Paragangliomas of the head and neck, also known

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1 J Neurosurg 121: , 2014 AANS, 2014 Jugulotympanic paragangliomas treated with Gamma Knife radiosurgery: a single-center review of 58 cases Clinical article Maria Luisa Gandía-González, M.D., 1 M. Elena Kusak, M.D., 2 Nuria Martínez Moreno, M.D., Ph.D., 2 Jorge Gutiérrez Sárraga, M.Sc., 2 Germán Rey, M.Sc., Ph.D., 2 and Roberto Martínez Álvarez, M.D., Ph.D. 2 1 Department of Neurosurgery, Hospital Universitario La Paz, Madrid; and 2 Department of Neurological Surgery and Gamma Knife Radiosurgery, Hospital Ruber Internacional, Madrid, Spain Object. Jugulotympanic paragangliomas (JTPs) are rare benign tumors whose surgical treatment is usually associated with partial resection of the lesion, high morbidity, and even death. Gamma Knife radiosurgery (GKRS) has been reported as a useful treatment option. The goal of this retrospective study is to analyze the role of GKRS in tumor volume control and clinical outcomes of these patients. Methods. A total of 75 patients with JTPs were treated with GKRS at the authors center from 1995 to The authors analyzed those treated during this period to allow for a minimal observation time of 2 years. The MR images and clinical reports of these patients were reviewed to assess clinical and volumetric outcomes of the tumors. The radiological and clinical assessments, along with a group of prognostic factors measured, were analyzed using descriptive methods. The time to volumetric and clinical progression was analyzed using the Kaplan-Meier method. Prognostic factors were identified using log-rank statistics and multivariate Cox regression models. Results. The mean follow-up was 86.4 months. The authors observed volumetric tumor control in 94.8% of cases. In 67.2% of cases, tumor volume decreased by a mean of 40.1% from the original size. Of patients with previous tinnitus, 54% reported complete recovery. Improvement of other symptoms was observed in 34.5% of cases. Overall, clinical control was achieved in 91.4% of cases. Previous embolization and familial history of paraganglioma were selected as significant prognostic factors for volumetric response to GKRS treatment in the univariate analysis. In multivariate analysis, no factors were significantly correlated with progression-free survival. No patient died of side effects related to GKRS treatment or tumor progression. Conclusions. Gamma Knife radiosurgery is an effective, safe, and efficient therapeutic option for the treatment of these tumors as a first-line treatment or in conjunction with traditional surgery, endovascular treatment, or conventional fractionated radiotherapy. ( Key Words jugulotympanic paraganglioma Gamma Knife radiosurgery tumor control clinical outcome stereotactic radiosurgery Abbreviations used in this paper: CN = cranial nerve; GKRS = Gamma Knife radiosurgery; HR = hazard ratio; JTP = jugulotympanic paraganglioma; SRS = stereotactic radiosurgery. Paragangliomas of the head and neck, also known as chemodectomas or glomus tumors, are highly vascular neuroendocrine neoplasms that arise from paraganglionic tissue. 6,23 These entities comprise tumors arising in the carotid body, the jugular bulb, the tympanic branch of the glossopharyngeal nerve (Jacobson s nerve), and the auricular branch of the vagus nerve (Arnold s nerve). 19 Those affecting the carotid body are by far the most common type, and surgery has been shown to be a safe treatment option for them. 22 However, treatment of jugulotympanic paragangliomas (JTPs) is challenging. These tumors are not as frequent as carotid body paragangliomas, with an estimated incidence of only 1 in 1.3 million, 10,13,21 and they are usually benign, slow-growing tumors. 19,22 Malignant variations occur in about 3% of cases, 9 and metastases can be observed in 1% 4% of cases. 3,13 Both benign and malignant variations cause very disabling symptoms; patients may present with severe hearing loss, tinnitus, other cranial nerve deficits, dizziness, and occasionally venous thrombosis. 23 Traditionally, the management of these tumors has involved microsurgical resection and/or radiation therapy, sometimes preceded by preoperative embolization. 12 Microsurgical removal can be accomplished through reasonably safe approaches, but even the most recent surgical 1158 J Neurosurg / Volume 121 / November 2014

