[Gamma knife radiosurgery for the treatment of severe epilepsy]. / Rôle de la radiochirurgie Gamma Knife dans le traitement des épilepsies sévères.

The Gamma Knife radiosurgery is a neurosurgical approach having now demonstrated well its efficiency, its low morbidity and its comfort in the treatment of numerous neurosurgical disorders. These advantages of this type of intervention make it a method of great interest in functional neurosurgery and quite particularly in surgery of epilepsy. French experience is a pionner one in this domain. If for several years the positive evolution of the epilepsy associated to brain lesions had been noticed after the Gamma Knife radiosurgical treatment, the use of this approach in surgery of the epilepsy is systematically estimated since 1993. Data are today available concerning the surgical treatment of the epilepsies originating in temporomesiale area without occupying process, epilepsies associated to hypothalamic hamartomas and epilepsies associated to cavernous angiomas or to low grade gliomas. The quality of the epileptological result obtained in these various indications associated to a very reduced morbidity lets suppose that the Gamma Knife radiosurgery could indeed have tomorrow a place within the sample group of surgical approaches dedicated to the treatment of severe epilepsies. However, a larger number of treated patients and a more prolonged follow-up remains necessary to estimate in a more definitive way this approach.

[Treatment of choroid melanoma by Gamma-Knife radiosurgery]. / Traitement du mélanome choroïdien par radiochirurgie Gamma-Knife.

Conservative treatment of uveal melanomas by Gamma Knife Radiosurgery is based on the use of cross fire technique with 201 Cobalt60 sources. A following of 13 months is available for the first case operated by Gamma-Knife Surgery in France. Technical baselines and one year preliminary results are reported. The diagnosis of uveal melanoma T3NOMO was established by converging results of clinical examination, angiography and echography. The definition of the target was based on stereotactic MRT examination. We delivered a dose of 50 Gys to the marginal isodose (50%). Today, one year after treatment the tumor decreased, the visual function was preserved. There were no side effect or complication.

[Radiosurgery: basic principles]. / La radiochirurgie: principes.

Radiosurgery is a way of treating in-brain lesions which uses convergence of very thin multiple ionisation beams in a unique focus point coinciding with the target. This enables obtaining a therapeutic effect without opening the skull, and thus avoiding eventual complications or contraindications of classical neurosurgery. In certain cases irradiation can be delivered with submillimetric precision. This particularly new approach is historically essentially based on the work of the Swedish neurosurgeon Lars Leksell in the 50s. Since that time new imaging techniques (e.g. digital imaging) have considerably widened indications. Three ionisation beam sources are generally used in this context: gamma rays emitted by radioactive cobalt 60 sources for the Gamma Knife, high energy LINAC X-rays modified in comparison to their classical use in external radiation therapy, and, more rarely, protons produced in cyclotrons. Several teams world-wide are still perfecting and refining this developing technique.

[Radiology of radiosurgery]. / Radiobiologie de la radiochirurgie.

Proper understanding of the fundamentals of radiosurgery and the main principles of radiobiology is a key point for the development and adaptation of therapeutic strategies and for the definition of indications. The prediction of local effects of radiosurgery requires taking into account both the target Volume and the marginal dose (energy,...) and not only the marginal dose which alone is poorly predictive of the outcome. Other additional factors such as topography, age, previous irradiations,... are likely to influence this risk relationship. The comparison of different dose regimens leads to proposing theoretical models for calculating radiobiological equivalences: the Biological Equivalent Dose (BED) Using these models one can think in terms of the practical consequences of dose fractionation. This allows, depending on the medical context, identifying the potential advantages of the radiosurgery or of a fractionated regimen. For small mid-sized vestibular schwannomas this approach indicates a clear advantage for a single-dose regimen. Retrospectively it has been possible to identify the dose-Volume relationship to the risk of neuropathy for facial motor function, facial sensitivity, and hearing.

