Stereotactic Radiosurgery For Arteriovenous Malformations Research Articles

1133 Biologically Effective Dose and Prediction of Obliteration of Arteriovenous Malformations in Pediatric Patients Treated by Gamma Knife Radiosurgery

INTRODUCTION: Stereotactic radiosurgery (SRS) represents an effective treatment for pediatric arteriovenous malformations (AVMs). Biologic effective dose (BED) is recognized as a predictive variable for outcomes in the adult population, but its role has never been studied in pediatric outcomes. METHODS: Retrospective data for = 18 years old patients treated with single-session SRS for AVM was collected from 1989 – 2019. BED calculations were performed using an a/b ratio of 2.47. Kaplan-Meier analysis was used to evaluate obliteration, new hemorrhage, and radiation-induced changes (RIC). Cox-regression analysis was used for obliteration prediction using two models (margin dose versus BED). RESULTS: One-hundred-ninety-seven patients [median age = 13.1 years, Interquartile range (IQR) = 5.2] were included; 72.6% presented initially with spontaneous hemorrhage. A median margin dose of 22 Gy (IQ = 4.0) with a median BED of 183.2Gy (IQR = 70.54) was used to treat AVMs with a median volume of 2.8 cm3 (IQR = 2.9). Following SRS, obliteration was confirmed in 115 patients (58.4%) using MRI and angiography at a median follow-up of 2.85 years (IQR = 2.26). The cumulative obliteration probability was 43.6% (95% CI = 36.1-50.3), 60.5% (95% CI+=2.2-67.4), 66.0% (95% CI= 56.0-73.7) at 3, 5 and 10 years respectively. In multivariate analysis, a BED >180 Gy [HR = 2.11, 95% CI=1.30-3.40, p = 0.002] in model 1, and a margin dose >20 Gy [HR = 1.90, 95% CI = 1.15-3.13, p = 0.019] in model 2, were associated with obliteration. An AVM nidus volume >4 cm3 was associated with lower obliteration rates in both models. The probability of symptomatic RIC at 10 years was 8.6% (95% CI = 3.5-13.4). Neither BED nor margin dose were associated with RIC occurrence, with the only predictive factor being deep AVM location [HR = 3, 95% CI = 1-9.1, p = 0.048]. CONCLUSIONS: This study confirms BED as a predictor for pediatric AVM obliteration. Optimization of BED in pediatric AVM SRS planning may improve cumulative obliteration rates.

Natural History and Histopathology of Expanding Cysts and Hematomas After Stereotactic Radiosurgery for Arteriovenous Malformations of the Brain: A Case Series

We reviewed the clinical course and histopathologic findings for cases involving the formation of expanding cysts and/or hematomas after gamma knife surgery (GKS) for arteriovenous malformations (AVMs). We report a single-center retrospective review of 18 patients who presented with cyst and/or hematoma expansion after GKS for AVMs between 1993 and 2023. Expanding cysts and hematomas were defined as well-demarcated cavities filled with fluid or well-marginated heterogenous hematomas presenting with expansion proximal to or in the location of the original AVM, respectively. Patient demographics, AVM characteristics, history of interventions and surgeries, and imaging and histopathologic features of expanding cysts and hematomas were collected for analysis. Among 1072 AVM patients treated using GKS, 18 presented with expanding cysts or hematomas during a total follow-up period of 16,757 patient-years (0.11 case/100 persons/patient-year). The time to cyst or hematoma identification was 4-13 years after initial GKS, with a mean duration of 8.6 years. Among the patients examined, 7 (38.9%) presented mainly with hematoma, 10 (55.6%) presented mainly with cysts, and 1 presented with approximately equal components of both. Among the 18 patients, 13 (72.2%) underwent craniotomy to treat cyst or hematoma expansion. All the specimens had similar histopathologic characteristics, including organizing hematoma with fresh and old hemorrhage, fibrinoid necrosis of the vessels, gliosis of normal brain tissue, infiltration of hemosiderin-laden histiocytes, and extravascular protein leakage. Our findings suggest that the formation of these 2 complications can be attributed to a common mechanism involving radiation-induced vascular damage in brain tissue adjacent to the AVM and subsequent chronic inflammation and capillary dilatation.

Biologically Effective Dose and Prediction of Obliteration of Arteriovenous Malformations in Pediatric Patients Treated by Gamma Knife Radiosurgery.

