediatric AVM rupture risk. The results suggest that future studies are warranted to determine a better scoring method to capture pediatric rupture risk, given the significant differences in clinical presentation in pediatric compared with adult AVM patients.

Hypofractionated Stereotactic Radiotherapy with CyberKnife for Large Arteriovenous Malformations and Arteriovenous Malformations Located in Eloquent Areas.

Literature has yet to establish an appropriate treatment strategy for large arteriovenous malformations (AVMs) and AVMs located in eloquent areas. In this study, the treatment outcomes of hypofractionated stereotactic radiotherapy (HSRT) with CyberKnife (CK) for large AVMs and AVMs in eloquent areas were evaluated. This study retrospectively evaluated 38 consecutive patients with AVMs treated with HSRT in the Japanese Red Cross Medical Center between August 2010 and July 2015. Obliteration rates and hemorrhage rates at 3- and 5-years of follow-up were calculated. Factors for hemorrhage and obliteration were analyzed with logistic regression analysis. Fourteen (36.8%) patients had a history of hemorrhage. Twenty (52.6%) AVMs were larger than 10 mL, and 34 (89.5%) AVMs were located in eloquent areas. The majority of the AVMs (84.2%) were classified into high grades (grades 3, 4, and 5) using the Spetzler-Martin grading scale. The median modified radiosurgery-based AVM score was 2.05, and the median Virginia Radiosurgery AVM Score was 3. The mean marginal dose was 24.5 ± 2.5 Gy. Twenty-three and 15 patients received three- and five-fraction stereotactic radiotherapy, respectively. At 3 and 5 years posttreatment, two (2.0%/year) and six (6.7%/year) patients had hemorrhage with obliteration rates of 15.2% and 16.7%, respectively. AVM localization in eloquent areas was a risk factor for obliteration failure. This study revealed that HSRT with CK for large AVMs and AVMs located in eloquent areas contributed to hemorrhage risk reduction and obliteration, at least in the early stages.

Stereotactic Radiosurgery for A Randomized Trial of Unruptured Brain Arteriovenous Malformations-Eligible Patients: A Meta-Analysis.

The outcomes of A Randomized Trial of Unruptured Brain Arteriovenous Malformations (ARUBA) were controversial, and they suggested that intervention is inferior to medical management for unruptured brain arteriovenous malformations (AVMs). However, several studies have shown that stereotactic radiosurgery (SRS) is an acceptable therapy for unruptured AVMs. To test the hypothesis that ARUBA intervention arm's SRS results are meaningfully inferior to those from similar populations reported by other studies. We performed a literature review to identify SRS studies of patients who met the eligibility criteria for ARUBA. Patient, AVM, treatment, and outcome data were extracted for statistical analysis. Regression analyses were pooled to identify factors associated with post-SRS obliteration and hemorrhage. The study cohort included 8 studies comprising 1620 ARUBA-eligible patients who underwent SRS. At the time of AVM diagnosis, 36% of patients were asymptomatic. The mean follow-up duration was 80 months. Rates of radiologic, symptomatic, and permanent radiation-induced changes were 45%, 11%, and 2%, respectively. The obliteration rate was 68% at last follow-up. The post-SRS hemorrhage and mortality rates were 8%, and 2%, respectively. Lower Spetzler-Martin grade (odds ratios [OR] = 0.84 [0.74-0.95], P = .005), lower radiosurgery-based AVM score (OR = 0.75 [0.64-0.95], P = .011), lower Virginia Radiosurgery AVM Scale (OR = 0.86 [0.78-0.95], P = .003), and higher margin dose (OR = 1.13 [1.02-1.25], P = .025) were associated with obliteration. SRS carries a favorable risk to benefit profile for appropriately selected ARUBA-eligible patients, particularly those with smaller volume AVMs. Our findings suggest that the results of ARUBA do not reflect the real-world safety and efficacy of SRS for unruptured AVMs.

