Volume-staged Stereotactic Radiosurgery Research Articles

Quantitative Analysis of Parenchymal Effects and Flow of Large Arteriovenous Malformations Managed With Stereotactic Radiosurgery.

Stereotactic radiosurgery (SRS) of larger arteriovenous malformations (AVM) is associated with an elevated incidence of adverse radiation effects (ARE). To date, volume-response and dose-response models have been used to predict such effects. To understand radiological outcomes and their hemodynamic effects on the regional brain. A retrospective analysis was conducted at our institution using a prospective registry of patients managed between 2014 and 2020. We included patients with AVM with a nidus larger than 5 cc who received either single-session or volume-staged Gamma Knife radiosurgery. AVM volume changes, volumes of parenchymal response, and obliteration were analyzed and correlated with transit times and diameters of feeding arteries and draining veins. Sixteen patients underwent single-session SRS, and 9 patients underwent volume-staged SRS. The average AVM volume was 12.6 cc (5.5-23). The AVM locations were predominantly lobar (80%) and 17 (68%) were in critical locations. The mean margin dose was 17.2 Gy (15-21), and the median V12Gy was 25.5 cc. Fourteen (56%) AVMs had a transit time shorter than 1 second. The median vein-artery ratio (sum diameter of the veins/sum diameter of feeding arteries) was 1.63 (range, 0.60-4.19). Asymptomatic parenchymal effects were detected in 13 (52%) patients and were symptomatic in 4 (16%) patients. The median time to ARE was 12 months (95% CI 7.6-16.4). On univariate analysis, significant predictors of ARE were lower vein-artery ratio ( P = .024), longer transit time ( P = .05), higher mean dose ( P = .028), and higher D95 ( P = .036). Transit times and vessel diameters are valuable predictors of the subsequent parenchymal response after SRS. A more quantitative understanding of blood flow is critical for predicting the effects on the regional brain after AVM radiosurgery.

Stereotactic radiosurgery for intermediate- and high-grade arteriovenous malformations: outcomes stratified by the supplemented Spetzler-Martin grading system.

The supplemented Spetzler-Martin (Supp-SM) grading system was developed to improve the predictive accuracy of surgical risk for patients with brain arteriovenous malformations (AVMs). The aim of this study was to apply the Supp-SM grading system to patients having stereotactic radiosurgery (SRS) for Spetzler-Martin (SM) intermediate- (grade III) or high-grade (grade IV-V) AVMs to enable comparison with published microsurgical series. In 219 patients who underwent SRS during the period from 1990 to 2016, the Supp-SM grade was calculated for SM grade III (n = 154) or SM grade IV-V (n = 65) AVMs. The Supp-SM grades in these patients were 4 (n = 14, 6%), 5 (n = 36, 16%), 6 (n = 67, 31%), 7 (n = 76, 35%), and 8-9 (n = 26, 12%). Sixty patients (27%) had deep AVMs (basal ganglia, thalamus, or brainstem). Thirty-nine patients (18%) had volume-staged SRS; 41 patients (19%) underwent repeat SRS. The median follow-up period was 69 months for SM grade III AVMs and 113 months for SM grade IV-V AVMs. AVM obliteration was confirmed in 163 patients (74%) at a median of 38 months after initial SRS. The obliteration rates at 4 and 8 years were 59% and 76%, respectively. Thirty-one patients (14%) had post-SRS deficits from hemorrhage (n = 7, 3%) or radiation injury (n = 24, 11%). Six patients (3%) died after SRS (hemorrhage, n = 5; radiation injury, n = 1). The rates of neurological decline or death at 4 and 8 years were 11% and 18%, respectively. Factors predictive of nonobliteration were deep location (HR 0.57, 95% CI 0.39-0.82, p = 0.003) and increasing AVM volume (HR 0.96, 95% CI 0.93-0.99, p = 0.002). Increasing AVM volume was the only factor associated with neurological decline (HR 1.05, 95% CI 1.02-1.08, p = 0.002). The Supp-SM grading score did not correlate with either obliteration (HR 0.94, 95% CI 0.82-1.09, p = 0.43) or neurological decline (HR 1.15, 95% CI 0.84-1.56, p = 0.38). The Supp-SM grading system was not predictive of outcomes after SRS of intermediate- or high-grade AVM. In a cohort that included a high percentage (47%) of "inoperable" AVMs according to Supp-SM grade (≥ 7), most patients had obliteration after SRS, although there was a high risk of neurological decline.

