The American Association of Physicists in Medicine (AAPM) formed Task Group 178 (TG-178) to perform the following tasks: review in-phantom and in-air calibration protocols for gamma stereotactic radiosurgery (GSR), suggest a dose rate calibration protocol that can be successfully utilized with all gamma stereotactic radiosurgery (GSR) devices, and update quality assurance (QA) protocols in TG-42 (AAPM Report 54, 1995) for static GSR devices. The TG-178 report recommends a GSR dose rate calibration formalism and provides tabulated data to implement it for ionization chambers commonly used in GSR dosimetry. The report also describes routine mechanical, dosimetric, and safety checks for GSR devices, and provides treatment process quality assurance recommendations. Sample worksheets, checklists, and practical suggestions regarding some QA procedures are given in appendices. The overall goal of the report is to make recommendations that help standardize GSR physics practices and promote the safe implementation of GSR technologies.

Gamma Knife radiosurgery is an established technique for non-urgent treatment of various intracranial pathologies. Intra-procedural dislodgement of the stereotactic frame is an uncommon occurrence that could lead to abortion of ongoing treatment and necessitate more invasive treatment strategies. In this case report, we describe a novel method for resumption of Gamma Knife treatment after an unplanned intra-procedural interruption. The case example involves a radiosurgical treatment of a Spetzler-Martin grade I arteriovenous malformation. Our technique involves integration of scans and coordinate systems from two imaging sessions using the composite isodose line to resolve translational differences, thereby limiting delivery of remaining shots to the untreated region of the lesion. MRI follow-up at 13 months showed a reduction in the nidus size with no evidence of any radiation injury to the surrounding brain parenchyma. We believe this technique will allow care teams to effectively salvage interrupted Gamma Knife procedures and reduce progression to more invasive treatment options.

INTRODUCTION:We report results from a prospective phase I/II trial for patients with centrally located, early-stage NSCLC receiving stereotactic body radiation therapy. METHODS:Eligible patients were medically inoperable with biopsy-proven NSCLC within 2 cm of the proximal bronchial tree or 5 mm of the mediastinal pleura or parietal pericardium. Phase I had four dose levels using 5 fractions: 9, 10, 11, and 12 Gy per fraction. The primary phase II objective was to determine if the maximum tolerated dose in phase I achieved local control greater than 80% at 2 years. RESULTS:Seventy-four patients were enrolled; 23 to phase I and 51 to phase II. Two phase I patients treated with 10 Gy × 5 fractions developed unrelated acute grade 3 lung toxicities which resolved. The phase II dose level selected was 11 Gy × 5 fractions. The median follow-up for living phase II patients was 27 months (range, 9 to 58 months). Two-year local control using 11 Gy × 5 fractions was 85% (95% confidence interval [CI]: 62%-95%). Two-year overall survival was 43% (95% CI: 28%-57%). Three patients (6%, 95% CI: 1%-17%) experienced acute grade 3 and 4 cardiac or pulmonary toxicities. Of the 41 patients evaluable for late cardiac and pulmonary toxicity, 11 (27%, 95% CI: 14%-43%) developed grade 3, 5 (12%, 95% CI: 4%-26%) developed grade 4, and 1 (4%, 95% CI: 0%-13%) died of grade 5 toxicity. CONCLUSION:Stereotactic body radiation therapy for central NSCLC using 11 Gy × 5 fractions is tolerable and has excellent local control, but is associated severe late toxicity in some patients.

Novel functional and metabolic MRI imaging provides the ability to analyze tumor tissue properties including tumor vasculature, vascular permeability, tumor cellularity, hypoxia, and tumor proliferation. Stereotactic radiosurgery involves the delivery of a very precise, focal dose of radiation to a target. Recent advances in MR imaging have the potential to improve accuracy for target volume delineation and to potentially improve outcome. Novel MR imaging techniques may also be used in subsequent post-treatment follow-up to distinguish between tumor recurrences versus non-neoplastic treatment-related changes. In this paper, we address multiparametric MR imaging and cerebral angiography as tools to reduce toxicity.

