Introduction
Esophageal cancer (EC), constituting 1% of all cancer
types, is a type of cancer, in which 482,300 cases are reported
worldwide every year. Despite its high mortality,
it constitutes 7% of gastrointestinal system tumors
and its incidence is lower compared to other malignancies. The high mortality rate carries EC to the 6th place
among the most common causes of death.[-] While it
is mostly seen in the Eastern Anatolia Region in Turkey,
Iran, Korea, Japan, China, and South Africa which are
among the countries, where EC is most common. Excessive
hot beverage consumption, alcohol use, and smoking
are considered important risk factors for EC.[,]
The choice of treatment modality for EC depends on
the stage of the disease. Although surgery is a curative
treatment option for EC,[,] it cannot be performed
because most patients are diagnosed at advanced stage.
Therefore, radiotherapy is a good approach in the treatment
of EC.[] The main purpose of radiotherapy is to
protect the healthy tissues around the target volume at
the maximum extent, while providing a homogeneous
dose distribution in the target volume.[,] Thanks to
the developing technology, volumetric modulated arc
therapy (VMAT) technique, which aims to protect
healthy organs better than conventional planning techniques,
has been developed. This technique is an improved
form of the intensity modulated radiotherapy
(IMRT) technique. In VMAT technique, the dose rate,
the positions and speeds of the multi-leaf collimators
change, and the gantry can rotate 360° around the patient.
The treatment delivery time in VMAT is shorter
compared to IMRT.[,]
The treatment planning systems (TPS) employ
the algorithms for optimization and dose calculation.
First, the optimization is carried out by algorithms
that optimize the dose distributions according to the
pre-set dose constraints of the target and organs at risk
(OARs). These optimization algorithms are used to determine
the combination of field shapes and segment
weights which achieve the desired planning. Eclipse
TPS used separate optimizers with dose-volume optimizer
for IMRT and progressive resolution optimizer
for VMAT. Recently, the photon optimizer algorithm
has been introduced for VMAT and IMRT optimization
generated by the dose-volume histogram (DVH)
estimation model.[,] The final dose distribution is
calculated using the more accurate analytical anisotropic
algorithm (AAA), which has been shown to be
superior in dose calculation for heterogeneous media
and small fields.[]
In the radiation therapy planning process, the final
dose calculation obtained by IMRT or VMAT technique
differs from the optimal DVH obtained by the optimization
process. An intermediate dose calculation (IDC)
module has been developed to solve this problem. IDC
module ensures the creation of the optimal plan by continuously
optimizing to obtain the desired DVH in line
with the dose-volume criteria determined by the user.
[,] There are few studies showing the effect of the
IDC module on the plan quality during optimization.
In this study, it was aimed to investigate the effect
of using the IDC module during the optimization of
VMAT on plan quality for ten thoracic and ten abdominal
EC patients. VMAT treatment plans created with and without IDC module were evaluated in terms of
dose-volume metrics, conformity index (CI), and homogeneity
index (HI).
Methods
Image Data Acquisition
A total of 20 patients with EC, including ten abdominal
and ten thoracic esophagus patients, who received
radiotherapy in Istanbul University Oncology Institute
included in this study. Patients were set up in supine
position with their arms over their heads using a wing
board. The patients" computed tomography (CT) image
data sets were acquired with 3 mm slice thickness
using a Philips Big Bore Brilliance CT scanner. 3DCT
image set of 20 patients were transferred to the Varian
Eclipse v15.6 TPS for both contouring and planning.
Delineation of Target Volume and OARs
CT, MRI, and PET-CT were used to delineate the target
volume by radiation oncologist and radiologist. The
target volume and OARs were contoured on the planning
CT by same radiation oncologist. The clinical target
volume (CTV) included the esophageal tumor, with
a margin for microscopic tumor extension, and the
adjacent lymph nodes. For the PTV, a 3-dimensional
margin of 5 mm was added to the CTV to account for
the variability in patient setup, uncertainty in target
definition, and organ motion. The lungs, heart, spinal
cord, kidneys, and liver were also delineated on the CT
image set as OARs. Target and OAR were delineated
according to report ICRU 83.[]
Treatment Planning and Dose Prescription
The treatment plans for abdominal and thoracic esophagus
patients were created using VMAT technique in
the Varian Eclipse v15.6 TPS by same medical physicist.
All plans were generated using 6 MV photon
beams from a Varian Trilogy Linac equipped with a
Millennium 120-leaf MLC. The prescription dose to
PTV was 5040 cGy with 180 cGy/fraction. Dose calculation
was carried out with AAA using a calculation
grid of 2.5 mm for all treatment plans.
The treatment plans were prepared with two full
arc; the gantry angles were adjusted between 181.0°
and 179.0° clockwise for the first arc and between
179.0° and 181.0° counter clockwise for the second arc.
The couch angle is set to 0°. The collimator angle was
defined 30° for first arc and 330° for second arc. The
dose rate was chosen as 600 MU/min. First, the plan
optimization was performed based on dose-volume constraints without IDC module and dose distribution
was calculated using AAA. OARs dose limits based
on the recommendations of the Quantitative Analyses
of Normal Tissue Effects in Clinic are given in Table
1.[] This plan was saved as an original plan. Then,
the original plan was re-optimized with same optimization
parameters with IDC module. Dose calculation
was made with same dose calculation algorithm.
