Faculty Bibliography

OBJECT: This study was conducted to examine the role of radiosurgery in the management of patients with recurrent or unresectable low-grade astrocytomas. METHODS: During a 13-year interval, 49 patients underwent stereotactic radiosurgery as part of multimodal treatment of their recurrent or unresectable low-grade astrocytomas. Thirty-seven of these patients (median age 14 years) harbored pilocytic astrocytomas and 12 patients harbored World Health Organization (WHO) Grade II fibrillary astrocytomas (median age 25 years). Tumors involved the brainstem in 22 cases, cerebellum in four, thalamus in six, temporal lobe in five, frontal lobe in four, and parietal lobe in three, as well as the hypothalamus, corpus callosum, insular cortex, optic tract, and third ventricle in one patient each. Each diagnosis was confirmed with the aid of stereotactic biopsy sampling in 17 patients, open biopsy sampling in five, partial resection in 13, and near-total resection in 14. Multimodal treatment included fractionated radiotherapy in 14 patients, stereotactic intracavitary irradiation in five, chemotherapy in two, cyst drainage in eight, ventriculoperitoneal shunt placement in five, and additional cytoreductive surgery in five. Tumor volumes ranged from 0.42 to 45.1 cm3. The median radiosurgical dose to the tumor margin was 15 Gy (range 9.6-22.5 Gy). After radiosurgery, serial neuroimaging demonstrated complete tumor resolution in 11 patients, reduced tumor volume in 12, stable tumor volume in 10, and delayed tumor progression in 16. No procedure-related death was encountered. Forty-five of 49 patients are alive at a median follow-up period of 32 months after radiosurgery and 63 months after diagnosis. Sixteen patients participated in follow-up review for more than 60 months. Three patients died of local tumor progression. CONCLUSIONS: Stereotactic radiosurgery is a potential alternative or adjunctive intervention in the management of selected patients with pilocytic or WHO Grade II fibrillary astrocytomas, usually performed for small-volume tumors in an attempt to avoid larger-field fractionated radiotherapy.

Management options for patients with vestibular schwannomas (acoustic neuromas) include observation, tumor resection, stereotactic radiosurgery, and fractionated radiotherapy. In this report the authors review their 15-year experience with radiosurgery and discuss indications and expectations in relation to the different approaches. They conducted a survey of neurosurgeons to determine management preferences in two different cases of intra- and extra-canalicular tumor presentations. Patient decisions must be based on quality information derived from peer-reviewed literature.

Stereotactic radiosurgery provided clinicians the ability to administer high single-doses of radiation to intracranial targets with relative safety. Analysis of clinical outcome from radiosurgery calls into question some of the radiobiological principles that have guided conventional fractionated radiotherapy in the past. The response of the tumor or target tissue being irradiated, as well as the response of the surrounding normal tissue, seems predominantly determined by the tumor or target vasculature. Injury to the tumor or target vasculature appears to contribute to the probability of developing normal tissue complications. Estimations of alpha/beta values from radiosurgical dose-response data consistently yield values that conflict with values from fractionated radiotherapy and with linear-quadratic theory. This indicates that projections from high-dose single-fractions to fractionated dose-equivalents made using the linear-quadratic formula are unreliable. Radiobiological analysis of clinical data from radiosurgery provides models for guiding treatment to achieve desired effects and provide reliable estimates of complications.

Laboratory studies have established the potential for neuronal transplantation to be of benefit to patients. Experimental studies in normal animals indicate that brain implantation of neurons seems safe. Implanted neurons integrated with the host brain, sent out axonal processes to communicate with other nerve cells, released transmitters (the chemical messengers of nerve cell communication), and demonstrated typical neuronal proteins. This article discusses phase I and II trials of neuronal transplantation in humans with small strokes in critical brain locations such as the basal ganglia region. More work is needed to confirm safety and to identify optimal measures of efficacy in this setting.

OBJECT: Renal cell carcinoma is a leading cause of death from cancer and its incidence is increasing. In many patients with renal cell cancer, metastasis to the brain develops at some time during the course of the disease. Corticosteroid therapy, radiotherapy, and resection have been the mainstays of treatment. Nonetheless, the median survival in patients with renal cell carcinoma metastasis is approximately 3 to 6 months. In this study the authors examined the efficacy of gamma knife surgery in treating renal cell carcinoma metastases to the brain and evaluated factors affecting long-term survival. METHODS: The authors conducted a retrospective review of 69 patients undergoing stereotactic radiosurgery for a total of 146 renal cell cancer metastases. Clinical and radiographic data encompassing a 14-year treatment interval were collected. Multivariate analyses were used to determine significant prognostic factors influencing survival. The overall median length of survival was 15 months (range 1-65 months) from the diagnosis of brain metastasis. After radiosurgery, the median survival was 13 months in patients without and 5 months in those with active extracranial disease. In a multivariate analysis, factors significantly affecting the rate of survival included the following: 1) younger patient age (p = 0.0076); 2) preoperative Karnofsky Performance Scale score (p = 0.0012); 3) time from initial cancer diagnosis to brain metastasis diagnosis (p = 0.0017); 4) treatment dose to the tumor margin (p = 0.0252); 5) maximal treatment dose (p = 0.0127); and 6) treatment isodose (p = 0.0354). Prior tumor resection, chemotherapy, immunotherapy, or whole-brain radiation therapy did not correlate with extended survival. Postradiosurgical imaging of the brain demonstrated that 63% of the metastases had decreased, 33% remained stable, and 4% eventually increased in size. Two patients (2.9%) later underwent a craniotomy and resection for a tumor refractory to radiosurgery or a new symptomatic metastasis. Eighty-three percent of patients died of progression of extracranial disease. CONCLUSIONS: Stereotactic radiosurgery for treatment of renal cell carcinoma metastases to the brain provides effective local tumor control in approximately 96% of patients and a median length of survival of 15 months. Early detection of brain metastases, aggressive treatment of systemic disease, and a therapeutic strategy including radiosurgery can offer patients an extended survival.