Gamma Knife Stereotactic Radiosurgery ( GKS ) for the treatment of Vestibular Schwannomas ( VS )

Introduction. Vestibular schwannomas (VS) or acoustic neuromas (AN) (as they are known to neurosurgeons) are benign tumors which originate at the junction between central nervous system myelin and peripheral nervous system myelin – an area known as the Obersteiner-Redlich area. Acoustic neuromas represent a special pathologic entity for neurosurgeons due to their important symptoms which need to be adressed as soon as possible and due to the secondary disfunctions which may appear if the tumors are not treated appropriately. Materials and methods. The study below presents the experience of the authors regarding the use of stereotactic radiosurgery for the treatment of acoustic neuromas. The authors focus on a population of 231 patients diagnosed and treated for VS over a period of 10 years at the „Bagdasar-Arseni“ University Hospital in Bucharest. This study compares the impact of Gamma Knife Surgery when performed alone or in association with open microneurosurgery. The authors assessed patients with tumors ranging between 0.25 and 14 cm3 in volume. Gamma Knife Surgery is used successfully to treat VS, both independantly or in association with open microsurgery. Results. The major complications of the treatment are represented by lack of response to treatment (less than 1% of patients) and cerebral edema (16.4% of patients). Conclusions. Given its multiple advantages, stereotactic radiosurgery is right now the tip of the spear regarding the therapeutical means available for VS. When the tumors met in daily practice are larger than the therapeutical resources of the devices used for Gamma Knife Surgery an open microsurgical approach may be att empted followed by stereotactic iradiation of the remnant tumor. Given the large number of successes reported in the literature and the small number of complications but also the ever progressing technology used to improve Gamma Knife devices, the authors consider stereotactic radiosurgery to be a very good solution for the treatment of VS. Furthermore, the improvement potential this technique has grants it the potential to improve standard of treatment for acoustic neuromas and the quality of life in patients with this disease.


INTRODUCTION
Vesti bular Schwannomas (also known as acousti c neuromas) are tumors which were described for the fi rst ti me by Sandifort in 1777 (1) and which were successfully removed for the fi rst ti me by Sir Charles Balance. These benign tumors have a slow growth and are derived from Schwann cells in nerve roots (more specifically the Obersteiner-Redlich area in which tranziti on is made from "central" myelin -produced by oligodendrocytes -and "peripheral" myelin produced by Schwann cells. These tumors appear frequently in the eight cranial nerve (VIII).
Vesti bular Schwannomas (Fig. 1) are relatively rare tumors with a reported incidence between 0.5 and 1.7 cases for every 100,000 people. These tumors appear mostly in the 5th or 6th decade of life and are rarely present in young pati ents (mostly in pati ents with neurofi -bromatosis II). VS account for 6-8% of all intracranial tumors and between 25 and 33% of all the tumors in the posterior cranial fossa. (2,6) Despite the lack of studies regarding the precise development of these tumors, a growing number of literature reports show that acousti c neuromas grow between 0.2 and 2 mm a year. (7) Due to the astonishing work of Prof. Dr. Lars Leksell (a professor of neurosurgery from Sweden), Prof. Dr. Ladislau Steiner (a Romanianborn professor of neurosurgery) and Prof. Dr. Borje Larsson (a radiobiologist from Sweden), in 1967 at the Karolinska Insti tute of Sweden, the fi rst Gamma Knife Stereotacti c Radiosurgery unit is built, designed to deliver precise microdoses of radiati on to various lesions of the human brain in order to destroy them. (8) Tipically, a Gamma Knife stereotacti c radiosurgery machine has 201 sources of Cobalt-60 of about 30 Curie. These sources are carefully enclosed into a shielded mechanism in such a way that no secondary beam of radiati on is produced. Using a helmet with various orifi ces that is mounted on the head of the pati ent, the 201 beams of radiati on converge into a single point, deep into the human brain where they induce sclerosis of the targeted lesion. (Fig. 2) This of course would not be possible without accurate MRI studies of the brain and the lesion.
If initi ally all VS had surgical indicati on as fi rst intent soluti on, the progress of technology and the birth of Gamma Knife stereotacti c radiosurgery changed the trend, making therapy more easy. Thus, today, Gamma Knife surgery is routinely used in countries in Western Europe while open microsurgery is reserved only as a back-up soluti on or is employed in very large tumors, where the structures of the cerebello-ponti ne angle and the posterior cranial fossa need to be decompressed. Stereotacti c radiosurgery is a relati vely new method which uses convergent beams of ionizing radiati ons to inacti vate or destroy one or more well-defi ned targets in the Central Nervous System, without ever needing an incision. The main advantages of the method are the fact that the multi ple beams of radiati on have no impact on surrounding brain ti ssue, the ammount of ti me spent in the hospital is reduced to a minimum, there is no need for general anesthesia and the results of this technique are excellent while having minimal complicati ons. Using this technique, control rates of up to 93-97% were achieved accompanied by hearing improvement in some cases. (10)(11)(12)(13)(14)(15)

