A multicenter, prospective pilot study of gamma knife radiosurgery for mesial temporal lobe epilepsy: seizure response, adverse events, and verbal memory.

OBJECTIVE: The safety, efficacy, and morbidity of radiosurgery (RS) must be established before it can be offered as an alternative to open surgery for unilateral mesial temporal lobe epilepsy. We report the 3-year outcomes of a multicenter, prospective pilot study of RS. METHODS: RS was randomized to 20 or 24Gy targeting the amygdala, hippocampus, and parahippocampal gyrus. Seizure diaries evaluated the final seizure remission between months 24 and 36. Verbal memory was evaluated at baseline and 24m with the Wechsler Memory Scale-Revised (WMS-R) and California Verbal Learning Test (CVLT). Patients were classified as having "significant improvement," "no change," and "significant impairment" based on relative change indices. RESULTS: Thirteen high-dose and 17 low-dose patients were treated. Both groups showed significant reductions in seizures by 1 year after treatment. At the 36-month follow-up evaluation, 67% of patients were free of seizures for the prior 12 months (high dose: 10/13, 76.9%; low dose: 10/17, 58.8%). Use of steroids, headaches, and visual field defects did not differ by dose or seizure remission. The prevalence of verbal memory impairment was 15% (4/26 patients); none declined on more than one measure. The prevalence of significant verbal memory improvements was 12% (3/26). INTERPRETATION: RS for unilateral mesial temporal lobe epilepsy offers seizure remission rates comparable with those reported previously for open surgery. There were no major safety concerns with high-dose RS compared with low-dose RS. Additional research is required to determine whether RS may be a treatment option for some patients with mesial temporal lobe epilepsy.

Gamma knife surgery for neurocytoma.

OBJECT: Although considered benign tumors, neurocytomas have various biological behaviors, histological patterns, and clinical courses. In the last 15 years, fractionated radiotherapy and radiosurgery in addition to microsurgery have been used in their management. In this study, the authors present their experience using Gamma Knife surgery (GKS) in the treatment of these tumors. METHODS: Between 1989 and 2004, the authors performed GKS in seven patients with a total of nine neurocytomas. Three patients harbored five recurrent tumors after a gross-total resection, three had progression of previous partially resected tumors, and one had undergone a tumor biopsy only. The mean tumor volume at the time of GKS ranged from 1.4 to 19.8 cm3 (mean 6.0 cm3). A mean peripheral dose of 16 Gy was prescribed to the tumor margin with the median isodose configuration of 32.5%. RESULTS: After a mean follow-up period of 60 months, four of the nine tumors treated disappeared and four shrank significantly. Because of secondary hemorrhage, an accurate tumor volume could not be determined in one. Four patients were asymptomatic during the follow-up period, and the condition of the patient who had residual hemiparesis from a previous transcortical resection of the tumor was stable. Additionally, the patient who experienced tumor hemorrhage required a shunt revision, and another patient died of sepsis due to a shunt infection. CONCLUSIONS: Based on this limited experience, GKS seems to be an appropriate management alternative. It offers control over the tumor with the benefits of minimal invasiveness and low morbidity rates. Recurrence, however, is not unusual following both microsurgery and GKS. Open-ended follow-up imaging is required to detect early recurrence and determine the need for retreatment.

Gamma knife surgery for trigeminal schwannoma.

