Introduction
Approximately 10%-30% of the cancer patients have
brain metastases, which are the most common intracranial
tumors.[] The standard treatment choice in brain tumors is the maximal surgical resection, followed by
adjuvant radiotherapy. Combining radiotherapy with
chemotherapy (concomitant and adjuvant temozolomide)
has revealed a higher survival benefit and lower
additional toxicity in patients with high-grade brain tumors. However, radiotherapy may have side effects on
the brain, including radiation necrosis, cognitive impairment,
and a high chance of tumor recurrence, which has
been considered the most common cause of treatment
failure.[] Moreover, there is evidence about the radiation
therapy for tumors in the head and neck region,
showing a correlation between the dose to the cochlea
and the degree of hearing loss observed.[-] At dose
levels of radiotherapy applied to most of the intracranial
brain tumors, the cochlea is the main organ affected and
the mean dose to the cochlea (Dmean) became an essential
factor mostly studies to determine the incidence and
degree of hearing loss.[,] Thus, different strategies of
dose prescription and modern planning techniques have
been tested to achieve better tumor control and better
sparing of the organs at risk (OARs).[,] The most common
strategies for RT are intensity-modulated radiation
therapy (IMRT) and volumetric-modulated arc therapy
(VMAT). VMAT is a subset of IMRT where radiation is
delivered in an arc instead of at static angles, allowing
the delivery of highly conformal dose distributions. The
idea of these techniques has arisen to selectively spare
the cochlear structures and to reduce the risk of radiation-
induced complications such as hearing loss during
brain radiotherapy.[]
IMRT technique delivers variable intensity radiation
with multiple radiation beams; thus, target volume
conformity and sparing of normal tissues and OARs
have been improved considerably.[] Moreover, IMRT
is able to produce inhomogeneous dose distributions,
resulting in the simultaneous delivery of different doses
per fraction to separate areas within the target volume.
On the other hand, VMAT allows simultaneous variation
of three parameters during the delivery of radiation
therapy, i.e., gantry rotation speed, treatment aperture
shape via movement of multileaf collimator (MLC)
leaves, and dose rate. This causes further improvement
in target volume conformity and OARs sparing.[] In
this study, we aimed to test the potential outcomes of
sparing the cochlea in radiotherapy to brain tumors in
20 patients using VMAT and IMRT techniques and set
various dosimetric objectives to compare dosimetric
parameters between VMAT and IMRT.
Methods
Selection and Description of the Patients
In total, 20 patients diagnosed with pathological grade
IV brain tumor were retrospectively enrolled in this
retrospective comparative clinical study. The mean
age of the patients was 52.1±8.64 years (range, 34?61 years). All patients underwent preoperative MRI or CT.
The present study was conducted in accordance with
the Ethics Committee Approval (Number: 2017/28) for
VMAT/IMRT planning and with the principles of the
WMA Declaration of Helsinki. Patient consent was not
obligatory, as stated by the Ethics Committee of our institute.
Datasets of 20 patients who had received either
IMRT or VMAT for a brain tumor at our institute were
included in this planning study. For all patients, the
dose prescribed to the planning target volume (PTV)
was 46 Gy followed by a boost of 60 Gy in 30 fractions.
Patients were positioned in the supine position
and immobilized with a thermoplastic mask. Normal
structures like the eyes, lenses, optic nerves, chiasm,
cochlea and brain stem were contoured and designated
as OARs (Fig. 1). Expanded contours were created with
safety margins of 3 mm around the brain stem and chiasm
and 5 mm around the optic nerve. The cochlea was
contoured on the T1 MRI sequence, as described by
Gao et al.[]
Fig 1: A radiographic image of the cochlea.
VMAT Planning
The VMAT plans were optimized in the research treatment
planning system (TPS) of Monaco® 5.1 (Elekta
AB Publ, Stockholm, Sweden), which relies on the
XVMC (X-ray voxel Monte Carlo) algorithm for dose
calculation.[] All VMAT plans were generated for
a 6 MV Elekta Synergy linear accelerator (LINAC)
equipped with an Agility MLC. Three fields were used
with a gantry angle beginning from 180°. The first field
was given with both clockwise and counter clockwise
gantry angle of 160° on the basis of tumor location,
and as the eyeballs and lenses of the patients did not take the initial dose. Moreover, the collimator angles
were given in between 50° and 70° on the basis of tumor
location. The second field was given in between
40° and 50° as all the PTVs were caught, the lens and
eyes were excluded from the exit dose, and the collimator
angle was given in between 50° and 70°. The third
field was given as half arc (180°) with a table angle of
55° and 305° on the basis of tumor location to protect
the healthy tissues of the patients.
