Comparison of Repeat Versus Initial Stereotactic Radiosurgery for Intracranial Arteriovenous Malformations: A Retrospective Multicenter Matched Cohort Study.

BACKGROUND AND OBJECTIVES: Studies comparing neurological and radiographic outcomes of repeat to initial stereotactic radiosurgery (SRS) intracranial arteriovenous malformations are scarce. Our aim was to perform a retrospective matched comparison of patients initially treated with SRS with those undergoing a second radiosurgical procedure. METHODS: We collected data from arteriovenous malformations managed in 21 centers that underwent initial and repeated radiosurgery from 1987 to 2022. Based on arteriovenous malformations volume, margin dose, deep venous drainage, deep, and critical location, we matched 1:1 patients who underwent an initial SRS for treatment-naive arteriovenous malformations and a group with repeated SRS treatment. RESULTS: After the selection process, our sample consisted of 328 patients in each group. Obliteration in the initial SRs group was 35.8% at 3 and 56.7% at 5 years post-SRS, while the repeat SRS group showed obliteration rates of 33.9% at 3 years and 58.6% at 5 years, without statistically significant differences (P = .75 and P = .88, respectively). There were no statistically significant differences between the 2 groups for obliteration rates (hazard ratio = 0.93; 95% CI, 0.77-1.13; P = .5), overall radiation-induced changes (RIC) (OR = 1.1; 95% CI, 0.75-1.6; P = .6), symptomatic RIC (OR = 0.78; 95% CI, 0.4-1.5; P = .4), and post-SRS hemorrhage (OR = 0.68; 95% CI; P = .3). CONCLUSION: In matched cohort analysis, a second SRS provides comparable outcomes in obliteration and RIC compared with the initial SRS. Dose reduction on repeat SRS may not be warranted.

Association of the combined stereotactic radiosurgery and embolization strategy and long-term outcomes in brain arteriovenous malformations with a volume >10 ml: A nationwide multicenter observational prospective cohort study.

BACKGROUND: To assess the long-term outcome of large brain arteriovenous malformations (AVMs) (volume > 10 ml) underwent combined embolization and stereotactic radiosurgery (E+SRS) versus SRS alone. METHODS: Patients were recruited from a nationwide multicenter prospective collaboration registry (MATCH study, August 2011-August 2021) and categorized into E+SRS and SRS alone cohorts. Propensity score-matched survival analysis was employed to control for potential confounding variables. The primary outcome was a composite event of non-fatal hemorrhagic stroke or death. Secondary outcomes were favorable patient outcomes, AVM obliteration, favorable neurological outcomes, seizure, worsened mRS score, radiation-induced changes (RIC), and embolization complications. Furthermore, the efficacy of distinct embolization strategies was evaluated. Hazard ratios (HRs) were computed utilizing Cox proportional hazard models. RESULTS: Among 1063 AVMs who underwent SRS with or without prior embolization, 176 patients met the enrollment criteria. Following propensity score matching, the final analysis encompassed 98 patients (49 pairs). Median (interquartile range) follow-up duration for primary outcomes spanned 5.4 (2.7-8.4) years. Overall, the E+SRS strategy demonstrated a trend toward reduced incidence of primary outcomes compared to the SRS alone strategy (1.44 vs 2.37 per 100 patient-years; HR, 0.58 [95 % CI, 0.17-1.93]). Regardless of embolization degree or strategy, stratified analyses further consistently revealed a similar trend, albeit without achieving statistical significance. Secondary outcomes generally exhibited equivalence, but the combined approach showed potential superiority in most measures. CONCLUSIONS: This study suggests a trend toward lower long-term non-fatal hemorrhagic stroke or death risks with the E+SRS strategy when compared to SRS alone in large AVMs (volume > 10 ml).

Stereotactic radiosurgery alone for brain arteriovenous malformations: a single-institute experience.

