RESEARCHHUMANCLINICAL STUDIES

RESEARCHHUMANCLINICAL STUDIES

Dale Ding, MD*

Robert M. Starke, MD, MSc*
Hideyuki Kano, MD, PhD
Peter Nakaji, MD
Gene H. Barnett, MD, MBA
David Mathieu, MDk
Veronica Chiang, MD#
Sacit B. Omay, MD#
Judith Hess, BA#
Heyoung L. McBride, MD
Norissa Honea, PhD
John Y.K. Lee, MD**
Gazanfar Rahmathulla, MD
Wendi A. Evanoff, BA
Michelle Alonso-Basanta, MD,
PhD**
L. Dade Lunsford, MD
Jason P. Sheehan, MD, PhD*
*Department of Neurological Surgery,
University of Virginia, Charlottesville, Virginia;
Department of Neurological Surgery,
University of Pittsburgh, Pittsburgh, Pennsylva-
nia; Department of Neurosurgery, Barrow
Neurological Institute, Phoenix, Arizona;
Department of Neurosurgery, Cleveland
Clinic, Cleveland, Ohio; kDepartment of
Surgery, Division of Neurosurgery, University
of Sherbrooke, Sherbrooke, Quebec, Canada;
#Department of Neurosurgery, Yale University,
New Haven, Connecticut; and **Department
of Neurosurgery, University of Pennsylvania,
Philadelphia, Pennsylvania
Correspondence:
Jason P. Sheehan, MD, PhD,
Department of Neurological Surgery,
University of Virginia,
P.O. Box 800212,
Gamma Knife Radiosurgery for Cerebellopontine
Angle Meningiomas: A Multicenter Study
BACKGROUND: Resection of cerebellopontine angle (CPA) meningiomas may result in
significant neurological morbidity. Radiosurgery offers a minimally invasive alternative
to surgery.
OBJECTIVE: To evaluate, in a multicenter cohort study, the outcomes of patients
harboring CPA meningiomas who underwent Gamma Knife radiosurgery (GKRS).
METHODS: From 7 institutions participating in the North American Gamma Knife
Consortium, 177 patients with benign CPA meningiomas treated with GKRS and at least
6 months radiologic follow-up were included for analysis. The mean age was 59 years
and 84% were female. Dizziness or imbalance (48%) and cranial nerve (CN) VIII dys-
function (45%) were the most common presenting symptoms. The median tumor
volume and prescription dose were 3.6 cc and 13 Gy, respectively. The mean radiologic
and clinical follow-up durations were 47 and 46 months, respectively. Multivariate
regression analyses were performed to identify the predictors of tumor progression and
neurological deterioration.
RESULTS: The actuarial rates of progression-free survival at 5 and 10 years were 93%
and 77%, respectively. Male sex (P = .014), prior fractionated radiation therapy (P = .010),
and ataxia at presentation (P = .002) were independent predictors of tumor progression.
Symptomatic adverse radiation effects and permanent neurological deterioration
were observed in 1.1% and 9% of patients, respectively. Facial spasms at presentation
(P = .007) and lower maximal dose (P = .011) were independently associated with
neurological deterioration.
CONCLUSION: GKRS is an effective therapy for CPA meningiomas. Depending on the
patient and tumor characteristics, radiosurgery can be an adjuvant treatment to initial
surgical resection or a standalone procedure that obviates the need for resection in
most patients.
KEY WORDS: Brain neoplasms, Cerebellopontine angle, Gamma knife, Intracranial meningioma, Radiosurgery
Neurosurgery 75:398408, 2014 DOI: 10.1227/NEU.0000000000000480 www.neurosurgery-online.com

Charlottesville, VA 22908.
E-mail: jps2f@hscmail.mcc.virginia.edu
Received, January 22, 2014.
Accepted, June 2, 2014.
Published Online, July 3, 2014.
Copyright 2014 by the
Congress of Neurological Surgeons.
SANS LifeLong Learning and
NEUROSURGERY offer CME for subscribers
that complete questions about featured
articles. Questions are located on the SANS
website (http://sans.cns.org/). Please read
the featured article and then log into SANS
for this educational offering.
M
eningiomas arising from the cerebello-
pontine angle (CPA) are relatively
uncommon, comprising only 1% of
intracranial meningiomas and 6% to 15% of
tumors occupying this anatomic region.1-4
Because of their intimate relationship with
ABBREVIATIONS: ARE, adverse radiation effect;
CN, cranial nerve; CPA, cerebellopontine angle;
EBRT, external beam radiation therapy; GKRS,
Gamma Knife radiosurgery; IAC, internal auditory
canal; NAGKC, North American Gamma knife
Consortium; PFS, progression-free survival; SRS,
stereotactic radiosurgery; WHO, World Health
Organization
adjacent neurovascular structures, including
the brainstem and cerebellum, multiple cranial
nerves (CNs), and the basilar arterys main trunk
and perforator branches, CPA meningiomas
represent a formidable surgical challenge. The
morbidity and mortality associated with surgical
resection of CPA meningiomas is not inconse-
quential.5,6 Radiosurgery has been demonstrated
to provide high rates of tumor control for skull
base meningiomas with acceptably low compli-
cation rates.7-10 As a result of the successful
outcomes afforded by radiosurgery, the manage-
ment paradigm for skull base tumors has largely
shifted away from aggressive surgical resection to
radiosurgery alone for tumors 30 mm or less in

398 | VOLUME 75 | NUMBER 4 | OCTOBER 2014 www.neurosurgery-online.com

Copyright Congress of Neurological Surgeons. Unauthorized reproduction of this article is prohibited


