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Yueh-Ying Han, Oren Berkowitz, Evelyn Talbott, Douglas Kondziolka, Maryann Donovan, and L. Dade Lunsford

Object

The authors evaluated the potential role of environmental risk factors, including exposure to diagnostic or therapeutic radiation and to wireless phones that emit nonionizing radiation, in the etiology of vestibular schwannoma (VS).

Methods

A total of 343 patients with VSs who underwent Gamma Knife surgery performed between 1997 and 2007 were age and sex matched to 343 control patients from the outpatient degenerative spinal disorders service at the University of Pittsburgh Medical Center. The authors obtained information on previous exposure to medical radiation, use of wireless phone technologies, and other environmental factors thought to be associated with the development of a VS. Conditional multivariate logistic regression was used to estimate adjusted odds ratios (aORs) and 95% confidence intervals (CIs).

Results

After adjusting for race, education, cigarette smoking, alcohol consumption, occupational exposure to noise, use of cell phones, and family history of cancer, the authors identified only a single factor that was associated with a higher risk of VS: individuals exposed to dental x-rays once a year (aOR = 2.27, 95% CI = 1.01–5.09) or once every 2–5 years (aOR = 2.65, 95% CI = 1.20–5.85), compared with those exposed less than once every 5 years. Of interest, a history of exposure to radiation related to head or head-and-neck computed tomography was associated with a reduced risk of VS (aOR = 0.52, 95% CI = 0.30–0.90). No relationship was found between the use of cell phones or cordless phones and VS.

Conclusions

Patients with acoustic neuromas reported significantly more exposure to dental x-rays than a matched cohort control group. Reducing the frequency of dental x-ray examinations may decrease the potential risk of VS.

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L. Dade Lunsford, Veronica Chiang, John R. Adler, Jason Sheehan, William Friedman, and Douglas Kondziolka

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Daniel Tonetti, Jagdish Bhatnagar, and L. Dade Lunsford

Object

The design of the Leksell Gamma Knife Perfexion facilitates stereotactic radiosurgery (SRS) on cervical spine targets provided that the target itself is located superior to the standard G stereotactic head frame base ring and does not move. This study was designed to measure potential deviations of targets in the upper cervical spine while using the currently available Leksell Coordinate Frame G.

Methods

A commercially available skull-and–cervical spine model was adapted for SRS using the Leksell Gamma Knife Perfexion. The Leksell Coordinate Frame G was attached to the model, and both CT and fluoroscopic imaging were performed to determine the potential for target deviation at standard Gamma Knife treatment angles of 70°, 90°, and 110°. In addition, target deviations observed at various heights of the patient positioning table were analyzed using a pair of orthogonal fluoroscopic images obtained at a standard 90° gamma angle and compared with target position as it relates to a reference bed height of 4.5 cm.

Results

An examination of multiple radiopaque targets embedded in or affixed to the model showed target deviations ranging from as low as 3.53 mm at the medial occiput–C1 junction to 15.56 mm at the C3–4 level during 70° extension. Target deviations at 110° flexion relative to targets on a 90° CT scan included deviations ranging from 0.58 mm at the medial occiput–C1 junction to 13.32 mm at the medial C3–4 level.

Relative to targets observed at the Perfexion table height of 4.5 cm, target deviation at a table height of 3 cm varied from 0.44 to 5.26 mm. At a table height of 5.5 cm, target deviation varied from 0.44 to 3.60 mm, and at a maximum height of 5.8 cm, target deviation varied from 0.62 to 4.30 mm.

Conclusions

Target deviation grossly exceeded clinical tolerance and was greater the farther the distance between the cranial base and the cervical spine target. Simple and reproducible methods that allow SRS centers to immobilize the patient's cervical spine using the currently available model G head frame are necessary to increase the range of targets that can be treated safely using the Leksell Gamma Knife Perfexion.

