Gamma Knife radiosurgery for posterior fossa meningiomas: a multicenter study

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OBJECT

Posterior fossa meningiomas represent a common yet challenging clinical entity. They are often associated with neurovascular structures and adjacent to the brainstem. Resection can be undertaken for posterior fossa meningiomas, but residual or recurrent tumor is frequent. Stereotactic radiosurgery (SRS) has been used to treat meningiomas, and this study evaluates the outcome of this approach for those located in the posterior fossa.

METHODS

At 7 medical centers participating in the North American Gamma Knife Consortium, 675 patients undergoing SRS for a posterior fossa meningioma were identified, and clinical and radiological data were obtained for these cases. Females outnumbered males at a ratio of 3.8 to 1, and the median patient age was 57.6 years (range 12–89 years). Prior resection was performed in 43.3% of the patient sample. The mean tumor volume was 6.5 cm3, and a median margin dose of 13.6 Gy (range 8–40 Gy) was delivered to the tumor.

RESULTS

At a mean follow-up of 60.1 months, tumor control was achieved in 91.2% of cases. Actuarial tumor control was 95%, 92%, and 81% at 3, 5, and 10 years after radiosurgery. Factors predictive of tumor progression included age greater than 65 years (hazard ratio [HR] 2.36, 95% CI 1.30–4.29, p = 0.005), prior history of radiotherapy (HR 5.19, 95% CI 1.69–15.94, p = 0.004), and increasing tumor volume (HR 1.05, 95% CI 1.01–1.08, p = 0.005). Clinical stability or improvement was achieved in 92.3% of patients. Increasing tumor volume (odds ratio [OR] 1.06, 95% CI 1.01–1.10, p = 0.009) and clival, petrous, or cerebellopontine angle location as compared with petroclival, tentorial, and foramen magnum location (OR 1.95, 95% CI 1.05–3.65, p = 0.036) were predictive of neurological decline after radiosurgery. After radiosurgery, ventriculoperitoneal shunt placement, resection, and radiation therapy were performed in 1.6%, 3.6%, and 1.5%, respectively.

CONCLUSIONS

Stereotactic radiosurgery affords a high rate of tumor control and neurological preservation for patients with posterior fossa meningiomas. Those with a smaller tumor volume and no prior radiation therapy were more likely to have a favorable response after radiosurgery. Rarely, additional procedures may be required for hydrocephalus or tumor progression.

ABBREVIATIONSCI = confidence interval; CN = cranial nerve; CPA = cerebellopontine angle; GKRS = Gamma Knife radiosurgery; HR = hazard ratio; OR = odds ratio; SRS = stereotactic radiosurgery.

Abstract

OBJECT

Posterior fossa meningiomas represent a common yet challenging clinical entity. They are often associated with neurovascular structures and adjacent to the brainstem. Resection can be undertaken for posterior fossa meningiomas, but residual or recurrent tumor is frequent. Stereotactic radiosurgery (SRS) has been used to treat meningiomas, and this study evaluates the outcome of this approach for those located in the posterior fossa.

METHODS

At 7 medical centers participating in the North American Gamma Knife Consortium, 675 patients undergoing SRS for a posterior fossa meningioma were identified, and clinical and radiological data were obtained for these cases. Females outnumbered males at a ratio of 3.8 to 1, and the median patient age was 57.6 years (range 12–89 years). Prior resection was performed in 43.3% of the patient sample. The mean tumor volume was 6.5 cm3, and a median margin dose of 13.6 Gy (range 8–40 Gy) was delivered to the tumor.

RESULTS

At a mean follow-up of 60.1 months, tumor control was achieved in 91.2% of cases. Actuarial tumor control was 95%, 92%, and 81% at 3, 5, and 10 years after radiosurgery. Factors predictive of tumor progression included age greater than 65 years (hazard ratio [HR] 2.36, 95% CI 1.30–4.29, p = 0.005), prior history of radiotherapy (HR 5.19, 95% CI 1.69–15.94, p = 0.004), and increasing tumor volume (HR 1.05, 95% CI 1.01–1.08, p = 0.005). Clinical stability or improvement was achieved in 92.3% of patients. Increasing tumor volume (odds ratio [OR] 1.06, 95% CI 1.01–1.10, p = 0.009) and clival, petrous, or cerebellopontine angle location as compared with petroclival, tentorial, and foramen magnum location (OR 1.95, 95% CI 1.05–3.65, p = 0.036) were predictive of neurological decline after radiosurgery. After radiosurgery, ventriculoperitoneal shunt placement, resection, and radiation therapy were performed in 1.6%, 3.6%, and 1.5%, respectively.

CONCLUSIONS

Stereotactic radiosurgery affords a high rate of tumor control and neurological preservation for patients with posterior fossa meningiomas. Those with a smaller tumor volume and no prior radiation therapy were more likely to have a favorable response after radiosurgery. Rarely, additional procedures may be required for hydrocephalus or tumor progression.

Of all intracranial meningiomas, approximately 7%–12% are located in the posterior fossa.13,16,56 Resection represents the upfront treatment for many patients with symptomatic or progressive posterior fossa meningiomas.50 However, the extent of resection can be limited by the meningioma's proximity to critical vascular and neural structures. Gross-total resection rates reported in the literature for posterior fossa meningiomas vary significantly, from 40% to 96%, and resections are often associated with significant morbidity, mortality, and recurrence.1–5,7,9–12,15–17,20–22,24,27,28,31–33,36,38,41–43,45–48,51,54,56 Extent of resection and morbidity rates vary by location of the tumor in the posterior fossa. For instance, in a recent study, morbidity following resection of petroclival meningiomas and cerebellopontine angle (CPA) meningiomas varied from 20.3% to 47% and 10.4% to 35.7%, respectively.14 In that same study, extent of complete resection for petroclival meningiomas and CPA meningiomas was 0–48% and 82%–86.1%, respectively.14

Some neurosurgeons have recommended radical resection for recurrent meningiomas to prolong life in neurologically stable patients.5 Others have advocated for aggressive maximal resection of meningiomas at first presentation with the use of radiosurgery to treat recurrent or residual meningiomas.8,11,26,60 Stereotactic radiosurgery (SRS) has become an acceptable treatment option for recurrent/residual meningiomas as well as an upfront option.6,29,30

The use of Gamma Knife radiosurgery (GKRS; Elekta AB) for intracranial meningiomas had been previously described in the literature. However, there are few large series for which meaningful statistical analysis can be performed. The posterior fossa has unique anatomical concerns in terms of mass effect, and radiosurgical constraints that differ from supratentorial meningiomas. In the current study, we evaluated the outcomes of patients with posterior fossa meningiomas treated with GKRS across a multiinstitutional experience spanning more than two decades.

Methods

Patient Population

Seven medical centers participating in the North American Gamma Knife Consortium obtained individual institutional review board approvals to participate in this study. A total of 675 patients were identified with posterior fossa meningiomas managed at least in part by GKRS (Table 1). At each center, retrospective clinical outcome analysis of patients with posterior fossa meningiomas who underwent GKRS was performed. The following centers contributed data for this study: the University of Pittsburgh (271 patients), Yale University (9 patients), Cleveland Clinic (12 patients), University of Sherbrooke (64 patients), Barrow Neurological Institute (118 patients), University of Pennsylvania (44 patients), and the University of Virginia (157 patients).