Volume Fractionation Stereotactic Radiosurgery for Large Volume Intracranial Arteriovenous Malformations.

Arteriovenous malformations (AVMs) are common intracranial vascular anomalies. Common treatment modalities used to manage AVMs are surgical excision, embolization, and stereotactic radiosurgery (SRS). Large AVMs are defined as AVMs larger than 10 cm3 and pose a therapeutic challenge with high rates of treatment-related morbidity and mortality. Single-stage SRS is a good option for small AVMs but carries high risks of radiation-induced complications in large AVMs. Volume-staged SRS (VS-SRS) is a newer strategy used in large AVMs that allows one to deliver an optimal radiation dose to the AVMs while reducing the risk of radiation damage to the normal brain. It involves the division of AVM into multiple small sectors which are irradiated at different time intervals with high radiation doses. Good obliteration rates with less risk of radiation-induced complications have been described in the literature with VS-SRS.

Volume staging for arteriovenous malformation SRS treatment using VMAT.

Volume staging involves dividing the target volume into smaller parts and treating each part separately. In this study, the feasibility of volume-staged stereotactic radiosurgery (VS-SRS) on a linear accelerator using volumetric modulated arc therapy (VMAT) and a frameless patient positioning system is investigated. Ten patients, previously treated with hypofractionated stereotactic radiotherapy with arteriovenous malformation (AVM) sized from 1.6 to 4.0cm in diameter, were selected. VS-SRS plans were created with the VMAT technique on the Varian Eclipse treatment planning system (TPS) using the TrueBeam STx linear accelerator. For each patient, an AVM-VMAT set was planned with the AVM as the target and a PTV-VMAT set using the (PTV=AVM+1mm) as the target. All targets were divided into two sub-volumes. The TPS data from the AVM-VMAT plans was compared to Gamma Knife (GK) VS-SRS plan data available in the literature. The AVM-VMAT and PTV-VMAT plans were compared to investigate the effect of a 1mm PTV margin on normal brain (NB) dose. End-to-end testing was performed using a GaFchromic EBT3 film and point-dose measurements. Dosimetric effects of multiple setups were investigated through film-to-film comparisons. Median target dose coverage, NB V12Gy , and conformity index for the AVM-VMAT plans were 97.5%, 17cm3 , and 0.8, respectively. PTV-VMAT plans attained comparable target dose coverage, but the average NB V12Gy increased by 48.9% when compared to the AVM-VMAT plans. Agreement of point-dose measurements with TPS calculations was -0.6% when averaged over all patients. Gamma analysis passing rates were above 90% for all film-to-film comparisons (2%/1mm criteria), and for the film to TPS comparison (5%/1mm). This work suggests that VMAT is capable of producing VS-SRS plans with similar dose falloff characteristics as GK plans. NB dose depends on PTV margin size, and two-stage treatment setups do not appear to contribute additional uncertainty to treatment delivery.

Adverse radiation effects in volume-staged radiosurgery for large arteriovenous malformations: a multiinstitutional study.

The optimal treatment paradigm for large arteriovenous malformations (AVMs) is controversial. One approach is volume-staged stereotactic radiosurgery (VS-SRS). The authors previously reported efficacy of VS-SRS for large AVMs in a multiinstitutional cohort; here they focus on risk of symptomatic adverse radiation effects (AREs). This is a multicentered retrospective review of patients treated with a planned prospective volume staging approach to stereotactically treat the entire nidus of an AVM, with volume stages separated by intervals of 3-6 months. A total of 9 radiosurgical centers treated 257 patients with VS-SRS between 1991 and 2016. The authors evaluated permanent, transient, and total ARE events that were symptomatic. Patients received 2-4 total volume stages. The median age was 33 years at the time of the first SRS volume stage, and the median follow-up was 5.7 years after VS-SRS. The median total AVM nidus volume was 23.25 cm3 (range 7.7-94.4 cm3), with a median margin dose per stage of 17 Gy (range 12-20 Gy). A total of 64 patients (25%) experienced an ARE, of which 19 were permanent. Rather than volume, maximal linear dimension in the Z (craniocaudal) dimension was associated with toxicity; a threshold length of 3.28 cm was associated with an ARE, with a 72.5% sensitivity and a 58.3% specificity. In addition, parietal lobe involvement for superficial lesions and temporal lobe involvement for deep lesions were associated with an ARE. Size remains the dominant predictor of toxicity following SRS, but overall rates of AREs were lower than anticipated based on baseline features, suggesting that dose and size were relatively dissociated through volume staging. Further techniques need to be assessed to optimize outcomes.

