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William J. Triffo, J. Daniel Bourland, Daniel E. Couture, Kevin P. McMullen, Stephen B. Tatter, and Padraig P. Morris

Vein of Galen aneurysmal malformations (VGAMs) are uncommon congenital malformations arising from fistulous communication with the median vein of the prosencephalon, a primitive precursor of midline cerebral venous structures. Angiographic embolization is the primary modality for treatment given historically poor microsurgical outcomes. Only a few reports of treatment by Gamma Knife radiosurgery (GKRS) exist in the literature, and the results are variable. The authors present 2 cases of VGAM in which GKRS provided definitive treatment with good outcome: one case involving antenatal presentation of a high-output, mural-type VGAM with complex clinical course refractory to multiple embolic procedures, and the other a choroidal-type VGAM presenting with hemorrhage in an adult and without a feasible embolic approach. With discussion of these cases and review of the literature, the authors advocate inclusion of GKRS as a therapeutic option for treatment of these complex lesions.

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D. Clay Cochran, Michael D. Chan, Mebea Aklilu, James F. Lovato, Natalie K. Alphonse, J. Daniel Bourland, James J. Urbanic, Kevin P. McMullen, Edward G. Shaw, Stephen B. Tatter, and Thomas L. Ellis

Object

Gamma Knife surgery (GKS) has been reported as an effective modality for treating brain metastases from renal cell carcinoma (RCC). The authors aimed to determine if targeted agents such as tyrosine kinase inhibitors, mammalian target of rapamycin inhibitors, and bevacizumab affect the patterns of failure of RCC after GKS.

Methods

Between 1999 and 2010, 61 patients with brain metastases from RCC were treated with GKS. A median dose of 20 Gy (range 13–24 Gy) was prescribed to the margin of each metastasis. Kaplan-Meier analysis was used to determine local control, distant failure, and overall survival rates. Cox proportional hazard regression was performed to determine the association between disease-related factors and survival.

Results

Overall survival at 1, 2, and 3 years was 38%, 17%, and 9%, respectively. Freedom from local failure at 1, 2, and 3 years was 74%, 61%, and 40%, respectively. The distant failure rate at 1, 2, and 3 years was 51%, 79%, and 89%, respectively. Twenty-seven percent of patients died of neurological disease. The median survival for patients receiving targeted agents (n = 24) was 16.6 months compared with 7.2 months (n = 37) for those not receiving targeted therapy (p = 0.04). Freedom from local failure at 1 year was 93% versus 60% for patients receiving and those not receiving targeted agents, respectively (p = 0.01). Multivariate analysis showed that the use of targeted agents (hazard ratio 3.02, p = 0.003) was the only factor that predicted for improved survival. Two patients experienced post-GKS hemorrhage within the treated volume.

Conclusions

Targeted agents appear to improve local control and overall survival in patients treated with GKS for metastastic RCC.

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Paul K. Kim, Thomas L. Ellis, Volker W. Stieber, Kevin P. McMullen, Edward G. Shaw, Thomas P. McCoy, Ralph B. D'Agostino, J. Daniel Bourland, Allan F. deGuzman, Kenneth E. Ekstrand, Michael R. Raber, and Stephen B. Tatter

Object

Salvage treatment of large, symptomatic brain metastases after failure of whole-brain radiotherapy (WBRT) remains challenging. When these lesions require resection, there are few options to lower expected rates of local recurrence at the resection cavity margin. The authors describe their experience in using Gamma Knife surgery (GKS) to target the resection cavity in patients whose tumors had progressed after WBRT.

Methods

The authors retrospectively identified 143 patients in whom GKS had been used to target a brain metastasis resection cavity between 2000 and 2005. Seventy-nine of these patients had undergone WBRT prior to resection and GKS. The median patient age was 53 years, and the median prescribed dose was 18 Gy (range 8–24 Gy), with resection cavities of relatively larger volume (> 15 cm3). The GKS dose was prescribed at the 40 to 95% isodose contour (mode 50%).

Local recurrence within 1 cm of the treatment volume occurred in four (5.1%) of 79 cases. The median duration of time to local recurrence was 6.1 months (range 2–13 months). The median duration of time to occurrence of distant metastases following GKS of the resection cavity was 10.8 months (range 2–86 months). Carcinomatous meningitis developed in four (5.1%) of 79 cases. Symptomatic radionecrosis requiring surgical treatment occurred in three (3.8%) of 79 cases. The median duration of survival following GKS of the resection cavity was 69.6 weeks. The median 2- and 5-year survival rates were 20.2 and 6.3%, respectively.

