Cerebellopontine angle (CPA) meningiomas are a. Stereotactic radiosurgery for cerebellopontine angle meningiomas. Clinical article

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1 J Neurosurg 120: , 2014 AANS, 2014 Stereotactic radiosurgery for cerebellopontine angle meningiomas Clinical article Seong-Hyun Park, M.D., Ph.D., 1,3,4 Hideyuki Kano, M.D., Ph.D., 1,3 Ajay Niranjan, M.Ch., 1,3 John C. Flickinger, M.D., 2,3 and L. Dade Lunsford, M.D. 1,3 Departments of 1 Neurological Surgery and 2 Radiation Oncology, and 3 Center for Image-Guided Neurosurgery, University of Pittsburgh, Pennsylvania; and 4 Department of Neurosurgery, Kyungpook National University Hospital, Daegu, South Korea Object. To assess the long-term outcomes of stereotactic radiosurgery (SRS) for cerebellopontine angle (CPA) meningiomas, the authors retrospectively reviewed data from a 20-year experience. They evaluated progression-free survival as well as improvement, stabilization, or deterioration in clinical symptoms. Methods. Seventy-four patients with CPA meningiomas underwent SRS involving various Gamma Knife technologies between 1990 and The most common presenting symptoms were dizziness or disequilibrium, hearing loss, facial sensory dysfunction, and headache. The median tumor volume was 3.0 cm 3 (range cm 3 ), and the median radiation dose to the tumor margin was 13 Gy (range Gy). The median follow-up period was 40 months (range months). Results. At last imaging follow-up, the tumor volume had decreased in 46 patients (62%), remained stable in 26 patients (35%), and increased in 2 patients (3%). The progression-free survival after SRS was 98% at 1 year, 98% at 3 years, and 95% at 5 years. At the last clinical follow-up, 23 patients (31%) showed neurological improvement, 43 patients (58%) showed no change in symptoms or signs, and 8 patients (11%) had worsening symptoms or signs. The neurological improvement rate after SRS was 16% at 1 year, 31% at 3 years, and 40% at 5 years. The post-srs deterioration rate was 5% at 1 year, 10% at 3 years, and 16% at 5 years. A multivariate analysis demonstrated that trigeminal neuralgia was the symptom most likely to worsen after SRS (HR 0.08, 95% CI ; p = 0.001). Asymptomatic peritumoral edema occurred in 4 patients (5%) after SRS, and symptomatic adverse radiation effects developed in 7 patients (9%). Conclusions. Stereotactic radiosurgery for CPA meningiomas provided a high tumor control rate and relatively low risk of ARE. Tumor compression of the trigeminal nerve by a CPA meningioma resulted in an increased rate of facial pain worsening in this patient experience. ( Key Words stereotactic radiosurgery Gamma Knife meningioma cerebellopontine angle Cerebellopontine angle (CPA) meningiomas are a relatively rare anatomical subgroup of meningiomas and comprise 6% 15% of all tumors in the region of the CPA. 15,20,23,24,27 Complete resection has often proved difficult because of the relationship of the tumor to critical neurovascular structures in the posterior fossa. 1,16,20,22 Stereotactic radiosurgery (SRS) has become an alternative frequently used management option for such tumors and is reported to lead to high tumor control rates and low complication rates. 13,18 In the present study, we Abbreviations used in this paper: ARE = adverse radiation effect; BNI = Barrow Neurological Institute; CPA = cerebellopontine angle; GR = Gardner-Robertson; HB = House-Brackmann; IAC = internal auditory canal; PFS = progression-free survival; SPGR = spoiled grass gradient recalled; SRS = stereotactic radiosurgery. evaluated clinical and imaging outcomes after Gamma Knife SRS for CPA meningiomas. We analyzed progression-free survival (PFS) and studied whether patients had improvement, stabilization, or deterioration in neurological function. Methods Patient Population The University of Pittsburgh Institutional Review Board approved this retrospective study. Between 1990 and 2010, 74 consecutive patients with CPA meningiomas underwent SRS with one of several Leksell Gamma Knife units (Elekta Inc. Atlanta; units U, B, C, 4C, and Perfexion) at the University of Pittsburgh Medical Center. 708 J Neurosurg / Volume 120 / March 2014

