James Nguyen

Gamma Knife surgery for skull base meningiomas

OBJECT Skull base meningiomas are challenging tumors owing in part to their close proximity to important neurovascular structures. Complete microsurgical resection can be associated with significant morbidity, and recurrence rates are not inconsequential. In this study, the authors evaluate the outcomes of skull base meningiomas treated with Gamma Knife surgery (GKS) both as an adjunct to microsurgery and as a primary treatment modality. METHODS The authors performed a retrospective review of a prospectively compiled database detailing the outcomes in 255 patients with skull base meningiomas treated at the University of Virginia from 1989 to 2006. All patients had a minimum follow-up of 24 months. The group comprised 54 male and 201 female patients, with a median age of 55 years (range 19-85 years). One hundred nine patients were treated with upfront radiosurgery, and 146 patients were treated with GKS following resection. Patients were assessed clinically and radiographically at routine intervals following GKS. Factors predictive of new neurological deficit following GKS were assessed via univariate and multivariate analysis, and Kaplan-Meier analysis and Cox multivariate regression analysis were used to assess factors predictive of tumor progression. RESULTS Meningiomas were centered over the cerebellopontine angle in 43 patients (17%), the clivus in 40 (16%), the petroclival region in 28 (11%), the petrous region in 6 (2%), and the parasellar region in 138 (54%). The median duration of follow-up was 6.5 years (range 2-18 years). The mean preradiosurgery tumor volume was 5.0 cm(3) (range 0.3-54.8 cm(3)). At most recent follow-up, 220 patients (86%) displayed either no change or a decrease in tumor volume, and 35 (14%) displayed an increase in volume. Actuarial progression-free survival at 3, 5, and 10 years was 99%, 96%, and 79%, respectively. In Cox multivariate analysis, pre-GKS covariates associated with tumor progression included age greater then 65 years (HR 3.41, 95% CI 1.63-7.13, p = 0.001) and decreasing dose to tumor margin (HR 0.90, 95% CI 0.80-1.00, p = 0.05). At most recent clinical follow-up, 230 patients (90%) demonstrated no change or improvement in their neurological condition and the condition of 25 patients had deteriorated (10%). In multivariate analysis, the factors predictive of new or worsening symptoms were increasing duration of follow-up (OR 1.01, 95% CI 1.00-1.02, p = 0.015), tumor progression (OR 2.91, 95% CI 1.60-5.31, p < 0.001), decreasing maximum dose (OR 0.90, 95% CI 0.84-0.97, p = 0.007), and petrous or clival location versus parasellar, petroclival, and cerebellopontine angle location (OR 3.47, 95% CI 1.23-9.74, p = 0.018). CONCLUSIONS Stereotactic radiosurgery offers a high rate of tumor control and neurological preservation in patients with skull base meningiomas. After radiosurgery, better outcomes were observed for those receiving an optimal radiosurgery dose and harboring tumors located in a cerebellopontine angle, parasellar, or petroclival location.

Treatment of glomus jugulare tumors with gamma knife radiosurgery.

Surgical resection, preoperative embolization, radiation therapy, and stereotactic radiosurgery have been used to treat glomus jugulare tumors (GJT). However, the optimal treatment of these tumors remains unclear. The authors report their data on treatment of GJTs with gamma knife radiosurgery (GKS).

Gamma Knife surgery for arteriovenous malformations in children.

