close

Вход

Забыли?

вход по аккаунту

?

00016489.2017.1386800

код для вставкиСкачать
Acta Oto-Laryngologica
ISSN: 0001-6489 (Print) 1651-2251 (Online) Journal homepage: http://www.tandfonline.com/loi/ioto20
Factors affecting hearing deterioration in
vestibular schwannoma patients treated with
gamma knife radiosurgery: the Asan Medical
Center experience
Marn Joon Park, Hong Ju Park, Jong Woo Chung, Do Heui Lee, Young Hyun
Cho, Young Jun Choi & Joong Ho Ahn
To cite this article: Marn Joon Park, Hong Ju Park, Jong Woo Chung, Do Heui Lee, Young Hyun
Cho, Young Jun Choi & Joong Ho Ahn (2017): Factors affecting hearing deterioration in vestibular
schwannoma patients treated with gamma knife radiosurgery: the Asan Medical Center experience,
Acta Oto-Laryngologica, DOI: 10.1080/00016489.2017.1386800
To link to this article: http://dx.doi.org/10.1080/00016489.2017.1386800
View supplementary material
Published online: 25 Oct 2017.
Submit your article to this journal
Article views: 5
View related articles
View Crossmark data
Full Terms & Conditions of access and use can be found at
http://www.tandfonline.com/action/journalInformation?journalCode=ioto20
Download by: [University of Florida]
Date: 27 October 2017, At: 22:56
ACTA OTO-LARYNGOLOGICA, 2017
https://doi.org/10.1080/00016489.2017.1386800
RESEARCH ARTICLE
Factors affecting hearing deterioration in vestibular schwannoma patients
treated with gamma knife radiosurgery: the Asan Medical Center experience
Marn Joon Parka, Hong Ju Parka, Jong Woo Chunga, Do Heui Leeb, Young Hyun Chob, Young Jun Choic and
Joong Ho Ahna
a
Downloaded by [University of Florida] at 22:56 27 October 2017
Department of Otorhinolaryngology Head & Neck Surgery, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Republic of
Korea; bDepartment of Neurosurgery, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Republic of Korea; cDepartment
of Radiology and Research Institute of Radiology, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Republic of Korea
ABSTRACT
ARTICLE HISTORY
Objectives: To investigate the changes in hearing and to determine factors predicting hearing deterioration in patients with vestibular schwannoma (VS) who undergo gamma knife radiosurgery (GKRS).
Design: A retrospective review of medical records in patients diagnosed with VS and initially treated
with GKRS at a tertiary care medical center between 1995 and 2015 was performed. Tumor factors
(location, volume), parameters related to irradiation to the tumor and cochlea, and distance between
the tumor and cochlea were reviewed.
Results: Fifty-six patients were included in the final analysis with a mean observation period following
GKRS as 24.4 ± 27.8 months. Prior to GKRS, the average pure tone threshold at 500, 1k, 2k, and 4k Hz
(PTA4) was 51.0 ± 29.7 dB HL. After GKRS, the mean PTA4 was 71.6 ± 33.3 dB HL. Significant independent
odds ratios for hearing deterioration were 8.5 for extracanalicular tumors, 18.8 for more than 10 shots
in GKRS, and 12.2 for a distance between the tumor center and cochlea modiolus less than 20 mm.
Conclusions: A significant hearing deterioration was shown in 2 years after GKRS. Tumor location,
number of radiation shots, and distance between the tumor and cochlea affected hearing level after
GKRS.
Received 26 July 2017
Revised 12 September 2017
Accepted 17 September 2017
Introduction
Vestibular schwannoma (VS) is a slow-growing benign
tumor mostly originating from the eighth cranial nerve that
accounts for 6–9% of all brain tumors [1]. Due to compression of the cranial nerves and nucleus, symptoms in VS
patients depend on tumor location.
The treatment options for VS include observation, microsurgical resection, and gamma knife radiosurgery (GKRS).
Because less than 25% of patients with VS experience significant hearing decline, some physicians prefer to perform
regular serial imaging follow-up, only considering an intervention upon symptomatic development or tumor growth
[2]. However, tumor manipulation may lead to complications such as further hearing deterioration, vertigo, or facial
palsy.
GKRS was first used in 1969 by Leksell et al. [3]. Since
then, advances in stereotactic radiosurgery and fractional
irradiation technology have led to a 90% tumor control rate,
as well as functional preservation of the cranial nerves.
Elliott et al. [4] reported an almost 50% rate of hearing preservation in patients treated with GKRS. Golfinos et al. [5]
particularly stressed the merits of GKRS in patients with
small-sized VS (less than 2.8 cm), and Mousavi et al. [6]
KEYWORDS
Vestibular schwannoma;
acoustic neuroma; gamma
knife stereotactic
radiosurgery; hearing
preservation; hearing
deterioration
argued that there was a better chance of hearing preservation in patients whose hearing is initially preserved.
Despite the benefits of GKRS, the auditory nerve function
is the least preserved of that of all cranial nerves in VS
patients managed by GKRS. A decline in hearing was
observed in 30–35% of patients, whereas over 98% of
patients with VS managed by GKRS showed preservation of
both the facial and trigeminal nerves [7].
Therefore, many recent studies have focused on hearing
preservation in VS after GKRS. However, it is still unclear
which clinical factors account for the hearing deterioration
and to what extent. Therefore, we investigated the changes
in hearing by frequency and prognostic factors for hearing
deterioration in patients with VS who underwent GKRS.
Methods
Study subjects
This retrospective review of medical records was performed
with patients confirmed with VS at a tertiary care medical
center in South Korea between January 1995 and December
2015. Among the 993 patients who were diagnosed with VS
in those 10 years, patients who underwent GKRS without
CONTACT Joong Ho Ahn
meniere@amc.seoul.kr
Department of Otolaryngology, Asan Medical Center, University of Ulsan College of Medicine, 88
Olympic-ro 43-gil, Songpa-gu, Seoul 05505, Republic of Korea
Supplemental data for this article can be accessed here.