TABLE 1

Characteristics of 675 patients with posterior fossa meningiomas treated with GKRS

CharacteristicTotal
Female sex (%)535 (79.3)
Age (yrs)
 Median57.6 ± 13.4
 Range12–89
Previous resection (%)292 (43.3)
Prior radiotherapy (%)11 (1.6)
Time from presentation to GKRS (mos)
 Mean ± SD28.8 ± 47.0
 Range0–324
Initial presentation (%)
 Headache227 (33.6)
 Subjective dizziness236 (35.0)
 Subjective cognitive alteration41 (6.1)
 CN III/IV/VI83 (13.1)
 CN V224 (33.3)
 CN VII54 (8.0)
 CN VIII193 (28.6)
 CN IX/X31 (4.6)
 CN XI3 (2.4)
 CN XII16 (2.4)
 Cerebellar alteration/deficit27 (4.0)
 Body weakness43 (6.4)
 Change in body sensation53 (7.9)
Location (%)
 Clival48 (7.1)
 Petroclival254 (37.6)
 Petrous33 (4.9)
 Tentorial145 (21.5)
 Cerebellopontine angle177 (26.2)
 Foramen magnum18 (2.7)
Tumor volume (cm3)
 Mean ± SD6.5 ± 6.2
 Range0.15–41.8
Follow-up (mos)
 Mean ± SD60.1 ± 45.4
 Range6–252

The records of patients with meningioma who underwent GKRS between 1988 and 2012 were evaluated by clinicians at each center for study inclusion. A database with selected variables was created and sent to all participating centers. Participating centers reviewed the medical records of their patients, entered the data in the spreadsheet, and removed all patient identifiers from the database. Pooled and de-identified data were screened by an independent third party for errors. Any uncertainties or ambiguities in the data were addressed to the contributing center. Afterward, data were transmitted to the first author, who along with his coauthors developed this report.

Patients were included in the study if they had a histologically diagnosed WHO Grade I meningioma located within the posterior fossa. In addition, patients were included in this study if they had clinical and neuroimaging features consistent with a benign meningioma of this neuroanatomical region. Clinical features would include a medical history absent of prior cancer and an intracranial tumor located in the posterior fossa with MRI and/or CT features most consistent with a meningioma. The neuroimaging features included an extraaxial location, contrast enhancement, dural attachment, and for some patients, tumor calcification. For inclusion, patients were required to have a minimum of 6 months of neuroimaging and clinical follow-up after GKRS.

Radiosurgical Technique

The Gamma Knife Models U, B, C, 4C, or Perfexion were used depending on the technology available at the time of treatment for the participating centers. The radiosurgery began with the application of the Leksell Model G stereotactic frame (Elekta AB) using local anesthetic supplemented by additional sedation as needed. After stereotactic frame placement, high-resolution stereotactic MRI was performed. In rare cases in which MRI was not feasible or when MRI distortion was a concern, a stereotactic CT scan was obtained. Thin-slice axial and/or coronal plane images were obtained after intravenous contrast administration. Radiosurgical dose planning was then performed by the neurosurgeon in conjunction with a radiation oncologist and medical physicist.

The mean volume of the posterior fossa meningiomas was 6.5 cm3 (range 0.15–41.8 cm3; Table 1). The median prescription dose delivered to the tumor margin was 13.6 Gy (range 8–40 Gy). The mean prescription isodose line was 48.5% (range 25%–65%; Table 2). Most of the dose plans involved a multiisocentric approach; a mean of 11 isocenters (range 1–59) were used. Dose selection was based on an empirical algorithm that included considerations related to tumor volume, proximity to critical structures such as the brainstem, preexisting neurological deficits, and history of previous treatment with fractionated radiation therapy.

TABLE 2

Gamma Knife radiosurgery parameters

CharacteristicValue ± SDRange
Median margin dose (Gy)13.6 ± 2.28–40
Mean maximum dose (Gy)28.6 ± 5.612–80
Mean isodose line (%)48.5 ± 5.325–65
Mean no. of isocenters11.0 ± 7.41–59

Clinical and Neuroimaging Follow-Up

Clinical and neuroimaging evaluations were generally performed at follow-up intervals of 6 months for the first 2 years after radiosurgery. In patients who demonstrated no evidence of tumor growth and absence of new neurological findings, follow-up intervals were later increased to every 1–2 years. Whenever feasible, patients underwent follow-up neurological examination and neuroimaging at the respective treating center. However, because participating institutions represent tertiary referral centers, some patients underwent follow-up evaluations by their local physicians. For such patients, clinical notes and actual neuroimaging studies (i.e., not just the radiological reports) were received and reviewed by the treating clinicians who performed the GKRS. The follow-up images were compared with the images obtained at the time of GKRS. Tumor dimensions were assessed in the axial, sagittal, and coronal planes and compared with the comparable measurements on the Gamma Knife neuroimaging studies. Tumor growth, as defined by an increase in 1 of these measurements beyond the tomographic margin of uncertainty within the planned treatment volume or adjacent to it, was considered tumor progression.

Statistical Analysis

Data are presented as median or mean and range for continuous variables, and as frequency and percentage for categorical variables. Calculations of normality were performed by ladder of powers and assessed graphically. Statistical analyses of categorical variables were performed using chi-square, Fisher's exact, and Mantel-Haenszel tests for linear association as appropriate. Statistics of means were conducted using the unpaired Student t-test, both with and without equal variance (Levene's test) as necessary and Wilcoxon rank-sum tests when variables were not normally distributed. The following dependent variables were assessed in univariate and multivariate analysis: tumor-free progression, worsening or new decline in neurological function, and favorable outcome (no tumor progression or worsening or new decline in neurological function). Kaplan-Meier risk of tumor progression was calculated. Factors predictive of tumor progression (p < 0.15) were entered into multivariate Cox regression analyses to assess hazard ratios (HRs). Clinical covariates predicting new or worsening neurological function with a univariate p value < 0.15 were included in multivariable logistic regression analyses. Additionally, clinical covariates predicting unfavorable outcome with a univariate p value < 0.15 were included in multivariable logistic regression analyses. Clinically significant variables and interaction expansion covariates were further assessed in both Cox and logistic multivariable analyses as deemed relevant. Those p values ≤ 0.05 were considered statistically significant.

Results

Patient and Tumor Attributes

Of the 675 patients, the median patient age was 57.6 years (range 12–89 years; Table 1). There was a clear sex predilection in the series, with 535 (79.3%) female patients and only 140 (20.7%) male patients. Two hundred and ninety-two patients (43.3%) had previously undergone resection with histologically confirmed WHO Grade I meningiomas. The remaining patients displayed neuroimaging and clinical features consistent with a benign meningioma. Prior fractionated radiation therapy had been used in 1.6% of patients. The most common presenting symptoms were headaches and dizziness in 33.6% and 35% of patients, respectively. Deficits were observed most frequently in cranial nerves (CNs) V (33.3%) and VIII (28.6%).