diameter or initial surgical debulking followed by adjuvant radio-
surgery for residual or recurrent disease.11 The rarity of CPA
meningiomas has limited the statistical power of previous radio-
surgery series describing the outcomes for these lesions. Our
objective was to identify predictors of long-term tumor control,
neurological morbidity, and overall functional outcomes for patients
harboring CPA meningiomas who were treated with radiosurgery.
We hypothesize that radiosurgery achieves high rates of long-term
tumor control with acceptably low complication rates for CPA
meningiomas. To test this hypothesis, we retrospectively evaluated
the outcomes of CPA meningioma patients who underwent
Gamma Knife radiosurgery (GKRS) at 7 centers participating in
the North American Gamma knife Consortium (NAGKC).
METHODS
Study Design
We performed a retrospective, multicenter cohort study of patients
with CPA meningiomas who were treated with GKRS. Because previous
studies included relatively few CPA meningioma patients, our intention
was to accrue a large number of patients from several institutions in order
to overcome this limitation.
Setting
A retrospective review of GKRS meningioma databases from 7
participants of the NAGKC was performed. Each center obtained
institutional review board approval for its own individual database. At
each institution, all consecutive patients with CPA meningiomas who
were treated with GKRS from 1988 to 2012 were identified. All patient
data were deidentified and then pooled into a central, cumulative database
comprising meningioma patients treated with GKRS from all 7
institutions. The pooled data were screened by an independent third
party for errors. All ambiguities were addressed by the contributing center
after which the cumulative database was sent to the institution of the
corresponding author for further analysis. The institutions that contrib-
uted patients to this study were the University of Virginia, Barrow
Neurological Institute, University of Pennsylvania, Cleveland Clinic,
University of Sherbrooke, Yale University, and University of Pittsburgh.
Participants
Inclusion criteria were tumor location in the CPA and a minimum of 6
months radiologic follow-up. Patients with complications following
treatment or tumor progression but less than 6 months of follow-up were
also included in the analysis. Surveillance neuroimaging, primarily magnetic
resonance imaging (MRI), was performed at approximately 6-month
intervals for 2 years after the GKRS procedure. If no radiologic or clinical
progression was evident 2 years after GKRS, further follow-up neuro-
imaging was performed at 1- to 2-year intervals. Additional neuroimaging
was performed if the patient developed new or worsening neurological
deficits. Clinical surveillance was performed at the participating institution
when possible. However, owing to the nature of being tertiary referral
centers for meningioma radiosurgery, some patients from the participating
institutions were evaluated by their local physicians. For those patients who
underwent follow-up outside of the treating institution, neuroimaging and
clinical data were transmitted to the GKRS center for review.
NEUROSURGERY
Copyright Congress of Neurological Surgeons. Unauthorized reproduction of this article is prohibited
RADIOSURGERY FOR CEREBELLOPONTINE ANGLE MENINGIOMAS
Variables
For those with a previous resection, a histopathologic diagnosis of World
Health Organization (WHO) grade I meningioma was an inclusion
criterion, whereas clinical and radiologic features consistent with a benign
meningioma were required for patients without tissue diagnosis. The
radiologic criteria for a diagnosis of a benign meningioma were contrast
enhancement, extra-axial location, dural attachment, and tumor calcifica-
tion in some patients. Clinical exclusion criterion was a history of
a nonmeningioma neoplasm, either primary intracranial or metastatic, in
the CPA. Adverse radiation effects (AREs) were defined as new or increased
peritumoral T2 hyperintensity on MRI. AREs were classified as symptom-
atic if they were accompanied by neurological deterioration.
The following patient, tumor, and treatment characteristics were analyzed
and related to GKRS outcomes: sex, age, age greater than 65 years, year of
GKRS, GKRS after the year 2000, time from initial symptoms to GKRS,
duration of radiologic follow-up, duration of clinical follow-up, pre-GKRS
resection, number of pre-GKRS resections, pre-GKRS external beam radiation
therapy (EBRT), total dose of pre-GRKS EBRT, headache at presentation,
symptoms other than headaches at presentation, ataxia at presentation, level of
cognition at presentation, cerebellar alterations at presentation, visual dis-
turbances at presentation, alterations in facial sensation at presentation, facial
weakness at presentation, facial spasms at presentation, hearing loss at
presentation, dizziness or imbalance at presentation, dysphagia at presentation,
alterations in body sensation at presentation, motor weakness at presentation,
tongue deviation at presentation, number of isocenters, prescription dose,
maximal dose, isodose line, and tumor volume. All of the listed factors were
assessed as potential covariates in the univariate model.
Data Sources and Measurement
Throughout the study period, the Leksell Gamma Knife models U, B, C,
4C, and Perfexion were used as each model became available and was
acquired by the participating NAGKC institutions. The GKRS procedure
was initiated with placement of a Leksell Model G stereotactic frame (Elekta
Inc, Norcross, Georgia) which was affixed to the patients calvarium at 4
points under local, or when necessary, general anesthesia. Following frame
placement, MRI without and with gadolinium contrast was performed to
delineate the tumor. If an MRI was not possible because of concerns of
safety, thin-slice computed tomography (CT) without and with contrast
was obtained instead. Dose planning was performed empirically based on
tumor anatomy and morphology, the position and proximity of adjacent
critical neurovascular structures, neurological symptoms at presentation,
and previous EBRT. All GKRS planning was collaboratively performed by
a neurosurgeon, radiation oncologist, and medical physicist.
Tumor histopathology, in those patients who underwent previous resection,
was evaluated by a neuropathologist at the treating institution. Radiologic
tumor characteristics, including tumor volume and location, were determined
by a neurosurgeon and neuroradiologist at the treating institution. An
independent third party, typically another neuroradiologist, was used to settle
any disagreement in the initial evaluation of any neuroimaging. Radiologic
follow-up was evaluated by the treating neurosurgeon and a neuroradiologist at
the treating institution. Initial clinical presentation and follow-up neurological
and overall clinical status was determined by the treating neurosurgeon.
Bias
Uniform reporting standards for initial and follow-up radiologic and clinical
evaluations were used at each participating institution to minimize reporting
bias. The accrual of data from multiple institutions mitigates the selection and
treatment biases of any individual treating physician or institution.
VOLUME 75 | NUMBER 4 | OCTOBER 2014 | 399
DING ET AL
Study Size
The study size was determined by the total number of patients who met
the eligibility criteria at each of the 7 participating institutions. We did not
set a minimum or maximum number of patients for each individual
institution or for the cumulative study.
Quantitative Variables
Tumor volume was calculated based on axial, sagittal, and coronal
dimensions as measured by the treating clinicians. Tumor growth was
defined as an increase in the initial tumor volume of greater than 15%, and
tumor regression was defined as a decrease in the initial tumor volume of
greater than 15%.12 Alterations of tumor volume within 15% of the
initial volume were defined as unchanged tumor growth. Tumor control
was defined as unchanged tumor growth or tumor regression.
Statistical Methods
Data are presented as mean and standard deviation for normally
distributed continuous variables, as median and first and third quartiles
(Q25 and Q75) for continuous variables that did not satisfy the normality
assumption, and as frequency and percentage for categorical variables.
Normality was assessed graphically and with the Shapiro-Wilk test.
Statistical analyses of categorical variables were performed by using the x2
test or Fisher exact test for linear association as appropriate. Statistics of
means were performed using the 2 independent sample t test, both with
and without equal variance (Levene test) as necessary and Wilcoxon rank
sum tests when variables were not normally distributed. Univariate and
multivariate logistic regression analyses were performed to assess the
predictors of worsening neurological function and favorable outcome. The
Kaplan-Meier risk of tumor progression was calculated and multivariate
analysis was performed with Cox proportional hazards regression analysis.
Factors predictive of tumor progression based on the univariate analysis
(P , .20) were entered into multivariate Cox proportional hazards regression
analysis to assess hazard ratios.13 Clinical covariates predicting new or
worsening neurological function with a univariate P value of ,.20 were
included in multivariable logistic regression analysis. Additionally, clinical
covariates predicting unfavorable outcome with a univariate P value of ,.20
were included in the multivariable logistic regression analysis. Clinically
significant variables and interaction expansion covariates were further assessed
in both Cox proportional hazards and logistic multivariable analysis as deemed
relevant. The c-statistic, or area under the curve, was calculated for each
multivariate model to assess its overall predictive value. Models are typically
considered reasonable when the c-statistic is greater than 0.7 and strong when
the c-statistic exceeds 0.8.13,14 P values of #.05 were considered statistically
significant. The hazard and odds ratios were calculated for statistically
significant variables identified in the Cox and logistic regression analyses,
respectively. Adjustment for multiple comparisons was performed only within
a single test (eg, analysis of variance with post hoc Bonferroni measure was
used to compare means between more than 2 groups). Additionally, the 95%
confidence interval was reported for each statistically significant variable.
All missing radiologic and clinical data were obtained, when possible,
from patients local physicians or referring hospitals. Patients with
missing follow-up data that resulted in less than 6 months radiologic
follow-up were excluded from the study. Patients lost to follow-up
before 6 months radiologic follow-up were excluded from the study.
For all patients included for analysis, the final radiologic and clinical
data reported in the study were those obtained from the most recent
follow-up.
400 | VOLUME 75 | NUMBER 4 | OCTOBER 2014
Copyright Congress of Neurological Surgeons. Unauthorized reproduction of this article is prohibited
RESULTS
Participants
A total of 191 patients with CPA meningiomas were treated with
GKRS and assessed for eligibility. Fourteen patients were excluded
because of inadequate radiologic follow-up (ie, less than 6 months)
yielding 177 patients for analysis from the 7 participating treatment
sites (Figure 1). The contribution from each institution was as
follows: University of Virginia (n = 43), Barrow Neurological
Institute (n = 30), University of Pennsylvania (n = 10), Cleveland
Clinic (n = 4), University of Sherbrooke (n = 16), Yale University
(n = 3), and University of Pittsburgh (n = 71).
Descriptive Data
The mean age of the 177 patients included in the study was
59.2 6 12.18 years with 149 females (84.2%). A total of 53
patients underwent pre-GKRS surgical resection (29.9%), includ-
ing 1 resection in 46 patients (26.0%), 2 resections in 6 patients
(3.4%), and 3 resections in 1 patient (0.6%). Three patients
(1.7%) were treated with EBRT before GKRS. No patient received
chemotherapy before GKRS. The most common presenting
symptoms were dizziness or imbalance in 85 patients (48.0%),
hearing loss indicative of CN VIII dysfunction in 80 patients
(45.2%), and alterations in facial sensation indicative of trigeminal
neuropathy in 69 patients (39.0%). No patient presented with
masseter (ie, motor CN V dysfunction) or trapezius weakness
(ie, CN XI dysfunction). Table 1 summarizes the demographics
and clinical presentations of the CPA meningioma patients.
The median tumor and treatment volumes were 3.6 (1.9, 6.2) cc
and 3.3 (1.8, 5.8) cc, respectively. The median prescription and
maximal radiosurgical doses were 13 (12.5, 14) Gy and 26 (26, 30)
Gy, respectively. The median isodose line was 50% (50, 50), and the
median number of isocenters was 9 (6, 16). Table 2 summarizes the
CPA meningioma characteristics and the radiosurgical parameters.
The mean durations of radiologic and clinical follow-up were 47.4 6
38.16 months and 45.8 6 36.02 months, respectively. Clinical
follow-up was unavailable for 1 patient included in the study.
Outcome Data
At last radiologic follow-up, tumor volume decreased in 82 patients
(46.3%), was unchanged in 81 patients (45.8%), and increased in 14
patients (7.9%). For the 82 patients with decreased tumor volume, the
median interval between GKRS and tumor regression was 29.8 (16.0,
50.8) months. For the 14 patients with increased tumor volume, the
median interval between GKRS and tumor growth was 40.5 (21.0,
66.8) months. The overall tumor control rate in this series of CPA
meningiomas was 92%. Table 3 summarizes the radiologic outcomes
following GKRS. Table 4 details the patient demographics, tumor
characteristics, and GKRS treatment parameters for the 14 patients
who had tumor progression and summarizes the comparison
between the patients with and without radiologic tumor progression.
Radiologic evidence of AREs was observed in 10 patients
(5.6%) at a median time of 10.5 (9.2, 13.8) months following
www.neurosurgery-online.com

