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Oleg Kopyov, Deane Jacques, Christopher Duma, Galen Buckwalter, Alex Kopyov, Abraham Lieberman, and Brian Copcutt

✓ The outcome of radiofrequency-guided posteroventral medial pallidotomy was investigated in 29 patients with recalcitrant Parkinson's disease. Extracellular recordings were obtained in the target region to differentiate the internal from the external globus pallidus, and distinct waveforms were recorded in each region. Stimulation of the target site further verified the lesion location. Of the 29 patients treated during the course of 1 year, none showed any adverse side effects (such as hemianopsia or hemiparesis) from the procedure. Significant and immediate improvement in motor involvement (dyskinesia, rigidity, dystonia, freezing, and tremor) was observed as measured by the Unified Parkinson's Disease Rating Scale and the Hoehn and Yahr scale. Patients experienced improvements in their condition as measured on a self-rating scale, and their ability to perform the activities of daily living was also significantly improved. Although the onset and duration of the effect of a single dose of levodopa did not change, the number of hours in an “off” state of dyskinesia per day was significantly decreased. These results provide further evidence, in a large group of patients, that posteroventral medial pallidotomy results in significant control of the motor symptoms of Parkinson's disease with a minimum of undesirable side effects.

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Christopher M. Duma, Deane B. Jacques, Oleg Kopyov, Rufus J. Mark, Brian Copcutt, and Halle K. Farokhi

Certain patients, for example elderly, high-risk surgical patients, may be unfit for radiofrequency thalamotomy to treat Parkinsonian tremor. Some patients, when given the opportunity, may choose to avoid an invasive surgical procedure. The authors retrospectively reviewed their experience using gamma knife radiosurgery for thalamotomies in this patient subpopulation.

Radiosurgical nucleus ventralis intermedius thalamotomy using the gamma knife unit was performed to make 38 lesions in 24 men and 10 women (median age 73 years, range 58-87 years) over a 5-year period. A median radiation dose of 130 Gy (range 100-165 Gy) was delivered to 38 nuclei (four patients underwent bilateral thalamotomy) using a single 4-mm collimator following classic anatomical landmarks. Twenty-nine lesions were made in the left nucleus ventralis intermedius thalamus for right-sided tremor. Patients were followed for a median of 28 months (range 6-58 months). Independent neurological evaluation of tremor based on the change in the Unified Parkinson's Disease Rating Scale tremor score was correlated with subjective patient evaluation. Comparison was made between a subgroup of patients in whom “low-dose” lesions were made (range 110-135 Gy, mean 120 Gy) and those in whom “high-dose” lesions were made (range 140-165 Gy, mean 160 Gy) for purposes of dose-response information.

Four thalamotomies (10.5%) failed, four (10.5%) produced mild improvement, 11 (29%) produced good improvement, and 10 (26%) produced excellent relief of tremor. In nine thalamotomies (24%) the tremor was eliminated completely. The median time to onset of improvement was 2 months (range 1 week-8 months) Concordance between an independent neurologist's evaluation and that of the patient was statistically significant (p < 0.001). Two patients who underwent unilateral thalamotomy experienced bilateral improvement of their tremor. There were no neurological complications. There was better tremor reduction in the high-dose group when compared with the low-dose group (p < 0.04).

Although less effective than other stereotactic techniques, gamma knife radiosurgical thalamotomy offers tremor control with minimal risk to a patient population unsuited for open surgery.

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Christopher M. Duma, Deane B. Jacques, Oleg V. Kopyov, Rufus J. Mark, Brian Copcutt, and Halle K. Farokhi

Object. Certain patients, for example, elderly high-risk surgical patients, may be unfit for radiofrequency thalamotomy to treat parkinsonian tremor. Some patients, when given the opportunity, may choose to avoid an invasive surgical procedure. The authors retrospectively reviewed their experience using gamma knife radiosurgery for thalamotomies in this patient subpopulation: 1) to determine the efficacy of the procedure; 2) to see if there is a dose—response relationship; 3) to review radiological findings of radiosurgical lesioning; and 4) to assess the risks of complications.