ß 2017 Acta Oto-Laryngologica AB (Ltd)
Downloaded by [University of Florida] at 22:56 27 October 2017
2
M. J. PARK ET AL.
Figure 1. Study design and patient recruitment. An illustrated description of the study design. Between 1995 and 2015, patients confirmed to have VS on TBMRI
who underwent GKRS were retrospectively reviewed. In total, 56 patients were recruited for the final statistical analysis. TBMRI: gadolinium-enhanced temporal
bone magnetic resonance imaging; GKRS: gamma knife radiosurgery; NF-II: neurofibromatosis type II; PTA: pure tone audiometry; SA: speech audiometry; VS: vestibular schwannoma.
any prior treatment (e.g. microsurgical resection) for VS
were included. Patients who did not undergo pure tone
audiometry (PTA) with speech audiometry (SA) both prior
to and after GKRS at least once were excluded. Additionally,
patients with bilateral VS and neurofibromatosis type II
(NF-II) were excluded. Patients with a follow-up period less
than 6 months following GKRS were also excluded. In total,
56 patients were included in the final analysis (Figure 1).
This study was approved by institutional review board (IRB)
of Asan Medical Center IRB (approval no. 2016-1007).
Gadolinium-enhanced temporal bone magnetic
resonance imaging
All 56 patients had temporal bone MRI (TBMRI) obtained
by using a 3T magnetic resonance imaging system (Achieva;
Philips Healthcare, Best, The Netherlands) with an 8-channel head coil. Coronal T1- and T2-weighted turbo spinecho, axial three-dimensional (3D) T2-weighted, pre-contrast
and post-contrast 3D fluid-attenuated inversion recovery
(FLAIR), and post-contrast T1-weighted imaging were performed. Gadolinium-DOTA (Dotarem; Guerbet, Paris,
France) at 0.2 mmol/kg of body weight was used for the
contrast enhancement. Board-certified radiologists confirmed
the diagnosis of VS.
Hearing assessments: pure tone audiometry and speech
audiometry
Initial hearing was assessed with PTA and SA. For PTA,
with the masking of the contralateral ear, warble-tone
thresholds were measured at 250, 500, 1000, 2000, 3000,
4000, and 8000 Hz and then averaged (PTA4). For SA, word
discrimination scores (WDSs) at 40 and 60 dB SPL in quiet
were measured using the Korean standard word lists
for adults [8]. Patients’ initial hearing levels were stratified
using the American Academy of Otolaryngology – Head and
Neck Surgery (AAO-HNS) classification [9] (Supplementary
Table S1).
GKRS and follow-up
In all cases, GKRS was performed by applying a Leksell
Gamma knife (B. and C. Elekta, Stockholm, Sweden) device in
the following order. First, a Leksell stereotactic coordinate
frame was applied on the recipients’ vertex. Then, a gadolinium contrast magnetic resonance T1-weighted image with
2-mm slice reconstruction on the axial plane was taken.
Afterward, the GKRS was designed using GammaPlan (Elekta)
instrument software. The prescribed dose at the tumor margin
was set at 12.2 ± 0.5 Gy (minimum, 10.0 Gy; maximum,
13.0 Gy) (Table 1), giving a 50% median isodose line. Leksell
GammaPlanV software (version 10.2.1, Stockholm, Sweden)
was used to accurately calculate the amount of irradiation
received at each point and a distance–dose curve for the
irradiation dosage was subsequently drawn (Figure 2).
After GKRS, all patients were admitted for 1 day.
Contrast-enhanced head computed tomography (CT) was
conducted immediately after GKRS to rule out any immediate GKRS-related complications. After discharge, the patients
were asked to attend a 1-week postoperative visit and a yearly
follow-up to undergo TBMRI using the above protocol. By
applying the criteria suggested by Kanzaki et al. [10] in 2003,
the response of VS to GKRS was categorized as regression,
stable, and progression. Patients were asked to undergo a
baseline hearing assessment within 1 month before the
administration of GKRS. However, due to the retrospective
nature of the study, only a small number of patients had their
hearing evaluated after GKRS, in an inconsistent manner.
R
Measured variables
Patient sex and age at diagnosis were collected. Changes in
clinical symptoms (tinnitus, facial palsy, vertigo, and facial
ACTA OTO-LARYNGOLOGICA
Table 1. Demographic and clinical characteristics of the study patients
(n ¼ 56).
Downloaded by [University of Florida] at 22:56 27 October 2017
Characteristics
Age at diagnosis
Sex (male/female), n (%)
Tumor characteristics
Lateralization (L/R), n (%)
Intracanalicular/extracanalicular, n (%)
Tumor volume (cm3)
LAD (mm)
Long–short-axis ratioa
Distance parameters
Center-to-center distance (mm)b
Minimal distance (mm)c
Irradiation parameters related to GKRS
Prescribed dose (Gy)
Maximal dose (Gy)
Minimal dose (Gy)
Mean dose (Gy)
Cochlear dose (Gy)
Number of shots
Observation period following GKRS (months)
Tumor response to GKRSd
Regression/stable/progression, n (%)
Immediate complications following GKRS, n (%)
Hydrocephalus
Limb weakness
Mean ± SD (Min–Max)
50.2 ± 12.0 (16–71)
24/32 (42.9/57.1)
30/26
15/41
2.07 ± 2.36
17.2 ± 6.9
1.60 ± 0.58
(53.6/46.4)
(26.8/73.2)
(0.01–9.10)
(4.0–30.8)
(1.0–4.4)
11.4 ± 6.0 (4.0–60.7)
3.3 ± 2.6 (1.0–13.3)
12.2 ± 0.5
24.1 ± 1.5
9.8 ± 1.5
17.0 ± 1.1
4.6 ± 1.8
8.5 ± 6.0
24.4 ± 27.8
(10.0–13.0)
(20.0–26.2)
(6.2–14.8)
(14.3–19.1)
(2.1–8.9)
(1–26)
(6.1–137.2)
24/26/6 (42.9/46.4/10.7)
2 (3.6)
1 (1.8)
GKRS: gamma knife radiosurgery; L: left; LAD: long-axis diameter; R: right; SD:
standard deviation.
a
Long-axis diameter divided by short-axis diameter.
b
Distance between the tumor center and cochlea modiolus (mm).
c
Minimal distance between the tumor and cochlea modiolus (mm).
d
Tumor response following GKRS was categorized by applying the generally
accepted criteria [19].