OBJECT The aim of this study was to evaluate the long-term imaging and clinical outcomes of intracranial arteriovenous malformations (AVMs) in children treated with Gamma Knife surgery (GKS). METHODS Between 1989 and 2007, 200 patients with AVMs who were 18 years of age or younger were treated at the University of Virginia Health System. Excluding 14 patients who had not reached 2-year follow-up, 186 patients comprised this study. Hemorrhage was the most common presenting symptom leading to the diagnosis of AVMs (71.5%). The mean nidus volume was 3.2 cm(3) at the time of GKS, and a mean prescription dose of 21.9 Gy was used. RESULTS After initial GKS, 49.5% of patients achieved total angiographic obliteration. Forty-one patients whose AVM nidi remained patent underwent additional GKS. The obliteration rate increased to 58.6% after a second or multiple GKS. Subtotal obliteration was achieved in 9 patients (4.8%). Forty-nine patients (26.3%) still had a patent residual nidus. In 19 patients (10.2%), obliteration was confirmed on MR imaging only. Ten patients had 17 hemorrhages during the follow-up period. The hemorrhage rate was 5.4% within 2 years after GKS and 0.8% between 2 and 5 years. Six patients developed neurological deficits along with the radiation-induced changes. Two patients developed asymptomatic meningiomas 10 and 12 years after GKS. After a mean clinical follow-up of 98 months, less than 4% of patients had difficulty attending school or developing a career. CONCLUSIONS Gamma Knife surgery offers a reasonable chance of obliteration of an AVM in pediatric patients. The incidence of symptomatic radiation-induced changes is relatively low; however, long-term clinical and imaging follow-up is required to identify delayed cyst formation and secondary tumors.

Gamma Knife surgery for parasellar meningiomas: long-term results including complications, predictive factors, and progression-free survival.

OBJECT Stereotactic radiosurgery serves as an important primary and adjuvant treatment option for patients with many types of intracranial meningiomas. This is particularly true for patients with parasellar meningiomas. In this study, the authors evaluated the outcomes of Gamma Knife surgery (GKS) used to treat parasellar meningiomas. METHODS The study is a retrospective review of the outcomes in 138 patients with meningiomas treated at the University of Virginia from 1989 to 2006; all patients had a minimum follow-up of 24 months. There were 31 men and 107 women whose mean age was 54 years (range 19-85 years). Eighty-four patients had previously undergone resection. The mean pre-GKS tumor volume was 7.5 ml (range 0.2-54.8 ml). Clinical and radiographic evaluations were performed, and factors related to favorable outcomes in each case were assessed. RESULTS The mean follow-up duration was 84 months (median 75.5 months, range 24-216 months). In 118 patients (86%), the tumor volume was unchanged or had decreased at last follow-up. Kaplan-Meier analysis demonstrated radiographic progression-free survival at 5 and 10 years to be 95.4% and 69%, respectively. Fourteen patients (10%) developed new cranial nerve palsies following GKS. Factors associated with tumor control included younger age, a higher isodose, and smaller tumor volume. A longer follow-up duration was associated with either a decrease or increase in tumor volume. Fourteen patients (10%) experienced new or worsening cranial nerve deficits after treatment. Factors associated with this occurrence were larger pretreatment tumor volume, lower peripheral radiation dose, lower maximum dose, tumor progression, and longer follow-up. CONCLUSIONS Gamma Knife surgery offers an acceptable rate of tumor control for parasellar meningiomas and accomplishes this with a low incidence of neurological deficits. Radiological control after radiosurgery is more likely in those patients with a smaller tumor volume and a higher prescription dose.

Gamma Knife surgery of meningiomas located in the posterior fossa: factors predictive of outcome and remission