OBJECT: Trigeminal schwannomas are rare intracranial tumors. In the past, resection and radiation therapy were the mainstays of their treatment. More recently, neurosurgeons have begun to use radiosurgery in the treatment of trigeminal schwannomas because of its successful use in the treatment of vestibular schwannomas. In this article the authors evaluate the radiological and clinical outcomes in a series of patients in whom Gamma Knife surgery (GKS) was used to treat trigeminal schwannomas. METHODS: Twenty-six patients with trigeminal schwannomas underwent GKS at the University of Virginia Lars Leksell Gamma Knife Center between 1989 and 2005. Five of these patients had neurofibromatosis and one patient was lost to follow up. The median tumor volume was 3.96 cm(3), and the mean follow-up period was 48.5 months. The median prescription radiation dose was 15 Gy, and the median prescription isodose configuration was 50%. There was clinical improvement in 18 patients (72%), a stable lesion in four patients (16%), and worsening of the disease in three patients (12%). On imaging, the schwannomas shrank in 12 patients (48%), remained stable in 10 patients (40%), and increased in size in three patients (12%). These results were comparable for primary and adjuvant GKSs. No tumor growth following GKS was observed in the patients with neurofibromatosis. CONCLUSIONS: Gamma Knife surgery affords a favorable risk-to-benefit profile for patients harboring trigeminal schwannomas. Larger studies with open-ended follow-up review will be necessary to determine the long-term results and complications of GKS in the treatment of trigeminal schwannomas.

Gamma knife surgery for focal brainstem gliomas.

OBJECT: Focal tumors, a distinct subgroup of which is composed of brainstem gliomas, may have an indolent clinical course. In the past, their management involved monitoring of open-ended imaging studies and shunt placement if cerebrospinal fluid diversion was required. Nonetheless, their treatment remains a significant challenge for neurosurgeons. Gamma Knife surgery (GKS) has recently been tried as an alternative to surgical extirpation. In the present study the authors assess clinical and imaging results in 20 patients who harbored focal brainstem gliomas treated with GKS between 1990 and 2001. METHODS: There were 10 male and 10 female patients with a mean age of 19.1 years. Sixteen tumors were located in the midbrain, three in the pons, and one in the medulla oblongata. The mean tumor volume at the time of GKS was 2.5 cm3. In 10 cases a tumor specimen was obtained either by open surgery or stereotactic biopsy, securing the diagnosis of pilocytic astrocytoma in five patients and nonpilocytic astrocytoma in five others. In the remaining 10 cases, the diagnosis was based on clinical and neuroimaging findings. The prescription Gamma Knife dose varied between 10 and 18 Gy, except in three patients who were receiving a boost to a site in which external-beam radiation was previously delivered. An average of four isocenters were utilized per GKS. Patients were followed up for a mean of 78.0 months. The tumors disappeared in four patients and shrank in 12 patients. Of these patients, one experienced transitory extrapyramidal symptoms and fluctuating impairment of consciousness (from somnolence to coma) for 6 months. Another patient whose tumor disappeared 3 years following GKS died of stroke 8 years postoperatively. The rest of the patients either remained stable or improved clinically. Tumor progression occurred in four patients; of these four, one patient developed hydrocephalus requiring a ventriculoperitoneal shunt, two showed neurological deterioration, and one 4-year-old boy died of tumor progression. CONCLUSIONS: Gamma Knife surgery may be an effective primary treatment or adjunct to open surgery for focal brainstem gliomas.

Subtotal obliteration of cerebral arteriovenous malformations after gamma knife surgery.