FIGURE 1. Flow diagram depicting the selection of eligible patients with cerebellopontine angle (CPA)
meningiomas who were included in the study for analysis of radiologic and clinical outcomes following gamma
knife radiosurgery (GKRS) treatment.
GKRS. Two patients had symptomatic AREs (1.1%). One patient
presented with headache and ataxia 11 months post-GKRS, and
another patient presented with new facial weakness 10 months post-
GRKS. The first patient was treated temporarily with cortico-
steroids, and the second patient was managed conservatively. No
surgical treatment was performed for AREs in any patient. There
were no cases of radiation-induced secondary tumor formation or
malignant transformation of the treated meningioma.
Clinical follow-up was available in 176 of the 177 patients
included in this study. At last clinical follow-up, overall neuro-
logical function was improved in 101 patients (57.4%),
unchanged in 60 patients (34.1%), and deteriorated in 15 patients
(8.5%). Of the 15 patients with permanent clinical deterioration,
4 had radiologic evidence of tumor progression (26.7%) and 1 had
symptomatic ARE (facial weakness) without tumor progression
(6.7%). The other patient with symptomatic ARE (headache and
ataxia) had tumor progression with ARE-related symptom
resolution at the most recent follow-up 29 months post-GKRS.
The remaining 10 of 15 patients with permanent clinical
deterioration did not have symptomatic AREs or tumor pro-
gression (66.7%). Table 5 summarizes the clinical outcomes
following GKRS. The most common new or worsening
neurological deficits, transient or permanent, were alterations
in facial sensation in 103 patients (58.5%), dizziness or
NEUROSURGERY
Copyright Congress of Neurological Surgeons. Unauthorized reproduction of this article is prohibited
RADIOSURGERY FOR CEREBELLOPONTINE ANGLE MENINGIOMAS
imbalance in 11 patients (6.3%), and hearing loss in 6 patients
(3.4%). Of note, post-GKRS CN V dysfunction, as determined
by alterations in facial sensation, was temporary in 96 patients
(54.5%) and permanent in 7 patients (4.0%). No patient
developed new or worsening motor weakness, trapezius weakness,
masseter weakness, dysphagia, or tongue deviation.
Seven patients underwent resection following GKRS (4.0%). One
resection was performed in 6 patients (3.4%), and 2 resections were
performed in 1 patient (0.6%), for symptomatic tumor progression.
The histology of all tumors resected after GKRS were WHO grade I
meningiomas. Three patients developed hydrocephalus (1.7%), and
2 of these patients underwent ventriculoperitoneal shunt placement
(1.1%). Seven patients (4.0%) died at a median interval of 73.0 (46.5,
132.8) months post-GRKS. The causes of death were intracerebral
hemorrhage in 1 patient, systemic cancer in 2 patients, and remained
unknown in 4 patients. Favorable outcome, defined herein as tumor
control and lack of neurological deterioration, was observed in 151
patients (85.8%), whereas unfavorable outcome (tumor progression
or neurological deterioration) was observed in 25 patients (14.2%).
Main Results
Based on Kaplan-Meier analysis, the actuarial rates of progression-
free survival (PFS) at 3, 5, 8, and 10 years were 96.5%, 92.5%,
77.2%, and 77.0%, respectively (Figure 2). Based on log-rank test,
VOLUME 75 | NUMBER 4 | OCTOBER 2014 | 401
DING ET AL