Volume staged stereotactic radiosurgery and endovascular embolization in the treatment of cerebral proliferative angiopathy: lessons learned

Purpose of the Article Cerebral proliferative angiopathy (CPA) is a rare and recently characterized vascular malformation that is often mistaken for a large, diffuse arteriovenous malformation (AVM). However, distinguishing the two entities is critical, as while the diseases may appear similar on imaging, they are completely different entities. The most distinguishing features of CPA compared to AVM are the presence of normal functioning brain within the ‘nidus’ of the abnormality and the proliferative nature of the nidus. While the management of AVM is considered well understood, the management of CPA is unclear. Typical treatment may include conservative management, targeted embolization, and/or surgical revascularization. Materials and Methods Here, we present a patient who was initially diagnosed with a large, diffuse AVM in the posterior fossa. Initially managed conservatively, the development of progressive, debilitating neurologic symptoms prompted treatment. We pursued staged endovascular intervention and improved her initial outlook. Thereafter, volume-staged stereotactic radiosurgery (VS-SRS) was pursued to attempt to achieve a definitive treatment. Results and Conclusions Ultimately, while the treatment proved successful clinically and radiographically, the post-treatment course was exceptionally challenging. In retrospect, it is clear the working diagnosis was incorrect, and CPA was the true diagnosis. To our knowledge, this is the first known application of this treatment approach for CPA. However, the post-treatment course and final clinical outcome likely reflect the important differences between AVM and CPA. For these reasons, we are cautious to recommend the treatment course as prescribed in this case but hope to highlight important lessons learned in managing this rare condition.

Volume-Staged Radiosurgery for Large Arteriovenous Malformation: Retrospective Analysis of 19 Cases

IntroductionThe effectiveness of Gamma Knife surgery (GKS) for small arteriovenous malformations (AVMs) is well known. However, for large AVMs, the prescribed dose should be decreased to reduce the risk of radiation damage, but it leads to a decrease in nidus obliteration rates. Therefore, it is very difficult to achieve complete obliteration of large AVMs in a single treatment, and methods using multiple irradiation such as volume-staged stereotactic radiosurgery (VS-SRS) have been suggested. We retrospectively reviewed our results of VS-SRS for large AVMs to assess the efficacy of VS-SRS.MethodsNineteen patients with AVMs of ≥10 ml and who consented to VS-SRS were treated by this surgical strategy and retrospectively analyzed. We excluded AVMs that were too large such as those >40 cc to avoid severe radiation damage. The components were divided mainly in the vertical direction, and each component was irradiated with a marginal dose of 18 Gy. Each irradiation was performed at intervals of 3-6 months, and the components with main feeders were irradiated first, and the components that included the main drainer were irradiated last. We tried to keep V18 to <10 ml if possible. The follow-up after GKS was performed by MRI every 6 months, and cerebral angiography was performed to confirm complete nidus obliteration, but if the patient refused, it was judged on the basis of MRI findings.ResultsNineteen patients with a mean age of 40.2 years underwent VS-SRS. Each compartment was irradiated at 3­-16 month (median, 3 months) intervals. The mean initial AVM volume was 19 ± 5.6 ml. Fourteen patients received two-stage radiosurgery and five received three-stage radiosurgery. The median target volume was 9.1 ml at stage 1, 9.0 ml at stage 2, and 10.1 ml at stage 3. The median margin dose was 18 Gy at each stage. The mean follow-up after the last stage of radiosurgery was 3.9 (1-11.4) years. Complete obliteration was confirmed by angiography in six patients, and by magnetic resonance angiography in one patient. The cumulative obliteration rates were 30.7% and 58.2% at 3 and 5 years following VS-SRS, respectively. The cumulative hemorrhage rates were 7.1% and 22.1% at 3 and 5 years, respectively. MRI showed T2-weighted prolongation in 15 patients (78.9%). Of these 15 patients, four were symptomatic (epilepsy in all) and two underwent surgical removal of symptomatic expanding hematomas.ConclusionsIn our experience, VS-SRS offers a viable treatment strategy in patients with large AVMs. Further optimization of the dose and volume at each stage is required.