OBJECTIVE: Brain arteriovenous malformations (BAVMs) represent an ongoing clinical challenge because of their complex nature. The long-term outcomes of BAVMs patients treated with stereotactic radiosurgery (SRS) alone are unclear. METHODS: We conducted a retrospective analysis of 201 patients treated for BAVMs from January 2010 to December 2019. The identified predictors of obliteration or hemorrhage in the multivariate analysis were estimated by odds ratios (ORs) with 95% confidence intervals (CIs). RESULTS: A total of 201 patients treated with gamma knife radiosurgery (GKRS) alone as the primary treatment for BAVMs were included. The mean age at GKRS treatment was 31.4 ± 1.1 years, and 61.2% of the patients were male. Multivariate logistic regression revealed that a higher radiosurgery-based AVM score (OR 1.847, 95% CI = 1.292-2.641; p = 0.001) was significantly associated with worse obliteration, and a higher margin dose significantly favored obliteration (OR 0.352, 95% CI = 0.189-0.658; p = 0.001). Multivariate analysis revealed that an increased lesion volume of 1 cm3 (OR 1.279, 95% CI = 1.023-1.600; p = 0.031) and a high margin dose (OR 0.363, 95% CI = 0.134-0.983; p = 0.046) were significant prognostic factors for post-SRS hemorrhage. CONCLUSIONS: In conclusion, our study investigated the available clinical and radiological prognostic factors for BAVMs and revealed that a higher margin dose significantly improved both the obliteration rate and nonhemorrhagic outcomes. Currently, the most appropriate candidates, Spetzler-Martin grade, and optimal radiation dose are still being defined by prospective trials.

Serum Vascular Endothelial Growth Factor and Endostatin as an Adjunct to Clinical Decision Making in Managing Radiation-induced Changes Post Gamma Knife Radiosurgery in Spetzler Martin Grade 3 Arteriovenous Malformations Patients: A Pilot Study.

BACKGROUND: Radiation induced changes (RIC) are the most common complications observed post Gamma Knife radiosurgery (GKRS) and may be observed within 6-18 months post procedure. It has been observed that almost one-third of RICs are symptomatic and half of them are persistent. There is no way to predict which patients will develop these changes and to what extent. METHODS: This was a prospective analytical pilot study with the aim of understanding the role of serum vascular endothelial growth factor (VEGF) and endostatin as predictive factors for clinically symptomatic RIC in intracranial arteriovenous malformations (AVMs) of Spetzler Martin (SM) grade 3 being managed with primary GKRS. RESULTS: A total of 15 patients were analyzed; 60% of them had a history of bleed. The median volume of AVM nidus was 4.36 mL. One-third of the patients had no imaging changes suggestive of RIC at 1 year follow-up and 2 of the patients had symptomatic RIC needing intervention. Before GKRS, the median values of serum concentration of endostatin and VEGF were 34.98 ng/mL and 168.37 pg/mL, respectively. The serum values of VEGF at 1 month post GKRS was much lower than the pre-GKRS values but not found to be predictive of RIC. No correlation could be observed with the levels of serum endostatin and RIC. CONCLUSIONS: Some patients may develop resistant edema and necrosis post GKRS for intracranial AVMs, which may warrant medical and surgical intervention. Serum biomarkers like VEGF and endostatin may vary in the post GKRS period and can be used to identify at-risk cases, however more studies are needed to decide on appropriate time of sampling and identify clinically relevant predictive factors.

Analysis of the treatment planning metrics and their correlation with morphology of intracranial lesions in Gamma Knife stereotactic radiosurgery.