2 Radiosurgery for cerebellopontine angle meningioma We excluded patients with neurofibromatosis, multiple meningiomas, those with fewer than 3 months of followup, and those whose prior surgical histology indicated that the tumor was atypical or anaplastic. Cerebellopontine angle meningiomas were defined as tumors whose maximal volume was centered at the anatomical junction of the lateral cerebellum, the pons, and the internal auditory meatus. The bulk of the tumor was superior to the jugular foramen and inferior to the trigeminal nerve. We did not include meningiomas that appeared to arise from the dura of the clivus, the foramen magnum, or the tentorium. Radiosurgery was considered in the following groups of patients: those with recurrent or residual tumors after primary resection; those with symptomatic primary tumors in locations associated with a high risk for complete resection; those with medical comorbidities or advanced age; and those younger patients who declined microsurgery or continued observation. The diagnosis of meningioma was determined in 60 patients based on typical imaging features (uniform contrast enhancement and a dural tail) and in 14 patients by pathological examination of tissue obtained at the time of prior surgery. There were 12 male and 62 female patients whose median age was 57 years (range years). In 14 patients who had undergone prior surgery, the median interval between resection and SRS was 45 months (range months). Nine of these 14 patients had recurrent tumors and underwent SRS at a median of 79 months (range months) after their last resection. Five patients with residual tumors underwent planned SRS at a median of 5 months (range 3 56 months) after resection. Seventy-one patients (96%) had neurological symptoms and/or signs at the time of SRS. The median symptom duration was 12 months (range months). The demographic and presenting characteristics of this study population of 74 patients are shown in Table 1. The most common presenting symptom was dizziness or disequilibrium, which was noted in 40 patients (54%). Thirty-eight patients (51%) had hearing loss, 26 (35%) had facial sensory dysfunction, and 24 (32%) had headache. Hearing measurements included pure tone average (average hearing level at 250 Hz, 500 Hz, l khz, and 4 khz) and speech discrimination score maximal scores. Hearing was classified according to the Gardner-Robertson (GR) classification system. 6 Before SRS, 29 patients (39%) had serviceable hearing (GR Class I II) and 9 (12%) had nonserviceable hearing (GR Class III V). Facial nerve function was classified according to the House-Brackmann (HB) grading system. 7 Four patients (5%), including 2 who had undergone prior surgery, had mild to moderate facial weakness (HB Grade II III). Four patients (5%), including 3 who had undergone prior surgery, had severe facial weakness (HB Grade IV VI). Tumors were classified by location in relationship to the internal auditory canal (IAC): 16 anterior in 13 patients (18%), posterior in 30 (41%), superior in 15 (20%), inferior in 4 (5%), and central in 12 (16%) to the IAC. Thirty patients (41%) had tumors that extended into the IAC. Radiosurgery Technique Our radiosurgery technique has been described in J Neurosurg / Volume 120 / March 2014 TABLE 1: Characteristics in 74 patients with CPA meningioma treated with SRS Factor Value female (%) 62 (84) median age in yrs (range) 57 (34 83) median symptom duration in mos (range) 12 (0 132) IAC extension (%) 30 (41) tumor relative to the IAC (%) anterior 13 (18) posterior 30 (41) superior 15 (20) inferior 4 (5) central 12 (16) median tumor vol in cm 3 (range) 3.0 ( ) prior microsurgery (%) 14 (19) initial symptoms (%) headache 24 (32) ataxia 10 (14) facial sensory dysfunction 26 (35) facial numbness 15 (20) facial paresthesia 3 (4) facial pain 8 (11) diplopia 6 (8) facial weakness (HB grade) 8 (11) II III 4 (5) IV VI 4 (5) hearing loss 38 (51) serviceable 29 (39) nonserviceable 9 (12) tinnitus 17 (23) dizziness or disequilibrium 40 (54) dysphagia 1 (1) detail in previous reports. 5 Patients underwent application of a model G Leksell stereotactic frame under local anesthesia. After attaching an imaging-compatible fiducial system to the frame, we performed either high-resolution CT or MRI in all patients. When patients had contraindication to MRI (for example, a pacemaker or ferrous metallic foreign bodies), axial plane stereotactic CT was performed and the scans were then reformatted into coronal and sagittal images. For patients who underwent MRI, an initial 3D localizer sequence, including axial, coronal, and sagittal MR images, was performed to define the region of interest. Then, a contrast-enhanced, high-resolution axial plane 3D spoiled grass gradient recalled (SPGR) acquisition in steady-state sequence was used to visualize the tumor. To evaluate the tumor morphology and the surrounding brain, T2-weighted MR images using fast spin echo also were acquired. To obtain images of inner ear structures and cranial nerves, T2-weighted volumeacquisition MRI with 1- or 1.5-mm slices was performed. Images were transferred to a computer workstation for dose planning. All patients received an intravenous dose 709