Conclusions

When metastases progress after WBRT and require resection, GKS targeting the resection cavity is a viable strategy. In 75 (94.9%) of 79 cases, GKS of the resection cavity in patients in whom WBRT had failed appears to have achieved its goal of local disease control.

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Courtney A. Jensen, Michael D. Chan, Thomas P. McCoy, J. Daniel Bourland, Allan F. deGuzman, Thomas L. Ellis, Kenneth E. Ekstrand, Kevin P. McMullen, Michael T. Munley, Edward G. Shaw, James J. Urbanic, and Stephen B. Tatter

Object

As a strategy to delay or avoid whole-brain radiotherapy (WBRT) after resection of a brain metastasis, the authors used high-resolution MR imaging and cavity-directed radiosurgery for the detection and treatment of further metastases.

Methods

Between April 2001 and October 2009, 112 resection cavities in 106 patients with no prior WBRT were treated using radiosurgery directed to the tumor cavity and for any synchronous brain metastases detected on high-resolution MR imaging at the time of radiosurgical planning. A median dose of 17 Gy to the 50% isodose line was prescribed to the gross tumor volume, defined as the rim of enhancement around the resection cavity. Patients were followed up via serial imaging, and new brain metastases were generally treated using additional radiosurgery, with salvage WBRT typically reserved for local treatment failure at a resection cavity, numerous failures, or failures occurring at short time intervals. Local and distant treatment failures were determined based on imaging results. Kaplan-Meier curves were generated to estimate local and distant treatment failure rates, overall survival, neurological cause–specific survival, and time delay to salvage WBRT.

Results

Radiosurgery was delivered to the resection cavity alone in 57.5% of patients, whereas 24.5% of patients also received treatment for 1 synchronous metastasis, 11.3% also received treatment for 2 synchronous metastases, and 6.6% also received treatment for 3–10 additional lesions. The median overall survival was 10.9 months. Overall survival at 1 year was 46.8%. The local tumor control rate at 1 year was 80.3%. The disease control rate in distant regions of the brain at 1 year was 35.4%, with a median time of 6.9 months to distant failure. Thirty-nine of 106 patients eventually received salvage WBRT, and the median time to salvage WBRT was 12.6 months. Kaplan-Meier estimates showed that the rate of requisite WBRT at 1 year was 45.9%. Neurological cause–specific survival at 1 year was 50.1%. Leptomeningeal failure occurred in 8 patients. One patient had treatment failure within the resection tract. Seven patients required reoperation: 2 for resection cavity recurrence, 3 for radiation necrosis, 1 for hydrocephalus, and 1 for a CSF cutaneous fistula. On multivariate analysis, a preoperative tumor diameter > 3 cm was predictive of local treatment failure.

Conclusions

Cavity-directed radiosurgery combined with high-resolution MR imaging detection and radiosurgical treatment of synchronous brain metastases is an effective strategy for delaying and even foregoing WBRT in most patients. This technique provides acceptable local disease control, although distant treatment failure remains significant.

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Christopher J. Balamucki, Volker W. Stieber, Thomas L. Ellis, Stephen B. Tatter, Allan F. DeGuzman, Kevin P. McMullen, James Lovato, Edward G. Shaw, Kenneth E. Ekstrand, J. Daniel Bourland, Michael T. Munley, Michael Robbins, and Charles Branch

Object

Gamma Knife surgery (GKS) is a treatment option for patients with refractory typical trigeminal neuralgia (TN), TN with atypical features, and atypical types of facial pain. The Gamma Knife’s 201 60Co sources decay with a half-life of 5.26 years. The authors examined whether the decrease in dose rate over 4.6 years between Co source replacements affected the control rates of facial pain in patients undergoing GKS.

Methods

The authors collected complete follow-up data on 239 of 326 GKS procedures performed in patients with facial pain. Patients were classified by their type of pain. The isocenter of a 4-mm collimator helmet was targeted at the proximal trigeminal nerve root, and the dose (80–90 Gy) was prescribed at the 100% isodose line. Patients reported the amount of pain control following radiosurgery by answering a standardized questionnaire.

Eighty percent of patients experienced greater than 50% pain relief, and 56% of patients experienced complete pain relief after GKS. Neither dose rate nor treatment time was significantly associated with either the control rate or degree of pain relief. A significant association between the type of facial pain and the pain control rate after GKS was observed (p < 0.001; Pearson chi-square test).

In their statistical analysis, the authors accounted for changes in prescription dose over time to prevent the dose rate from being a confounding variable. There was no observable effect of the dose rate or of the treatment duration within the typical period to source replacement.

Conclusions

Patients with facial pain appear to receive consistent treatment with GKS at any time during the first half-life of the Co sources.