Stereotactic Radiosurgical Treatment of Cerebral Arteriovenous Malformations

doi:10.4065/70.3.214

Mayo Clinic Proceedings

Volume 70, Issue 3, March 1995, Pages 214-222

https://doi.org/10.4065/70.3.214 Get rights and content

Objective

To assess the role of clinical factors, size of lesion, site of involvement, and radiation dose in patients with cerebral arteriovenous malformations (AVMs) who underwent stereotactic radiosurgical treatment.

Design

We reviewed the results in 121 patients with cerebral AVMs treated with the Leksell “Gamma Knife” between January 1990 and December 1993 at the Mayo Clinic in Rochester, Minnesota.

Material and Methods

The following strict dosevolume protocol was used: AVMs 2.0 cm or smaller in diameter (volume, 4.2 cm³ or less) received 20 Gy to the margin of the nidus, those between 2.1 and 3.0 cm in diameter (4.3 to 14.1 cm³) received 18 Gy to the margin, and those that exceeded 3.0 cm in diameter (more than 14.1 cm³) received 16 Gy to the margin. Lesions that involved the brain stem received a radiosurgical dose of 18 Gy or less to the margin. Patients participated in regular follow-up clinical and imaging studies for up to 55 months.

Results

Follow-up cerebral angiography in 43 patients demonstrated total obliteration of the AVM nidus in 31 (72.1 %), including 5 of 7 (71.4%) who had AVMs with a volume larger than 10 cm³, Clinical follow-up revealed that 111 patients (91.7%) had a stable or improved outcome, 3 had a nonfatal AVM hemorrhage, 2 suffered a fatal hemorrhage, and 2 died of causes not directly attributed to the AVM or radiosurgical treatment. Two patients had new or increased, nondisabling neurologic deficits as a result of treatment, and one patient had a temporary partial evelid ptosis.

Conclusion

Our findings suggest that previous theories about the relationship between AVM size and rate of obliteration after radiosnrgical treatment may need revision. Our experience confirms that radiosurgical treatment for cerebral AVMs is safe and effective, even in cases for which the latency period before obliteration is longer than 2 years.

Section snippets

PATIENTS AND METHODS

Study Population.—Between January 1990 and December 1993, we used the Leksell Gamma Knife to treat 121 patients with parenchymal cerebral AVMs. Patients with dural AVMs and angiographically occult vascular malformations (including cavernous malformations) were excluded from this analysis. The mean age of these patients was 38 years (range, 3 to 78). The study group consisted of approximately equal numbers of male (N = 61) and female (N = 60) patients. Of the 121 AVMs, 53 (44%) had bled at least

RESULTS

Clinical Follow-Up.—The acute toxic reactions noted in this study were the occurrence of focal seizures in two patients on the first and second days after treatment. In both patients, long-term anticonvulsant therapy had been necessary for a preexisting seizure disorder. At the most recent clinical follow-up of all 121 patients between 6 and 55 months after the radiosurgical procedure, 89 patients (74%) were neurologically stable (Table 3). An additional 22 patients (18%) experienced neurologic

DISCUSSION

A decade ago, radiosurgical techniques were poorly understood and used only as a last-resort treatment of AVMs by a handful of neurosurgeons and radiation therapists in a small group of desperate patients with inoperable lesions. More recently, our experience with radiosurgical procedures has grown and matured, the natural history of intracranial AVMs has become more clear, realistic data on the risks associated with various treatment options for AVMs have become available, and the financial

CONCLUSION

Radiosurgical treatment is now one of the mainstays of management of patients with intracranial AVMs. Radiosurgical results are superior to the natural history of untreated AVMs and, in certain instances, are superior to the results of conventional surgical treatment.

Acknowledgment

The Department of Health Sciences Research and Yoshihiro oshihiro Yamamoto, M.D., D.M.Sc., Department of Neurologic Surgery, provided assistance with the statistical analysis, and Angela K. Kollasch prepared the submitted manuscript.

