Hearing Preservation in Patients With Unilateral Vestibular
Schwannoma Who Undergo Stereotactic Radiosurgery
Reinterpretation of the Auditory Brainstem Response
Jung Ho Han, MD1,3; Dong Gyu Kim, MD, PhD2,3; Hyun-Tai Chung, PhD2,3; Sun Ha Paek, MD2,3; Chul-Kee Park, MD2,3;
Chae-Yong Kim, MD1,3; Young-Hoon Kim, MD1,3; Jin Wook Kim, MD2,3; Yong Hwy Kim, MD2,3; Sang Woo Song, MD2,3;
In Kyung Kim, MD2,3; and Hee-Won Jung, MD2,3
BACKGROUND: The objective of this study was to identify the prognostic factors for hearing preservation that would allow the more
accurate stratification of patients who undergo stereotactic radiosurgery (SRS) for unilateral, sporadic vestibular schwannoma (VS).
METHODS: In total, 119 patients with VS who had serviceable hearing underwent SRS as primary treatment. The mean (?standard
deviation) patient age was 48 ? 11 years, and the mean (?standard deviation) follow-up duration was 55.2 ? 35.7 months. The median
marginal radiotherapy dose was 12.0 grays (Gy), and the mean (?standard deviation) tumor volume was 1.95 ? 2.24 cm3. The mean
(?standard deviation) pure tone average (PTA) score was 26 ? 12 decibels (dB) (range, 4-50 dB), and the mean (?standard devia-
tion) maximum speech discrimination score was 91 ? 12% (range, 52-100%). The mean (?standard deviation) baseline values for the
interlatency (IL) of waves I and III (IL I-III) and the IL of waves I through V (IL I-V) on auditory brainstem response were 2.58 ? 0.60
milliseconds (mS) (range, 1.92-4.30 mS) and 4.80 ? 0.61 mS (range, 3.80-6.40 mS), respectively. RESULTS: In multivariate analysis,
the PTA score and IL I-V were significant and independent prognostic factors (hazard ratio, 1.072; 95% confidence interval, 1.046-
1.098; P < .001; and hazard ratio, 1.534; 95% confidence interval, 1.008-2.336; P ¼ .046, respectively). By using the PTA score and IL I-
V, the patients were classified into 4 groups. The ratios of patients with serviceable hearing after SRS were 89.6%, 64.0%, 25.8%, and
6.7%, respectively, in Groups A through D (P < .001). CONCLUSIONS: The current results indicated that the classification system
based on using the PTA score and the IL I-V of the auditory brainstem response may be useful and specific for predicting the rate of
hearing preservation in each individual. Cancer 2012;118:5441-7. V
C2012 American Cancer Society.
KEYWORDS: radiosurgery, vestibular schwannoma, hearing preservation, classification system, auditory brainstem response.
In 1988, Gardner and Robertson described a classification system for predicting hearing preservation in patients who
underwent surgery for unilateral vestibular schwannoma (VS).1This system, called the Gardner-Robertson classification
system (G-R classification), is simple, straightforward, and can be performed from memory. Thus, the G-R classification
also has been useful for classifying hearing levels both before and after stereotactic radiosurgery (SRS) for VS,2-5although
thissystem wasbasedonthe resultsfroma surgicalseriesofpatients withVS.
SRS was first designed in 1951 by Lars Leksell,6and the use of SRS was expanded to include the treatment of VS in
1969.7Since the publication of Leksell’s 1971 report,7numerous efforts have been made to increase the tumor control
rate and reducethe riskof cranial nerve injury.Consequently, many reportson long-term outcomes after SRS forVS indi-
cated notonlyexcellentprogression-freesurvivalratesof92%to100%butalsooutstandingpreservationofthe trigeminal
nerve and facial nerve in 92% to 100% and 94% to 100% of patients, respectively, even with the lower marginal tumor
doses of 12 to 13 grays (Gy).4,8-18However, hearing preservation still falls short of our expectations; the range after SRS
tems are the G-R classification and the American Academy of Otolaryngology-Head and Neck Surgery guidelines for
hearing preservation in VS.1,23These 2 classification systems rely on the results of audiometry, pure tone average (PTA)
and maximumspeechdiscrimination score(SDS).