Methods. Radiosurgical nucleus ventralis intermedius thalamotomy using the gamma knife unit was performed to make 38 lesions in 24 men and 10 women (median age 73 years, range 58–87 years) over a 5-year period. A median radiation dose of 130 Gy (range 100–165 Gy) was delivered to 38 nuclei (four patients underwent bilateral thalamotomy) using a single 4-mm collimator following classic anatomical landmarks. Twenty-nine lesions were made in the left nucleus ventralis intermedius thalamus for right-sided tremor. Patients were followed for a median of 28 months (range 6–58 months). Independent neurological evaluation of tremor based on the change in the Unified Parkinson's Disease Rating Scale tremor score was correlated with subjective patient evaluation. Comparison was made between a subgroup of patients in whom “low-dose” lesions were made (range 110–135 Gy, mean 120 Gy) and those in whom “high-dose” lesions were made (range 140–165 Gy, mean 160 Gy) for purposes of dose—response information.

Four thalamotomies (10.5%) failed, four (10.5%) produced mild improvement, 11 (29%) produced good improvement, and 10 (26%) produced excellent relief of tremor. In nine thalamotomies (24%) the tremor was eliminated completely. The median time to onset of improvement was 2 months (range 1 week–8 months). Concordance between an independent neurologist's evaluation and that of the patient was statistically significant (p < 0.001). Two patients who underwent unilateral thalamotomy experienced bilateral improvement in their tremor. There were no neurological complications. There was better tremor reduction in the high-dose group than in the low-dose group (p < 0.04).

Conclusions. Although less effective than other stereotactic techniques, gamma knife radiosurgery for thalamotomy offers tremor control with minimal risk to patients unsuited for open surgery.

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Hideyuki Kano, Jason Sheehan, Penny K. Sneed, Heyoung L. McBride, Byron Young, Christopher Duma, David Mathieu, Zachary Seymour, Michael W. McDermott, Douglas Kondziolka, Aditya Iyer, and L. Dade Lunsford

OBJECT

Stereotactic radiosurgery (SRS) is a potentially important option for patients with skull base chondrosarcomas. The object of this study was to analyze the outcomes of SRS for chondrosarcoma patients who underwent this treatment as a part of multimodality management.

METHODS

Seven participating centers of the North American Gamma Knife Consortium (NAGKC) identified 46 patients who underwent SRS for skull base chondrosarcomas. Thirty-six patients had previously undergone tumor resections and 5 had been treated with fractionated radiation therapy (RT). The median tumor volume was 8.0 cm3 (range 0.9–28.2 cm3), and the median margin dose was 15 Gy (range 10.5–20 Gy). Kaplan-Meier analysis was used to calculate progression-free and overall survival rates.

RESULTS

At a median follow-up of 75 months after SRS, 8 patients were dead. The actuarial overall survival after SRS was 89% at 3 years, 86% at 5 years, and 76% at 10 years. Local tumor progression occurred in 10 patients. The rate of progression-free survival (PFS) after SRS was 88% at 3 years, 85% at 5 years, and 70% at 10 years. Prior RT was significantly associated with shorter PFS. Eight patients required salvage resection, and 3 patients (7%) developed adverse radiation effects. Cranial nerve deficits improved in 22 (56%) of the 39 patients who deficits before SRS. Clinical improvement after SRS was noted in patients with abducens nerve paralysis (61%), oculomotor nerve paralysis (50%), lower cranial nerve dysfunction (50%), optic neuropathy (43%), facial neuropathy (38%), trochlear nerve paralysis (33%), trigeminal neuropathy (12%), and hearing loss (10%).

CONCLUSIONS

Stereotactic radiosurgery for skull base chondrosarcomas is an important adjuvant option for the treatment of these rare tumors, as part of a team approach that includes initial surgical removal of symptomatic larger tumors.

