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Corbin A. Helis, Ryan T. Hughes, Michael T. Munley, J. Daniel Bourland, Travis Jacobson, John T. Lucas Jr., Christina K. Cramer, Stephen B. Tatter, Adrian W. Laxton and Michael D. Chan

OBJECTIVE

Gamma Knife radiosurgery (GKRS) is a commonly used procedure for medically refractory trigeminal neuralgia (TN), with repeat GKRS routinely done in cases of pain relapse. The results of a third GKRS in cases of further pain relapse have not been well described. In this study, the authors report the largest series of patients treated with a third GKRS for TN to date.

METHODS

Retrospective review of institutional electronic medical records and a GKRS database was performed to identify patients who had been treated with a third GKRS at the authors’ institution in the period from 2010 to 2018. Telephone interviews were used to collect long-term follow-up data. Pain outcomes were measured using the Barrow Neurological Institute (BNI) pain intensity scale, with a score ≤ IIIb indicating successful treatment.

RESULTS

Twenty-two nerves in 21 patients had sufficient follow-up to determine BNI pain score outcomes. Eighteen of 22 cases had a successful third GKRS, with a median durability of pain relief of 3.88 years. There was no significant difference in the durability of pain relief after a third GKRS compared with those of institutional historical controls of prior series of first and second GKRS procedures. Ten cases had new or worsening facial numbness, with 1 case being bothersome. Four cases of toxicity other than facial numbness were reported, including 1 case of corneal abrasions and possible neurotrophic keratopathy. No cases of anesthesia dolorosa were reported. No factors predicting treatment success or the durability of pain relief were identified. Nonnumbness toxicity was more common in those with a proximally placed shot at the third GKRS.

CONCLUSIONS

A third GKRS is an effective treatment option for TN patients who have pain relapse after repeat GKRS. Pain outcomes of a third GKRS are similar to those following a first or second GKRS. Toxicity is tolerable in patients with a distally placed shot at the third GKRS.

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Corbin A. Helis, Emory McTyre, Michael T. Munley, J. Daniel Bourland, John T. Lucas Jr., Christina K. Cramer, Stephen B. Tatter, Adrian W. Laxton and Michael D. Chan

OBJECTIVE

A small subset of patients with trigeminal neuralgia (TN) will experience bilateral symptoms. Treatment in these patients is controversial because the population is heterogeneous and patients may have nonvascular etiologies of their pain. This study reports treatment outcomes in the largest cohort of patients with bilateral TN who have undergone Gamma Knife radiosurgery (GKRS) to date.

METHODS

A retrospective chart review identified 51 individual nerves in 34 patients with bilateral TN who were treated with GKRS at the authors’ institution between 2001 and 2015, with 12 nerves in 11 patients undergoing repeat GKRS for recurrent or persistent symptoms. Long-term follow-up was obtained by telephone interview. Pain outcomes were measured using the Barrow Neurological Institute (BNI) pain scale, with BNI IIIb or better considered a successful treatment.

RESULTS

There was sufficient follow-up to determine treatment outcomes for 48 individual nerves in 33 patients. Of these nerves, 42 (88%) achieved at least BNI IIIb pain relief. The median duration of pain relief was 1.9 years, and 1-, 3-, and 5-year pain relief rates were 64%, 44%, and 44%, respectively. No patients experienced bothersome facial numbness, and 1 case of anesthesia dolorosa and 2 cases of corneal dryness were reported. Patients with a history of definite or possible multiple sclerosis were significantly more likely to experience BNI IV–V relapse. There was no statistically significant difference in treatment outcomes between patients in this series versus a large cohort of patients with unilateral TN treated at the authors’ institution. There was sufficient follow-up to determine treatment outcomes for 11 individual nerves in 10 patients treated with repeat GKRS. Ten nerves (91%) improved to at least BNI IIIb after treatment. The median duration of pain relief was 2.8 years, with 1-, 3-, and 5-year rates of pain relief of 79%, 53%, and 53%, respectively. There was no statistically significant difference in outcomes between initial and repeat GKRS. One case of bothersome facial numbness and 1 case of corneal dryness were reported, with no patients developing anesthesia dolorosa with retreatment.

CONCLUSIONS

GKRS is a safe, well-tolerated treatment for patients with medically refractory bilateral TN. Efficacy of treatment appears similar to that in patients with unilateral TN. GKRS can be safely repeated in this population if necessary.

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Will H. McKay, Emory R. McTyre, Catherine Okoukoni, Natalie K. Alphonse-Sullivan, Jimmy Ruiz, Michael T. Munley, Shadi Qasem, Hui-Wen Lo, Fei Xing, Adrian W. Laxton, Stephen B. Tatter, Kounosuke Watabe and Michael D. Chan

OBJECTIVE

There are a variety of salvage options available for patients with brain metastases who experience local failure after stereotactic radiosurgery (SRS). These options include resection, whole-brain radiation therapy, laser thermoablation, and repeat SRS. There is little data on the safety and efficacy of repeat SRS following local failure of a prior radiosurgical procedure. This study evaluates the clinical outcomes and dosimetric characteristics of patients who experienced tumor recurrence and were subsequently treated with repeat SRS.

METHODS

Between 2002 and 2015, 32 patients were treated with repeat SRS for local recurrence of ≥ 1 brain metastasis following initial SRS treatment. The Kaplan-Meier method was used to estimate time-to-event outcomes including overall survival (OS), local failure, and radiation necrosis. Cox proportional hazards analysis was performed for predictor variables of interest for each outcome. Composite dose-volume histograms were constructed for each reirradiated lesion, and these were then used to develop a predictive dosimetric model for radiation necrosis.

RESULTS

Forty-six lesions in 32 patients were re-treated with a second course of SRS after local failure. A median dose of 20 Gy (range 14–22 Gy) was delivered to the tumor margin at the time of repeat SRS. Local control at 1 year was 79% (95% CI 67%–94%). Estimated 1-year OS was 70% (95% CI 55%–88%). Twelve patients had died at the most recent follow-up, with 8/12 patients experiencing neurological death (as described in Patchell et al.). Eleven of 46 (24%) lesions in 11 separate patients treated with repeat SRS were associated with symptomatic radiation necrosis. Freedom from radiation necrosis at 1 year was 71% (95% CI 57%–88%). Analysis of dosimetric data revealed that the volume of a lesion receiving 40 Gy (V40Gy) was the most predictive factor for the development of radiation necrosis (p = 0.003). The following V40Gy thresholds were associated with 10%, 20%, and 50% probabilities of radiation necrosis, respectively: 0.28 cm3 (95% CI 3%–28%), 0.76 cm3 (95% CI 9%–39%), 1.60 cm3 (95% CI 26%–74%).

CONCLUSIONS

Repeat SRS appears to be an effective salvage option for patients with brain metastases experiencing local failure following initial SRS treatment. This series demonstrates durable local control and, although rates of radiation necrosis are significant, repeat SRS may be indicated for select cases of local disease recurrence. Because the V40Gy is predictive of radiation necrosis, limiting this value during treatment planning may allow for a reduction in radiation necrosis rates.

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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.

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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.