[Dosimetric planning for radiosurgical treatment of vestibular schwannomas]. / Planification dosimétrique dans le traitement radiochirurgical des schwannomes vestibulaires.

Dosimetry planning is certainly the most typical neurosurgical instant in the radiosurgical procedure for the treatment of vestibular schwannomas (VS). Indeed, it is a key-moment in which the therapeutical choices will have a major influence on the clinical results, in terms of efficacy and safety. The therapist has to inform the patient about the rationale of the treatment, its limitations, the expected results, and the specific risks. Deep knowledge of the radiosurgical technique, of the principles of dosimetry, and of the therapist's personal experience, allows an a posteriori analytical study of the influence of the dosimetry therapeutic choices on the patient's outcome. Correlation between the preoperative therapeutic choices and the postoperative clinico-radiological information is mandatory to optimize therapeutic strategies. These therapeutic choices should be the result of a reflection integrating the clinical status of the patient, an understanding of the specific pathology of VS, awareness of the other therapeutic choices, and knowledge of radiological and surgical anatomy. The way a certain number of parameters will be defined during the dosimetry planning will have a major influence on the clinical results. This explains wide variability of clinical results from one operator to another, for the same radiological and radiosurgical tools. This emphasizes the need for specific and long-term training, associated with continuous education and a good knowledge of the very active literature.

[Stereotactic mapping for radiosurgical treatment of vestibular schwannomas]. / Imagerie stéréotaxique de repérage dans le traitement radiochirurgical des schwannomes vestibulaires.

RATIONALE: As an exclusively image-guided surgery method, radiosurgery requires special attention in the choice of imaging modalities and acquisition parameters must be set with extreme care. METHODS: Quality control for resolution and accuracy of computed tomography (CT) scanners must be performed. Magnetic resonance imaging (MRI) distortions should be limited through magnetic field homogeneity adjustment (shimming) and acquisition parameters optimization. These inaccuracies should then be quantified through systematic combination of MRI and CT in the radiosurgery planning system. MRI pulse sequences selection criteria are defined by their ability to delineate tumor contrast enhancement and to image cranial nerves and vessels relative arrangement in the cistern and canal. Topography of the petrous structures, such as cochlea, vestibulum and facial nerve canal should be visible. Exact definition of real extension of the lesion at the end of the canal may require specific technical solutions. These technical requirements must be balanced depending on the lesion Volume staging (Koos), the treatment history (microsurgery), the clinical condition (hearing quality), the pathological context (NF2) or the age of the patient. RESULTS: T1-weighted Volumetric MRI pulse sequences (3D-T1) show a contrast enhanced signal that is useful for both the pons interface delineation in Koos III cases, and the canal ending in Ohata A and B. On the other hand, 3D-T1 introduce inaccuracies from magnetic susceptibility distortions and partial Volume effects. High resolution CISS T2-weighted Volumetric pulse sequences (3D-T2) give superior stereotaxic definition attributable to their better resolution (half a millimeter) minimizing partial Volume effects and to their lower magnetic susceptibility minimizing distortions. 3D-T2 allows direct nerve visualization. Moreover, this pulse sequence 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 post-microsurgery conditions. CONCLUSIONS: Radiology phase quality is critical and its complexity requires a high commitment to obtain satisfactory clinical results. Solelt the 3D-T1 MRI modality seems to us not to comply to minimum security criteria.

[Preservation of hearing function in the radiosurgical treatment of unilateral vestibular schwannomas. Preliminary results]. / Préservation de la fonctionnalité auditive dans le traitement radiochirurgical des schwannomes vestibulaires unilatéraux. Résultats préliminaires.