DOI: 10.1002/cncr.27501, Received: January 3, 2012; Revised: January 29, 2012; Accepted: January 30, 2012, Published online May 8, 2012 in Wiley Online
Corresponding author: Dong Gyu Kim, MD, PhD, Department of Neurosurgery, Seoul National University College of Medicine, 101 Daehang-ro Jongno-gu, Seoul
110-744, Korea; Fax: (011) 822-744-8459; firstname.lastname@example.org
1Department of Neurosurgery, Seoul National University Bundang Hospital, Gyeonggi-do, Korea;2Department of Neurosurgery, Seoul National University Hospital,
Seoul, Korea;3Department of Neurosurgery, Seoul National University College of Medicine, Seoul, Korea
November 1, 2012
However, to efficiently stratify patients according to
the outcomes of treatment modalities used, a thorough
statistical analysis is required. In that sense, the aforemen-
tioned classification systems seem to be deficient in their
ability to predict the exact rates of hearing preservation
among patients who undergo SRS for VS, although a
trend toward differences in hearing preservation between
the classes is obvious. In fact, from 10.9% to 39.2% of
ing. Conversely, hearing can be preserved in approxi-
mately 50% of patients who have a hearing level of G-R
Class 2after SRSforVS.2,22,24
Therefore, there appears to be a needfor better strat-
ification of patients with VS to refine the ability to predict
hearing preservation among patients who undergo SRS.
Thus, we performed this study based on our experience
over 10 years in treating patients with VS using SRS to
identify the prognostic factors of hearing preservation that
wouldallowusto stratifypatients moreappropriately.
MATERIALS AND METHODS
Between1998and 2009,728patientswithVS underwent
SRS at Seoul National University Hospital, Seoul, Korea.
The inclusion criteria were as follows: 1) SRS as the
primary treatment for VS; 2) sporadic unilateral VS; 3)
patients with serviceable hearing, defined as a hearing
level of G-R Class I or II,1at the time of SRS; 4) regular
audiometry follow-up; 5) patients who had auditory
brainstem response (ABR) testing before SRS as a rou-
tine examination of their auditory function; and 6) no
surgical resection of VS within 12 months after SRS.
Therefore, 119 patients (66.5%) among the 179 patients
who had sporadic unilateral VS and serviceable hearing
underwent radiosurgery as a primary treatment and were
enrolled in the current study (Fig. 1). All patient data
were collected from hospital charts and radiologic stud-
ies in accordance with the case record form approved by
the institutional review board. The clinical characteris-
tics are summarized in Table 1.
B, model C, or Perfexion; Elekta Instrument AB, Stock-
holm, Sweden). A treatment plan was generated using the
Leksell GammaPlan system (Elekta Instrument AB) based
on thin-sliced magnetic resonance (MR) images. T1-
weighted, 3-dimensional, multiplanar, rapid-acquisition,
gradient echo MR scan images were obtained before and
after gadolinium enhancement to determine the target
volume. The median marginal dose was 12.0 Gy (mean ?
standard deviation, 12.2 ? 0.9 Gy; range, 11-20 Gy), and
the median prescription isodose line was 50% (mean ?
standard deviation, 50.3 ? 2.3%; range, 45-70%). The
final prescription dose, expressed as a marginal dose, and
the associated treatment parameters are summarized in
Figure 1. In total, 728 patients underwent stereotactic radio-
surgery (SRS) for vestibular schwannoma (VS) at Seoul
National University Hospital between 1998 and 2009. Sixty-
three patients were diagnosed with neurofibromatosis type 2.
Two hundred patients had undergone previous surgical
resection, and 1 patient had received radiotherapy for VS.
Two-hundred eighty-five patients had no serviceable hearing
at the time of SRS. Four patients underwent additional surgi-
cal resection within 12 months after SRS for VS. Four patients
were lost to follow-up. Twelve patients had no follow-up audi-
ometry examination. Forty patients did not exhibit the audi-
tory brainstem response at the time of SRS. Thus, 119 patients
with sporadic, unilateral VS and serviceable hearing under-
went SRS as primary treatment and were enrolled in the cur-
Table 1. Patient Characteristics and Stereotactic
Characteristic Mean6SD [Range]
Age, y 48?11 [21-71]
No. of men (%)
No. of women (%)
Follow-up duration, mo
Tumor volume, cm3
Marginal dose prescribed, Gy
Mean cochlear dose, Gy
Maximum cochlear dose, Gy
No. of shots
Pure tone average, dB
Speech discrimination score, %
IL I-III, mS
IL I-V, mS
Abbreviations: dB, decibels; Gy, grays; IL I-III, the interlatency between
waves I and III on the auditory brainstem response; IL I-V, the interlatency
between waves I and III or between waves I and V on the auditory brain-
stem response; mS, milliseconds; SD, standard deviation.
