ANALYSIS OF TREATMENT OUTCOMES WITH LINAC BASED STEREOTACTIC RADIOSURGERY IN INTRACRANIAL ARTERIOVENOUS MALFORMATIONS Dr. Maitri P Gandhi 1, Dr. Chandni P Shah 2 1 Junior resident, Gujarat Cancer & Research Institute, Ahmedabad, Gujarat 2 Third Year Resident, Gujarat Cancer & Research Institute, Ahmedabad, Gujarat INTRODUCTION ABSTRACT Arteriovenous malformations (AVMs) are networks of coiled feeding arteries and draining veins that are not properly connected by capillaries. Radiosurgical treatment of arteriovenous malformations has slow and progressive vaso-occlusive effects. Stereotactic Radiosurgery (SRS) treatment applies controlled radiation dosage to the volume of the brain occupied by the AVM. While this treatment does not require an incision and craniotomy (with their own inherent risks), three or more years may pass before the complete effects are known, during which time patients are at risk of bleeding. MATERIALS AND METHODS 30 patients, 24 male and 6 female with a mean age of 33 years, who underwent LINAC-based SRS for brain AVMs from the year 2003 to 2013 in the Radiation Oncology department at Gujarat Cancer & Research Institute, were retrospectively analyzed for clinical and radiological response. A highly conformal radiotherapy treatment was delivered to a precisely delineated target volume using stereotactic localization techniques. These patients were evaluated for changes in clinical and radiological findings post-treatment. RESULTS 33% of the patients had pre-treatment hemorrhage. Median AVM nidal volume was 2.29 cm 3 (1cm - 4.6cm) and was treated with a mean dose of 15.6Gy at an average of 95% isodose line. Out of 30 patients, 4 patients were either lost to follow-up or no postoperative scans were available. Amongst the 26 patients who were available for follow up at 3 years, 88.5 % patients had complete symptomatic relief. At the mean follow-up of 31 months, 84.6% patients had a complete resolution of their AVM, and 15.4% patients had a partial closure. CONCLUSION Frame based SRS is an effective modality of treatment for intracranial AVMs which helps to achieve considerable symptom free and overall survival. KEYWORDS: Arteriovenous Malformation, Nidus, LINAC-based Stereotactic radiosurgery, Response. 147
INTRODUCTION Arteriovenous malformations (AVMs) are networks of coiled feeding arteries and draining veins that are not properly connected by capillaries. They are very rare and occur in 0.1% of the general population [1]. It is important to treat an AVM because it may bleed and cause symptoms like severe headache, weakness, numbness, paralysis, seizures, vision loss, hearing loss, speech problems and other neurological deficit [2]. Majority of the series in the radiotherapy literature have median Arteriovenous Malformations have diameters ranging from 1 to 2 cm [3-7]. The treatment of such malformations includes neurosurgery, endovascular surgery and radiotherapy [8]. Some patients who have the AVM nidus very close to the critical neural structures are not suitable candidates for neurosurgery. Stereotactic Radiosurgery (SRS) is an acceptable alternative to microsurgery with high obliteration rates and low risk for treatment related morbidity and mortality [9]. The goal of stereotactic radiosurgery is to eliminate the risk of catastrophic intracranial hemorrhage. Stereotaxy refers to using a precise 3-D mapping technique to guide a procedure. We use X-knife which is a LINAC-based SRS unit. The accuracy of SRS is about 0.2mm (plus or minus 0.1 mm) and maximum 1 mm [10]. In the present study we have evaluated the clinical and radiological outcome of stereotactic radiosurgery in the patients of arteriovenous malformation of brain. METHODS AND MATERIALS A retrospective analysis was performed for all the patients of intracranial arteriovenous malformations treated with stereotactic radiosurgery in Radiotherapy department at Gujarat Cancer & research institute during 2010 to 2013. A total of 30 patients were studied, amongst which 24 patients were male and 5 were female with median age of 33 years and 1 pediatric patient. Symptoms of the patients at presentation are as follows: Table1: Symptom-wise distribution of the patients at time of presentation Symptoms Patients with symptom Headache 19 Loss of Consciousness 11 Giddiness 17 Vomiting 7 Paresis 9 Convulsions 8 Vision Loss 2 Hearing Loss 2 Neurological Deficit 15 Pre-treatment evaluation was done. All cases were evaluated by neuro-radiologists, neurosurgeons, and radiation oncologists prior to treatment. Neurosurgery was done in 5 patients as the initial treatment, whereas 2 patients had undergone embolization and 1 patient had received radiosurgery before presenting at our institute. The radiological characteristics of arteriovenous malformations were studied. Table 2: Arteriovenous malformation characteristics in 30 patients treated with Stereotactic radiosurgery. AVM CHARACTERISTICS Location No. of patients Parietal 11 Temporal 3 Temporo Parietal 1 Occipital 2 Thalamus 5 Basal Ganglia 1 Cerebellum 1 Fronto Parietal 2 148
