Introduction
Nasopharyngeal cancer is a unique carcinoma among
head-and-neck cancers due to its epidemiology, histologic
features, and sensitivity to radiotherapy (RT) and chemotherapy. In the treatment of nasopharyngeal cancer,
high-dose RT is the main treatment for the primary
tumor and neck region due to the anatomical location
of the nasopharynx, bilateral retropharyngeal lymph
node involvement in the early period, and difficulty in accessing this area surgically.[] However, when high
doses of RT are given, risky organs such as the spinal
cord, optic nerve, optic chiasm, pituitary, brain, brain
stem, and important structures near the target, such as
the temporomandibular joint, salivary glands, thyroid
gland, larynx, and oropharyngeal mucosa are problematic
in terms of late morbidity.[-] For RT of nasopharyngeal
cancer, the field size is generally large, and high
doses are applied; therefore, significant sequelae and
side effects are expected to occur due to critical structures
in the local environment. Conventional RT techniques
applied in the past involved treatment from two
mutually parallel fields. With the development of technology,
innovations, and treatment advances in recent
years, there has been a transition from conventional
therapy to conformal therapy, intensity-modulated RT
(IMRT), and volumetric arc therapy (VMAT).[-]
Conformal delivery of a target volume prescribed
dose that minimizes the dose to normal tissues is possible
with the introduction of IMRT in the discipline of
RT, thereby reducing radiation-induced post-therapy
complications. Even faster and more effective delivery
of higher or equivalent dose distributions is possible
with VMAT.[,]
With these developments in treatment planning
techniques, inhomogeneity in the irradiated area is an
important problem. For nasopharyngeal cancer treatments
behind the nasal cavity, where the air passage expands,
the beam often passes through an air layer before
reaching the surface of the tumor. In such cases, electronic
balance is not fully formed at the air-tumor intersection
resulting in dose reductions in the air-tissue
intersection. Many studies show that the magnitude of
the dose decrease in the air-tissue interface depends on
the geometry of the air gap, the volume of the space, the
size of the irradiated area, and the photon energy used.
[-] In addition, external contour changes, which
are automatically transferred to the treatment planning
system after computed tomography (CT) imaging and
have an important place in beam entrances, can also
create similar problems. When treating patients with
nasopharyngeal cancer using VMAT, the gantry irradiates
with 360° rotation from all angles, and the speed,
field shape, and dose rate constantly change during the
rotation.[] For this reason, changes that may occur,
especially in the contour of the auricle, may cause alterations
in the treatment volume dose distribution
and critical structure doses due to changes in beam entrance
distance, angle of entry, and scattering.
The American Association of Physicists in Medicine,
Task Group 176 (TG-176), recommended that the immobilization devices be contoured considering
dosimetric effects.[] However, dosimetric effects
due to the change in the volume of the body structure
still need to be clarified as there are no guidelines for
defining body contour. Treatment planning priorities
are given in radiation therapy oncology group (RTOG)
guidelines as critical normal structure limitations and
target volume dose specifications for planning targets
(salivary glands) and other normal structures.[] In
terms of planning objectives, the auricular region was
chosen due to its proximity to the salivary glands and
because it could create an external contour change effect
due to the use of masks. We aimed to compare
VMAT treatment plans made with and without correction
of body contours (the auricle) manually in all
sections. In the final comparison, the target volume for
both planning dose-volume histograms and dose criteria
for critical organs were evaluated.
Methods
Patient Characteristics
This study included 19 patients treated for nasopharynx
cancer at our institution. Four patients had stage
2 disease (21%), seven had Stage 3 disease (37%), and
eight had Stage 4 disease (42%). We selected patients
treated with IMRT using the VMAT technique and
performed a retrospective analysis with the appropriate
Local Ethics Committee approval A-46 on January
07, 2021.
Imaging and Contouring
A thermoplastic head and shoulder mask were used
to immobilize patients in the supine position. The
planning CT was achieved with a 2.5 mm slice thickness
from the head to the carina on a Discovery RT
scanner (GE Healthcare, WI, and USA). The RT
planning CT for detected primary tumors and metastatic
lymph nodes was fused with positron emission
tomography-CT and magnetic resonance images.