2 Gamma knife radiosurgery in jugulotympanic paragangliomas series reported incomplete tumor removal in up to 20% of patients. 23 Furthermore, significant morbidity and reduced quality of life are common downsides of surgical therapy, 11,14,16,23 with 50% of patients experiencing permanent lower cranial nerve palsies after surgery. 23 Finally, it should also be acknowledged that, according to recent publications, surgery carries a mortality rate of about 4%. 22,26 To avoid the significant morbidity associated with excision, conventional radiotherapy has been used increasingly in the treatment of JTPs. 2,28 However, this treatment has side effects. 23 Because of its efficacy and precision, Gamma Knife radiosurgery (GKRS) has been used successfully to treat JTPs in many centers, 4,5,7 9,15,19,20,24,26,29 minimizing the radiation adverse effects. Gamma Knife radiosurgery was performed in 75 patients with JTPs at our center. According to our review of the literature, it is one of the largest cohorts of patients reported to date. Unlike previous studies, where the short follow-up may have made it difficult to draw conclusions about these slow-growing tumors, we evaluated clinical and radiological outcomes during long-term follow-up in a large group of patients. Such a large cohort with long-term follow-up has not been reported previously in the literature. Methods Patient Population We retrospectively reviewed the prospectively maintained database of the Gamma Knife Unit at the International Ruber Hospital of Madrid and searched for JTPs cases. During an 18-year period, from January 1995 to December 2012, 75 patients were radiosurgically treated for JTPs at our institution. Medical records, imaging studies, and operative reports were reviewed. To allow for an observation time of at least 2 years in these slow-growing tumors, 13 patients treated after 2010 were excluded. Four other patients were lost to follow-up. A final cohort of 58 patients with complete outcome data were analyzed, with a mean follow-up of 86.4 months and a median follow-up of 76.6 months. J Neurosurg / Volume 121 / November 2014 Management Patients were treated with GKRS after all therapeutic options were considered by a multidisciplinary team of neurosurgeons and radiation oncologists. All patients were treated with the Leksell Gamma Knife (Models B, 4C, and PFX; Elekta AB) using existing planning software. Stereotactic radiosurgery (SRS) was performed in a single session in all cases. The mean marginal dose was 13.6 Gy (range Gy), and the mean maximum dose was 25.2 Gy (range Gy). The mean isodose line was 55.3% (range 40% 65%), the mean number of isocenters was 10.8 (range 2 29). The doses received by critical structures were a maximal dose of 10 Gy to the brainstem and of 11 Gy to the facial nerve. Although we tried to minimize the dose received by cranial nerves (CNs) V and VIII and lower, in some cases they were included in the tumor, and they received the same dose as the tumor itself. All radiosurgical treatments were performed by the same team of neurosurgeons and radiation oncologists. Clinical and Radiological Outcome Assessment Clinical outcomes were assessed by a complete neurological examination that included cranial nerve function. Patients were assessed by an otolaryngology specialist, a neurologist, or a neurosurgeon who were not directly involved in the care of the patients. Patients underwent follow-up at annual intervals beginning 12 months after undergoing SRS. The patient s neurological status prior to treatment was used as a reference point, and outcomes were expressed in terms of change from this baseline as improved, unchanged, or worse. Asymptomatic patients without new neurological deficits were classified as unchanged. To evaluate the tumor, MRI sequences (T1, T2, fat suppression, and T1 after gadolinium administration) were routinely acquired in all patients. Radiosurgical planning was performed using MR images obtained under stereotactic conditions. After SRS, the same MRI sequences were acquired to evaluate for variations in tumor size. Follow-up imaging was performed at annual intervals beginning 12 months after surgery to assess the radiographic response to treatment. A neuroradiologist not directly involved in the care of the patient classified the tumor size as decreased, increased, or unchanged. Change in tumor size was reported as cubic centimeters of volume. Tumors were considered controlled if they were reported as decreased or unchanged on the follow-up volume images. Statistical Analysis In a descriptive analysis, frequencies and percentages are given for the categorical variables, and mean, median, and ranges are given for continuous variables. The following potential prognostic factors at diagnosis were studied in a univariate analysis: sex, age, right or left location, paraganglioma familial history, tumor volume, ataxia, lower cranial nerve neuropathy, previous treatment with radiotherapy, previous embolization treatment, and previously operated tumor at baseline. Marginal dose, maximal dose, and number of isocenters were selected as the most relevant variables related with SRS radiation for the univariate and multivariate analysis. The correlation of all the baseline characteristics with the radiological and clinical outcomes in terms of time to progression was analyzed using the univariate log-rank test and proportional hazards Cox regression. Frequency tables and summary statistics were used to show the distribution of the baseline characteristics in the response groups (increased, unchanged, or decreased volume for volumetric outcomes; improved, unchanged, or worse for clinical outcomes). The variables showing statistical significance at the 10% level in the univariate analysis along with other clinically relevant variables of known prognostic value were entered in a multivariate logistic regression model. The hazard ratios (HRs) and their confidence intervals are displayed for the variables included in the univariate and multivariate regression models. 1159