Recently, radiation induced necrosis in the brain has been treated using bevacizumab, an anti-VEGF antibody. We validated the VEGF specificity by comparing the therapeutic efficacy of anti-VEGF with non-specific isotype control antibody. Additionally, we found that VEGF over-expression and RN developed simultaneously, which precludes preventative anti-VEGF treatment.

Purpose To develop a Gamma Knife-based mouse model of late time-to-onset, cerebral radiation necrosis (RN) with serial evaluation by magnetic resonance imaging (MRI) and histology. Methods and Materials Mice were irradiated with the Leksell Gamma Knife® (GK) PerfexionTM (Elekta AB; Stockholm, Sweden) with total single-hemispheric radiation doses (TRD) of 45- to 60-Gy, delivered in one to three fractions. RN was measured using T2-weighted MR images, while confirmation of tissue damage was assessed histologically by hematoxylin & eosin, trichrome, and PTAH staining. Results MRI measurements demonstrate that TRD is a more important determinant of both time-to-onset and progression of RN than fractionation. The development of RN is significantly slower in mice irradiated with 45-Gy than 50- or 60-Gy, where RN development is similar. Irradiated mouse brains demonstrate all of the pathologic features observed clinically in patients with confirmed RN. A semi-quantitative (0 to 3) histologic grading system, capturing both the extent and severity of injury, is described and illustrated. Tissue damage, as assessed by a histologic score, correlates well with total necrotic volume measured by MRI (correlation coefficient = 0.948, with p<0.0001), and with post-irradiation time (correlation coefficient = 0.508, with p<0.0001). Conclusions Following GK irradiation, mice develop late time-to-onset cerebral RN histology mirroring clinical observations. MR imaging provides reliable quantification of the necrotic volume that correlates well with histologic score. This mouse model of RN will provide a platform for mechanism of action studies, the identification of imaging biomarkers of RN, and the development of clinical studies for improved mitigation and neuroprotection.

BACKGROUND:While most meningiomas are benign, aggressive meningiomas are associated with high levels of recurrence and mortality. A single institution's Gamma Knife radiosurgical experience with atypical and malignant meningiomas is presented, stratified by the most recent WHO classification.METHODS:Thirty-one patients with atypical and 4 patients with malignant meningiomas treated with Gamma Knife radiosurgery between July 2000 and July 2011 were retrospectively reviewed. All patients underwent prior surgical resection. Overall survival was the primary endpoint and rate of disease recurrence in the brain was a secondary endpoint. Patients who had previous radiotherapy or prior surgical resection were included. Kaplan-Meier and Cox proportional hazards models were used to estimate survival and identify factors predictive of recurrence and survival.RESULTS:Post-Gamma Knife recurrence was identified in 11 patients (31.4%) with a median overall survival of 36 months and progression-free survival of 25.8 months. Nine patients (25.7%) had died. Three-year overall survival (OS) and progression-free survival (PFS) rates were 78.0% and 65.0%, respectively. WHO grade II 3-year OS and PFS were 83.4% and 70.1%, while WHO grade III 3-year OS and PFS were 33.3% and 0%. Recurrence rate was significantly higher in patients with a prior history of benign meningioma, nuclear atypia, high mitotic rate, spontaneous necrosis, and WHO grade III diagnosis on univariate analysis; only WHO grade III diagnosis was significant on multivariate analysis. Overall survival was adversely affected in patients with WHO grade III diagnosis, prior history of benign meningioma, prior fractionated radiotherapy, larger tumor volume, and higher isocenter number on univariate analysis; WHO grade III diagnosis and larger treated tumor volume were significant on multivariate analysis.CONCLUSION:Atypical and anaplastic meningiomas remain difficult tumors to treat. WHO grade III diagnosis and treated tumor volume were significantly predictive of recurrence and survival on multivariate analysis in aggressive meningioma patients treated with radiosurgery. Larger tumor size predicts poor survival, while nuclear atypia, necrosis, and increased mitotic rate are risk factors for recurrence. Clinical and pathologic predictors may help identify patients that are at higher risk for recurrence.