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.

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.

Dose response and architecture in volume staged radiosurgery for large arteriovenous malformations: A multi-institutional study

BackgroundOptimal treatment paradigm for large arteriovenous malformations (AVMs) is controversial. Volume-staged stereotactic radiosurgery (VS-SRS) provides an effective option for these high-risk lesions, but optimizing treatment for these recalcitrant and rare lesions has proven difficult. MethodsThis is a multi-centered retrospective review of patients treated with a planned prospective volume staging approach to stereotactically treat the entire nidus of an AVM with volume stages separated by intervals of 3–6 months. A total of 9 radiosurgical centers treated 257 patients with VS-SRS between 1991 and 2016. We evaluated near complete response (nCR), obliteration, cure, and overall survival. ResultsWith a median age of 33 years old at the time of first SRS volume stage, patients received 2–4 total volume stages and a median follow up of 5.7 years after VS-SRS. The median total AVM nidus volume was 23.25 cc (range: 7.7–94.4 cc) with a median margin dose per stage of 17 Gy (range: 12–20 Gy). Total AVM volume, margin dose per stage, compact nidus, lack of prior embolization, and lack of thalamic location involvement were all associated with improved outcomes. Dose >/= 17.5 Gy was strongly associated with improved rates of nCR, obliteration, and cure. With dose >/= 17.5 Gy, 5- and 10-year cure rates were 33.7% and 76.8% in evaluable patients compared to 23.7% and 34.7% of patients with 17 Gy and 6.4% and 20.6% with <17 Gy per volume-stage (p = 0.004). Obliteration rates in diffuse nidus architecture with <17 Gy were particularly poor with none achieving obliteration compared to 32.3% with doses >/= 17 Gy at 5 years (p = 0.007). Comparatively, lesions with a compact nidus architecture exhibited obliteration rates at 5 years were 10.7% vs 9.3% vs 26.6% for dose >17 Gy vs 17 Gy vs >/=17.5 Gy. ConclusionVS-SRS is an option for upfront treatment of large AVMs. Higher dose was associated with improved rates of nCR, obliteration, and cure suggesting that larger volumetric responses may facilitate salvage therapy and optimize the chance for cure.

Hyperbaric oxygen therapy in the treatment of malign edema complication after arteriovenous malformation radiosurgery

A 16-year-old female patient with headache was admitted to our hospital. Radiological examination showed a Spetzler-Martin Grade III arteriovenous malformation (AVM) located at the left frontal lobe. Volume-staged stereotactic radiosurgery (SRS) treatment performed in two fractions at three-month intervals and post-procedural period were uneventful. Eight months later the patient was admitted to our hospital with headache, vomiting, right-sided facial palsy and right upper extremity paresthesia. Radiological examination demonstrated severe vasogenic edema in the left centrum semiovale and temporal region. Due to severe and steroid-resistant malign edema, hyperbaric oxygen (HBO2) therapy was performed as an alternative treatment option. Neurological symptoms resolved completely after HBO2. Radiological examination demonstrated serious improvement of brain edema and mass effect.

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.

How to improve obliteration rates during volume-staged stereotactic radiosurgery for large arteriovenous malformations.