Stereotactic radiosurgery (SRS) represents an effective treatment for pediatric arteriovenous malformations (AVMs). Biological effective dose (BED) has shown promising results in 2 previous studies as a predictive variable for outcomes in adults, but its role has never been studied in pediatric outcomes. Retrospective data for patients 18 years or younger treated with a single-session SRS for AVMs were collected from 1989 to 2019. BED calculations were performed using an α/β ratio of 2.47. Kaplan-Meier analysis was used to evaluate obliteration, new hemorrhage, and radiation-induced changes (RIC). Cox-regression analysis was used for obliteration prediction using 2 models (margin dose vs BED). One hundred ninety-seven patients (median age = 13.1 years, IQR = 5.2) were included; 72.6% (143/197) of them presented initially with spontaneous hemorrhage. A median margin dose of 22 Gy (IQR = 4.0) with a median BED of 183.2 Gy (IQR = 70.54) was used to treat AVM with a median volume of 2.8 cm 3 (IQR = 2.9). After SRS, obliteration was confirmed in 115/197 patients (58.4%) using magnetic resonance imaging and angiography at a median follow-up of 2.85 years (IQR = 2.26). The cumulative obliteration probability was 43.6% (95% CI = 36.1-50.3), 60.5% (95% CI+ = 2.2-67.4), and 66.0% (95% CI = 56.0-73.7) at 3, 5, and 10 years, respectively. In Cox multivariate analysis, a BED >180 Gy (hazard ratio [HR] = 2.11, 95% CI = 1.30-3.40, P = .002) in model 1 and a margin dose >20 Gy (HR = 1.90, 95% CI = 1.15-3.13, P = .019) in model 2 were associated with obliteration. An AVM nidus volume >4 cm 3 was associated with lower obliteration rates in both models. The probability of symptomatic RIC at 10 years was 8.6% (95% CI = 3.5-13.4). Neither BED nor margin dose was associated with RIC occurrence, with the only predictive factor being deep AVM location (HR = 3, 95% CI = 1-9.1, P = .048). This study confirms BED as a predictor for pediatric AVM obliteration. Optimization of BED in pediatric AVM SRS planning may improve cumulative obliteration rates.

Effect of Cobalt-60 Calibration Dose-Rate on Arteriovenous Malformation Obliteration after Stereotactic Radiosurgery

Stereotactic radiosurgery (SRS) dose rate - how old the cobalt-60 sources are - is known to influence outcomes for some neurologic conditions and benign tumors, but it is not known if SRS dose rate influences arteriovenous malformation (AVM) obliteration. The objective of this study is to determine the association between cobalt-60 calibration dose rate and cerebral AVM obliteration in patients treated with SRS. Our hypothesis is that higher SRS dose rates are associated with increased incidence of cerebral AVM obliteration. We performed a retrospective study of 361 patients undergoing 411 AVM-directed SRS treatments between 2005 and 2019 at a single institution. Obliteration was confirmed with digital subtraction angiogram or MRI (if patient refused angiography). Lesion characteristics, SRS treatment details, and post-treatment obliteration and toxicities were recorded. Univariate and multivariate proportional hazards regression models of AVM outcomes with regard to SRS dose rate were performed, controlling for factors such as Spetzler-Martin Grade, maximum AVM extent, prior hemorrhage and prior embolization. At 10 years post-SRS, 68% of AVMs were obliterated on follow-up imaging. Dose rates >2.9 Gy/min were found to be significantly associated with AVM obliteration compared to those <2.1 Gy/min (p = 0.034, Gray's test). AVM size or Spetzler-Martin grade were also associated with obliteration, with obliteration more likely for smaller lesions, particularly those <3 cm in maximal diameter, or with lower Spetzler-Martin grade. Higher dose rates were not associated with development of post-SRS radiologic or symptomatic edema, though larger AVM volume was associated with both types of edema. Patients with cerebral AVMs treated with higher SRS dose rates (from fresh cobalt-60 sources) experience higher incidences of obliteration, without a significant change in the risk of post-treatment edema. These findings suggest that clinics offering SRS for AVMs should regularly renew cobalt-60 radiation sources to maintain high therapeutic dose rates.