3
numbness) and audiometric data before and after GKRS
were also reviewed. The time interval after GKRS was
regarded as the ‘observation period’, and the final state of
the tumor was assessed.
On the obtained TBMRI, the location of the tumor was
identified according to its presence on the contrast-enhanced
T1-weighted image: VS limited to the intra-auditory canal
(IAC) was defined as ‘intracanalicular’ (Figure 3(A)),
whereas VS partially overlapping between the IAC and cerebellopontine angle or located predominantly at the cerebellopontine angle was defined as ‘extracanalicular’ (Figure 3(B)).
The long- and short-axis diameters were measured, and the
long–short-axis ratio (the long-axis diameter divided by
the short-axis diameter) was calculated for each tumor. On
T2-weighted imaging, the spatial relationship between the
cochlea and the tumor was analyzed, and the following two
distance parameters were defined (Figure 4): center-to-center
distance, the distance between the tumor center and the
cochlea modiolus; minimal distance, the minimal distance
between the tumor and the cochlea modiolus.
For the variables associated with GKRS, the parameters
reflecting the dose of irradiation were defined as follows:
prescribed dose, the ‘intended dose’ at the 50% median isodose line, drawn along the border of the tumor; mean dose,
Figure 2. Dose of irradiation to the tumor, cochlea, and adjacent structures during GKRS in VS patients. An explanatory model for the higher irradiation dose to the
cochlea that elevates the risk of hearing deterioration according to the tumor location in GKRS planning. The upper plots show the percentage deposition of the
irradiation dose in relation to the relative distance in the GKRS while the lower images show magnified T2-weighted TBMRI of two VS patients. A shows a rightsided intracanalicular VS in a 34-year-old male, whereas B shows a right-sided extracanalicular VS in a 44-year-old female. By using Leksell GammaPlanV (version
10.2.1), the expected irradiation discrimination margin (yellow line; light-gray line in black & white printing) is designed to be almost parallel to the border of the
tumor (red line; dark-gray line in black & white printing). Although the minimal and central distances between the cochlea (arrowheads) and the expected margin
of irradiation are much shorter in intracanalicular VS (A) than in extracanalicular VS (B), note that a similar dose of irradiation is administered to the cochlea in the
two patients. Additionally, it is notable that the slope of the tangent is much more precipitous in an intracanalicular tumor (16.23) than in an extracanalicular tumor
(5.06) at the point where 50% of the maximum irradiation is expected. This model is a possible explanation of the poorer hearing in patients with extracanalicular
VS following GKRS.
R
Downloaded by [University of Florida] at 22:56 27 October 2017
4
M. J. PARK ET AL.
Figure 3. Definitions of intracanalicular and extracanalicular VSs. Gd-enhanced T1-weighted images of TBMRI of two patients diagnosed with VS. Image A shows an
intracanalicular VS (arrow) located exclusively in the right internal auditory canal. Image B shows an extracanalicular VS (arrow) extruding out to the cerebellopontine angle.
Table 2. Changes in clinical manifestations following GKRS (n ¼ 56).
Cranial nerve function
b
PTA4 (dB HL)
Word discrimination score (%)b
Initial hearing, n (%)
Serviceable/nonserviceable
Tinnitus, n (%)
Facial palsy, n (%)
Vertigo, n (%)
Facial numbness, n (%)
Initial
(prior to GKRS)
Final
(following GKRS)
p Valuea
51 ± 30 (3–100)
55 ± 42 (0–100)
72 ± 33 (5–120)
39 ± 39 (0–100)
<.001
.001
28/28 (50/50)
28 (50.0)
1 (1.8)
18 (32.1)
1 (1.8)
13/43 (23.2/76.8)
32 (57.1)
6 (10.7)
28 (50)
3 (5.4)
.003
.449
.113
.054
.618
GKRS: gamma knife radiosurgery; PTA4: average pure tone threshold at 500,
1000, 2000, and 4000 Hz; SD: standard deviation.
a
Comparison between the initial and final states: p values were calculated
using a paired t-test with Bonferroni correction, chi-square test, or Fisher’s
exact test. Bold text indicates p < .05.
b
Values are presented as mean ± SD (Min–Max).
Figure 4. Definition of the distance parameters: spatial relationship between
the cochlea and the tumor. Magnified TBMRI of a 53-year-old female patient
diagnosed with left extracanalicular-type VS. A T2-weighted image shows the
inner ear structure as well as the tumor (arrowhead, basal turn of the left cochlea; asterisk, left lateral semicircular canal). Distance parameters reflecting the
spatial relationship between the cochlea and the tumor were measured. Arrow
A indicates the minimal distance, defined as the length between the cochlea
modiolus and the tumor; Arrow B indicates the center-to-center distance,
defined as the length between the cochlea modiolus and the center of the
tumor.
the average dose of irradiation received at the 50% median
isodose line; maximal dose, the maximal amount of irradiation received along the 50% median isodose line; minimal
dose, the minimal amount of irradiation received along the
50% median isodose line; cochlear dose, the average irradiation dosage at four points at the cochlea border. The number of fractioned beams of irradiation given to the tumor to
achieve the target dose of irradiation was defined as the
‘number of shots’, which was determined by the physician
(D.H.L.).