OBJECTIVEThe management of large-volume arteriovenous malformations (AVMs) with stereotactic radiosurgery (SRS) remains challenging. The authors retrospectively tested the hypothesis that AVM obliteration rates can be improved by increasing the percentage volume of an AVM that receives a minimal threshold dose of radiation.METHODSIn 1992, the authors prospectively began to stage anatomical components in order to deliver higher single doses to AVMs > 15 cm3 in volume. Since that time 60 patients with large AVMs have undergone volume-staged SRS (VS-SRS). The median interval between the first stage and the second stage was 4.5 months (2.8-13.8 months). The median target volume was 11.6 cm3 (range 4.3-26 cm3) in the first-stage SRS and 10.6 cm3 (range 2.8-33.7 cm3) in the second-stage SRS. The median margin dose was 16 Gy (range 13-18 Gy) for both SRS stages.RESULTSAVM obliteration after the initial two staged volumetric SRS treatments was confirmed by MRI alone in 4 patients and by angiography in 11 patients at a median follow-up of 82 months (range 0.4-206 months) after VS-SRS. The post-VS-SRS obliteration rates on angiography were 4% at 3 years, 13% at 4 years, 23% at 5 years, and 27% at 10 years. In multivariate analysis, only ≥ 20-Gy volume coverage was significantly associated with higher total obliteration rates confirmed by angiography. When the margin dose is ≥ 17 Gy and the 20-Gy SRS volume included ≥ 63% of the total target volume, the angiographically confirmed obliteration rates increased to 61% at 5 years and 70% at 10 years.CONCLUSIONSThe outcomes of prospective VS-SRS for large AVMs can be improved by prescribing an AVM margin dose of ≥ 17 Gy and adding additional isocenters so that ≥ 63% of the internal AVM dose receives more than 20 Gy.

Volume-staged stereotactic radiosurgery for large intracranial arteriovenous malformations

Stereotactic radiosurgery (SRS) is an effective treatment option for intracranial arteriovenous malformations (AVM). However, the treatment of large AVMs (nidus volume ≥12cm3) with single-session SRS alone yields generally poor outcomes. Volume-staged SRS (VS-SRS) is a therapeutic strategy for large AVMs which seeks to avoid the disadvantages of single-session SRS, but reports regarding its efficacy remain limited. The aim of this retrospective cohort study is to assess the outcomes of VS-SRS for large AVMs. We identified all AVM patients who underwent VS-SRS at our institution from 2000 to 2015 with ≥12months follow-up. Baseline and outcomes data were analyzed. A total of 12 patients were selected for the study cohort, with a median age of 30years. The median maximum AVM diameter and nidus volume were 4.3cm and 13.6cm3, respectively. The Spetzler–Martin grade was III and IV each in six AVMs (50%). All patients underwent VS-SRS in two stages, and the median margin dose was 17Gy for both VS-SRS procedures. The median time interval between the two procedures was three months. After a median radiologic follow-up duration of 39months, the median degree of AVM volume reduction (evaluable in nine patients) was 87% (range 12–99%). The rates of radiologically evident, symptomatic, and permanent radiation-induced changes were 58%, 25%, and 8%, respectively. There were no cases of post-SRS hemorrhage. VS-SRS substantially reduces the size of large AVMs. A potential role for VS-SRS may be to facilitate subsequent definitive intervention to obliterate a shrunken, residual nidus.

Volume-Staged Stereotactic Radiosurgery for Intracranial Arteriovenous Malformations: Outcomes Based on an 18-Year Experience.

Radiation-based treatment options of large intracranial arteriovenous malformations (AVM) must balance the likelihood of obliteration with the risk of adverse radiation effects (ARE). To analyze the efficacy and risks of volume-staged stereotactic radiosurgery (VS-SRS) for AVM. Retrospective study of 34 AVM patients having VS-SRS between 1997 and 2012. A median of 2 stages (range, 2-4) was used to treat a median AVM volume of 22.2 cm 3 (range, 7.4-56.7). The median AVM margin dose was 16 Gy (range, 14-18); the median radiosurgery-based AVM score was 2.81 (range, 1.54-6.45). The median follow-up after VS-SRS was 8.2 years (range, 3-13.3). Nidus obliteration was noted in 18 patients (53%) after VS-SRS. The rate of obliteration was 14% at 3 years, 54% at 5 years, and 75% at 7 years. Six patients (18%) had 11 bleeds after VS-SRS. Two patients (6%) remained neurologically stable, 2 (6%) patients had significant deficits, and 2 patients (6%) died. The actuarial risk of a first bleed after VS-SRS was 6% at 1 year, 12% at 3 years, and 19% at 7 years. Six patients (18%) underwent repeat SRS; all achieved nidus obliteration for an overall cure rate of 71%. Two patients (6%) had a permanent ARE after VS-SRS or repeat SRS. VS-SRS permitted large volume intracranial AVM to be treated with a low rate of ARE. Further study is needed on dose escalation and decreasing the treatment volume per stage to determine if this will increase the rate of obliteration with this technique.