OBJECT: Subtotal obliteration of cerebral arteriovenous malformations (AVMs) after Gamma Knife surgery (GKS) implies a complete angiographic disappearance of the AVM nidus but persistence of an early filling draining vein, indicating that residual shunting is still present; hence, per definition there is still a patent AVM and the risk of bleeding is not eliminated. The aim of this study was to determine the risk of hemorrhage for patients with subtotal obliteration of AVMs. METHODS: After GKS for cerebral AVMs, follow-up angiography demonstrated a subtotally obliterated lesion in 159 patients. Of these, in 16 patients a subtotally obliterated AVM developed after a second GKS was performed for the partially obliterated lesion. The mean age of these patients was 35.2 years at the time of the diagnosis of subtotally obliterated AVMs. The lesion volumes at the time of initial GKS treatment ranged from 0.1 to 11.5 cm3 (mean 2.5 cm3). The mean peripheral dose used in the 175 GKS treatments was 22.5 Gy (median 23 Gy, range 15-31 Gy). To achieve total obliteration of the AVM, 23 patients underwent a new GKS targeting the proximal end of the early filling vein. The mean peripheral dose given in these cases was 23 Gy (median 24, range 18-25 Gy). The incidence of subtotally obliterated AVMs was 7.6% from a total of 2093 AVMs treated and in which follow-up imaging was available. The diagnosis of subtotally obliterated AVMs was made a mean of 29.4 months (range 4-178 months) after GKS. The number of patient-years at risk (from the time of the diagnosis of subtotally obliterated AVMs until either the confirmation of a total obliteration of the lesion on angiography or the time of the latest follow-up angiographic study that still visualized the early filling vein) was a mean of 3.9 years, ranging from 0.5 to 13.5 years, and a total of 601 patient-years. There was no case of bleeding after the diagnosis of subtotally obliterated AVMs. Of 90 patients who did not undergo further treatment and in whom follow-up angiography studies were available, the same early filling veins still filled in 24 (26.7%), and the subtotally obliterated AVMs were subsequently obliterated in 66 patients (73.3%). In 19 patients who underwent repeated GKS for subtotally obliterated AVMs and in whom follow-up angiography studies were available, the AVMs were obliterated in 15 (78.9%) and remained patent in four (21.1%). CONCLUSIONS: The fact that none of the patients with subtotally obliterated AVMs suffered a rupture is not compatible with the assumption of an unchanged risk of hemorrhage for these lesions, and implies that the protection from rebleeding in patients with subtotal obliteration is significant. Subtotal obliteration does not necessarily seem to be a stage of an ongoing obliteration. At least in some cases it represents an end point of this process, with no subsequent obliteration occurring. This observation requires further confirmation by open-ended follow-up imaging.

Gamma Knife surgery for Cushing's disease.

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 to 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.

Gamma Knife surgery for adrenocorticotropic hormone-producing pituitary adenomas after bilateral adrenalectomy.

OBJECT: Patients with adrenocorticotropic hormone (ACTH)-secreting pituitary adenomas may require a bilateral adrenalectomy to treat their Cushing's disease. Approximately one third of these patients, however, will experience progressive enlargement of the residual pituitary adenoma, develop hyperpigmentation, and have an elevated level of serum ACTH. These patients with Nelson's syndrome can be treated with Gamma Knife surgery (GKS). METHODS: The prospectively collected University of Virginia Gamma Knife database of patients with pituitary adenomas was reviewed to identify all individuals with Nelson's syndrome who were treated with GKS. Twenty-three patients with a minimum of 6 months of follow up were identified in the database. These patients were assessed for tumor control (that is, lack of tumor growth over time) with neuroimaging studies (median follow-up duration 22 months) and for biochemical normalization of their ACTH levels (median follow-up duration 50 months). Neuroimaging follow-up studies were available for 22 patients, and endocrine follow up was available for 15 patients in whom elevation of ACTH levels was documented prior to GKS. In the 22 patients in whom neuroimaging follow-up studies were available, 12 had a decrease in tumor size, eight had no tumor growth, and two had an increase in tumor volume. Ten of 15 patients with elevated ACTH levels prior to GKS showed a decrease in their ACTH levels at last follow up; three of these 10 patients achieved normal ACTH levels (< 50 pg/ml) and the other five patients with initially elevated values had an increase in ACTH levels. Ten patients were thoroughly evaluated for post-GKS pituitary function; four were found to have new pituitary hormone deficiency and six did not have hypopituitarism after GKS. One patient suffered a permanent third cranial nerve palsy and four patients are now deceased. CONCLUSIONS: Gamma Knife surgery may control the residual pituitary adenoma and decrease ACTH levels in patients with Nelson's syndrome. Delayed hypopituitarism or cranial nerve palsies can occur after GKS. Patients with Nelson's syndrome require continued multidisciplinary follow-up care. Given the difficulties associated with management of Nelson's syndrome, even the modest results of GKS may be helpful for a number of patients.

Gamma knife surgery for metastatic brainstem tumors.