November 1, 2012
Baseline evaluations, including audiometry and ABR, were
performed within 1 to 3 months before SRS. After SRS,
patients usually were followed at 1 month, 3 months, 6
months, 12 months, 18 months, and 24 months and annu-
ally thereafter. A clinical evaluation, which included a phys-
ical and neurologic examination, was performed at each
visit. Audiometry and ABR usually were performed every 6
months for the first 2 years after SRS. Additional audiome-
try and/or ABR assessments were based on patients’ percep-
tions of hearing deterioration.
PTA was calculated by averaging audiometric
masked bone conduction responses at 500 Hz, 1000 Hz,
and 2000 Hz. SDS was recorded to establish a pretreat-
ment audiometricgrade, aspreviouslydescribed.1
Auditory Brainstem Response Measurements
ABR testing was performed with a 4-channel evoked
potentials system (Spirit model; Nicolet Electronics,
Madison, Wis). Insert receivers were used in all patients.
The stimuli were 95-decibel (dB), rarefaction polarity
clicks with a stimulus duration of 100 milliseconds (mS).
The contralateral masking was set at 50 dB. The surface
electrode montage was the frontal zone to A1 or A2 (ear-
lobe) with the common ground at the frontal pole zero.
The stimulus rate was 7.7 Hz. The average sample size
was 1000 repetitions performed twice. Parameters were
changed based on selection of the ABR with the best mor-
phologic characteristics and replicability. Subdermal nee-
When ABRtesting produced no response, regardless
ABR testing obtained in this cohort were coded for each
interlatency (IL) of wave I and wave III (IL I-III) and IL I
through V (IL I-V), which was regarded as the maximum
value for ABR of the auditory pathway with serviceable
hearing in the presence of VS. However, the real ABR val-
ues in patients who had no response on ABR testing may
be greater than those estimated in this study. The values
used were4.3mSforIL-IIIand 6.4mSforILI-V.
Definition of Hearing Response and Other
PTA and SDS were recorded to establish a post-treatment
audiometric grade in the same way as in the pretreatment
evaluation. After assessing post-SRS hearing status during
follow-up, audiometries were treated as censored observa-
tions if serviceable hearing was preserved within G-R
Class I or II. Radiation dose to the cochlea was deter-
mined from retrieved treatment backup files, including
T2-weighted, volume-acquisition MR imaging divided
Kaplan-Meier survival plots were used to estimate the
overall survival with serviceable hearing. The log-rank test
(level of significance, a ¼ .05) was used to assess differen-
ces in overall survival with serviceable hearing between
the groups. The chi-square test was used to compare nom-
inal variables between the groups. A Pearson correlation
analysis was performed to identify bivariate correlations
between 2 continuous variables. The Cox proportional
hazards model (level of significance, a ¼ .05) was used to
adjust for covariates. A backward, stepwise method was
used for the multivariate analysis to identify the possible
new prognostic factors of hearing preservation and to
reduce the chance of type II error; variables were consid-
ered for multivariate analysis only if they were associated
with a dependent variable in each analysis at the P < .10
level. These statistical analyses were performed using
PASW Statistics (version 17.0.2; SPSS Inc., Chicago, Ill).
To identify the statistical cutoff value for each covariate
and classification and regression tree (CART) of hearing
preservation, the free software R (version 2.12.2; rpart
package; R Foundation for Statistical Computing,
Vienna, Austria; available from: http://www.r-projec-
t.org/ accessed February 24, 2012) was used.
Forty-five patients (37.8%) were men, and 74 (62.2%)
were women. The mean patient age (?standard devia-
tion) was 48 ? 11 years (range, 21-71 years), and the
mean follow-up duration (?standard deviation) was 55.2
? 35.7 months (range, 12.3-158 months). The mean tu-
mor volume (?standard deviation) was 1.95 ? 2.24 cm3
(range, 0.03-9.10 cm3). The mean number of shots was 8
(range, 1-20 shots). The mean PTA score (?standard
deviation) was 26 ? 12 decibels (dB) (range, 4-50 dB).
The mean SDS (?standard deviation) was 91% ? 12%
(range, 52%-100%). Thus, according to the G-R classifi-
cation, 79 patients (66.4%) had a Class 1 hearing level,
and 40patients (33.6%)hadaClass 2 hearinglevel.