Volume-Staged Stereotactic Radiosurgery for Intracranial Arteriovenous Malformations: Outcomes Based on an 18-Year Experience

Volume-Staged Stereotactic Radiosurgery for Intracranial Arteriovenous Malformations: Outcomes Based on an 18-Year Experience

Hemorrhage During the Latency Period Following Volume-Staged Stereotactic Radiosurgery for Large Arteriovenous Malformations

Hemorrhage During the Latency Period Following Volume-Staged Stereotactic Radiosurgery for Large Arteriovenous Malformations

Outcomes of Volume-Staged Radiosurgery for Cerebral Arteriovenous Malformations Larger Than 20 cm3 with More Than 3 Years of Follow-Up

Treatment of extremely large cerebral arteriovenous malformations (AVMs) is challenging. Although volume-staged stereotactic radiosurgery (SRS) is a possible multimodal treatment option for such lesions, reports of these procedures are scarce. We evaluated the efficacy and safety of volume-staged SRS in patients with AVMs >20 cm(3) with >3 years of follow-up. Between 2005 and 2012, 18 patients with AVMs >20 cm(3) were treated by volume-staged SRS. The median target volume was 38 cm(3) (interquartile range, 31-53 cm(3)). Treatment was conducted in 2-3 stages with a median interval of 6 months. The median follow-up period from the last SRS treatment was 53 months (interquartile range, 41-75 months). Complete nidus obliteration was achieved in 6 patients (33%), and the obliteration rate at 5 years after initial SRS was 35% by the Kaplan-Meier method. The annual hemorrhage rate after last SRS treatment was 3.9% (95% confidence interval, 0.8%-11.5%). Radiation-induced adverse effects occurred in 2 patients. In our series, volume-staged SRS for AVMs >20 cm(3) achieved a nidus obliteration rate of 35% at 5 years. There was still a high risk for hemorrhage (∼ 4% per year) after treatment, which seemed to be higher than the rate commonly observed in the posttreatment course of single-session SRS for average-size AVMs. Further cases will help determine whether volume-staged SRS could be routinely considered, based on its efficacy and risks, including comparison with the natural history of large AVMs.

Volume-staged radiosurgery for large arteriovenous malformations: an evolving paradigm.

OBJECT Large arteriovenous malformations (AVMs) remain difficult to treat, and ideal treatment parameters for volume-staged stereotactic radiosurgery (VS-SRS) are still unknown. The object of this study was to compare VS-SRS treatment outcomes for AVMs larger than 10 ml during 2 eras; Era 1 was 1992-March 2004, and Era 2 was May 2004-2008. In Era 2 the authors prospectively decreased the AVM treatment volume, increased the radiation dose per stage, and shortened the interval between stages. METHODS All cases of VS-SRS treatment for AVM performed at a single institution were retrospectively reviewed. RESULTS Of 69 patients intended for VS-SRS, 63 completed all stages. The median patient age at the first stage of VS-SRS was 34 years (range 9-68 years). The median modified radiosurgery-based AVM score (mRBAS), total AVM volume, and volume per stage in Era 1 versus Era 2 were 3.6 versus 2.7, 27.3 ml versus 18.9 ml, and 15.0 ml versus 6.8 ml, respectively. The median radiation dose per stage was 15.5 Gy in Era 1 and 17.0 Gy in Era 2, and the median clinical follow-up period in living patients was 8.6 years in Era 1 and 4.8 years in Era 2. All outcomes were measured from the first stage of VS-SRS. Near or complete obliteration was more common in Era 2 (log-rank test, p = 0.0003), with 3- and 5-year probabilities of 5% and 21%, respectively, in Era 1 compared with 24% and 68% in Era 2. Radiosurgical dose, AVM volume per stage, total AVM volume, era, compact nidus, Spetzler-Martin grade, and mRBAS were significantly associated with near or complete obliteration on univariate analysis. Dose was a strong predictor of response (Cox proportional hazards, p < 0.001, HR 6.99), with 3- and 5-year probabilities of near or complete obliteration of 5% and 16%, respectively, at a dose < 17 Gy versus 23% and 74% at a dose ≥ 17 Gy. Dose per stage, compact nidus, and total AVM volume remained significant predictors of near or complete obliteration on multivariate analysis. Seventeen patients (25%) had salvage surgery, SRS, and/or embolization. Allowing for salvage therapy, the probability of cure was more common in Era 2 (log-rank test, p = 0.0007) with 5-year probabilities of 0% in Era 1 versus 41% in Era 2. The strong trend toward improved cure in Era 2 persisted on multivariate analysis even when considering mRBAS (Cox proportional hazards, p = 0.055, HR 4.01, 95% CI 0.97-16.59). The complication rate was 29% in Era 1 compared with 13% in Era 2 (Cox proportional hazards, not significant). CONCLUSIONS VS-SRS is an option to obliterate or downsize large AVMs. Decreasing the AVM treatment volume per stage to ≤ 8 ml with this technique allowed a higher dose per fraction and decreased time to response, as well as improved rates of near obliteration and cure without increasing complications. Reducing the volume of these very large lesions can facilitate a surgical approach for cure.

