Prognostic value of nidus sphericity in brain AVMs treated with Gamma Knife Radiosurgery: a preliminary study.

Risk of Hemorrhage and Obliteration Rates of LINAC-Based Radiosurgery for Cerebral Arteriovenous Malformations Treated After Prior Partial Embolization

Treatment outcome after linac-based radiosurgery in cerebral arteriovenous malformations (AVM): Factors affecting obliteration

Object. A consecutive series of 240 patients with arteriovenous malformations (AVMs) treated by gamma knife radiosurgery (GKS) between March 1993 and March 1999 was evaluated to assess the efficacy and safety of radiosurgery for cerebral AVMs larger than 10 cm3 in volume. Methods. Seventy-six patients (32%) had AVM nidus volumes of more than 10 cm3. During radiosurgery, targeting and delineation of AVM nidi were based on integrated stereotactic magnetic resonance (MR) imaging and x-ray angiography. The radiation treatment was performed using multiple small isocenters to improve conformity of the treatment volume. The mean dose inside the nidus was kept between 20 Gy and 24 Gy. The margin dose ranged between 15 to 18 Gy placed at the 55 to 60% isodose centers. Follow up ranged from 12 to 73 months. There was complete obliteration in 24 patients with an AVM volume of more than 10 cm3 and in 91 patients with an AVM volume of less than 10 cm3. The latency for complete obliteration in larger-volume AVMs was significantly longer. In Kaplan—Meier analysis, the complete obliteration rate in 40 months was 77% in AVMs with volumes between 10 to 15 cm3, as compared with 25% for AVMs with a volume of more than 15 cm3. In the latter, the obliteration rate had increased to 58% at 50 months. The follow-up MR images revealed that large-volume AVMs had higher incidences of postradiosurgical edema, petechiae, and hemorrhage. The bleeding rate before cure was 9.2% (seven of 76) for AVMs with a volume exceeding 10 cm3, and 1.8% (three of 164) for AVMs with a volume less than 10 cm3. Although focal edema was more frequently found in large AVMs, most of the cases were reversible. Permanent neurological complications were found in 3.9% (three of 76) of the patients with an AVM volume of more than 10 cm3, 3.8% (three of 80) of those with AVM volume of 3 to 10 cm3, and 2.4% (two of 84) of those with an AVM volume less than 3 cm3. These differences in complications rate were not significant. Conclusions. Recent improvement of radiosurgery in conjunction with stereotactic MR targeting and multiplanar dose planning has permitted the treatment of larger AVMs. It is suggested that gamma knife radiosurgery is effective for treating AVMs as large as 30 cm3 in volume with an acceptable risk.

Brain arteriovenous malformations (AVM) are complex vascular pathologies with a significant risk of hemorrhage. Stereotactic radiosurgery (SRS) is an effective treatment modality for AVM, initially popularized on the Gamma Knife (Elekta AB, Stockholm, Sweden) platform, and now benefits from the modern advances in linear accelerator (LINAC)-based platforms. This study evaluates the outcomes of LINAC-based SRS/hypofractionated stereotactic radiotherapy (hFSRT) for cerebral AVMs. Between December 2018 and April 2024, 15 patients with cerebral AVMs underwent SRS/hFSRT at a tertiary government hospital. Patient selection was based on AVM size, location, surgical unsuitability, and patient preference. All patients underwent MRI and cerebral angiography for nidus delineation. SRS was planned using Monaco TPS (treatment planning system) (Elekta AB, Stockholm, Sweden)with VMAT (volumetric modulated arc therapy) technique, delivering a median dose of 20 Gy in single fractions for small AVMs and 28 Gy infour fractions for large AVMs. Patients were followed up with annual MRI and angiography to assess obliteration. The cohort had a median age of 22 years, with a median nidus volume of 3.76 cc. The crude obliteration rate was 60%, confirmed by MRI/angiography. Actuarial obliteration rates at two, three, and five years were 65.71%, 73.57%, and 77.14%, respectively. Smaller AVMs (<3 cc) and those with a modified AVM radiosurgery score <1.5 had nearly 100% obliteration rates. Large AVMs (>10 cc) treated with hypofractionated SRT showed partial responses only. Significant predictors of obliteration included prescription dose, AVM volume, and modified AVM radiosurgery score. LINAC-based SRS demonstrates comparable efficacy to other modalities for treating cerebral AVMs, with obliteration rates influenced by dose, AVM volume, and pre-treatment radiosurgery score. Larger AVMs pose a greater challenge, suggesting a need for adjunctive treatments or higher fractionated doses to improve outcomes.