Purpose: To quantify the effectiveness of SB415286, a specific inhibitor of GSK-3 beta, as a neuroprotectant against radiation-induced central nervous system (brain) necrosis in a mouse model.Methods and Materials: Cohorts of mice were treated with SB415286 or dimethyl sulfoxide (DMSO) prior to irradiation with a single 45-Gy fraction targeted to the left hemisphere (brain) using a gamma knife machine. The onset and progression of radiation necrosis (RN) were monitored longitudinally by noninvasive in vivo small-animal magnetic resonance imaging (MRI) beginning 13 weeks postirradiation. MRI-derived necrotic volumes for SB415286- and DMSO-treated mice were compared. MRI results were supported by correlative histology.Results: Mice treated with SB415286 showed significant protection from radiation-induced necrosis, as determined by in vivo MRI with histologic validation. MRI-derived necrotic volumes were significantly smaller at all postirradiation time points in SB415286-treated animals. Although the irradiated hemispheres of the DMSO-treated mice demonstrated many of the classic histologic features of RN, including fibrinoid vascular necrosis, vascular telangiectasia, hemorrhage, and tissue loss, the irradiated hemispheres of the SB415286-treated mice consistently showed only minimal tissue damage. These studies confirmed that treatment with a GSK-3 beta inhibitor dramatically reduced delayed time-to-onset necrosis in irradiated brain.Conclusions: The unilateral cerebral hemispheric stereotactic radiation surgery mouse model in concert with longitudinal MRI monitoring provided a powerful platform for studying the onset and progression of RN and for developing and testing new neuroprotectants. Effectiveness of SB415286 as a neuroprotectant against necrosis motivates potential clinical trials of it or other GSK-3 beta inhibitors. (C) 2014 Elsevier Inc.

PURPOSE:Accurate noninvasive diagnosis is vital for effective treatment planning. Presently, standard anatomical magnetic resonance imaging (MRI) is incapable of differentiating recurring tumor from delayed radiation injury, as both lesions are hyperintense in both postcontrast T1- and T2-weighted images. Further studies are therefore necessary to identify an MRI paradigm that can differentially diagnose these pathologies. Mouse glioma and radiation injury models provide a powerful platform for this purpose. METHODS AND MATERIALS:Two MRI contrasts that are widely used in the clinic were chosen for application to a glioma/radiation-injury model: diffusion weighted imaging, from which the apparent diffusion coefficient (ADC) is obtained, and magnetization transfer contrast, from which the magnetization transfer ratio (MTR) is obtained. These metrics were evaluated longitudinally, first in each lesion type alone-glioma versus irradiation - and then in a combined irradiated glioma model. RESULTS:MTR was found to be consistently decreased in all lesions compared to nonlesion brain tissue (contralateral hemisphere), with limited specificity between lesion types. In contrast, ADC, though less sensitive to the presence of pathology, was increased in radiation injury and decreased in tumors. In the irradiated glioma model, ADC also increased immediately after irradiation, but decreased as the tumor regrew. CONCLUSIONS:ADC is a better metric than MTR for differentiating glioma from radiation injury. However, MTR was more sensitive to both tumor and radiation injury than ADC, suggesting a possible role in detecting lesions that do not enhance strongly on T1-weighted images.

