Stereotactic radiosurgery at a low marginal dose for the treatment of pediatric arteriovenous malformations: obliteration, complications, and functional outcomes

Object Stereotactic radiosurgery (SRS) is an established treatment modality for brain arteriovenous malformations (AVMs) in children, but the optimal treatment parameters and associated treatment-related complications are not fully understood. The authors present their single-institution experience of using SRS, at a relatively low marginal dose, to treat AVMs in children for nearly 20 years; they report angiographic outcomes, posttreatment hemorrhage rates, adverse treatment-related events, and functional outcomes. Methods The authors conducted a retrospective review of 2 cohorts of children (18 years of age or younger) with AVMs treated from 1991 to 1998 and from 2000 to 2010. Results A total of 80 patients with follow-up data after SRS were identified. Mean age at SRS was 12.7 years, and 56% of patients had hemorrhage at the time of presentation. Median target volume was 3.1 cm3 (range 0.09–62.3 cm3), and median prescription marginal dose used was 17.5 Gy (range 12–20 Gy). Angiograms acquired 3 years after treatment were available for 47% of patients; AVM obliteration was achieved in 52% of patients who received a dose of 18–20 Gy and in 16% who received less than 18 Gy. At 5 years after SRS, the cumulative incidence of hemorrhage was 25% (95% CI 16%–37%). No permanent neurological deficits occurred in patients who did not experience posttreatment hemorrhage. Overall, good functional outcomes (modified Rankin Scale Scores 0–2) were observed for 78% of patients; for 66% of patients, functional status improved or remained the same as before treatment. Conclusions A low marginal dose minimizes SRS-related neurological deficits but leads to low rates of obliteration and high rates of hemorrhage. To maximize AVM obliteration and minimize posttreatment hemorrhage, the authors recommend a prescription marginal dose of 18 Gy or more. In addition, SRS-related symptoms such as headache and seizures should be considered when discussing risks and benefits of SRS for treating AVMs in children.

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Stereotactic radiosurgery for sylvian fissure arteriovenous malformations with emphasis on hemorrhage risks and seizure outcomes

Journal of Neurosurgery ◽

10.3171/2014.5.jns132244 ◽

2014 ◽

Vol 121 (3) ◽

pp. 637-644 ◽

Cited By ~ 8

Author(s):

Greg Bowden ◽

Hideyuki Kano ◽

Daniel Tonetti ◽

Ajay Niranjan ◽

John Flickinger ◽

...

Keyword(s):

Stereotactic Radiosurgery ◽

Arteriovenous Malformations ◽

Seizure Control ◽

Cyst Formation ◽

Target Volume ◽

Sylvian Fissure ◽

Neurological Deficits ◽

Single Institution ◽

Latency Interval

Object Sylvian fissure arteriovenous malformations (AVMs) present substantial management challenges because of the critical adjacent blood vessels and functional brain. The authors investigated the outcomes, especially hemorrhage and seizure activity, after stereotactic radiosurgery (SRS) of AVMs within or adjacent to the sylvian fissure. Methods This retrospective single-institution analysis examined the authors' experiences with Gamma Knife surgery for AVMs of the sylvian fissure in cases treated from 1987 through 2009. During this time, 87 patients underwent SRS for AVMs in the region of the sylvian fissure. Before undergoing SRS, 40 (46%) of these patients had experienced hemorrhage and 36 (41%) had had seizures. The median target volume of the AVM was 3.85 cm3 (range 0.1–17.7 cm3), and the median marginal dose of radiation was 20 Gy (range 13–25 Gy). Results Over a median follow-up period of 64 months (range 3–275 months), AVM obliteration was confirmed by MRI or angiography for 43 patients. The actuarial rates of confirmation of total obliteration were 35% at 3 years, 60% at 4 and 5 years, and 76% at 10 years. Of the 36 patients who had experienced seizures before SRS, 19 (53%) achieved outcomes of Engel class I after treatment. The rate of seizure improvement was 29% at 3 years, 36% at 5 years, 50% at 10 years, and 60% at 15 years. No seizures developed after SRS in patients who had been seizure free before treatment. The actuarial rate of AVM hemorrhage after SRS was 5% at 1, 5, and 10 years. This rate equated to an annual hemorrhage rate during the latency interval of 1%; no hemorrhages occurred after confirmed obliteration. No permanent neurological deficits developed as an adverse effect of radiation; however, delayed cyst formation occurred in 3 patients. Conclusions Stereotactic radiosurgery was an effective treatment for AVMs within the region of the sylvian fissure, particularly for smaller-volume AVMs. After SRS, a low rate of hemorrhage and improved seizure control were also evident.

