Stereotactic Radiosurgery For Arteriovenous Malformations Research Articles

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.

Automated Deep Learning-Based Image Segmentation for the Correction of Normal Brain Dose-Volume Parameters in Brain SRS for Cerebral AVMs

Brain radiation necrosis (RN) is a dose-limiting toxicity of stereotactic radiosurgery (SRS) for cerebral arteriovenous malformations (AVMs). Prior studies show a significant relationship between the probability of RN and the volume of brain receiving high doses, in particular, the volume receiving at least 12Gy (V12). However, due to the prohibitive time cost of manually segmenting brain from other intracranial tissues, prior studies have treated all intracranial tissues homogenously as brain. Large AVMs can cause significant anatomical distortions, with dilated ventricles, draining veins, and embolized nidus elements potentially displacing brain tissue from the high dose volume. We hypothesized that there would be a significant difference between estimated V12 for all intracranial tissues (V12ic) and V12 for brain parenchyma specifically (V12brain) in AVM cases. To assess the difference between V12ic and V12brain (ΔV12), we used a convolutional neural network (CNN) to auto-segment magnetic resonance images (MRIs) from SRS-treated patients into vascular structures, CSF, and brain tissue, fusing the segmented images with treatment plans to calculate V12ic and V12brain. SRS plans from 8 AVM patients who underwent single stage SRS and 4 who underwent multistage SRS were included. For multistage SRS plans, each stage was treated as an independent plan, for a total of 16 analyzed treatment plans. A previously trained CNN was used to automatically segment multiparametric pre-treatment MRIs into arteries, veins, CSF, embolized vessels, and brain parenchyma. Segmentation labels were converted into contours and registered to treatment plans. Dose-volume histograms were generated, from which V12ic and V12brain for all intracranial tissue and brain parenchyma, respectively, were analyzed. We assessed the relationship between ΔV12 (V12ic - V12brain) and target volume using linear regression. Median target volume was 1.75cc (range [0.22-9.95cc]). Median V12ic was 8.31cc (range [2.1-21.4cc]) while median V12brain was 4.0cc (range [1.3-13.3cc]). Median ΔV12 was 3.7cc (range [0.46-9.4cc]). There was a significant linear relationship between target volume and ΔV12 (Pearson r2 = 0.57, p < 0.01), with larger targets associated with a greater ΔV12. Anatomical distortions produced by an AVM nidus can produce a significant difference between V12ic and V12brain, an effect that is more pronounced for larger lesions. Further studies are needed to directly assess the relationship between V12brain and likelihood of post-SRS RN; however, estimating dose to brain tissue specifically may help identify patients who can safely receive dose-escalated therapy as well as patients who require a more conservative approach. CNN-based automated segmentation provides a means of overcoming the previously prohibitive time cost of performing such an analysis.

Clinico-Radiologic Outcomes After Stereotactic Radiosurgery for Patients with Complex High-Risk Multiple Arteriovenous Malformations

The present study aims to define the outcome and risks of patients with multiple arteriovenous malformations (AVMs) treated by stereotactic radiosurgery (SRS). We retrospectively analyzed the records of 1232 patients with AVMs who underwent SRS at our center between 1987 and 2017. We identified 10 patients who had SRS for multiple AVMs (total of 25). Eight patients presented with intracranial hemorrhage before SRS. Four patients had hereditary hemorrhagic telangiectasia. A Spetzler-Martin grade I AVM was diagnosed in 11 AVMs, grade II in 7, grade III in 6, and grade IV in 1 AVM. The median maximum diameter was 12 mm, the median target volume was 1.1 cm3, and the median margin dose was 20 Gy. Twenty-four AVMs were treated with single-session SRS, and 1 AVM was treated with volume-staged SRS. The angiographic complete obliteration rate of each AVM was 18.2%, 58.0%, and 66.4% at 3, 5, and 7 years, respectively. The angiographic complete obliteration rate of all treated AVMs in each patient was 11.1%, 51.4%, and 51.4% at 3, 5, and 7 years, respectively. In multivariate analysis, higher marginal dose (≥18 Gy, P= 0.031) was significantly associated with complete obliteration of AVMs. After obliteration of all their AVMs was confirmed no patient bled. Patients with complex multiple AVMs often presented with a brain hemorrhage. Reduction in bleeding risk after SRS requires complete obliteration that is more likely if the initial AVM margin dose is ≥18 Gy for each AVM.