Upfront and Repeated Gamma-Knife Radiosurgery for Small (≤5 mL) Unruptured Brain Arteriovenous Malformation: A Cohort of 249 Consecutive Patients

According to A Randomized Trial of Unruptured Brain Arteriovenous Malformations (ARUBA), conservative treatment seems to be superior to any intervention for unruptured brain arteriovenous malformations (AVMs). This study aims to evaluate safety and efficacy of upfront and repeated Gamma-Knife Radiosurgery (GKRS) in patients harboring small AVMs fulfilling the inclusion criteria of ARUBA. A retrospective study was conducted to evaluate outcomes of unruptured naive brain AVM with a volume ⩽ 5 mL eligible to ARUBA treated by GKRS with at least 3 years of follow-up. From 1992 to 2014, 249 patients fulfilled the inclusion criteria of this study. The median age was 36 years (range: 18-78 years). The median treated volume of the nidus was 1.3 mL (range: 0.4-5 mL) and 63% of the AVM were in eloquent areas. Radiosurgery-based AVM score was 1-1.8 (76%), the Spetzler-Martin grade was II-III (73%), and the Virginia Radiosurgery AVM scale was ≤1 point (75%). The overall AVM obliteration rate was 77.1% after up to 3 GKRS sessions. The median dose at the margin was 24 Gy (15-25 Gy) and the median follow-up was 45 months (range: 36-205 months). Eight patients (3.2%) experienced hemorrhage after GKRS, corresponding to a post-GKRS hemorrhage annual rate of 1.03%. Permanent symptomatic radio-induced changes rate was 2% (4 increased seizures, 1 neurologic deficit). The very low toxicity rate and the high occlusion rate suggest in favor of upfront and repeated GKRS for unruptured small AVMs (⩽5 mL).

Two-Fraction Proton Beam Stereotactic Radiosurgery for Cerebral Arteriovenous Malformations

Stereotactic radiosurgery (SRS) is a well-established treatment option that can obliterate cerebral arteriovenous malformations (AVMs). However, larger AVMs are more challenging to manage, with lower rates of obliteration and higher risk of complications. In this study, we report the obliteration rate and associated adverse effects of planned two-fraction proton SRS (PSRS) used to treat patients with larger AVMs that were deemed inoperable.A retrospective analysis including 75 patients with cerebral AVMs who received two-fraction PSRS at our institution between 1991 and 2019 was conducted. The median AVM nidus volume was 21.5 cc (range 1.4-58.1 cc). AVMs were located in critical/deep locations (basal ganglia, thalamus, or brainstem) in 21.3%. The median total dose for PSRS was 16 Gy(RBE) delivered in two fractions at a median of 7 days apart (range 1-82 days). Factors associated with obliteration and hemorrhage were assessed via univariable and multivariable analyses.Median follow up was 90 months (range 0.9-223.4 months). Total (8 patients, 11%) or partial (28 patients, 37%) obliteration was achieved among 48% of AVMs at a median time of 85.4 months (range 12.2-222.7 months). Five-year cumulative incidence of total obliteration was 29%. Five-year cumulative incidence of hemorrhage post-PSRS was 33%. Lesions with higher AVM scores were more likely to hemorrhage (P = 0.042). The most common adverse effect was Grade 1 headache acutely (11%) and long-term (9%). One patient developed a Grade 2 generalized seizure disorder.Planned two-fraction PSRS may be an effective and safe treatment option for achieving obliteration in patients with larger cerebral AVMs that are inoperable. Post-treatment hemorrhage remains a potential adverse event.D.W. Kim: None. G. Lee: None. P.H. Chapman: None. M.R. Bussiere: Consultant; American College of Radiology. J. Daartz: None. J.S. Loeffler: None. H.A. Shih: Employee; Dartmouth Hitchcock. Research Grant; AbbVie, NIH. Honoraria; UpToDate. Consultant; Cleveland Clinic. Speaker's Bureau; prIME Oncology. advisory; The Radiosurgery Society. director of clinical operations; Massachusetts General Hospital. clinical operational leader; Massachusetts General Hospital.

External Validation of the R2eD AVM Score to Predict the Likelihood of Rupture Presentation of Brain Arteriovenous Malformations

The R2eD AVM scoring system has been recently proposed to predict the risk of hemorrhagic presentation of brain arteriovenous malformations (AVMs). To perform the first external validation of this R2eD AVM score. Over a retrospective 10-yr period from 2009 to 2019, 122 patients with brain AVMs fit the inclusion criteria. All components required to calculate the R2eD AVM score had to be available. Patient demographics and score calculations were recorded, as well as the circumstances of their presentation. Multivariable analysis was performed to assess predictors of rupture in the study cohort. Next, area under the receiver operating characteristics and linear-by-linear association were employed to assess the effectiveness of the models. The mean age of the entire cohort was 45.2 yr, and 8% of patients were nonwhite. A total of 48 (39.3%) patients presented with AVM rupture. In univariable analysis, all 5 categories demonstrated P <.15 association with rupture risk. In multivariable analysis, race (nonwhite), size <3cm, and exclusive deep venous drainage remained in the model with an area under the curve (AUC) of 0.677. The utilization of the R2eD AVM score yielded an AUC of 0.711. Even though mitigated by sample size, this study demonstrated acceptable external validity of the R2eD AVM score.