INTRODUCTION: Preservation of functional hearing can be now attempted during the surgical treatment of a vestibular schwannomas. The probability of functional hearing preservation for each of the neurosurgical approaches is currently under evaluation. We report here a preliminary evaluation of our radiosurgical experience. MATERIAL AND METHOD: In Marseilles, we performed 800 gamma-knife procedures for cochleovestibular schwannomas by between July 1992 and December 2000. These patients were evaluated systematically according to a prospective methodology. We report here the study of the population of 211 patients with unilateral schwannoma and a functional preoperative hearing (Gardner and Robertson 1 or 2) treated as first intention, with a follow-up longer than two years. RESULTS: Hearing was improved with the radiosurgery in 3% of cases with a average gain of 10 decibels. Average loss in decibel on the four main frequencies (500, 1,000, 2,000, 4,000 Hz) was 17 dB. The probability of functional hearing preservation with radio surgery was high: 73%. However, this probability depended on numerous factors related to the patient and to the "operative technique". The main parameters of predictability were limited preoperative tonal loss, Gardner and Robertson stage 1 (versus 2), multiisocentric planning, peripheral dose lower than 13 Gy. So a Gardner and Robertson stage 1 intracanalicular tumor treated in accordance with "the state of the art" with a gamma-knife and a marginal dose inferior to 13 Gy has a probability of functional conservation at 2 years greater than 95%. CONCLUSION: Our results are preliminary and they require the confirmation of a more extensive and more prolonged follow-up. However, the large size of this population and the systematic methodology should help us in determining more precisely the place of radiosurgery and especially to better inform the patients of their chances of hearing preservation according to their individual risk profile.

[Experimental radiosurgery in rats using gamma a "gamma knife". Description of a stereotactic device for small laboratory animals]. / Radiochirurgie expérimentale chez le rat par "gamma knife". Description d'un cadre stéréotaxique pour le petit animal de laboratoire.

To allow the experimental use in rats of a Gamma Knife Radiosurgical Unit, a stereotactic device adapted from the conventional Kopf's device was developed. To control the accuracy of the coordinate system based on the De Groot's rat stereotactic atlas, experimental radiosurgical lesions were made on the left striatum. The isodose curve distribution of the 4 mm collimator was calculated with the dose planning software used in Gamma Knife and superimposed on the left striatum target. Doses of 200 Gy were administered to the left striatum in six rats. The results were evaluated 21, 34 and 47 days later. At 34 and 47 days necrotic lesions were exactly as targeted. In a second group of 48 rats receiving a doses of 100 Gy, no lesions were observed after 7, 15, 24, 31, 45 days. However, in all rats sacrificed 59, 72 and 90 days after day radiation, a necrotic lesion was always present and confirmed that at each time the lesions were precisely targeted. This apparatus allows precise and reproducible gamma irradiation lesion in rat brain without expensive and time consuming imaging techniques. This device provides a useful system to observe the experimental effects of radiosurgery on the central nervous system in rats.

[Gamma-knife radiosurgery for brainstem arteriovenous malformations. Preliminary results]. / Traitement radiochirurgical gamma-knife des malformations artério-veineuses du tronc cérébral. Résultats préliminaires.

BACKGROUND AND PURPOSE: Microsurgical resection have the advantage to be immediately effective according to bleeding risk and is the reference treatment for cerebral arteriovenous malformations. For cerebral arteriovenous malformations located in the brainstem gamma-knife radiosurgery due to its low invasivity is classically a first line treatment. We reviewed the Marseilles experience to assess the efficacy and safety of gamma-knife radiosurgery for brain stem arteriovenous malformations. METHODS: We analyzed retrospectively data of 45 patients with an arteriovenous malformation located in the brain stem treated in Marseilles by gamma-knife radiosurgery by between 07/92 and 12/99. Mean age was 42 years, there were 5 children. Arteriovenous malformations were located in the pons or midbrain for the majority of the patients. Intraaxial lesion was found in 82% of patients. Hemorrhage prior to radiosurgery occurred in 75% of the patients. Gamma-knife procedure was the first treatment of the arteriovenous malformations for 29 patients (65%); previous surgery was performed in 34 patients (15%). Mean nidus volume was 550 mm(3) (32-14 196 mm(3)). Mean margin dose was of 23 Gy (range 15-30 Gy). Follow up was available for 25 patients (mean 18 months). RESULTS: One patient presented a transient worsening of his neurological status, and 2 patients developed a fixed deficit. Two patients underwent rebleeding at an interval of 12 to 36 months after the gamma-knife procedure. At last angiographic follow-up (13 patients), the obliteration rate was 82% of the arteriovenous malformations. A second procedure was proposed to a patient with only partial occlusion at 3 years. CONCLUSIONS: Gamma-knife radiosurgery can achieve good obliteration rate of brain stem arteriovenous malformations with low morbidity and may be a valuable first-choice therapy for such arteriovenous malformations. A larger population and longer follow up are mandatory in order to confirm these preliminary results.