Meningioma location was classified by the participating centers based upon the location of the majority (i.e., maximum volume) of the tumor. Locations were categorized based upon commonly used neuroanatomical regions of the skull base.2,3,5,27,55,59 Meningioma locations included 7.1% clival, 37.6% petroclival, 4.9% petrous, 21.5% tentorial, 26.2% CPA, and 2.7% foramen magnum. Mean tumor volume was 6.5 cm3. Mean follow up was 60.1 months (range 6–252 months). Preradiosurgical patient characteristics, presentations, and tumor characteristics are detailed in Table 1.

Radiological Outcome

The mean follow-up duration was 60.1 ± 45.4 months (range 6–252 months). Following radiosurgery, tumor volume decreased by a mean of 1.6 cm3 to a mean posttreatment volume of 4.9 ± 5.9 cm3 (range 0–33 cm3; Table 3). At the last follow-up evaluation, 59 patients (8.8%) had an increase in tumor size, 275 (41.0%) had a decrease in tumor size, and 336 (50.2%) displayed no change in tumor size. Thus, the overall rate of tumor control (i.e., stable or decreased tumor) was 91.2%.

TABLE 3

Overall clinical and tumor outcomes

CharacteristicOutcome
Pre-GKRS tumor volume (cm3)
 Mean ± SD6.5 ± 6.2
 Range0.15–41.8
Post-GKRS tumor volume (cm3)
 Mean ± SD4.9 ± 5.9
 Range0–33
Tumor volume (%)
 Decrease336 (50.2)
 No change275 (41.0)
 Increase59 (8.8)
Clinical outcome (%)
 No change424 (64.9)
 Improvement179 (27.4)
 New or worsening neurological function50 (7.7)
Overall outcome (%)
 Favorable557 (85.8)
 Unfavorable92 (14.2)
Post-GKRS (%)
 Hydrocephalus14 (2.1)
 Ventriculoperitoneal shunt placement11 (1.7)
 Radiotherapy10 (1.5)
 Resection24 (3.6)

Kaplan-Meier analysis demonstrated radiological progression-free survival at 3, 5, 10, and 12 years to be 95%, 92%, 81%, and 77% respectively (Fig. 1). Factors predictive of tumor progression in univariate analysis are displayed in Table 4. Patients with a history of prior resection were not more likely to have tumor progression (HR 1.10, 95% CI 0.65–1.85, p = 0.719; Fig. 2 upper). Progression-free tumor survival according to mean volume is presented in Fig. 2 lower. There was no statistically significant difference in progression-free survival according to tumor location (Fig. 3).

FIG. 1.
FIG. 1.

Kaplan-Meier plot of progression-free survival after SRS for all 675 patients with posterior fossa meningiomas. Numbers in parentheses represent the number of patients reaching each significant timeline milestone.

FIG. 2.
FIG. 2.

Kaplan-Meier plot of progression-free survival after SRS for patients with and without a prior resection (upper), and for patients with tumors < 6.5 cm3 versus those with tumors ≥ 6.5 cm3 (lower). Numbers in parentheses represent the number of patients reaching each significant timeline milestone.

FIG. 3.
FIG. 3.

Kaplan-Meier plot of progression-free survival after SRS for meningiomas in a specific location in the posterior fossa. Figure is available in color online only.

TABLE 4

Factors predictive of tumor progression in univariate and multivariate analyses*

AnalysisPre-GKRS VariablesHR (95% CI)p Value
Univariate
Age >65 years1.95 (1.13–3.34)0.016
Increasing time from symptom onset1.01 (1.00–1.01)0.011
Prior radiotherapy6.87 (3.22–14.67)<0.001
Increasing tumor volume1.04 (1.01–1.08)0.010
Multivariate
Age >65 years2.36 (1.30–4.29)0.005
Increasing tumor volume1.05 (1.01–1.08)0.005
Prior radiotherapy5.19 (1.69–15.94)0.004

Factors predictive of tumor recurrence (p < 0.15). There was a trend toward increased tumor progression with increasing time from symptom onset in multivariate analysis (HR 1.01, 95% CI 1.00–1.01, p = 0.065).

In Cox multivariate analysis, pre-GKRS covariates predictive of tumor progression included age greater than 65 years (HR 2.36, 95% CI 1.30–4.29, p = 0.005), prior history of conventional radiotherapy (HR 5.19, 95% CI 1.69–15.94, p = 0.004), and increasing tumor volume (HR 1.05, 95% CI 1.01–1.08, p = 0.005; Table 4). There was a trend toward tumor progression with increasing time from symptom onset to GKRS in multivariate analysis (HR 1.01, 95% CI 1.00–1.01, p = 0.065). An absence of pre-GKRS resection was not predictive of tumor progression in multivariate analysis when controlling for other covariates or when assessing for interaction between potential relevant covariates. Patients with tumor progression after radiosurgery were 5.16 times more likely to have new or worsening neurological function (95% CI 2.58–10.31, p < 0.001)

Clinical Outcomes

At last clinical follow-up, 424 patients (64.9%) demonstrated no change in clinical outcome, 179 (27.4%) had improvement in clinical outcome, and 50 (7.7%) had new or worsening neurological function (Table 3). Specific alterations in clinical signs and symptoms following GKRS are detailed in Table 5. Following GKRS, new or worsening CN dysfunction was observed most commonly in CN V followed by aggregate dysfunction of CNs III/IV/VI and least commonly in lower cranial nerves including CN IX through XII (Table 5). Following radiosurgery, 24 patients (3.6%) required resection and 10 (1.5%) underwent radiation therapy to treat tumor progression. Of the 653 patients with reliable clinical follow-up information, 14 patients (2.1%) developed hydrocephalus apparent on radiological imaging, and 11 (1.7%) required ventriculoperitoneal shunt placement.

TABLE 5

Specific alterations in clinical signs and symptoms following GKRS

CharacteristicPresentation (%)New or Worsening Function (%)
Subjective dizziness236 (35.0)34 (5.1)
Subjective cognitive alteration41 (6.1)15 (2.2)
CN III/IV/VI83 (13.1)21 (3.3)
CN V224 (33.3)28 (4.2)
CN VII54 (8.0)8 (1.2)
CN VIII193 (28.6)12 (1.8)
CN IX/X31 (4.6)6 (0.9)
CN XI3 (2.4)1 (0.2)
CN XII16 (2.4)3 (0.5)
Ataxia4 (12.4)14 (2.1)
Other cerebellar alteration/deficit27 (4.0)27 (4.0)
Body weakness43 (6.4)10 (1.5)
Change body sensation53 (7.9)8 (1.2)

Univariate predictors of new or worsening neurological function after GKRS are displayed in Table 6. These predictors of new or worsening neurological function after GKRS within the univariate analysis were male sex; clival, petrous, and CPA location; prior conventional radiotherapy; symptomatic presentation other than headache; peripheral and maximal dose; and increasing tumor volume (Table 6). In multivariate analysis, increasing tumor volume (OR 1.06, 95% CI 1.01–1.10, p = 0.009) and clival, petrous, or CPA location versus petroclival, tentorial, and foramen magnum location (OR 1.95, 95% CI 1.05–3.65, p = 0.036) were predictive of new or worsening neurological function after radiosurgery.