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Douglas Kondziolka, L. Dade Lunsford, John C. Flickinger, Ronald F. Young, Sandra Vermeulen, Christopher M. Duma, Deane B. Jacques, Robert W. Rand, Jean Regis, Jean-Claude Peragut, Luis Manera, Mel H. Epstein, and Christer Lindquist

✓ A multiinstitutional study was conducted to evaluate the technique, dose-selection parameters, and results of gamma knife stereotactic radiosurgery in the management of trigeminal neuralgia. Fifty patients at five centers underwent radiosurgery performed with a single 4-mm isocenter targeted at the nerve root entry zone. Thirty-two patients had undergone prior surgery, and the mean number of procedures that had been performed was 2.8 (range 1–7). The target dose of the radiosurgery used in the current study varied from 60 to 90 Gy. The median follow-up period after radiosurgery was 18 months (range 11–36 months). Twenty-nine patients (58%) responded with excellent control (pain free), 18 (36%) obtained good control (50%–90% relief), and three (6%) experienced treatment failure. The median time to pain relief was 1 month (range 1 day–6.7 months). Responses remained consistent for up to 3 years postradiosurgery in all cases except three (6%) in which the patients had pain recurrence at 5, 7, and 10 months. At 2 years, 54% of patients were pain free and 88% had 50% to 100% relief.

A maximum radiosurgical dose of 70 Gy or greater was associated with a significantly greater chance of complete pain relief (72% vs. 9%, p = 0.0003). Three patients (6%) developed increased facial paresthesia after radiosurgery, which resolved totally in one case and improved in another. No patient developed other deficits or deafferentation pain. The proximal trigeminal nerve and root entry zone, which is well defined on magnetic resonance imaging, is an appropriate anatomical target for radiosurgery. Radiosurgery using the gamma unit is an additional effective surgical approach for the management of medically or surgically refractory trigeminal neuralgia. A longer-term follow-up review is warranted.

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Jason P. Sheehan, Shota Tanaka, Michael J. Link, Bruce E. Pollock, Douglas Kondziolka, David Mathieu, Christopher Duma, A. Byron Young, Anthony M. Kaufmann, Heyoung McBride, Peter A. Weisskopf, Zhiyuan Xu, Hideyuki Kano, Huai-che Yang, and L. Dade Lunsford

Object

Glomus tumors are rare skull base neoplasms that frequently involve critical cerebrovascular structures and lower cranial nerves. Complete resection is often difficult and may increase cranial nerve deficits. Stereotactic radiosurgery has gained an increasing role in the management of glomus tumors. The authors of this study examine the outcomes after radiosurgery in a large, multicenter patient population.

Methods

Under the auspices of the North American Gamma Knife Consortium, 8 Gamma Knife surgery centers that treat glomus tumors combined their outcome data retrospectively. One hundred thirty-four patient procedures were included in the study (134 procedures in 132 patients, with each procedure being analyzed separately). Prior resection was performed in 51 patients, and prior fractionated external beam radiotherapy was performed in 6 patients. The patients' median age at the time of radiosurgery was 59 years. Forty percent had pulsatile tinnitus at the time of radiosurgery. The median dose to the tumor margin was 15 Gy. The median duration of follow-up was 50.5 months (range 5–220 months).

Results

Overall tumor control was achieved in 93% of patients at last follow-up; actuarial tumor control was 88% at 5 years postradiosurgery. Absence of trigeminal nerve dysfunction at the time of radiosurgery (p = 0.001) and higher number of isocenters (p = 0.005) were statistically associated with tumor progression–free tumor survival. Patients demonstrating new or progressive cranial nerve deficits were also likely to demonstrate tumor progression (p = 0.002). Pulsatile tinnitus improved in 49% of patients who reported it at presentation. New or progressive cranial nerve deficits were noted in 15% of patients; improvement in preexisting cranial nerve deficits was observed in 11% of patients. No patient died as a result of tumor progression.

Conclusions

Gamma Knife surgery was a well-tolerated management strategy that provided a high rate of long-term glomus tumor control. Symptomatic tinnitus improved in almost one-half of the patients. Overall neurological status and cranial nerve function were preserved or improved in the vast majority of patients after radiosurgery.