OBJECT Although numerous studies have analyzed the role of stereotactic radiosurgery for intracranial meningiomas, few studies have assessed outcomes of posterior fossa meningiomas after stereotactic radiosurgery. In this study, the authors evaluate the outcomes of posterior fossa meningiomas treated with Gamma Knife surgery (GKS). The authors also assess factors predictive of new postoperative neurological deficits and tumor progression. METHODS A retrospective review was performed of a prospectively compiled database documenting the outcomes of 152 patients with posterior fossa meningiomas treated at the University of Virginia from 1990 to 2006. All patients had a minimum follow-up of 24 months. There were 30 males and 122 females, with a median age of 58 years (range 12-82 years). Seventy-five patients were treated with radiosurgery initially, and 77 patients were treated with GKS after resection. Patients were assessed clinically and radiographically at routine intervals following GKS. Factors predictive of new neurological deficit following GKS were assessed via univariate and multivariate analysis, and Kaplan-Meier analysis and Cox multivariate regression analysis were used to assess factors predictive of tumor progression. RESULTS Patients had meningiomas centered over the tentorium (35 patients, 23%), cerebellopontine angle (43 patients, 28%), petroclival region (28 patients, 18%), petrous region (6 patients, 4%), and clivus (40 patients, 26%). The median follow-up was 7 years (range 2-16 years). The mean preradiosurgical tumor volume was 5.7 cm(3) (range 0.3-33 cm(3)), and mean postradiosurgical tumor volume was 4.9 cm(3) (range 0.1-33 cm(3)). At last follow-up, 55 patients (36%) displayed no change in tumor volume, 78 (51%) displayed a decrease in volume, and 19 (13%) displayed an increase in volume. Kaplan-Meier analysis demonstrated radiographic progression-free survival at 3, 5, and 10 years to be 98%, 96%, and 78%, respectively. In Cox multivariable analysis, pre-GKS covariates associated with tumor progression included age greater than 65 years (hazard ratio [HR] 3.24, 95% CI 1.12-9.37; p = 0.03) and a low dose to the tumor margin (HR 0.76, 95% CI 0.60-0.97; p = 0.03), and post-GKS covariates included shunt-dependent hydrocephalus (HR 25.0, 95% CI 3.72-100.0; p = 0.001). At last clinical follow-up, 139 patients (91%) demonstrated no change or improvement in their neurological condition, and 13 patients showed symptom deterioration (9%). In multivariate analysis, the only factors predictive of new or worsening symptoms were clival or petrous location (OR 4.0, 95% CI 1.1-13.7; p = 0.03). CONCLUSIONS Gamma Knife surgery offers an acceptable rate of tumor control for posterior fossa meningiomas and accomplishes this with a low incidence of neurological deficits. In patients selected for GKS, tumor progression is associated with age greater than 65 years and decreasing dose to the tumor margin. Clival- or petrous-based locations are predictive of an increased risk of new or worsening neurological deficit following GKS.

Gamma Knife Radiosurgery for Intracranial Hemangioblastomas—Outcome at 3 Years

OBJECT To define the role of Gamma Knife radiosurgery (GKRS) for the treatment of patients with hemangioblastomas. METHODS Between 1992 and 2009, 26 hemangioblastomas in 14 patients (9 female and 5 male) were treated with GKRS. Mean age of patients at the time of treatment was 45.1 years (range 25-61). von Hippel-Lindau disease was established in 7 patients, and 7 patients had sporadic hemangioblastomas. Twenty-one tumors were solid, 4 were cystic, and 1 had both components. Four patients were treated with upfront radiosurgery, and 10 were treated following a resection. Mean tumor volume was 1.65 cm3 (range 0.08-9.02, median 1.1 cm3). Mean dose to the tumor margin was 18 Gy (range 10-25, median 18). Patients were assessed clinically and radiologically at 6- to 12-month intervals following GKRS. The median follow-up was 3 years (range 0.5-12 years). Kaplan-Meier analysis was used to assess factors predictive of tumor progression, and factors predictive in univariate analysis (P < 0.10) were entered into Cox multivariate regression analysis. RESULTS On follow-up, 4 tumors were stable in volume (15%), 14 decreased (54%), and 8 increased (31%). Local tumor control rates at 1, 5, and 10 years was 89%, 74%, and 50%, respectively. There was a trend toward tumor progression in sporadic patients (P = 0.10), women (P = 0.09), and larger tumors (P = 0.10). In patients with multiple hemangioblastomas as compared to those with only a solitary hemangioblastoma, the radiosurgically treated lesion was 7.9 times more likely to progress after GKRS treatment (P = 0.018). This remained the only significant predictor in multivarialble analysis. At the last clinical follow-up, seven patients showed no change or improvement in their symptoms and seven deteriorated. CONCLUSION Stereotactic radiosurgery offers a reasonable rate of tumor control and preservation of neurologic function in patients with hemangioblastomas. Patients with multiple hemangioblastomas are less likely to exhibit long-term tumor control of treated lesions following radiosurgery.