BACKGROUND: Gamma Knife Radiosurgery (GKRS) has established a role in treating various benign brain pathologies. The radiosurgery planning necessitates a proper understanding of radiation dose distribution in relation to the target lesion and surrounding eloquent area. The quality of a radiosurgery plan is determined by various planning parameters. Here, we have reviewed various GKRS planning parameters and analyzed their correlation with the morphology of treated brain lesions. METHOD: A total of 430 treatment plans (71 meningioma, 133 vestibular schwannoma/VS, 150 arteriovenous malformation/AVM, 76 pituitary adenoma/PA treated with GKRS between December 2013 and May 2023) were analyzed for target coverage (TC), conformity index (CI), homogeneity index (HI), and gradient index (GI). RESULT: The values of CIPaddick and CILomax for PA were lower and differed significantly from meningioma, VS, and AVM. The value of HI for PA was higher and differed significantly when compared with meningioma, VS, and AVM. The values of HI for AVM were also significantly higher than VS and meningioma. The mean GI was 3.02, 2.92, 3.03, and 2.88 for meningioma, VS, AVM, and PA, respectively. The value of GI for meningioma and AVM was significantly higher when compared with the values for VS and PA. The mean TC was 0.94 for meningioma, 0.96 for VS, 0.95 for AVM, and 0.90 for PA. The value TC of PA was lower and differed significantly when compared with VS, AVM, and meningioma. Lesions with a volume of ≤1 cc had poor planning metrics as the spillage of radiation may be higher. CONCLUSION: The GKRS planning parameters depend on the size, shape, nature, and location of intracranial lesions. Therefore, each treatment plan needs to be evaluated thoroughly and a long-term follow-up is needed to establish their relation with clinical outcome.

Long-Term Outcome of Time-Staged Gamma Knife Radiosurgery for Large Arteriovenous Malformations.

BACKGROUND: Treatment for large (> 10 mL) arteriovenous malformations (AVMs) remains highly challenging. This study evaluated long-term effect of time-staged gamma knife radiosurgery (GKS) for large AVMs. METHODS: For patients with large AVMs treated by time-staged GKS over 10 years, time-staged GKS was repeated every three years targeting the entire nidus if total obliteration was not achieved. Obliteration rate and post-GKS complications were assessed based on 10 mL volume interval of AVMs. Prognostic factors for these outcomes were evaluated using Cox regression analysis. RESULTS: Ninety-six patients were analyzed. For AVMs in the 10-20 mL subgroup, a dose ≥ 13.5Gy yielded higher obliteration rate in the first GKS. In the 20-30 mL subgroup, a second GKS significantly boosted obliteration. AVMs > 30 mL did not achieve any obliteration with the first GKS. Among 35 (36.4%) cases lost to follow-up, 7 (7.2%) were lost due to GKS complications. Kaplan-Meier analysis showed that each subgroup needed different time for achieving 50% favorable obliteration outcome rate: 3.5, 6.5, and 8.2 years for 10-20 mL, 20-30 mL, and > 30 mL subgroup, respectively. Total obliteration rate calculated by intention-to-treat method: 73%, 51.7%, 35.7%, respectively, 61.5% overall. Post-GKS hemorrhage and chronic encapsulated expanding hematoma (CEEH) occurred in 13.5% and 8.3% of cases, respectively. Two patients died. Dose and volume were significant prognostic factors for obliteration. Initial AVM volume was a significant prognostic factor of post-GKS hemorrhage and CEEH. CONCLUSION: Time-staged GKS for large AVMs less than 30 mL has highly favorable long-term outcome and a tolerable complication rate.

Sustaining consistent cobalt-60 dose rate enhances radiosurgical outcomes in brain arteriovenous malformation management.

BACKGROUND AND PURPOSE: The impact of cobalt-60 dose rate (Co-60 DR) on outcomes of stereotactic radiosurgery (SRS) for brain arteriovenous malformations (AVMs) remains fully elucidated. This study explored the association between Co-60 DR and SRS outcomes in AVM treatment. MATERIALS AND METHODS: 772 AVM patients from 1990 to 2020 were included. High DR was defined as ≥ 2.4 Gy/min. AVM patients were categorized into 3 cohorts based on the nidus volume: small (<5 mL), medium (≥5 mL and < 10 mL), and large (≥10 mL). The primary endpoint was AVM obliteration; secondary endpoints included post-SRS hemorrhage. RESULTS: Cumulative obliteration rates of the large AVM were significantly increased in the high DR group than those in the low DR group (84 % vs. 45 % at 5 years, log-rank test; p = 0.011). Multivariable analysis showed that the obliteration rate was significantly elevated for the high DR group in the large AVM cohort with an adjusted hazard ratio (HR) of 1.78 (95 % confidence interval [CI]: 1.00-3.17, p = 0.049). Post-SRS hemorrhage rates of the entire cohort were significantly decreased in the high DR group than in the low DR group (2.5 % vs. 5.3 % at 5 years, log-rank test; p = 0.035). Multivariable analysis revealed post-SRS hemorrhage was reduced in the high DR group with an adjusted HR of 0.47 (95 % CI: 0.24-0.92, p = 0.026). CONCLUSION: High DR may lead to increased efficiency for large AVMs and decreased post-SRS hemorrhage in all AVM cases. Sustaining a higher Co-60 DR could potentially yield favorable outcomes for SRS for AVMs.