Early obliteration of pediatric brain arteriovenous malformations after stereotactic radiosurgery: an international multicenter study.

Stereotactic radiosurgery (SRS) is a treatment option for pediatric brain arteriovenous malformations (AVMs), and early obliteration could encourage SRS utilization for a subset of particularly radiosensitive lesions. The objective of this study was to determine predictors of early obliteration after SRS for pediatric AVMs. The authors performed a retrospective review of the International Radiosurgery Research Foundation AVM database. Obliterated pediatric AVMs were sorted into early (obliteration ≤ 24 months after SRS) and late (obliteration > 24 months after SRS) responders. Predictors of early obliteration were identified, and the outcomes of each group were compared. The overall study cohort was composed of 345 pediatric patients with obliterated AVMs. The early and late obliteration cohorts were made up of 95 (28%) and 250 (72%) patients, respectively. Independent predictors of early obliteration were female sex, a single SRS treatment, a higher margin dose, a higher isodose line, a deep AVM location, and a smaller AVM volume. The crude rate of post-SRS hemorrhage was 50% lower in the early (3.2%) than in the late (6.4%) obliteration cohorts, but this difference was not statistically significant (p = 0.248). The other outcomes of the early versus late obliteration cohorts were similar, with respect to symptomatic radiation-induced changes (RICs), cyst formation, and tumor formation. Approximately one-quarter of pediatric AVMs that become obliterated after SRS will achieve this radiological endpoint within 24 months of initial SRS. The authors identified multiple factors associated with early obliteration, which may aid in prognostication and management. The overall risks of delayed hemorrhage, RICs, cyst formation, and tumor formation were not statistically different in patients with early versus late obliteration.

Stereotactic Radiosurgery for Brain Arteriovenous Malformations: Evaluation of Obliteration and Review of Associated Predictors

BackgroundHigh arteriovenous malformation (AVM) obliteration rates have been reported with stereotactic radiosurgery (SRS), and multiple factors have been found to be associated with AVM obliteration. These predictors have been inconsistent throughout studies. We aimed to analyze our experience with linear accelerator (LINAC)-based SRS for brain AVMs, evaluate outcomes, assess factors associated with AVM obliteration and review the various reported predictors of AVM obliteration. MethodsElectronic medical records were retrospectively reviewed to identify consecutive patients with brain AVMs treated with SRS over a 27-year period with at least 2 years of follow-up. Logistic regression analysis was performed to identify factors associated with AVM obliteration. ResultsOne hundred twenty-eight patients with 142 brain AVMs treated with SRS were included. Mean age was 34.4 years. Fifty-two percent of AVMs were associated with a hemorrhage before SRS, and 14.8% were previously embolized. Mean clinical and angiographic follow-up times were 67.8 months and 58.6 months, respectively. The median Spetzler-Martin grade was 3. Mean maximal AVM diameter was 2.8 cm and mean AVM target volume was 7.4 cm3 with a median radiation dose of 16 Gy. Complete AVM obliteration was achieved in 80.3%. Radiation-related signs and symptoms were encountered in 32.4%, only 4.9% of which consisted of a permanent deficit. Post-SRS AVM-related hemorrhage occurred in 6.3% of cases. In multivariate analysis, factors associated with AVM obliteration included younger patient age (P = .019), male gender (P = .008), smaller AVM diameter (P = .04), smaller AVM target volume (P = .009), smaller isodose surface volume (P = .005), a higher delivered radiation dose (P = .013), and having only one major draining vein (P = .04). ConclusionsAVM obliteration with LINAC-based radiosurgery was safe and effective and achieved complete AVM obliteration in about 80% of cases. The most prominent predictors of AVM success included AVM size, AVM volume, radiation dose, number of draining veins and patient age.

Stereotactic radiosurgery for pediatric brain arteriovenous malformations: long-term outcomes.