For Monte Carlo-based VMAT planning for the patients,
two arcs for each field, 180 control points for each
arc, statistic as one, and grid size as 0.3 were chosen.
IMRT Planning
For generating IMRT plans for the patients, ELECTA
TPS of Elekta Monaco 5.1, which relies on the XVMC
algorithm (X-ray voxel Monte Carlo), was used for
dose calculation. All IMRT plans were generated in a
6 MV Elekta Synergy LINAC, equipped with an Agility
MLC. IMRT planning was performed with six fields
using a multileaf collimator delivery method in dynamic
mode. The initial gantry angles of these six fields
were chosen as 260°, 230°, 170°, 140°, 110°, and 70°.
Collimator or table angle was not used for any of these
fields.
Evaluation of Treatment Plans
Monte Carlo algorithm was used for both plans. After
contour radiation was entered by the oncologist,
VMAT and IMRT plans were performed by a medical
physicist. VMAT plans were performed twice to spare
and not to spare (standard) the cochlea contour in optimized
condition. For both VMAT plans, the same
angles and cost functions were used. The maximum
control point for each arc used in the VMAT plan was
chosen as 180.
The IMRT plans were performed twice to spare and
not to spare (standard) the cochlea contour in optimized
condition. For both IMRT plans, the same angles and
cost functions were used. The planning of these IMRT
plans was adjusted at 15 segments of each field.
For both techniques, cochlear sparing was targeted
as PTV covering 100% of the volume at 95% of the
target volume dose. In plans where 95% of PTV was
covered by 100% of target volume dose, the conformity
index enhancer, planned template additional field, or
cost functions were not used.
Statistical Analysis
All dosimetric values were reported in descriptive
statistics as mean±SD and median (minimum?maximum) values. Dosimetric parameters were tested for
normal distribution using the Kolmogorov-Smirnov
test. Because two different plans were generated in the
CT image set of every patient, the data were considered
matched pair and paired tests were used to compare
the two plans. For two non-normally distributed dependent
variables, a corresponding non-parametric
test Wilcoxon test was used, and for more than two
non-normally distributed dependent variables, the
Friedman test was used. All statistical analyses were
performed with a 5% level of significance, and p<0.05
was considered statistically significant. The analysis
was performed using the MedCalc Statistical Software
version 12.7.7 program (MedCalc Software bvba, Ostend,
Belgium; http://www.medcalc.org; 2013).
Results
The VMAT and IMRT plans met the planning objectives
for 20 patients (10 male and 10 female), as mentioned
in the protocol. The characteristics and total
dosimetric results of the patients are given in Table
1. The mean age of the patients who underwent total
(n=18) or subtotal (n=2) brain surgery was 52.1±8.64
years, and the tumors were located in the temporal
(n=6), parietal (n=8), frontal (n=4) and parieto-occipital
(n=2) regions of the brain. The median clinical
target (CT) volume was 161.34 cm3 (min-max: 41.95-
320).
Table 1: Demographics of the patients (n=20)
The dosimetric data obtained from generated dosevolume
histograms are presented in Table 2. When
the dosimetric parameters of PTV were compared at
the coverage of the treatment target dose at 46 Gy, the whole target receiving at least 95% of the prescription
dose (D95%) was statistically higher in VMAT plans
compared to the IMRT plans (p=0.010). The minimum
dose at PTV 46 Gy was also significantly higher in the
VMAT plan than the IMRT plan (p=0.001), while there
was no statistical difference in mean and maximum
dose at PTV 46 Gy among two treatment modalities.
However, the dose to receive at least 95% of 60 Gy and
the mean, maximum and minimum doses at PTV 60
Gy were comparable between VMAT and IMRT plans
(Table 2). The doses to receive 98%, 95%, 5% and 2%
of PTV were also comparable between the two methods.
The conformity and homogeneity indexes of two
methods were the same; however, a significantly higher
monitor unit (MU) was noted in the VMAT plan when
compared with the IMRT plan (p=0.034).