3 S. H. Park et al. of mg methylprednisolone after radiosurgery, and all were discharged from the hospital within 2 hours. The SRS treatment parameters are shown in Table 2. The tumor volume was determined at the time of treatment planning, the goal of which was to envelop the 3D tumor volume in a highly conformal and selective dose plan. The median tumor volume was 3.0 cm 3 (range cm 3 ). The median prescription dose delivered to the tumor margin was 13 Gy (range Gy). The median prescription isodose line was 50% (range 45% 55%). The maximum radiation dose varied from 22 to 50 Gy (median 26 Gy). Follow-Up Examination Patients were instructed to undergo clinical and imaging assessment after SRS at 6-month intervals during the 1st year, annually for 2 years, and at less frequent intervals thereafter (every 4 years past Year 10). A neurological evaluation was performed to assess clinical outcomes at the time of imaging. Either MRI or CT was performed to evaluate tumor response and to detect any adverse radiation effect (ARE). All patients had a minimum of 3 months of follow-up (median 40 months, range months). Fifty-eight patients (78%) had more than 2 years of follow-up. We used the Barrow Neurological Institute (BNI) pain intensity score to evaluate patients with associated trigeminal neuralgia. 21 Patients with BNI pain Scores I IIIb were considered to have a satisfactory treatment outcome. Treatment failure was defined as BNI Scores IV and V. A trigeminal neuralgia recurrence was defined as a relapse to a lower score after first experiencing an initially greater level of pain relief. A decrease or increase in tumor size was defined as a 15% or greater change in tumor volume compared with the volume at the time of SRS. 25 Follow-up tumor volumes were estimated by multiplying the largest imaging x, y, and z dimensions by 0.5. Statistical Analysis For statistical analysis, we constructed Kaplan-Meier plots for PFS and symptom improvement and deterioration rates starting from the date of SRS and continuing until the last follow-up MRI and clinical assessment. The improvement rate of neurological symptoms was defined as the following: number of patients with improvement in neurological symptoms divided by total number of patients. The deterioration rate of neurological symptoms was defined as the following: number of patients with deterioration in neurological symptoms divided by total number of patients. The following variables were assessed with a p value of less than 0.05 set as significant: TABLE 2: Stereotactic radiosurgery treatment parameters Factor Value (range) median margin dose in Gy 13 (11 16) median max dose in Gy 26 (22 50) median isodose line in % 50 (45 55) median no. of isocenters 8 (2 18) age, sex, symptom duration, tumor location, IAC extension, tumor volume, prior microsurgery, history of hydrocephalus, initial presenting symptoms, tumor margin dose, maximal dose, isodose line, number of isocenters, and Karnofsky Performance Scale score. The univariate analysis was performed using the log-rank test (categorical data) and the Cox proportional hazards model (continuous data). Prognostic factors of symptom deterioration in the univariate analysis (p < 0.2) were entered into the multivariate analysis. The multivariate analysis was performed using the Cox proportional hazards model. A comparison of variables was performed using the Fisher exact test, the Mann-Whitney U-test, and Kruskal-Wallis test. Standard statistical processing software (SPSS, version 18.0) was used. Results Imaging Outcomes At the last imaging follow-up, tumor volumes had decreased in 46 patients (62%), remained stable in 26 patients (35%), and increased in 2 patients (3%) (Table 3). In these 2 patients tumor progression was documented at 14.6 months and 17.1 months after SRS, respectively. Kap lan- Meier analysis showed that the PFS after SRS was 98% at 1 year, 98% at 3 years, and 95% at 5 years (Fig. 1). None of the aforementioned evaluated factors proved significant in the univariate analysis. In 4 patients (5%), asymptomatic peritumoral new high signal intensity was demonstrated on T2-weighted MR images at a median of 9.7 months (range months) after SRS. After