Long term treatment efficacy & complications of hypofractionated stereotactic radiosurgery in brain arteriovenous malformations

ObjectiveTo evaluate long term treatment efficacy and complications of hypofractionated stereotactic radiosurgery (hfSRS) and identify factors that predict outcomes. MethodsA retrospective review was conducted on 34 consecutive patients who received hfSRS from 2008 to 2017. Demographic, clinical, angio-architectural characteristics, and radiosurgery data were extracted from the Clinical Data Analysis and Reporting System and our unit’s iPlan (BrainLAB, Munich) system. Data was analysed using SPSS. Results5-year obliteration rate was 39.1%. Most patients (n = 29, 85.3%) recovered well with GOS of 4–5. 26.9% (n = 9) patients have at least one post-radiosurgery complication including hemorrhage, neurological deficits, radionecrosis. Neurological morbidity and mortality was 17.6% (n = 6). A higher modified radiosurgery arteriovenous malformation score (mRBAS) is associated with a lower 5-year obliteration rate (Rho = -0.486, p = 0.025). None of the bAVM were obliterated once mRBAS exceeds 5.35. As expected, a larger 20-Gy volume outside lesion is associated with more complications and poorer GOS. Interestingly, irradiated drainage vein volume indexed to AVM volume (iiDVV) correlates with increased risks of post-hfSRS haemorrhage (Rho = 0.472, p = 0.031) and reduced event-free survival (Rho = −0.472, p = 0.031). Once iiDVV exceeds 20%, a high rebleeding rate after hfSRS is anticipated (AUC under ROC 0.889). ConclusionHypofractionated stereotactic radiosurgery is an alternative radiosurgery treatment for bAVM unsuitable for single-fraction SRS. mRBAS predicts obliteration rate and morbidity in hfSRS. Index irradiated drainage vein volume (iiDVV) is associated with event-free survival and rebleeding and should be minimized if feasible.

Long-Term Outcomes Of Hypofractionated Stereotactic Radiotherapy For Treatment Of Arteriovenous Malformation

To evaluate the long-term obliteration and toxicity outcomes of arteriovenous malformation (AVM) treated with hypofractionated stereotactic radiotherapy (HSRT). Retrospective analysis of 40 patients treated for AVMs from 2004-2007 was performed. All the patients were treated with LINAC-based HSRT in five consecutive daily fractions to a prescription dose of 35 Gy using a median isodose line of 80% to the periphery. Eleven patients were lost to follow up and the remaining 29 were included in this study. Patients underwent regular follow up with MRIs and subsequent cerebral angiography for confirmation of nidus obliteration. Acute and long-term toxicity data were collected including rates of symptomatic radiation necrosis (RN), cerebral cyst formation, intracranial hemorrhage (ICH), and death. The median follow-up was 13 years (range 0.9-15.3 years). 20 (69%) were male and 9 (31%) were female. The median age at treatment was 44 years (range 14-62). The most common presenting symptom was intracranial hemorrhage (ICH) (13 pts; 45%). Five patients underwent embolization prior to HSRT. Four lesions were in eloquent locations (13.8%), defined as basal ganglia, thalamus, or brainstem. The median greatest diameter and volume measured 3.9 cm (range 1.8-8.7) and 11.43 cc (range 1.33-108.55), respectively. Median modified Radiosurgery Based AVM Score (mRBAS) was 2.02 (range 0.51-12.45). 23 of the 29 lesions obliterated (79%) with median time to obliteration of 3 years. 25 of the patients (86%) experienced radiation-induced adverse effects. 18 patients (62%) had symptoms that persisted beyond three years post-treatment. Eight patients (28%) had cerebral cyst formation. Seven patients (28%) underwent resection of chronic RN with a median time to surgery of 8 years. Four patients suffered post-treatment ICH with one patient death from associated complications. The experience at this single institution illustrates the importance of long-term follow up in evaluating the treatment of AVM with LINAC-based HSRT. While the obliteration rate of 79% is above average for the treatment of large AVM, a toxicity rate of 86%, which included chronic RN and cyst formation requiring intervention may substantially complicate long-term management and negatively impact quality of life. Risk of long-term HSRT complications must be weighed carefully against risk of hemorrhage and other complications associated with conservative management and open surgery for these lesions.