Correlation Between Post-Radiosurgery Perinidal Hyperintensity and AVM Obliteration Following LINAC-Based Stereotactic Radiosurgery

We studied the correlation between new-onset perinidal hyperintensity (PH) on T2-weighted magnetic resonance imaging and obliteration of intracranial arteriovenous malformation (AVM) after stereotactic radiosurgery (SRS). A retrospective study of 148 patients with an intracranial AVM who underwent SRS between September 2005 and June 2018 and had ≥1 radiological follow-up (early magnetic resonance imaging) 12-18 months after SRS was performed to analyze the correlation between PH (graded from 0 to 2) and AVM obliteration. Of the 148 patients, 95 were male. The mean patient age was 27.7 ± 12.4 years. Of the 148 AVMs, 105 (70.9%) were obliterated at a median follow-up of 27 months (interquartile range, 14-48 months). The cumulative 3-, 5-, 10-year obliteration rate was 51.8%, 70.8%, and 91.8%, respectively. New-onset PH was observed in 58 AVMs (39.2%; 50 obliterated and 8 not obliterated). No association was found between the pretreatment variables or dose delivered and the development of PH. Grade 2 PH was associated with the risk of symptoms developing compared with grade 1 PH (37.5% vs. 4%; P= 0.002). Symptomatic PH was more likely to develop in patients with a larger AVM (P= 0.05). On multivariate analysis, the presence of a single draining vein (odds ratio [OR], 2.9; 95% confidence interval [CI], 1.3-6.8), a lower median AVM volume (OR, 0.97; 95% CI, 0.6-0.89), a mean marginal radiation dose (OR, 1.29; 95% CI, 1.02-1.64), and the presence of PH (OR, 3.16; 95% CI, 1.29-7.71) were independent predictors of AVM obliteration. The incidence of PH after SRS for AVM was 39.2%. PH was an independent predictor of AVM obliteration after SRS. Grade 2 PH and a larger AVM volume were associated with symptomatic PH.

Application of 4D Flow MRI to Predict Clinical Outcomes after Stereotactic Radiosurgery (SRS) for Cerebral Arteriovenous Malformations (AVMs)

<h3>Purpose/Objective(s)</h3> SRS is standard of care for unresectable cerebral AVMs. Nidus obliteration is the standard clinical metric of treatment success but can take years to occur. Hemorrhage risk is uncertain during this latency period. We hypothesized that early changes in blood flow through feeding arteries after SRS would predict future nidus obliteration and hemorrhage risk. We used 4D flow MRI to prospectively measure blood flow in feeding arteries prior to and 6 months after AVM SRS and correlated the early blood flow response to SRS to later clinical outcomes. <h3>Materials/Methods</h3> <i>Patients:</i> Patients undergoing SRS for AVM were enrolled prospectively. 4D flow MRI was performed prior to SRS and 6 months post-treatment. <i>Imaging:</i> Imaging was performed on a 3T scanner with dedicated head coil. 4D flow sequences were based on a 3D spoiled gradient echo sequence. Three directional velocity encoding gradients were used with Venc 100-200 cm/s. Additional MRI sequences were obtained to identify the nidus and feeding arteries. <i>Flow Analysis:</i> In each case the dominant feeding artery was identified. Mean blood flow over the cardiac cycle was measured in a proximal segment of the feeding artery. Blood flow was measured in the same location both before and 6 months after SRS. Blood flow was measured using software with FDA clearance for clinical 4D flow post-processing. Response was defined as fractional arterial blood flow after treatment vs. before treatment. <i>Statistical Analysis:</i> We defined the cut-off between ‘responders' and ‘non-responders' as the median blood flow response. Survival analysis was performed to assess the relationship between binarized blood flow response and nidus obliteration, with bleeding or death prior to obliteration treated as competing risks. Gray's test was used to assess for equality in the cumulative incidence functions for obliteration or bleeding/death between responders and non-responders. <h3>Results</h3> 18 subjects have completed pre- and post-treatment imaging. Median time to post-treatment imaging was 179 Days (IQR 169-202 Days). Median response was 0.52 (IQR 0.44-0.84). Median follow up is 755 Days (IQR 438-1188 Days). There have been no deaths. Amongst responders, there have been 4 obliteration events and 0 bleeding events. Amongst non-responders there have been 0 obliteration events and 2 bleeding events. There is a trend toward an increase in cumulative incidence of obliteration amongst responders (p=0.08) and in bleeding amongst non-responders (p=0.11). <h3>Conclusion</h3> Preliminary results suggest 4D flow MRI may be an early predictor of clinical outcomes after AVM SRS. Further follow up with additional events will be required to confirm a predictive relationship and to determine an optimal cutoff for distinguishing responders from non-responders.