SRS, 2 patients (3%) developed symptomatic hydrocephalus at an interval of 2 months and 45 months, respectively, and both patients underwent placement of a ventriculoperitoneal shunt. Overall Clinical Outcomes At the last clinical follow-up, 23 patients (31%) had improvement of their neurological symptoms, 43 patients (58%) had stable symptoms, and 8 patients (11%) had symptom deterioration. No patients required repeat radiosurgery during the follow-up period. After SRS, a single patient required delayed resection for pain relief of trigeminal neuralgia despite an absence of tumor progression. Four patients, whose median age at the time of radiosurgery was 79 years (range years), died at a median of 85 months (range months) after SRS. One patient died due to colon cancer, and 3 died of unknown causes. One patient developed an out-of-field glioblastoma in the superior frontal lobe 11 months after SRS. This patient opted for conservative management and died 3 months after diagnosis of the glioblastoma. Improvement of Prior Neurological Symptoms The most common symptom to improve after SRS (in 8 of 23 overall patients with improvement) was dizziness or disequilibrium. Sixteen (70%) of these 23 patients had a decrease in tumor volume and 7 patients (30%) had no change in volume. Other symptoms noted to improve included facial sensory dysfunction in 6, hearing loss in 5, diplopia in 3, headache in 2, and facial weakness in 710 J Neurosurg / Volume 120 / March 2014

4 Radiosurgery for cerebellopontine angle meningioma TABLE 3: Overall clinical and radiological outcomes after SRS Tumor Vol Prior Symptoms Unchanged Improved Worse Overall (%) stable (35) decreased (62) increased (3) overall (%) 43 (58) 23 (31) 8 (11) 74 (100) 1. Three patients experienced improvement in multiple preradiosurgery symptoms. In those with clinical improvement, the median symptom duration was 12 months (range 1 72 months). Improvement of prior neurological symptoms was reported at a median of 12 months (range months) after SRS. Kaplan-Meier analysis demonstrated that the improvement rate of neurological function after SRS was 16% at 1 year, 31% at 3 years, and 40% at 5 years (Fig. 2). Deterioration of Neurological Function Eight patients had further worsening of neurological function during the follow-up period. Six of these patients had a decrease in tumor volume, 1 had no change in volume, and 1 had an increase in tumor volume. Worsening control of trigeminal neuralgia was reported by 4 patients. One patient reported further hearing loss, tinnitus, headache, facial weakness, and worsening ataxia. There was no significant relationship between overall clinical outcome and imaging response after SRS (p = 0.2). Seven patients (9%) developed a symptomatic ARE, defined as neurological deterioration with new peritumoral reactive change but no imaging evidence of tumor progression. An ARE after radiosurgery was documented at a median interval of 20 months (range 8 38 months). Neurological deterioration was demonstrated at median follow-up of 23 months (range 8 45 months). Kaplan-Meier analysis showed that the rate of neurological deterioration after SRS was 5% at 1 year, 10% at 3 years, and 16% at 5 years (Fig. 3). The presence of trigeminal neuralgia was the only symptom statistically associated with clinical worsening (p < 0.001, univariate analysis; p = 0.001, HR 0.08, 95% CI , multivariate analysis; Table 4). Cranial Nerve Dysfunction Before SRS, 26 patients (35%) had facial sensory dysfunction. After SRS, facial sensory dysfunction improved in 6 patients. Facial sensory dysfunction remained unchanged in 16 but worsened in 4 patients (Table 5). Trigeminal neuralgia was observed in 8 patients (BNI pain score of II in 2 patients, IIIa in 5, and IIIb in 1) before SRS. Trigeminal neuralgia improved in 2 patients (BNI pain score of I in both) and remained unchanged in 2 patients (BNI pain score of IIIa in both) but worsened in 4 patients (BNI pain score of IIIb in 3 and IV in 1). Im- Fig. 1. Kaplan-Meier curve showing PFS after SRS. J Neurosurg / Volume 120 / March 2014 Fig. 2. Kaplan-Meier curve showing improvement rate of neurological symptoms after SRS. 711