Statistical analysis
A paired t-test with Bonferroni correction and a chi-square
test or Fisher’s exact test were used to compare the
changes in the clinical values and proportions between the
initial and final states (Table 2 and Figure 5). Student’s
t-test and chi-square/Fisher’s exact test were used for the
comparison of the mean values and proportions between
the preserved and deteriorated hearing groups (Table 3).
To compare the clinical variables between serviceable and
nonserviceable hearing (Supplementary Table S2) and
between intra- and extracanalicular VS (Table 6), Student’s
t-test with Levene’s test and chi-square/Fisher’s exact test
were used to assess the equality of variances. One-way
independent analysis of variance (ANOVA) was used to
evaluate the significance differences in the level of changes
associated with each frequency before and after GKRS
(Figure 6). To calculate the odds ratio (OR) for hearing
deterioration for each clinical factor, binary logistic regression analysis was used. Multivariate binary logistic regression analysis with backward elimination was performed
with variables found to be significant (p < .05) in univariate
analysis. The estimated ORs and 95% confidence intervals
(CIs) were calculated as well (Tables 4 and 5). Two-sided
p values less than .05 were considered significant. All statistical analyses were performed using IBM SPSS software
version 23.0 (IBM, Armonk, NY).
ACTA OTO-LARYNGOLOGICA
5
Downloaded by [University of Florida] at 22:56 27 October 2017
and the mean tumor volume was 2.07 cm3. The mean distance from the central portion of the tumor to the center of
the cochlea modiolus was 11.4 mm and the mean minimal
distance between the tumor margin and the modiolus was
3.3 mm. Although a mean of 12.2 Gy of irradiation was
designed to be given at the tumor margin, a mean value of
17.0 Gy was actually irradiated at the tumor margin when calculated retrospectively. The mean irradiation dose received at
the cochlea was determined to be 4.6 Gy, with a minimum of
2.1 Gy and a maximum of 8.9 Gy. The average number of
shots given was 8.5, ranging from 1 to 26. The mean observation period after GKRS was 24.4 months. Upon follow-up, 24
patients (42.9%) had tumor regression, 26 (46.4%) had a stable tumor, and six (10.7%) had tumor progression despite
GKRS. Four patients (7.1%) had additional microsurgical
resection of the tumor for uncontrolled growth despite
GKRS. Immediately after GKRS, one patient (1.8%) complained of mild weakness of the lower limb but showed spontaneous recovery within 1 month with conservative
management. Hydrocephalus was evident in two patients
(3.6%) in contrast-enhanced head CT following GKRS. One
patient had spontaneous shrinkage of the ventricle upon close
follow-up, whereas another patient had persistent hydrocephalus with no symptoms. This patient underwent a ventricleperitoneal shunt insertion for hydrocephalus management.
Changes in the clinical outcome after GKRS
Following GKRS, a significant increase was seen in the
PTA4 and a decrease in the WDS, with an increased proportion of patients with nonserviceable hearing (both p < .05)
(Table 2). In comparison, no significant changes were
observed in the other clinical manifestations. There was a
significant increase in the pure tone thresholds at each frequency and a decrease in the WDS in all 56 patients and in
patients with serviceable hearing (Figure 5). Similarly, in the
nonserviceable hearing patient group, significant changes
were seen in every register, except 250 Hz and WDS. There
were no differences between the level of changes in each frequency (Figure 6).
Factors associated with hearing deterioration
Figure 5. Changes in hearing following GKRS. Changes in hearing from before
GKRS to the final hearing in terms of frequencies and word discrimination
scores. In all 56 patients (above) and in the serviceable hearing group (middle),
all seven frequencies showed a significant increase in the pure tone threshold
(left) in addition to a significant decrease in word discrimination scores (right).
In the nonserviceable hearing group (below), the word discrimination score
(right) and the pure tone threshold (left) showed no significant increase with
250 Hz but the pure tone threshold level significantly increased from 500 to
8000 Hz. p < .05 is indicated with an asterisk ().
Results
Patient characteristics
This study included 56 patients – 24 men (42.9%) and 32
women (57.1%) – with a median age at diagnosis of 50.2
years. Patient characteristics are summarized in Table 1.
Among the 56 VSs, 15 (26.8%) were intracanalicular tumors,
The center-to-center distance was higher in the preserved
hearing group in all patients and in the serviceable hearing
group (both p < .05 (Table 3). The dose of irradiation at the
cochlea was higher in the group with hearing deterioration
in all patients and in patients with serviceable hearing (both
p < .05). Although the number of shots given was significantly higher in the hearing deterioration group only in
nonserviceable hearing patients (p < .05), weak significance
was shown for a higher number of shots in all 56 patients in
the hearing deterioration group (p < .1). A higher proportion of extracanalicular tumors and a lower long–short-axis
ratio were seen in patients with serviceable hearing in the
hearing deterioration group (all p < .05).
Univariate analyses showed that center-to-center distance
(>20 mm), cochlear irradiation dose (>5 Gy), number of
6
M. J. PARK ET AL.
Table 3. Comparison of clinical characteristics according to hearing deteriorationa following GKRS.