BackgroundCerebral arterio venous malformations (AVM) are a major causal factor for intracranial hemorrhage, which result in permanent disability or death. The molecular mechanisms of AVM are complex, and their pathogenesis remains an enigma. Current research on cerebral AVM is focused on characterizing the molecular features of AVM nidus to elucidate the aberrant signaling pathways. The initial stimuli that lead to the development of AVM nidus structures between a dilated artery and a vein are however not known.MethodsIn order to understand the molecular basis of development of cerebral AVM, we used in-depth RNA sequencing with the total RNA isolated from cerebral AVM nidus. Immunoblot and qRT-PCR assays were used to study the differential gene expression in AVM nidus, and immunofluorescence staining was used to study the expression pattern of aberrant proteins in AVM nidus and control tissues. Immunohistochemistry was used to study the expression pattern of aberrant proteins in AVM nidus and control tissues.ResultsThe transcriptome study has identified 38 differentially expressed genes in cerebral AVM nidus, of which 35 genes were upregulated and 3 genes were downregulated. A final modular analysis identified an upregulation of ALDH1A2, a key rate-limiting enzyme of retinoic acid signaling pathway. Further analysis revealed that CYR61, a regulator of angiogenesis, and the target gene for retinoic acid signaling is upregulated in AVM nidus. We observed that astrocytes associated with AVM nidus are abnormal with increased expression of GFAP and Vimentin. Triple immunofluorescence staining of the AVM nidus revealed that CYR61 was also overexpressed in the abnormal astrocytes associated with AVM tissue.ConclusionUsing high-throughput RNA sequencing analysis and immunostaining, we report deregulated expression of retinoic acid signaling genes in AVM nidus and its associated astrocytes and speculate that this might trigger the abnormal angiogenesis and the development of cerebral AVM in humans.

Background: We proposed an algorithm to automate the components within the identification of components within the nidus of cerebral arteriovenous malformations (AVMs) which may be used to analyze the relationship between its diffuseness and treatment outcomes following stereotactic radiosurgery (SRS). Objectives: to determine the impact of the diffuseness of the AVM nidus on SRS outcomes. Methods: This study conducted regular follow-ups of 209 patients with unruptured AVMs who underwent SRS. The diffuseness of the AVM nidus was estimated by quantifying the proportions of vascular nidal component, brain parenchyma, and cerebrospinal fluid in T2-weighted MRIs. We used Cox regression analysis to characterize the association between nidal diffuseness and treatment outcomes in terms of obliteration rate and radiation-induced change (RICs) rate following SRS. Results: The median AVM volume was 20.7 cm³. The median duration of imaging follow-up was 51 months after SRS. The overall AVM obliteration rate was 68.4%. RICs were identified in 156 of the 209 patients (74.6%). The median proportions of the nidus of AVM and brain parenchyma components within the prescription isodose range were 30.2 and 52.2%, respectively. Cox regression multivariate analysis revealed that the only factor associated with AVM obliteration rate after SRS was AVM volume. However, a larger AVM volume (>20 mL) and a larger proportion of brain parenchyma (>50%) within the prescription isodose range were both correlated with a higher RIC rate following SRS. Conclusions: The diffuseness of the nidus indeed appears to affect the RIC rate following SRS in patients with unruptured AVMs.