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Effects of high-dose irradiation on vascularization: Physiopathology and clinical consequences
2019, Cancer/Radiotherapie
Une revue de la littérature a été réalisée afin de mieux comprendre les effets de la radiothérapie à haute dose par fraction sur la vascularisation tumorale et ses conséquences. Les fortes doses d’irradiation entraînent la mort des cellules endothéliales par apoptose via la voie de la céramide. Les conséquences vasculaires sont alors multiples, avec une augmentation de la perméabilité, une diminution du flux sanguin, une augmentation de l’hypoxie et de la nécrose intratumorale. Cette nécrose est à l’origine d’une mort indirecte des cellules cancéreuses dans les jours suivants l’irradiation. Si l’importance de ce processus de mort cellulaire indirecte dans le contrôle tumoral reste controversée, elle permet cependant d’expliquer les bons résultats cliniques de la radiothérapie stéréotaxique. La radiothérapie stéréotaxique est donc un traitement qui agit via le microenvironnement tumoral. Les récidives tumorales dans cet environnement hypoxique sont plus lentes en raison de la perturbation des mécanismes de revascularisation, mais sont également plus agressives, avec une résistance accrue aux traitements et un risque plus élevé de métastases. À plus long terme, l’atteinte vasculaire est liée à une inflammation chronique et un processus cicatriciel pathologique qui aboutit à l’occlusion vasculaire. Ce phénomène est à la base du traitement des malformations artérioveineuses mais est également responsable d’une atteinte des tissus sains pouvant induire des complications chroniques. C’est pour cela que les irradiations à forte dose ne peuvent être réalisées qu’en utilisant les modalités techniques de la radiothérapie en conditions stéréotaxiques. Celle-ci permet en effet de délivrer une dose élevée dans le volume cible avec un haut niveau de précision, ce qui permet de réduire la dose reçue par les organes sains environnants.
A review of the literature has been conducted to better understand the effect of stereotactic radiotherapy on tumour vascularization and their consequences. High irradiation doses cause the death of endothelial cells by apoptosis through the ceramide pathway. Vascular consequences are multiple: increased permeability, decreased blood flow, increased hypoxia and tumoral necrosis. This necrosis causes an indirect death of the cancer cells in the days following the irradiation. The importance of indirect cell death in tumour control remains controversial, but it can explain the good clinical results of stereotactic radiotherapy. Stereotactic radiotherapy is a treatment of the tumour microenvironment. Tumour recurrence in this hypoxic environment is slower through disturbance of revascularization mechanisms but also more aggressive, with increased resistance to treatment and a higher risk of metastasis. In a longer time, vascular damage leads to chronic inflammation and a dysfunctional healing process resulting in vascular occlusion. This phenomenon is used in the treatment of arteriovenous malformations but is also responsible for damage to healthy tissues responsible for chronic complications. This is why high-dose irradiation can only be delivered using stereotactic radiotherapy, which reduces the irradiated volume.
Surgical management of giant intracranial arteriovenous malformations: A single center experience over 32 years
2015, World Neurosurgery
Citation Excerpt :
Radiation therapy, in the form of radiosurgery and hypofractionated radiotherapy, has also played a significant role in the treatment of AVMs. Single-fraction SRS has proven effective in treating AVMs with nidal volumes less than 14 cm3 or 3 cm in diameter, with complete occlusion rates reported at 72% to 96% (12, 17, 27, 61); however, larger lesions have resulted in lukewarm results (11, 18, 32). Several studies have demonstrated that both nonobliteration and complication rates increased when AVMs exceed 10 cm3.
Treatment of giant intracranial arteriovenous malformations (gAVMs) is a formidable challenge for neurosurgeons and carries significant morbidity and mortality rates for patients compared with smaller AVMs. In this study, we reviewed the treatments, angiographic results, and clinical outcomes in 64 patients with gAVMs who were treated at Henry Ford Hospital between 1980 and 2012.
The arteriovenous malformation (AVM) database at our institution was queried for patients with gAVMs (≥6 cm) and data regarding patient demographics, presentation, AVM angioarchitecture, and treatments were collected. Functional outcomes as well as complications were analyzed.
Of the 64 patients, 33 (51.6%) were female and 31 (48.4%) were male, with an average age of 45.7 years (SD ± 15.5). The most common symptoms on presentation were headaches (50%), seizures (50%), and hemorrhage (41%). The mean AVM size was 6.65 cm (range, 6−9 cm). Only 6 AVMs (9.4%) were located in the posterior fossa. The most common Spetzler-Martin grade was V, seen in 64% of patients. Of the 64 patients, 42 (66%) underwent surgical excision, 10 (15.5%) declined any treatment, 8 (12.5%) were deemed inoperable and followed conservatively, 2 (3%) had stand-alone embolization, 1 (1.5%) had embolization before stereotactic radiosurgery, and 1 (1.5%) received stereotactic radiosurgery only. Complete obliteration was achieved in 90% of the surgical patients. Mortality rate was 19% in the surgical cohort compared with 22% in the observation cohort (P = 0.770).
