Establishment of a Therapeutic Ratio for Gamma Knife Radiosurgery of Trigeminal Neuralgia: The Critical Importance of Biologically Effective Dose Versus Physical Dose.

OBJECTIVE: How variations of treatment time affect the safety and efficacy of Gamma Knife (GK) radiosurgery is a matter of considerable debate. With the relative simplicity of treatment planning for trigeminal neuralgia (TN), this question has been addressed in a group of these patients. Using the concept of the biologically effective dose (BED), the effect of the two key variables, dose and treatment time, were considered. METHODS: A retrospective analysis was performed of 408 TN cases treated from 1997 to 2010. Treatment involved the use of a single 4 mm isocenter. If conditions allowed, the isocenter was placed at a median distance of 7.5 mm from the emergence of the trigeminal nerve from the brain stem. The effects were assessed in terms of the incidence of the complication, hypoesthesia, and in terms of efficacy using the incidence of pain free after 30 days and 1 and 2 years. These responses were evaluated with respect to both the physical dose and the BED, the latter using a bi-exponential repair model. RESULTS: RE-evaluation showed that the prescription doses, at the 100% isodose, varied from 75 to 97.9 Gy, delivered in 25-135 minutes. The relationship between the physical dose and the incidence of hypoesthesia was not significant; the overall incidence was ∼20%. However, a clear relationship was found between the BED and the incidence of hypoesthesia, with the incidence increasing from <5% after a BED of ∼1800 Gy2.47 to 42% after ∼2600 Gy2.47. Efficacy, in terms of freedom from pain, was ∼90%, irrespective of the BED (1550-2600 Gy2.47) at 1 and 2 years. The data suggested that "pain free" status developed more slowly at lower BED values. CONCLUSIONS: These results strongly suggest that safety and efficacy might be better achieved by prescribing a specific BED instead of a physical dose. A dose and time to BED conversion table has been prepared to enable iso-BED prescriptions. This finding could dramatically change dose-planning strategies in the future. However, this concept requires validation for other indications for which more complex dose planning is required.

Radiosurgery for vestibular schwannomas.

This article investigates the role of radiosurgery and stereotactic radiotherapy in the management of vestibular schwannomas (VS), reviewing the authors' own prospective cohort and the current literature. For patients with large Stage IV VS (according to the Koos classification), a combined approach with deliberate partial microsurgical removal followed by radiosurgery to the residual tumor is proposed. The authors' cohort is unique with respect to the size of the population and the length of the follow-up, and demonstrates the efficacy and safety of VS radiosurgery, with particular regard to its high rate of hearing preservation.

A quantitative comparison of radiosurgical treatment parameters in vestibular schwannomas: the Leksell Gamma Knife Perfexion versus Model 4C.

PURPOSE: The world's first Gamma Knife Perfexion (PFX)was installed in Marseille in July 2006. The aim of this study was to investigate the impact of the PFX technology on the quality of dose planning for vestibular schwannomas (VS). METHODS: When the PFX was first introduced, a comparative randomized prospective study of 200 patients was conducted.Seventy-eight of the 200 patients in that study had VS, of whom 38 were randomized to treatment with the Gamma Knife Model 4C (group 4C) and 40 were randomized to treatment with PFX (group P1). The authors also incorporated a matched group of 40 patients with VS consecutively treated with PFX after the initial learning curve period (group P2). Dose planning was compared and evaluated by measuring the conformity index (CI), selectivity index (SI), gradient index(GI), energy index (EI), unit isocenters (UI) and cochlear dose. Patients were also stratified into subgroups according to target volume (> or = 0.5 ml). RESULTS: In the whole population, CI, EI and cochlear dose were significantly better in group P2 (CI=0.917, EI=1.35,cochlear dose=3.55) than in group 4C (CI=0.864, EI=1.27,cochlear dose=5.10). In the subgroup of lesions > or = 0.5 ml, CI,GI, EI, UI and cochlear dose in group P2 (CI=0.929, GI=2.67, EI=1.37, UI=10.6, cochlear dose=3.55) were significantly better than in group 4C (CI=0.874, GI=2.85, EI=1.30, UI=14.5, cochlear dose=5.10). CONCLUSIONS: The investigation of the dose planning capabilities of the PFX on a cohort of VS demonstrates a better conformity and energy distribution, with better cochlear sparing and without any particular drawback. In addition,there is an improvement in peripheral dose gradient in larger lesions. Further clinical studies will be required before drawing any conclusions about the clinical benefit achieved by these dose planning improvements.