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.

Repeat stereotactic radiosurgery for cerebral arteriovenous malformations.

The purpose of this retrospective, single-institution study was to evaluate radiological and clinical outcomes of patients managed with repeat stereotactic radiosurgery (SRS) for residual cerebral arteriovenous malformation (AVM) after prior SRS. The authors evaluated the clinical and radiological outcomes of consecutive patients treated with repeat single-session SRS for a residual brain AVM from 1989 to 2021. In total, 170 patients underwent repeat SRS for AVM (90 [52.9%] females; median [interquartile range] age at the first SRS procedure 28 [21.5] years; median [interquartile range] age at the second SRS procedure 32 [22.5] years). After repeat SRS, the actuarial 3-, 5-, and 10-year AVM obliteration rates were 37.6%, 57.3%, and 80.9%, respectively. Higher obliteration rates were associated with margin dose ≥ 19 Gy (p = 0.001). After the second SRS procedure, hemorrhage occurred in 8.2% of patients and was lethal in 1 patient. The risk factors of intracranial hemorrhage were age < 18 years (p = 0.03) and residual AVM diameter > 20 mm (p = 0.004). Lower obliteration rates were noted in patients with residual AVM diameter > 20 mm (p = 0.04) and those < 18 years of age (p = 0.04). Asymptomatic, symptomatic, and permanent radiation-induced changes (RICs) after the second SRS procedure occurred in 25.9%, 8.8%, and 5.3% of patients, respectively, and were associated with RIC after the first SRS procedure (p = 0.006). There was 1 case of a radiation-induced meningioma 12 years after SRS. Repeat SRS is a reasonable therapeutic option, in particular for patients with residual AVM. Repeat SRS was associated with more favorable outcomes in adult patients and those with residual AVM smaller than 20 mm in maximum diameter. To increase the rate of residual AVM obliteration, a prescription dose ≥ 19 Gy should ideally be used for repeat SRS.

Dosimetric effects of embolization material artefacts in arteriovenous malformations stereotactic radiosurgery on treatment planning calculation.

Background and PurposeStereotactic Radiosurgery (SRS) is a specialized radiotherapy treatment technique for Arteriovenous Malformations (AVM) in which Computed Tomography (CT) images are used for dose calculations. The purpose of this study was to investigate CT image distortions caused by embolic agents and quantify the influence of these distortions on dose calculations.MethodsEight AVM patients administered embolic agents prior to SRS were included. Original plans were compared to new recalculated plans using two sets of images. The first set was created by masking the embolic material and artefacts, the second was the diagnostic CT images. In addition, treatment plans were created for an anthropomorphic phantom with water inserts, then with known volumes of embolic materials to study the dosimetric effect of each material.ResultsRelative to patients’ original plans, maximum Monitor Unit (MU) difference was −4.4% with whole brain masking, −1.3% with artefact masking, −4.1% with embolic masking, and −4.5% with artefact-free diagnostic images. Calculated dose differences were within ± 3.5% for all plans. In phantom, Gamma pass rate was 96% for both embolic agents with conformal fields and 99.9% with dynamic arcs. Dose and MU differences in phantom plans were negligible.ConclusionRelative dose differences between the original plans and the corrected ones were not clinically remarkable. We recommend evaluating the effect of embolic materials on individual patients’ plans. The whole brain corrected planning CT images or diagnostic CT images could be utilized to calculate the magnitude of dose reduction caused by embolic materials and correct it if necessary.

LINAC stereotactic radiosurgery for brain arteriovenous malformations: An updated single centre analysis of outcomes

Arteriovenous malformations (AVM) of the brain are congenital, high pressure vascular malformations, which are at risk of haemorrhage. Stereotactic radiosurgery (SRS) can obliterate the nidus by delivering a precise high dose of ionising radiation in a single fraction. This paper updates long term AVM obliteration rates, time to obliteration and retreatment outcomes in LINAC delivered SRS treatment at the Royal Adelaide Hospital. A retrospective review of a prospectively maintained AVM SRS database supplemented by clinical case notes, patient correspondence and electronic medical records was performed. 89 AVMs received primary SRS treatment for which the crude obliteration rate was 61% (68% for 79 patients with adequate follow up). Higher marginal dose, smaller nidus size and lower Pollock-Flickinger (PF) score were significantly associated with AVM obliteration. The crude obliteration rates for patients with adequate follow-up and AVM diameter < 3 cm vs ≥ 3 cm were 76% vs 48%, respectively, and 93% with PF score < 1.0. Median time to obliteration was 36 months. Higher dose and lower PF score were associated with earlier obliteration. The crude obliteration rate after second SRS was 56% (9/16 patients) and no significant associations were found. These obliteration rates after primary and retreatment LINAC SRS are comparable to other studies. Marginal dose and PF score were the main predictors of obliteration overall as well as early (<36 months) obliteration.