TABLE 1. Patient Demographics and Clinical Presentationsa TABLE 3. Summary of Radiologic Outcomes Following GKRS
Treatment of CPA Meningiomasa
Female, n (%) 149 (84.2)
Age, mean 6 SD y 59.2 6 12.18 Tumor volume at last follow-up,b n (%)
Pre-GKRS resection, n (%) 53 (29.9) Decreased 82 (46.3)
Number of prior resections, n (%) Unchanged 81 (45.8)
One 46 (26.0) Increased 14 (7.9)
Two 6 (3.4) Interval between GKRS and decrease in tumor 29.8 (16.0, 50.8)
Three 1 (0.6) volume, median (Q25, Q75) mo
Pre-GKRS radiation therapy, n (%) 3 (1.7) Interval between GKRS and increase in tumor 40.5 (21.0, 66.8)
Symptoms at presentation, n (%) volume, median (Q25, Q75) mo
Dizziness or imbalance 85 (48.0) Adverse radiation effects, n (%)
Hearing loss 80 (45.2) Overall 10 (5.6)
Alterations in facial sensation 69 (39.0) Asymptomatic 8 (4.5)
Headache 53 (29.9) Symptomatic 2 (1.1)
Ataxia 24 (13.6) Interval between GKRS and adverse radiation 10.5 (9.2, 13.8)
Facial weakness 17 (9.6) effects, median (Q25, Q75) mo
Alterations in body sensation 16 (9.0)
a
Alterations in cognition 13 (7.3) GKRS, gamma knife radiosurgery; CPA, cerebellopontine angle; Q25, first quartile;
Motor weakness 10 (5.6) Q75, third quartile.
b
Alterations in cerebellar function 9 (5.1) Increase = tumor growth by greater than 15% of initial volume; decrease = tumor
shrinkage by greater than 15% of initial volume; unchanged = tumor growth or
Dysphagia 8 (4.5)
shrinkage by 15% of initial volume or less.
Alterations in visual function 7 (4.0)
Tongue deviation 4 (2.3)
Facial spasms 3 (1.7)
were independent predictors of new or worsening neurological
a
SD, standard deviation; GKRS, gamma knife radiosurgery. deficits in the multivariate logistic regression analysis. Table 7
details the results of the univariate and multivariate logistic
regression analyses for independent predictors of neurological
the PFS for female patients was better than that for male patients deterioration. Ataxia at presentation (P = .037), alteration in
(P = .009, Figure 3), and the PFS for patients not treated with pre- facial sensation at presentation (P = .007), and hearing loss at
GKRS EBRT was better than that for patients who were treated presentation (P = .023) were independent predictors of
with pre-GKRS EBRT (P = .041, Figure 4), and the PFS for unfavorable outcome in the multivariate logistic regression
patients without ataxia at presentation was better than that for analysis. Table 8 details the results of the univariate and
patients presenting with ataxia (P = .004, Figure 5). It should be multivariate logistic regression analyses for independent pre-
noted that the PFS rates for the distinct subgroups in Figures 3, 4, dictors of unfavorable outcome. Goodness of fit of all 3
and 5 diverge at relatively early time points in the follow-up periods. multivariate models were acceptable. The c-statistics for the
Male sex (P = .014), pre-GKRS EBRT (P = .010), and ataxia multivariate models for tumor progression (Table 6), new or
at presentation (P = .002) were independent predictors of tumor worsening neurological deficit (Table 7), and unfavorable
progression in the Cox proportional hazards multivariate outcome (Table 8) were 0.675, 0.757, and 0.784, respectively.
regression analysis. Table 6 details the results of the univariate
and multivariate Cox proportional hazards regression analyses DISCUSSION
for independent predictors of tumor progression. Facial spasms
at presentation (P = .007) and lower maximal dose (P = .011) Skull base meningiomas are guarded by significant natural
barriers that contribute to the difficulty of complete yet safe
resection. Contemporary management of skull base tumors,
including CPA meningiomas, has shifted from a traditional
TABLE 2. Median (Q25, Q75) Tumor Characteristics and GKRS
approach of aggressive surgical gross total resection to an approach
Treatment Parametersa
of radiosurgery alone for small tumors, maximal safe surgical
Initial tumor volume, cc 3.6 (1.9, 6.2) debulking with adjuvant radiosurgery for residual or recurrent
Treatment volume, cc 3.3 (1.8, 5.8) disease, or EBRT for large or morphologically irregular lesions that
Prescription dose, Gy 13 (12.5, 14) are not amenable to surgical debulking. Nevertheless, successful
Maximal dose, Gy 26 (26, 30)
Isodose line, % 50 (50, 50)
long-term management of CPA meningiomas requires a multidis-
Number of isocenters 9 (6, 16) ciplinary approach tailored to the individual characteristics of the
patient and tumor. With a myriad of singular or combination
a treatment options available to patients harboring these daunting
GKRS, gamma knife radiosurgery; Q25, first quartile; Q75, third quartile.
lesions, it is crucial that the outcomes of surgical resection, EBRT,

402 | VOLUME 75 | NUMBER 4 | OCTOBER 2014 www.neurosurgery-online.com

Copyright Congress of Neurological Surgeons. Unauthorized reproduction of this article is prohibited

 RADIOSURGERY FOR CEREBELLOPONTINE ANGLE MENINGIOMAS

TABLE 4. Patient Demographics, Tumor Characteristics, and GKRS TABLE 5. Summary of Clinical Outcomes Following GKRS
Parameters of Patients With and Without Radiologic Evidence of Treatment of CPA Meningiomasa,b
Tumor Progressiona
Overall neurological function, n (%)
Patients With Patients Without Improvement 101 (57.4)
Radiologic Tumor Radiologic Tumor Unchanged 60 (34.1)
Progression Progression P Deterioration 15 (8.5)
Factor (n = 14) (n = 163) Value New or worsening neurological deficit, n (%)
Female sex, n (%) 9 (64.3) 140 (85.9) .033b Alterations in facial sensation 103 (58.5)
Age, mean 6 SD y 63.4 6 11.16 58.8 6 12.23 .173 Dizziness or imbalance 11 (6.3)
Pre-GKRS 6 (42.9) 47 (28.8) .272 Hearing loss 6 (3.4)
resection, n (%) Ataxia 5 (2.8)
Pre-GKRS 2 (14.3) 1 (0.6) .001b Facial weakness 4 (2.3)
radiation Alterations in cognition 3 (1.7)
therapy, n (%) Alterations in cerebellar function 3 (1.7)
Initial tumor 5.8 (2.2, 8.5) 3.4 (1.8, 6.2) .070 Alterations in visual function 2 (1.1)
volume, Facial spasms 2 (1.1)
median (Q25, Alterations in body sensation 1 (0.6)
Q75) cc Post-GKRS hydrocephalus and ventriculoperitoneal shunt,
Treatment 5.2 (1.9, 8.3) 3.3 (1.8, 5.7) .195 n (%)
volume, Hydrocephalus 3 (1.7)
median (Q25, Ventriculoperitoneal shunt 2 (1.1)
Q75) cc
Prescription dose, 12.5 (12, 14) 13 (12.5, 14) .100 a
GKRS, gamma knife radiosurgery; CPA, cerebellopontine angle.
b
median (Q25, Clinical follow-up was available for 176 of the 177 patients included in this study.
Q75) Gy
Maximal dose, 25.5 (23, 30) 27 (26, 30) .191
median (Q25, a detailed analysis of the surgical outcomes of 347 patients with
Q75) Gy CPA meningiomas with a particular focus on the tumors
Isodose line, 50 (50, 54) 50 (50, 50) .326 relationship to the internal auditory canal (IAC). In that series,
median (Q25,
Simpson grade I or II resection was achieved in 86% of patients.
Q75), %
Number of 9.5 (6, 18) 9 (6, 15) .952 Good facial nerve function (House-Brackmann grade I or II) and
isocenters, hearing preservation were achieved in 89% and 91% of patients,
median (Q25, respectively. Patients with CPA meningiomas located superior to
Q75) the IAC or originating between the IAC and sigmoid sinus had

a
SD, standard deviation; GKRS, gamma knife radiosurgery; Q25, first quartile; Q75,
third quartile.
b
Statistically significant (P , .05).

and stereotactic radiosurgery (SRS) are critically evaluated so an

optimal therapeutic strategy may be devised.