A treatment paradigm for high-grade brain arteriovenous malformations: volume-staged radiosurgical downgrading followed by microsurgical resection.

The surgical treatment of many large arteriovenous malformations (AVMs) is associated with substantial risks, and many are considered inoperable. Furthermore, AVMs larger than 3 cm in diameter are not usually treated with conventional single-session radiosurgery encompassing the entire AVM volume. Volume-staged stereotactic radiosurgery (VS-SRS) is an option for large AVMs, but it has mixed results. The authors report on a series of patients with high-grade AVMs who underwent multiple VS-SRS sessions with resultant downgrading of the AVMs, followed by resection. A cohort of patients was retrieved from a single-institution AVM patient registry consisting of prospectively collected data. VS-SRS was performed as a planned intentional treatment. Surgery was considered as salvage therapy in select patients. Sixteen AVMs underwent VS-SRS followed by surgery. Four AVMs presented with rupture. The mean patient age was 25.3 years (range 13-54 years). The average initial Spetzler-Martin grade before any treatment was 4, while the average supplemented Spetzler-Martin grade (Spetzler-Martin plus Lawton-Young) was 7.1. The average AVM size in maximum dimension was 5.9 cm (range 3.3-10 cm). All AVMs were supratentorial in location and all except one were in eloquent areas of the brain, with 7 involving primary motor cortex. The mean number of VS-SRS sessions was 2.7 (range 2-5 sessions). The mean interval between first VS-SRS session and resection was 5.7 years. There were 4 hemorrhages that occurred after VS-SRS. The average Spetzler-Martin grade was reduced to 2.5 (downgrade, -1.5) and the average supplemented Spetzler-Martin grade was reduced to 5.6 (downgrade, -1.5). The maximum AVM size was reduced to an average of 3.0 cm (downsize=-2.9 cm). The mean modified Rankin Scale (mRS) scores were 1.2, 2.3, and 2.2 before VS-SRS, before surgery, and at last follow-up, respectively (mean follow-up, 6.9 years). Fifteen AVMs were cured after surgery. Ten patients had good outcomes at last follow-up (7 with mRS Score 0 or 1, and 3 with mRS Score 2). There were 2 deaths (both mRS Score 1 before treatment) and 4 patients with mRS Score 3 outcome (from mRS Scores 0, 1, and 2 [n=2]). Volume-staged SRS can downgrade AVMs, transforming high-grade AVMs (initially considered inoperable) into operable AVMs with acceptable surgical risks. This treatment paradigm offers an alternative to conservative observation for young patients with unruptured AVMs and long life expectancy, where the risk of hemorrhage is substantial. Difficult AVMs were cured in 15 patients. Surgical morbidity associated with downgraded AVMs is reduced to that of postradiosurgical/preoperative supplemented Spetzler-Martin grades, not their initial AVM grades.