Purpose: To quantify the effectiveness of anti-VEGF antibodies (bevacizumab and B20-4.1.1) as mitigators of radiation-induced, central nervous system (brain) necrosis in a mouse model.Experimental Design: Cohorts of mice were irradiated with single-fraction 50-or 60-Gy doses of radiation targeted to the left hemisphere (brain) using the Leksell Perfexion Gamma Knife. The onset and progression of radiation necrosis were monitored longitudinally by in vivo, small-animal MRI, beginning 4 weeks after irradiation. MRI-derived necrotic volumes for antibody (Ab)-treated and untreated mice were compared. MRI results were supported by correlative histology.Results: Hematoxylin and eosin-stained sections of brains from irradiated, non-Ab-treated mice confirmed profound tissue damage, including regions of fibrinoid vascular necrosis, vascular telangiectasia, hemorrhage, loss of neurons, and edema. Treatment with the murine anti-VEGF antibody B20-4.1.1 mitigated radiation-induced changes in an extraordinary, highly statistically significant manner. The development of radiation necrosis in mice under treatment with bevacizumab (a humanized anti-VEGF antibody) was intermediate between that for B20-4.1.1-treated and non-Ab-treated animals. MRI findings were validated by histologic assessment, which confirmed that anti-VEGF antibody treatment dramatically reduced late-onset necrosis in irradiated brain.Conclusions: The single-hemispheric irradiation mouse model, with longitudinal MRI monitoring, provides a powerful platform for studying the onset and progression of radiation necrosis and for developing and testing new therapies. The observation that anti-VEGF antibodies are effective mitigants of necrosis in our mouse model will enable a wide variety of studies aimed at dose optimization and timing and mechanism of action with direct relevance to ongoing clinical trials of bevacizumab as a treatment for radiation necrosis.

PURPOSE:To evaluate local control rates and predictors of individual tumor local control for brain metastases from non-small cell lung cancer (NSCLC) treated with stereotactic radiosurgery (SRS). METHODS AND MATERIALS:Between June 1998 and May 2011, 401 brain metastases in 228 patients were treated with Gamma Knife single-fraction SRS. Local failure was defined as an increase in lesion size after SRS. Local control was estimated using the Kaplan-Meier method. The Cox proportional hazards model was used for univariate and multivariate analysis. Receiver operating characteristic analysis was used to identify an optimal cutpoint for conformality index relative to local control. A P value <.05 was considered statistically significant. RESULTS:Median age was 60 years (range, 27-84 years). There were 66 cerebellar metastases (16%) and 335 supratentorial metastases (84%). The median prescription dose was 20 Gy (range, 14-24 Gy). Median overall survival from time of SRS was 12.1 months. The estimated local control at 12 months was 74%. On multivariate analysis, cerebellar location (hazard ratio [HR] 1.94, P=.009), larger tumor volume (HR 1.09, P<.001), and lower conformality (HR 0.700, P=.044) were significant independent predictors of local failure. Conformality index cutpoints of 1.4-1.9 were predictive of local control, whereas a cutpoint of 1.75 was the most predictive (P=.001). The adjusted Kaplan-Meier 1-year local control for conformality index ≥ 1.75 was 84% versus 69% for conformality index <1.75, controlling for tumor volume and location. The 1-year adjusted local control for cerebellar lesions was 60%, compared with 77% for supratentorial lesions, controlling for tumor volume and conformality index. CONCLUSIONS:Cerebellar tumor location, lower conformality index, and larger tumor volume were significant independent predictors of local failure after SRS for brain metastases from NSCLC. These results warrant further investigation in a prospective setting.