Ventricle 4 Size of nidus (cm) No. of patients <1 3 1-2 9 2-3 14 3-4 4 Patients selected for stereotactic radiosurgery had AVMs of <4 cm nidus. All the patients were treated with a stereotactic frame (BROWN-ROBERTS-WELLS) fixed to the patient s skull. CT Angiogram was taken and target (nidus) delineation and planning was done using RADIONICS TREATMENT PLANNING SYSTEM. Treatment was given using multiple non coplanar single isocentric beams with 6MV linear accelerator after verification. The patients had received dose of 15 Gy to 20 Gy per fraction at 95% isodose line. The patients were advised to come for the follow-up after 1 month of treatment and then every 6 monthly for 3 years. CT Angiogram was done at 6 monthly interval and radiological as well as symptomatic improvement was assessed. RESULTS At the end of 3 years, 26 patients were available for follow-up and 4 patients were lost to follow up. Table 3: Symptomatic improvement in patients treated with SRS Symptoms No. of Patients symptomatic at presentation No. of Patients symptomatic on last follow-up (3 years) Headache 19 2 Loss of Consciousness 11 0 Giddiness 17 0 Vomiting 7 0 Paresis 9 1 Convulsions 8 0 Vision Loss 2 0 Hearing Loss 2 0 Neurological Deficit 15 1 Out of the 26 patients available at 3 years follow up, 88.5% (23) patients had complete symptomatic relief. Amongst the 3 symptomatic patients, 1 patient had both headache and neurological deficit, 1 patient had persistent paresis and 1 patient suffered from headache occasionally. Table 4: Radiological response in patients treated with SRS: Size of AVM nidus(cm) No. of patients Complete obliteration Partial obliteration Lost to follow up <1 3 3 0 0 1-2 9 6 1 2 2-3 14 11 2 1 3-4 4 2 1 1 Out of 26 patients, 84.6% (22) of patients had complete radiological response, i.e., they had complete resolution of the nidus. Also, 4 patients had partial obliteration of the nidus. 149
DISCUSSION An AVM is a complex network of vascular channels consisting of arterial feeders, an AVM nidus, and enlarged venous outflow channels, all of which are demonstrable at angiography. Successful AVM management is dependent upon the lesion and location, the hemodynamics and morphology, the patient s clinical condition [11], and the treatment modalities selected. The goal of all these modalities is total obliteration of the AVM, restoration of normal cerebral function, and preservation of life and neurological function [12]. Surgery has a risk of rupture and injury to brain and embolization has a chance of recurrences. Different studies have analyzed the effectiveness of SRS in AVM. The SALT group studied effectiveness of SRS in 169 patients of AVM. The overall obliteration rate was 64%. The dose used was 15 to 28 Gy [13]. A study by Zabel et al. showed 50% complete obliteration rates on MR angiography after 3 years in patients of cerebral AVM treated with linac based radiosurgery. Median time period to complete obliteration was 22.4 months (range, 4.5 months to 5.9 years) [14]. In another study by Zabel et al, overall complete obliteration rate in CT angiography was 53%. Median time was 24.6 months (range, 4.8 to 50 months) [2]. A study done by Dutta et al showed obliteration rates for AVMs of <3 cm between 80%-100% with the marginal dose of 20 Gy to 22 Gy, and in larger AVMs >3 cm, the obliteration rate was 30-60% with a dose of 15 Gy to 20 Gy with complication rate of 20%-30%. A higher obliteration rate was obtained with the dose of 25 Gy to 45Gy with high complication rates [15]. Engenhart et al used LINAC-based stereotactic radiosurgery to treat AVMs of median volume 6 cc with a dose of 10-29 Gy and reported obliteration rate of 33% at 3 years [3]. The obliteration rates for arteriovenous malformations vary widely in the literature (table 5). Table 5: Comparative Results of similar studies Study Patients Dose(Gy) 2-Year obliteration rate (%) Friedman et al.[16] 158 15-18 78 Colombo et al.[17] 97 18-40 75 Betti et al.[18] 66 Upto 40 66 Souhami et al.[19] 33 50-55 62 Loeffl er et al.[20] 16 15-25 73 Patel et al.[13] 16 15-17 75 Our study 30 15-20 84.6 Explanation for this variation in the results of obliteration rates are due to differences in reporting methodology, doses prescribed, prior treatment, accuracy of AVM nidus delineation and treatment technique [14]. CONCLUSION We can conclude that stereotactic radiosurgery is a safe and effective modality of treatment of AVM of brain with excellent functional outcome. LINAC-based SRS using X-knife has very good precision and accuracy in treatment. We can deliver high dose to the target area with minimum dose to the critical structures like lens, brain stem, optic nerve, optic chiasma, cochlea and pituitary gland. Stereotactic radiosurgery is a minimally invasive technique as compared to a more risky neurosurgery and it is also effective for surgically inaccessible sites of intracerebral arteriovenous malformations. We can achieve higher obliteration rates of cerebral arteriovenous malformation with appropriate selection of patients, accurate imaging and delineation of AVM nidus, optimal planning and treatment techniques, proper selection of dose and careful follow-up [9]. REFERENCES 1. Mohr JP, Kejda-Scharler J, Pile-Spellman J. Diagnosis and treatment of arteriovenous malformations. Curr Neurol Neurosci Rep 2013; 13:324. 2. Zabel A. et al. Treatment outcome after linac-based radiosurgery in cerebral arteriovenous malformations (AVM): Factors affecting obliteration. International Journal of Radiation Oncology Biology Physics, Volume 60, Issue 1, S244 3. Engenhart R et al. The role of high dose, single-fraction irradiation in small and large intracranial arteriovenous malformations. Int J Radiat Oncol Biol Phys 1994;30:521-529 4. Flickinger JC et al. A dose response analysis of arteriovenous malformation obliteration after radiosurgery. Int J Radiat Oncol Biol Phys 1996;36:873-879. 150
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