All patients (n ¼ 56)
Downloaded by [University of Florida] at 22:56 27 October 2017
Preserved
(n ¼ 28)
Deteriorated
(n ¼ 28)
Age, y
51.0 ± 10.3
49.5 ± 13.7
Sex (M/F), n (%)
10/18 (36/64)
14/14 (50/50)
58.3 ± 32.1
43.6 ± 25.5
Initial PTA4 (DB HL)
Initial WDS (%)
55.6 ± 40.7
55.2 ± 43.8
Distance parameters
14.2 ± 3.8
10.9 ± 4.4
Center-to-center (mm)b
3.3 ± 2.8
3.3 ± 2.5
Minimal distance (mm)c
Radiation parameters
Prescribed dose (Gy)
12.2 ± 0.4
12.1 ± 0.7
Maximal dose (Gy)
23.8 ± 1.6
24.3 ± 1.3
Minimal dose (Gy)
9.9 ± 1.7
9.8 ± 1.4
Mean dose (Gy)
17.1 ± 0.9
16.9 ± 1.2
Cochlear dose (Gy)
3.7 ± 1.3
5.4 ± 1.8
Number of shots
6.9 ± 5.3
9.9 ± 6.4
Tumor characteristics
1.71 ± 2.28
2.43 ± 2.42
Tumor volume (cm3)
Intra/extracanalicular, n (%) 11/17 (39/61)
4/24 (14/86)
LAD (mm)
15.8 ± 7.3
18.7 ± 6.2
1.6 ± 0.4
1.6 ± 0.7
Long–short-axis ratiob
Tumor response to GKRSf
Regression/stable/
8/17/3 (29/61/10) 17/8/3 (61/29/10)
progression, n (%)
Serviceable hearing (n ¼ 28)
Nonserviceable hearing (n ¼ 28)
p valueb
Preserved
(n ¼ 13)
Deteriorated
(n ¼ 15)
p valueb
.645
.280
.064
.976
45.3 ± 9.7
5/8 (38/62)
33.5 ± 16.9
88.7 ± 13.2
53.1 ± 7.8
7/8 (47/53)
27.2 ± 15.3
92.5 ± 16.5
.047
.963
15.5 ± 4.6
4.0 ± 3.7
.922
.149
.978
.636
.015
.076
.257
.068
.123
.843
.050
Preserved
(n ¼ 15)
Deteriorated
(n ¼ 13)
p valueb
.025
.662
.307
.514
55.3 ± 9.0
5/10 (33/67)
80.5 ± 24.9
24.0 ± 30.4
45.3 ± 17.6
7/6 (54/46)
62.2 ± 21.8
12.8 ± 18.4
.064
.274
.051
.262
9.8 ± 4.1
3.9 ± 2.9
.032
.887
11.6 ± 5.7
2.4 ± 1.3
11.1 ± 4.7
3.0 ± 2.1
.810
.367
12.1 ± 0.4
23.8 ± 1.6
9.7 ± 2.3
17.1 ± 0.9
3.2 ± 0.8
6.8 ± 5.3
11.9 ± 0.7
23.9 ± 1.4
9.6 ± 1.1
16.5 ± 1.0
4.5 ± 1.1
8.4 ± 4.6
.362
.764
.910
.137
.037
.424
12.2 ± 0.4
23.8 ± 1.7
10.0 ± 1.1
17.0 ± 1.0
4.6 ± 1.5
7.3 ± 3.6
12.4 ± 0.5
24.8 ± 1.0
10.1 ± 1.6
17.3 ± 1.2
6.2 ± 1.9
11.1 ± 4.2
.298
.075
.883
.453
.197
.017
1.41 ± 1.93
7/6 (54/46)
14.5 ± 7.9
1.7 ± 0.5
2.47 ± 2.59
2/13 (13/87)
18.0 ± 6.5
1.4 ± 0.3
.244
.042
.204
.046
2.05 ± 2.59
4/11 (27/73)
16.8 ± 7.2
1.5 ± 0.3
2.21 ± 2.26
2/11 (15/85)
19.2 ± 5.9
1.9 ± 1.0
.862
.655
.346
.112
3/9/1 (23/29/8) 9/5/1 (60/33/7)
.093
5/8/2 (33/53/13) 7/4/2 (54/31/15)
.473
F: female; GKRS: gamma knife radiosurgery; LAD: long-axis diameter; M: male; PTA4: average pure tone threshold at 500, 1000, 2000, and 4000 Hz; WDS: word
discrimination score.
Values indicate the mean ± standard deviation.
a
Definition of deteriorated hearing: patient with DPTA4 greater than or equal to 15 dB HL (final PTA4 following GKRS – PTA4 prior to GKRS); preserved hearing:
patient with DPTA4 less than 15 dB HL.
b
For the comparison of the mean values between the preserved hearing group and the deteriorated hearing group, a Student's t-test was used. To compare the
differences in the proportion, a chi-square test or a Fisher's exact test was used. Bold text indicates p < .05.
c
Distance between the tumor center and the cochlea modiolus (mm).
d
Minimal distance between the tumor and the cochlea modiolus (mm).
e
Long-axis diameter divided by short-axis diameter.
f
Tumor response following GKRS was categorized by applying the generally accepted criteria [19].
Discussion
Figure 6. Changes in pure tone thresholds at each frequency (n ¼ 56). In all 56
patients, ~PTA (final PTA – pre-GKRS PTA) at each of the seven frequencies
(250, 500, 1000, 2000, 3000, 4000, 8000 Hz) were calculated and are shown in
Figure 4. ~PTAs at all seven frequencies were compared using a one-way independent ANOVA test, which showed no significant differences between the frequencies (p ¼ .703).
shots given (>10), tumor location (extracanalicular tumors),
and tumor volume (>0.6 cm3) were significantly associated
with hearing deterioration (DPTA4 15 dB HL) (Table 4).
Subsequent multivariate analyses showed that a center-tocenter distance less than 20 mm, more than 10 shots, and
extracanalicular tumors were independent predictive factors
for hearing deterioration in all 56 patients and in patients
with serviceable hearing (all p < .05) (Table 5).
The present study shows the degree of hearing changes and
the factors related to hearing deterioration following GKRS
in 56 patients diagnosed with VS. During the mean observation period of 2 years, we found a significant decrease in
hearing at all frequencies and in word discrimination. In
addition, tumor location, tumor volume, number of shots,
amount of irradiation received at the level of the cochlea,
and distance between the tumor and cochlea modiolus were
related to hearing deterioration. An extracanalicular VS,
more than 10 shots, and a distance between the tumor center and cochlea modiolus less than 20 mm were independent
risk factors for hearing deterioration in all 56 patients, with
a higher OR evident in patients who presented with serviceable hearing. Therefore, this study reveals the changes in the
final hearing outcomes of VS patients treated with GKRS
and allows final hearing to be predicted from initial clinical
variables.