Clinical diagnostic reference levels in neuroradiology based on clinical indication.

This study focuses on patient radiation exposure in interventional neuroradiology (INR) procedures, a field that has advanced significantly since its inception in the 1980s. INR employs minimally invasive techniques to treat complex cerebrovascular diseases in the head, neck, and spine. The study establishes diagnostic reference levels (DRLs) for three clinical indications (CIs): stroke (S), brain aneurysms (ANs), and brain arteriovenous malformation (AVM). Data from 209 adult patients were analyzed, and DRLs were determined in terms of various dosimetric and technical quantities. For stroke, the established DRLs median values were found to be 78 Gy cm2, 378 mGy, 118 mGy, 12 min, 442 images, and 15 runs. Similarly, DRLs for brain AN are 85 Gy cm2, 611 mGy, 95.5 mGy, 19.5, 717 images, and 26 runs. For brain AVM, the DRL's are 180 Gy cm2, 1144 mGy, 537 mGy, 36 min, 1375 images, and 31 runs. Notably, this study is unique in reporting DRLs for specific CIs within INR procedures, providing valuable insights for optimizing patient safety and radiation exposure management.

Pathologic features of brain hemorrhage after radiation treatment: case series with somatic mutation analysis.

BACKGROUND: Radiation treatment for diseases of the brain can result in hemorrhagic adverse radiation effects. The underlying pathologic substrate of brain bleeding after irradiation has not been elucidated, nor potential associations with induced somatic mutations. METHODS: We retrospectively reviewed our department's pathology database over 5 years and identified 5 biopsy specimens (4 patients) for hemorrhagic lesions after brain irradiation. Tissues with active malignancy were excluded. Samples were characterized using H&E, Perl's Prussian Blue, and Masson's Trichrome; immunostaining for B-cells (anti-CD20), T-cells (anti-CD3), endothelium (anti-CD31), macrophages (anti-CD163), α-smooth muscle actin, and TUNEL. DNA analysis was done by two panels of next-generation sequencing for somatic mutations associated with known cerebrovascular anomalies. RESULTS: One lesion involved hemorrhagic expansion among multifocal microbleeds that had developed after craniospinal irradiation for distant medulloblastoma treatment. Three bleeds arose in the bed of focally irradiated arteriovenous malformations (AVM) after confirmed obliteration. A fifth specimen involved the radiation field distinct from an irradiated AVM bed. From these, 2 patterns of hemorrhagic vascular pathology were identified: encapsulated hematomas and cavernous-like malformations. All lesions included telangiectasias with dysmorphic endothelium, consistent with primordial cavernous malformations with an associated inflammatory response. DNA analysis demonstrated genetic variants in PIK3CA and/or PTEN genes but excluded mutations in CCM genes. CONCLUSIONS: Despite pathologic heterogeneity, brain bleeding after irradiation is uniformly associated with primordial cavernous-like telangiectasias and disruption of genes implicated in dysangiogenesis but not genes implicated as causative of cerebral cavernous malformations. This may implicate a novel signaling axis as an area for future study.

Long-Term Outcomes After Stereotactic Radiosurgery for Pediatric Brain Arteriovenous Malformations: A Systematic Review.