MATERIALS AND METHODS
The authors present a study of 231 consecuti ve pati ents, diagnosed, treated and followedup for VS over a period of 10 years (Jan. 2004 -Jan. 2014) at the "Bagdasar-Arseni" University Hospital in Bucharest. All the pati ents have, at some point during their treatment, received Gamma Knife Surgery, either as fi rst intenti on treatment or as a follow-up treatment aft er open microsurgery. All the pati ents were sub-jected to a protocol consisti ng of Clinical Assessment, Computed Tomography imaging, Admission, MRI Imaging, GKS/Surgery + GKS, Recovery, Discharge, Follow-up. (See Table 1) The followup period ranges between 3 and 7 years and consisted of clinical and MRI investi gati ons every 6 months for the fi rst 3 years, aft er which MRI imaging was performed yearly. The authors excluded from the study all pati ents that had been admitt ed for tumor relapses.
During this study, the authors used a Model C Gamma Knife Surgery Device, outf itt ed with an advanced three-dimensional positi oning system of the pati ent in relati onship with the radiati on sources. The System was installed at the "Bagdasar-Arseni" University Hospital in 2004 and since then a number of more than 2194 interventi ons were performed. Out of the 2194 interventi ons, a number of 231 were for patients with VS. The mean tumor volume for the 231 pati ents was of 5.35 cm 3 , ranging from 0.25 cm 3 and up to 14.0 cm 3 . For the treatment of these tumors the authors used between 1 and 15 doses of radiati on with a marginal dose ranging between 12 and 14 Gy, on isodoses ranging between 45 and 60%. (See Table 1 for decision making algorhythm). A number of 127 pati ents had been previously operated on, and were receiving secondary iradiati on for the remnant tumor, while 104 pati ents received Gamma Knife Surgery as fi rst intent therapy, given the fact that their tumors were smaller than 3 cm 3 -which is an important criteria for successful fi rst intent radiosurgery. Nevertheless, the criti cal volume of 3 cm 3 can be achieved using an open surgical interventi on followed by Gamma Knife Surgery -a technique used with great success in the case of large tumors in very diffi cult locati ons.

RESULTS
The results were divided into two groups based on whether the pati ent had received GKS as fi rst intent therapy (Group 1) or whether the pati ents received GKS aft er prior microsurgery (Group 2).
Group 1: For the 104 pati ents that received Gamma Knife surgery, a number of 71 (68.2%) pati ents showed tumor regression (Fig. 3a and  3b). A number of 31 pati ents (29.8%) did not show any sign of regression while the tumor maintained its dimension. A number of 2 patients (2%) showed no response to treatment as the tumors grew ( Fig. 4a and 4b).
Group 2: For the 127 pati ents that were operated on and then received Gamma Knife Surgery, 90 pati ents (71%) showed shrinkage of the tumor, 33 pati ents (26%) showed constant tumor dimension while 4 pati ents (3%) showed a slow growth of the tumor.

COMPLICATIONS
The follow up was performed using clinical and MRI studies performed at 6 months for a period of 3 years aft er which, the check-up was scheduled once a year. The fi rst complicati on met in the 231 pati ents was the ineff ecti veness of the treatment. A number of 2 pati ents (0.85%) treated using GKS as fi rst intenti on did not respond to the treatment and required open surgery to have the tumor removed. The second most important complicati on was postirradiati on cerebral edema which was noti ced in 38 cases (16.4%) and treated appropriately.
Other frequent complicati ons, which were met in pati ents that were operated on, were permanent and transient facial palsies noti ced in 36 cases (15.6%) of the pati ents, trigeminal palsies in 29 cases (12.5%) with large tumors, and trigeminal neuralgia in 9 cases (3.8%). Patients with large tumors (>8 cm 3 ) showed good compliance with the treatment and had a very good evoluti on.

CONCLUSIONS
Gamma Knife Stereotacti c Radiosurgery (GKS) for VS is one of the most advanced thera-peuti cal opti ons availabe worldwide. When tumor size surpasses the therapeuti cal resources of the radiosurgery device, a microsurgical approach can be carried out to shrink the tumor and follow-up Gamma Knife Surgery is possible.
Given the large number of therapeuti cal successes reported and the small number of complicati ons, the authors believe this method is highly valuable. As technique improves so does technology implemented in Gamma Knife machines. Three dimensional resoluti on increases, the radiati on doses used get smaller and the pati ents'quality of life improves as literature quotes cases of hearing improvement. (14) Since the introducti on of Gamma Knife Surgery, pati ents older than 75 with important comorbidities can benefi t as well from treatment for vesti bular schwannomas. (15,16) The only reasonable doubt regarding Gamma Knife Surgery today is the possible malignant degenerati on of acousti c neuromas, however, up unti l this moment there is no menti on in the literature of such a case. (2,9) The main and most useful tool for follow up is high resoluti on MRI scanning as it allows the surgeon to noti ce the growth patt ern of the tumor and greatly infl uences the therapeuti cal protocol.