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.

Object. Pituitary adenomas are very common neoplasms, constituting between 10 and 20% of all primary brain tumors. Historically, the treatment armamentarium for pituitary adenomas has included medical management, microsurgery, and fractionated radiotherapy. More recently, radiosurgery has emerged as a viable treatment option. The goal of this research was to define more fully the efficacy, safety, and role of radiosurgery in the treatment of pituitary adenomas. Methods. Medical literature databases were searched for articles pertaining to pituitary adenomas and stereotactic radiosurgery. Each study was examined to determine the number of patients, radiosurgical parameters (for example, maximal dose and tumor margin dose), duration of follow-up review, tumor growth control rate, complications, and rate of hormone normalization in the case of functioning adenomas. A total of 35 peer-reviewed studies involving 1621 patients were examined. Radiosurgery resulted in the control of tumor size in approximately 90% of treated patients. The reported rates of hormone normalization for functioning adenomas varied substantially. This was due in part to widespread differences in endocrinological criteria used for the postradiosurgical assessment. The risks of hypopituitarism, radiation-induced neoplasia, and cerebral vasculopathy associated with radiosurgery appeared lower than those for fractionated radiation therapy. Nevertheless, further observation will be required to understand the true probabilities. The incidence of other serious complications following radiosurgery was quite low. Conclusions. Although microsurgery remains the primary treatment modality in most cases, stereotactic radiosurgery offers both safe and effective treatment for recurrent or residual pituitary adenomas. In rare instances, radiosurgery may be the best initial treatment for patients with pituitary adenomas. Further refinements in the radiosurgical technique will likely lead to improved outcomes.

Object: In this study the authors address the efficacy and safety of Gamma Knife surgery (GKS) in patients with adrenocorticotropic hormone–secreting pituitary adenomas. Methods: A review of data collected from a prospective GKS database between January 1990 and March 2005 was performed in patients with Cushing's disease. All but one patient underwent resection for a pituitary tumor, without achieving remission. Successful endocrine outcome after GKS was defined as a normal 24-hour urinary free cortisol (UFC) concentration posttreatment after a minimum of 1 year of follow up. Patient records were also evaluated for changes in tumor volume, development of new hormone deficiencies, visual acuity, cranial nerve neuropathies, and radiation-induced imaging changes. Ninety evaluable patients had undergone GKS, with a mean endocrine follow-up duration of 45 months (range 12–132 months). The mean dose to the tumor margin was 23 Gy (median 25 Gy). Normal 24-hour UFC levels were achieved in 49 patients (54%), with an average time of 13 months after treatment (range 2–67 months). In the 49 patients in whom a tumor was visible on the planning magnetic resonance (MR) image, a decrease in tumor size occurred in 39 (80%), in seven patients there was no change in size, and tumor growth occurred in three patients. Ten patients (20%) experienced a relapse of Cushing's disease after initial remission; the mean time to recurrence was 27 months (range 6–60 months). Seven of these patients underwent repeated GKS, with three patients achieving a second remission. New hormone deficiencies developed in 20 patients (22%), with hypothyroidism being the most common endocrinopathy after GKS. Five patients experienced new visual deficits or third, fourth, or sixth cranial nerve deficits; two of these patients had undergone prior conventional fractionated radiation therapy, and four of them had received previous GKS. Radiation-induced changes were observed on MR images in three patients; one had symptoms attributable to these changes. Conclusions: Gamma Knife surgery is an effective treatment for persistent Cushing's disease. Adenomas with cavernous sinus invasion that are not amenable to resection are treatable with the Gamma Knife. A second GKS treatment appears to increase the risk of cranial nerve damage. These results demonstrate the value of combining two neurosurgical treatment modalities—microsurgical resection and GKS—in the management of pituitary adenomas.

Brain arteriovenous malformations (AVMs) are anomalous direct shunts between cerebral arteries and veins that convalesce into a vascular nidus. The treatment strategies for AVMs are challenging and variable. Intracranial hemorrhage and seizures comprise the most common presentations of AVMs. However, incidental AVMs are being diagnosed with increasing frequency due to widespread use of noninvasive neuroimaging. The balance between the estimated cumulative lifetime hemorrhage risk vs the risk of intervention is often the major determinant for treatment. Current management options include surgical resection, embolization, stereotactic radiosurgery (SRS), and observation. Complete nidal obliteration is the goal of AVM intervention. The risks and benefits of interventions vary and can be employed in a combinatorial fashion. Resection of the AVM nidus affords high rates of immediate obliteration, but it is invasive and carries a moderate risk of neurologic morbidity. AVM embolization is minimally invasive, but cure can only be achieved in a minority of lesions. SRS is also minimally invasive and has little immediate morbidity, but AVM obliteration occurs in a delayed fashion, so the patient remains at risk for hemorrhage during the latency period. Whether obliteration can be achieved in unruptured AVMs with a lower risk of stroke or death compared to the natural history of AVMs remains controversial. Over the past 5 years, multicenter prospective and retrospective studies describing AVM natural history and treatment outcomes have been published. This review provides a contemporary and comprehensive discussion of the natural history, pathobiology, and interventions for brain AVMs.