Pediatric Intracranial Arteriovenous Malformation: Long-Term Outcomes with Linear Accelerator (LINAC)-Based Radiosurgery

PurposeTo analyze and report the long-term outcomes of intracranial arteriovenous malformations (AVM) treated with linear accelerator (LINAC)-based radiosurgery (LBRS) in the pediatric population. Methods and MaterialsA series of 34 pediatric patients (≤18 years old) who were treated between 2002 and 2016 were analyzed. All patients were treated with LBRS in a single fraction, with a median dose of 16.8 Gy to the 80% isodose line. Median age at treatment was 14.4 years (range 5.5-18.9). Median AVM volume was 2.91 mL (range 0.228-27.313). Median modified radiosurgery-based AVM score was 0.83 (range 0.18-2.96). The most common presenting symptom was intracranial hemorrhage (ICH) (n = 22, 64.7%). Nine patients underwent intervention before LBRS, which included prior embolization or resection. Seven lesions were in eloquent locations, defined as basal ganglia, thalamus, or brainstem. Cerebral angiography was done to confirm obliteration. ResultsMedian follow-up time was 98 months (range 36-200 months). Twenty-two of the 34 lesions were obliterated (64.7%) with median time to obliteration of 37 months (range 14-79). No deaths occurred during the follow up period; however, two patients experienced ICH after treatment. Three other patients were treated for symptomatic radiation necrosis. ConclusionsTreatment of intracranial AVM with LBRS in the pediatric population is demonstrated to be safe and effective with long-term follow up.

Abstract TP490: Long Term Clinical Results of Linear Accelerator Stereotactic Radiosurgery for Cerebral Arteriovenous Malformations: A Single Institution Experience of 18 Years

Introduction: Cerebral arteriovenous malformation (AVM) is an intracranial pial vascular lesion which is treated with microsurgery, endovascular treatment or stereotactic radiosurgery (SRS). We introduce the long-term clinical results of linear accelerator (LINAC) stereotactic radiosurgery for cerebral AVM which is treated in single institution for 18 years period. Methods: Retrospective chart review was held in cerebral AVM patients treated with Novalis (BrainLAB AG, Heimstetten, Germany) stereotactic radiotherapy from 2001 to 2018. Clinical results such as obliteration rate, hemorrhage rate after SRS, and radiosurgery related adverse event was analyzed. Furthermore, predictors for obliteration and symptomatic radiosurgery induced adverse event was analyzed with multivariate logistic regression test. Results: Among 117 patients with cerebral AVMs treated with LINAC-based SRS, 72 were included in study. Total obliteration rate was 80.6% (58/72) for mean 57.0±48.3 months follow up period. Post-SRS hemorrhage and mortality rate was 6.9% (4/72) and 1.4% (1/72), respectively. Mean radiation dose and volume was 22.8Gy and 3.7cc, respectively. Independent predictive factors for nidus obliteration was: (1) radiation dose (OR 1.43, 95% CI 1.04-2.08, p=0.0374), (2) Ruptured AVM (OR 12.18, 95% CI 2.38-86.47, p=0.0054), (3) Virginia AVM score (OR 0.21, 95% CI 0.07-0.53, p=0.0028), and (4) follow up period months (OR 1.03, 95% CI 1.01-1.06, p=0.0261). Independent risk factors for symptomatic radiosurgery related adverse event was radiation volume (OR 1.61, 95% CI 1.09-2.65, p=0.0326). Conclusion: LINAC-based SRS is effective and relatively safe method for treatment of cerebral AVMs. Independent predictive factors for obliteration was high radiation dosage, ruptured status, low Virginia AVM score, and long follow up period. High radiation volume was related to symptomatic radiation induced adverse event.