A combination of embolization and radiosurgery is used as a common strategy for the treatment of large and complex cerebral arteriovenous malformations (AVMs). This study presents the experiences of partially embolized cerebral AVMs followed by Gamma Knife surgery (GKS) and assesses predictive factors for AVM obliteration and hemorrhage. The interventional neuroradiology database that was reviewed included 404 patients who underwent AVM embolization. Using this database, the authors retrospectively analyzed all partially embolized AVM cases followed by GKS for a residual nidus. Except for cases of complete AVM obliteration, the authors excluded all patients with radiological follow-up of less than 2 years. Logistic regression analysis was used to analyze the predictive factors related to AVM obliteration and hemorrhage following GKS. Kaplan-Meier analysis was used to evaluate the obliteration with a cutoff AVM nidus volume of 3 cm(3) and 10 cm(3). One hundred sixty-two patients qualified for the study. The median patient age was 26 years and 48.8% were female. Hemorrhage presented as the most common symptom (48.1%). The median preembolization volume of an AVM was 14.3 cm(3). The median volume and margin dose for GKS were 10.92 cm(3) and 16.0 Gy, respectively. The median radiological and clinical follow-up intervals were 47 and 79 months, respectively. The annual hemorrhage rate was 1.71% and total obliteration rate was 56.8%. Noneloquent area (p = 0.004), superficial location (p < 0.001), decreased volume (p < 0.001), lower Spetzler-Martin grade (p < 0.001), lower Virginia Radiosurgery AVM Scale (RAS; p < 0.001), lower Pollock-Flickinger score (p < 0.001), lower modified Pollock-Flickinger score (p < 0.001), increased maximum dose (p < 0.001), and increased margin dose (p < 0.001) were found to be statistically significant in predicting the probability of AVM obliteration in the univariate analysis. In the multivariate analysis, only volume (p = 0.016) was found to be an independent prognostic factor for AVM obliteration. The log-rank (Mantel-Cox) test of the Kaplan-Meier analysis (chi-square = 54.402, p < 0.001) showed a significantly decreased obliteration rate of different cutoff AVM volume groups of less than 3 cm(3), 3-10 cm(3), and more than 10 cm(3). No independent prognostic factor was found for AVM hemorrhage in multivariate analysis. Partially embolized AVMs are amenable to successful treatment with GKS. The volume of the nidus significantly influences the outcome of radiosurgical treatment. The Virginia RAS and Pollock-Flickinger score were found to be reliable scoring systems for selection of patient candidates and prediction of partially embolized AVM closure and complications for GKS.

The appropriate dose during stereotactic radiosurgery (SRS) of cerebral arteriovenous malformations (AVMs) remains a matter of debate. In the present study, the authors retrospectively evaluated the association of using a prescribed dose calculated utilizing the K index with the obliteration rate of cerebral AVMs after SRS. The authors performed a retrospective analysis of the Cleveland Clinic SRS database. All patients undergoing Gamma Knife radiosurgery for cerebral AVMs from 1997 to 2010 were selected. Regression techniques and Kaplan-Meier analyses were used to investigate the effect of divergence from the optimal K index dose on the rate of AVM obliteration. In the study period 152 patients (mean age 43.6 years; 53.9% of treatments were performed in females) underwent 165 Gamma Knife radiosurgery treatments for AVMs. In a univariate analysis Spetzler-Martin grade (OR 0.63 [95% CI 0.42-0.93]), higher AVM score (OR 0.43 [95% CI 0.27-0.70]), larger AVM volume (OR 0.88 [95% CI 0.82-0.94]), and higher maximum diameter (OR 0.56 [95% CI 0.41-0.77]) were associated with a lower rate of AVM obliteration. Higher margin dose (OR 1.16 [95% CI 1.08-1.24]) and higher maximum dose (OR 1.08 [95% CI 1.04-1.13]) were associated with a higher obliteration rate. To further examine the effect of prescribed dose divergence from the calculated K index dose, cases were classified to groups depending on the AVM volume and dose variance from the ideal K index dose. Contingency tables and Kaplan-Meier curves were then created, and no significant differences in rates of obliteration were noted among the different groups. Gamma Knife radiosurgery for cerebral AVMs remains an effective and safe treatment modality. Smaller AVMs may receive doses less than the calculated K index dose without an apparent effect on obliteration rates.

Cerebral arteriovenous malformations (AVM) are pathological connections between arteries and veins without capillaries. Stereotactic radiosurgery (RS) is a proven and accepted treatment method for cerebral AVMs. Our objective was to analyze the factors influencing the clinical outcome in patients suffering from AVMs. We retrospectively reviewed 199 patients who were treated with Gamma-Knife RS for intracranial AVMs between 13 October 2005 and 31 October 2010. There were 89 male, 110 female patients with a median age of 32 years (range, 3-74 years). Obliteration was assessed with MRI angiography and DSA imaging. Complete obliteration rate after RS was 71 % (141 out of 199), including second RS treatments. In terms of obliteration rates, there was no significant difference between patients younger and older than 21 years old (p=0.669). After RS, 3 patients died due to intracranial hemorrhage and 1 died of heart disease. Death from AVM was determined as 1.5 %. Intracranial hemorrhage was observed in 7 (3.5 %) patients post-RS. Obliteration was found to be associated with Spetzler-Martin Grade, Pollock-Flickinger Grade, AVM volume, RS dose, bleeding history before RS and no previous embolization before RS. Gamma knife RS is an effective treatment method for the treatment of AVMs both for pediatric and adult patients. It provides high obliteration and low mortality rates.