TABLE 6

Factors predictive of new or worsening symptoms following radiosurgery in univariate and multivariate analyses*

AnalysisPre-GKRS VariablesOR (95% CI)p Value
Univariate
Male sex2.62 (0.84–3.09)0.148
Location
 Clival, petrous, CPA1.61 (0.90–2.87)0.106
 Petroclival, tentorium, foramen magnum1
Prior radiotherapy5.43 (1.36–21.67)0.017
Symptomatic presentation other than headache2.35 (0.92–6.05)0.076
Increasing peripheral dose0.83 (0.69–0.99)0.034
Increasing maximal dose0.95 (0.89–1.01)0.147
Isodose volume1.06 (1.01–1.10)0.008
Increasing volume1.05 (1.01–1.09)0.024
Multivariate
Location
 Clival, petrous, CPA1.95 (1.05–3.65)0.036
 Petroclival, tentorium, foramen magnum1
Increasing tumor volume1.06 (1.01–1.10)0.009

Factors predictive of tumor recurrence (p < 0.15).

Favorable Outcome After SRS

A favorable outcome, defined as tumor control along with neurological stability or improvement, was achieved in 557 (85.8%) of 649 patients. An unfavorable outcome (i.e., tumor progression and/or new or worsening neurological function) was found in 92 patients (14.2%). Univariate predictors of overall outcome are demonstrated in Table 7. Multivariate predictors of an unfavorable outcome included increasing tumor volume (OR 3.24, 95% CI 1.12–9.37, p = 0.001) and a history of prior conventional radiotherapy (OR 13.46, 95% CI 2.4–75.22, p = 0.003).

TABLE 7

Factors predictive of an unfavorable outcome in univariate and multivariate analyses*

AnalysisVariablesOR (95% CI)p Value
Univariate
Increasing tumor volume1.06 (1.02–1.09)0.001
Symptomatic other than headache1.79 (0.95–3.40)0.074
Prior radiotherapy26.38 (5.50–126.35)<0.001
Increasing time from symptom onset1.01 (1.0–1.01)0.046
Margin dose0.88 (0.77–1.00)0.051
Isodose line0.96 (0.92–0.99)0.013
Multivariate
Increasing tumor volume3.24 (1.12–9.37)0.001
Prior radiotherapy13.46 (2.4–75.22)0.003

Favorable outcome defined as no tumor progression or new or worsening neurological function. Factors predictive of tumor recurrence (p < 0.15).

Other Serious Adverse Effects

In the current study, there was no evidence of radiation-induced tumor formation or malignant transformation of an existing meningioma.

Discussion

Posterior Fossa Location and Resection

Meningiomas involving the posterior fossa comprise approximately 7%–12% of all meningiomas.13,16,56 Posterior fossa meningiomas present a unique set of challenges as compared with those involving the supratentorial region. Posterior fossa meningiomas are often closely associated with critical arteries, venous sinuses, cranial nerves, and the brainstem, and such proximity to critical structures makes resection more challenging. Also, their resulting growth can lead to mass effect that is less tolerated than their supratentorial counterparts. In instances of appreciable mass effect, hydrocephalus, or significant histological uncertainty, resection remains a valuable approach. Nevertheless, complete resection rates for posterior fossa meningiomas vary substantially, with rates ranging from 40% to 96%.1–5,7,9–12,15–17,20–22,24,27,28,31–33,36,38,41–43,45–48,51,54,56

Although some continue to advocate for aggressive resection, others have instead proposed a more conservative approach involving subtotal resection that is guided by relief of mass effect and preservation of neurological function.6,9,34,60 In published series, this contemporary approach has led to morbidity and mortality rates of 0%–13% and 13%–40%, respectively. Recurrence rates after an initial resection vary from 12% to 91%.1–5,7,9–12,15–17,20–22,24,27,28,31–33,36,38,41–43,45–48,51,54,56 Such recurrences depend upon the length of follow-up, characteristics of the tumor, and the extent of the initial resection. Although repeat resection is feasible, repeat resection is associated with increased morbidity and mortality due to difficult resection planes.5,7,22,24,60

Radiation Therapy

Radiation therapy has been used for some patients with intracranial meningiomas, including ones involving the posterior fossa. Progression-free survival rates at 5 and 10 years after conventional radiotherapy range from 73% to 92% and 61% to 83%, respectively.23,25,26,35,40,57 More contemporary techniques such as intensity-modulated radiation therapy and proton therapy offer increased conformality and more sparing of critical structures compared with conventional techniques.44,58 The lower integral dose and higher conformality that are touted as the advantages of intensity-modulated radiation therapy and proton beam over conventional radiotherapy techniques for meningiomas have been longstanding features of radiosurgery. While radiotherapy has been used for large volume or poorly delineated posterior fossa meningiomas, its role for smaller to moderately sized and well-demarcated meningiomas involving the posterior fossa has largely been displaced by SRS.

Stereotactic Radiosurgery

Radiosurgery has proven to be an important tool in the treatment of meningiomas, with most large radiosurgical series demonstrating tumor control rates of 85% or higher for patients with Grade I meningiomas.49 Following radiosurgery, tumor control has generally been accompanied by neurological preservation or improvement in the majority of patients.49 However, most radiosurgical series have looked broadly at meningiomas of various locations, and few have focused on the challenges associated with meningiomas of the posterior fossa.

In the published literature, there are only a few radiosurgical series that focus exclusively on posterior fossa meningiomas (Table 8). In an earlier series by the University of Pittsburgh team, Subach and colleagues reported on their experience with 62 patients exhibiting petroclival meningiomas. Of these 62 patients, 39 (63%) had at least 1 prior resection. With a median follow-up of 37 months, tumor control was achieved in 92% of patients, and neurological status improved in 21% and remained stable in 66% of patients.55 In a later series by that same group, tumor control and neurological preservation were achieved in 90% and 85%, respectively, of 168 patients with petroclival meningiomas who underwent GKRS.18 In another study by the group in Verona, Italy, Nicolato and colleagues39 used GKRS to treat 57 patients with 62 posterior fossa meningiomas. With a median follow-up of 28.7 months, tumor regression was observed in 55% of cases and stability in another 40%.39 Transient side effects due to radiosurgically induced edema were noted in 6.5%, but there were no instances of permanent morbidity associated with GKRS in this series.39 More recently from the University of Virginia, a series of 152 patients with posterior fossa meningiomas were evaluated after GKRS. With a median follow-up of 84 months, tumor control and neurological preservation were achieved in 87% and 91% of patients, respectively.52 Smaller radiosurgical series confirm the efficacy and safety of radiosurgery for patients with posterior fossa meningiomas, even of the foramen magnum.53,61

TABLE 8

Major radiosurgical series for posterior fossa meningiomas

Authors & YearNo. of PatientsMedian or Mean Follow-Up (mos)Tumor Control (%)Neurological Preservation (%)Complications (%)
Subach et al., 1998623792878
Nicolato et al., 20015728.7951006.5
Flannery et al., 20101687290858
Starke et al., 20105601001000
Starke et al., 20111528487919
Zenonos et al., 201224471001000
Current series675609192.37.7