Radiosurgery with the world's first fully robotized Leksell Gamma Knife PerfeXion in clinical use: a 200-patient prospective, randomized, controlled comparison with the Gamma Knife 4C.

OBJECTIVE: The world's first Leksell Gamma Knife PerfeXion (Elekta Instrument AB, Stockholm, Sweden) for radiosurgery of the head and neck became operational at Timone University Hospital in Marseille on July 10, 2006. To allow strict evaluation of the capabilities, advantages, disadvantages, and limitations of this new technology, patients were enrolled in a prospective, randomized trial. METHODS: In 66 working days, between July 10 and December 20, 2006, 363 patients were treated by gamma knife surgery at Timone University Hospital, Marseille. Of these patients, 200 were eligible for the comparative prospective study (inclusion criteria were informed consent obtained, tumor or vascular indication, and no previous radiosurgery or radiotherapy). In accordance with the blinded randomization process, 100 patients were treated with the Leksell Gamma Knife 4C (Elekta Instrument AB) and Gamma Knife 100 (Elekta Instrument AB) with the Leksell Gamma Knife PerfeXion. Dose planning parameters, dosimetry measurements on the patient's body, workflow, patient comfort, quality assurance procedure, and a series of other treatment-related parameters were systematically and prospectively evaluated in both arms of the trial. RESULTS: No technical failure of the treatment procedure was encountered. The new dose-planning system led to the use of composite shots in 39.4% of the patients. The median number of different collimator sizes used was larger with the PerfeXion than with the 4C (2 and 1, respectively). The mean number of isocenters used was lower (10.67 and 13.08, respectively). The median total treatment time was significantly shorter with the PerfeXion (40 and 60 minutes, respectively), but there was no significant difference in the median radiation time (34.02 and 33.40 minutes, respectively). The procedure was performed using only a single run in 98.99% of the PerfeXion cases and in 42% of the 4C cases. Collision risk on the 4C forced us to change the frame gamma angle for at least 1 shot in 24% of the patients and led to treatment in manual mode for at least 1 shot in 21% of the patients. Collision risk requiring technical adaptation did not occur with the PerfeXion. In 1 patient treated with the PerfeXion, the system required a direct collision check. In terms of dose to structures outside the target area, the PerfeXion delivers 8.2 times less to the vertex, 10 times less to the thyroid, 12.9 times less to the sternum, and 15 times less to the gonads. CONCLUSION: Our prospective study indicates that procedures with the PerfeXion were collision-free, even with very eccentric lesions (e.g., multiple metastases). The duration of the surgical procedure, the amount of time required for nurse, physicist, and physician intervention on the machine, and the duration of the quality assurance procedure were all shown to be dramatically reduced with the PerfeXion gamma knife. Patient protection is greatly improved with the PerfeXion. In our experience, the technological advances of the Leksell Gamma Knife PerfeXion will make a very significant contribution to future progress in head and neck radiosurgery.

Hearing preservation after gamma knife radiosurgery for vestibular schwannomas presenting with high-level hearing.

OBJECTIVE: The aim of this study was to evaluate long-term hearing preservation after gamma knife radiosurgery (GKS) for vestibular schwannomas in patients with initially normal or subnormal hearing (Gardner-Robertson Class 1) and to determine the predictive factors for functional hearing preservation. METHODS: Since July 1992, more than 2053 vestibular schwannomas have been treated by GKS and followed at the Timone University Hospital, Marseille. A minimum of 3 years of follow-up (range, 3-11 years; median, 48 months) is available for 74 patients (without neurofibromatosis Type 2 or previous surgery) with Gardner-Robertson Class 1 hearing. RESULTS: The average age of the patients was 47.5 years (range, 17-76 years). The number of tumors in Koos Stage I was 8, the average number in Stage II was 21, the average number in Stage III was 43, and the average number in Stage IV was 2. The median number of isocenters was 8 (range, 2-45), and the median marginal dose was 12 Gy (range, 9-13 Gy). At the time of the last follow-up evaluation, 78.4% of the patients had preserved functional hearing. Tumor control was achieved in 93% of the cases. The probability of preserving functional hearing was higher in patients who had an initial symptom other than hearing decrease (91.1%), in patients younger than 50 years (83.7%), and in those treated with a dose to the cochlea of less than 4 Gy (90.9%). CONCLUSION: This study shows that the probability of preserving functional hearing in the long term after GKS for patients presenting with unilateral vestibular schwannomas is very high. The positive predictive factors appear to be young age, an initial symptom other than hearing decrease, and a low dose to the cochlea.