Organs at risk (OAR) and target volumes were contoured
according to RTOG guidelines. Gross tumor
volume (GTV) of the primary tumor and metastatic
lymph nodes were defined according to clinical and
radiological findings. The following three clinical
target volumes (CTV) were delineated: CTV 66-70
Gy covered the primary tumor and metastatic lymph
node and was defined by adding 5 mm to the GTV,
CTV 60 Gy included both the whole nasopharynx
and the whole involved nodal level, and CTV 54 Gy
covered high-risk regions and elective bilateral cervical lymph nodes. Planning target volume (PTV)
was defined by adding 3 mm in all directions for all
CTV. For nasopharyngeal carcinoma, OAR included
the optic chiasm, optic nerves, oral cavity, brain stem,
cochlea, temporomandibular junction, parotid gland,
spinal cord, and muscles of the pharynx.
Treatment Planning and Data Analysis
The structures for all patients were identical except for
the external contour. The same physicist automatically
generated two structure sets with two body structures
with a value of -350 Hounsfield Unit (HU) for all patients.
Auricular correction (Ext-a) values were made
manually slice-by-slice, while the other values (Ext-b)
used the automatically created contour. The dose distributions
with Ext-a CT were then calculated using
identical VMAT plans and optimization as those generated
with Ext-b CT and the same optimization process
in the Treatment Planning System using an Eclipse
version 10.0 progressive resolution optimizer (Varian
Medical System, Palo Alto, CA, USA).
Each VMAT plan generated two full arcs with
energy of 6 MV. The simultaneous integrated boost
technique was used with three target volumes. For
the calculation of dose distributions, the anisotropic
analytic algorithm was used. The dose calculation
grid was 2 mm. The median dose of RT was 70 Gy
(range 66-70 Gy) in 33 fractions. All treatments were
delivered using a RapidArc linear accelerator (Varian
Medical System, Palo Alto, CA, USA). The RT volume
verification for image-guided RT was conducted with
cone-beam CT or kV for each fraction. Dosimetric
comparisons for maximum dose (Dmax), dose to
95% of the target volume (D95), and dose to 2% of the
target volume (D2) for each target volume were performed
for all plans. The homogeneity ındex (HI) and
conformity index (CI) were also calculated.
The maximum and mean dose to each parotid
gland and cochlea were evaluated due to their proximity
to the auricle.
In addition, the time from the start to the end of auricular
contouring was recorded for each patient plan
to determine the additional workload when manual
contouring was added to the planning.
Statistical Analysis
The computer software SPSS version 21 for Windows
(IBM Corp. Armonk, NY, USA) was used for all statistical
analyses. The statistical significance of the
differences was analyzed using the paired t-test and
Wilcoxon signed-rank test. Significance was considered
at p<0.05 level.
Results
Some PTV has a close relationship with critical organs
such as the optic tract brainstem; therefore, RT doses
were changed due to this association. The target data
of the plans made in Ext-a and Ext-b are given in Table
1, and the data of critical organs are shown in Table 2.
Due to the use of different dose schemes in patients,
the target volume and critical structure doses are provided
based on % evaluation.
Table 1 Target volume dosimetric comparisons
Table 2 Dosimetric comparisons in organs at risk
Comparison of HI, CI, Dmax, D95%, and D2% showed
statistically significant differences. When plans were
compared, statistical significance was demonstrated
between the groups for HI, CI, Dmax, D95, and D2. Still,
since the values for both plans were acceptable, the
need for auricular contour correction may vary according
to the patient. Figure 1 shows the dose distribution
and auricular contour for 26 Gy.
Fig. 1. Color wash dose distributions on transverse computed tomography (CT) views for (a) Ext-a (left) and (b) Ext-b
(right) for a representative case. Color wash dose range: 26 Gy (blue)-70 Gy (red).
No difference was observed for cochlea when evaluated
in terms of normal tissue doses. However, a statistically
significant increase in parotid mean dose was
observed, especially in patients with level 2 cervical
lymph node metastasis when the auricular contour was
corrected in planning (p<0.001).
The mean additional time required for the fully
manual procedure in Ext-a without the use of any additional
tools was 6.7±1.2 min and 2.3±0.3 when done
with the drawing tools adaptive option on the Eclipse
Treatment Planning System. For Ext-b, no additional
time was spent as the Treatment Planning System automatic
contour option was used.