3 M. L. Gandía-González et al. Results There were 40 women and 18 men with a mean age of 52.4 years (range years); 32 patients (55%) had left-sided tumors and 26 patients (45%) had right-sided tumors. The most common symptom at presentation was tinnitus. Four patients were known familial cases. Of the 58 patients reviewed, 18 had undergone prior microsurgical treatment and had histological confirmation of their tumors. Four of these patients had also been treated previously with embolization and 3 patients had received radiotherapy. Forty patients had not been treated surgically before GKRS. In these patients, the diagnosis had been established on the basis of imaging studies (CT scanning, MRI, or angiography) and clinical presentation. Of the 40 patients not treated with surgery, 6 had received endovascular treatment and 1 had received only radiotherapy before being referred to our institution. Nine percent of patients presented with ataxia. Hearing loss was present at diagnosis in 79.3% of 58 patients (94.4% in patients who had undergone previous surgery, 72.5% who had not undergone previous surgery). Overall, 72.4% patients presented with lower cranial nerve neuropathy before SRS (83.3% in operated and 67.5% in nonoperated patients). Images obtained before SRS demonstrated a tumor volume that ranged from 0.32 to 62.2 cm 3 (mean 12 cm 3, median 9.3 cm 3 ). Follow-up imaging revealed an increased volume in 3 patients (5.2%). Thirty-nine patients (67.2%) exhibited a decrease in tumor volume, and 16 patients (27.6%) showed no change in tumor size. Thus, tumor control was achieved in 55 patients (94.8%) (Fig. 1). The decrease in tumor volume observed in 39 patients was accurately measured. The mean volume decrease was 5.6 cm 3 (range cm 3 ), corresponding to a reduction in size of 40.1% (range 5% 95%). Five patients (8.6%) experienced clinical worsening after treatment. Causes of impairment included hearing loss in 4 patients and dysphagia in 1 patient. In 3 of these patients the impairment was related to tumor growth (2 with hearing loss and 1 with dysphagia). All patients reported improvement of their previous tinnitus, but only 54% of cases reported complete recovery. Most of these patients reported this improvement at the first control visit 12 months after treatment. In addition to tinnitus, 20 patients (34.5%) showed improvement in other symptoms after GKRS. Thirty-three patients (56.9%) showed no clinical changes according to the most recent follow-up data available (Fig. 2). No patient died during the perioperative period. Three patients died later of other unrelated causes, and none experienced clinical deterioration in terms of JTP progression or treatment-related side effects before death. In a univariate analysis using the Kaplan-Meier method and log-rank statistics, the independent risk factors with statistical significance less than 10% were previous embolization (p = ) and paraganglioma familial history (p = ) for the volumetric progression (Table 1). Lateral right location (p = ) was an independent risk factor for clinical progression (Table 2). Several multivariate Cox regression models have been tested. The predictive factors included in the models were the factors mentioned above that reached a p value < 0.10 in the univariate analysis. No independent predictive factors reached 5% statistical significance in the multivariate logistic regression for clinical or radiological outcomes alone (Figs. 3 and 4). Due to the high number of patients free from progression (55 for volumetric assessment and 53 for clinical assessment), the median time to progression was not reached at the time of the analysis, and high censoring made it impossible to calculate HRs for some variables. Discussion Paragangliomas of the head and neck are uncommon tumors. According to Neskey and colleagues, 22 carotid paraganglioma is the most frequent among them, representing 63% 78% of cases followed by JTPs and vagal paragangiomas. Jugulotympanic paragangliomas represent 0.03% of Fig. 1. Pie chart showing the tumor volume outcomes at the end of follow-up. Fig. 2. Pie chart showing the clinical outcomes at the end of followup (tinnitus is not included) J Neurosurg / Volume 121 / November 2014