The current series represents the largest one to date for posterior fossa meningiomas treated with radiosurgery (Table 8). This series has sufficient statistical power to permit subgroup analysis to evaluate the effect of tumor location, and the study also gives a broader assessment of neurological complications associated with GKRS. In the current series, tumor control was achieved in 91.2% of patients at last follow-up. Just if not more importantly, neurological preservation was accomplished in 92.3% of patients. Thus, based upon the high chance of tumor control and neurological preservation observed in the current series, those with small to moderately sized posterior fossa meningiomas for whom relief of mass effect is not required would appear well served by GKRS. Those with a smaller tumor volume and no prior radiation therapy were more likely to achieve both tumor control and a favorable neurological outcome after radiosurgery of their posterior fossa meningiomas. The benefit of a smaller tumor volume at the time of radiosurgery does underscore the benefits of a cytoreductive but neurologically preserving surgery for those patients who have larger tumors at initial presentation. In terms of prior radiotherapy, patients in whom radiation therapy was unsuccessful likely exhibit a more aggressive tumor. Also, prior radiotherapy can require a reduction in the radiosurgical dose below that which might be optimal. Thus, the radiosurgical cohort that had unsuccessful prior radiotherapy is an inherently more challenging one to manage, and the prescription dose lower than what would likely have been given in the absence of prior ionizing radiation makes tumor control less likely.

Cranial nerve dysfunction after GKRS varied depending upon the nerve. Cranial nerve V and aggregate CN III, IV, and VI dysfunction were most common whereas lower CN dysfunction was exceedingly rare (Table 4). The risk factors for CN palsy after GKRS are likely multifactorial. Variability of the CNs to ionizing radiation may be due in part to the functionality (e.g., special sensory, visceral sensory, visceral motor, and somatic motor), relative radioresistance, vascular supply to the nerve, and irradiated length of a particular nerve. In particular, CN V can routinely tolerate a maximum dose of 80 Gy in cases of trigeminal neuralgia when such a dose is delivered to a small volume of the nerve. While the doses used in this series to treat meningiomas were substantially lower than 80 Gy, the length of nerve irradiated and the integrated dose to the nerve have been shown to be related to and affect the probability of trigeminal nerve dysfunction after GKRS, and these parameters were likely responsible for some of the CN V dysfunction.34 Tumor location (e.g., petrous vs petroclival) also affected the likelihood of new or worsening neurological symptoms following radiosurgery. In cases in which the tumor may have a broader interface with the brainstem or traversing cranial nerves, neurological dysfunction may occur with a higher probability after radiosurgery.

Similarly to patients undergoing resection, radiation therapy, or no treatment, longitudinal follow-up of patients after radiosurgery is required. In the current series, 2.1% of patients with posterior fossa meningiomas developed hydrocephalus following radiosurgery. The incidence of postradiosurgical hydrocephalus compares favorably with the 16% incidence noted in a recent surgical series of posterior fossa meningiomas by Nanda et al.37 Cerebrospinal fluid malabsorption from a high protein level has been postulated to be the cause of postradiosurgical hydrocephalus.19 Such patients require CSF diversion, typically with a shunt as was the case in 1.6% of patients in the current series. Tumor progression in the current series was rare, but 5.1% of patients in the current series required additional intervention for their meningioma. Close surveillance with neuroimaging and clinical assessments will allow detection of problems and timely intervention when necessary for radiosurgical patients.

Study Limitations

The current study represents the largest radiosurgical one to date on this particular indication. Nevertheless, the study has limitations worth noting. The participating centers use a common radiosurgical platform and dose planning software. The outcomes, both favorable and unfavorable, may not be representative of other commercially available systems. Also, radiosurgery comprises a significant portion of the practice of the contributing clinicians in this study. We did not examine the learning curve for this indication nor did we examine the number of cases required to maintain proficiency. In addition, the radiosurgical techniques for planning, treatment, and delivery have evolved over the time span of this study. We do not account for the evolution of the field in assessing outcomes with posterior fossa meningiomas.

The study suffers from inherent biases of a retrospective study. These include selection bias and a lack of a control arm to the study. In particular, selection criteria varied from center to center and as a function of time as the field of radiosurgery has evolved over the past two decades. Also, not all of the tumors were histologically confirmed to be a meningioma. Thus, it is possible that some other benign skull-based lesions were included in this study. However, any patient with histology inconsistent with a WHO Grade I meningioma was excluded from the study. This is true of preradiosurgical histology and histology obtained at the time of resection following failed radiosurgery.

Conclusions

Gamma Knife radiosurgery affords tumor control and neurological preservation in the vast majority of patients with posterior fossa meningiomas. While resection continues to be of value for relief of mass effect and histological confirmation in ambiguous cases, radiosurgery either as an upfront treatment or an adjuvant one after prior resection represents a valuable neurosurgical tool for treatment of patients with posterior fossa meningiomas.

Acknowledgment

We appreciate the assistance of Ms. Sharon DeCesare with coordination of data for the North American Gamma Knife Consortium.

Author Contributions

Conception and design: Sheehan. Acquisition of data: Kano, Barnett, Mathieu, Chiang, Yu, Hess, McBride, Honea, Nakaji, Lee, Rahmathaulla, Evanoff, Alonso-Basanta, Lunsford. Analysis and interpretation of data: Starke, Lunsford. Drafting the article: Sheehan. Critically revising the article: Sheehan, Starke, Kano, Barnett, Mathieu, Chiang, Yu, McBride, Nakaji, Lee, Alonso-Basanta, Lunsford.

References

  • 1

    Adegbite ABKhan MIPaine KWTan LK: The recurrence of intracranial meningiomas after surgical treatment. J Neurosurg 58:51561983

  • 2

    Al-Mefty O: Clinoidal meningiomas. J Neurosurg 73:8408491990

  • 3

    Al-Mefty OFox JLSmith RR: Petrosal approach for petroclival meningiomas. Neurosurgery 22:5105171988

  • 4

    Arnautović KIAl-Mefty O: Primary meningiomas of the jugular fossa. J Neurosurg 97:12202002

  • 5

    Arnautović KIAl-Mefty OHusain M: Ventral foramen magnum meninigiomas. J Neurosurg 92:1 Suppl71802000

  • 6

    Asthagiri ARHelm GASheehan JP: Current concepts in management of meningiomas and schwannomas. Neurol Clin 25:12091230xi2007

  • 7

    Babu RPSekhar LNWright DC: Extreme lateral transcondylar approach: technical improvements and lessons learned. J Neurosurg 81:49591994

  • 8

    Barbaro NMGutin PHWilson CBSheline GEBoldrey EBWara WM: Radiation therapy in the treatment of partially resected meningiomas. Neurosurgery 20:5255281987

  • 9

    Bassiouni HNtoukas VAsgari SSandalcioglu EIStolke DSeifert V: Foramen magnum meningiomas: clinical outcome after microsurgical resection via a posterolateral suboccipital retrocondylar approach. Neurosurgery 59:117711872006

  • 10

    Bertalanffy HGilsbach JMMayfrank LKlein HMKawase TSeeger W: Microsurgical management of ventral and ventrolateral foramen magnum meningiomas. Acta Neurochir Suppl 65:82851996