OBJECT: The authors review imaging and clinical outcomes in patients with metastatic brainstem tumors treated using Gamma Knife surgery (GKS). METHODS: Between March 1989 and March 2005, 53 patients (24 men and 29 women) with metastatic brainstem lesions underwent GKS. The metastatic deposits were located in the midbrain in eight patients, the pons in 42, and the medulla oblongata in three. Lung cancer was the most common primary malignancy, followed by breast cancer, melanoma, and renal cell carcinoma. The mean volume of the metastatic deposits at the time of treatment was 2.8 cm3 (range 0.05-21 cm3). The prescription doses varied from 9 to 25 Gy (mean 17.6 Gy). Imaging follow-up studies were not completed in 16 patients, because of the short-term survival in 11 and patient refusal in five. Of the remaining 37 patients, who underwent an imaging follow-up evaluation at a mean of 9.8 months (range 1-25 months), the tumors disappeared in seven, shrank in 22, remained unchanged in three, and grew in five. All but one of 18 patients with asymptomatic brainstem deposits remained free of symptoms. In 35 patients with symptomatic brainstem deposits, neurological symptoms improved in 21, remained stable in 11, and worsened in three. At the time of this study, 10 patients were alive, and their survival ranged from 3 to 52 months after treatment. Thirty-four patients died of extracranial disease, three of the progressing metastatic brainstem lesion, and six of additional progressing intracranial deposits in other parts of the brain. The overall median survival period was 11 months after GKS. In terms of survival, the absence of active extracranial disease was the only favorable prognostic factor. Neither previous whole-brain radiation therapy nor a single brainstem metastasis was statistically related to the duration of survival. CONCLUSIONS: Compared with allowing a metastatic brainstem lesion to take its natural course, GKS prolongs survival. The risks associated with such treatment are low. The severity of systemic diseases largely determines the prognosis of metastases to the brainstem.

Gamma knife surgery-induced meningioma. Report of two cases and review of the literature.

Gamma Knife surgery (GKS) is a minimally invasive neurosurgical technique. During the past 30 years, radiosurgery has been performed for a number of intracranial disorders with a generally low incidence of side effects. Although radiation-induced neoplasia following radiotherapy is well documented, there are few reports of this complication following radiosurgery. The authors are engaged in an ongoing project in which they are studying the delayed adverse effects of radiosurgical changes in 2500 patients with arteriovenous malformations (AVMs) treated within a 30-year period. The cases of 1333 patients treated by the senior author (L.S.) have been reviewed thus far. A subset of 288 patients in this group underwent neuroimaging and participated in clinical follow up for at least 10 years. The authors report two cases of radiosurgically induced neoplasia. In both cases the patient was treated with GKS for an AVM. Longer than 10 years after GKS, each of the patients was found to have an incidental, uniformly enhancing, dura-based mass lesion near the site of the AVM. These lesions displayed the imaging characteristics of a meningioma. Because in both cases the lesion has displayed no evidence of a mass effect, they continue to be followed using serial neuroimaging. These are the fifth and sixth cases meeting the criteria for radiation-induced neoplasms defined by Cahan, et al., in 1998. Although radiosurgery is generally considered quite safe, the incidence of radiation-induced neoplasms is not known. These cases and the few others detailed in the literature emphasize the need for long-term neurosurgical follow-up review in patients after radiosurgery.

Assessment of imaging studies used with radiosurgery: a volumetric algorithm and an estimation of its error. Technical note.

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.

Gamma surgery in the treatment of nonsecretory pituitary macroadenoma.