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Mihir Gupta, Varun Sagi, Aditya Mittal, Anudeep Yekula, Devan Hawkins, Justin Shimizu, Pate J. Duddleston, Kathleen Thomas, Steven J. Goetsch, John F. Alksne, David W. Hodgens, Kenneth Ott, Kenneth T. Shimizu, Christopher Duma, and Sharona Ben-Haim

OBJECTIVE

Gamma Knife radiosurgery (GKRS) is an established surgical option for the treatment of trigeminal neuralgia (TN), particularly for high-risk surgical candidates and those with recurrent pain. However, outcomes after three or more GKRS treatments have rarely been reported. Herein, the authors reviewed outcomes among patients who had undergone three or more GKRS procedures for recurrent TN.

METHODS

The authors conducted a multicenter retrospective analysis of patients who had undergone at least three GKRS treatments for TN between July 1997 and April 2019 at two different institutions. Clinical characteristics, radiosurgical dosimetry and technique, pain outcomes, and complications were reviewed. Pain outcomes were scored on the Barrow Neurological Institute (BNI) scale, including time to pain relief (BNI score ≤ III) and recurrence (BNI score > III).

RESULTS

A total of 30 patients were identified, including 16 women and 14 men. Median pain duration prior to the first GKRS treatment was 10 years. Three patients (10%) had multiple sclerosis. Time to pain relief was longer after the third treatment (p = 0.0003), whereas time to pain recurrence was similar across each of the successive treatments (p = 0.842). Complete or partial pain relief was achieved in 93.1% of patients after the third treatment. The maximum pain relief achieved after the third treatment was significantly better among patients with no prior percutaneous procedures (p = 0.0111) and patients with shorter durations of pain before initiation of GKRS therapy (p = 0.0449). New or progressive facial sensory dysfunction occurred in 29% of patients after the third GKRS treatment and was reported as bothersome in 14%. One patient developed facial twitching, while another experienced persistent lacrimation. No statistically significant predictors of adverse effects following the third treatment were found. Over a median of 39 months of follow-up, 77% of patients maintained complete or partial pain relief. Three patients underwent a fourth GKRS treatment, including one who ultimately received five treatments; all of them reported sustained pain relief at the extended follow-up.

CONCLUSIONS

The authors describe the largest series to date of patients undergoing three or more GKRS treatments for refractory TN. A third treatment may produce outcomes similar to those of the first two treatments in terms of long-term pain relief, recurrence, and adverse effects.

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Christopher M. Duma, Brian S. Kim, Peter V. Chen, Marianne E. Plunkett, Ralph Mackintosh, Marlon S. Mathews, Ryan M. Casserly, Gustavo A. Mendez, Daniel J. Furman, Garrett Smith, Nathan Oh, Chad A. Caraway, Ami R. Sanathara, Robert O. Dillman, Azzurra-Sky Riley, David Weiland, Lian Stemler, Ruslana Cannell, Daniela Alexandru Abrams, Alexa Smith, Christopher M. Owen, Burton Eisenberg, and Michael Brant-Zawadzki

OBJECTIVE

Glioblastoma multiforme (GBM) is composed of cells that migrate through the brain along predictable white matter pathways. Targeting white matter pathways adjacent to, and leading away from, the original contrast-enhancing tumor site (termed leading-edge radiosurgery [LERS]) with single-fraction stereotactic radiosurgery as a boost to standard therapy could limit the spread of glioma cells and improve clinical outcomes.

METHODS

Between December 2000 and May 2016, after an initial diagnosis of GBM and prior to or during standard radiation therapy and carmustine or temozolomide chemotherapy, 174 patients treated with radiosurgery to the leading edge (LE) of tumor cell migration were reviewed. The LE was defined as a region outside the contrast-enhancing tumor nidus, defined by FLAIR MRI. The median age of patients was 59 years (range 22–87 years). Patients underwent LERS a median of 18 days from original diagnosis. The median target volume of 48.5 cm3 (range 2.5–220.0 cm3) of LE tissue was targeted using a median dose of 8 Gy (range 6–14 Gy) at the 50% isodose line.