Contrary to the better described obliteration- and hemorrhage-related data after stereotactic radiosurgery (SRS) of brain arteriovenous malformations (AVMs) in pediatric patients, estimates of the rarer complications, including cyst and tumor formation, are limited in the literature. The aim of the present study was to assess the long-term outcomes and risks of SRS for AVMs in pediatric patients (age < 18 years). The authors retrospectively analyzed the International Radiosurgery Research Foundation pediatric AVM database for the years 1987 to 2018. AVM obliteration, post-SRS hemorrhage, cyst formation, and tumor formation were assessed. Cumulative probabilities, adjusted for the competing risk of death, were calculated. The study cohort comprised 539 pediatric AVM patients (mean follow-up 85.8 months). AVM obliteration was observed in 64.3% of patients, with cumulative probabilities of 63.6% (95% CI 58.8%-68.0%), 77.1% (95% CI 72.1%-81.3%), and 88.1% (95% CI 82.5%-92.0%) over 5, 10, and 15 years, respectively. Post-SRS hemorrhage was observed in 8.4% of patients, with cumulative probabilities of 4.9% (95% CI 3.1%-7.2%), 9.7% (95% CI 6.4%-13.7%), and 14.5% (95% CI 9.5%-20.5%) over 5, 10, and 15 years, respectively. Cyst formation was observed in 2.1% of patients, with cumulative probabilities of 5.5% (95% CI 2.3%-10.7%) and 6.9% (95% CI 3.1%-12.9%) over 10 and 15 years, respectively. Meningiomas were observed in 2 patients (0.4%) at 10 and 12 years after SRS, with a cumulative probability of 3.1% (95% CI 0.6%-9.7%) over 15 years. AVM obliteration can be expected after SRS in the majority of the pediatric population, with a relatively low risk of hemorrhage during the latency period. Cyst and benign tumor formation after SRS can be observed in 7% and 3% of patients over 15 years, respectively. Longitudinal surveillance for delayed neoplasia is prudent despite its low incidence.

Abstract TP491: Hypofractionated Stereotactic Radiosurgery for Brain AVM Post Aruba: Obliteration, Complication, and Hemorrhage Rates

Introduction: Patients harboring brain AVMs associated with moderate-high surgical morbidity (large lesions, deep location and eloquent cortex) are increasingly undergoing hypofractionated stereotactic radiosurgery (SRS) at our institution. Most published literature is based on a single fraction SRS technique. In this review we sought to evaluate/present our hypofractionated SRS experience using the Accuray Cyberknife device. Hypothesis: Cyberknife Stereotactic Radiosurgery (C-SRS) can be used for a high risk brain arteriovenous malformations (AVMs) with high rates of successful complete obliteration and low rates of hemorrhagic, death and major disability. Methods: We performed a retrospective analysis of all patients having undergone Cyberknife SRS for brain AVMs between 2013-2019 at a large community based tertiary care health system and identified 33 patients. Of these patients 12 had a minimum of 2 year follow-up. We divided the patients into hemorrhagic and non-hemorrhagic presentations, prior endovascular treatment with embolization and based on Spetzler Martin grades. Results: 58% males with median age of 44 and 9% presenting with hemorrhage. Median planning target volume (PTV) was 7.2 cc (range 1.25-15.56 cc) and median HFSRT dose was three fractions (range 3-5) of 10.25 Gy (range 8.5-11 Gy) each. Complete obliteration was achieved in 100% of patients after salvage SRS 21 Gy x1 fraction to a residual AVM volume in 2 patients. The median time to obliteration was 747 days. 3 of 12 patients suffered radiation necrosis1 patient with a large AVM (maximum diameter of 4 cm and PTV of 12.6 cc) suffered re-hemorrhage and radiation necrosis, but ultimately completely obliterated after 402 days and was left with mRS ≤2). Conclusion: Although we have a small sample size, fractionated SRS with Cyberknife resulted in 100% obliteration, low rates recurrent hemorrhage and low morbidity (no mortality). These outcomes are superior to published single fraction radiosurgery results in high risk patients. Further study with a prospective multicenter registry or as part of a larger RCT is warranted.