OBJECT: The authors report on a retrospective analysis of the imaging and clinical outcomes following gamma surgery in 100 patients with nonsecretory pituitary macroadenoma. METHODS: Between June 1989 and March 2004, 100 consecutive patients with nonsecretory pituitary macroadenoma were treated at the Lars Leksell Center for Gamma Surgery, University of Virginia Health System (Charlottesville, VA). Ninety-two patients had residual or recurrent macroadenoma following one or more surgical procedures. In eight patients, gamma surgery was the primary treatment. Ten patients received conventional fractionated radiotherapy before the gamma surgery. Sixty-nine patients required hormone replacement therapy for one or more deficits before gamma knife treatment. Peripheral doses between 5 and 25 Gy (mean 18.5 Gy) were administered. Imaging and endocrinological follow-up evaluations were performed in 90 patients; these studies ranged from 6 to 142 months (mean 44.9 months) and 6 to 127 months (mean 47.9 months), respectively. Tumor volume decreased in 59 patients (65.6%), remained unchanged in 24 (26.7%), and increased in seven (7.8%). The minimal effective peripheral dose was 12 Gy; peripheral doses greater than 20 Gy did not seem to provide additional benefit. Of 61 patients with a partially or fully functioning pituitary gland and follow-up data, 12 (19.7%) suffered new hormone deficits following gamma surgery. In patients with endocrinological follow-up data that had been collected over more than 2 years, the rate of new deficits was 25%. No neurological morbidity or death was related to treatment. CONCLUSIONS: Current experience suggests that gamma surgery is an appropriate means of managing recurrent or residual nonsecretory pituitary macroadenoma following microsurgery and a primary treatment in selected patients. To evaluate definite rates of recurrence and new endocrine deficiencies, long-term follow-up studies are needed.

Stereotactic radiosurgery for pituitary adenomas: a review of the literature and our experience.

Pituitary adenomas are not just one of the most common intracranial tumors but also one of the most difficult to cure. Neurosurgeons have adapted their tools to include precise ionizing radiation in the form of the gamma knife to treat pituitary adenomas. The use of the gamma knife in the management of pituitary adenomas following microsurgery or in selected cases as a primary treatment is safe. The combined application of transsphenoidal surgery and Gamma Knife surgery is beneficial in many difficult cases. However in some patients, optimal control of tumor growth and normalization of hypersecretory states are not achieved. Innovative improvements in operative and radiosurgical techniques are required to avoid pituitary insufficiency and to reduce the number of the cases in which optimal radiosurgery is not feasible because of close tumor proximity to the optic pathways.

Late cyst formation following gamma knife surgery of arteriovenous malformations.

OBJECT: The authors present data concerning the development of cysts following gamma knife surgery (GKS) in 1203 consecutive patients with arteriovenous malformations (AVMs) treated by the senior author (L.S.). The cyst was defined as a fluid-filled cavity at the site of a treated AVM. Cases involving regions corresponding to previous hematoma cavities were excluded. The incidence of cyst formation was assessed using magnetic resonance imaging studies performed in 196 cases with more than 10 years of follow up, in 332 cases with 5 to 10 years of follow up, and in 675 cases with less than 5 years of follow up. One hundred five cases were lost to follow-up study. The Cox regression method was used to analyze the factors related to cyst formation. METHODS: The incidence of cyst formation in the entire patient population was 1.6 and 3.6% in those undergoing follow-up examination for more than 5 years. Ten of 20 cysts developed between 10 to 23 years, nine between 5 to 10 years, and one in less than 5 years following the treatment. Cyst fluid aspiration, cystoperitoneal shunt placement, or craniotomy were used in three symptomatic cases. Analysis of age, sex, and treatment parameters yielded no significant relationship with cyst formation; however, radiation-induced tissue change following GKS (p = 0.027) and prior embolization (p = 0.011) were related to cyst formation. CONCLUSIONS: Overall, the incidence of cyst formation in patients who underwent GKS for AVM was 1.6%. The development of the cyst was related to the duration of the follow-up period. When cysts are symptomatic, surgical intervention should be performed.

Gamma knife surgery for brain metastases from lung cancer.