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Stereotactic radiosurgery for arteriovenous malformations, Part 5: management of brainstem arteriovenous malformations

Journal of Neurosurgery ◽

10.3171/2011.9.jns11176 ◽

2012 ◽

Vol 116 (1) ◽

pp. 44-53 ◽

Cited By ~ 41

Author(s):

Hideyuki Kano ◽

Douglas Kondziolka ◽

John C. Flickinger ◽

Huai-che Yang ◽

Thomas J. Flannery ◽

...

Keyword(s):

Stereotactic Radiosurgery ◽

Arteriovenous Malformations ◽

Radiation Effects ◽

Latency Period ◽

Target Volume ◽

Neurological Deficits ◽

Latency Interval ◽

Brain Avms

Object In this paper, the authors' goal was to define the long-term outcomes and risks of stereotactic radiosurgery (SRS) for arteriovenous malformations (AVMs) of the medulla, pons, and midbrain. Methods Between 1987 and 2006, the authors performed Gamma Knife surgery in 996 patients with brain AVMs; 67 patients had AVMs in the brainstem. In this series, 51 patients (76%) had a prior hemorrhage. The median target volume was 1.4 cm3 (range 0.1–13.4 cm3). The median margin dose was 20 Gy (range 14–25.6 Gy). Results Obliteration of the AVMs was eventually documented in 35 patients at a median follow-up of 73 months (range 6–269 months). The actuarial rates of documentation of total obliteration were 41%, 70%, 70%, and 76% at 3, 4, 5, and 10 years, respectively. Higher rates of AVM obliteration were associated only with a higher margin dose. Four patients (6%) suffered a hemorrhage during the latency period, and 2 patients died. The rate of AVM hemorrhage after SRS was 3.0%, 3.0%, and 5.8% at 1, 5, and 10 years, respectively. The overall annual hemorrhage rate was 1.9%. Permanent neurological deficits due to adverse radiation effects (AREs) developed in 7 patients (10%) after SRS, and a delayed cyst developed in 2 patients (3%). One patient died at an outside institution with symptoms of AREs and unrecognized hydrocephalus. Higher 12-Gy volumes and higher Spetzler-Martin grades were associated with a higher risk of symptomatic AREs. Ten of 22 patients who had ocular dysfunction before SRS had improvement, 9 were unchanged, and 3 were worse due to AREs. Eight of 14 patients who had hemiparesis before SRS improved, 5 were unchanged, and 1 was worse. Conclusions Although hemorrhage after obliteration did not occur in this series, patients remained at risk during the latency interval until obliteration occurred. Thirty-eight percent of the patients who had neurological deficits due to prior hemorrhage improved. Higher dose delivery in association with conformal and highly selective SRS is required for safe and effective radiosurgery.

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Endovascular Therapy Followed by Stereotactic Radiosurgery for Cerebral Arteriovenous Malformations

Interventional Neuroradiology ◽

10.1177/15910199060120s128 ◽

2006 ◽

Vol 12 (1_suppl) ◽

pp. 163-166 ◽

Cited By ~ 5

Author(s):

Y. Arai ◽

Y. Handa ◽

H. Ishii ◽

Y. Ueda ◽

H. Uno ◽

...

Keyword(s):

Stereotactic Radiosurgery ◽

Arteriovenous Malformations ◽

High Rate ◽

Neurological Deficits ◽

Cerebral Arteriovenous Malformations ◽

Increased Risk ◽

Irradiation Therapy ◽

Complete Obliteration ◽

Vascular Structures

Pre-radiosurgical embolization was carried out using cyanoacrylate in seven of 13 patients with cerebral arteriovenous malformations (AVMs) treated by stereotactic radiosurgery (SRS) with a linear accelerator (LINAC). The aim of embolization before SRS was the reduction of AVM volume and/or the elimination of vascular structures bearing an increased risk of haemorrhage. Staged-volume SRS was also performed in two patients because of residual irregular shaped nidus of AVMs even after the embolizations. Complete obliteration of the AVM nidus on angiogram was presented in five patients with embolizations (including one with staged-volume SRS) and in three of six patients with SRS alone, during follow-up periods after radiosurgery. No patients experienced haemorrhagic events after SRS. Although transient neurological symptoms were observed after embolizations in two patients, no permanent neurological deficits were presented in all patients with SRS. Pre-radiosurgical embolization may allow the effective influence on irradiation therapy in relatively large AVMs and promote more frequent obliteration in more small sized AVMs compared to those with SRS alone. However, further study must be needed to determine whether staged-volume SRS provides a high rate of AVM obliteration and its safeness.