Stereotactic radiosurgery for ruptured versus unruptured intracranial arteriovenous malformations.

Background: There are a limited data examining the effects of prior hemorrhage on outcomes after stereotactic radiosurgery (SRS). The goal of this study was to identify risk factors for arteriovenous malformation (AVM) rupture and compare outcomes, including post-SRS hemorrhage, between patients presenting with ruptured and unruptured AVMs.Methods: A retrospective review of consecutive patients undergoing SRS for intracranial AVMs between 2009 and 2019 at our institution was conducted. Chi-square and multivariable logistic regression analyses were utilized to identify patient and AVM factors associated with AVM rupture at presentation and outcomes after SRS including the development of recurrent hemorrhage in both ruptured and unruptured groups.Results: Of 210 consecutive patients with intracranial AVMs treated with SRS, 73 patients (34.8%) presented with AVM rupture. Factors associated with AVM rupture included smaller AVM diameter, deep venous drainage, cerebellar location, and the presence of intranidal aneurysms (P < 0.05). In 188 patients with adequate follow-up time (mean 42.7 months), the overall post-SRS hemorrhage rate was 8.5% and was not significantly different between ruptured and unruptured groups (10.3 vs. 7.5%, P = 0.51). There were no significant differences in obliteration rate, time to obliteration, or adverse effects requiring surgery or steroids between unruptured and ruptured groups.Conclusion: Smaller AVM size, deep venous drainage, and associated intranidal aneurysms were associated with rupture at presentation. AVM rupture at presentation was not associated with an increased risk of recurrent hemorrhage or other complication after SRS when compared to unruptured AVM presentation. Obliteration rates were similar between ruptured and unruptured groups.

Chronic encapsulated expanding hematomas after stereotactic radiosurgery for intracranial arteriovenous malformations.

Cerebral arteriovenous malformations (AVMs) are rare cerebral vascular lesions that are associated with high morbidity and mortality from hemorrhage; however, stereotactic radiosurgery (SRS) is a well-validated treatment modality. Few reports have delineated a subgroup of patients who develop delayed chronic encapsulated expanding hematomas (CEEHs) despite angiographic evidence of AVM obliteration following radiosurgery. In this report, the authors performed a retrospective review of more than 1000 radiosurgically treated intracranial AVM cases to delineate the incidence and management of this rare entity. Between 1988 and 2019, 1010 patients with intracranial AVM underwent Gamma Knife SRS at the University of Pittsburgh Medical Center. In addition to a review of a prospective institutional database, the authors performed a retrospective chart review of the departmental AVM database to specifically identify patients with CEEH. Pertinent clinical and radiological characteristics as well as patient outcomes were recorded and analyzed. Nine hundred fifty patients with intracranial AVM (94%) had sufficient clinical follow-up for analysis. Of these, 6 patients with CEEH underwent delayed resection (incidence rate of 0.0045 event per person-year). These patients included 4 males and 2 females with a mean age of 45.3 ± 13.8 years at the time of initial SRS. Four patients had smaller AVM volumes (4.9-10 cm3), and 3 of them were treated with a single SRS procedure. Two patients had larger-volume AVMs (55 and 56 cm3), and both underwent multimodal management that included staged SRS and embolization. Time to initial recognition of the CEEH after initial SRS ranged between 66 and 243 months. The time between CEEH recognition and resection ranged from 2 to 9 months. Resection was required because of progressive neurological symptoms that correlated with imaging evidence of gradual hematoma expansion. All 6 patients had angiographically confirmed obliteration of their AVM. Pathology revealed a mixed chronicity hematoma with areas of fibrosed blood vessels and rare areas of neovascularization with immature blood vessels but no evidence of a persistent AVM. All 6 patients reported persistent clinical improvement after hematoma resection. CEEH after SRS for AVM is a rare complication with an incidence rate of 0.0045 event per person-year over the authors' 30-year experience. When clinical symptoms progress and imaging reveals progressive enlargement over time, complete resection of a CEEH results in significant clinical recovery. Knowledge of this rare entity facilitates timely detection and eventual surgical intervention to achieve optimal outcomes.