The mean (?standard deviation) baseline values of
IL I-III and IL I-V were 2.58 ? 0.60 mS (range, 1.92-
4.30 mS) and 4.80 ? 0.61 mS (range, 3.80-6.40 mS),
respectively. The mean (?standard deviation) interaural
differences in IL I-III (ID-IL I-III) and ID-IL I-V were
0.45 ? 0.59 mS (range, ?0.48 to 2.30 mS) and 0.70 ?
Hearing Preservation in VS After SRS/Han et al
November 1, 2012
The mean (?standard deviation) of the maximum
cochlear dose was 8.13 ? 3.02 Gy (range, 2.40-16.6 Gy).
The mean (?standard deviation) of the mean cochlear
dose was4.30? 1.51Gy(range,1.40-8.30Gy).Theclin-
Hearing-Preservation Rate and Its Prognostic
Until the last clinical follow-up, in total, 51 patients
(42.9%) lost their serviceable hearing. The median sur-
vival with serviceable hearing was 67 months after SRS.
The actuarial rates of hearing preservation were 79.7%,
68.5%, 62.5%, 59.9%, and 56.2% at 6 months, 12
months, 24 months, 36 months, and 60 months after
In the univariate analyses, G-R class, PTA score,
SDS, IL I-V, and ID-IL I-V were associated significantly
with hearing outcome. In addition, the tumor volume
and mean cochlear dose were associated with the preserva-
tion of serviceable hearing; however, they did not reach
statistical significance. On multivariate analysis, only
PTA score and IL I-V remained as significant and inde-
pendent prognostic factors (hazard ratio, 1.072 [95%
confidence interval, 1.046-1.098; P < .001] and 1.534
[95% confidence interval, 1.008-2.336; P ¼ .046],
respectively). The remaining covariates, including the G-
R class, mean cochlear dose, and SDS, were removed dur-
ing the process of the multivariate analysis that involved
use of the backward-stepwise method. Results of the sta-
Classification and Regression Tree Analysis and
New Classification for Hearing Preservation
Using PTA score and IL I-V, which we identified as sig-
nificant and independent prognostic variables of hearing
preservation, a CART comprising 119 patients was
Figure 2. This is a Kaplan-Meier plot of survival with servicea-
ble hearing in patients with vestibular schwannoma. Until the
last clinical follow-up, in total, 51 patients (42.9%) lost their
serviceable hearing. The median survival with serviceable
hearing was 67 months after stereotactic radiosurgery (SRS).
The actuarial rates of hearing preservation were 79.7%,
68.5%, 62.5%, 59.9%, and 56.2% at 6 months, 12 months, 24
months, 36 months, and 60 months, respectively, after SRS.
Table 2. Prognostic Factors Related to Hearing Preservation After Stereotactic Radiosurgery for Vestibular Schwannoma
Univariate Analysis Multivariate Analysis
VariableHRP HRP 95% CI
Marginal dose prescribed
No. of shots
Gardner-Robertson Class 2 vs Class 1
Pure tone average
Speech discrimination score
Mean cochlear dose
Maximum cochlear dose
Interaural difference in IL I-III
Interaural difference in IL I-V
Abbreviations: CI, confidence interval; IL I-III, the interlatency between wave I and II on the auditory brainstem response; IL I-V, the interlatency between wave
I and III or between wave I and V on the auditory brainstem response; HR, hazard ratio.
aThese covariates were analyzed in the multivariate analysis using the backward stepwise method with a Cox proportional hazards model.
bThe difference in these covariates was statistically significant.
November 1, 2012
created. We identified 3 nodes (ie, branching points). The
tree was split by a PTA score of 21 mS and then by an IL
I-V of 5.225 mS. Finally, a PTA of 31 mS split the tree
(Fig. 3). On the basis of the terminal nodes, we catego-
rized thepatientsinto 4 groups(Table3,Fig. 4).