P03.08 Large cerebral arteriovenous malformations management with Volume-staged gamma knife radiosurgery

Abstract BACKGROUND Large cerebral arteriovenous malformations (AVM) pose a management dilemma because of the limited success of any single treatment modality by itself. Surgery alone is associated with significant morbidity and mortality. Similarly, embolization alone has limited efficacy. Volume-staged gamma knife radiosurgery (VSGR) has been developed for the treatment of large AVMs, to increase the efficacy and improve safety of treatment of these lesions. The aim of the study was to assess the efficacy and safety of VSGR technique for the treatment of large cerebral AVMs. METHODS The study included patients treated by VSGR between May 2009 and July 2015. All cases had large AVMs (&gt;10 cc). These were 29 patients. RESULTS Twenty-four patients completed radiographic follow up with 15 obliteration cases (62.5%). There was a total of 56 sessions performed. The mean AVM volume was 16 cc (10.1–29.3 cc). The mean prescription dose was 18 Gy (14–22 Gy). The mean follow up duration was 43 months (21–73 months). One patient died during follow up from unrelated cause. Two cases suffered haemorrhage during follow up. Symptomatic edema developed in 5 (17%) patients. The factors affecting obliteration were smaller total volume, higher dose/stage, non-deep location, compact AVM, AVM score less than 3, &gt;18 Gy dose and &lt;15 cc total volume. The factors affecting symptomatic edema were smaller total volume and shorter time between first and last sessions (p 0.012). T2 image changes were affected by SM grade 3 or more (p 0.013) and AVM score 3 or more (p 0.014). CONCLUSION VSGR provides an effective and safe treatment option for large cerebral AVMs. Smaller AVM volume is associated with higher obliteration rate.

An Outcomes-based Analysis of Patients Treated for Arteriovenous Malformation by Frameless LINAC-based Stereotactic Radiosurgery Using 3-Dimensional Rotational Angiography

Arteriovenous Malformation (AVM) nidus localization remains a significant radiosurgical challenge. Previous work at our institution utilizing phantom models demonstrated superior nidus visualization and geometric accuracy with use of 3-dimensional rotational angiography (3DRA) compared to digital angiography orthogonal image pairs. Incorporation of 3DRA into the radiosurgery (RS) planning process in 2009 has since allowed for a frameless LINAC-based approach to treatment. We evaluated clinical outcomes for patients treated in the time since adopting this technique. Clinical data were queried for all patients treated at our institution for AVM by single-fraction RS from 2010 to present. Post-RS surveillance for nidus obliteration and radiation-induced changes (RIC) consisted of an MRI every six months for two years, then annually. Beyond two years, confirmatory cerebral angiography was recommended for any patient with MRI suggestive of nidus obliteration. Patients were excluded if they lacked sufficient post-RS radiographic assessment, defined as either MRI, CTA, or cerebral angiography at least two years after RS. Maximum diameter (MD) and volume were measured for each lesion and used to calculate a modified Radiosurgery-based AVM Score (mRBAS). RICs were identified and classified as radiologic, symptomatic, or permanent. Excellent outcome was defined as nidus obliteration without intracranial hemorrhage (ICH) or symptomatic/permanent RIC. Clinical predictors of study outcomes were identified through univariate and multivariate (MVA) logistic regression and backwards elimination was used to optimize a predictive model for each outcome. A total of 65 AVMs in 62 patients were included with a median follow-up of 67 months. Median age at treatment was 31 years. Of these lesions, 58% presented with ICH. Prior intervention took place in 23% of cases. Median MD, volume, and mRBAS were 2.3cm, 1.93cc, and 1.16, respectively. 3DRA was utilized during treatment planning in 78% of cases. Treatments were delivered to a median isocenter and periphery dose of 2000 cGy and 1600 cGy, respectively. Obliteration was observed in 63% of cases with 88% confirmed angiographically. Median time-to-obliteration was 32 months. Radiologic, symptomatic, and permanent RICs developed in 40%, 8%, and 3% of cases, respectively. Post-RS ICH occurred in four patients with one ICH-related death. MVA showed that younger age and smaller MD predicted for obliteration. Larger MD predicted for radiologic RIC. Female gender and lower mRBAS predicted for excellent outcome. Incorporation of 3DRA in the RS planning process has allowed for a frameless approach to AVM treatment. Since instituting this technique, we have achieved obliteration and excellent outcome rates comparable to frame-based approaches with minimal treatment-related morbidity.