Predictive Factors for Arteriovenous Malformation Obliteration After Stereotactic Radiosurgery: A Single-Center Study

Stereotactic radiosurgery (SRS) is particularly useful for treatment of deep arteriovenous malformations (AVMs) in eloquent territory with a high associated surgical risk. Prior studies have demonstrated high rates of AVM obliteration with SRS (60%-80%) in a latency period of 2-4 years for complete obliteration. Studies have identified several factors associated with successful obliteration of the AVM nidus; however, these present inconsistent and conflicting data. The aim of this single-center study was to examine factors associated with successful obliteration of AVMs treated with SRS. A retrospective review was performed of 210 consecutive patients undergoing SRS for brain AVMs between 2010 and 2019. The χ2 test and logistic regression analysis were used to identify patient and AVM factors associated with successful obliteration. Younger age (P= 0.034) and prior embolization (P= 0.012) were associated with complete obliteration. The presence of coronary artery disease was associated with incomplete obliteration (P= 0.04). No AVM characteristics were statistically associated with complete obliteration, although superficial venous drainage (P= 0.08) and frontal location (P= 0.06) trended toward significance. Successful obliteration of the AVM nidus was significantly associated with younger age and prior embolization. The presence of coronary artery disease negatively affected obliteration rates. These results add to the mixed results seen in the literature and emphasize the need for continued studies to delineate more specific patient and AVM factors that contribute to successful obliteration.

Seizure Rates After Stereotactic Radiosurgery for Cerebral AVMs: A Single Center Study

Seizure control after stereotactic radiosurgery (SRS) for arteriovenous malformations (AVMs) is an area of growing interest, with previous studies reporting up to 70% seizure freedom after treatment. The goals of this study were to identify specific patient and AVM characteristics associated with seizure presentation and seizure outcomes after SRS treatment. A retrospective review of consecutive patients undergoing SRS for brain AVMs between 2009 and 2019 at our institution was conducted. Chi-squared and logistic regression analyses were utilized to identify patient and AVM factors associated with preoperative seizure presentation and development of new onset seizures after SRS. Two hundred ten consecutive patients presenting with AVMs treated with SRS were reviewed. Factors associated with seizure presentation included larger AVM size (P= 0.02), superficial venous drainage (P< 0.05), and parietal location (P= 0.04). Of 188 patients with follow-up (90%), 30 patients presented with seizures and 14 (47%) were seizure-free post-SRS. Of 158 patients presenting without seizure, 29 (18%) developed de novo seizures during follow-up. De novo post-SRS seizures were associated with prior craniotomy for resection of AVM (P= 0.04), post-treatment hemorrhage (P= 0.02), parietal location (P= 0.05), adverse effect requiring steroids (P < 0.01), and adverse effect requiring surgery (P < 0.01). Seizures are a common presentation of brain AVMs and can be treated effectively with SRS. However, seizures can also be a complication of SRS and are associated with post-treatment hemorrhage, edema, and need for future open surgery.

Effect of Prior Embolization on Outcomes After Stereotactic Radiosurgery for Pediatric Brain Arteriovenous Malformations: An International Multicenter Study.

Pediatric brain arteriovenous malformations (AVMs) are a significant cause of morbidity but the role of multimodal therapy in the treatment of these lesions is not well understood. To compare the outcomes of stereotactic radiosurgery (SRS) with and without prior embolization for pediatric AVMs. We retrospectively evaluated the International Radiosurgery Research Foundation pediatric AVM database. AVMs were categorized, based on use of pre-embolization (E+SRS)or lack thereof (SRS-only). Outcomes were compared in unadjusted and inverse probability weight (IPW)-adjusted models. Favorable outcome was defined as obliteration without post-SRS hemorrhage or permanent radiation-induced changes (RIC). The E+SRS and SRS-only cohorts comprised 91 and 448 patients, respectively. In unadjusted models, the SRS-only cohort had higher rates of obliteration (68.5%vs 43.3%, <.001) and favorable outcome (61.2%vs 36.3%, P<.001) but a lower rate of symptomatic RIC (9.0%vs 16.7%, P=.031). The IPW-adjusted rates of every outcome were similar between the 2 cohorts. However, cumulative obliteration rates at 3, 5, 8, and 10 yr remained higher in the absence of prior embolization (46.3%, 64.6%, 72.6%, and 77.4% for SRS-only vs 24.4%, 37.2%, 44.1%, and 48.7% for E+SRS cohorts, respectively; SHR=0.449 [0.238-0.846], P=.013). Embolization appears to decrease cumulative obliteration rates after SRS for pediatric AVMs without affecting the risk of post-treatment hemorrhage or adverse radiation effects arguingagainst the routine use of pre-SRS embolization. While endovascular therapy can be considered for occlusion of high-risk angioarchitectural features prior toSRS, future studies are necessary to clarify its role.