[Ballistic quality assurance]. / Assurance qualité balistique.

This review describes the ballistic quality assurance for stereotactic intracranial irradiation treatments delivered with Gamma Knife® either dedicated or adapted medical linear accelerators. Specific and periodic controls should be performed in order to check the mechanical stability for both irradiation and collimation systems. If this step remains under the responsibility of the medical physicist, it should be done in agreement with the manufacturer's technical support. At this time, there are no recent published guidelines. With technological developments, both frequency and accuracy should be assessed in each institution according to the treatment mode: single versus hypofractionnated dose, circular collimator versus micro-multileaf collimators. In addition, "end-to-end" techniques are mandatory to find the origin of potential discrepancies and to estimate the global ballistic accuracy of the delivered treatment. Indeed, they include frames, non-invasive immobilization devices, localizers, multimodal imaging for delineation and in-room positioning imaging systems. The final precision that could be reasonably achieved is more or less 1mm.

[Medical devices needed for stereotactic radiosurgery and intracranial stereotactic radiotherapy]. / Équipements requis pour la mise en œuvre de la radiochirurgie et de la radiothérapie en conditions stéréotaxiques intracrânienne.

Since the previous special issue of Cancer Radiothérapie dedicated to radiosurgery in 1998, many important technological and computer developments have improved external beam radiotherapy treatment device performances. Whereas the Gamma Knife(®) was the gold standard for intracranial radiosurgery, new linear accelerator developments have led to new possibilities for the clinicians. This article describes quickly the different devices available for cranial radiosurgery or fractionated stereotactic radiotherapy.

[Role of radiosurgery and stereotactic radiotherapy in the management of vestibular schwannomas]. / Radiochirurgie et radiothérapie stéréotaxique des schwannomes vestibulaires.

PURPOSE OF THE STUDY: In order to investigate the role of radiosurgery and stereotactic radiotherapy in the management of vestibular schwannomas, we have reviewed our own prospective cohort and the main series of the modern literature. PATIENTS AND METHODS: Between July 14th 1992 and June 1st 2011, 2991 vestibular schwannomas were operated on the Stereotactic and Functional Neurosurgery Department of Timone University Hospital. All the patients have been evaluated prospectively, with a follow up longer than 3 years for 2336 patients, excluding patients suffering from type 2 neurofibromatosis (148 patients). In 7% of the patients, the vestibular schwannoma had previously been resected. According to Koos classification, in 17.6% of the patients, vestibular schwannomas were stage I, 51.8% stage II, 27% stage III and 3.6% stage IV. The mean tumour volume was 2.63 cm(3). According to Garner Robertson classification, the hearing was still functional at the time of radiosurgery in 46% and subnormal in 20.9% of the patients. RESULTS: Long term tumour control was achieved in 97.5% of the patients. A transient facial palsy was observed in 0.5% of the cases. The rate of trigeminal injury was 0.5%. Useful hearing was preserved at 3 years in 78%. This rate reached 95% in patients with no past history of sudden hearing loss. Other predictors of functional hearing preservation are the young age, the small size of the lesion and a dose to the modiulus of the cochlea lower than 4Gy. We observed no radio-induced tumour. Only large, Koos IV vestibular schwannomas are contraindicated for upfront radiosurgery. In these patients, we propose a combined approach with a deliberately partial microsurgical removal, followed by a radiosurgery of the residue. CONCLUSION: This cohort is unique by the size of the population and the length of the follow up and results demonstrate the efficacy of radiosurgery and its safety, especially its high rate of hearing preservation.