BACKGROUND: The long-term outcomes after stereotactic radiosurgery (SRS) for pediatric brain arteriovenous malformations (AVMs) remain poorly understood given the paucity of longitudinal studies. A systematic review was conducted to pool cumulative incidences for all outcomes. METHODS: PubMed, Embase, and Web of Science were queried to systematically extract potential references. The articles relating to AVMs treated via SRS were required to be written in English, involve pediatric patients (<18 years of age), and include a mean follow-up period of >5 years. Individual patient data were obtained to construct a pooled Kaplan-Meier plot on obliteration rates over time. RESULTS: Among the 6 studies involving 1315 pediatric patients averaging a follow-up period of 86.6 months (range, 6-276), AVM obliteration was observed in 66.1% with cumulative probabilities of 48.28% (95% confidence interval [CI], 41.89-54.68), 76.11% (95% CI, 67.50-84.72), 77.48% (95% CI, 66.37-88.59) over 3, 5, and 10 years, respectively. The cumulative incidence of post-SRS hemorrhage, tumors, cysts, and de novo seizures was 7.2%, 0.3%, 1.6%, and 1.5%, respectively. The cumulative incidence of radiation-induced necrosis, edema, radiologic radiation-induced changes (RICs), symptomatic RICs, and permanent RICs were 8.0%, 1.4%, 28.0%, 8.7%, and 4.9%, respectively. CONCLUSIONS: Studies assessing long-term outcomes after SRS are moderate in quality and retrospective. Thus, interpretation with caution is advised given the variable degree of loss to follow-up, which suggests that complication rates may be higher than the values stated in the literature. Future prospective studies are needed to validate these findings.

Hyperbaric Oxygen Therapy as an Alternative Therapeutic Option for Radiation-Induced Necrosis Following Radiotherapy for Intracranial Pathologies.

BACKGROUND: Radiotherapy (RT) is a feasible adjuvant therapeutic option for managing intracranial pathologies. One of the late complications of RT that frequently develops within months following RT is radiation necrosis (RN). Corticosteroids are the first-line therapeutic option for RNs; however, in case of unfavorable outcomes or intolerability, several other options, including bevacizumab, laser interstitial thermal therapy, surgery, and hyperbaric oxygen therapy (HBOT). Our goal was to investigate the feasibility and efficacy of the application of HBOT in RNs following RT and help physicians make decisions based on the latest data in the literature. METHODS: We provide a comprehensive review of the literature on the current issues of utilization of HBOT in RNs. RESULTS: We included 11 studies with a total of 46 patients who underwent HBOT. Most of the cases were diagnosed with brain tumors or arteriovenous malformations. Improvement was achieved in most of the cases. DISCUSSION: HBOT is a noninvasive therapeutic intervention that can play a role in adjuvant therapy concurrent with RT and chemotherapy and treating RNs. HBOT resolves the RN through 3 mechanisms, including angiogenesis, anti-inflammatory modulation, and cellular repair. Previous studies demonstrated that HBOT is a feasible and well-tolerated therapeutic option that has shown promising results in improving clinical and radiological outcomes in intracranial RNs. Complications of HBOT are usually mild and reversible. CONCLUSIONS: HBOT is a feasible and effective therapeutic option in steroid-refractory RNs and is associated with favorable outcomes and a low rate of side effects.

Pediatric cerebral cavernous malformations and stereotactic radiosurgery: an analysis of 50 cases from a multicentric study.