Radiosurgery: operative technique, pitfalls and tips.

RATIONALE: From frame placement to dose administration, each step of the procedure must be optimized in every detail for better preservation of global precision, accuracy, safety and efficacy. METHODS: Quality control for resolution, accuracy and acquisition parameter optimization of both computed tomography (CT) scanners and magnetic resonance imaging (MRI) must be performed. Inaccuracies should then be quantified through systematic combination of MRI and CT in the radiosurgery planning system. Topography of petrous structures such as cochlea, vestibulum and facial nerve canal should be visible on the CT scan. T1-weighted volumetric MRI pulse sequences (3DT1) show a contrast-enhanced signal that is useful for both the pons interface delineation in Koos III cases, and the canal ending. High-resolution CISS T2-weighted volumetric pulse sequences (3DT2) allow direct nerve visualization and give superior stereotactic definition attributable to their better resolution minimizing partial volume effects and to their lower magnetic susceptibility minimizing distortions. The 3DT2 pulse sequences with contrast injection, show improved distinction between the pons and the nerves due to signal differences within the schwannomas. Fat saturation pulse sequences are of interest in postmicrosurgery conditions. The previous technical requirements and the dose planning elaboration will be balanced depending on the lesion volume staging (Koos), treatment history (microsurgery), clinical condition (hearing quality), pathological context (NF2) or age of the patient. The recommended marginal dose is 11-12 Gy. Tumor volume delineation allows the calculation of conformity, selectivity and gradient indexes. These global indexes must be weighted according to the relationship to critical structures and functional status of the patient. CONCLUSIONS: As an exclusively image-guided surgical method, radiosurgery requires special attention in the choice of imaging modalities and their acquisition parameters need extreme care. Technical nuances during the elaboration of the dose planning itself will directly influence both the toxicity risk and the chance of cure.

Lateral positioning technique for the treatment of far-lateral targets with the Leksell gamma knife: technical note.

OBJECTIVE: To describe a procedure for Leksell gamma knife (LGK) radiosurgery in a lateral position, for treatment of far-lateral intracranial lesions. METHODS: Positioning of the patient in the lateral decubitus position during LGK treatment switches the x and y axis coordinates. This increases the range of the x axis from 52 to 148 mm to 40 to 160 mm (i.e., 12 mm in each direction). RESULTS: Conversion of the coordinates of the isocenters is easily performed with simple mathematical algorithms and does not impair the precision of target positioning at the isocenters during LGK radiosurgery. CONCLUSION: LGK treatment in the lateral decubitus position is a simple accurate procedure for the treatment of far-lateral lesions that cannot be reached with normal supine positioning.

Impact of the model C and Automatic Positioning System on gamma knife radiosurgery: an evaluation in vestibular schwannomas.

OBJECT: The technical advances associated with the model C gamma knife include a robotized system enabling automatic positioning of the stereotactic coordinates. The purpose of this study was to analyze the clinical impact of this technical modification. METHODS: The authors studied a sample of patients with vestibular schwannoma (VS). This sample included three groups treated using gamma knife radiosurgery. Group I comprised 21 patients with VS treated just before the installation of the Automatic Positioning System (APS). Group II included patients in Group I with new dose plans created using the APS (in other words, simulated dose plans). Group III consisted of a control group of 20 patients matched for tumor grade with the previous group and treated recently with the APS. Treatment times were calculated after correcting the time for each shot according to the age of the sources after reloading. The treatment times, including total time, irradiation time, and duration of the neurosurgical procedure, were analyzed. In addition, dose planning including number of isocenters, number of different collimators, malfunctions, and the conformity and selectivity indices were recorded. The trend was to reduce the mean number of collimator runs from 7.9 to 1.2 and to increase the mean number of shots from 7.9 to 15.6, mostly by using the 4-mm collimator exclusively. The APS-related conformity and selectivity were improved from 95 to 97% and from 78 to 84%, respectively. The total treatment time was reduced by 53%, and time required to interact with the patient in the room was considerably reduced (75%), giving the neurosurgeon greater freedom to perform other tasks during the treatment period. The reduction of the time spent by the neurosurgeon at work in the room was 84%. The total radiation time was increased by 54%. CONCLUSIONS: The preliminary results of this study indicate that the robotization of the gamma knife is likely a major advance in radiosurgery.