Faculty Bibliography

OBJECT: Radiosurgery and radiation therapy represent important but unique treatment paradigms for patients with certain neoplasms, vascular lesions, or functional disorders. The authors discuss their differences. METHODS: Reviewing the authors' experiences shows how the roles of these approaches vary just as their techniques differ. The distinct differences include the method of target localization (intraoperative compared with pretreatment) and irradiation (focused compared with wide-field), their radiobiology (effects of a single high-dose compared with multiple fractions), the physicians and other health personnel involved in the conduct of these procedures (surgical team compared with radiation team), and the expectations that follow treatment. During the last decade, considerable confusion has grown regarding nomenclature, requisite physician training, and the roles of the physician and surgeon. Ten years ago, two task forces on radiosurgery were created by national organizations in neurosurgery and radiation oncology to address these issues of procedural conduct and quality-assurance requirements. At the present time these guidelines are widely ignored. Currently, many patients, payers, and regulatory agencies are bewildered. What are the differences among stereotactic radiosurgery, fractionated radiation therapy, and stereotactic radiation therapy? Radiosurgery is to radiation therapy as microsurgery is to "microtherapy." CONCLUSIONS: In this report the authors discuss terminology, training, and physician roles in this expanding field.

PURPOSE: To define tumor control and clinical outcomes of radiosurgery to marginal tumor doses of 12-13 Gy for unilateral acoustic neuroma patients. METHODS AND MATERIALS: Three hundred thirteen patients with previously untreated unilateral acoustic neuromas (vestibular schwannomas) underwent gamma knife radiosurgery between February 1991 and February 2001 with marginal tumor doses of 12-13 Gy (median, 13 Gy). Median follow-up was 24 months (maximum, 115 months; 36 patients with > or =60 months). Maximum doses were 20-26 Gy (median, 26 Gy), and treatment volumes were 0.04-21.4 mL (median, 1.1 mL). RESULTS: The actuarial 6-year clinical tumor control rate (no requirement for surgical intervention) for the entire series was 98.6 +/- 1.1%. Two patients required tumor resection; one had a complete resection for solid tumor growth and one required partial resection for an enlarging adjacent subarachnoid cyst. Six-year actuarial rates for preservation of facial nerve function, normal trigeminal nerve function, unchanged hearing level, and useful hearing were 100%, 95.6 +/- 1.8%, 70.3 +/- 5.8%, and 78.6 +/- 5.1%, respectively. The risk of developing trigeminal neuropathy correlated with increasing tumor volume (p = 0.038). CONCLUSIONS: Acoustic neuroma radiosurgery with doses of 12-13 Gy provides high rates of tumor control and cranial nerve preservation.

LARS LEKSELL BEGAN radiobiological investigations to study the effect of high-dose focused radiation on the central nervous system more than 5 decades ago. Although the effects of radiosurgery on the brain tumor microenvironment are still under investigation, radiosurgery has become a preferred management modality for many intracranial tumors and vascular malformations. The effects and the pathogenesis of biological effects after radiosurgery may be unique. The need for basic research concerning the radiobiological effects of high-dose, single-fraction, ionizing radiation on nervous system tissue is crucial. Information from those studies would be useful in devising strategies to avoid, prevent, or ameliorate damage to normal tissue without compromising treatment efficacy. The development of future applications of radiosurgery will depend on an increase in our understanding of the radiobiology of radiosurgery, which in turn will affect the efficacy of treatment. This article analyzes the current state of radiosurgery research with regard to the nature of central nervous system effects, the techniques developed to increase therapeutic efficacy, investigations into the use of radiosurgery for functional disorders, radiosurgery as a tool for investigations into basic central nervous system biology, and the additional areas that require further investigation.

BACKGROUND: Brain metastases are the most common type of intracranial tumor. Until recently, whole brain fractionated radiation therapy (WBRT) was the mainstay of treatment, thereby confining the role of neurosurgeons to resection of an occasional solitary, accessible, and symptomatic brain metastasis. Median survival after surgery and radiation typically ranged from 5 to 11 months. METHODS: We analyzed various demographic incidence reports and our series of brain metastasis patients treated with radiosurgery. During a 15-year interval (1987-2002), radiosurgery was performed on 5,032 patients of whom 1,088 (21.6%) had metastatic brain tumors. RESULTS: In the United States, 266,820 to 533,640 new cases of brain metastases will be diagnosed in the year 2003. Evidence to date demonstrates that radiosurgery provides effective local tumor control for brain metastases. Important prognostic factors affecting patient survival include the absence of active systemic disease, the patient's preoperative performance status, age, and the number of metastases. Survival and local tumor control rates attained with radiosurgery are superior to those of either conventional surgery or WBRT. The morbidity associated with radiosurgery of brain metastasis is very low, and the mortality rate approaches zero. CONCLUSIONS: Compelling evidence indicates that radiosurgery is an effective neurosurgical management strategy for intracranial brain metastases. Quite often, favorable tumor control and survival can be achieved without WBRT. With radiosurgery as a therapeutic option, neurosurgeons now have a vastly expanded armamentarium for treatment of patients with brain metastases. The large number of patients with brain metastases who require care by a neurosurgeon for optimal treatment has significant implications for both the patterns of neurosurgical training and practice in the United States.

OBJECTIVE: Neurotransplantation has focused on disorders that involve subcortical brain targets. We evaluated the concepts of epileptic focus repair and changes in animal behavior through replacement of lost hippocampal neurons. The safety of hippocampal neurotransplantation was assessed in the rat kainic acid (KA) epilepsy model. METHODS: Sixty-three rats were studied and classified into six groups: KA plus 40,000 LBS-Neurons (Layton BioScience, Sunnyvale, CA; n = 13); KA plus 80,000 cells (n = 12); KA plus media (n = 9); no-KA plus 40,000 cells (n = 12); no-KA plus 80,000 cells (n = 12); and no-KA plus media (n = 5). Clinical observation (2 h daily) and electroencephalogram recording (3 h every other week) were performed to check for seizures until Week 11 after KA injection. On Week 12, the Morris water maze test was performed to assess spatial learning and memory. RESULTS: Four rats were excluded because of intracranial hematoma or abscess. In the clinical observation of seizures, the no-KA plus media group had significantly fewer seizures than rats that received KA followed by injection of 40,000 cells, 80,000 cells, or media (P = 0.001, 0.0004, and 0.004, respectively). On electroencephalographic analysis, there was no significant difference between any of the groups. Transplanted rats with KA-induced epilepsy did not have an increased number of seizures. In the Morris water maze test, the hidden platform task showed that the KA plus 80,000 cell group had significantly longer swim latencies than groups with no-KA plus 40,000 cells (P = 0.035) or no-KA plus 80,000 cells (P = 0.015), demonstrating the behavioral deficits caused by KA injection. The probe trial showed no significant difference for the percentage of time in the target quadrant between any of the groups. Histological studies showed that 26 (59%) of 44 transplanted rats had evidence of graft survival. CONCLUSION: The safety of cortical neurotransplantation was demonstrated, even in an animal model predisposed to epilepsy. We did not find evidence for cessation of seizures or improvement in behavior using this model.