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Georgios Zenonos, Douglas Kondziolka, John C. Flickinger, Paul Gardner, and L. Dade Lunsford

Object

Microsurgical management of foramen magnum meningiomas (FMMs) can be associated with significant morbidity and mortality. Stereotactic radiosurgery may be an efficient and safe alternative treatment modality for such tumors. The object of this study was to increase the documented experience with Gamma Knife surgery (GKS) for FMMs and to delineate its role in an overall management paradigm.

Methods

The authors report on their experience with 24 patients harboring FMMs managed with GKS. Twelve patients had primary symptomatic tumors, 5 had asymptomatic but enlarging primary tumors, and 7 had recurrent or residual tumors after a prior surgery.

Results

Follow-up clinical and imaging data were available in 21 patients at a median follow-up of 47 months (range 3–128 months). Ten patients had measurable tumor regression, which was defined as an overall volume reduction > 25%. Eleven patients had no further tumor growth. Two patients died as a result of advanced comorbidities before follow-up imaging. One patient was living 8 years after GKS but had no clinical evaluation. Ten of 17 symptomatic patients with at least 6 months of follow-up had symptom improvement, and 7 remained clinically stable. Smaller tumors were more likely to regress. No patient suffered an adverse radiation effect after radiosurgery.

Conclusions

Gamma Knife surgery was a safe management strategy for small, minimally symptomatic, or growing FMMs as well as for residual tumors following conservative microsurgical removal.

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Douglas Kondziolka, Seyed H. Mousavi, Hideyuki Kano, John C. Flickinger, and L. Dade Lunsford

Object

Management recommendations for patients with smaller-volume or newly diagnosed vestibular schwannomas (< 4 cm3) need to be based on an understanding of the anticipated natural history of the tumor and the side effects it produces. The natural history can then be compared with the risks and benefits of therapeutic intervention using a minimally invasive strategy such as stereotactic radiosurgery (SRS).

Methods

The authors reviewed the emerging literature stemming from recent recommendations to “wait and scan” (observation) and compared this strategy with published outcomes after early intervention using SRS or results from matched cohort studies of resection and SRS.

Results

Various retrospective studies indicate that vestibular schwannomas grow at a rate of 0–3.9 mm per year and double in volume between 1.65 and 4.4 years. Stereotactic radiosurgery arrests growth in up to 98% of patients when studied at intervals of 10–15 years. Most patients who select “wait and scan” note gradually decreasing hearing function leading to the loss of useful hearing by 5 years. In contrast, current studies indicate that 3–5 years after Gamma Knife surgery, 61%–80% of patients maintain useful hearing (speech discrimination score > 50%, pure tone average < 50).

Conclusions

Based on published data on both volume and hearing preservation for both strategies, the authors devised a management recommendation for patients with small vestibular schwannomas. When resection is not chosen by the patient, the authors believe that early SRS intervention, in contrast to observation, results in long-term tumor control and improved rates of hearing preservation.

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Jason Sheehan and Chun Po Yen

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Jason Sheehan and David Schlesinger

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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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Hideyuki Kano, Douglas Kondziolka, John C. Flickinger, Kyung-Jae Park, Aditya Iyer, Huai-che Yang, Xiaomin Liu, Edward A. Monaco III, Ajay Niranjan, and L. Dade Lunsford

Object

In this paper the authors' goal was to define the long-term benefits and risks of stereotactic radiosurgery (SRS) for patients with arteriovenous malformations (AVMs) who underwent prior embolization.

Methods

Between 1987 and 2006, the authors performed Gamma Knife surgery in 996 patients with brain AVMs; 120 patients underwent embolization followed by SRS. In this series, 64 patients (53%) had at least one prior hemorrhage. The median number of embolizations varied from 1 to 5. The median target volume was 6.6 cm3 (range 0.2–26.3 cm3). The median margin dose was 18 Gy (range 13.5–25 Gy).