Volume-Staged Gamma Knife Radiosurgery for Large Brain Arteriovenous Malformation

Large brain arteriovenous malformations (AVMs) pose a management dilemma because of the limited success of any single treatment modality by itself. Surgery alone is associated with significant morbidity and mortality. Similarly, embolization alone has limited efficacy. Volume-staged Gamma Knife radiosurgery (VSGR) has been developed for the treatment of large AVMs to increase the efficacy and improve safety of treatment of these lesions. The aim of this study was to assess the efficacy and safety of VSGR technique for the treatment of large brain AVMs. The study included patients treated by VSGR between May 2009 and July 2015. All patients had large AVMs (>10 mL). There were 29 patients. Twenty-four patients completed radiographic follow-up, with 15 obliteration cases (62.5%). A total of 56 sessions were performed. The mean AVM volume was 16 mL (range, 10.1-29.3 mL). The mean prescription dose was 18 Gy (range, 14-22 Gy). The mean follow-up duration was 43 months (range, 21-73 months). One patient died during follow-up of an unrelated cause. Two patients had hemorrhage during follow-up. Symptomatic edema developed in 5 patients (17%). The factors affecting obliteration were smaller total volume, higher dose/stage, nondeep location, compact AVM, AVM score <3, >18 Gy dose, and <15 mL total volume. The factors affecting symptomatic edema were smaller total volume and shorter time between first and last sessions (P= 0.012). T2 image changes were affected by Spetzler-Martin grade ≥3 (P= 0.013) and AVM score ≥3 (P= 0.014). VSGR provides an effective and safe treatment option for large brain AVMs. Smaller AVM volume is associated with higher obliteration rate.

Seizure Presentation in Patients With Brain Arteriovenous Malformations Treated With Stereotactic Radiosurgery: A Multicenter Study

Abstract INTRODUCTION Seizures are the second most common clinical presentation in patients with brain arteriovenous malformations (AVMs), and they are the most common presentation of unruptured AVMs. The aim of this multicenter, retrospective cohort study was to identify predictors of seizure presentation in AVM patients treated with stereotactic radiosurgery (SRS). METHODS We performed a retrospective review of AVM patients treated with SRS at 8 participating International Radiosurgery Research Foundation sites. Patient and AVM characteristics were compared between those with versus without a seizure presentation in univariable and multivariable models. Subgroup analysis of patients with cortical AVMs was performed. RESULTS The study cohort comprised 2333 AVM patients, including 419 (18%) with and 1914 (82%) without a seizure presentation. Prior AVM resection (OR = 7.65, P = .001), lack of prior AVM hemorrhage (OR = 0.004, P &lt; .001), cortical AVM location (OR = 1559.42, P &lt; .001), lower Spetzler-Martin (SM) grade (OR = 0.51, P = .007), and higher Virginia Radiosurgery AVM Score (VRAS; OR = 1.46, P = .008) were independent predictors of seizure presentation. The rate of seizure presentation in patients with cortical AVMs was 27%. Prior AVM resection (OR = 8.36, P &lt; .001), lack of prior AVM hemorrhage (OR = 0.004, P &lt; .001), and temporal AVM location (OR = 4.15, P &lt; .001) were independent predictors of seizure presentation for cortical AVMs. CONCLUSION We identified multiple factors associated with seizure presentation in AVM patients selected to undergo SRS. Prior AVM resection, cortical AVM location, and lack of prior AVM hemorrhage were the strongest predictors of pre-SRS seizures. SM grade and VRAS may have a role in seizure risk stratification. Among cortical AVMs, temporal lobe localization was predictive of seizure presentation.

Is Biological Effective Dose (BED) Predictive of Outcomes After Radiosurgery for Cerebral Arteriovenous Malformations?