  • 11

    Black PMVillavicencio ATRhouddou CLoeffler JS: Aggressive surgery and focal radiation in the management of meningiomas of the skull base: preservation of function with maintenance of local control. Acta Neurochir (Wien) 143:5555622001

  • 12

    Bruneau MGeorge B: Foramen magnum meningiomas: detailed surgical approaches and technical aspects at Lariboisière Hospital and review of the literature. Neurosurg Rev 31:19332008

  • 13

    Castellano FRuggiero G: Meningiomas of the posterior fossa. Acta Radiol Suppl 104:11771953

  • 14

    Chen CMHuang APKuo LTTu YK: Contemporary surgical outcome for skull base meningiomas. Neurosurg Rev 34:2812962011

  • 15

    Cho CWAl-Mefty O: Combined petrosal approach to petroclival meningiomas. Neurosurgery 51:7087182002

  • 16

    Cudlip SAWilkins PRJohnston FGMoore AJMarsh HTBell BA: Posterior fossa meningiomas: surgical experience in 52 cases. Acta Neurochir (Wien) 140:100710121998

  • 17

    Erkmen KPravdenkova SAl-Mefty O: Surgical management of petroclival meningiomas: factors determining the choice of approach. Neurosurg Focus 19:2E72005

  • 18

    Flannery TJKano HLunsford LDSirin STormenti MNiranjan A: Long-term control of petroclival meningiomas through radiosurgery. J Neurosurg 112:9579642010

  • 19

    Fujimoto AMatsumura AMaruno TYasuda SYamamoto MNose T: Normal pressure hydrocephalus after gamma knife radiosurgery for cerebellopontine angle meningioma. J Clin Neurosci 11:7857872004

  • 20

    George BDematons CCophignon J: Lateral approach to the anterior portion of the foramen magnum. Application to surgical removal of 14 benign tumors: technical note. Surg Neurol 29:4844901988

  • 21

    George BLot GBoissonnet H: Meningioma of the foramen magnum: a series of 40 cases. Surg Neurol 47:3713791997

  • 22

    George BLot GVelut SGelbert FMourier KL: [French language Society of Neurosurgery. 44th Annual Congress. Brussels, 8–12 June 1993 Tumors of the foramen magnum.]. Neurochirurgie 39:Suppl 11891993. (Fr)

  • 23

    Glaholm JBloom HJCrow JH: The role of radiotherapy in the management of intracranial meningiomas: the Royal Marsden Hospital experience with 186 patients. Int J Radiat Oncol Biol Phys 18:7557611990

  • 24

    Goel ADesai KMuzumdar D: Surgery on anterior foramen magnum meningiomas using a conventional posterior suboccipital approach: a report on an experience with 17 cases. Neurosurgery 49:1021072001

  • 25

    Goldsmith BJLarson DA: Conventional radiation therapy for skull base meningiomas. Neurosurg Clin N Am 11:6056152000

  • 26

    Goldsmith BJWara WMWilson CBLarson DA: Postoperative irradiation for subtotally resected meningiomas. A retrospective analysis of 140 patients treated from 1967 to 1990. J Neurosurg 80:1952011994. (Erratum in J Neurosurg 80:

  • 27

    Harrison MJal-Mefty O: Tentorial meningiomas. Clin Neurosurg 44:4514661997

  • 28

    Kandenwein JARichter HPAntoniadis G: Foramen magnum meningiomas—experience with the posterior suboccipital approach. Br J Neurosurg 23:33392009

  • 29

    Kondziolka DLevy EINiranjan AFlickinger JCLunsford LD: Long-term outcomes after meningioma radiosurgery: physician and patient perspectives. J Neurosurg 91:44501999

  • 30

    Kondziolka DMathieu DLunsford LDMartin JJMadhok RNiranjan A: Radiosurgery as definitive management of intracranial meningiomas. Neurosurgery 62:53602008

  • 31

    Kratimenos GPCrockard HA: The far lateral approach for ventrally placed foramen magnum and upper cervical spine tumours. Br J Neurosurg 7:1291401993

  • 32

    Levy WJLatchaw JHahn JFSawhny BBay JDohn DF: Spinal neurofibromas: a report of 66 cases and a comparison with meningiomas. Neurosurgery 18:3313341986

  • 33

    Levy WJ JrBay JDohn D: Spinal cord meningioma. J Neurosurg 57:8048121982

  • 34

    Massager NMurata NTamura MDevriendt DLevivier MRégis J: Influence of nerve radiation dose in the incidence of trigeminal dysfunction after trigeminal neuralgia radiosurgery. Neurosurgery 60:6816882007

  • 35

    Mendenhall WMMorris CGAmdur RJFoote KDFriedman WA: Radiotherapy alone or after subtotal resection for benign skull base meningiomas. Cancer 98:147314822003

  • 36

    Meyer FBEbersold MJReese DF: Benign tumors of the foramen magnum. J Neurosurg 61:1361421984

  • 37

    Nanda AJavalkar VBanerjee AD: Petroclival meningiomas: study on outcomes, complications and recurrence rates. J Neurosurg 114:126812772011

  • 38

    Nanda AVincent DAVannemreddy PSBaskaya MKChanda A: Far-lateral approach to intradural lesions of the foramen magnum without resection of the occipital condyle. J Neurosurg 96:3023092002

  • 39

    Nicolato AForoni RPellegrino MFerraresi PAlessandrini FGerosa M: Gamma knife radiosurgery in meningiomas of the posterior fossa. Experience with 62 treated lesions. Minim Invasive Neurosurg 44:2112172001

  • 40

    Nutting CBrada MBrazil LSibtain ASaran FWestbury C: Radiotherapy in the treatment of benign meningioma of the skull base. J Neurosurg 90:8238271999

  • 41

    Pamir MNKiliç TOzduman KTüre U: Experience of a single institution treating foramen magnum meningiomas. J Clin Neurosci 11:8638672004

  • 42

    Parlato CTessitore ESchonauer CMoraci A: Management of benign craniovertebral junction tumors. Acta Neurochir (Wien) 145:31362003

  • 43

    Pirotte BDavid PNoterman JBrotchi J: Lower clivus and foramen magnum anterolateral meningiomas: surgical strategy. Neurol Res 20:5775841998

  • 44

    Pirzkall ADebus JHaering PRhein BGrosser KHHöss A: Intensity modulated radiotherapy (IMRT) for recurrent, residual, or untreated skull-base meningiomas: preliminary clinical experience. Int J Radiat Oncol Biol Phys 55:3623722003

  • 45

    Roberti FSekhar LNKalavakonda CWright DC: Posterior fossa meningiomas: surgical experience in 161 cases. Surg Neurol 56:8212001

  • 46

    Salas ESekhar LNZiyal IMCaputy AJWright DC: Variations of the extreme-lateral craniocervical approach: anatomical study and clinical analysis of 69 patients. J Neurosurg 90:2 Suppl2062191999

  • 47

    Samii MKlekamp JCarvalho G: Surgical results for meningiomas of the craniocervical junction. Neurosurgery 39:108610951996

  • 48

    Sen CNSekhar LN: An extreme lateral approach to intradural lesions of the cervical spine and foramen magnum. Neurosurgery 27:1972041990