Results

After embolization, 25 patients (21%) developed symptomatic neurological deficits. The overall rates of total obliteration documented by either angiography or MRI were 35%, 53%, 55%, and 59% at 3, 4, 5, and 10 years, respectively. Factors associated with a higher rate of AVM obliteration were smaller target volume, smaller maximum diameter, higher margin dose, timing of embolization during the most recent 10-year period (1997–2006), and lower Pollock-Flickinger score. Nine patients (8%) had a hemorrhage during the latency period, and 7 patients died of hemorrhage. The actuarial rates of AVM hemorrhage after SRS were 0.8%, 3.5%, 5.4%, 7.7%, and 7.7% at 1, 2, 3, 5, and 10 years, respectively. The overall annual hemorrhage rate was 2.7%. Factors associated with a higher risk of hemorrhage after SRS were a larger target volume and a larger number of prior hemorrhages. Permanent neurological deficits due to adverse radiation effects (AREs) developed in 3 patients (2.5%) after SRS, and 1 patient had delayed cyst formation 210 months after SRS. No patient died of AREs. A larger 12-Gy volume was associated with higher risk of symptomatic AREs. Using a case-control matched approach, the authors found that patients who underwent embolization prior to SRS had a lower rate of total obliteration (p = 0.028) than patients who had not undergone embolization.

Conclusions

In this 20-year experience, the authors found that prior embolization reduced the rate of total obliteration after SRS, and that the risks of hemorrhage during the latency period were not affected by prior embolization. For patients who underwent embolization to volumes smaller than 8 cm3, success was significantly improved. A margin dose of 18 Gy or more also improved success. In the future, the role of embolization after SRS should be explored.

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Ramesh Grandhi, Douglas Kondziolka, David Panczykowski, Edward A. Monaco III, Hideyuki Kano, Ajay Niranjan, John C. Flickinger, and L. Dade Lunsford

Object

To better establish the role of stereotactic radiosurgery (SRS) in treating patients with 10 or more intracranial metastases, the authors assessed clinical outcomes and identified prognostic factors associated with survival and tumor control in patients who underwent radiosurgery using the Leksell Gamma Knife Perfexion (LGK PFX) unit.

Methods

The authors retrospectively reviewed data in all patients who had undergone LGK PFX surgery to treat 10 or more brain metastases in a single session at the University of Pittsburgh. Posttreatment imaging studies were used to assess tumor response, and patient records were reviewed for clinical follow-up data. All data were collected by a neurosurgeon who had not participated in patient care.

Results

Sixty-one patients with 10 or more brain metastases underwent SRS for the treatment of 806 tumors (mean 13.2 lesions). Seven patients (11.5%) had no previous therapy. Stereotactic radiosurgery was the sole prior treatment modality in 8 patients (13.1%), 22 (36.1%) underwent whole-brain radiation therapy (WBRT) only, and 16 (26.2%) had prior SRS and WBRT. The total treated tumor volume ranged from 0.14 to 40.21 cm3, and the median radiation dose to the tumor margin was 16 Gy. The median survival following SRS for 10 or more brain metastases was 4 months, with improved survival in patients with fewer than 14 brain metastases, a nonmelanomatous primary tumor, controlled systemic disease, a better Karnofsky Performance Scale score, and a lower recursive partitioning analysis (RPA) class. Prior cerebral treatment did not influence survival. The median survival for a patient with fewer than 14 brain metastases, a nonmelanomatous primary tumor, and controlled systemic disease was 21.0 months. Sustained local tumor control was achieved in 81% of patients. Prior WBRT predicted the development of new adverse radiation effects.

Conclusions

Stereotactic radiosurgery safely and effectively treats intracranial disease with a high rate of local control in patients with 10 or more brain metastases. In patients with fewer metastases, a nonmelanomatous primary lesion, controlled systemic disease, and a low RPA class, SRS may be most valuable. In selected patients, it can be considered as first-line treatment.