[Recommendation of the working group commissioned by the French Nuclear Safety Authority on stereotactic radiation therapy]. / Avis du groupe de travail missionné par l'Autorité de sûreté nucléaire concernant la radiothérapie stéréotaxique.

PURPOSE: At the request of the French nuclear safety authority (Autorité de Sûreté Nucléaire, ASN) a working party of multidisciplinary experts was initiated to elaborate a report regarding propositions for the clinical practice of stereotactic radiation therapy and the related medical physics. MATERIAL AND METHODS: Several stereotactic radiation therapy experts were audited by the working party, especially neurosurgeons and neuroradiologists, as well as radiation oncologists, medical physicists and radiation technologists. An international survey was conducted looking at legal requirements and guidelines concerning stereotactic radiation therapy. A national survey was conducted in France among 29 departments performing stereotactic radiation therapy. The working party report was submitted for advice to the permanent group of medical experts of ASN. RESULTS: Among the 13 countries who responded, very few have legal documents. Some of them are stating that stereotactic radiation therapy must be performed in a radiotherapy department and only by well-trained professionals. Guidelines describing the role of each participant have been published in the USA. In France, stereotactic radiation therapy is performed with dedicated machines or adapted linear accelerators. In 2009, within the 29 departments, 4247 patients were treated with stereotactic radiation therapy representing 4% of the patients treated with external beam radiation therapy. Intracranial lesions were: 3383 and extracranial: 864. The working party of multidisciplinary experts made 7 recommendations. The first one saying that stereotactic radiation therapy must be considered as a radiotherapy. The permanent group of medical experts is asking to modify the "décret du 19 mars 2007" regarding "radiosurgery". CONCLUSION: The medical benefit of stereotactic radiation therapy is well admitted and it is an increasingly used technique. This work through practical guidelines and legal propositions intends to promote a well-controlled development of this radiotherapy technique.

Effect of the Gamma Knife on trigeminal neuralgia.

The Gamma Knife radiosurgical treatment of 20 patients suffering from trigeminal neuralgia is reported. Eleven patients received radiosurgical treatment with the goal of pain relief. Six had secondary trigeminal neuralgia due to AVM, large cavernous sinus and petrous bone meningiomas, trigeminal neurinoma, or chordoma; 5 others had essential trigeminal neuralgia. Radiosurgical treatment was considered only after the failure of conventional medical and surgical treatment. For the other 9 patients, the control of the tumor was the main objective (four acoustic and one trigeminal neurinoma, one petroclival chordoma, and three tumors of the cavernous sinus: one hemangiopericytoma, one metastasis, one meningioma). We have not been using this method for sufficient time to evaluate long-term results. However, we believe that a large majority of our patients benefited greatly from this technique with a rapid clinical improvement, which is a reflection of the relevance of the chosen target.

Effect of gamma knife on secondary trigeminal neuralgia.

The following study was conducted to evaluate the results of Gamma Knife stereotactic radiosurgery in the management of secondary trigeminal neuralgia. 53 patients suffering from secondary trigeminal neuralgia were studied and the results reported. We defined four therapeutic groups: group I correspond to essential trigeminal neuralgia. The primary aim was tumor control in group IV and pain cessation in group III and II (visualization of the fifth nerve root was possible in group II but not in group III). The target dose of the radiosurgery used in the current study varied from 20 to 40 Gy in group III and IV and from 70 to 90 Gy in group I and II. At short-term follow-up, 37 patients (74%) were pain-free, 9 patients (18%) were improved (50%-90% relief) and only 4 patients (8%) experienced treatment failure. Among the patients with early treatment success, 10 patients experienced a complete recurrence of pain in the four succeeding years, and 11 initially pain-free patients deteriorated to partial pain relief. The median time to pain relief was three months (range 1 day to 1 year). The mean follow-up was 32 months (range 7 to 60 months). No patient developed increased facial pain or deafferentation pain. Among the 53 patients, only two exhibit a slight facial hypesthesia and one patient described motor fasciculation related to Gamma Knife treatment. In our experience Gamma Knife surgery appears a safe and effective method for the treatment of secondary trigeminal neuralgia.