4 Gamma knife radiosurgery in jugulotympanic paragangliomas TABLE 1: Prognostic factors related to volumetric tumor progression-free survival: univariate analysis* Variable p Value HR 95% CI lateral location (lt/rt) sex (M/F) previous radiotherapy (yes/no) previous embolization (yes) ataxia (yes/no) familial antecedents (yes) previous surgery (yes/no) age (<55/ 55 yrs) tumor vol (<10/ 10 cm 3 ) marginal dose (<13.5/ 13.5 Gy) lower cranial nerve involvement (yes/no) age tumor vol marginal dose maximal dose no. of isocenters * Values in boldface are statistically significant. = Hazard ratio could not be calculated due to the low number of progression events in some groups. The categories with higher risk are shown for the significant prognostic factors. Log-rank test Cox regression. all neoplasms and 0.6% of all head and neck tumors. 23 Their incidence in the general population is only 1 in 1.3 million, and they grow very slowly. 13 Jansen and colleagues estimated the growth rate of these tumors to be 0.79 mm per year. 17 Because JTPs are seen so infrequently, it is difficult to find large numbers of patients to study. In addition, because of their slow-growing nature, it is important to study patients with these tumors for many years after treatment. For these reasons, there have been few review articles that provide information on large number of patients with JTPs with long-term follow-up. TABLE 2: Prognostic factors related to clinical tumor progression-free survival: univariate analysis* Variable p Value HR 95% CI lateral location (rt) sex (M/F) previous radiotherapy (yes/no) previous embolization (yes/no) ataxia (yes/no) familial antecedents (yes/no) previous surgery (yes/no) age (<55/ 55 yrs) tumor vol (<10/ 10 cm 3 ) marginal dose (<13.5/ 13.5 Gy) lower cranial nerve involvement (yes/no) age tumor vol marginal dose maximal dose no. of isocenters * Values in boldface are statistically significant. = Hazard ratio could not be calculated due to the low number of progression events in some groups. The categories with higher risk are shown for the significant prognostic factors. Log-rank test/cox regression. J Neurosurg / Volume 121 / November

5 M. L. Gandía-González et al. Fig. 3. Kaplan-Meier curve for volumetric progression. One of the largest cohorts was published by Liscák et al. 19 in These authors described the results of a first multicenter study of 66 cases, of which 52 were followed during a median of 24 months. However, the largest multicenter series was recently reported by Sheehan et al. 26 They observed 132 patients for a median of 50.5 months and found a high rate of long-term tumor control. In spite of our smaller number of patients, we assessed clinical and imaging outcomes of these patients for a longer median follow-up period, and our results are comparable to those in the large North American series. In 2002 Eustacchio et al. 4 reported a single-center review of 19 cases that had been observed for a median of 86.4 months. This follow-up is the longest in a singlecenter review to date. In 2008 Sharma et al. 24 published the largest single-center series, in which 24 cases of paraganglioma treated using GKRS were analyzed during a mean of 26.1 months. Fig. 4. Kaplan-Meier curve for clinical progression J Neurosurg / Volume 121 / November 2014

6 Gamma knife radiosurgery in jugulotympanic paragangliomas To the best of our knowledge, there has been no single-center study of a group of patients as large as the one we report here, with 75 patients treated and 58 analyzed. The patients we report on were followed for a mean of 86.4 months, a longer period than most of the series we found in the literature. These tumors pose a difficult therapeutic challenge because of their location and highly vascular nature. Several management options, including surgical removal, endovascular embolization, and radiotherapy, have been described elsewhere. 26 Their surgical management is associated with poor local control and a high incidence of recurrence, morbidity, and mortality. 25 Surgical approaches are challenging because of the proximity of critical vascular and neural structures that are frequently invaded by the tumor. 1,18 Jackson and colleagues 16 reviewed 18 cases of incompletely resected tumors and found that 9 of them had progressed to the point that they required further interventions. The proximity of these tumors to the cranial nerves, specifically, to CNs VII through XII, elevates the risk of postoperative deficits. Neskey and colleagues 22 found a transient cranial nerve deficit during the 1st postoperative month in 96% of cases, with 50% experiencing permanent deficits. This is consistent with the rates of deficits reported in other series. In the one reported by Jackson et al., 16 new deficits were found in CNs IX, X, XI, and XII in 39%, 25%, 26%, and 21% of cases, respectively. Green et al. 11 reported on 52 patients who experienced complications such as pneumonia, pulmonary embolus, aspiration, and meningitis after microsurgery. In this series 19% of patients were subsequently treated for vocal cord paralysis, 8% required thyroplasty, and 8% required prolonged feedings via a nasogastric tube. Additionally, 29% of patients reported persistent hoarseness and 29% reported dysphagia. These deficits are very disabling and negatively affect the quality of life and psychological well being of the patient. Another therapeutic option for the treatment of JTPs is radiotherapy, which was first used in the 1950s as adjuvant treatment. In 1990 Springate and Weichselbaum 28 published the first meta-analysis of patients treated with radiotherapy alone and reported tumor control in 93% of cases. According to Bitaraf et al., 2 radiotherapy provided tumor control in 61% 94% of cases, using doses of Gy. However, treatment of these tumors with radiotherapy is not without side effects. Acute complications such as mastoiditis, dermatitis, alopecia, mucositis, otitis, taste alterations, or cerebrovascular events have been reported in 4% 20% of patients. 