Faculty Bibliography

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.

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.

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.

INTRODUCTION: Meningiomas are common intracranial benign tumors that can be surgically excised. However, their intimate involvement with critical neurovascular structures often prevent their complete resection. Gamma Knife radiosurgery is a minimally invasive option which provides excellent tumor control as both an adjunct and primary therapy. MATERIALS AND METHODS: Between September 1987 and December 2004, 964 patients underwent Gamma Knife radiosurgery at the University of Pittsburgh for the diagnosis of meningioma. The majority of patients had tumors located at the skull base. All imaging and clinical follow-up was reviewed. RESULTS: Overall, Gamma Knife radiosurgery provides 5- and 10-year actuarial tumor control rates of 93% for benign meningiomas. The 5-year actuarial control rate for patients with atypical and malignant meningiomas was 83 +/- 7 and 72 +/- 10%, respectively. The incidence of adverse radiation effect ranged from 5.7 to 16%; however, the incidence was gradually reduced with the advent of magnetic resonance imaging and lower dosing since 1991. CONCLUSION: Gamma Knife radiosurgery is an attractive option for patients with intracranial meningiomas. It can be used as both primary treatment based on imaging diagnosis alone, or as an adjunct treatment after craniotomy. It provides long-term tumor control with minimal adverse sequelae.

Systematic human pathological background to brain tumor radiosurgery explaining biological and pathophysiological effects of focused irradiation barely exists. The goal of this study was to explore histopathological changes evoked by single high-dose irradiation in a set of different brain tumors following Gamma Knife radiosurgery (GKRS). Light microscopy revealed that GKRS evokes degenerative and proliferative pathological changes in the parenchyma, stroma and vessels of the irradiated tumors. Three main histological types of gamma radiolesions, that is acute, subacute and chronic variants of tissue reactions were recognized in different neoplasms irrespective of their ontogenetic nature. Acute type gamma radiolesions were characterized mainly with necrotic changes and appeared either early or in a delayed time interval. Subacute type gamma radiolesions expressed resorptive activity also with early or delayed chronology. Chronic type lesions showed a reparative tendency but presented only at the delayed stage. These changes seem to follow each other consecutively. There was no significant relation between morphological characteristics of the generated tissue reaction and the time interval elapsed after GKRS. This relative time and environment autonomy of the developed pathological lesions with similar histological picture in different neoplasms suggests either a vascular mechanism or/and a genetically directed origin presumably induced by the ionizing energy of high-dose irradiation.