Additive Fabrication of a Vascular 3D Phantom for Stereotactic Radiosurgery of Arteriovenous Malformations.

In this study, an efficient methodology for manufacturing a realistic three-dimensional (3D) cerebrovascular phantom resembling a brain arteriovenous malformation (AVM) for applications in stereotactic radiosurgery is presented. The AVM vascular structure was 3D reconstructed from brain computed tomography (CT) data acquired from a patient. For the phantom fabrication, stereolithography was used to produce the AVM model and combined with silicone casting to mimic the brain parenchyma surrounding the vascular structure. This model was made with tissues-equivalent materials for radiology. The hollow vascular system of the phantom was filled with a contrast agent usually employed on patients for CT scans. The radiological response of the phantom was tested and compared with the one of the clinical case. The constructed model demonstrated to be a very accurate physical representation of the AVM and its vasculature and good morphological consistency was observed between the model and the patient-specific source anatomy. These results suggest that the proposed method has potential to be used to fabricate patient-specific phantoms for neurovascular radiosurgery applications and medical research.

The Role of Biological Effective Dose in Predicting Obliteration After Stereotactic Radiosurgery of Cerebral Arteriovenous Malformations

ObjectiveTo determine whether biological effective dose (BED) was predictive of obliteration after stereotactic radiosurgery (SRS) for cerebral arteriovenous malformations (AVMs). Patients and MethodsWe studied patients undergoing single-session AVM SRS between January 1, 1990, and December 31, 2014, with at least 2 years of imaging follow-up. Excluded were patients with syndromic AVM, previous SRS or embolization, and patients treated with volume-staged SRS. Biological effective dose was calculated using a mono-exponential model described by Jones and Hopewell. The primary outcome was likelihood of total obliteration defined by digital subtraction angiography or magnetic resonance imaging (MRI). Variables were analyzed as continuous and dichotomous variables based on the maximum value of (sensitivity–[1–specificity]). ResultsThis study included 352 patients (360 AVM, median follow-up, 5.9 years). The median margin dose prescribed was 18.75 Gy (interquartile range [IQR]: 18 to 20 Gy). Two hundred fifty-nine patients (71.9%) had obliteration shown by angiography (n=176) or MRI (n=83) at a median of 36 months after SRS (IQR: 26 to 44 months). Higher BED was associated with increased likelihood of obliteration in univariate Cox regression analyses, when treated as either a dichotomous (≥133 Gy; hazard ratio [HR],1.52; 95% confidence interval [CI], 1.19 to 1.95; P<.001) or continuous variable (HR, 1.00, 95% CI, 1.0002 to 1.005; P=.04). In multivariable analyses including dichotomized BED and location, BED remained associated with obliteration (P=.001). ConclusionBiological effective dose ≥133 Gy was predictive of AVM obliteration after single-session SRS within the prescribed margin dose range 15 to 25 Gy. Further study is warranted to determine whether BED optimization should be considered as well as treatment dose for AVM SRS planning.