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Onyx embolization prior to stereotactic radiosurgery for brain arteriovenous malformations: a single-center treatment algorithm

Journal of NeuroInterventional Surgery ◽

10.1136/neurintsurg-2017-013084 ◽

2017 ◽

Vol 10 (3) ◽

pp. 258-267 ◽

Cited By ~ 5

Author(s):

John D Nerva ◽

Jason Barber ◽

Michael R Levitt ◽

Jason K Rockhill ◽

Danial K Hallam ◽

...

Keyword(s):

Stereotactic Radiosurgery ◽

Complication Rate ◽

Arteriovenous Malformations ◽

Treatment Algorithm ◽

Latency Period ◽

Neurological Deficits ◽

Brain Arteriovenous Malformations ◽

Radiographic Outcomes ◽

Ethylene Copolymer

BackgroundEmbolization before stereotactic radiosurgery (SRS) for brain arteriovenous malformations (BAVMs) is controversial.ObjectiveTo compare clinical and radiographic outcomes in patients undergoing pre-SRS embolization with ethylene copolymer (Onyx) with outcomes in patients undergoing SRS alone.MethodsSeventy consecutive patients with BAVMs who underwent SRS were retrospectively reviewed. Univariate and multivariate analyses were performed to assess the factors associated with radiographic obliteration and complication.ResultsForty-one (59%) patients presented without BAVM rupture and 29 (41%) patients presented with rupture. Pre-SRS embolization was used in 20 patients (28.6%; 7 unruptured and 13 ruptured). Twenty-five of 70 (36%) patients sustained a complication from treatment, including 6 (9%) patients with a post-SRS latency period hemorrhage. Ten (14%) patients had persistent neurological deficits after treatment. Functional outcome (as modified Rankin Scale), complication rate, and radiographic obliteration at last follow-up were not significantly different between embolized and non-embolized groups in both unruptured and ruptured BAVMs. For unruptured BAVMs, 3- and 5-year rates of radiographic obliteration were 23% and 73% for non-embolized patients and 20% and 60% for embolized patients, respectively. For ruptured BAVMs, 3- and 5-year rates of radiographic obliteration were 45% and 72% for non-embolized patients and 53% and 82% for embolized patients, respectively.ConclusionPre-SRS embolization with Onyx was not associated with worse clinical or radiographic outcomes than SRS treatment without embolization. Pre-SRS embolization has a low complication rate and can safely be used to target high-risk BAVM features in carefully selected patients destined for SRS.

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

Journal of Neurosurgery ◽

10.3171/2018.2.jns172964 ◽

2019 ◽

Vol 130 (6) ◽

pp. 1809-1816 ◽

Cited By ~ 3

Author(s):

Hideyuki Kano ◽

John C. Flickinger ◽

Aya Nakamura ◽

Rachel C. Jacobs ◽

Daniel A. Tonetti ◽

...

Keyword(s):

Multivariate Analysis ◽

Stereotactic Radiosurgery ◽

Large Volume ◽

Arteriovenous Malformations ◽

Target Volume ◽

Second Stage ◽

Percentage Volume ◽

Median Margin ◽

Median Interval

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.

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Evolution of the Management of Tentorial Dural Arteriovenous Malformations

Neurosurgery ◽

10.1227/01.neu.0000053221.22954.85 ◽

2003 ◽

Vol 52 (4) ◽

pp. 750-762 ◽

Cited By ~ 111

Author(s):

Patrick R. Tomak ◽

Harry J. Cloft ◽

Akihiko Kaga ◽

C. Michael Cawley ◽

Jacques Dion ◽

...

Keyword(s):