Stereotactic Radiosurgery for Pediatric Brain Arteriovenous Malformations: Long-Term Outcomes

Abstract INTRODUCTION Contrary to the better described obliteration and hemorrhage data after stereotactic radiosurgery (SRS) treatment of brain arteriovenous malformations (AVMs) in pediatric patients, estimates of the rarer complications including cyst and tumor formation are limited in the literature. The aim of the study was to assess the long-term outcomes and risks of SRS for AVMs in pediatric (age &lt; 18 yr) patients. METHODS We retrospectively analyzed the International Radiosurgery Research Foundation pediatric AVM database from 1987 to 2018. AVM obliteration, post-SRS hemorrhage, cyst formation, and tumor formation were assessed. Cumulative probabilities, adjusted for competing risk of death, were calculated. RESULTS The study cohort comprised 539 pediatric AVM patients (mean follow-up: 85.8 mo). AVM obliteration was observed in 64.3% of patients, with cumulative probabilities of 63.6% (95% CI: 58.8%-68.0%), 77.1% (95% CI: 72.1%-81.3%), and 88.1% (95% CI: 82.5%-92.0%) over 5, 10, and 15 yr, respectively. Post-SRS hemorrhage was observed in 8.4% of patients, with cumulative probabilities of 4.9% (95% CI: 3.1%-7.2%), 9.7% (95% CI: 6.4%-13.7%), and 14.5% (95% CI: 9.5%-20.5%) over 5, 10, and 15 yr, respectively. Cyst formation was observed in 2.1% of patients, with cumulative probabilities of 5.5% (95% CI: 2.3%-10.7%) and 6.9% (95% CI: 3.1%-12.9%) over 10 and 15 yr, respectively. Meningioma was observed in 2 patients (0.4%) at 10 and 12 yr after SRS, with cumulative probability of 3.1% (95% CI: 0.6%-9.7%) over 15 yr. CONCLUSION AVM obliteration can be expected after SRS in the majority of the pediatric population, with a relatively low risk of hemorrhage during the latency period. Cyst and benign tumor formation after SRS can be observed in 7% and 3% of patients over 15 yr, respectively. Longitudinal surveillance for delayed neoplasia is prudent despite its low incidence.

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.

Risk of Brain Arteriovenous Malformation Hemorrhage Before and After Stereotactic Radiosurgery.

Background and Purpose- Understanding the hemorrhage risks associated with brain arteriovenous malformations (AVMs) before and after stereotactic radiosurgery (SRS) is important. The aims of this multicenter, retrospective cohort study are to evaluate and compare the rates of pre- and post-SRS AVM hemorrhage and identify risk factors. Methods- We pooled AVM SRS data from 8 institutions participating in the International Radiosurgery Research Foundation. Predictors of post-SRS hemorrhage were determined using a multivariate logistic regression model. Pre- and post-SRS hemorrhage rates were compared using Fisher exact test. Ruptured and unruptured AVMs were matched in a 1:1 ratio using propensity scores, and their outcomes were compared. Results- The study cohort comprised 2320 AVM patients who underwent SRS. Deep AVM location (odds ratio, 1.86; 95% CI, 1.19-2.92; P=0.007), the presence of an AVM-associated arterial aneurysm (odds ratio, 2.44; 95% CI, 1.63-3.66; P<0.001), and lower SRS margin dose (odds ratio, 0.93; 95% CI, 0.88-0.98; P=0.005) were independent predictors of post-SRS hemorrhage. The post-SRS hemorrhage rate was lower for obliterated versus patent AVMs (6.0 versus 22.3 hemorrhages/1000 person-years; P<0.001). The AVM hemorrhage rate decreased from 15.4 hemorrhages/1000 person-years before SRS to 11.9 after SRS ( P=0.001). The outcomes of the matched ruptured versus unruptured AVM cohorts were similar. Conclusions- SRS appears to reduce the risk of AVM hemorrhage, although this effect is predominantly driven by obliteration. Deep-seated AVMs are more likely to rupture during the latency period after SRS. AVM-associated aneurysms should be considered for selective occlusion before SRS of the nidus to ameliorate the post-SRS hemorrhage rate of these lesions.

Correlation of Appearance of MRI Perinidal T2 Hyperintensity Signal and Eventual Nidus Obliteration Following Photon Radiosurgery of Brain AVMs: Combined Results of LINAC and Gamma Knife Centers