A case of delayed cyst formation post brain AVM stereotactic radiosurgery for arteriovenous malformation: Case report

Arteriovenous malformations (AVMs) are a rare cause of cerebrovascular abnormality with incidence of about 1 in 100,000 people per year and point prevalence of about 0.2%. AVMs are associated with serious complications such as intracranial haemorrhage (2–4% a year, 16% and 29% at 10 and 20 years after diagnosis), seizures (10–30%), focal neurologic deficits, and headaches. The management options are surveillance, endovascular embolization, microsurgical excision and stereotactic radiosurgery (SRS).In SRS Stereotactically focused high energy beams of photons induce progressive thrombosis by fibro-intimal hyperplasia and subsequent luminal obliteration. These changes usually take one to three years known as “latency period”. Complications are reported in 8% of patients undergoing SRS, including radiographic parenchymal lesions, cranial nerve deficits, seizures, headaches, and cyst formation.Cyst formation is reported in about 1.2 % of patients undergoing SRS. While the exact mechanism of post SRS cyst formation is unclear, it is hypothesized that it might be due to damage to the blood brain barrier and increased vessel wall permeability. Delayed cyst formation is reported with latency period between 3 and 10 years after radiotherapy for treatment of cerebrovascular AVMs. However, cystic formation with longer latency periods (in one case upto 17 years) after radiotherapy for other causes such as nasopharyngeal cancers have been reported.Here we report a case of delayed cyst formation after SRS for cerebrovascular AVM with latency period of 20 years.

Embolization of Brain Arteriovenous Malformations With Versus Without Onyx Before Stereotactic Radiosurgery.

Embolization of brain arteriovenous malformations (AVMs) using ethylene-vinyl alcohol copolymer (Onyx) embolization may influence the treatment effects of stereotactic radiosurgery (SRS) differently than other embolysates. To compare the outcomes of pre-SRS AVM embolization with vs without Onyx through a multicenter, retrospective matched cohort study. We retrospectively reviewed International Radiosurgery Research Foundation AVM databases from 1987 to 2018. Embolized AVMs treated with SRS were selected and categorized based on embolysate usage into Onyx embolization (OE+SRS) or non-Onyx embolization (NOE+SRS) cohorts. The 2 cohorts were matched in a 1:1 ratio using de novo AVM features for comparative analysis of outcomes. The matched cohorts each comprised 45 patients. Crude AVM obliteration rates were similar between the matched OE+SRS vs NOE+SRS cohorts (47%vs 51%; odds ratio [OR]=0.837, P=.673). Cumulative probabilities of obliteration were also similar between the OE+SRS vs NOE+SRS cohorts (subhazard ratio=0.992, P=.980). Rates of post-SRS hemorrhage, all-cause mortality, radiation-induced changes, cyst formation, and embolization-associated complications were similar between the matched cohorts. Sensitivity analysis for AVMs in the OE+SRS cohort embolized with Onyx alone revealed a higher rate of asymptomatic embolization-associated complications in this subgroup compared to the NOE+SRS cohort (36%vs 15%; OR=3.297, P=.034), but the symptomatic complication rates were similar. Nidal embolization using Onyx does not appear to differentially impact the outcomes of AVM SRS compared with non-Onyx embolysates. The embolic agent selected for pre-SRS AVM embolization should reflect both the experience of the neurointerventionalist and target of endovascular intervention.

Magnetic Resonance Perfusion Changes of Arteriovenous Malformations Treated with Stereotactic Radiosurgery

The latency period from stereotactic radiosurgery (SRS) to obliteration of arteriovenous malformations (AVM) requires continuous imaging surveillance. Magnetic resonance (MR) perfusion is promising for noninvasive monitoring of AVMs after SRS. We studied longitudinal MR perfusion changes of brain AVMs treated with SRS. Consecutive patients treated for brain AVMs using SRS who had MR perfusion imaging studies performed before and at least once after SRS were studied. We estimated ipsilateral/contralateral brain hemisphere ratios of MR perfusion indexes, including regional cerebral blood flow (rCBF) and relative cerebral blood volume (rCBV), in the AVM nidus, perinidal region, and remote anterior and posterior brain regions. Eleven patients (6 women; median age, 21 years) underwent SRS (median prescription dose, 18 Gy; range, 12-20 Gy) for brain AVMs (median Spetzler-Martin grade 2 and median volume 4.6 mL). Before the SRS, rCBV and rCBF ratios were significantly higher in the AVM nidus compared with other investigated brain regions (P < 0.001). Median time from SRS to the first and last post-SRS MR perfusion studies was 8 and 35 months, respectively. There was a statically significant decrease of rCBV (P= 0.043) and rCBF (P= 0.036) ratios in the AVM nidus, but not other brain regions, during post-SRS follow-up. There is a gradual decrease of rCBV and rCBF in the AVM nidus after SRS. MR perfusion imaging is promising for monitoring of hemodynamic changes of AVMs after SRS. Larger studies investigating clinical value of MR perfusion imaging for AVMs after SRS are warranted.