Stereotactic radiosurgery (RS) is an effective tool in treating brain arteriovenous malformations (AVMs). Careful study of AVM angiographic characteristics may improve results. To report the long-term outcomes of Gamma Knife RS (GKRS) in brain AVMs, focusing on how the angioarchitectural and hemodynamic parameters of AVMs affect the post-RS results. This was a retrospective, longitudinal study of 697 consecutive GKRS treatments of brain AVMs in 662 patients performed at a single center between 1993 and 2005. The mean age of the patients was 37 years; the median AVM volume was 3.6 cm(3); and the mean follow-up was 11 years. Forty-five percent of patients presented with intracranial hemorrhage; 44% underwent embolization; and 7% had multiple RSs. AVM characteristics in the RS-planning angiograms were analyzed, and their relationship to the post-RS obliteration rate was determined by univariate and multivariate analyses. The obliteration rate after a single RS was 69.3%; after multiple RS, it was 75%. Positive predictors of obliteration included compact nidus (odds ratio = 3.16; 95% confidence interval, 1.92-5.22), undilated feeders (odds ratio = 0.36; 95% confidence interval, 0.23-0.57), smaller AVM volume (odds ratio = 0.95; 95% confidence interval, 0.92-0.99), and higher marginal dose (odds ratio = 1.16; 95% confidence interval, 1.06-1.27). Improvement or clinical stability was observed in 89.3% of patients; postprocedural bleeding was noted in 6.1%; and clinical worsening attributable to RS was seen in 3.8%. The annual risk of hemorrhage in the 4 years after RS was 1.2%. GKRS yielded a good long-term clinical outcome in most patients. Certain angiographic features of brain AVMs such as a well-defined nidus and undilated feeder arteries contribute to AVM occlusion by RS. GKRS can be regarded as the treatment of choice for AVMs <6 cm(3), even after bleeding.

The management of non-hemorrhagic arteriovenous malformations (AVMs) remains a subject of debate, even more since the ARUBA trial. Here, we report the obliteration rate, the risk of hemorrhage and the functional outcomes after Gamma Knife radiosurgery (GKRS) as first-line treatment for non-hemorrhagic AVMs treated before the ARUBA publication, in a reference university center with multimodal AVM treatments available. We retrospectively analyzed data from a continuous series of 172 patients harboring unruptured AVMs treated by GKRS as first-line treatment in our Lille University Hospital, France, between April 2004 and December 2013. The primary outcome was obliteration rate. Secondary outcomes were the hemorrhage rate, the modified Rankin Scale (mRS), morbidity and epilepsy control at last follow-up. The minimal follow-up period was of 3 years. Median age at presentation was 40 years (IQR 28; 51). Median follow-up was 8.8 years (IQR 6.8; 11.3). Median target volume was 1.9 cm3 (IQR 0.8–3.3 cm3), median Spetzler-Martin grade: 2 (IQR 1–2), median Pollock-Flickinger score: 1.07 (IQR 0.82–2.94), median Virginia score: 1 (IQR 1–2). Median treatment dose was 24 Gy at 50% isodose line. Twenty-three patients underwent a second GKRS after a median time of 58 months after first GKRS. The overall obliteration rate was of 76%, based primarily on cerebral angiography and/or rarely only upon MRI. Hemorrhage during the post-treatment follow-up was reported in 18 (10%) patients (annual risk of 1.1%). Transient post-GKRS morbidity was reported in 14 cases (8%) and persistent neurological deficit in 8 (4.6%) of patients. At last follow-up, 86% of patients had a mRS ≤ 1. Concerning patients with pretherapeutic epilepsy, 84.6% of them were seizure-free at last follow-up. GKRS as first-line therapeutic option for unruptured cerebral AVMs achieves high obliteration rates (76%) while maintaining a high-level patient’s autonomy. All hemorrhagic events occurred during the first 4 years after the initial GKRS. In cases with epilepsy, there was 84.6% seizure free at last follow-up. Permanent morbidity was reported in only 4.6%.