Treatment of gAVMs carries significant morbidity and mortality; however, good outcomes are attainable with a multimodal treatment approach in carefully selected patients.
Radiosurgery of cerebral arteriovenous malformations: A prescription algorithm
2009, Cancer/Radiotherapie
Étudier des facteurs pronostiques d’oblitération et des facteurs prédictifs pour la radionécrose cérébrale dans l’objectif d’élaborer un algorithme de prescription du traitement des malformations artérioveineuses cérébrales par radiochirurgie.
Une radiochirurgie a été délivrée chez 179 patients, par arc thérapie (84 %), ou par des faisceaux fixes (16 %) de rayons X de 6 ou 10 MV, avec deux microcollimateurs. L’IRM a été utilisée pour rechercher une radionécrose, l’artériographie pour juger de l’évolution de la malformation artérioveineuse.
Une oblitération a été obtenue dans 82,7 % des cas avec un délai moyen de 3,1 ans. Les facteurs pronostiques étaient : forme simple du nidus (risque relatif [RR] = 2,8 ; p < 0,0001), moins de quatre embolisations avant la radiochirurgie (RR = 2,9 ; p < 0,0001), dose prescrite en périphérie d’au moins 18 Gy (RR = 2 ; p = 0,0002), nidus de moins de 8 cm³ (RR = 1,9 ; p = 0,0002) et moins de six positions de table (RR = 1,4 ; p = 0,05). Le taux de radionécrose était de 11,2 % ; son délai moyen de survenue de 18 mois. Les facteurs prédictifs étaient : traitement par faisceaux fixes (selon le logiciel RR = 9,1 ; p < 0,0001 et RR = 15,1 ; p = 0,01), patient âgé de moins de 30 ans (RR = 2,5 ; p = 0,04), profondeur de la malformation artérioveineuse cérébrale d’au moins 7 cm (RR = 7,6 ; p = 0,008), volume cérébral inclus dans l’isodose 12 Gy (V12 Gy) de 11 cm³ ou plus (RR = 7,8 ; p = 0,05).
Un algorithme de prescription du traitement stéréotaxique des malformations artérioveineuses cérébrales a été réalisé en prenant en compte la dose prescrite à la périphérie (≥ 18 Gy) et le V12 Gy.
To study prognostic factors of obliteration and risk factors of brain radiation necrosis in order to propose an algorithm for radiosurgery prescription for cerebral arteriovenous malformations (cAVM).
One hundred and seventy-nine patients were analysed. Radiosurgery delivered 6 or 10 MV X-rays by arc therapy in 84% of cases, or by fixed field in 16% of cases using two different micro-multileaf collimators (micro-MLC). Follow-up consisted of screening radiation necrosis by MRI every 6 months, and assessing local control by arteriography every 2 years. Obliteration was defined as at least 95% reduction of cAVM volume. Cox proportional hazard model was used to evaluate the local control and the appearance of radiation necrosis over time.
Local control rate was 82.7% with the mean follow-up of 3.1 years (0.5–11). Significant prognostic factors were: simple nidus (RR = 2.8, p < 0.0001), number of embolizations before radiosurgery below 4 (RR = 2.9, p < 0.0001), prescribed dose to the periphery of at least 18 Gy (RR = 2, p = 0.0002), nidus volume below 8 cm³ (RR = 1.9, p = 0.0002), and number of table positions below six (RR = 1.4, p = 0.05). Radiation necrosis rate was 11.2% with a mean time to onset of 18 months. Significant predictive factors were: fixed field versus arc therapy (according to MLC RR = 9.1, p < 0.0001, and RR = 15.1, p = 0.01), age below 30 years (RR = 2.5, p = 0.04), depth of cAVM greater than or equal to 7 cm (RR = 7.6, p = 0.008), and volume of brain tissue covered by the 12 Gy isodose (V12 Gy) of at least 11 cm³ (RR = 7.8, p = 0.05).
A radiosurgery prescription algorithm taking into account the prescribed dose to the periphery (≥ 18 Gy) and reduction of V12 Gy was elaborated from these data.
Radiosurgery for epilepsy
2006, Lancet Neurology
Citation Excerpt :
Given these restrictions, some useful data may still be harvested. Studies from the past 25 years of seizure outcomes after radiosurgery with gamma knife, LINAC, proton beams, and heavy charged particles6,15,16,34–49 are most notable for the wide range of seizure outcome reported, with improvement rates varying from 20%44 to 85%15 or no effect at all.37 In some cases, radiosurgery induced a deterioration of seizure control: for example, seven of 39 patients had an increase in seizure frequency after proton-beam irradiation.41
Radiosurgery is an emerging therapeutic approach for the treatment of medically intractable epileptogenic foci. A favourable seizure outcome was first reported in studies of the effects of radiosurgery in the treatment of arteriovenous malformations and tumours. Radiosurgery has since been applied to the treatment of complex partial seizures with mesial-temporal-lobe onset. Nearly simultaneously, experimental evidence supporting the usefulness of radiosurgery to improve or abolish seizures has confirmed that stereotactic irradiation can preferentially affect epileptogenic versus normal cortex. Further work is clearly needed, but this technique might become an important approach in the management of mesial-temporal and extratemporal epilepsy, especially if refractory seizures arise from eloquent cortex or surgically challenging regions of brain.
Arteriovenous Malformations Treated With Frameless Robotic Radiosurgery Using Non-Invasive Angiography: Long-Term Outcomes of a Single Center Pilot Study
2020, Frontiers in Oncology
Neurological outcome and efficacy of AVM treatment
2017, Brain Arteriovenous Malformations: Pathogenesis, Epidemiology, Diagnosis, Treatment and Outcome