Gamma Knife radiosurgery of large skull base meningiomas

OBJECT Stereotactic radiosurgery (SRS) has become a common treatment modality for intracranial meningiomas. Skull base meningiomas greater than 8 cm3 in volume have been found to have worse outcomes following SRS. When symptomatic, patients with these tumors are often initially treated with resection. For tumors located in close proximity to eloquent structures or in patients unwilling or unable to undergo a resection, SRS may be an acceptable therapeutic approach. In this study, the authors review the SRS outcomes of skull base meningiomas greater than 8 cm3 in volume, which corresponds to a lesion with an approximate diameter of 2.5 cm. METHODS The authors reviewed the data in a prospectively compiled database documenting the outcomes of 469 patients with skull base meningiomas treated with single-session Gamma Knife radiosurgery (GKRS). Seventy-five patients had tumors greater than 8 cm3 in volume, which was defined as a large tumor. All patients had a minimum follow-up of 6 months, but patients were included if they had a complication at any time point. Thirty patients were treated with upfront GKRS, and 45 were treated following microsurgery. Patient and tumor characteristics were assessed to determine predictors of new or worsening neurological function and tumor progression following GKRS. RESULTS After a mean follow-up of 6.5 years (range 0.5-21 years), the tumor volume was unchanged in 37 patients (49%), decreased in 26 patients (35%), and increased in 12 patients (16%). Actuarial rates of progression-free survival at 3, 5, and 10 years were 90.3%, 88.6%, and 77.2%, respectively. Four patients had new or worsened edema following GKRS, but preexisting edema decreased in 3 patients. In Cox multivariable analysis, covariates associated with tumor progression were 1) presentation with any cranial nerve (CN) deficit from III to VI (hazard ratio [HR] 3.78, 95% CI 1.91-7.45; p<0.001), history of radiotherapy (HR 12.06, 95% CI 2.04-71.27; p=0.006), and tumor volume greater than 14 cm3 (HR 6.86, 95% CI 0.88-53.36; p=0.066). In those patients with detailed clinical follow-up (n=64), neurological function was unchanged in 37 patients (58%), improved in 16 patients (25%), and deteriorated in 11 patients (17%). In multivariate analysis, the factors predictive of new or worsening neurological function were history of surgery (OR 3.00, 95% CI 1.13-7.95; p=0.027), presentation with any CN deficit from III to VI (OR 3.94, 95% CI 1.49-10.24; p=0.007), and decreasing maximal dose (OR 0.76, 95% CI 0.63-0.93; p=0.007). Tumor progression was present in 64% of patients with new or worsening neurological decline. CONCLUSIONS Stereotactic radiosurgery affords a reasonable rate of tumor control for large skull base meningiomas and does so with a low incidence of neurological deficits. Those with a tumor less than 14 cm3 in volume and without presenting CN deficit from III to VI were more likely to have effective tumor control.

Timing and risk factors for new brain metastasis formation in patients initially treated only with Gamma Knife surgery. Clinical article.