Surgical Resection of Cerebellopontine

Angle Meningiomas
The rate of postoperative recurrence for meningiomas depends
on the extent of surgical resection.15 Large, infiltrating CPA
meningiomas are difficult to completely resect without sacrificing
a substantial degree of cranial nerve function. Sekhar and
Jannetta5 surgically resected CPA meningiomas in 22 patients
and achieved complete excision in 14 tumors (64%). Five
patients acquired new postoperative CN palsies (23%) and, over
FIGURE 2. Actuarial progression-free survival over time following GKRS for
a mean follow-up period of 5 years, there was 1 tumor recurrence
patients with CPA meningiomas. CPA, cerebellopontine angle; GKRS, gamma
in the complete resection cohort (7%) and 1 reoperation in the knife radiosurgery.
subtotal resection cohort (13%). Nakamura et al16 performed

NEUROSURGERY VOLUME 75 | NUMBER 4 | OCTOBER 2014 | 403

Copyright Congress of Neurological Surgeons. Unauthorized reproduction of this article is prohibited

DING ET AL

FIGURE 3. Actuarial progression-free survival over time for male vs female patients
with CPA meningiomas following treatment with GKRS. Tumor control was FIGURE 5. Actuarial progression-free survival over time following GKRS
significantly worse in male patients (P = .009, log-rank test). CPA, cerebellopontine treatment for CPA meningioma patients who did and did not present with
angle; GKRS, gamma knife radiosurgery. ataxia. Tumor control was significantly worse in patients who presented with
ataxia (P = .004, log-rank test). CPA, cerebellopontine angle; GKRS, gamma
knife radiosurgery.
the highest rates of favorable CN VII and VIII outcome following
resection. Schaller et al17 reported better postoperative facial and
auditory function for retromeatal compared with premeatal CPA patients. The rates of short-term (duration less than 6 months)
meningiomas, which may be attributed to the larger size of and long-term (duration greater than 6 months) complications
retromeatal lesions at the time of diagnosis and the earlier time were 46% and 17%, respectively. Roser at al19 reported gross
course of symptomatic presentation for premeatal lesions. total resection, facial nerve functional preservation, and cochlear
A recent surgical series by Kane et al18 reported the outcomes of nerve functional preservation rates of 86%, 86%, and 77%,
24 patients with CPA meningiomas of which 13 had extension respectively, in a study of 72 patients with CPA meningiomas
into the IAC. The most common presenting symptoms were involving the IAC. Prior studies of surgically treated CPA
hearing loss, headache, vertigo, and ataxia, and the mean tumor
volume was 35 cc. Gross total resection was achieved in 50% of
TABLE 6. Univariate and Multivariate Cox Proportional Hazards
Regression Analyses for Independent Predictors of Tumor
Progressiona
Hazard P
Factor Ratio 95% CI Value
Univariate analysisb
Male sex 4.013 1.304-12.345 .015
Pre-GKRS radiation therapy 4.841 0.952-24.607 .057
Ataxia 4.506 1.465-13.860 .009
Alteration in cerebellar 6.870 1.381-34.185 .019
function
Hearing loss 3.747 1.165-12.050 .027
Lower prescription dose 1.364 1.001-1.859 .049
Multivariate analysis
Male sex 4.450 1.361-14.550 .014
Pre-GKRS radiation therapy 11.481 1.810-72.845 .010
Ataxia 6.584 1.943-22.308 .002
a
GKRS, gamma knife radiosurgery; CI, confidence interval.
FIGURE 4. Actuarial progression-free survival over time for CPA meningioma b
Increased age (P = .089), GKRS treatment after the year 2000 (P = .066), facial
patients who did and did not undergo radiation therapy prior to treatment with weakness at presentation (P = .128), dizziness at presentation (P = .069), alterations
GRKS. Tumor control was significantly worse in patients who underwent pre-GKRS in body sensation at presentation (P = .104), lower maximal dose (P = .110), and
radiation therapy (P = .041, log-rank test). CPA, cerebellopontine angle; GKRS, higher volume (P = .109) were also included in the multivariate analysis for P values
gamma knife radiosurgery; RT, radiotherapy. less than 0.20.

404 | VOLUME 75 | NUMBER 4 | OCTOBER 2014 www.neurosurgery-online.com

Copyright Congress of Neurological Surgeons. Unauthorized reproduction of this article is prohibited

 RADIOSURGERY FOR CEREBELLOPONTINE ANGLE MENINGIOMAS

series comprising only CPA meningiomas has not been published.

TABLE 7. Univariate and Multivariate Logistic Regression Analyses Much like meningioma SRS series, similar EBRT series include CPA
for Independent Predictors of New or Worsening Neurological lesions along with meningiomas arising from other skull base
Deficita lesions.22 Therefore, we may approximate the EBRT outcomes
Factor Odds Ratio 95% CI P Value for CPA meningiomas by extrapolating them from larger, more
Univariate analysisb
inclusive skull base meningioma EBRT series. A recent study by
Facial spasm 24.308 2.064-286.278 .011 Han et al compared the outcomes of SRS, hypofractionated
Lower maximal dose 1.200 1.035-1.393 .016 stereotactic radiotherapy, and fractionated stereotactic radiotherapy
Multivariate analysis skull base meningiomas with median tumor sizes of 2.8 cm, 4.8 cm,
Facial spasm 33.558 2.653-424.475 .007 and 11.1 cm, respectively, and did not find significant differences in
Lower maximal dose 1.230 1.048-1.443 .011 the rates of tumor control (P = .25) or clinical response (P = .16)
among the 3 treatment modalities.23 In a study of 189 patients with
a
GKRS, gamma knife radiosurgery; EBRT, external beam radiation therapy; CI, large skull base meningiomas (median volume, 53 cc) treated with
confidence interval.
b
FRST, Debus et al24 reported tumor control rates of 97% and 96%
Pre-GKRS resection (P = .153), pre-GKRS EBRT (P = .168), ataxia at presentation
(P = .139), alterations in facial sensation at presentation (P = .110), and lower at 5 and 10 years, respectively, for WHO grade I tumors. The
prescription dose (P = .123) were also included in the multivariate analysis for resolution rate of pretreatment CN dysfunction was 28%, and the
P values less than 0.20. rate of clinically significant radiation-induced toxicity was 2%.
EBRT is still used in rare instances of large CPA meningiomas that
are precluded from surgical debulking by patient medical comorbid-
meningiomas have postoperative rates of facial nerve dysfunction
ities or patient refusal of surgery.24,25 Other fractionated radiotherapy
as high as 30%.4 Surgical resection is still a first-line treatment for
approaches, such as intensity-modulated radiation therapy and
CPA meningiomas, especially those large and symptomatic
proton beam therapy, allow for improved dose conformality, thereby
secondary to brainstem compression or obstructive hydroceph-
increasing the safety and efficacy of treatment.26 Combs et al27
alus.4,16,19-21 However, it is clear that, despite advances in
treated 507 patients with skull base meningiomas with fractionated
microsurgical technique and technology, the morbidity associated
stereotactic radiotherapy (74%) and intensity-modulated radiation
with surgical resection of CPA meningiomas remains substantial.
therapy (26%) and attained tumor control rates of 95% and 88% at
External Beam Radiation Therapy Outcomes for 5 and 10 years, respectively. Over a median follow-up period of 107
Cerebellopontine Angle Meningiomas months, 85% of patients either remained clinically stable or
experienced clinical improvement. However, no randomized trials
Because of the excellent rates of tumor control and relatively low comparing the 2 modalities for skull base meningiomas have been
rates of neurological morbidity associated with radiosurgery, published. Given the disparities in the tumor characteristics currently
fractionated EBRT, which generally includes radiation-based treat- treated with EBRT compared with radiosurgery, such a trial is
ment delivered in greater than 5 fractions, is used less often than in unlikely to ever occur. Furthermore, there are inherent disparities in
the past for skull base meningiomas. Despite a number of reports patient selection, tumor type, tumor location, and follow-up duration
regarding the EBRT results for skull base meningiomas, an EBRT between our series and the aforementioned EBRT series. Specifically,
CPA meningiomas represent only a minor fraction of EBRT
TABLE 8. Univariate and Multivariate Logistic Regression Analyses meningiomas series. Because of the relatively infrequent occurrence
for Independent Predictors of Unfavorable Outcomea,b of these tumors, there are no EBRT series reporting outcomes for
CPA meningiomas in the literature.
Factor Odds Ratio 95% CI P Value
Univariate analysis
Pre-GKRS EBRT 12.870 1.121-147.700 .040 Key Results
Ataxia 3.020 1.101-8.279 .032
The long-term PFS rates, 93% at 5 years and 77% at 10 years,
Alteration in facial sensation 1.430 1.013-2.020 .042
Hearing loss 2.565 1.064-6.180 .036 were reasonably high with an overall tumor control rate of 92%
Lower prescription dose 1.420 1.064-1.898 .017 over a mean radiologic follow-up of 47.4 months. The median
Lower maximal dose 1.122 1.006-1.252 .039 interval between GKRS and tumor growth was 40.5 months. The
Multivariate analysis rates of post-GKRS surgical resection for symptomatic tumor
Ataxia 3.168 1.072-9.366 .037 progression and post-GKRS ventriculoperitoneal shunt placement
Alteration in facial sensation 1.689 1.153-2.474 .007 for symptomatic hydrocephalus were 4% and 1%, respectively. Male
Hearing loss 3.033 1.166-7.887 .023
sex (P = .014), pre-GKRS EBRT (P = .010), and ataxia at
a
GKRS, gamma knife radiosurgery; EBRT, external beam radiation therapy; CI, presentation (P = .002) were independent predictors of tumor
confidence interval. progression. The rate of symptomatic AREs in this study was low at
b
Unfavorable outcome = tumor progression or new or worsening neurological 1.1%. Including those that were transient, new or worsening
deficit.
neurological deficits were most commonly alterations in facial