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Stereotactic Radiosurgical Treatment of Cerebral Arteriovenous Malformations

Objective

Design

Material and Methods

Results

Conclusion

Section snippets

PATIENTS AND METHODS

RESULTS

DISCUSSION

CONCLUSION

Acknowledgment

Int J Radiat Oncol Biol Phys

Radiosurgery in cerebral arteriovcnous malformations

Clinical outcome of radiosurgery for cerebral arterio-venous malformations

J Neurosurg

Stereotactic radiosurgery with the linear accelerator: treatment of arteriovenous malformations

Neurosurgery

Linear accelerator radiosurgery of cerebral arteriovenous malformations: an update

Neurosurgery

Heavy charged-particle Bragg peak radiosurgery for intracranial vascular disorders

Radiat Res

Stereotactic heavy-ion Bragg peak radiosurgery for intra-cranial vascular disorders: method for treatment of deep arteriovenous malformations

Br J Radio

Linear accelerator radiosurgery for arteriovenous malformations

J Neurosurg

Results of stereotactic radiosurgery of arteriovenous malformations: an analysis of 52 cases

J Neurol Neurosurg Psychiatry

Bragg-peak proton-beam therapy for arteriovenous malformations of the brain

N Engl J Med

Stereotactic radiosurgery for arteriovenous malformations of the brain

J Neurosurg