OBJECT Stereotactic radiosurgery has been shown to afford a reasonable chance of local tumor control. However, new brain metastasis can arise following successful local tumor control from radiosurgery. This study evaluates the timing, number, and risk factors for development of subsequent new brain metastasis in a group of patients treated with stereotactic radiosurgery alone. METHODS One hundred seventeen patients with histologically confirmed metastatic cancer underwent Gamma Knife surgery (GKS) to treat all brain metastases demonstrable on MR imaging. Patients were followed clinically and radiologically at approximately 3-month intervals for a median of 14.4 months (range 0.37-51.8 months). Follow-up MR images were evaluated for evidence of new brain metastasis formation. Statistical analyses were performed to determine the timing, number, and risk factors for development of new brain metastases. RESULTS The median time to development of a new brain metastasis was 8.8 months. Patients with 3 or more metastases at the time of initial radiosurgery or those with cancer histologies other than non-small cell lung carcinoma were found to be at increased risk for early formation of new brain metastasis (p < 0.05). The mean number of new metastases per patient was 1.6 (range 0-11). Those with a higher Karnofsky Performance Scale score at the time of initial GKS were significantly more likely to develop a greater number of brain metastases by the last follow-up evaluation. CONCLUSIONS The timing and number of new brain metastases developing in patients treated with GKS alone is not inconsequential. Those with 3 or more metastases at the time of radiosurgery and those with cancer histology other than non-small cell lung carcinoma were at greater risk of early formation of new brain metastasis. Frequent follow-up evaluations, such as at 3-month intervals, appears appropriate in this patient population, particularly in high-risk patients. When detected early, salvage treatments including repeat radiosurgery can be used to treat new brain metastasis.

Temozolomide-induced inhibition of pituitary adenoma cells

OBJECT Aggressive pituitary adenomas frequently require multimodality treatment including pituitary-suppressive medications, microsurgery, and radiation therapy or radiosurgery. The effectiveness of temozolomide in terms of growth suppression and decreased hormonal production is evaluated. METHODS Three pituitary adenoma cell lines--MMQ, GH3, and AtT20--were used. A dose escalation of temozolomide was performed for each cell line, and inhibition of cell proliferation was assessed using an MTT assay. Concentrations of temozolomide that produced statistically significant inhibition of cell proliferation for each cell type were identified. Extent of apoptosis for each selected temozolomide concentration was studied using TUNEL staining. The effect of temozolomide on prolactin secretion in MMQ and GH3 cells was also measured via ELISA. RESULTS Significant inhibition of cell proliferation was noted for MMQ and GH3 cells at a concentration of 250 μM temozolomide. The AtT20 cells demonstrated statistically significant cell inhibition at a concentration of only 50 μM temozolomide (p < 0.05). Apoptosis significantly increased in all cell lines in as little as 24 hours of incubation at the respective temozolomide concentrations (p < 0.05). Prolactin secretion in the prolactin secreting MMQ and GH3 cell lines was inhibited by 250 μM temozolomide. CONCLUSIONS Temozolomide inhibits cell proliferation and induces apoptotic cell death in aggressive pituitary adenoma cells. A reduction in hormonal secretion in prolactinoma cells was also afforded by temozolomide. Temozolomide may prove useful in the multimodality management of aggressive pituitary adenomas.

Gamma knife radiosurgery of meningiomas involving the foramen magnum.

Background: Foramen magnum meningiomas represent a challenging clinical entity. Although resection is performed for those with a mass effect, complete resection is not always feasible. For some patients, stereotactic radiosurgery may be used as the primary treatment modality. We evaluatedthe long-term outcome of Gamma Knife radiosurgery (GKRS) for the treatment of patientswith a foramen magnum meningioma. Materials and Methods: Between 1991 and 2005, 222 patients with a meningioma in the posterior fossa were treated with GKRS at the University of Virginia. Of these patients, 5 had meningiomas involving the foramen magnum. At the time of GKRS, the median age of the patients was 60 years (range, 51–78). Three patients were treated with radiosurgery following an initial resection and 2 were treated with upfront radiosurgery. The patients were assessed clinically and radiologically at routine intervals following GKRS. Results: The median tumor volume was 6.8 cc (range 1.9–17 cc). The GKRS tumor received a marginal dose of 12 Gy (range 10–15), and the median number of isocenters was 5 (range 3–19). The mean follow-up was 6 years (range 4–13). One lesion increased in size following GKRS requiring a second treatment, resulting in size stabilization. At the time of the last follow-up, all meningiomas had either demonstrated no growth (n = 4) or reduction in size (n = 1). No patients experienced post-radiotherapy complications. Conclusions: GKRS affords a high rate of tumor control and preservation of neurologic function for patients with foramen magnum meningiomas. Further study of its role in the neurosurgical management of such patients seems warranted.