OBJECT: The authors conducted a study to evaluate the safety and efficacy of gamma knife surgery (GKS) for the treatment of brain metastases from lung cancer. METHODS: Between February 1993 and May 2003 191 patients underwent treatment for 424 brain metastases from non-small (171 cases) and small cell lung carcinoma (20 cases). Imaging and clinical status were monitored every 3 months following the treatment. Kaplan-Meier survival curves, Cox proportional hazards regression for risk factor analysis, and nonparametric methods for evaluating tumor response were used. There was no difference in median survival following combined whole-brain radiation therapy (WBRT) and gamma knife surgery (14 months) and GKS alone (15 months). There was also no difference between the median survival rates for either tumor type. In the multivariate analysis, age less than 65 years, Karnofsky Performance Scale score greater than 70, normal neurological status, multiple GKS treatments, and pre-GKS craniotomy were related to longer survival. Tumor control rates varied according to the volume of the metastases and were as follows: 84.4% (< 0.5 cm3), 94% (0.5-2 cm3), 89.1% (2-4 cm3), 93.4% (4-8 cm3), 85.7% (8-14 cm3), and 87.5% (> 14 cm3). Four lesions required post-GKS craniotomy due to swelling or rapid tumor progression. The rate of tumor shrinkage was higher when a volume was 2 cm3, lower in cystic lesions, lower in tumors with previous WBRT, and lower for margin doses less than 14 Gy. CONCLUSIONS: The risk-benefit ratio of GKS in this series was satisfactory. There was no difference in response rates of the two tumor types, and WBRT did not improve the duration of survival.

Gamma knife surgery for trigeminal neuralgia: outcomes and prognostic factors.

OBJECT: Microvascular decompression (MVD) and percutaneous ablation surgery have historically been the treatments of choice for medically refractory trigeminal neuralgia (TN). Gamma knife surgery (GKS) has been used as an alternative, minimally invasive treatment in TN. In the present study, the authors evaluated the long-term results of GKS in the treatment of TN. METHODS: From 1996 to 2003, 151 cases of TN were treated with GKS. In this group, radiosurgery was performed once in 136 patients, twice in 14 patients, and three times in one patient. The types of TN were as follows: 122 patients with typical TN, three with atypical TN, four with multiple sclerosis-associated TN, and seven with TN and a history of a cavernous sinus tumor. In each case, the chosen radiosurgical target was located 2 to 4 mm anterior to the entry of the trigeminal nerve into the pons. The maximal radiation doses ranged from 50 to 90 Gy. The median age of the patients was 68 years (range 22-90 years), and the median time from diagnosis to GKS was 72 months (range 1-276 months). The median follow up was 19 months (range 2-96 months). Clinical outcomes and postradiosurgical magnetic resonance (MR) imaging studies were analyzed. Univariate and multivariate analyses were performed to evaluate factors that correlated with a favorable, pain-free outcome. The mean time to relief of pain was 24 days (range 1-180 days). Forty-seven, 45, and 34% of patients were pain free without medication at the 1-, 2-, and 3-year follow ups, respectively. Ninety, 77, and 70% of patients experienced some improvement in pain at the 1-, 2-, and 3-year follow ups, respectively. Thirty-three (27%) of 122 patients with initial improvement subsequently experienced pain recurrence a median of 12 months (range 2-34 months) post-GKS. Among those whose symptoms recurred, 14 patients underwent additional GKS, six MVD, four glycerol injection, and one patient a percutaneous radiofrequency rhizotomy. Twelve patients (9%) suffered the onset of new facial numbness post-GKS. Changes on MR images post-GKS were noted in nine patients (7%). On univariate analysis, right-sided neuralgia (p = 0.0002) and a previous neurectomy (p = 0.04) correlated with a pain-free outcome; on multivariate analysis, both rightsided neuralgia (p = 0.032) and patient age (p = 0.05) were statistically significant. New onset of facial numbness following GKS correlated with undergoing more than one GKS (p = 0.002). CONCLUSIONS: At the last follow up, GKS effected pain relief in 44% of patients. Some degree of pain improvement at 3 years post-GKS was noted in 70% of patients with TN. Although less effective than MVD, GKS remains a reasonable treatment option for those unwilling or unable to undergo more invasive surgical approaches and offers a low risk of side effects.

Gamma knife surgery for the treatment of intracranial metastases from breast cancer.