Discussion
Accurate determination of body contour in calculating
RT dose distribution in treatment planning is important
for precise dose calculation. There are many studies
on changes in the target volume and critical organ
doses caused by variations in external contour due to
reasons such as weight loss during treatment. When
Wang et al.[] compared the second plan after the 18th
fraction in 15 patients with nasopharyngeal cancer and
the initial treatment plan, for the hybrid and new plan,
the mean dose of the left and right parotid increased by
2.97 Gy and 2.57 Gy, respectively. They stated that anatomical
changes during treatment might increase the dose to critical organs, and replanning may benefit the
patient. Loo et al.[] investigated tumor shrinkage and
contour changes that may occur during the treatment of
head and neck cancers. The change in the planned and
administered dose during RT for five patients was evaluated
by recalculating all doses on eight megavoltages CT
(MVCT) images taken daily in different weeks. As a result,
the dose increased from 26.2 Gy by an average of
7.3 Gy (range 1.1-11.6 Gy) in the contralateral parotid.
It was observed that the contralateral parotid dose increased
an average of 19.3% (range 8.2-41.5%) in each
fraction, while the ipsilateral parotid dose increased an
average of 30.2% (17.1-55.8%). The investigators stated
that there were significant changes in parotid volume
and dose during treatment and that adaptive therapy
could be helpful in evaluating this change.
Chen et al.[] evaluated the effect of weight loss on
target volume and OAR in 25 patients with nasopharyngeal
cancer. They found that the dose to the brain stem
and spinal cord increased in all plans by pulling the body
contour change in 2, 3, and 5 mm symmetrically from
all directions, and the dose to the parotid was lower than
in the original plan. They explained that they did not
consider the parotid gland's volumetric and positional
changes for the low dose in the parotid gland.
In our study, in patients with level 2 cervical lymph
node metastases whose auricular contour was corrected,
the dose change in automatic contour planning
was 43.94%, while it was 45.81% in corrected contour planning (p<0.001). Although within the clinical acceptance
criteria in terms of other volumes, we saw a
change in the way; it is given in Table 1.
Lee et al.[] evaluated the dosimetric effect of external
contour on VMAT plans at different HU values in patients
with prostate and head and neck cancers. VMAT
plans with 180 HU were compared with those obtained
with external contours at -350, -700, and -980 HU
values. The choice of -180 HU for the original VMAT
plan was selected due to the lack of a guideline for defining
body structure. In the AAPM TG-176 report, it is
stated that the HU threshold value should be lower than
-980 HU to incorporate immobilization devices such
as thermoplastic mask, pillow, or vacuum bag into the
body structure while shaping the external contour.[]
We used external contours with a predefined threshold
value (-350 HU) automatically created with the Eclipse
body searching tool for all patients in our clinic.
These studies are generally designed to consider
patients" weight loss status or possibilities. However,
during contouring at the beginning of treatment, depending
on the clinical routine or the user, an external
contour is usually created with automatic contouring,
and no specific correction is applied to a particular area.
Wu et al.[] investigated the dose difference caused by
changes in anatomy due to weight loss during RT. They
evaluated the dose distribution in IMRT/VMAT treatment
using different possibilities for narrowing and
widening the external contour from different directions
at the same rate. They stated that while body contour
expansion causes coverage loss, body contour reduction
increases the dose given to OAR. They noted that
RT personnel could determine the necessity for re-simulation
and replanning according to external contour
changes. In addition to these evaluations, the need for
additional manual correction, as in our study, is an issue
that RT personnel should evaluate. In such cases, the
planning time may be longer; however, the tools of today's
contouring stations offer more practical solutions,
and the processes can be completed in a shorter time.
There are no studies on the effect of automatic contour
correction, especially on an inclined surface such
as an auricle. Thus, our study aimed to evaluate the
target volume and dose change in critical organs using
different body contours.
Conclusion
The value of using adaptive therapy for patients for reasons
such as weight loss or tumor shrinkage is inevitable.
Nowadays, treatment device configurations continue to be developed with features that allow adaptive therapy.
Changes in the external contour of the patient should
be considered with this technology and checked by RT
personnel. It was observed that plans with and without
auricle correction were dosimetrically within the clinical
acceptance criteria. Still, the parotid mean dose increased
in plans with contour correction, especially in
patients with level 2 involvement. Although changes in
other dosimetric parameters are considered clinically
insignificant, it is important to minimize errors during
RT to provide more accurate patient treatment.
Peer-review: Externally peer-reviewed.
Conflict of Interest: All authors declared no conflict of interest.
Ethics Committee Approval: The study was approved by
the Cerrahpaşa Faculty of Medicine Clinical Research Ethics
Committee (no: A-46, date: 07/01/2021).
Financial Support: None declared.
Authorship contributions: Concept - S.Ç.K., Ö.U.; Design
- S.Ç.K., E.K.; Supervision - S.Ç.K., Ö.U.; Materials - M.D.;
Data collection and/or processing - S.Ç.K., E.K., M.D.; Data
analysis and/or interpretation - M.D., G.C.; Literature search
- S.Ç.K., M.D.; Writing - S.Ç.K.; Critical review - Ö.U.
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