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Nicolas Massager, José Lorenzoni, Daniel Devriendt, Françoise Desmedt, Jacques Brotchi and Marc Levivier

Object. Gamma knife surgery (GKS) has emerged as a suitable treatment of pharmacologically resistant idiopathic trigeminal neuralgia. The optimal radiation dose and target for this therapy, however, remain to be defined. The authors analyzed the results of GKS in which a high dose of radiation and a distal target was used, to determine the best parameters for this treatment.

Methods. The authors evaluated results in 47 patients who were treated with this approach. All patients underwent clinical and magnetic resonance imaging examinations at 6 weeks, 6 months, and 1 year post-GKS. Fifteen potential prognostic factors associated with favorable pain control were studied.

The mean follow-up period was 16 months (range 6–42 months). The initial pain relief was excellent (100% pain control) in 32 patients, good (90–99% pain control) in seven patients, fair (50–89% pain control) in three patients, and poor (< 50% pain control) in five patients. The actuarial curve of pain relief displayed a 59% rate of excellent pain control and a 71% excellent or good pain control at 42 months after radiosurgery. Radiosurgery-induced facial numbness was bothersome for two patients and mild for 18 patients. Three prognostic factors were found to be statistically significant factors for successful pain relief: a shorter distance between the target and the brainstem, a higher radiation dose delivered to the brainstem, and the development of a facial sensory disturbance after radiosurgery.

Conclusions. To optimize pain control and minimize complications of this therapy, we recommend that the nerve be targeted at a distance of 5 to 8 mm from the brainstem.

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Marc Levivier, Jose Lorenzoni, Nicolas Massager, Salvador Ruiz, Daniel Devriendt and Jacques Brotchi

Object

The authors report their experience using the Leksell gamma knife C (GK-C) for the treatment of meningioma and vestibular schwannoma (VS).

Methods

In December 1999, the first commercially available clinical GK-C was installed at the Université Libre de Bruxelles (Erasme Hospital, Brussels, Belgium). In January 2000, the system was upgraded and equipped with the automatic positioning system (APS). Between February 2000 and February 2003, the APS-equipped GK-C was used to perform 532 radiosurgical treatments, including those in 97 meningiomas and 101 VSs.

Meningioma and VS represent 18 and 19%, respectively, of lesions in patients treated with GK-C at the authors' center. The mean number of isocenters per lesion was 9.5 (range 1–36): 18.1 (range 1–36) for meningioma and 12.8 (range 1–27) for VS. In 77.6% of the cases, the authors used a single helmet of collimators (55.5% in meningioma and 74.3% in VS). The most frequently used collimator size was 4 mm (46.7%). Whereas it was 4 mm in cases of VS (64.3%), it was 8 mm in cases of meningioma (41.6%). The APS could be used in 86% of the cases, either alone (79%) or in combination with trunnions (7%). There was a difference in the APS-based treatment success rate in meningiomas (85%) and VSs (94%). A significant difference was also noted in the conformity of the radiosurgical treatments between the two lesions.

Conclusions

The APS-equipped GK-C represents an evolutionary step in radiosurgery. It requires adjustments by the treating team for its specific limitations, which vary among indications, as exemplified by the differences inherent between meningioma and VS in this series.

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Marc Levivier, David Wikler Jr., Nicolas Massager, Philippe David, Daniel Devriendt, Jose Lorenzoni, Benoit Pirotte, Françoise Desmedt, Stephane Simon Jr., Serge Goldman, Paul Van Houtte and Jacques Brotchi

Object. The authors review their experience with the clinical development and routine use of positron emission tomography (PET) during stereotactic procedures, including the use of PET-guided gamma knife radiosurgery (GKS).

Methods. Techniques have been developed for the routine use of stereotactic PET, and accumulated experience using PET-guided stereotactic procedures over the past 10 years includes more than 150 stereotactic biopsies, 43 neuronavigation procedures, and 34 cases treated with GKS. Positron emission tomography—guided GKS was performed in 24 patients with primary brain tumors (four pilocytic astrocytomas, five low-grade astrocytomas or oligodendrogliomas, seven anaplastic astrocytomas or ependymomas, five glioblastomas, and three neurocytomas), five patients with metastases (single or multiple lesions), and five patients with pituitary adenomas.

Conclusions. Data obtained with PET scanning can be integrated with GKS treatment planning, enabling access to metabolic information with high spatial accuracy. Positron emission tomography data can be successfully combined with magnetic resonance imaging data to provide specific information for defining the target volume for the radiosurgical treatment in patients with recurrent brain tumors, such as glioma, metastasis, and pituitary adenoma. This approach is particularly useful for optimizing target selection for infiltrating or ill-defined brain lesions. The use of PET scanning contributed data in 31 cases (93%) and information that was specifically utilized to adapt the target volume in 25 cases (74%). It would seem that the integration of PET data into GKS treatment planning may represent an important step toward further developments in radiosurgery: this approach provides additional information that may open new perspectives for the optimization of the treatment of brain tumors.

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György T. Szeifert, Isabelle Salmon, Sandrine Rorive, Nicolas Massager, Daniel Devriendt, Stephan Simon, Jacques Brotchi and Marc Levivier

Object. The aim of this study was to analyze the cellular immune response and histopathological changes in secondary brain tumors after gamma knife surgery (GKS).