A wide variety of radiologic changes occur within and adjacent to the nidus of arteriovenous malformations (AVMs) after stereotactic radiosurgery (SRS). Our objective was to study the magnetic resonance imaging(MRI)-defined changes following photon radiosurgery of AVMs and specifically to correlate the appearance of a perinidal T2 hyperintensity signal with the eventual angiographic obliteration of an AVM nidus in response to SRS treatment. This retrospective study was conducted on 62 patients with brain AVMs who received photon SRS treatments between 2004 and 2017, using either a technique based on a linear accelerator at the Alexandria LINAC Radiosurgery Center in Egypt (21 patients/AVMs) or a technique based on a gamma unit at the Koto Memorial Gamma Knife Center in Japan (41 patients/AVMs). All patients included in the study had serial clinical and radiologic follow-ups for ≥ 2 years after SRS treatments. In the combined study series of 62 patients/AVMs treated with photon SRS, the follow-up MRIs revealed that 50 AVMs (80.6%) showed nonvisualized nidus and 12 AVMs (19.4%) showed decreased nidus size. Radiation-induced changes, defined as appearance of perinidal T2 hyperintensities in post-SRS MRIs, occurred in 34 patients (54.8%). Of the 35 patients with available follow-up angiographic studies, 30 AVMs (85.7%) demonstrated complete nidus obliteration at a mean of 36 months (range: 8-66 months) after SRS. Of the 30 AVMs with both MRI evidence of a nonvisualized nidus and angiographic verification of complete nidus obliteration, 20 AVMs (66.7%) were associated with prior MRI evidence of the appearance of a perinidal T2 hyperintensity signal at an average of 12 months (range: 6-45 months) after SRS. Of the five AVMs with both MRI evidence of decreased nidus size and angiographic verification of partial nidus obliteration, four AVMs (80%) showed perinidal T2 hyperintensity signal on post-SRS follow-up MRIs. Lower Spetzler-Martin grade (p = 0.013), smaller AVM volume (p = 0.017), and appearance of post-SRS perinidal T2 hyperintensity signal (p = 0.007) were the statistically significant independent predictors of AVM obliteration. The appearance of perinidal T2 hyperintensity signal in the post-SRS MRIs had a sensitivity of 66.7%, a specificity of 20%, and an overall accuracy of 60% in predicting the eventual obliteration of the AVM nidus. The present study may help improve our current understanding of the mechanisms behind the radiation-induced tissue changes following AVM SRS. Because the SRS-induced hemodynamic changes within the AVM nidus initiate the cascade of the subsequent formation of perinidal vasogenic brain edema, the appearance of perinidal high T2 signal in the follow-up MRIs after SRS would be a valuable indicator of the AVM response to SRS. The development of perinidal hyperintensity was the strongest predictive factor of AVM obliteration (p = 0.007), with relatively high sensitivity (66.7%) and accuracy (60%) and fairly low specificity (20%), as a prognostic sign of eventual complete angiographic obliteration of the AVM nidus following SRS.

When hoofbeats are zebras: Late onset niemann-pick disease type C overlapping with frontotemporal dementia

Stereotactic radiosurgery is widely used to treat brain arteriovenous malformation; however, detailed information on late radiation-induced complications (LRICs) is scarce. The goal of the present study was to characterize the incidence, risk factors, and clinical outcomes of LRICs based on our long-term follow-up data.The outcomes of consecutive patients who underwent stereotactic radiosurgery for arteriovenous malformations at our institution in 1990–2010 were analyzed. Cyst formation/encapsulated hematoma (CF/EH) and radiation-induced tumor were defined as LRICs. Cumulative incidence rates were calculated using the Kaplan-Meier method. Risk factors for CF/EH were analyzed using a Cox proportional hazard model.A total of 581 patients with mean and median follow-up periods of 11.8 and 10.1 years, respectively (range, 2.0–26.7 years), were analyzed. CF/EH was observed in 30 patients (5.2%). The median time to progression was 11.8 years (range, 1.9–23.9 years). Cumulative incidence rates were 0.8%, 2.8%, 7.6%, and 9.7% at 5, 10, 15, and 20 years, respectively. A multivariate analysis showed that lobar location and maximal diameter ≥22 mm were significant risk factors for CF/EH. Overall, the functional outcomes were mild, moderate, and severe/fatal in 26 (87%), 1 (3%), and 3 (10%) patients, respectively. Radiation-induced tumor was confirmed in only 1 patient (0.17%).An increased nidus size and lobar location are risk factors for CF/EH. Although the CF/EH incidence is low, some LRICs develop after long periods. Extended follow-up is warranted, particularly of patients with risk factors.

Re-Evaluating Clinical Outcomes for AVM Stereotactic Radiosurgery.