First selective amygdalohippocampal radiosurgery for 'mesial temporal lobe epilepsy'.

All the well-documented radiosurgery of epilepsy cases are secondary epilepsies with space-occupying lesions. These results have prompted the idea of testing radiosurgery as a new way of treating epilepsy without space-occupying lesions. We have treated 4 patients with 'mesial temporal lobe epilepsy'. The preoperative evaluation programme was one we usually perform for patients selected for microsurgery of epilepsy. We report the baselines of this treatment, the radiosurgical protocol details, and preliminary results for the first patient treated (follow-up 16 months). Since treatment, the patient has been seizure free, but it is too soon to draw long-term conclusions about the efficiency of the radiosurgery of epilepsy. Morphological (MRI) and functional (PET scan) changes are discussed in relation to our technical choices. Our amygdaloentorhinohippocampal target has been selectively injured.

First biochemical evidence of differential functional effects following Gamma Knife surgery.

Clinical experience with radiosurgery for epilepsy on lesions located in highly functional areas has suggested the possibility of Gamma-Knife-induced functional effects without deterioration of the underlying cerebral cortex. To investigate these hypothetical functional changes, we have developed a special frame dedicated to small-animal radiosurgical experimental models, allowing purely atlasguided protocols. The left striatum of the first series of rats was targeted with high doses (200 Gy maximum) for validation of this new device. The same target was used with lower doses (50 Gy at the 50% isodose) in the second series to evaluate the biochemical changes and their chronology. The main biochemical changes occurred between 59 and 90 days after Gamma Knife irradiation, with different amplitudes depending on the biochemical parameter observed. Differential effects were first observed between glutamate decarboxylase and choline acetyltransferase, and secondarily between excitatory amino acids (AAs) and non-excitatory AAs, particularly gamma-aminobutyric acid. These preliminary results need to be confirmed and completed by further experimental studies. However, Gamma-Knife-induced differential biochemical effects provide the basis for a promising new concept for functional radiosurgery and particularly the Gamma Knife surgery of epilepsy.

Pineal region tumors: the role of stereotactic radiosurgery.

Between July 1992 and August 1995, 11 patients with pineal region tumors (PRTs) were treated at our center. Ages ranged from 8 to 72 years (median 21). Diagnosis was confirmed by histological examination in 7 patients. The remaining cases had strong neuroradiological and marker evidence of the diagnosis, so that a stereotactic biopsy could be avoided. The pathological diagnoses were pinealocytoma (n = 1), tectal astrocytoma (n = 1), germinoma (n = 2), pinealoblastoma (n = 2), and meningioma (n = 3). The marginal dose of these tumors ranged from 12 to 18-20 Gy. Conventional external radiotherapy was never used in this series. With a median follow-up of 12.3 months (range 2-34), all tumors responded to treatment and disappeared or ceased growing. We observed no mortality or major morbidity. One patient (tectal astrocytoma) had a mild radiation-induced reaction, with headache and transient worsening of an abducent nerve palsy, which were controlled with steroids. In germinomas and pinealoblastomas, recovery of normal cerebrospinal fluid circulation was observed in less than 7 days, in parallel with major tumor shrinkage. In this study we confirm that radiosurgery can be an effective and safe alternative for the treatment of pinealocytomas and low-grade tectal gliomas. Moreover, we consider that the characteristics of the radiosurgery technique suggest the method should be evaluated for the treatment of malignant PRTs.