  • 49

    Sheehan JPWilliams BJYen CP: Stereotactic radiosurgery for WHO grade I meningiomas. J Neurooncol 99:4074162010

  • 50

    Simpson D: The recurrence of intracranial meningiomas after surgical treatment. J Neurol Neurosurg Psychiatry 20:22391957

  • 51

    Stafford SLPerry ASuman VJMeyer FBScheithauer BWLohse CM: Primarily resected meningiomas: outcome and prognostic factors in 581 Mayo Clinic patients, 1978 through 1988. Mayo Clin Proc 73:9369421998

  • 52

    Starke RMNguyen JHRainey JWilliams BJSherman JHSavage J: Gamma Knife surgery of meningiomas located in the posterior fossa: factors predictive of outcome and remission. J Neurosurg 114:139914092011

  • 53

    Starke RMNguyen JHReames DLRainey JSheehan JP: Gamma knife radiosurgery of meningiomas involving the foramen magnum. J Craniovertebr Junction Spine 1:23282010

  • 54

    Strang RDal-Mefty O: Small skull base meningiomas. Surgical management. Clin Neurosurg 48:3203392001

  • 55

    Subach BRLunsford LDKondziolka DMaitz AHFlickinger JC: Management of petroclival meningiomas by stereotactic radiosurgery. Neurosurgery 42:4374451998

  • 56

    Symon LPell MSingh L: Surgical management of posterior cranial fossa meningiomas. Br J Neurosurg 7:5996091993

  • 57

    Taylor BW JrMarcus RB JrFriedman WABallinger WE JrMillion RR: The meningioma controversy: postoperative radiation therapy. Int J Radiat Oncol Biol Phys 15:2993041988

  • 58

    Weber DCLomax AJRutz HPStadelmann OEgger ETimmermann B: Spot-scanning proton radiation therapy for recurrent, residual or untreated intracranial meningiomas. Radiother Oncol 71:2512582004

  • 59

    Yaşargil MG: Meningiomas. Microneurosurgery: Microneurosurgery of CNS Tumors StuttgartGeorg Thieme1996. Vol IV B:134165

  • 60

    Zachenhofer IWolfsberger SAichholzer MBertalanffy ARoessler KKitz K: 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 58:28362006

  • 61

    Zenonos GKondziolka DFlickinger JCGardner PLunsford LD: Gamma Knife surgery in the treatment paradigm for foramen magnum meningiomas. J Neurosurg 117:8648732012

If the inline PDF is not rendering correctly, you can download the PDF file here.

Article Information

Correspondence Jason P. Sheehan, Department of Neurological Surgery, University of Virginia, Charlottesville, VA 22908. email jsheehan@virginia.edu.

INCLUDE WHEN CITING Published online April 10, 2015; DOI: 10.3171/2014.10.JNS14139.

DISCLOSURE Dr. Lunsford is a consultant and stockholder in AB Elekta.

© AANS, except where prohibited by US copyright law.

Headings

Figures

  • View in gallery

    Kaplan-Meier plot of progression-free survival after SRS for all 675 patients with posterior fossa meningiomas. Numbers in parentheses represent the number of patients reaching each significant timeline milestone.

  • View in gallery

    Kaplan-Meier plot of progression-free survival after SRS for patients with and without a prior resection (upper), and for patients with tumors < 6.5 cm3 versus those with tumors ≥ 6.5 cm3 (lower). Numbers in parentheses represent the number of patients reaching each significant timeline milestone.

  • View in gallery

    Kaplan-Meier plot of progression-free survival after SRS for meningiomas in a specific location in the posterior fossa. Figure is available in color online only.

References

1

Adegbite ABKhan MIPaine KWTan LK: The recurrence of intracranial meningiomas after surgical treatment. J Neurosurg 58:51561983

2

Al-Mefty O: Clinoidal meningiomas. J Neurosurg 73:8408491990

3

Al-Mefty OFox JLSmith RR: Petrosal approach for petroclival meningiomas. Neurosurgery 22:5105171988

4

Arnautović KIAl-Mefty O: Primary meningiomas of the jugular fossa. J Neurosurg 97:12202002

5

Arnautović KIAl-Mefty OHusain M: Ventral foramen magnum meninigiomas. J Neurosurg 92:1 Suppl71802000

6

Asthagiri ARHelm GASheehan JP: Current concepts in management of meningiomas and schwannomas. Neurol Clin 25:12091230xi2007

7

Babu RPSekhar LNWright DC: Extreme lateral transcondylar approach: technical improvements and lessons learned. J Neurosurg 81:49591994

8

Barbaro NMGutin PHWilson CBSheline GEBoldrey EBWara WM: Radiation therapy in the treatment of partially resected meningiomas. Neurosurgery 20:5255281987

9

Bassiouni HNtoukas VAsgari SSandalcioglu EIStolke DSeifert V: Foramen magnum meningiomas: clinical outcome after microsurgical resection via a posterolateral suboccipital retrocondylar approach. Neurosurgery 59:117711872006

10

Bertalanffy HGilsbach JMMayfrank LKlein HMKawase TSeeger W: Microsurgical management of ventral and ventrolateral foramen magnum meningiomas. Acta Neurochir Suppl 65:82851996

11

Black PMVillavicencio ATRhouddou CLoeffler JS: Aggressive surgery and focal radiation in the management of meningiomas of the skull base: preservation of function with maintenance of local control. Acta Neurochir (Wien) 143:5555622001

12

Bruneau MGeorge B: Foramen magnum meningiomas: detailed surgical approaches and technical aspects at Lariboisière Hospital and review of the literature. Neurosurg Rev 31:19332008

13

Castellano FRuggiero G: Meningiomas of the posterior fossa. Acta Radiol Suppl 104:11771953

14

Chen CMHuang APKuo LTTu YK: Contemporary surgical outcome for skull base meningiomas. Neurosurg Rev 34:2812962011

15

Cho CWAl-Mefty O: Combined petrosal approach to petroclival meningiomas. Neurosurgery 51:7087182002

16

Cudlip SAWilkins PRJohnston FGMoore AJMarsh HTBell BA: Posterior fossa meningiomas: surgical experience in 52 cases. Acta Neurochir (Wien) 140:100710121998

17

Erkmen KPravdenkova SAl-Mefty O: Surgical management of petroclival meningiomas: factors determining the choice of approach. Neurosurg Focus 19:2E72005

18

Flannery TJKano HLunsford LDSirin STormenti MNiranjan A: Long-term control of petroclival meningiomas through radiosurgery. J Neurosurg 112:9579642010

19

Fujimoto AMatsumura AMaruno TYasuda SYamamoto MNose T: Normal pressure hydrocephalus after gamma knife radiosurgery for cerebellopontine angle meningioma. J Clin Neurosci 11:7857872004

20

George BDematons CCophignon J: Lateral approach to the anterior portion of the foramen magnum. Application to surgical removal of 14 benign tumors: technical note. Surg Neurol 29:4844901988

21

George BLot GBoissonnet H: Meningioma of the foramen magnum: a series of 40 cases. Surg Neurol 47:3713791997