5 S. H. Park et al. Fig. 3. Kaplan-Meier curve showing deterioration rate of neurological symptoms after SRS. provement of pre-srs trigeminal sensory function was detected at a median of 21 months (range months). Worsened sensory loss was detected at a median of 18 months (range 8 31 months). Fourteen of 20 patients without improvement of facial sensory dysfunction had a decrease in tumor volume. All 6 patients with improvement had a decrease in tumor volume. All 4 patients who suffered an increase in trigeminal neuralgia paradoxically also had a decrease in tumor volume. Statistically, there was no association between tumor volume regression and either improvement or worsening of trigeminal sensory function (p = 0.28). Diplopia was observed in 6 patients (8%) before SRS; it improved in 3 patients and remained unchanged in 3 patients. Eight patients (11%) (HB Grade II in 1, III in 3, IV in 1, and VI in 3) had facial weakness before SRS, and 5 of these patients had undergone prior surgery; 6 patients (HB Grade III in 2, IV in 1, VI in 3) remained stable, 1 (HB Grade II) had improvement, and 1 (HB Grade III) worsened. In 21 (55%) of 38 patients with pre-srs hearing loss the tumor extended into the IAC, whereas in 9 (25%) of 36 patients without hearing loss the tumor extended into the IAC. Tumor extension into the IAC was significantly associated with hearing loss before SRS (p = 0.01). A complaint of tinnitus was not associated with IAC extension (p = 0.18) Among 38 patients with pre-srs hearing loss (GR Class I II in 29 and III V in 9), hearing function remained stable in 32 patients (GR Class I II in 23 and III V in 9), improved in 5 patients (GR Class I II in 5), and worsened in 1 patient (GR Class I II in 1). Improvement in pre-srs hearing loss was noted at a median of 12 months (range 6 42 months), whereas increased hearing loss was detected at a median of 20 months. The median radiation dose to the cochlea in 32 patients with unchanged hearing function was 3.2 Gy (range Gy). In 5 patients with hearing improvement, 3 had IAC tumor extension, 2 had no IAC extension, and the median radiation dose to the cochlea was 2.5 Gy (range Gy). The cochlea dose in 1 patient with reduced hearing function and IAC tumor extension was 5.2 Gy. We found no significant association between hearing function outcomes and either radiation dose to the cochlea or the presence of IAC tumor extension (p = 0.31 and p = 0.94, respectively). Tinnitus was observed in 17 patients (23%) before SRS. Tinnitus worsened in 1 patient and remained unchanged in 16 after SRS. Discussion Resection has been considered as the first-line option for patients with CPA meningiomas associated with mass effect and symptoms such as ataxia and headache. Despite continued advances in skull base microsurgery, surgery for CPA meningioma remains challenging because potential injury of adjacent critical vascular structures, cranial nerves, or the brainstem may have a major deleterious effect on postoperative quality of life. 1,16,20,22,27 During the last 20 years, SRS has become an important alternative option for CPA meningiomas. 9,17,26,28 The twin goals of SRS are to maintain or improve function and achieve long-term tumor control. Tumor Control After SRS Pollock et al. 19 have reported that the PFS rate after radiosurgery was equivalent to the PFS obtained after TABLE 4: Statistical analysis of symptom worsening after SRS* Multivariate Analysis Variable Univariate p Value p Value Hazard Ratio 95% CI prior microsurgery NA trigeminal neuralgia < hearing loss NA margin dose NA isocenters NA * The univariate analysis was performed using the log-rank test (categorical data) and the Cox proportional hazards model (continuous data). The multivariate analysis was performed using the Cox proportional hazards model. Prognostic factors of symptom deterioration in univariate analysis (p < 0.2) were entered into multivariate analysis. NA = not applicable. 712 J Neurosurg / Volume 120 / March 2014

6 Radiosurgery for cerebellopontine angle meningioma TABLE 5: Cranial nerve clinical response after SRS Response After SRS Cranial Nerve Deficits Before SRS Improved Unchanged Worse facial sensory dysfunction trigeminal neuralgia BNI pain score I 2 II 2 IIIa 5 2 IIIb 1 3 IV 1 diplopia facial weakness HB grade II 1 1 III IV 1 1 VI 3 3 hearing loss serviceable (GR Class I II) nonserviceable (GR Class III V) tinnitus dysphagia a Simpson Grade 1 resection of small- to medium-size intracranial meningiomas. In the present study, tumor volumes decreased in 62% of patients, remained stable in 35%, and increased in 3%. We identified no specific pre-srs clinical factors that were associated with failure of radiosurgery as defined by delayed tumor progression. The PFS rate after SRS was 98% at 1 year and 95% at 5 years. Nicolato et al. 17 documented the reduction of tumor volumes in 55% of patients