Table 2: Dosimetric comparison of the VMAT (n=10) and
IMRT (n=10) plans for different planning target
volumes
All VMAT and IMRT plans were able to meet the
constraints placed on OARs and PTV. When dosimetric
variables for OARs were compared, no significant
difference was found for the dose to cover 95% of both
contralateral and total cochlea among VMAT and
IMRT plans, even the mean and maximum doses to
cochlear structures did not differ among two methods.
Considering PTV 46 Gy (Table 3), the doses to the
left eye and left optic nerve were found to be higher in
the IMRT plan (p=0.041 and 0.023, respectively), while
the doses to the optic chiasm and brain stem were
higher in the VMAT plan (p=0.001 and 0.002, respectively).
The same difference was also seen in the doses
to the left eye and left optic nerve at PTV 60 Gy that
is to note considerably higher doses in the IMRT plan
compared to the VMAT plan (p=0.019 for both). However,
the doses to the optic chiasm and brain stem were
nearly similar between two modalities. Other doses to
the right eye, both lenses and right optic nerve, were
statistically comparable for both plans.
Table 3: Dosimetric comparison of the VMAT (n=10) and IMRT (n=10) plans for organs at risk
Discussion
Brain tumors are one of the aggressive tumors carrying
poor prognosis in cancer patients. An estimated 15% to
30% of these cancer patients will develop brain metastases
during the course of their illness.[] A multimodality
treatment approach, including surgical intervention,
radiotherapy and/or stereotactic radiosurgery
(SRS) for intracranial tumors, may result in improvement
in local control and neurologic symptoms of the
disease and expectantly in quality of life and survival
of patients.[] With advanced radiation technology,
such as VMAT and IMRT techniques, it is possible to
carry out radiotherapy with cochlear sparing and reduce
cochlear impairing or hearing loss.[,,,] Because
of several factors, including relatively low total
prescription dose and poor prognosis associated with
radiotherapy in patients with multiple brain tumors,
potential radiation-induced toxicity to the OARs has
been overlooked and underestimated.[] Thus, in this
retrospective study, we compared two modalities of
radiotherapy, VMAT and IMRT, in the patients with
brain tumor concerning the sparing effect on cochlea,
by comparing dosimetric parameters. VMAT is a technique
of rotational radiotherapy that delivers a highly
conformal radiation dose to the target by simultaneously
modulating gantry rotation, dose rate, and
multileaf collimator pattern in linear accelerator.[]
Although VMAT system was claimed to be an advantageous
conformal technique over the IMRT system in
reducing the total number of MU and subsequently the
beam on time, which may improve patient tolerance
of treatment and potentially reduce leakage radiation
dose to the patients,[] in the present study, a significantly
higher MU was detected in VMAT plan when
compared with IMRT plan. However, VMAT plans
may be superior concerning decreasing the dose to
the OARs, including the optic and auditory structures.
[] In our study, sparing the cochlea was comparable
among VMAT and IMRT plans about decreasing the
applied dose, but VMAT was considerably surpassing
to spare the eye and optic nerve but not the optic chiasm
and brain stem compared with IMRT technique.
In clinical practice, radiotherapy has been observed
to result in ear pain and fluid collection in the middle
ear, which may cause otitis media and hearing loss.
Radiation-induced hearing loss is a serious complication
of radiotherapy in patients with brain tumors,
which significantly affects the overall quality of life.
[,] The frequency of radiation-induced damage
to ear function was reported as high as 37% in patients
treated with IMRT.[] By reducing the dose to
the hearing apparatus, the incidence of hearing loss
is likely to decline, and probably this is valid for both
VMAT and IMRT planning since sparing the cochlea
did not change the resultant doses to cover 95% of
both total and contralateral cochlea. No difference was
found in the mean, maximum and minimum doses to
these structures for both techniques. In the future, a
follow-up study is suggested to prove this consideration
by calculating the ratio of hearing loss in a large
population of patients with brain tumors
There are few publications focused on the protection
of the hearing apparatus to compare between
VMAT and IMRT. In a study by Vanetti et al., the radiation doses in VMAT and IMRT were compared for
head and neck cancer, and VMAT plans outperformed
IMRT plans concerning homogeneity and conformity
in PTV, as well as providing a better sparing effect on
the OARs.[] In another study, Gao et al. compared the
impacts of using SmartArc-based VMAT (VMAT-S)
and step-and-shoot IMRT on hearing apparatus doses,
as well as other involved OARs such as brain stem and
spinal cord in the patient with nasopharyngeal carcinoma.