NEUROSURGERY VOLUME 75 | NUMBER 4 | OCTOBER 2014 | 405

Copyright Congress of Neurological Surgeons. Unauthorized reproduction of this article is prohibited

DING ET AL
sensation, suggesting CN V neuropathy (59%); dizziness or
imbalance, suggesting CN VIII or cerebellar dysfunction (6%);
and hearing loss, suggesting CN VIII neuropathy (3%). Permanent
neurological deterioration was observed in 9% of patients. Facial
spasms at presentation (P = .007) and lower maximal dose (P = .011)
were independent predictors of permanent neurological deteriora-
tion, and ataxia at presentation (P = .037), alteration in facial
sensation at presentation (P = .007), and hearing loss at presentation
(P = .023) were independent predictors of unfavorable outcome
(ie, tumor progression or permanent neurological deterioration).
Limitations
This multicenter study of SRS for CPA meningiomas is the
largest SRS series ever reported for meningiomas arising from this
location, but it remains limited by its retrospective design. As with
any retrospective analysis, our study is limited by the treatment
and selection biases of the treating physicians and institutions. By
including data from several different institutions, each with its own
distinct referral patterns, we hope that some of these selection
biases are mitigated. We acknowledge that the statistical power of
our Cox proportional hazards and logistic regression analyses is
a limitation in the context of the assessed covariates.28,29 Along
with other potential biases, the limited overall power of this study
may diminish the generalizability of our results. However, the
patient and tumor characteristics found to be predictive of
radiologic and clinical outcomes in this study are similar to those
that have been determined to be predictors in larger series
including all skull base meningiomas.7,30
Because of the multicenter nature of this study and the
heterogeneous morphology of tumor growth in the patients with
post-GKRS tumor progression, we are unable to comment on the
proportion of tumor progressions that were outside of the 50%
isodose line. Because CPA meningiomas do not result in early
mortality in the vast majority of patients, the data for overall survival
was not obtained. Additionally, the radiologic presence of brainstem
indentation secondary to local mass effect and of peritumoral edema
with direct adhesion to the pia was unable to be noted in this study.
The study is not randomized, and there is no control group of
conservatively managed patients. We do not have CPA meningi-
omas patients with comparable demographics and tumor character-
istics who were treated with either EBRT or microsurgery with
which to compare our SRS outcomes, although the goal of this study
was not to compare SRS with the other 2 treatment modalities.
Rather, SRS should play a complementary role in the multidisci-
plinary management of patients harboring these lesions.
Our intention was to include only WHO grade I CPA
meningiomas. However, since 70% of patients were treated with
radiosurgery alone without surgical resection, histologic confirma-
tion of the presumed tumor grade and pathology were not available
for the majority of patients in this study. Although unlikely, it is
possible that, in those patients who were treated for presumed
benign CPA meningiomas based on neuroimaging characteristics
alone, some of the lesions were, in fact, nonmeningioma extra-axial
tumors, such as vestibular schwannomas, or nonbenign meningi-
406 | VOLUME 75 | NUMBER 4 | OCTOBER 2014
Copyright Congress of Neurological Surgeons. Unauthorized reproduction of this article is prohibited
omas. Only 4% of patients underwent further post-GRKS surgical
resection, and the diagnosis of a WHO grade I meningioma was
made in all 7 cases. Finally, the efficacy of hypofractionated GKRS
via the Extend system, which has the potential to safely treat large
skull base tumors, was not evaluated in this study.31,32
Interpretation: Radiosurgery Outcomes for
Cerebellopontine Angle Meningiomas
Radiosurgery was traditionally used following surgical resection
for the treatment of residual or recurrent tumors. In the modern era
of skull base tumor management, radiosurgery is being utilized as an
initial treatment in an increasing proportion of patients with CPA
meningiomas. Until the current series, it has been difficult to
separately analyze the outcomes for meningiomas of the CPA owing
to their rarity. Prior meningioma radiosurgery series have evaluated
the outcomes cumulatively for posterior fossa meningiomas or skull
base meningiomas.7,33-37 By combining GRKS data from multiple
institutions in a joint effort to define patient, tumor, and treatment
factors predictive of successful and poor outcomes, we are able to
provide a detailed analysis of radiosurgical efficacy in the treatment
of CPA meningiomas based on a large number of cases.
We reported excellent rates of both long-term actuarial and overall
tumor control for CPA meningiomas treated with radiosurgery. A
previous single-institution study of 255 skull base meningiomas,
including 17% located in the CPA, demonstrated similar 5- and 10-
year PFS rates of 96% and 79%, respectively.7 Pollock et al8
reviewed the radiosurgery outcomes of 416 patients with menin-
giomas, the majority of which involved the skull base or tentorium
(81%), and achieved tumor control rates at 5 and 10 years of 96%
and 89%, respectively. For small to moderately sized meningiomas,
primary radiosurgical treatment has been shown to provide
equivalent tumor control rates to Simpson grade I surgical resection
and superior tumor control rates to grade II, III and IV resections.11
Given the technical difficulty and operative morbidity associated
with aggressive resection of even moderately sized meningiomas in
the CPA, radiosurgery appears to provide a minimally invasive and
efficacious alternative for long-term tumor control. However, since
the median interval between radiosurgical treatment and tumor
growth in those patients with tumor progression was 40.5 months,
it is clear that rigorous radiologic and clinical follow-up are needed
beyond 5 years in order to better define the risks and benefits of
radiosurgery for CPA meningiomas.
Male sex has been previously identified to be a negative prognostic
factor for tumor control.8,38 Although not definitely proven, the
gender disparity in meningioma radiosurgery outcomes suggests
a biological difference in the meningiomas acquired by male vs female
patients. Negative progesterone receptor status has been correlated
with an increased rate of meningioma recurrence.39 In contrast,
positive estrogen receptor status, although uncommon, has been
linked to increased rates of meningioma progression, recurrence, and
clinical aggressiveness.40 The poorer response of meningiomas to
radiosurgery in males suggests that a difference in serum levels of
progesterone and estrogen may predispose male patients to the
development of more biologically aggressive or radioresistant lesions.
www.neurosurgery-online.com