with posterior fossa meningiomas; they reported that in 40% of patients tumor volume was stable but noted delayed tumor progression in 5%. Starke et al. 26 reported that 51% of patients with posterior fossa meningiomas (including 28% of patients with CPA meningiomas) displayed a decrease in tumor volume, 36% had no change in volume, and 13% had an increase in volume. The PFS rates at 3, 5, and 10 years were 98%, 96%, and 78%, respectively. Zachenhofer et al. 28 reported that overall control of tumor growth after radiosurgery was achieved in 94% of patients. Our data showed that SRS can provide outcomes similar to those in other reports related to posterior fossa meningiomas. J Neurosurg / Volume 120 / March 2014 Symptom Improvement and Deterioration After SRS In the present study, 23 patients (31%) had improvement of their prior neurological symptoms, 43 patients (58%) had no change in symptoms, and 8 patients (11%) had exacerbation of symptoms. There were no significant clinical factors associated with symptom improvement following SRS. The improvement rate of neurological symptoms after SRS was 16% at 1 year, 31% at 3 years, and 40% at 5 years. Iwai et al. 9 reported that neurological status improved in 15% of patients with skull base meningiomas. Starke et al. 26 reported that 91% of patients with posterior fossa meningiomas had no change or improvement in their neurological condition and 9% of patients showed symptom deterioration. Flannery et al. 4 demonstrated that neurological status improved in 26% of patients with petroclival meningiomas, remained stable in 58%, and worsened in 15%. They suggested that symptomatic improvement may be related to tumor regression, which in turn reduces the risk of cranial nerve demyelination. Demyelinating injuries of cranial nerve potentially lead to a blockade of ephaptic transmission. Eight patients suffered worsening symptoms after SRS: 7 due to ARE and 1 due to tumor progression. In multivariate analysis, patients in whom trigeminal neuralgia was present before SRS had an increased risk of worsening trigeminal neuralgia after SRS (p = 0.001). The rate of additional neurological symptoms after SRS was 5% at 1 year, 10% at 3 years, and 16% at 5 years. Postradiosurgery AREs were detected at a median of 20 months. Posttreatment facial, trigeminal, and auditory neuropathy usually occurred 1 24 months after SRS (median onset 6 months post-srs). 14 An ARE, defined as a new neurological symptom or sign in the absence of measurable tumor volume change (and often associated with imaging evidence of peritumoral T2 reactive changes), was the main cause of neurological deterioration in our study. There was no strong association between symptom improvement or deterioration and change in tumor volume after SRS (p = 0.2). Both clinical and imaging follow-up is important to evaluate treatment-related toxicity. 713

7 S. H. Park et al. Trigeminal Neuralgia Associated With CPA Meningiomas Trigeminal neuralgia resulting from adjacent tumor compression of the fifth cranial nerve is difficult to control by radiosurgery alone. 2,8,11 Total resection of the tumor is likely the most effective method to achieve pain control, but complete removal is not always feasible and may be associated with additional trigeminal sensory loss. 2 The pathophysiology of tumor-associated typical trigeminal neuralgia may be related to displacement of a blood vessel into the root entry zone of the trigeminal nerve, or direct compression from the tumor itself. 10 Huang et al. 8 reported that the only statistically significant factor related to pain relief was tumor-volume shrinkage. Our results confirmed that all 6 patients with improvement of trigeminal neuralgia had a decrease in tumor volume. Because of the small number of patients, we could not demonstrate a statistical relationship between tumor regression and improvement of trigeminal sensation (p = 0.28). In a previous report from our center, we found that petroclival meningioma regression was not associated with trigeminal pain relief (p = 0.09). 11 Tumor-related trigeminal neuralgia often persisted to varying degrees after radiosurgery, even though SRS provided effective tumor control. 