Traditional outcome measures after stereotactic radiosurgery (SRS) for cerebral arteriovenous malformations (AVMs) have focused predominantly on angiographic obliteration and general neurologic complications. Several grading scales attempting to predict the outcome for specific patients have previously been proposed and validated, and are outlined here. These have largely been based on both AVM and patient characteristics and attempt to predict obliteration. However, the most practical and clinically oriented goal in the management of AVMs is the prospective avoidance of neurological sequelae manifesting in the form of stroke or death, regardless of AVM obliteration. Long-term outcomes following SRS have demonstrated stroke or death rates of 1.5-2.0% per year for the first 5 years after SRS, followed by 0.2-0.4% annual risk thereafter. This focus on the avoidance of stroke or death is additionally crucial for direct comparisons to non-interventional natural history data. Here, we discuss the history of outcomes data on radiosurgery for AVMs and propose a re-evaluation of clinical outcome that is of most utility to the patient.

Radiation-Induced Changes After Stereotactic Radiosurgery for Brain Arteriovenous Malformations: A Systematic Review and Meta-Analysis.

Radiation-induced changes (RICs) are the most common complication of stereotactic radiosurgery (SRS) for brain arteriovenous malformations (AVMs), and they appear as perinidal T2-weighted hyperintensities on magnetic resonance imaging, with or without associated neurological symptoms. To determine the rates of RIC after AVM SRS and identify risk factors. A literature review was performed using PubMed and MEDLINE to identify studies reporting RIC in AVM patients treated with SRS. RICs were classified as radiologic (any neuroimaging evidence), symptomatic (any associated neurological deterioration, regardless of duration), and permanent (neurological decline without recovery). Baseline, treatment, and outcomes data were extracted for statistical analysis. Based on pooled data from 51 studies, the overall rates of radiologic, symptomatic, and permanent RIC after AVM SRS were 35.5% (1143/3222 patients, 32 studies), 9.2% (499/5447 patients, 46 studies), and 3.8% (202/5272 patients, 39 studies), respectively. Radiologic RIC was significantly associated with lack of prior AVM rupture (odds ratio [OR]=0.57; 95% confidence interval [CI]: 0.47-0.69; P<.001) and treatment with repeat SRS (OR=6.19; 95% CI: 2.42-15.85; P<.001). Symptomatic RIC was significantly associated with deep AVM location (OR=0.38; 95% CI: 0.21-0.67; P<.001). Approximately 1 in 3 patients with AVMs treated with SRS develop radiologically evident RIC, and of those with radiologic RIC, 1 in 4 develop neurological symptoms. Lack of prior AVM hemorrhage and repeat SRS are risk factors for radiologic RIC, and deep nidus location is a risk factor for symptomatic RIC.

Stereotactic Radiosurgery for Pediatric Versus Adult Brain Arteriovenous Malformations

Background and Purpose- The aim of this international, multicenter, retrospective matched cohort study is to directly compare the outcomes after stereotactic radiosurgery (SRS) for brain arteriovenous malformations (AVM) in pediatric versus adult patients. Methods- We performed a retrospective review of patients with AVM who underwent SRS at 8 institutions participating in the International Gamma Knife Research Foundation from 1987 to 2014. Patients were categorized into pediatric (<18 years of age) and adult (≥18 years of age) cohorts and matched in a 1:1 ratio using propensity scores. Favorable outcome was defined as AVM obliteration, no post-SRS hemorrhage, and no permanently symptomatic radiation-induced changes. Results- From a total of 2191 patients who were eligible for inclusion in the overall study cohort, 315 were selected for each of the matched cohorts. There were no significant differences between matched pediatric versus adult cohorts with respect to the rates of favorable outcome (59% versus 58%; P=0.936), AVM obliteration (62% versus 63%; P=0.934), post-SRS hemorrhage (9% versus 7%; P=0.298), radiological radiation-induced changes (26% versus 26%; P=0.837), symptomatic radiation-induced changes (7% versus 9%; P=0.383), or permanent radiation-induced changes (2% versus 3%; P=0.589). The all-cause mortality rate was significantly lower in the matched pediatric cohort (3% versus 10%; P=0.003). Conclusions- The outcomes after SRS for comparable AVMs in pediatric versus adult patients were not found to be appreciably different. SRS remains a reasonable treatment option for appropriately selected pediatric patients with AVM, who harbor a high cumulative lifetime hemorrhage risk. Age seems to be a poor predictor of AVM outcomes after SRS.