An anthropomorphic head phantom, constructed from a water-equivalent plastic shell with only a spherical target, was modified to include a nonspherical target (pituitary) and an adjacent organ at risk (OAR) (optic chiasm), within 2 mm, simulating the anatomy encountered when treating acromegaly. The target and OAR spatial proximity provided a more realistic treatment planning and dose delivery exercise. A separate dosimetry insert contained two TLD for absolute dosimetry and radiochromic film, in the sagittal and coronal planes, for relative dosimetry. The prescription was 25 Gy to 90% of the GTV, with ≤ 10% of the OAR volume receiving ≥ 8 Gy for the phantom trial. The modified phantom was used to test the rigor of the treatment planning process and phantom reproducibility using a Gamma Knife, CyberKnife, and linear accelerator (linac)-based radiosurgery system. Delivery reproducibility was tested by repeating each irradiation three times. TLD results from three irradiations on a CyberKnife and Gamma Knife agreed with the calculated target dose to within ± 4% with a maximum coefficient of variation of ± 2.1%. Gamma analysis in the coronal and sagittal film planes showed an average passing rate of 99.4% and 99.5% using ± 5%/3 mm criteria, respectively. Results from the linac irradiation were within ± 6.2% for TLD with a coefficient of variation of ± 0.1%. Distance to agreement was calculated to be 1.2 mm and 1.3mm along the inferior and superior edges of the target in the sagittal film plane, and 1.2 mm for both superior and inferior edges in the coronal film plane. A modified, anatomically realistic SRS phantom was developed that provided a realistic clinical planning and delivery challenge that can be used to credential institutions wanting to participate in NCI-funded clinical trials.

BACKGROUND:This study tested the hypothesis that time of day of treatment with stereotactic radiosurgery (SRS) has an effect on local control (LC) and overall survival (OS) in a large cohort of patients with non-small cell lung cancer (NSCLC) brain metastases. METHODS:At Washington University in St. Louis, 437 patients with NSCLC were treated with SRS for NSCLC brain metastases. Receiver operating characteristics analysis was used to identify an optimal cut-point for OS relative to time of day. Kaplan-Meier log-rank statistics, and Cox regression univariate and multivariate analysis were employed to isolate any independent effect of treatment time on OS and LC. Matched-pair analysis was performed to isolate any independent effect of time on OS and LC of day while controlling for confounding variables. RESULTS:Receiver operating characteristics analysis identified a cut-point of 11:41 AM as providing the highest predictive value for OS. On univariate analysis, late SRS was associated with decreased OS, as was age, Karnofsky performance status, risk-stratification schemes, extracranial disease status, and overall burden of brain metastases. On univariate analysis for LC, late SRS was associated with decreased LC, as was burden of brain metastases. On multivariate analysis, only Graded Prognostic Assessment remained predictive of OS, and total number of targets and total tumor volume remained predictive of LC. Matched-pair analysis demonstrated no significant effect of time of day on LC or OS. CONCLUSIONS:Although earlier treatment appears to be associated with improved LC and OS, treatment time fails to remain significant when accounting for confounding variables.

Background Breast cancer is the second most common cause of brain metastases in the United States. Although breast cancer induced brain metastases represent an incurable condition, some patients experience prolonged survival. In this retrospective study, we examine a cohort of patients with brain metastases from breast cancer treated with Gamma Knife stereotactic radiosurgery to identify factors that predict better outcomes. Methods A retrospective database of 100 patients treated for brain metastases due to breast cancer via Gamma Knife radiosurgery (GKS) from July 1998 through March 2009 was reviewed. Patients who received radiosurgery as sole treatment, as a planned boost after whole brain radiotherapy or surgical resection, or as salvage after prior whole brain radiation therapy (WBRT) or surgical resection were included. Prognostic factors identified to be significant for survival in previous brain metastasis studies were analyzed for significance by univariate and multivariate Cox analysis. Results Overall, the median brain progression-free survival time was 7.1 months and the median survival time was 12.3 months. No prognostic variables were significant for brain progression-free survival. For patients treated with a planned GKS after WBRT, GKS as sole treatment, GKS salvage after WBRT, GKS boost after surgery, or GKS for surgical salvage the median survival times (MSTs) were as follows: 12.2 months, 12.4 months, 9.5 months, 27.6 months and 33.4 months respectively. Differences between the groups were not significant ( p = 0.06); however, GKS boost after surgery and GKS for salvage after surgery did have a trend toward better overall survival. The MST for patients of age <65 years was 14.5 months, compared to age ≥65 which was 7.7 months ( p = 0.06) and remained a significant prognostic factor for overall survival on multivariate analysis. The MST for patients with a single lesion was 16.9 months, not significantly different than the MST of 14.5 months for patients with 2–3 lesions. However patients with >3 lesions had a MST of 5.9 months, which was significantly worse. Breast cancer subtype as approximated by biomarkers and KPS were not significant predictors of overall survival and stage at initial diagnosis was inversely associated with survival. Conclusion Stereotactic radiosurgery offers good local control and prolonged survival in selected patients. Age and number of lesions are strong predictors of overall survival.