11 Our results showed that new symptoms developed in 8 patients after SRS, and in 4 the new symptom was trigeminal neuralgia. Hearing Loss Associated With CPA Meningiomas Cerebellopontine angle meningiomas that extend into IAC often affect hearing function. Our results showed that tumor extension within the IAC was related to preexisting hearing loss (p = 0.01). Hearing preservation after radiosurgery for CPA meningiomas has rarely been reported. In the present study, overall, some measurable hearing was achieved in 73 (99%) of 74 patients with CPA meningiomas. Twenty-eight (97%) of 29 patients with serviceable hearing before SRS had stable or improved hearing function after SRS. The median radiation dose to the cochlea was 3.2 Gy in patients with unchanged hearing after SRS, 2.5 Gy in patients with improved hearing, and 5.2 Gy in a single patient who had deterioration in hearing. Perhaps related to the small number of patients, we found no statistical relationship between hearing outcomes and radiation dose to the cochlea (p = 0.31). Similarly, tumor extension into the IAC (p = 0.94) was not related to hearing outcomes. In contrast, we found that both cochlea dose and intracanalicular tumor location were associated with hearing preservation in patients with vestibular schwannomas. 12 Several theories have been put forward to explain hearing deterioration after SRS. These theories include damage to the cochlear primary sensory cells, injury to the cochlear nerve by the tumor, injury to the cochlear nerve by radiation, and compression or thrombosis of the internal auditory artery, leading to ischemic injury of the cochlea. 3,12 In CPA meningiomas, the greater distance between the lateral tumor margin and the cochlea may explain the high rate of hearing preservation. At the time of the procedure we also advocate that the patient undergo at least 1 whole-brain MRI sequence to exclude a lesion outside of the CPA target. In the present study, a single patient was diagnosed with an out-offield glioblastoma in the superior frontal lobe 11 months after SRS. Unfortunately, the stereotactic MRI done at the time of SRS did not include views of the brain region where the glioblastoma was eventually found 11 months later and all prior studies were destroyed. To reduce AREs after radiosurgery for CPA meningiomas, high-resolution MRI is necessary to visualize both the tumor and regional brain environment. Careful evaluation of stereotactic MRI sequences that include 1-mm SPGR, whole-brain T2-weighted images and 0.5- to 1-mm T2 volume-acquisition images is critical. Limitations of the Present Study Although the present report is one of the largest SRS series to date focused on CPA meningiomas, there are some limitations of such a retrospective analysis. These limitations include the median follow-up of 40 months. In the future, potential patient-referral and -selection biases could be reduced by using a multicenter outcome analysis from data collected by the North American Gamma Knife Consortium. Conclusions We found that SRS for CPA meningiomas provided effective tumor control, an acceptable rate of improvement of neurological symptoms, and a low risk of radiationinduced complications. Patients with a preexisting trigeminal neuralgia associated CPA meningiomas proved more likely to experience pain worsening over long-term follow-up. Acknowledgment We thank Dr. Douglas Kondziolka (NYU Langone Medical Center) for significant contribution to patient management. Disclosure Dr. Lunsford is a consultant for and stockholder in Elekta AB. The work described in this report was funded by a research grant to Dr. Kano from the Osaka Medical Research Foundation for Incurable Diseases. Author contributions to the study and manuscript preparation include the following. Conception and design: Kano. Acquisition of data: Park. Analysis and interpretation of data: Park. Drafting the article: Kano, Park, Lunsford. 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: Kano. Statistical analysis: Park. Study supervision: Kano, Lunsford. References 1. Baroncini M, Thines L, Reyns N, Schapira S, Vincent C, Lejeune JP: Retrosigmoid approach for meningiomas of the cerebellopontine angle: results of surgery and place of additional treatments. Acta Neurochir (Wien) 153: , Cheng TM, Cascino TL, Onofrio BM: Comprehensive study of diagnosis and treatment of trigeminal neuralgia secondary to tumors. Neurology 43: , Delbrouck C, Hassid S, Massager N, Choufani G, David P, Devriendt D, et al: Preservation of hearing in vestibular schwannomas treated by radiosurgery using Leksell Gamma 714 J Neurosurg / Volume 120 / March 2014