OBJECTIVE: Cerebral cavernous malformations (CCMs) are the second most common vascular anomaly affecting the CNS in children. Although stereotactic radiosurgery (SRS) has been proposed as an alternative to microsurgery in the management of selected cases in adults, there is a paucity of studies focusing on pediatric patients. The aim of this study was to present the outcomes and associated risks of SRS in this subgroup of patients. METHODS: This retrospective multicenter study included pediatric patients treated with single-session SRS for CCMs. The annual hemorrhage rate (AHR) was calculated before and after SRS in hemorrhagic lesions. The Engel classification was used to describe post-SRS epileptic control. Adverse radiation effects (AREs) and the occurrence of new neurological deficits were recorded. RESULTS: The study included 50 patients (median age 15.1 [IQR 5.6] years) harboring 62 CCMs. Forty-two (84%) and 22 (44%) patients had a history of hemorrhage or epilepsy prior to SRS, respectively. The AHR from diagnosis to SRS excluding the first hemorrhage was 7.19 per 100 CCM-years, dropping to 3.15 per 100 CCM-years after treatment. The cumulative risk of first hemorrhage after SRS was 7.4% (95% CI 0%-14.3%) at 5 years and 23.6% (95% CI 0%-42.2%) at 10 years. Eight hemorrhagic events involving 6 CCMs in 6 patients were recorded in the post-SRS follow-up period; 4 patients presented with transient symptoms and 4 with permanent symptoms. Of the 22 patients with pre-SRS seizures, 11 were seizure free at the last follow-up (Engel class I), 6 experienced improvement (Engel class II or III), 5 had no improvement (Engel class IVA or IVB), and 1 experienced worsening (Engel class IVC). Radiographic AREs were documented in 14.5% (9/62) of CCMs, with 4 being symptomatic. CONCLUSIONS: Single-session SRS reduces the CCM hemorrhage rate in the pediatric population and provides adequate seizure control.

Repeat stereotactic radiosurgery for persistent cerebral arteriovenous malformations in pediatric patients.

OBJECTIVE: The purpose of this study was to describe the long-term outcomes and associated risks related to repeat stereotactic radiosurgery (SRS) for persistent arteriovenous malformations (AVMs) in pediatric patients. METHODS: Under the auspices of the International Radiosurgery Research Foundation, this retrospective multicenter study analyzed pediatric patients who underwent repeat, single-session SRS between 1987 and 2022. The primary outcome variable was a favorable outcome, defined as nidus obliteration without hemorrhage or neurological deterioration. Secondary outcomes included rates and probabilities of hemorrhage, radiation-induced changes (RICs), and cyst or tumor formation. RESULTS: The cohort included 83 pediatric patients. The median patient age was 11 years at initial SRS and 15 years at repeat SRS. Fifty-seven children (68.7%) were managed exclusively using SRS, and 42 (50.6%) experienced hemorrhage prior to SRS. Median AVM diameter and volume were substantially different between the first (25 mm and 4.5 cm3, respectively) and second (16.5 mm and 1.6 cm3, respectively) SRS, while prescription dose and isodose line remained similar. At the 5-year follow-up evaluation from the second SRS, nidus obliteration was achieved in 42 patients (50.6%), with favorable outcome in 37 (44.6%). The median time to nidus obliteration and hemorrhage was 35.5 and 38.5 months, respectively. The yearly cumulative probability of favorable outcome increased from 2.5% (95% CI 0.5%-7.8%) at 1 year to 44% (95% CI 32%-55%) at 5 years. The probability of achieving obliteration followed a similar pattern and reached 51% (95% CI 38%-62%) at 5 years. The 5-year risk of hemorrhage during the latency period after the second SRS reached 8% (95% CI 3.2%-16%). Radiographically, 25 children (30.1%) had RICs, but only 5 (6%) were symptomatic. Delayed cyst formation occurred in 7.2% of patients, with a median onset of 47 months. No radiation-induced neoplasia was observed. CONCLUSIONS: The study results showed nidus obliteration in most pediatric patients who underwent repeat SRS for persistent AVMs. The risks of symptomatic RICs and latency period hemorrhage were quite low. These findings suggest that repeat radiosurgery should be considered when treating pediatric patients with residual AVM after prior SRS. Further study is needed to define the role of repeat SRS more fully in this population.

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

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

Effect of cerebral arteriovenous malformation location on outcomes of repeat, single-fraction stereotactic radiosurgery: a matched-cohort analysis.