✓ The Gamma Knife has played an increasingly important role in the neurosurgical treatment of patients. Intracranial lesions are not removed by radiosurgery. Rather, the goal of treatment is to induce tumor control. During planning, the creation of dose–volume histograms requires an accurate volumetric analysis of intracranial lesions selected for radiosurgery. In addition, an accurate follow-up imaging analysis of tumor volume is essential for assessing the results of radiosurgery. Nevertheless, sources of volumetric error and their expected magnitudes must be properly understood so that the operator may correctly interpret apparent changes in tumor volume. In this paper, the authors examine the often-neglected contributions of imaging geometry (principally image slice thickness and separation) to overall volumetric error. One of the fundamental sources of volumetric error is that resulting from the geometry of the acquisition protocol. The authors consider the image sampling geometry of tomographic modalities and its contribution to volumetric error through a simulation framework in which a synthetic digital tumor is taken as the primary model. Because the exact volume of the digital phantom can be computed, the volume estimates derived from tomographic “slicing” can be directly compared precisely and independently from other error sources. In addition to providing empirical bounds on volumetric error, this approach provides a tool for guiding the specification of imaging protocols when a specific volumetric accuracy, or volume change sensitivity, for particular structures is sought a priori. Using computational geometry techniques, the volumetric error associated with image acquisition geometry was shown to be dependent on the number of slices through the region of interest (ROI) and the lesion volume. With a minimum of five slices through the ROI, the volume of a compact lesion could be calculated accurately with less than 10% error, which was the predetermined goal for the purposes of computing accurate dose–volume histograms and determining follow-up changes in tumor volume. Accurate dose–volume histograms can be generated and follow-up volumetric assessments performed, assuming accurate lesion delineation, when the object is visualized on at least five axial slices. Volumetric analysis based on fewer than five slices yields unacceptably larger errors (that is, > 10%). These volumetric findings are particularly relevant for radiosurgical treatment planning and follow-up analysis. Through the application of this volumetric methodology and a greater understanding of the error associated with it, neurosurgeons can better perform radiosurgery and assess its outcome.

To evaluate patient selection criteria, methodology, safety and clinical outcomes of stereotactic body radiotherapy (SBRT) for treatment of vertebral metastases. Eight centers from the United States (n = 5), Canada (n = 2) and Germany (n = 1) participated in the retrospective study and analyzed 301 patients with 387 vertebral metastases. No patient had been exposed to prior radiation at the treatment site. All patients were treated with linac-based SBRT using cone-beam CT image-guidance and online correction of set-up errors in six degrees of freedom. 387 spinal metastases were treated and the median follow-up was 11.8 months. The median number of consecutive vertebrae treated in a single volume was one (range, 1-6), and the median total dose was 24 Gy (range 8-60 Gy) in 3 fractions (range 1-20). The median EQD210 was 38 Gy (range 12-81 Gy). Median overall survival (OS) was 19.5 months and local tumor control (LC) at two years was 83.9%. On multivariate analysis for OS, male sex (p < 0.001; HR = 0.44), performance status <90 (p < 0.001; HR = 0.46), presence of visceral metastases (p = 0.007; HR = 0.50), uncontrolled systemic disease (p = 0.007; HR = 0.45), >1 vertebra treated with SBRT (p = 0.04; HR = 0.62) were correlated with worse outcomes. For LC, an interval between primary diagnosis of cancer and SBRT of ≤30 months (p = 0.01; HR = 0.27) and histology of primary disease (NSCLC, renal cell cancer, melanoma, other) (p = 0.01; HR = 0.21) were correlated with worse LC. Vertebral compression fractures progressed and developed de novo in 4.1% and 3.6%, respectively. Other adverse events were rare and no radiation induced myelopathy reported. This multi-institutional cohort study reports high rates of efficacy with spine SBRT. At this time the optimal fractionation within high dose practice is unknown.