RESULTS

The median overall survival was 23 months (mean 43 months) from diagnosis. The 2-, 3-, 5-, 7-, and 10-year actual overall survival rates after LERS were 39%, 26%, 16%, 10%, and 4%, respectively. Nine percent of patients developed treatment-related imaging-documented changes due to LERS. Nineteen percent of patients were hospitalized for management of edema, 22% for resection of a tumor cyst or new tumor bulk, and 2% for shunting to treat hydrocephalus throughout the course of their disease. Of the patients still alive, Karnofsky Performance Scale scores remained stable in 90% of patients and decreased by 1–3 grades in 10% due to symptomatic treatment-related imaging changes.

CONCLUSIONS

LERS is a safe and effective upfront adjunctive therapy for patients with newly diagnosed GBM. Limitations of this study include a single-center experience and single-institution determination of the LE tumor target. Use of a leading-edge calculation algorithm will be described to achieve a consistent approach to defining the LE target for general use. A multicenter trial will further elucidate its value in the treatment of GBM.

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Hideyuki Kano, Takashi Shuto, Yoshiyasu Iwai, Jason Sheehan, Masaaki Yamamoto, Heyoung L. McBride, Mitsuya Sato, Toru Serizawa, Shoji Yomo, Akihito Moriki, Yukihiko Kohda, Byron Young, Satoshi Suzuki, Hiroyuki Kenai, Christopher Duma, Yasuhiro Kikuchi, David Mathieu, Atsuya Akabane, Osamu Nagano, Douglas Kondziolka, and L. Dade Lunsford

OBJECT

The purpose of this study was to evaluate the role of stereotactic radiosurgery (SRS) in the management of intracranial hemangioblastomas.

METHODS

Six participating centers of the North American Gamma Knife Consortium and 13 Japanese Gamma Knife centers identified 186 patients with 517 hemangioblastomas who underwent SRS. Eighty patients had 335 hemangioblastomas associated with von Hippel–Lindau disease (VHL) and 106 patients had 182 sporadic hemangioblastomas. The median target volume was 0.2 cm3 (median diameter 7 mm) in patients with VHL and 0.7 cm3 (median diameter 11 mm) in those with sporadic hemangioblastoma. The median margin dose was 18 Gy in VHL patients and 15 Gy in those with sporadic hemangioblastomas.

RESULTS

At a median of 5 years (range 0.5–18 years) after treatment, 20 patients had died of intracranial disease progression and 9 patients had died of other causes. The overall survival after SRS was 94% at 3 years, 90% at 5 years, and 74% at 10 years. Factors associated with longer survival included younger age, absence of neurological symptoms, fewer tumors, and higher Karnofsky Performance Status. Thirty-three (41%) of the 80 patients with VHL developed new tumors and 17 (16%) of the106 patients with sporadic hemangioblastoma had recurrences of residual tumor from the original tumor. The 5-year rate of developing a new tumor was 43% for VHL patients, and the 5-year rate of developing a recurrence of residual tumor from the original tumor was 24% for sporadic hemangioblastoma patients. Factors associated with a reduced risk of developing a new tumor or recurrences of residual tumor from the original tumor included younger age, fewer tumors, and sporadic rather than VHL-associated hemangioblastomas. The local tumor control rate for treated tumors was 92% at 3 years, 89% at 5 years, and 79% at 10 years. Factors associated with an improved local tumor control rate included VHL-associated hemangioblastoma, solid tumor, smaller tumor volume, and higher margin dose. Thirteen patients (7%) developed adverse radiation effects (ARE) after SRS, and one of these patients died due to ARE.

CONCLUSIONS

When either sporadic or VHL-associated tumors were observed to grow on serial imaging studies, SRS provided tumor control in 79%–92% of tumors.