Abstract INTRODUCTION Reports have shown that radiation dose directly correlates with the chance of nidus obliteration after stereotactic radiosurgery (SRS) for arteriovenous malformations (AVMs). However, recent studies have shown that the rate of obliteration was greater in patients having SRS before 2000. As the effect of radiation on cell viability is both dose- and time-dependent, one explanation may be that contemporary SRS, which utilizes more isocenters of radiation to improve dose conformality, takes longer to deliver the same radiation dose, thereby reducing its effectiveness. Biological effective dose (BED) is a metric that incorporates both dose and treatment time and has been shown to correlate with enhanced cell kill in Vitro, as well as normal tissue toxicity in animal models. METHODS A retrospective study of patients having single-session AVM SRS between 1990 and 2009 with a minimum of 2 yr follow-up. Excluded were patients having prior radiation or embolization, as well as patients having volume-staged SRS. BED was calculated using the mono-exponential model described by Jones and Hopewell. The primary outcomes of the study were time to obliteration and chance of excellent outcome (nidus obliteration with no new deficits). RESULTS Three hundred twenty-one patients (328 AVMs) met inclusion criteria (median follow-up, 6.7 yr). BED was associated with both decreased time to obliteration and excellent outcome in univariate Cox regression analyses, both when treated as a dichotomous (P = .002, HR = 1.51 for obliteration; P = .001, HR = 1.61 for outcome) or continuous variable (P = .049, HR = 1.002 for obliteration; P = .01, HR = 1.00 for outcome). In multivariable analyses including dichotomized BED and modified Radiosurgery-Based Arteriovenous Malformation Score as covariates, BED remained significantly associated with both time to obliteration (P = .01, HR = 1.46) and excellent outcome (P = .04, HR = 1.40). CONCLUSION BED was predictive of outcomes after AVM SRS. Further study is warranted to determine whether BED optimization should be considered as well as a prescribed treatment dose for SRS treatment planning.

Seizure Presentation in Patients with Brain Arteriovenous Malformations Treated with Stereotactic Radiosurgery: A Multicenter Study

Seizures are the second most common clinical presentation in patients with brain arteriovenous malformations (AVMs) and the most common presentation of unruptured AVMs. The aim of the present multicenter, retrospective cohort study was to identify the predictors of seizure presentation in patients with AVM who had undergone stereotactic radiosurgery (SRS). We performed a retrospective review of patients with AVM who had been treated with SRS at 8 participating International Radiosurgery Research Foundation sites. The patient and AVM characteristics were compared between those with and without seizure presentation in univariable and multivariable models. A subgroup analysis of patients with cortical AVMs was performed. The study cohort included 2333 patients with AVM, including 419 (18%) with and 1914 (82%) without a seizure presentation. Previous AVM resection (odds ratio [OR], 7.65; P= 0.001), a lack of previous AVM hemorrhage (OR, 0.004; P < 0.001), a cortical AVM location (OR, 1559.42; P < 0.001), a lower Spetzler-Martin grade (OR, 0.51; P= 0.007), and a higher Virginia radiosurgery AVM score (OR, 1.46; P= 0.008) were independent predictors of seizure presentation. The rate of seizure presentation in patients with cortical AVMs was 27%. Previous AVM resection (OR, 8.36; P < 0.001), a lack of previous AVM hemorrhage (OR, 0.004; P < 0.001), and temporal AVM location (OR, 4.15; P<0.001) were independent predictors of seizure presentation for cortical AVMs. We identified multiple factors associated with seizure presentation in patients with AVM to undergo SRS. Previous AVM resection, a cortical AVM location, and a lack of previous AVM hemorrhage were the strongest predictors of pre-SRS seizures. The Spetzler-Martin grade and Virginia radiosurgery AVM score might have a role in seizure risk stratification. For cortical AVMs, a temporal lobe location was predictive of seizure presentation.

Awake craniotomy for excision of arteriovenous malformations? A qualitative comparison study with stereotactic radiosurgery

Treatment of arteriovenous malformations (AVM) located at the eloquent area has been a challenge. Awake brain mapping allows identification of a non-eloquent gyrus for intervention and can potentially facilitate resection with preservation of functions. An alternative treatment option is stereotactic radiosurgery (SRS). The objective of this study was to perform a qualitative comparison of the treatment outcome of awake AVM excision versus SRS. We conducted a 13-year retrospective review of AVM excision under awake craniotomy performed at Prince of Wales Hospital, Hong Kong, from 2003 to 2016. Patients’ presentation, Spetzler-Martin (SM) grading, rate of obliteration and complication were reviewed and analyzed with the modified radiosurgery-based AVM score (RS score). Six patients had excision of AVM under awake mapping during this period of time. Two were SM Grade II and four were SM Grade III. Five located at the peri-rolandic region while one at the temporal language area. None had failed mapping. Five out of six achieved complete obliteration (83.3%). Qualitative comparative analysis had revealed better treatment outcome with awake AVM excision as compared to SRS with the obliteration rate of 100% versus 96% for RS score ≤1.00, 100% versus 78% for RS score 1.01–1.50, and 66% versus 50% for RS score >2.00 respectively. In conclusion, awake mapping and excision of AVMs at the eloquent area is feasible. Qualitative comparative analysis had revealed higher obliteration rate with awake AVM excision as compared to SRS.