Previous EBRT is also known to predispose meningiomas to a less
favorable response to subsequent radiosurgery.41 It remains poorly
understood whether treatment with EBRT increases the radio-
resistance of meningiomas or whether those tumors that have failed
EBRT are inherently more aggressive lesions.
The incidences of radiosurgery-induced symptomatic AREs and
permanent neurological deficits were relatively low. The rate of
peritumoral edema following radiosurgery of skull base meningio-
mas is known to be lower than that of convexity, parafalcine, and
parasagittal meningiomas.42,43 Furthermore, the proportion of
patients who required postradiosurgery tumor resection or
ventriculoperitoneal shunt placement was also acceptably low.
Despite our finding of an increased likelihood of permanent
neurological deterioration with lower maximal dose, it is important
to note that the selection of margin and maximal radiosurgical
doses is frequently affected by tumor volume, proximity to
surrounding critical structures such as the brainstem and cranial
nerves, tumor histopathology, previous treatments if any, and
preexisting neurological signs or symptoms. Owing to the complex
interrelationship between radiosurgical dose and tumor volume,
the association between radiosurgical dose and neurological deficits
may not be consistently observed across all meningioma radio-
surgery series. Additionally, cases of post-GKRS tumor progression
did not always correlate with new or worsening neurological deficits
and vice versa. In general, the experience of the treating clinicians
will dictate the minimum acceptable dose to achieve tumor control
while minimizing the risk to surrounding critical neural structures.
Dysfunction of CNs V, VII, and VIII and of the cerebellum
appeared to have the highest correlation with poor neurological or
overall outcome following radiosurgery. The specific cranial
neuropathy and the presence of cerebellar dysfunction are a product
of the specific growth patterns of meningiomas residing in the CPA.
In relationship to the tumor, CN V lies superior and the cerebellum
lies posterior, whereas the position of CNs VII and VIII vary widely
based on its anatomic boundaries and relationship to the IAC.
Although the relationship of CPA meningiomas to the IAC is
known to affect surgical prognosis, its effect on radiosurgical
outcomes has not yet been defined. Our results indicate that, in
addition to radiologically defined tumor characteristics, the patients
clinical presentation must be taken into account when considering
radiosurgery for CPA meningiomas and when counseling patients
regarding the outcomes afforded by radiosurgery. In a study of
radiosurgery for petroclival meningiomas, Flannery et al38 sug-
gested that the improvement of cranial neuropathy following
radiosurgery may, in part, be due to tumor regression that reduces
the risk of pathological cranial nerve demyelination. Of note,
previous surgical resection was not predictive of poorer radiologic
or clinical outcomes, thereby further supporting the complemen-
tary roles of microsurgery and radiosurgery for the management of
CPA meningiomas.
Generalizability
Owing to the multiple centers from which the analyzed outcomes
data were collected, we believe the results obtained from the current
NEUROSURGERY
Copyright Congress of Neurological Surgeons. Unauthorized reproduction of this article is prohibited
RADIOSURGERY FOR CEREBELLOPONTINE ANGLE MENINGIOMAS
study can be readily generalized to all patients with small to medium
(ie, less than 30 mm in maximal diameter) CPA meningiomas,
including those who have undergone previous EBRT and/or
resection. However, our results do not reflect the outcomes for
WHO grade II and III meningiomas, which are known to behave
more aggressively than their grade I counterparts,44 or nonmenin-
gioma CPA tumors, such as vestibular schwannomas, and therefore
should not be applied to patients diagnosed with these pathologies.
Furthermore, the treatment of large CPA meningiomas (ie, greater
than 30 mm in diameter or 14 cc in volume) is not typically
performed with single-session GKRS. Rather, radiation-based
therapy for large skull base tumors is more commonly delivered
by multisession (ie, 25 fractions) radiosurgery or various types of
EBRT (eg, stereotactic radiotherapy or intensity-modulated radio-
therapy). Thus, our results may not be directly translatable to
patients with large CPA meningiomas and should be interpreted
with caution in patients with a large meningioma.
CONCLUSION
Stereotactic radiosurgery offers a favorable risk-to-benefit pro-
file for meningiomas residing in the CPA. Small to moderately
sized tumors may be effectively treated with radiosurgery as an
initial therapeutic modality. Larger tumors should be surgically
debulked, if possible, with radiosurgery reserved in those cases for
significant residual or recurrent disease. Patients presenting with
symptoms suggestive of cerebellar compression or CN V or VIII
dysfunction are at greatest risk for experiencing an unfavorable
clinical or radiologic outcome following radiosurgery.
Disclosure
Dr Lunsford is a consultant and stockholder in AB Elekta. The other authors
have no personal, financial, or institutional interest in any of the drugs, materials, or
devices described in this article.
REFERENCES
1. Brackmann DE, Bartels LJ. Rare tumors of the cerebellopontine angle. Otolaryngol
Head Neck Surg (1979). 1980;88(5):555-559.
2. Laird FJ, Harner SG, Laws ER Jr, Reese DF. Meningiomas of the cerebellopontine
angle. Otolaryngol Head Neck Surg. 1985;93(2):163-167.
3. Thomsen J. Cerebellopontine angle tumours, other than acoustic neuromas. A
report on 34 cases. A presentation of 7 bilateral acoustic neuromas. Acta
Otolaryngol. 1976;82(1-2):106-111.
4. Voss NF, Vrionis FD, Heilman CB, Robertson JH. Meningiomas of the
cerebellopontine angle. Surg Neurol. 2000;53(5):439-446; discussion 446-447.
5. Sekhar LN, Jannetta PJ. Cerebellopontine angle meningiomas. Microsurgical
excision and follow-up results. J Neurosurg. 1984;60(3):500-505.
6. 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. 1995;112(2):228-234.
7. Starke RM, Williams BJ, Hiles C, Nguyen JH, Elsharkawy MY, Sheehan JP. Gamma
knife surgery for skull base meningiomas. J Neurosurg. 2012;116(3):588-597.
8. Pollock BE, Stafford SL, Link MJ, Brown PD, Garces YI, Foote RL. Single-
fraction radiosurgery of benign intracranial meningiomas. Neurosurgery. 2012;71
(3):604-612; discussion 613.
9. Zachenhofer I, Wolfsberger S, Aichholzer M, 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. 2006;58(1):28-36; discussion 28-36.
VOLUME 75 | NUMBER 4 | OCTOBER 2014 | 407
DING ET AL
10. Nicolato A, Foroni R, Pellegrino M, et al. Gamma knife radiosurgery in
meningiomas of the posterior fossa. Experience with 62 treated lesions. Minim