23 Facial palsy, hearing loss, temporal bone or brain radionecrosis, and radiation-induced tumors have been reported as chronic complications. 23 In the 1990s, SRS began to be used for the treatment of these lesions. This is a minimally invasive therapeutic option that enables the patient to be treated in a single session with minimal radiation exposure to the surrounding healthy tissues. The precision and accuracy of GKRS minimizes adverse effects to the lowest possible level. The posttreatment morbidity is very low, and to date there have been no reports of treatment-associated mortality. Liscák and colleagues 19 were the first to study a large cohort of 52 patients. In their multicenter study, the authors were able to demonstrate clinical tumor control in 90% of patients and tumor size control in 60% of patients. Successive review articles have since been published that demonstrate that GKRS provides good control of symptoms and tumor volume (Table 3). The rate of control of tumor volume varies between 71% and 100% in these studies. The rate of tumor volume control that we achieved corroborates the rates previously reported in the literature (Fig. 5). Previous embolization and familial history of paraganglioma were related to tumor growth after GKRS in the univariate analysis. However, these factors were not statistically correlated with progression-free survival in the multivariate analysis. The low rate of volumetric progression could explain why no factors have been identified as independent risk factors. In terms of clinical control, the majority of patients did not experience changes after treatment. The rate of clinical control that we observed is similar to those previously reported by other authors. One patient who experienced dysphagia as new deficit was found to have tumor growth. Another 2 patients experienced decreased hearing acuity, which was also associated with increased tumor volume. This supports the hypothesis described by Sheehan et al. 26 that the development of new or worsening cranial nerve deficits is a good predictor of tumor growth. TABLE 3: Single- and multicenter studies of patients with JTPs treated with GKRS Follow-Up (mos) Control (%) Authors & Year Type of Review No. of Patients Median Mean Tumor Clinical Liscák et al., 1999 multicenter Eustacchio et al., 2002 single center Sheehan et al., 2005 single center Varma et al., 2006 single center Gerosa et al., 2006 single center Sharma et al., 2008 single center Ganz & Abdelkarim, 2009 single center Miller et al., 2009 single center Sheehan et al., 2012 multicenter 132 (134 procedures) present study single center J Neurosurg / Volume 121 / November

7 M. L. Gandía-González et al. According to our review and the reports of other authors, tinnitus and hearing loss are the symptoms found to improve most significantly after treatment with GKRS. All patients with tinnitus reported some degree of improvement, perhaps because they had become accustomed it; however, only 54% experienced complete recovery. Additionally, we found that several patients had improved symptoms of lower cranial nerve palsies, which has also been described by other authors. None of the risk factors included in the multivariate analysis reached statistical significance for clinical progression-free survival, which may be due to the low rate of clinical progression. A larger series and a longer follow-up would be useful to uncover these factors. The current study and the previous literature prove that GKRS is not only effective at controlling the growth of JTPs but is also effective at controlling the clinical symptoms of these tumors. In 2 cases, hearing loss was related to tumor growth. Tumor growth was not observed in the other 2 cases. Gamma Knife radiosurgery may have been responsible for this clinical worsening. Sheehan et al. 27 reported 2 cases of GKRS-induced meningiomas in patients treated for arteriovenous malformations. In the present series, we did not observe radiation-induced neoplasia, malignant transformation, or other symptoms or signs related to the GKRS treatment of JTPs; however, we recommend that these patients be followed for an extended period. Overall, the rate of reported side effects with GKRS is much lower than the rate of side effects with radiotherapy. In 2004 Gottfried and colleagues 10 published a study in which SRS and microsurgery were compared. They found that both methods achieved similar levels of tumor control. Even though they recognized that a big difference exists in morbidity favoring SRS, they expressed reservations about SRS due to the lack of long-term studies of such slow-growing tumors and were unable to evaluate the