WITHDRAWN: Predictors for complete obliteration of arteriovenous malformations following stereotactic radiosurgery

// Zengpanpan Ye 1, * , Xiaolin Ai 1, * , Xin Hu 1, * , Chao You 1 , Andrew Faramand 2 and Fang Fang 1 1 Department of Neurosurgery, West China Hospital of Sichuan University, Chengdu, Sichuan, China 2 Department of Neurosurgery, University of Pittsburgh Medical Center, Pittsburgh, Pennsylvania, United States of America * These authors contributed equally to this work Correspondence to: Fang Fang, email: jipin_li@163.com Keywords: arteriovenous malformation; radiosurgery; obliteration rate Received: September 22, 2017&nbsp;&nbsp;&nbsp;&nbsp;&nbsp; Accepted: October 27, 2017&nbsp;&nbsp;&nbsp;&nbsp;&nbsp; Published: December 21, 2017 ABSTRACT Objective: Radiosurgery is one of the management options used to treat cerebral arteriovenous malformation (AVM). The primary goal of treatment is the complete obliteration of AVM. Multiple factors have been proposed predicting complete AVM obliteration. This meta-analysis aims to assess the predictors of complete obliteration following stereotactic radiosurgery. Materials and Methods: A literature search was conducted using the databases PubMed, Cochrane Central Register of Controlled Trials and EMBASE. Articles discussing predictors of obliteration of AVM following radiosurgery were included. Odd ratio and 95% confidence intervals were used to assess the predictive ability of identified predictors. Results: Higher obliteration rates were observed in previously ruptured AVM (OR: 1.21, 95% CI, 1.02&ndash;1.43, p = 0.03), lower Spetzler-Martin grade (OR: 1.66, 95% CI, 1.11&ndash;2.50, p = 0.01), and in AVM receiving a higher marginal dose (OR: 1.18, 95% CI, 1.11&ndash;1.24, p &lt; 0.001). In contrast, deep AVM location (OR: 0.51, 95% CI, 0.39&ndash;0.67, p &lt; 0.001), eloquence (OR: 0.67, 95% CI, 0.42&ndash;1.06, p = 0.09), prior embolization (OR: 0.83, 95% CI, 0.72&ndash;0.95, p = 0.006), larger target volume (OR: 0.82, 95% CI, 0.71&ndash;0.95, p = 0.009), and a higher Radiosurgery-based AVM score (RBAS) (OR: 0.48, 95% CI, 0.36&ndash;0.65, p &lt; 0.001) were associated with lower obliteration rates. Conclusions: A previously ruptured AVM, a lower Spetzler-Martin grade, a higher marginal dose, non-deep location, no prior embolization, smaller target volume, and lower RBAS were identified as positive predictors for obliteration. Particularly, patients with AVM categorized as having a lower RBAS, radiosurgery should be considered as a first management option for a higher obliteration rate. However, factors such as age, eloquence and sex were not found to influence obliteration rates.

Salvage Therapy for Brain Arteriovenous Malformations After Failure of Gamma Knife Stereotactic Radiosurgery.

The aim of this study was to investigate delayed complications in patients with brain arteriovenous malformation (BAVM) after Gamma Knife stereotactic radiosurgery and to present the salvage therapy experiences of patients with BAVM with radiation-induced changes (RICs) or intracranial hemorrhage (ICH). This cohort consisted of 44 patients with BAVM who underwent failed GKRS between 2000 and 2015. These patients were further divided into an RIC group (23 patients) and an ICH group (21 patients) based on their post-GKRS complications. The patients' characteristics, treatment strategies, and long-term outcomes were analyzed. The modified Rankin Scale was used to assess the neurologic status of each patient. In our study, the marginal dose and radiosurgery-based arteriovenous malformation score were not significantly different between the 2 groups. Craniotomy was performed in 26 patients (9 patients with ICH and 17 patients with RICs), and histologic examination showed cavernous angioma changes in 6 patients. In addition, 6 patients underwent repeat radiosurgery in the ICH group, and 7 patients used bevacizumab in the RIC group. Thirty patients showed good outcomes at the last follow-up (modified Rankin Scale score <3). Salvage therapy for patients with BAVM should be performed based on the latency period and lesion characteristics of each individual. Prompt treatment and a longer follow-up are recommended to achieve good clinical outcomes.