The exact mechanism and factors contributing to hearing
decline in patients with untreated VS are not yet fully
understood. In patients with NF-II, the tumor itself was
shown to secrete neurotoxins, and a higher concentration of
secreted toxin was related to more aggressive hearing
decline, regardless of tumor size, and volume [11]. However,
in patients with unilateral and sporadic VS, it is unclear
whether these toxins are related to advanced hearing decline.
Our study shows that none of these clinical factors were
associated with a poorer degree of hearing in patients with
ACTA OTO-LARYNGOLOGICA
7
Table 4. Univariate analysis of factors associated with hearing deteriorationa in VS patients following GKRS.
All patients (n ¼ 56)
OR (95% CI)
Downloaded by [University of Florida] at 22:56 27 October 2017
Age >60 y
Distance parameters
Center-to-center distance <20 mm
Minimal distance <2 mm
Radiation parameters
Maximal dose >24 Gy
Minimal dose >10 Gy
Mean dose >17 Gy
Cochlear dose >5 Gy
Number of shots >10 shots
Tumor characteristics
Extra-/intra-canalicular
Volume >0.6 cm3
Long–short-axis ratio <1.5
Tumor response to GKRSc
Regression
Stable
Progression
Serviceable hearing (n ¼ 28)
p value
b
OR (95% CI)
Nonserviceable hearing (n ¼ 28)
p value
b
OR (95% CI)
p valueb
1.62 (0.59–8.54)
.399
6.00 (0.60–60.16)
.128
0.98 (0.22–4.34)
.978
9.00 (1.03–78.94)
1.56 (0.24–10.14)
.047
.641
7.58 (1.20–48.00)
1.95 (0.27–13.98)
.031
.506
3.00 (0.27–33.09)
1.19 (0.55–10.87)
.370
.608
1.67
2.46
1.71
6.64
8.00
(0.53–5.28)
(0.67–9.03)
(0.46–6.39)
(1.48–14.54)
(2.19-29.25)
.385
.174
.428
.009
.002
1.13
1.46
2.22
6.29
8.25
.885
.665
.379
.047
.024
3.43
1.91
2.33
6.40
7.58
(0.65–18.22)
(0.33–11.01)
(0.40–13.61)
(1.18–34.61)
(1.20–48.00)
.148
.472
.346
.031
.031
11.50 (3.24–40.86)
5.31 (1.57–17.97)
2.06 (0.71–5.98)
<.001
.024
.184
21.68 (3.02–155.36)
6.50 (1.60–50.69)
3.20 (0.68–15.07)
<.001
.013
.141
2.00 (0.30–13.27)
1.67 (0.31–9.01)
1.68 (0.32–8.76)
.473
.553
.538
1 (reference)
0.27 (0.08–0.85)
0.50 (0.08–3.06)
.084
.069
.453
1 (reference)
0.19 (0.03–1.02)
0.33 (0.02–7.14)
.152
.052
.482
1 (reference)
0.36 (0.07–1.88)
0.71 (0.07–6.92)
.473
.224
.772
(0.23–5.54)
(0.26–8.05)
(0.38–13.18)
(1.02–38.65)
(1.33–51.26)
CI: confidence interval; GKRS: gamma knife radiosurgery; OR: odds ratio.
a
Deterioration of hearing defined as DPTA4 greater than or equal to 15 dB HL (final PTA4 following GKRS – PTA4 prior to GKRS).
b
Univariate binary logistic regression analysis was used to calculate the OR. Bold text indicates p < .05.
c
Tumor response following GKRS was categorized by applying the generally accepted criteria [19].
Table 5. Multivariate analysis of factors associated with hearing deteriorationa in VS patients following GKRS.
All patients (n ¼ 56)
Distance parameter
Center-to-center distance <20 mm
Radiation parameters
Cochlear dose >5 Gy
Number of shots >10
Tumor characteristics
Extra-/intra-canalicular
Volume >0.6 cm3
Serviceable hearing (n ¼ 28)
Nonserviceable hearing (n ¼ 28)
OR (95% CI)
p value
OR (95% CI)
p value
OR (95% CI)
p valueb
12.23 (2.31–254.59)
.015
17.20 (1.44–167.07)
.019
7.42 (0.38–146.58)
.188
3.55 (0.69–18.26)
18.75 (1.58–223.08)
.129
.032
1.06 (0.06–4.50)
37.02 (1.36–305.61)
.197
.020
12.03 (0.78–186.11)
14.68 (0.53–406.00)
.075
.113
8.54 (1.29–56.34)
2.30 (0.34–15.49)
.026
.391
28.25 (1.78–783.97)
17.66 (0.71–43.93)
.026
.080
3.97 (0.10–156.64)
3.35 (0.09–120.56)
.462
.509
b
b
CI: confidence interval; GKRS: gamma knife radiosurgery; OR: odds ratio.
a
Deterioration of hearing defined as DPTA4 greater than or equal to 15 dB HL (final PTA4 following GKRS – PTA4 prior to GKRS).
b
Multivariate binary logistic regression analysis was used to calculate the OR. Bold text indicates p < .05.
unilateral VS (Supplementary Table S2), indicating the need
for future studies in VS patients who are managed with surveillance alone.