The ratios of patients who preserved their servicea-
ble hearing during follow-up differed significantly (P <
.001) between groups, and the ratios of patients with serv-
iceable hearing at the last clinical follow-up were 89.6%,
64%, 25.8%, and 6.7% for groups A through D,
Although numerous studies have suggested possible prog-
nostic factors for hearing preservation, such as radiation
dose to the cochlea or its structures, the length of irradi-
ated cochlear nerve, marginal dose to the tumor itself, and
age,2,21,24-32these factors still are debated, and we do not
ing after SRS for VS. However, a consistent prognostic
factor of hearing preservation in the management of
patients with VS is the level of hearing before treatment,
even in surgical series.1,33Therefore, the previous classifi-
cation systems have been based on results from audiome-
try using the PTAscore and SDS.1,23In the current study,
the PTA score was identified as 1 of the significant and in-
dependent covariates related to hearing preservation,
which appears to be the same result obtained in previous
However, SDS and G-R class itself were removed in
the multivariate analysis. One possible reason is that the
PTAscorehadasignificant correlation withSDS (correla-
tion coefficient, ?0.688; P < .001), although the PTA
score does not usually match up exactly with SDS, as
described by Gardner and Robertson Gardner in their
report.1Thus,theclassificationsystemsbasedon 2 covari-
ates with significant correlation to each other may fall
vation in patients who undergo SRS for VS. Conse-
quently, there is huge variation in the level of hearing
Figure 3. By using the pure tone average (PTA) and the inter-
latency of waves I through V (IL I-V) on the auditory brain-
stem response—the significant and independent prognostic
variables of hearing preservation—a classification and regres-
sion tree that included 119 patients was created. Three nodes
(or branching points) were identified. The tree was split by a
PTA of 21 milliseconds (mS) and then by an IL I-V of 5.225
mS. Finally, a PTA of 31 mS split the tree.
Table 3. Risk Group Splits Based on the Results From Classification and Regression Tree Analysis
Risk Group No. of PatientsNo. With Hearing
Group A: PTA?20
Group B: IL I-V<5.225 mS and 21?PTA?30
Group C: IL I-V<5.225 mS and 31?PTA?50
Group D: IL I-V?5.225 mS and PTA?50
Abbreviations: IL I-V, the interlatency between wave I and V on the auditory brainstem response; mS, milliseconds; PTA, pure tone average score.
Figure 4. This chart illustrates the rates of serviceable hearing
in the 4 groups based on a classification and regression tree
analysis of the groups.
Hearing Preservation in VS After SRS/Han et al
November 1, 2012
preservation even within each subgroup,2,22,24which may
One of the noteworthy findings of the current study
is that1 value of ABR—ILI-V—was identifiedas a signifi-
cant prognostic factor for hearing preservation, even in the
multivariate analysis. Similar findings about the possible
relation between ABR results and hearing preservation
have been recently reported, although the results were not
confirmed in multivariate analysis.22Badie et al35directly
measured the intracanalicular pressure of the internal audi-
tory canal in patients with VS and demonstrated that the
intracanalicular pressure correlates well with absolute wave
V latencyandILI-V ofABR.AlthoughABR is nota direct
measure of hearing function, studies have indicated an
association between hearing loss and delays in wave V and
IL I-V.35,36In addition, patients who had G-R Class 1
pared with patients who had G-R Class 2 hearing, but the
difference between the groups did not reach statistical sig-
sure may not correlated exactly with hearing function in
the setting of VS but may have an independent effect on
hearing outcome. Therefore, the huge intraclass variation
of hearing preservation in the same G-R class may be
caused by the differences in intracanalicular pressure
among patients who undergo SRS for VS, which could
explain the finding that patients with G-R Class 1 hearing
lose their serviceable hearing. Conversely, patients with G-
By using the CART analysis, we were able to catego-
rize our patients into 4 groups and refine the relative risk
of losing serviceable hearing in each group after SRS for
VS. This finding seems to be important in the proper
selection of patients whose serviceable hearing should be
preserved and in predicting the hearing loss of each
In summary, the level of hearing, expressed as the
PTA score, and the intracanalicular pressure, measured as
the IL I-V on the ABR examination, appear to be signifi-
cant and independent prognostic factors for hearing pres-
ervation in patients who undergo SRS for VS. The
classification system using these 2 covariates may be more
useful and specific for predicting the hearing-preservation
rate in an individual than the systems that use only the
correlations among audiometry results. To preserve serv-
iceable hearing in each patient with VS, an individualized
treatment strategy may be beneficial according to the clas-
sification system. The findings of this study and the accu-
racy of the classification system should be scrutinized in
the nearfutureinalarger groupof patients.
This study was supported by grant 02-2011-006 from the Seoul
National University Bundang Hospital Research Fund.
CONFLICT OF INTEREST DISCLOSURES
The authors made no disclosures.
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