Faculty Bibliography

OBJECTIVE: Vestibular schwannomas present significant management challenges in patients with neurofibromatosis Type 2 (NF2). We evaluated the results of gamma knife radiosurgery for the management of these tumors, focusing on tumor response, hearing preservation, and other factors affecting outcomes. METHODS: Stereotactic radiosurgery was performed to manage 74 schwannomas in 62 patients. Ipsilateral serviceable hearing was present in 35% of tumors before the procedure. The mean tumor volume was 5.7 cm3. The mean margin and maximum dose used were 14 and 27.5 Gy, respectively. Cox regression analyses were performed to identify factors affecting outcomes. RESULTS: The median follow-up period was 53 months, and two patients were lost to follow-up. Actuarial local control rates at were 85, 81, and 81% at 5, 10, and 15 years, respectively. Tumor volume was significant as a predictor of local control. Since 1992, using current radiosurgery techniques (magnetic resonance imaging scan targeting and reduced margin dose to 14 Gy or less), the actuarial serviceable hearing preservation rate is 73% at 1 year, 59% at 2 years, and 48% at 5 years after radiosurgery. Facial neuropathy occurred in 8% of tumors, trigeminal neuropathy occurred in 4%, and vestibular dysfunction occurred in 4%. Radiation dose and tumor volume were predictive of development of new deficits. No radiosurgery-associated secondary tumors or atypical or malignant changes were noted. CONCLUSION: Stereotactic radiosurgery is a safe and effective management modality for neurofibromatosis Type 2 vestibular schwannomas. Although results do not seem to be as good as for patients with sporadic unilateral tumors, gamma knife radiosurgery results seem favorable and indicate that radiosurgery should be strongly considered for primary tumor management in selected patients.

Advances in neuroimaging, stereotactic techniques, and robotic technology in the last decade have significantly expanded the applications of radiosurgery. Radiosurgery has become a preferred management modality for many intracranial tumors such as schwannomas, menigiomas and metastatic tumors. While indications of radiosurgery continue to expand, further investigations are critical to understand the mechanism of biological response of CNS tissues to radiation as well as the potential of long-term adverse effects. The effects and the pathogenesis of biologic effects following radiosurgery may be unique. The need for basic research concerning the radiobiology of high-dose single-fraction ionizing radiation on nervous system tissue is crucial. The development of future applications of radiosurgery will depend upon our understanding of radiobiology of radiosurgery. The present review examines the state of radiobiological investigations into the nature of CNS effects, the newer techniques developed, and the use of radiosurgery as a tool for understanding basic CNS biology.

The role of radiosurgery for cavernous malformations of the brain remains to be fully defined. We have used Gamma Knife radiosurgery for selected patients with symptomatic, hemorrhagic malformations in high-risk brain locations. Indications, techniques, and results are presented.

Stereotactic radiosurgery has become an integral part of conventional and advanced skull base surgery. Despite the advances in skull base techniques, the goal of total resection of such tumors is often problematic and associated with significant risk to critical structures of the skull base, including those within the cavernous sinus, those in the petrous apex, and the jugular bulb. Aggressive resection of such tumors sometimes results in severe adverse neurological events, ranging from permanent extraocular movement deficits to hearing loss, facial weakness, and difficulties with vagal and glossopharyngeal function. Gamma Knife radiosurgery is a primary alternative option for these patients. It minimizes the risks of open surgical techniques and preserves existing cranial nerve function in most patients and achieves tumor growth arrest. Adjuvant radiosurgery is used for larger tumors after their initial partial resection. Gamma Knife radiosurgery becomes an adjuvant tool to provide longterm tumor growth control of a significantly reduced tumor volume.

Selecting optimal doses for radiosurgery requires a thorough consideration of existing dose-response data for radiation injury of brain and surrounding structures and of the doseresponse for the desired endpoint (tumor control, obliteration of a vascular malformation, relief of trigeminal neuralgia, etc.). This paper reviews the radiobiological and physics principles that should be considered in dose selection as well as information from retrospective and prospective clinical investigations of radiosurgery.

BACKGROUND AND PURPOSE: The authors characterize the detection of additional intracranial metastases in cancer patients at the time of stereotactic radiosurgery (SRS) using a specialized high-resolution magnetic resonance imaging (MRI) protocol. METHODS: A retrospective review of 150 consecutive radiosurgical procedures for patients with < or =5 known metastatic intracranial tumors diagnosed using MRI was undertaken at a single center. On the day of SRS, all patients underwent rigid head fixation in a stereotactic frame followed by a specialized MRI using a 3-dimensional fast spoiled-gradient sequence on a 1.5-tesla magnet with double-dose gadolinium. Axial imaging was performed using 2-mm cuts and no gap. RESULTS: Additional metastases were detected in 29.3% of patients. The number of known tumors before SRS was predictive of additional metastases being found (p = 0.014). In multivariate analysis, we more frequently found additional metastases at radiosurgery in patients with 3-5 previously known metastases (p = 0.005), in patients with non-small cell lung cancer (p = 0.012) and in patients with a longer time interval between their diagnostic MRI and their stereotactic MRI (p = 0.030). Age, sex and prior fractionated radiation therapy were not predictive factors. CONCLUSION: Our specialized protocol of high-resolution, double-dose contrast-enhanced MRI is a reliable method to evaluate the extent of intracranial disease in patients with known brain metastasis. Treatment planning for radiosurgery, radiation therapy and open surgical therapy are all impacted by improved metastasis detection.

The term radiosurgery signifies any kind of application of ionizing radiation energy, in experimental biology or clinical medicine, aiming at the precise and complete destruction of chosen target structures containing healthy and/or pathological cells, without significant concomitant or late radiation damage to adjacent tissues. The goal of this study is to explore the short- and long-term pathophysiological effects of high-dose focused irradiation on neural tissue and its pathologies with histological, electron-microscopical tissue culture and biological-biochemical methods. Radiosurgical pathology focuses its scope and microscope on tissue, cellular, genetic and molecular changes in the human organism and experimental animals, or in cell lines and other in vitro experiments, generated by the ionizing radiation delivered from radiosurgical devices.

The effects of radiosurgery on brain tumor tissue remain to be defined. Effects are dose, volume, time, and tumor histology dependent. In this report, we discuss data from resected specimens after radiosurgery, and work to develop a classification method for radiosurgery effects.

Radiosurgery is a minimally invasive technique designed to elicit a specific radiobiologic response at the target tissue using focused ionizing radiation delivered in single procedure. Radiosurgery was originally devised to treat intracranial lesions by delivering a high dose of radiation precisely at the intracranial target using stereotactic guidance. The term was coined and the field defined by Lars Leksell, a visionary leader of neurosurgery at the Karolinska Institute in Stockholm. Refinements in stereotactic methodologies, major improvements in dose planning software, and advances in neurodiagnostic imaging, all facilitated the increasingly broad application of brain radiosurgical methodologies. New technologies have continued to evolve and are still emerging. A variety of different radiosurgery techniques have been developed during the past 4 decades. Radiosurgery is now being used even for extracranial lesions such as spinal tumors, lung, liver, and prostate pathologies. Numerous studies have examined the benefits and risks of radiosurgery performed with various devices. The long-term results of radiosurgery are now available and have established it as an effective noninvasive management strategy for many brain disorders. Radiosurgery is now considered a mainstream neurosurgical modality for treatment of vascular malformations, tumors, trigeminal neuralgia, movement disorders, and perhaps epilepsy. Its role as a tool for spine and body surgery is also under evaluation.