Arteriovenous Malformations ◽

Therapeutic Strategy ◽

Transarterial Embolization ◽

Treatment Strategies ◽

Venous Drainage ◽

Neurological Deficits ◽

Transvenous Embolization ◽

Single Institution ◽

Clinical Presentations

Abstract OBJECTIVE Tentorial dural arteriovenous malformations (DAVMs) are uncommon lesions associated with an aggressive natural history. Controversy exists regarding their optimal treatment. We present a single-institution series of tentorial DAVMs treated during a 12-year period, address the current controversies, and present the rationale for our current therapeutic strategy. METHODS Twenty-two patients with tentorial DAVMs were treated between 1988 and 2000. Treatment consisted of transarterial or transvenous embolization, surgical resection, disconnection of venous drainage, or a combination of these therapies. The clinical presentations, radiological features, treatment strategies, and results were studied. RESULTS Eighteen patients (82%) presented with intracranial hemorrhage or progressive neurological deficits. Retrograde leptomeningeal venous drainage was documented in 22 cases (100%), classifying the lesions as Borden Type III. Angiographic follow-up monitoring was performed for 0 to 120 months and clinical follow-up monitoring for 1 to 120 months. Posttreatment angiography demonstrated obliteration in 22 cases (100%). Two patients experienced neurological decline after endovascular treatment and died. All of the 20 surviving patients exhibited clinical improvement; there were no episodes of rehemorrhage or new neurological deficits. Outcomes were excellent in 17 cases (77%), good in 2 cases (9%), and fair in 1 case (5%), and there were 2 deaths (9%). CONCLUSION Tentorial DAVMs are aggressive lesions that require prompt total angiographic obliteration. Disconnection of the venous drainage from the fistula may be accomplished with transarterial embolization to the venous side, transvenous embolization, or surgical disconnection of the fistula. We think that extensive nidal resections carry more risk and are unnecessary. We do not think there is a role for stereotactic radiosurgery in the treatment of these lesions.

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Endovascular Therapy Followed by Stereotactic Radiosurgery for Cerebral Arteriovenous Malformations

Rivista di Neuroradiologia ◽

10.1177/197140099500800628 ◽

1995 ◽

Vol 8 (6) ◽

pp. 163-166

Author(s):

Y. Arai ◽

Y. Handa ◽

H. Ishii ◽

Y. Ueda ◽

H. Uno ◽

...

Keyword(s):

Stereotactic Radiosurgery ◽

Arteriovenous Malformations ◽

High Rate ◽

Neurological Deficits ◽

Cerebral Arteriovenous Malformations ◽

Increased Risk ◽

Irradiation Therapy ◽

Complete Obliteration ◽

Vascular Structures

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Stereotactic radiosurgery for arteriovenous malformations, Part 2: management of pediatric patients

Journal of Neurosurgery Pediatrics ◽

10.3171/2011.9.peds10458 ◽

2012 ◽

Vol 9 (1) ◽

pp. 1-10 ◽

Cited By ~ 69

Author(s):

Hideyuki Kano ◽

Douglas Kondziolka ◽

John C. Flickinger ◽

Huai-che Yang ◽

Thomas J. Flannery ◽

...

Keyword(s):

Stereotactic Radiosurgery ◽

Arteriovenous Malformations ◽

Radiation Effects ◽

Pediatric Patients ◽

Cyst Formation ◽

Target Volume ◽

Brain Regions ◽

Neurological Deficits ◽

Maximum Diameter ◽

Latency Interval

Object The authors conducted a study to define the long-term outcomes and risks of stereotactic radiosurgery (SRS) for pediatric arteriovenous malformations (AVMs). Methods Between 1987 and 2006, the authors performed Gamma Knife surgery in 996 patients with brain AVMs; 135 patients were younger than 18 years of age. The median maximum diameter and target volumes were 2.0 cm (range 0.6–5.2 cm) and 2.5 cm3 (range 0.1–17.5 cm3), respectively. The median margin dose was 20 Gy (range 15–25 Gy). Results The actuarial rates of total obliteration documented by angiography or MR imaging at 71.3 months (range 6–264 months) were 45%, 64%, 67%, and 72% at 3, 4, 5, and 10 years, respectively. The median time to complete angiographically documented obliteration was 48.9 months. Of 81 patients with 4 or more years of follow-up, 57 patients (70%) had total obliteration documented by angiography. Factors associated with a higher rate of documented AVM obliteration were smaller AVM target volume, smaller maximum diameter, and larger margin dose. In 8 patients (6%) a hemorrhage occurred during the latency interval, and 1 patient died. The rates of AVM hemorrhage after SRS were 0%, 1.6%, 2.4%, 5.5%, and 10.0% at 1, 2, 3, 5, and 10 years, respectively. The overall annual hemorrhage rate was 1.8%. Larger volume AVMs were associated with a significantly higher risk of hemorrhage after SRS. Permanent neurological deficits due to adverse radiation effects developed in 2 patients (1.5%) after SRS, and in 1 patient (0.7%) delayed cyst formation occurred. Conclusions Stereotactic radiosurgery is a gradually effective and relatively safe management option for pediatric patients in whom surgery is considered to pose excessive risks. Although hemorrhage after AVM obliteration did not occur in the present series, patients remain at risk during the latency interval until obliteration is complete. The best candidates for SRS are pediatric patients with smaller volume AVMs located in critical brain regions.