During recent decades, the success rate for the management of VS with GKRS has been increasing and there has
been a decrease in the dysfunction rate of the cranial nerves
V, VII, and VII and in postoperative complications, such as
hydrocephalus. Our study found a controlled tumor (regression or stable tumor) in 50 patients (89.3%) who underwent
GKRS (Table 1), similar to the outcomes of recently published articles [12]. The ratio of patients with serviceable
hearing to patients with nonserviceable hearing significantly
changed from 1:1 to 1:3.3. However, although there was an
increase in the percentage, no significant changes were
observed in the proportion of patients with tinnitus, facial
palsy, vertigo, and facial numbness. When compared with
other articles, our rate of vertigo and tinnitus development
was higher [13]. Our results have also counted the number
of patients with ‘transient’ dysfunction of the lower cranial
nerve, in addition to patients with ‘permanent’ dysfunction,
which explains the higher rate of lower cranial nerve dysfunction following GKRS in our study compared with previous reports. Once the deterioration in hearing began after
GKRS, none of the patients showed hearing, facial palsy,
and facial numbness recovery. In contrast, three patients
(5.3%) with tinnitus and 11 patients (19.6%) with vertigo
achieved a full recovery upon conservative management during the follow-up period (data not shown). The immediate
post-GKRS complication rate in our study was less than 5%.
Altogether, our 10-year results show similar rates of tumor
control and complications to previous studies.
Many previous attempts have been made to ascertain
what truly determines the overall hearing following GKRS.
Kano et al. [12] and Han et al. [14] reported that older
patients (>60 years) with poorer initial hearing were more
likely to have hearing deterioration following GKRS. Hayden
et al. [15] argued that a poorer hearing outcome was associated with a larger tumor volume, but this finding was not in
accordance with those of other studies. The irradiation dosage delivered to the tumor was also found to be an adverse
factor when it comes to hearing preservation in the treatment of VS. Foote et al. [16] believed that a mean dose
greater than 12 Gy administered to the tumor margin was
associated with a poorer hearing outcome. Yoma et al. [17]
measured the amount of irradiation at the cochlea in a similar fashion to our study, showing that a cochlear dosage
8
M. J. PARK ET AL.
Table 6. Comparison of clinical parameters between intracanalicular and
extracanalicular VS (n ¼ 56).
3
Tumor volume (cm )
Long–short-axis ratio
Number of shots
Cochlear dose (Gy)
Downloaded by [University of Florida] at 22:56 27 October 2017
a
Intracanalicular
Extracanalicular
p valuea
0.20 ± 0.02
2.0 ± 0.2
3.5 ± 0.5
3.4 ± 1.3
2.76 ± 0.38
1.5 ± 0.1
10.1 ± 1.0
5.1 ± 1.7
<.001
.002
<.001
.034
p value calculated by using Student's t-test. Bold text indicates p < .05.
larger than 4.2 Gy was significantly associated with hearing
deterioration after GKRS. Massager et al. [18] claimed that
patients with VS with a small intracanalicular volume were
more likely to have their cochlea exposed to radiation during GKRS and suggested that the cochlear dose should be
reduced to less than 4.2 Gy, if possible. In 2013, Linsky et al.
published an article on the received radiation dose and the
tolerance of suborgans in the human temporal bone in
patients with VS treated with GKRS [19]. The basal turn
near the modiolus and the inferior part of the cochlea were
the most susceptible, with a received dose greater than
12 Gy in 10–15% of cases. Although our results did not
show increased risk in the older age group and with a
higher dose of irradiation at the tumor, in addition to the
differences in the degree of initial hearing with hearing
deterioration, we did find that a cochlear dose exceeding
5 Gy, tumor volume over 600 cm3, extracanalicular volume,
and a center-to-center distance more than 20 mm were significantly associated with hearing deterioration.
Combining these previous findings with our results, we
strongly suggest that the irradiation dose to the cochlea, particularly the modiolus, is the most important determining
factor for hearing preservation in VS patients undergoing
GKRS. In addition, we identified significant differences
in clinical parameters in intra-versus extracanalicular VS
(Table 6). Intracanalicular VSs showed a smaller tumor volume and higher long–short-axis ratio (indicative of a more
cylinder-like shape), reflecting the tumors’ predominant
location in the IAC. In addition, significant differences were
seen in the number of shots given and the irradiation dose
to the cochlea between intra- and extracanalicular VS.
To account for these findings, an explanatory model is
presented in Figure 2. The dose of irradiation received at
each point follows an almost normal distribution pattern,
with the maximal dose at the center of the tumor and 50%
of the maximum dose (mean dose) at the border of the
tumor, as designed during GKRS planning with the obtained
MR image. This explains why a longer center-to-center distance is associated with poorer hearing preservation, because
the cochlea will receive a higher dose of irradiation when
the cochlea is closer to the tumor. Using patients A and B
in Figure 2 as examples, the 50% iso-radiation dosage at the
tumor margin (yellow) and the maximal dose received at the
center of the tumor were almost identical in the two
patients. In addition, the dose received at the point of the
cochlea modiolus was almost similar in the two cases, even
though patient B shows a longer distance between the cochlea and the tumor. The slope of each tangent was calculated
at the point of the 50% maximal dose given, with a higher
slope of 16.23 in patient A (intracanalicular, cylinder-shaped,
and lower tumor volume) and a slope of 5.06 in patient B
(extracanalicular, round-shaped, and larger tumor volume).
It can be acknowledged that the lower the slope of a tangent, the lower the likelihood that the targeting tissue be
accurately discriminated and the organs preserved. Thus, we
conclude that the tumor location and the distance between
the cochlea and the tumor are the two most important factors determining VS patients’ hearing outcome following
GKRS.
Regarding hearing preservation and rehabilitation, the
tumor should be managed more prudently in patients
with initial serviceable hearing (class A and B). Clinicians
should be careful when planning interventions, and a more
precise effort should be made when GKRS is designed
in these patients. In addition, many audiologists have
reported successful hearing rehabilitation in patients with
moderate-degree sensorineural hearing loss (average pure
tone thresholds >50 dB HL and WDS >50%) with various
hearing aids [20]. Because patients classified as class C
(PTA4 > 50 dB HL and WDS >50%) could be candidates for
hearing rehabilitation with hearing aids, an effort should
also be made in class C hearing patients.