Methods. Two hundred ten patients with cerebral metastases underwent GKS. Seven patients underwent subsequent craniotomy for tumor removal between 1 and 33 months after GKS. Four of these patients had one tumor, two patients had two tumors, and one patient had three. Histological and immunohistochemical investigations were performed. In addition to routine H & E and Mallory trichrome staining, immunohistochemical reactions were conducted to characterize the phenotypic nature of the cell population contributing to the tissue immune response to neoplastic deposits after radiosurgery.

Light microscopy revealed an intensive lymphocytic infiltration in the parenchyma and stroma of tumor samples obtained in patients in whom surgery was performed over 6 months after GKS. Contrary to this, extensive areas of tissue necrosis with either an absent or scanty lymphoid population were observed in the poorly controlled neoplastic specimens obtained in cases in which surgery was undertaken in patients less than 6 months after GKS. Immunohistochemical characterization demonstrated the predominance of CD3-positive T cells in the lymphoid infiltration.

Conclusions. Histopathological findings of the present study are consistent with a cellular immune response of natural killer cells against metastatic brain tumors, presumably stimulated by the ionizing energy of focused radiation.

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Nicolas Massager, Ouzi Nissim, Carine Delbrouck, Isabelle Delpierre, Daniel Devriendt, Françoise Desmedt, David Wikler, Jacques Brotchi and Marc Levivier

Object

The purpose of this study was to measure the dose of radiation delivered to the cochlea during a Gamma knife surgery (GKS) procedure for treatment of patients with vestibular schwannomas (VSs), and to analyze the relationship between cochlear irradiation and the hearing outcome of these patients.

Methods

Eighty-two patients with VSs were treated with GKS using a marginal dose of 12 Gy. No patient had neurofibromatosis Type 2 disease, and all had a Gardner–Robertson hearing class of I to IV before treatment, and a radiological and audiological follow-up of at least 1-year after GKS. The dosimetric data of the volume of the cochlea were retrospectively analyzed and were correlated with the auditory outcome of patients.

Results

The mean radiation dose delivered to the cochlear volume ranged from 1.30 to 10.00 Gy (median 4.15 Gy). The cochlea received significantly higher radiation doses in patients with worsening of hearing after GKS. A highly significant association between the cochlear and the intracanalicular dose of radiation delivered during GKS was found.

Conclusions

During GKS for VSs, relatively high doses of radiation can be delivered to the cochlea. Worsening of hearing after GKS can be the consequence of either radiation injury to the cochlea or the irradiation dose delivered into the auditory canal, or both.

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György T. Szeifert, Nicolas Massager, Daniel DeVriendt, Philippe David, Françoise De Smedt, Sandrine Rorive, Isabelle Salmon, Jacques Brotchi and Marc Levivier

Object. The purpose of this study was to compare histopathological changes with imaging findings in different tumors after gamma knife radiosurgery (GKS).

Methods. Five patients of a series of 220 treated with GKS underwent craniotomy for tumor removal 3 to 12 months after radiosurgery. There were two patients with multiple cerebral metastases, one with vestibular schwannoma, one with malignant glioma, and one with meningioma. A portion of normal brain tissue outside the prescription dose volume was acquired wherever possible to facilitate examination of the effects of radiosurgery. Histopathological and immunohistochemical investigations were performed. In addition to the routine hematoxylin and eosin and Mallory trichrome stains, immunohistochemical reactions were also performed for Factor VIII—associated antigen (FVIII) and CD34 antigen to study vascular endothelial effects of the irradiation.

Endothelial cells of vessels in the normal brain tissue covering the tumor, outside of the prescription isodose volume, expressed marked CD34 and FVIII positivity. In the irradiated targeted tumor tissue samples, however, both reactions decreased remarkably.

Conclusions. The results of the present immunohistochemical study provide support to the experimental hypothesis that vascular endothelial cells are the principal targets of single high-dose irradiation. The loss of central contrast enhancement of tumor tissue following radiosurgery might be consequence of the vascular damage.

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Marc Levivier, David Wikier, Serge Goldman, Philippe David, Thierry Metens, Nicolas Massager, Massimo Gerosa, Daniel Devriendt, Françoise Desmedt, Stephane Simon, Paul Van Houtte and Jacques Brotchi

✓ The purpose of this study was to assess the use of positron emission tomography (PET) as a stereotactic planning modality for gamma knife radiosurgery (GKS).

The authors developed and validated a technique for fiducial marker imaging, importation, and handling of PET data for integration into GammaPlan planning software. The clinical feasibility in applying this approach to a selected group of patients presenting with recurrent glial tumors or metastases was evaluated.

Positron emission tomography data can be integrated into GammaPlan, allowing a high spatial accuracy, as validated using a phantom. Positron emission tomography data were successfully combined with magnetic resonance (MR) images to define the target volume for the radiosurgical treatment of patients with recurrent glioma or metastasis. This approach may contribute to optimizing target selection for infiltrating or ill-defined brain lesions. Because PET is also useful for the pretreatment and follow-up evaluation, the use of stereotactic PET in these patients can enable an accurate comparison of PET-based metabolic data with MR-based anatomical data. This could give a better understanding of the metabolic changes following radiosurgery.

The ability to use PET data in GKS represents a crucial step toward further developments in radiosurgery, as this approach provides additional information that may open new perspectives for the optimization of the treatment of brain tumors.