OBJECT: The goal of this study was to evaluate the effectiveness and limitations of gamma knife surgery (GKS) in the treatment of intracranial breast carcinoma lesions. METHODS: A retrospective analysis of the GKS database at the University of Virginia Health System identified 43 patients with a total of 84 lesions who were treated between 1989 and 2000. All patients who received treatment were included in this study. Imaging studies were available in 35 patients with 67 treated lesions. The overall duration of median survival was 13 months (95% confidence interval [CI] 7-16 months) after radiosurgery. A univariable Cox regression analysis revealed that a single lesion (p = 0.035), a high Karnofsky Performance Scale (KPS) score (p = 0.019), and a high Score Index for Radiosurgery (SIR) in Brain Metastases (p = 0.036) were associated with a significantly lengthened time to local treatment failure. The median duration of survival for patients grouped according to the SIR as low, middle, and high was 3, 8, and 21 months, respectively (p = 0.00033). A multivariable analysis showed that a high KPS score (p = 0.006), a high SIR (p = 0.014), and advanced age (0.038) were predictive of survival. The 1-, 2-, 3-, and 5-year survival rates were 49, 23, 12, and 2%, respectively. The overall median time to local treatment failure was 10 months (95% CI 6-14 months) after GKS. A univariable analysis demonstrated that a single lesion, higher KPS score, and a higher SIR were associated with a significantly longer time until local treatment failure. A multivariable analysis showed that a higher KPS score and SIR and patients who had received chemotherapy were associated with a significantly longer time to local treatment failure. Neuroimaging scores given for the enhancement pattern (ring-enhancing, heterogeneous, and homogeneous signal), amount of necrosis (none, < 50%, and > 50%), and mass effect (none, mild, moderate, and severe) of each treated lesion did not correlate with survival or local treatment failure. CONCLUSIONS: The SIR and the KPS score are prognostic factors in patients whose intracranial breast cancer metastases are treated with GKS. The SIR, which includes the KPS score, patient age, systemic disease status, largest lesion volume, and number of lesions, can be used to identify those patients with breast cancer metastasis who would benefit from GKS better than KPS score alone. The contribution of whole-brain radiation therapy to GKS with regard to local tumor control or survival could not be identified.

Gamma surgery for melanoma metastases in the brain.

OBJECT: The aim of this study was to evaluate the usefulness and limitations of gamma surgery (GS) in the treatment of brain metastases from melanoma. METHODS: Imaging and clinical outcomes in 45 patients treated for 92 brain metastases from melanoma between October 1989 and October 1999 were retrospectively analyzed. Follow-up imaging studies were available in 35 patients with 66 treated lesions. Twenty-four percent of the lesions disappeared, 35% shrank, 23% remained unchanged, and 18% increased in size. No undue radiation-induced changes were observed in the surrounding brain. Clinical data were available in all patients. No deaths or neurological morbidity related to GS was observed. The median survival time, calculated using the Kaplan-Meier method, was 10.4 months from the time of GS. In both univariate and multivariate Cox regression analyses, a single brain lesion and lack of visceral metastases were statistically predictive of a better prognosis. Six of eight patients with solitary metastasis (that is, a single brain metastasis with no primary visceral tumor) were still alive at the close of the study, none of them with disease progression, with a follow-up period ranging between 14 and 82 months. Sixteen patients in this series received adjunctive whole-brain radiation therapy, which had no impact on their survival time or local and distant control of the brain disease. CONCLUSIONS: Gamma surgery is effective in treating melanoma metastases in the brain. It appears that the radiobiology of a single high dose overcomes the radioresistance barrier, yielding better results than fractionated radiation.

Long-term results of gamma knife surgery for partially embolized arteriovenous malformations.