8 Radiosurgery for cerebellopontine angle meningioma Knife: preliminary report of a prospective Belgian clinical study. Acta Otorhinolaryngol Belg 57: , Flannery TJ, Kano H, Lunsford LD, Sirin S, Tormenti M, Niranjan A, et al: Long-term control of petroclival meningiomas through radiosurgery. Clinical article. J Neurosurg 112: , Flickinger JC, Kondziolka D, Niranjan A, Maitz A, Voynov G, Lunsford LD: Acoustic neuroma radiosurgery with marginal tumor doses of 12 to 13 Gy. Int J Radiat Oncol Biol Phys 60: , Gardner G, Robertson JH: Hearing preservation in unilateral acoustic neuroma surgery. Ann Otol Rhinol Laryngol 97: 55 66, House JW, Brackmann DE: Facial nerve grading system. Otolaryngol Head Neck Surg 93: , Huang CF, Tu HT, Liu WS, Lin LY: Gamma Knife surgery for trigeminal pain caused by benign brain tumors. J Neurosurg 109 Suppl: , Iwai Y, Yamanaka K, Ikeda H: Gamma Knife radiosurgery for skull base meningioma: long-term results of low-dose treatment. Clinical article. J Neurosurg 109: , Jannetta PJ: Treatment of trigeminal neuralgia by suboccipital and transtentorial cranial operations. Clin Neurosurg 24: , Kano H, Awan NR, Flannery TJ, Iyer A, Flickinger JC, Lunsford LD, et al: Stereotactic radiosurgery for patients with trigeminal neuralgia associated with petroclival meningiomas. Stereotact Funct Neurosurg 89:17 24, Kano H, Kondziolka D, Khan A, Flickinger JC, Lunsford LD: Predictors of hearing preservation after stereotactic radiosurgery for acoustic neuroma. Clinical article. J Neurosurg 111: , Kollová A, Liscák R, Novotný J Jr, Vladyka V, Simonová G, Janousková L: Gamma Knife surgery for benign meningioma. J Neurosurg 107: , Lunsford LD, Niranjan A, Flickinger JC, Maitz A, Kondziolka D: Radiosurgery of vestibular schwannomas: summary of experience in 829 cases. J Neurosurg 102 Suppl: , Moffat DA, Saunders JE, McElveen JT Jr, McFerran DJ, Hardy DG: Unusual cerebello-pontine angle tumours. J Laryngol Otol 107: , Nakamura M, Roser F, Dormiani M, Matthies C, Vorkapic P, Samii M: Facial and cochlear nerve function after surgery of cerebellopontine angle meningiomas. Neurosurgery 57:77 90, Nicolato A, Foroni R, Pellegrino M, Ferraresi P, Alessandrini F, Gerosa M, et al: Gamma knife radiosurgery in meningiomas of the posterior fossa. Experience with 62 treated lesions. Minim Invasive Neurosurg 44: , Pollock BE, Stafford SL, Link MJ, Brown PD, Garces YI, Foote RL: Single-fraction radiosurgery of benign intracranial meningiomas. Neurosurgery 71: , Pollock BE, Stafford SL, Utter A, Giannini C, Schreiner SA: Stereotactic radiosurgery provides equivalent tumor control to Simpson Grade 1 resection for patients with small- to medium-size meningiomas. Int J Radiat Oncol Biol Phys 55: , Roberti F, Sekhar LN, Kalavakonda C, Wright DC: Posterior fossa meningiomas: surgical experience in 161 cases. Surg Neurol 56:8 21, Rogers CL, Shetter AG, Fiedler JA, Smith KA, Han PP, Speiser BL: Gamma knife radiosurgery for trigeminal neuralgia: the initial experience of The Barrow Neurological Institute. Int J Radiat Oncol Biol Phys 47: , Roser F, Nakamura M, Dormiani M, Matthies C, Vorkapic P, Samii M: Meningiomas of the cerebellopontine angle with extension into the internal auditory canal. J Neurosurg 102:17 23, Schaller B, Heilbronner R, Pfaltz CR, Probst RR, Gratzl O: Preoperative and postoperative auditory and facial nerve function in cerebellopontine angle meningiomas. Otolaryngol Head Neck Surg 112: , Schaller B, Merlo A, Gratzl O, Probst R: Premeatal and retromeatal cerebellopontine angle meningioma. Two distinct clinical entities. Acta Neurochir (Wien) 141: , Snell JW, Sheehan J, Stroila M, Steiner L: Assessment of imaging studies used with radiosurgery: a volumetric algorithm and an estimation of its error. Technical note. J Neurosurg 104: , Starke RM, Nguyen JH, Rainey J, Williams BJ, Sherman JH, Savage J, et al: Gamma Knife surgery of meningiomas located in the posterior fossa: factors predictive of outcome and remission. Clinical article. J Neurosurg 114: , Voss NF, Vrionis FD, Heilman CB, Robertson JH: Meningiomas of the cerebellopontine angle. Surg Neurol 53: , Zachenhofer I, Wolfsberger S, Aichholzer M, Bertalanffy A, Roessler K, Kitz K, et al: Gamma-knife radiosurgery for cranial base meningiomas: experience of tumor control, clinical course, and morbidity in a follow-up of more than 8 years. Neurosurgery 58:28 36, 2006 Manuscript submitted July 24, Accepted November 11, Please include this information when citing this paper: published online December 13, 2013; DOI: / JNS Address correspondence to: Hideyuki Kano, M.D., Ph.D., Department of Neurological Surgery, University of Pittsburgh, Ste. B-400, UPMC Presbyterian, 200 Lothrop St., Pittsburgh, PA kanoh@upmc.edu. J Neurosurg / Volume 120 / March