They found that VMAT-S was significantly superior
about PTV coverage and the protection of ear
function compared with IMRT. The doses of middle
ears, cochleas and vestibules were significantly lower in
the VMATS plan.[] However, in our study, the conformity
and homogeneity indexes of VMAT and IMRT
were the same, and the sparing effect for cochlea was
also similar between two techniques. Moreover, IMRT
was significantly superior over VMAT concerningPTV
coverage at 46 Gy. However, the doses of optical organs
such as eye and optic nerve were significantly lower in
the VMAT plan compared with the IMRT plan. These
variances in results are inevitable since the sites tumors
of the study population and the relevant exposed sites
to the radiotherapies are varied among studies. To the
best of our knowledge, this is the first report to compare
VMAT and IMRT techniques in patients with
brain tumors in terms of cochlear sparing.
Reducing the dose of radiotherapy and minimizing
both acute and late toxicity of treatment in normal
tissues is highly crucial for the patients and clinicians.
[20] IMRT has become a modality of choice, allowing
similar or better target coverage by providing more
freedom in the beam arrangement and by achieving
good conformity and sparing and avoiding normal
tissues as compared to other conformal radiotherapies.[] On the other hand, VMAT delivers a modulated
beam in one or more arcs, mostly providing
similar target coverage and normal tissue sparing as
IMRT while substantially decreasing the treatment
time. Despite, including limited numbers of patients,
dosimetric analysis and radiotherapy planning studies
have revealed the noninferiority of VMAT over
IMRT in cancer patients.[-] To demonstrate the
differences in planning quality between VMAT and
IMRT methods for glioblastoma, Briere et al. analyzed
the dose distributions of 90 clinical treatment plans,
45 patients treated with VMAT and 45 with IMRT.
VMAT was found to be superior in sparing of the
brainstem, the ipsilateral and contralateral cochlear
and contralateral lens. They concluded that VMAT
for glioblastoma patients could provide similar target coverage, superior sparing of the brainstem and
cochleae, and be delivered in a shorter period of time
compared with IMRT.[] As a limitation in our study,
the treatment time was not analyzed, but we could not
show any distinction among the patients with a brain
tumor treated by VMAT or IMRT in terms of sparing
the cochlea. However, our results of comparing the
dosimetric variables between the two techniques are
valuable to offer no inferiority of VMAT in comparison
to IMRT. Hence, VMAT may suggest a clinical
efficiency and the quality of the treatment experience
by shortening the time of therapies in patients with
intracranial tumors. Thus, the choice of two modalities
for the treatment of cancers appears to base on
the institutional or clinical experience, and suggested
varied advantages and efficiencies among the types of
cancers. The clinical outcomes of different planning
in radiotherapies need further investigation.
Conclusion
Since VMAT and IMRT planning have the same effect
on sparing the cochlea; no superiority can be suggested
among these two plans during radiotherapy.
The choice of plan for the treatment of brain tumors
appears to base on the clinical experience, especially
for patients who may experience hearing loss.
Peer-review: Externally peer-reviewed.
Conflict of Interest: None of the authors have any conflicts
of interest or financial ties to disclose.
Ethics Committee Approval: The present study was
approved by the Ethics Committee Approval (Number:
2017/28) for VMAT/IMRT planning and conducted in accordance
with the principles of the WMA Declaration of
Helsinki. Patient consent was not obligatory, as stated by the
Ethics Committee of our institute.
Financial Support: None declared.
Authorship contributions: Concept - G.P.S.G., E.E.Ö.;
Design - G.P.S.G., E.E.Ö.; Supervision - G.P.S.G., E.E.Ö.;
Funding - E.E.Ö.; Materials - E.E.; Data collection and/or
processing - G.P.S.G., E.E.Ö.; Data analysis and/or interpretation
- G.P.S.G., E.E.Ö.; Literature search - G.P.S.G., E.E.Ö.;
Writing - G.P.S.G., E.E.Ö.; Critical review - G.P.S.G., E.E.Ö.
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