BACKGROUND: The effectiveness and risk of gamma knife surgery (GKS) in the management of partially embolized cerebral arteriovenous malformations (AVMs) remain to be elucidated. OBJECTIVE: To evaluate the long-term imaging and clinical outcomes of GKS in AVM patients who had undergone previous partial embolization and compare the results with patients treated with GKS alone. METHODS: A total of 215 embolized AVMs were analyzed. The mean patient age was 32.9 years. The mean volume of the nidus was 4.6 mL (range, 0.1-29.4 mL), and the mean prescription dose was 19.6 Gy (range, 4-28 Gy). This group was compared with 729 nonembolized AVMs. RESULTS: After embolization and GKS, angiographically confirmed total obliteration of the AVMs was significantly lower (33%) compared with patients in whom GKS was used alone (60.9%; P < .001). However, the mean nidus size was larger and the Spetzler-Martin grade was higher for the embolized AVMs compared with the nonembolized AVMs. Radiation-induced changes occurred more often in the embolized (43.4%) than the nonembolized (33.4%) AVMs (P = .028). Permanent neurological deficits associated with radiation-induced changes occurred in 2.7% of the embolized compared with 1.3% of the nonembolized patients (P = .14). CONCLUSION: In our retrospective and historical series, the long-term results suggest that the obliteration rate is significantly lower in embolized AVMs compared with nonembolized AVMs, also because of the fact that the combined treatment is applied to higher grade AVMs; the percentage of grade III-V AVMs was 58.6% and 48.8% for nonembolized AVMs.

Gamma knife surgery for brainstem arteriovenous malformations.

OBJECTIVE: To evaluate the long-term imaging and clinical outcomes of patients with brainstem arteriovenous malformations (AVMs) treated with Gamma Knife surgery (GKS). METHODS: The study included 85 patients with brainstem AVMs undergoing GKS during the period 1989-2007. The locations of the nidi were the midbrain in 42 patients, pons in 31 patients, and medulla oblongata in 12 patients. The volume of the nidi ranged from 0.1-8.9 mL (median 1.4 mL, mean 1.9 mL), and the prescription dose ranged from 5-32 Gy (median 20 Gy, mean 19.9 Gy). After the initial Gamma procedure, 18 patients had repeat GKS for AVM residuals that were still patent. Two patients had a third GKS 7 years and 16 years after a failed repeat GKS. Clinical follow-up ranged from 24-252 months with a mean of 100 months (median 102 months) after the initial GKS. RESULTS: GKS yielded a total angiographic obliteration in 50 (58.8%) patients and subtotal obliteration in 4 (4.7%) patients. In 22 (25.9%) patients, the AVMs remained patent. In 9 patients (10.6%), no flow voids were observed on magnetic resonance imaging (MRI), but angiographic confirmation was unavailable. A small nidus volume and a high prescription dose were significantly associated with increased AVM obliteration rate. Radiation-induced changes developed in 34 patients (40%); 24 were asymptomatic, 1 patient had only headache, and 9 patients developed neurologic deficits. One patient developed a large cyst 6 years after GKS. CONCLUSIONS: Given the poor surgical outcome of brainstem AVMs, the results of 59% nidus obliteration and 6% permanent neurologic deficits make GKS a reasonable management of these difficult lesions.

Gamma Knife surgery for pituitary adenomas: factors related to radiological and endocrine outcomes.

OBJECT: Gamma Knife surgery (GKS) is a common treatment for recurrent or residual pituitary adenomas. This study evaluates a large cohort of patients with a pituitary adenoma to characterize factors related to endocrine remission, control of tumor growth, and development of pituitary deficiency. METHODS: A total of 418 patients who underwent GKS with a minimum follow-up of 6 months (median 31 months) and for whom there was complete follow-up were evaluated. Statistical analysis was performed to evaluate for significant factors (p < 0.05) related to treatment outcomes. RESULTS: In patients with a secretory pituitary adenoma, the median time to endocrine remission was 48.9 months. The tumor margin radiation dose was inversely correlated with time to endocrine remission. Smaller adenoma volume correlated with improved endocrine remission in those with secretory adenomas. Cessation of pituitary suppressive medications at the time of GKS had a trend toward statistical significance in regard to influencing endocrine remission. In 90.3% of patients there was tumor control. A higher margin radiation dose significantly affected control of adenoma growth. New onset of a pituitary hormone deficiency following GKS was seen in 24.4% of patients. Treatment with pituitary hormone suppressive medication at the time of GKS, a prior craniotomy, and larger adenoma volume at the time of radiosurgery were significantly related to loss of pituitary function. CONCLUSIONS: Smaller adenoma volume improves the probability of endocrine remission and lowers the risk of new pituitary hormone deficiency with GKS. A higher margin dose offers a greater chance of endocrine remission and control of tumor growth.