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Stereotactic Radiosurgery for Motor Cortex Region Arteriovenous Malformations

Neurosurgery ◽

10.1097/00006123-200101000-00013 ◽

2001 ◽

Vol 48 (1) ◽

pp. 70-77 ◽

Cited By ~ 8

Author(s):

Constantinos G. Hadjipanayis ◽

Elad I. Levy ◽

Ajay Niranjan ◽

Andrew D. Firlik ◽

Douglas Kondziolka ◽

...

Keyword(s):

Motor Cortex ◽

Stereotactic Radiosurgery ◽

Arteriovenous Malformations ◽

Target Volume ◽

Complete Obliteration ◽

Target Volumes ◽

Group 3 ◽

Group 2 ◽

Group 1

Abstract OBJECTIVE The optimal management of arteriovenous malformations (AVMs) in critical brain locations remains controversial. To reduce the risk of an AVM hemorrhage and to enhance the possibility of preserving neurological function, stereotactic radiosurgery was performed in 33 patients with newly diagnosed or residual AVMs located within the motor cortex. The role of embolization also was examined. METHODS During a 9-year study period, 33 patients with AVMs located primarily in the motor cortex region were treated with stereotactic radiosurgery. These patients were followed up radiographically for a minimum of 36 months, or less if obliteration was documented before 36 months had elapsed. Of the 33 patients, 9 underwent embolization and 1 underwent microsurgery before radiosurgery. Nine patients required a second radiosurgery. The mean AVM target volume was 4.35 cc, and the average radiation dose to the AVM margin was 20 Gy. The median follow-up was 36 months (range, 10–91 mo), and angiographic follow-up of eligible patients was performed 24 or 36 months after radiosurgery. RESULTS Results were stratified by radiosurgical target volumes: less than 3 cc (Group 1), 3 to 10 cc (Group 2), and greater than 10 cc (Group 3). Overall (including second radiosurgery), 13 (87%) of 15 patients in Group 1 had complete obliteration confirmed by angiography. Nine (64%) of 14 patients in Group 2 exhibited nidus obliteration, and one (25%) of four patients in Group 3 demonstrated obliteration on a magnetic resonance imaging scan. Eight patients (24%) underwent second-stage radiosurgery after angiography revealed a persistent AVM nidus; three patients demonstrated complete obliteration on follow-up angiography. The obliteration rate was higher (87%) for AVMs with less than 3 cc target volume and lower (56%) for those with target volumes larger than 3 cc. One patient experienced worsening neurological function after radiosurgery, and one died from delayed AVM hemorrhage during the latency period. No patient bled after angiographically confirmed AVM obliteration. CONCLUSION Stereotactic radiosurgery is a successful and safe management option for patients with motor cortex AVMs. The obliteration of AVMs and the attendant low morbidity rates indicate a primary role for radiosurgery in these patients. Staged radiosurgery may be necessary to increase obliteration rates for larger AVMs or for those that are not obliterated after the first procedure.

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The Outcomes of Radiosurgery for Arteriovenous Malformations—Experience of a Tertiary Cancer Center from India

Indian Journal of Neurosurgery ◽

10.1055/s-0041-1724464 ◽

2021 ◽

Author(s):

Sanjay M. Hunugundmath ◽

Sumit Basu ◽

Bhooshan Zade ◽

Vikram Maiya ◽

Rahul Sharma ◽

...

Keyword(s):

Stereotactic Radiosurgery ◽

Planning Target Volume ◽

Arteriovenous Malformations ◽

Target Volume ◽

Cancer Center ◽

Median Dose ◽

Noninvasive Treatment ◽

Entire Cohort ◽

Tertiary Cancer Center

Abstract Objectives This article assesses the treatment outcomes in the patients diagnosed with arteriovenous malformations (AVMs) treated with stereotactic radiosurgery. Materials and Methods We retrospectively analyzed 30 patients diagnosed with AVM treated between 2010 and 2018.The median age at presentation was 30 years (range: 14–60 years). The median planning target volume (PTV) was 6.8 mL (range: 0.9–54 mL). The median dose prescribed was 18 Gy (range: 16–24 Gy). Modified radiosurgery-based AVM grading score was calculated for all the patients. Results The median follow-up of the entire cohort was 60 months (range: 24–96 months). The obliteration rates for patients followed up for 3 and 5 years were 75 and 86.1%, respectively. Age (< 35 years; p = 0.007) and PTV (< 7 mL; p = 0.04), had better obliteration rates. Three patients had hemorrhage, from the AVM after irradiation. None of them were fatal. Conclusion Stereotactic radiosurgery is a preferred noninvasive treatment modality with acceptable morbidity.

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