Interestingly, we have also discovered that stable tumors
showed the lowest likelihood of hearing loss, followed by
progressive tumors, despite GKRS, although the significance
was weak in patients with serviceable hearing. We believe
that these findings could be due to excess irradiation that
enabled the complete eradication of the tumor in patients
with tumor regression and the effect of tumor re-growth in
patients with progressive tumors. However, due to the low
power of the study, this hypothesis needs to be proven in
future studies.
Our study has some limitations due to its retrospective
nature: (1) the time to hearing deterioration following GKRS
was not reviewed, (2) there were no protocols for a uniform
hearing assessment in all patients, (3) although most of the
patients underwent the baseline hearing assessment prior to
GKRS, only a small percentage of the patients had their
hearing assessed following GKRS, (4) there was a marked
difference in the follow-up period among the patients, with
a standard deviation of 27.8 months, and (5) despite effort
to include GKRS recipients from the last 10 years to minimize the time period bias, we acknowledge that two different
gamma knife irradiation and planning devices were applied.
So as to not regard any early hearing deterioration as the
‘final hearing’, we have excluded patients with less than a 6month follow-up. Although the data were not presented, we
observed no significant additional changes in patients’ hearing after the 6-month follow-up period.
Disclosure statement
The authors have no conflicts of interest to disclose.
References
[1]
Yamakami I, Uchino Y, Kobayashi E, et al. Conservative management, gamma-knife radiosurgery, and microsurgery for
ACTA OTO-LARYNGOLOGICA
[2]
[3]
[4]
[5]
[6]
Downloaded by [University of Florida] at 22:56 27 October 2017
[7]
[8]
[9]
[10]
acoustic neurinomas: a systematic review of outcome and risk
of three therapeutic options. Neurol Res. 2003;25:682–690.
Jethanamest D, Rivera AM, Ji H, et al. Conservative management of vestibular schwannoma: predictors of growth and hearing. Laryngoscope. 2015;125:2163–2168.
Leksell L. A note on the treatment of acoustic tumours. Acta
Chir Scand. 1971;137:763–765.
Elliott A, Hebb AL, Walling S, et al. Hearing preservation in
vestibular schwannoma management. Am J Otolaryngol.
2015;36:526–534.
Golfinos JG, Hill TC, Rokosh R, et al. A matched cohort comparison of clinical outcomes following microsurgical resection
or stereotactic radiosurgery for patients with small- and
medium-sized vestibular schwannomas. J Neurosurg. 2016;125:
1472–1482.
Mousavi SH, Kano H, Faraji AH, et al. Hearing preservation up
to 3 years after gamma knife radiosurgery for Gardner–
Robertson class I patients with vestibular Schwannomas.
Neurosurgery. 2015;76:584–590. discussion 90-1.
Noren G. Long-term complications following gamma knife
radiosurgery of vestibular schwannomas. Stereotact Funct
Neurosurg. 1998;70(Suppl1):65–73.
Lee J. Standardization of Korean speech audiometry. Audiol
Speech Res. 2016;12:S7–S9.
Committee on hearing and equilibrium guidelines for the evaluation of hearing preservation in acoustic neuroma (vestibular
schwannoma): committee on hearing and equilibrium.
Otolaryngol Head Neck Surg. 1995;113:179–180.
Kanzaki J, Tos M, Sanna M, et al. New and modified reporting
systems from the consensus meeting on systems for reporting
results in vestibular schwannoma. Otol Neurotol. 2003;24:
642–648. discussion 8-9.
[11]
[12]
[13]
[14]
[15]
[16]
[17]
[18]
[19]
[20]
9
Asthagiri AR, Vasquez RA, Butman JA, et al. Mechanisms of hearing loss in neurofibromatosis type 2. PLoS One. 2012;7:e46132.
Kano H, Kondziolka D, Khan A, et al. Predictors of hearing
preservation after stereotactic radiosurgery for acoustic neuroma: clinical article. J Neurosurg. 2013;119(Suppl):863–873.
Flickinger JC, Kondziolka D, Niranjan A, et al. Results of
acoustic neuroma radiosurgery: an analysis of 5 years’ experience using current methods. J Neurosurg. 2013;119(Suppl):1–6.
Han JH, Kim DG, Chung HT, et al. Hearing preservation in
patients with unilateral vestibular schwannoma who undergo
stereotactic radiosurgery: reinterpretation of the auditory brainstem response. Cancer. 2012;118:5441–5447.
Hayden Gephart MG, Hansasuta A, Balise RR, et al. Cochlea
radiation dose correlates with hearing loss after stereotactic
radiosurgery of vestibular schwannoma. World Neurosurg.
2013;80:359–363.
Foote KD, Friedman WA, Buatti JM, et al. Analysis of risk factors associated with radiosurgery for vestibular schwannoma.
J Neurosurg. 2001;95:440–449.
Yomo S, Carron R, Thomassin JM, et al. Longitudinal analysis
of hearing before and after radiosurgery for vestibular schwannoma. J Neurosurg. 2012;117:877–885.
Massager N, Nissim O, Delbrouck C, etet al. Irradiation of
cochlear structures during vestibular schwannoma radiosurgery
and associated hearing outcome. J Neurosurg. 2013;119(Suppl):
733–739.
Linskey ME, Johnstone PA, O’Leary M, et al. Radiation exposure of normal temporal bone structures during stereotactically
guided gamma knife surgery for vestibular schwannomas.
J Neurosurg. 2013;119(Suppl):800–806.
Aazh H, Moore BC. Audiological rehabilitation for facilitating
hearing aid use: a review. J Am Acad Audiol. 2017;28:
248–260.
Документ
Категория
Без категории
Просмотров
2
Размер файла
1 394 Кб
Теги
00016489, 1386800, 2017
1/--страниц
Пожаловаться на содержимое документа