OBJECTIVE There are few reported series regarding volume-staged Gamma Knife radiosurgery (GKRS) for the treatment of large, complex, cerebral arteriovenous malformations (AVMs). The object of this study was to report the results of using volume-staged Gamma Knife radiosurgery for patients affected by large and complex AVMs. METHODS Data from 20 patients with large AVMs were prospectively included in the authors' AVM database between 2004 and 2012. A staging strategy was used when treating lesion volumes larger than 10 cm3. Hemorrhage and seizures were the presenting clinical feature for 6 (30%) and 8 (40%) patients, respectively. The median AVM volume was 15.9 cm3 (range 10.1-34.3 cm3). The mean interval between stages (± standard deviation) was 15 months (± 9 months). The median margin dose for each stage was 20 Gy (range 18-25 Gy). RESULTS Obliteration was confirmed in 8 (42%) patients after a mean follow-up of 45 months (range 19-87 months). A significant reduction (> 75%) of the original nidal volume was achieved in 4 (20%) patients. Engel Class I-II seizure status was reported by 75% of patients presenting with seizures (50% Engel Class I and 25% Engel Class II) after radiosurgery. After radiosurgery, 71.5% (5/7) of patients who had presented with a worsening neurological deficit reported a complete resolution or amelioration. None of the patients who presented acutely because of hemorrhage experienced a new bleeding episode during follow-up. One (5%) patient developed radionecrosis that caused sensorimotor hemisyndrome. Two (10%) patients sustained a bleeding episode after GKRS, although only 1 (5%) was symptomatic. High nidal flow rate and a time interval between stages of less than 11.7 months were factors significantly associated with AVM obliteration (p = 0.021 and p = 0.041, respectively). Patient age younger than 44 years was significantly associated with a greater than 75% reduction in AVM volume but not with AVM obliteration (p = 0.024). CONCLUSIONS According to the results of this study, volume-staged GKRS is an effective and safe treatment strategy for large, complex, cerebral AVMs for which microsurgery or endovascular approaches could carry substantially higher risks to the patient. Radiation doses up to 20 Gy can be safely administered. The time interval between stages should be shorter than 11.7 months to increase the chance of obliteration. High nidal flow and a patient age younger than 44 years were factors associated with nidus obliteration and significant nidus reduction, respectively.

To define the factors of importance for the obliteration of cerebral arteriovenous malformations (AVMs), thus making a prediction of the probability for obliteration possible. In 945 AVMs of a series of 1319 patients treated with the gamma knife during 1970 to 1990, the relationship between patient, AVMs, and treatment parameters on the one hand and the obliteration of the nidus on the other was analyzed. The obliteration rate increased both with increased minimum (lowest periphery) and average dose and decreased with increased AVM volume. The minimum dose to the AVMs was the decisive dose factor for the treatment result. The higher the minimum dose, the higher the chance for total obliteration. The curve illustrating this relation increased logarithmically to a value of 87%. A higher average dose shortened the latency to AVM obliteration. For the obliterated cases, the larger the malformation, the lower the minimum dose used. This prompted us to relate the obliteration rate to the product minimum dose (AVM volume)1/3 (K index). The obliteration rate increased linearly with the K index up to a value of approximately 27, and for higher K values, the obliteration rate had a constant value of approximately 80%. For the group of 273 cases treated with a minimum dose of at least 25 Gy, the obliteration rate at the study end point (defined as 2-yr latency) was 80% (95% confidence interval = 75-85%). If obliterations that occurred beyond the end point are included, the obliteration rate increased to 85% (81-89%). The probability of obliteration of AVMs after gamma knife surgery is related both to the lowest dose to the AVMs and the AVM volume, and it can be predicted using the K index.

Stereotactic linac-based radiosurgery in the treatment of cerebral arteriovenous malformations located deep, involving corpus callosum, motor cortex, or brainstem

Clinical outcome and complications of gamma knife radiosurgery for intracranial arteriovenous malformations