OBJECTIVE: Patients with deep-seated arteriovenous malformations (AVMs) have a higher rate of unfavorable outcome and lower rate of nidus obliteration after primary stereotactic radiosurgery (SRS). The aim of this study was to evaluate and quantify the effect of AVM location on repeat SRS outcomes. METHODS: This retrospective, multicenter study involved 505 AVM patients managed with repeat, single-session SRS. The endpoints were nidus obliteration, hemorrhage in the latency period, radiation-induced changes (RICs), and favorable outcome. Patients were split on the basis of AVM location into the deep (brainstem, basal ganglia, thalamus, deep cerebellum, and corpus callosum) and superficial cohorts. The cohorts were matched 1:1 on the basis of the covariate balancing score for volume, eloquence of location, and prescription dose. RESULTS: After matching, 149 patients remained in each cohort. The 5-year cumulative probability rates for favorable outcome (probability difference -18%, 95% CI -30.9 to -5.8%, p = 0.004) and AVM obliteration (probability difference -18%, 95% CI -30.1% to -6.4%, p = 0.007) were significantly lower in the deep AVM cohort. No significant differences were observed in the 5-year cumulative probability rates for hemorrhage (probability difference 3%, 95% CI -2.4% to 8.5%, p = 0.28) or RICs (probability difference 1%, 95% CI -10.6% to 11.7%, p = 0.92). The median time to delayed cyst formation was longer with deep-seated AVMs (deep 62 months vs superficial 12 months, p = 0.047). CONCLUSIONS: AVMs located in deep regions had significantly lower favorable outcomes and obliteration rates compared with superficial lesions after repeat SRS. Although the rates of hemorrhage in the latency period and RICs in the two cohorts were comparable, delayed cyst formation occurred later in patients with deep-seated AVMs.

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

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

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

BACKGROUND: To explore the therapeutic outcomes of CyberKnife based fractionated stereotactic radiotherapy (CKFRT) for patients with cerebral arteriovenous malformations (AVM). METHODS: Between January 2008 and October 2020, 45 patients underwent CKFRT for cerebral AVMs as a first treatment. The delineation of AVM targets included AVM nidus. The mean target volume was 4.07 cm3, and 9 lesions (20%) were larger than 10.0 cm3. The mean marginal dose was 24 Gy (range, 20-35 Gy). CKFRT was delivered in median 3 fractions (range, 2 âˆ¼ 5 fractions). AVM obliteration following CKFRT was confirmed by magnetic resonance imaging or angiography. RESULTS: During a median follow-up of 47 (5-148) months, complete obliteration and partial obliteration of AVM after CKFRT were obtained in 23 (51%) and 13 (29%) patients, respectively. Median time to complete obliteration was 39 (15-63) months. The cumulative probability of complete obliteration rate at 3 years was 47%. Complete obliteration rate of AVM was associated with Radiosurgery-based AVM score, which was consisted of AVM volume, patients age, and AVM location. One (2%) patient had hemorrhage during the follow-up period. CONCLUSIONS: CKFRT is an effective primary treatment for patients with cerebral AVMs with a low hemorrhage risk.

Incorporation of Brain Connectomics for Stereotactic Radiosurgery Treatment Planning.

BACKGROUND AND IMPORTANCE: Neurosurgeons have integrated neuroanatomy-based tractography to avoid critical structures during dose planning. However, they have yet to integrate more comprehensive connectome networks for radiosurgical planning. CLINICAL PRESENTATION: A young man presented with a Spetzler-Martin Grade 3 right temporal arteriovenous malformation. DISCUSSION: As proof of concept, we incorporated connectomic networks including default mode network, optic radiation and central executive network into the Gamma Knife radiosurgical treatment planning workflow. Connectome networks were created from T1 anatomic and diffusion-weighted images magnetic resonance images using Quicktome software. The resulting networks were voxel-encoded in the magnetic resonance images, imported into GammaPlan, and segmented by image thresholding. The GammaPlan Lightning optimizer was used to create radiosurgical plans with a dose of 20 Gy to the 50% isodose line delivered to the arteriovenous malformation nidus both with and without treating these networks as risk structures. When taking into account the connectome networks, a maximum dose restriction of 14 Gy was placed on each network during lightning dose planning. With default mode network, optic radiation, and central executive network as risk structures, the maximum dose and V 12Gy were reduced by 23.4% and 88.3%, 20% and 34.3%, and 29.8% and 63.2%, respectively. CONCLUSION: We were able to incorporate connectomes into radiosurgical dose planning approaches. This allowed for dose reductions to the networks while still achieving delivery of a therapeutic dose to the target volume.

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

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