possibility of future recurrences. Ivan and colleagues 15 conducted a meta-analysis in which they compared the morbidity of surgery and SRS. In that study, 869 patients were separated into 4 groups according to the treatment they had received: subtotal resection, gross-total resection, subtotal resection combined with SRS, or SRS alone. Patients undergoing SRS alone experienced the lowest rates of recurrence of these 4 groups. In addition, the incidence of lower cranial nerve deficits was found to be higher in gross-total resection than in those who underwent SRS alone. A larger number of patients and a longer follow-up are necessary to detect statistically significant risk factors related to the volumetric or clinical progression of JTPs; however, our review demonstrates that the rates of tumor control observed in previously published studies during periods of short-term follow-up are maintained when the follow-up interval is prolonged. Our review corroborates the findings of Eustacchio et al. 4 and other authors 7,9,19,20,24 26,29 that GKRS provides good clinical and tumor control that persists for long periods of time after treatment. Additionally, death related to GKRS has not been described, and the morbidity associated with GKRS is very low and not disabling. Thus, GKRS should be considered Fig. 5. Magnetic resonance images obtained in a patient with a large left-sided JTP. A: Axial and coronal images obtained at the time of GKRS treatment. B: Axial and coronal images obtained 72 months after treatment. C: Axial and coronal images obtained 112 months posttreatment. a viable option in the primary treatment of these neoplasms, alone or in combination with other therapeutic treatment options. Conclusions Our experience with GKRS for JTPs confirms that it is an effective, safe, and efficient therapeutic option for these tumors, either as a first-line treatment or associated with surgery, endovascular treatment, or radiotherapy. Acknowledgments We would like to thank Drs. A. Rodríguez-Hernández and G. Palatucci for their collaboration with the preparation of the manuscript, A. de Campos Kusak for his assistance with the graphic material, and J. Gómez for his collaboration with the statistical content J Neurosurg / Volume 121 / November 2014

8 Gamma knife radiosurgery in jugulotympanic paragangliomas Disclosure Dr. Martínez Álvarez is a consultant with Elekta AB. The authors report no other conflict of interest concerning the materials or methods used in this study or the findings specified in this paper. Author contributions to the study and manuscript preparation include the following. Conception and design: all authors. Acquisition of data: Gandía-González, Kusak. Analysis and interpretation of data: Gandía-González. Drafting the article: Gandía-González. Critically revising the article: all authors. Reviewed submitted version of manuscript: all authors. Approved the final version of the manuscript on behalf of all authors: Gandía-González. Statistical analysis: Gandía-González. Administrative/technical/material support: Gandía-González, Kusak, Martínez Moreno, Gutiérrez Sárraga, Martínez Álvarez. Study supervision: all authors. References 1. 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Skull Base 21: , Poznanovic SA, Cass SP, Kavanagh BD: Short-term tumor control and acute toxicity after stereotactic radiosurgery for glomus jugulare tumors. Otolaryngol Head Neck Surg 134: , Sharma MS, Gupta A, Kale SS, Agrawal D, Mahapatra AK, Sharma BS: Gamma knife radiosurgery for glomus jugulare tumors: therapeutic advantages of minimalism in the skull base. Neurol India 56:57 61, Sheehan JP, Kondziolka D, Flickinger J, Lunsford LD: Gamma knife surgery for glomus jugulare tumors: an intermediate report on efficacy and safety. J Neurosurg 102 Suppl: , Sheehan JP, Tanaka S, Link MJ, Pollock BE, Kondziolka D, Mathieu D, et al: Gamma Knife surgery for the management of glomus tumors: a multicenter study. Clinical article. J Neurosurg 117: , Sheehan JP, Yen CP, Steiner L: Gamma Knife surgery induced meningioma. Report of two cases and review of the literature. J Neurosurg 105: , Springate SC, Weichselbaum RR: Radiation or surgery for chemodectoma of the temporal bone: a review of local control and complications. Head Neck 12: , Varma A, Nathoo N, Neyman G, Suh JH, Ross J, Park J, et al: Gamma knife radiosurgery for glomus jugulare tumors: volumetric analysis in 17 patients. Neurosurgery 59: , 2006 Manuscript submitted September 2, Accepted May 5, Portions of this work were presented in poster form at the Congress of Neurological Surgeons Annual Meeting, San Francisco, California, October 16 21, 2010, and at the European Association of Neuro-Oncology, Maastricht, the Netherlands, September 16 19, Please include this information when citing this paper: published online June 13, 2014; DOI: / JNS Address correspondence to: Maria Luisa Gandía González, M.D., Department of Gamma Knife Radiosurgery, Hospital Ruber Internacional, Calle La Masó, 38, Madrid 28034, Spain. marisagg4@ hotmail.com. J Neurosurg / Volume 121 / November