One of the most important aspects of quality assurance (QA) in radiation therapy is redundancy of patient treatment dose calculation. This work is focused on the patient-specific time and 3D dose treatment plan verification for stereotactic radio-surgery using Leksell Gamma Knife Perfexion (LGK PFX). The virtual model of LGK PFX was developed in MATLAB, based on the physical dimensions provided by the manufacturer. The ring-specific linear attenuation coefficients (LAC) and output factors (OFs) reported by the manufacturer were replaced by the measurement-based collimator size-specific OFs and a single LAC = 0.0065 mm(-1). Calculation depths for each LGK PFX shot were obtained by ray-tracing technique, and the dose calculation formalism was similar to the one used by GammaPlan treatment planning software versions 8 and 9. The architecture of the QA process was based on the in-house online database search of the LGK PFX database search for plan-specific information. A series of QA phantom plans was examined to verify geometric and dosimetric accuracy of the software. The accuracy of the QA process was further evaluated through evaluation of a series of patient plans. The shot time/focus point dose verification for each shot took less than 1 sec/shot with full 3D isodose verification taking about 30 sec/shot on a desktop PC. GammaPlan database access time took less than 0.05 sec. The geometric accuracy (location of the point of maximum dose) of the phantom and patient plan was dependent on the resolution of the original dose matrix and was of the order of 1 dose element. Dosimetric accuracy of the independently calculated phantom and patient point (focus) doses was within 3.5% from the GammaPlan, with the mean = 2.3% and SD= 1.1%. The process for independent pretreatment patient-specific Gamma Knife Perfexion time and dose verification was created and validated.

Object: The Gamma Knife Extend system is designed for noninvasive fractioned radiosurgery. Such a system theoretically allows clinicians to use radiosurgery for larger volumes and targets near eloquent areas and re-treatments, which were previously not possible in a single fraction. Here we describe the Washington University initial clinical experience with dose, fractionation, patient setup, and outcomes.

BACKGROUND:Gamma Knife radiosurgery (GKS) is a primary treatment modality for small, surgically-challenging meningiomas of the skull base in carefully selected patients. Despite the overall low incidence of complications from this procedure, rare instances of hemorrhagic events following GKS have been reported. In fact, only a single, probable case of acute hemorrhage after GKS for a meningioma exists in the literature.CASE DESCRIPTION:The authors present the case of a 59-year-old female treated with GKS to a clival meningioma who suffered an acute intra- and peritumoral hemorrhage within three hours after the procedure. The patient also had an ST-elevation myocardial infarction associated with the hemorrhage. At the time of her GKS she was taking aspirin and clopidogrel for treatment of coronary artery disease with multiple cardiac stents. Cerebral catheter angiography failed to reveal a source for the hemorrhage.CONCLUSION:Acute hemorrhage following GKS to a meningioma is a rare, but potentially serious, complication and consideration should be given to counseling patients of this risk prior to treatment. We hypothesize that acute change to the structural integrity of the vascular endothelium after GKS may have precipitated cerebrovascular dysfunction resulting in hemorrhage. While the administration of anti-platelet therapy may have been a contributing factor to his event, it appears that the low incidence of acute tumoral bleeding after GKS does not justify routinely discontinuing anti-platelet and/or anti-coagulation in patients with severe associated medical co-morbidities.