22

George BLot GVelut SGelbert FMourier KL: [French language Society of Neurosurgery. 44th Annual Congress. Brussels, 8–12 June 1993 Tumors of the foramen magnum.]. Neurochirurgie 39:Suppl 11891993. (Fr)

23

Glaholm JBloom HJCrow JH: The role of radiotherapy in the management of intracranial meningiomas: the Royal Marsden Hospital experience with 186 patients. Int J Radiat Oncol Biol Phys 18:7557611990

24

Goel ADesai KMuzumdar D: Surgery on anterior foramen magnum meningiomas using a conventional posterior suboccipital approach: a report on an experience with 17 cases. Neurosurgery 49:1021072001

25

Goldsmith BJLarson DA: Conventional radiation therapy for skull base meningiomas. Neurosurg Clin N Am 11:6056152000

26

Goldsmith BJWara WMWilson CBLarson DA: Postoperative irradiation for subtotally resected meningiomas. A retrospective analysis of 140 patients treated from 1967 to 1990. J Neurosurg 80:1952011994. (Erratum in J Neurosurg 80:

27

Harrison MJal-Mefty O: Tentorial meningiomas. Clin Neurosurg 44:4514661997

28

Kandenwein JARichter HPAntoniadis G: Foramen magnum meningiomas—experience with the posterior suboccipital approach. Br J Neurosurg 23:33392009

29

Kondziolka DLevy EINiranjan AFlickinger JCLunsford LD: Long-term outcomes after meningioma radiosurgery: physician and patient perspectives. J Neurosurg 91:44501999

30

Kondziolka DMathieu DLunsford LDMartin JJMadhok RNiranjan A: Radiosurgery as definitive management of intracranial meningiomas. Neurosurgery 62:53602008

31

Kratimenos GPCrockard HA: The far lateral approach for ventrally placed foramen magnum and upper cervical spine tumours. Br J Neurosurg 7:1291401993

32

Levy WJLatchaw JHahn JFSawhny BBay JDohn DF: Spinal neurofibromas: a report of 66 cases and a comparison with meningiomas. Neurosurgery 18:3313341986

33

Levy WJ JrBay JDohn D: Spinal cord meningioma. J Neurosurg 57:8048121982

34

Massager NMurata NTamura MDevriendt DLevivier MRégis J: Influence of nerve radiation dose in the incidence of trigeminal dysfunction after trigeminal neuralgia radiosurgery. Neurosurgery 60:6816882007

35

Mendenhall WMMorris CGAmdur RJFoote KDFriedman WA: Radiotherapy alone or after subtotal resection for benign skull base meningiomas. Cancer 98:147314822003

36

Meyer FBEbersold MJReese DF: Benign tumors of the foramen magnum. J Neurosurg 61:1361421984

37

Nanda AJavalkar VBanerjee AD: Petroclival meningiomas: study on outcomes, complications and recurrence rates. J Neurosurg 114:126812772011

38

Nanda AVincent DAVannemreddy PSBaskaya MKChanda A: Far-lateral approach to intradural lesions of the foramen magnum without resection of the occipital condyle. J Neurosurg 96:3023092002

39

Nicolato AForoni RPellegrino MFerraresi PAlessandrini FGerosa M: Gamma knife radiosurgery in meningiomas of the posterior fossa. Experience with 62 treated lesions. Minim Invasive Neurosurg 44:2112172001

40

Nutting CBrada MBrazil LSibtain ASaran FWestbury C: Radiotherapy in the treatment of benign meningioma of the skull base. J Neurosurg 90:8238271999

41

Pamir MNKiliç TOzduman KTüre U: Experience of a single institution treating foramen magnum meningiomas. J Clin Neurosci 11:8638672004

42

Parlato CTessitore ESchonauer CMoraci A: Management of benign craniovertebral junction tumors. Acta Neurochir (Wien) 145:31362003

43

Pirotte BDavid PNoterman JBrotchi J: Lower clivus and foramen magnum anterolateral meningiomas: surgical strategy. Neurol Res 20:5775841998

44

Pirzkall ADebus JHaering PRhein BGrosser KHHöss A: Intensity modulated radiotherapy (IMRT) for recurrent, residual, or untreated skull-base meningiomas: preliminary clinical experience. Int J Radiat Oncol Biol Phys 55:3623722003

45

Roberti FSekhar LNKalavakonda CWright DC: Posterior fossa meningiomas: surgical experience in 161 cases. Surg Neurol 56:8212001

46

Salas ESekhar LNZiyal IMCaputy AJWright DC: Variations of the extreme-lateral craniocervical approach: anatomical study and clinical analysis of 69 patients. J Neurosurg 90:2 Suppl2062191999

47

Samii MKlekamp JCarvalho G: Surgical results for meningiomas of the craniocervical junction. Neurosurgery 39:108610951996

48

Sen CNSekhar LN: An extreme lateral approach to intradural lesions of the cervical spine and foramen magnum. Neurosurgery 27:1972041990

49

Sheehan JPWilliams BJYen CP: Stereotactic radiosurgery for WHO grade I meningiomas. J Neurooncol 99:4074162010

50

Simpson D: The recurrence of intracranial meningiomas after surgical treatment. J Neurol Neurosurg Psychiatry 20:22391957

51

Stafford SLPerry ASuman VJMeyer FBScheithauer BWLohse CM: Primarily resected meningiomas: outcome and prognostic factors in 581 Mayo Clinic patients, 1978 through 1988. Mayo Clin Proc 73:9369421998

52

Starke RMNguyen JHRainey JWilliams BJSherman JHSavage J: Gamma Knife surgery of meningiomas located in the posterior fossa: factors predictive of outcome and remission. J Neurosurg 114:139914092011

53

Starke RMNguyen JHReames DLRainey JSheehan JP: Gamma knife radiosurgery of meningiomas involving the foramen magnum. J Craniovertebr Junction Spine 1:23282010

54

Strang RDal-Mefty O: Small skull base meningiomas. Surgical management. Clin Neurosurg 48:3203392001

55

Subach BRLunsford LDKondziolka DMaitz AHFlickinger JC: Management of petroclival meningiomas by stereotactic radiosurgery. Neurosurgery 42:4374451998

56

Symon LPell MSingh L: Surgical management of posterior cranial fossa meningiomas. Br J Neurosurg 7:5996091993

57

Taylor BW JrMarcus RB JrFriedman WABallinger WE JrMillion RR: The meningioma controversy: postoperative radiation therapy. Int J Radiat Oncol Biol Phys 15:2993041988

58

Weber DCLomax AJRutz HPStadelmann OEgger ETimmermann B: Spot-scanning proton radiation therapy for recurrent, residual or untreated intracranial meningiomas. Radiother Oncol 71:2512582004

59

Yaşargil MG: Meningiomas. Microneurosurgery: Microneurosurgery of CNS Tumors StuttgartGeorg Thieme1996. Vol IV B:134165

60

Zachenhofer IWolfsberger SAichholzer MBertalanffy ARoessler KKitz K: 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 58:28362006

61

Zenonos GKondziolka DFlickinger JCGardner PLunsford LD: Gamma Knife surgery in the treatment paradigm for foramen magnum meningiomas. J Neurosurg 117:8648732012

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