Invasive Neurosurg. 2001;44(4):211-217.
11. 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.
2003;55(4):1000-1005.
12. 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. 2006;104(1):157-162.
13. Altman DG. Practical Statistics for Medical Research. Boca Raton, Florida:
Chapman & Hall/CRC; 1999.
14. Hosmer DW, Lemeshow S, eds. Applied Logistic Regression. New York, NY: John
Wiley & Sons; 1989.
15. Simpson D. The recurrence of intracranial meningiomas after surgical treatment.
J Neurol Neurosurg Psychiatry. 1957;20(1):22-39.
16. Nakamura M, Roser F, Dormiani M, Matthies C, Vorkapic P, Samii M. Facial and
cochlear nerve function after surgery of cerebellopontine angle meningiomas.
Neurosurgery. 2005;57(1):77-90; discussion 77-90.
17. Schaller B, Merlo A, Gratzl O, Probst R. Premeatal and retromeatal cerebello-
pontine angle meningioma. Two distinct clinical entities. Acta Neurochir (Wien).
1999;141(5):465-471.
18. Kane AJ, Sughrue ME, Rutkowski MJ, Berger MS, McDermott MW, Parsa AT.
Clinical and surgical considerations for cerebellopontine angle meningiomas.
J Clin Neurosci. 2011;18(6):755-759.
19. 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. 2005;102(1):17-23.
20. Roberti F, Sekhar LN, Kalavakonda C, Wright DC. Posterior fossa meningiomas:
surgical experience in 161 cases. Surg Neurol. 2001;56(1):8-20; discussion 20-21.
21. 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). 2011;153
(10):1931-1940; discussion 1940.
22. Nutting C, Brada M, Brazil L, et al. Radiotherapy in the treatment of benign
meningioma of the skull base. J Neurosurg. 1999;90(5):823-827.
23. Han J, Girvigian MR, Chen JC, et al. A comparative study of stereotactic
radiosurgery, hypofractionated, and fractionated stereotactic radiotherapy in the
treatment of skull base meningioma [published online ahead of print]. Am J Clin
Oncol. 2012.
24. Debus J, Wuendrich M, Pirzkall A, et al. High efficacy of fractionated stereotactic
radiotherapy of large base-of-skull meningiomas: long-term results. J Clin Oncol.
2001;19(15):3547-3553.
25. Minniti G, Clarke E, Cavallo L, et al. Fractionated stereotactic conformal
radiotherapy for large benign skull base meningiomas. Radiat Oncol. 2011;6:36.
26. Combs SE, Ganswindt U, Foote RL, Kondziolka D, Tonn JC. State-of-the-art
treatment alternatives for base of skull meningiomas: complementing and
controversial indications for neurosurgery, stereotactic and robotic based radio-
surgery or modern fractionated radiation techniques. Radiat Oncol. 2012;7:226.
27. Combs SE, Adeberg S, Dittmar JO, et al. Skull base meningiomas: long-term
results and patient self-reported outcome in 507 patients treated with fractionated
stereotactic radiotherapy (FSRT) or intensity modulated radiotherapy (IMRT).
Radiother Oncol. 2013;106(2):186-191.
28. Sampson JH, Lad SP, Herndon JE II, Starke RM, Kondziolka D. SEER insights.
J Neurosurg. 2014;120(2):297-298.
29. Kiehna EN, Starke RM, Pouratian N, Dumont AS. Standards for reporting
randomized controlled trials in neurosurgery. J Neurosurg. 2011;114(2):280-285.
30. Kondziolka D, Mathieu D, Lunsford LD, et al. Radiosurgery as definitive
management of intracranial meningiomas. Neurosurgery. 2008;62(1):53-58;
discussion 58-60.
31. Sayer FT, Sherman JH, Yen CP, Schlesinger DJ, Kersh R, Sheehan JP. Initial
experience with the eXtend System: a relocatable frame system for multiple-session
gamma knife radiosurgery. World Neurosurg. 2011;75(5-6):665-672.
32. Schlesinger D, Xu Z, Taylor F, Yen CP, Sheehan J. Interfraction and intrafraction
performance of the Gamma Knife Extend system for patient positioning and
immobilization. J Neurosurg. 2012;117(suppl):217-224.
33. Pendl G, Schrottner O, Eustacchio S, Feichtinger K, Ganz J. Stereotactic radiosurgery
of skull base meningiomas. Minim Invasive Neurosurg. 1997;40(3):87-90.
408 | VOLUME 75 | NUMBER 4 | OCTOBER 2014
Copyright Congress of Neurological Surgeons. Unauthorized reproduction of this article is prohibited
34. Iwai Y, Yamanaka K, Yasui T, et al. Gamma knife surgery for skull base
meningiomas. The effectiveness of low-dose treatment. Surg Neurol. 1999;52(1):
40-44; discussion 44-45.
35. Morita A, Coffey RJ, Foote RL, Schiff D, Gorman D. Risk of injury to cranial
nerves after gamma knife radiosurgery for skull base meningiomas: experience in
88 patients. J Neurosurg. 1999;90(1):42-49.
36. Pollock BE, Link MJ, Foote RL, Stafford SL, Brown PD, Schomberg PJ.
Radiosurgery as primary management for meningiomas extending into the internal
auditory canal. Stereotact Funct Neurosurg. 2004;82(2-3):98-103.
37. Sheehan JP, Williams BJ, Yen CP. Stereotactic radiosurgery for WHO grade I
meningiomas. J Neurooncol. 2010;99(3):407-416.
38. Flannery TJ, Kano H, Lunsford LD, et al. Long-term control of petroclival
meningiomas through radiosurgery. J Neurosurg. 2010;112(5):957-964.
39. Maiuri F, De Caro MB, Esposito F, et al. Recurrences of meningiomas: predictive
value of pathological features and hormonal and growth factors. J Neurooncol.
2007;82(1):63-68.
40. Pravdenkova S, Al-Mefty O, Sawyer J, Husain M. Progesterone and estrogen
receptors: opposing prognostic indicators in meningiomas. J Neurosurg. 2006;105
(2):163-173.
41. Pollock BE, Stafford SL, Link MJ, Garces YI, Foote RL. Stereotactic radiosurgery of
World Health Organization grade II and III intracranial meningiomas: treatment
results on the basis of a 22-year experience. Cancer. 2012;118(4):1048-1054.
42. Ding D, Xu Z, McNeill IT, Yen CP, Sheehan JP. Radiosurgery for parasagittal and
parafalcine meningiomas. J Neurosurg. 2013;119(4):871-877.
43. Kondziolka D, Flickinger JC, Perez B. Judicious resection and/or radiosurgery for
parasagittal meningiomas: outcomes from a multicenter review. Gamma Knife
Meningioma Study Group. Neurosurgery. 1998;43(3):405-413; discussion 413-414.
44. Ding D, Starke RM, Hantzmon J, Yen CP, Williams BJ, Sheehan JP. The role of
radiosurgery in the management of WHO Grade II and III intracranial
meningiomas. Neurosurg Focus. 2013;35(6):E16.
Acknowledgment
The authors appreciate the assistance of Sharon DeCesare with coordination of
data for the North American Gamma Knife Consortium.
CME QUESTIONS:
1. For cerebellopontine angle meningiomas, what are the ten
year actuarial rates of progression-free survival following
gamma knife radiosurgery?
A. 90 to 99%
B. 80 to 89%
C. 70 to 79%
D. 60 to 69%
E. 50 to 59%
2. What is the incidence of symptomatic adverse radiation effects
following gamma knife radiosurgery for cerebellopontine
angle meningiomas?
A. 1 to 5%
B. 6 to 10%
C. 11 to 15%
D. 16 to 20%
E. 20 to 25%
3. Following gamma knife radiosurgery of cerebellopontine angle
meningiomas, what is an independent predictor of clinical or
radiographic progression?
A. Prior radiotherapy
B. Male gender
C. Lower maximal dose
D. Ataxia on presentation
E. Patient agesss
www.neurosurgery-online.com