Carlos J Perez-Torres, John A Engelbach, Jeremy Cates, Dinesh K Thotala, Robert E Drzymala, Joseph JH Ackerman, and Joel R Garbow Department of Radiology, Washington University in Saint Louis, Saint Louis, Missouri, United States, Department of Radiation Oncology, Washington University in Saint Louis, Saint Louis, Missouri, United States, Department of Chemistry, Washington University in Saint Louis, Saint Louis, Missouri, United States

PURPOSE:To identify risk factors for the development of chest wall (CW) pain after thoracic stereotactic body radiotherapy (SBRT).METHODS AND MATERIALS:A registry of patients with lung lesions treated with lung SBRT was explored to identify patients treated with 54 Gy in three fractions or 50 Gy in five fractions. One hundred and forty-six lesions in 140 patients were identified; complete electronic treatment plans were available on 86 CWs. The CW was contoured as a 3 cm outward expansion from the involved lung. Univariate and multivariate analyses were used to correlate patient, tumor, and dosimetric factors to the development of CW toxicity.RESULTS:CW pain occurred in 22 patients (15.7%). The Kaplan-Meier estimated risk of CW pain at 2 years was 20.1% (95% C.I., 13.2-28.8%). On univariate analysis of patient factors, elevated BMI (p=0.026) and connective tissue disease (p=0.036) correlated with CW pain. The percent of CW receiving 30, 35, or 40 Gy was most predictive of CW pain on multivariate analysis using logistic regression, while V40 alone was predictive using Cox regression. A V30 threshold of 0.7% and V40 threshold of 0.19% was correlated with a 15% risk of CW pain.CONCLUSIONS:We have described patient and dosimetric parameters that correlate with CW pain after lung SBRT. The risk of CW pain may be mitigated by attempting to reduce the relative proportion of CW receiving 30-40 Gy during treatment planning.

OBJECT:Large cerebral arteriovenous malformations (AVMs) are often not amenable to direct resection or stereotactic radiosurgery (SRS) treatment. An alternative treatment strategy is staged endovascular embolization followed by SRS (Embo/SRS). The object of this study was to examine the experience at Washington University in St. Louis with Embo/SRS for large AVMs and review the results in earlier case series.METHODS:Twenty-one cases involving patients with large AVMs treated with Embo/SRS between 1994 and 2006 were retrospectively evaluated. The AVM size (before and after embolization), procedural complications, radiological outcome, and neurological outcome were examined. Radiological success was defined as AVM obliteration as demonstrated by catheter angiography, CT angiography, or MR angiography. Radiological failure was defined as residual AVM as demonstrated by catheter angiography, CT angiography, or MR angiography performed at least 3 years after SRS.RESULTS:The maximum diameter of all AVMs in this series was > 3 cm (mean 4.2 cm); 12 (57%) were Spetzler-Martin Grade IV or V. Clinical follow-up was available in 20 of 21 cases; radiological follow-up was available in 19 of 21 cases (mean duration of follow-up 3.6 years). Forty-three embolization procedures were performed; 8 embolization-related complications occurred, leading to transient neurological deficits in 5 patients (24%), minor permanent neurological deficits in 3 patients (14%), and major permanent neurological deficits in none (0%). Twenty-one SRS procedures were performed; 1 radiation-induced complication occurred (5%), leading to a permanent minor neurological deficit. Of the 20 patients with clinical follow-up, none experienced cerebral hemorrhage. In the 19 patients with radiological follow-up, AVM obliteration was confirmed by catheter angiography in 13, MR angiography in 2, and CT angiography in 1. Residual nidus was found in 3 patients. In patients with follow-up catheter angiography, the AVM obliteration rate was 81% (13 of 16 cases).CONCLUSIONS:Staged endovascular embolization followed by SRS provides an effective means of treating large AVMs not amenable to standard surgical or SRS treatment. The outcomes and complication rates reported in this series compare favorably to the results of other reported therapeutic strategies for this very challenging patient population.