This planning process was carried out for 20 patients.
The plan normalization was made that 95% of the PTV
received 50.4 Gy.
Table 1 Dose limits for OARs
The DVHs of VMAT plans with and without IDC
module for one abdominal and one thoracic esophagus
patient are shown in Figures 1 and 2, respectively.
Fig. 1. The dose-volume histogram of volumetric modulated arc technique plans with and without intermediate dose
calculation module for one abdominal esophagus patient.
PTV: Planning target volume; IDC: Intermediate dose calculation; Gy: Gray.
Fig. 2. The dose-volume histogram of volumetric modulated arc technique plans with and without intermediate dose
calculation module for one thoracic esophagus patient.
PTV: Planning target volume; IDC: Intermediate dose calculation; Gy: Gray.
Dosimetric Evaluation
To evaluate the quality of plans, CI value was calculated
using Equation (1);
VHV represents the PTV volume, VTIH represents the
volume of the 95% isodose line, and PTVPIH represents
the target volume covered by the 95% isodose line.
[15,16] Plans with a CI=1 are ideal plans. D2% (nearmaximum),
D98% (near-minimum), and D50% (median
dose) for PTV were recorded through DVH. HI
was calculated by the following Equation (2) based on
ICRU 83.[]
where, D2 represents the dose received by 2% of PTV, D98
represents the dose received by 98% of PTV, and D50 represents
the dose received by 50% of PTV.[] The ideal
value of HI is 0. Lower values of HI indicate a more homogeneous
dose distribution. As critical organs, lung-PTV
(V5,V10,V20, and Dmean), heart (Dmean and V30), liver (Dmean),
bilateral kidney (Dmean, V12,V20,V23, and V28), and spinal
cord (Dmax and D1cc) doses were evaluated. Furthermore,
MU values were compared.
Statistical Analysis
Statistical analysis was performed in the SPSS (version
22.0) program. As the statistical comparison method, Wil-coxon-Signed Rank Test was used due to the small sample
size. P<0.05 value was considered statistically significant.
Results
Evaluation of PTV and OARs Doses in Abdominal
EC Patients
For abdominal EC patients, D2, D98, Dmean, CI, and HI
values for PTVs in the plans created using AAA v15.6
with and without IDC module are given in Table 2.
The MU values of the plans are also shown in Table 2.
The lung-PTV (V5,V10,V20, and Dmean), heart (Dmean and
V30), liver (Dmean), bilateral kidney (Dmean, V12,V20,V23,
and V28), and spinal cord (Dmax and D1cc) dose values in
plans created using AAA v15.6 with and without IDC
module for abdominal EC patients are given in Table 3.
Table 2 PTV doses of patients with abdominal esophageal cancer
Table 3 OARs doses of abdominal EC patients
Evaluation of PTV and OARs Doses in Thoracic
EC Patients
For thoracic EC patients, D2, D98, Dmean, CI, and HI values
for PTVs in the plans created using AAA v15.6 with and
without IDC module are given in Table 4. The MU values
of the plans are also shown in Table 4. The lung-PTV
(V5,V10,V20, and Dmean), heart (Dmean and V30), and spinal
cord (Dmax and D1cc) dose values in plans created using
AAA v15.6 with and without IDC module for thoracic
EC patients are given in Table 5.
Table 4 PTV doses for thoracic esophagus patients
Table 5 OAR doses of thoracic esophagus patients
Discussion
Radiotherapy plays a predominant role within multimodal
treatment concepts for ECs due to protecting
esophageal shape and function.[16,17] In recent years, clinical studies have shown that IMRT and VMATbased
techniques are better than conventional 3-dimensional
conformal radiation therapy with respect
to improved PTV coverage and OARs sparing in the
treatment of ECs.[,]
The treatment plans using IMRT and VMAT techniques
are associated with a precise target volume
and minimized side effects due to enhanced protection
of the normal organ, but not always as desired. It
requires the development of optimization algorithms
used to reach an effective treatment plan in the optimization
process. For this purpose, an intermediate
dose option has been developed in the Eclipse TPS.
In this study, it was aimed to investigate the effect of
using the IDC module during the optimization of
VMAT on plan quality for ten thoracic and ten abdominal
EC patients.
When the data obtained at the end of the study
were examined, CI and HI parameters were found to
be significantly lower in treatment plans which optimized
with IDC module for both abdominal and EC
patients. In addition to these, D2, Dmean, and MU parameters
of PTVs also showed improvement. In addition
to these, in the presence of IDC module, spinal
cord Dmax value was found to be 3200±507 cGy for
thoracic esophagus patients. It was 3281±470.8 cGy
in plans without IDC module.
Akbaş et al.[] investigated the dosimetric impact
of IDC on heterogeneous region radiotherapy
planning. In their study, the treatment plans were created
using AAA with and without IDC for 12 patients
with maxillary sinus cancer patients. In this study,
they reported that the HI and CI values were 0.090
and 1.142 and 0.067 and 1.055 for plans generated
using AAA v15.1 without IDC and AAA v15.1 with
IDC, respectively.
Kan et al.[] reported that there was no difference
according to the application of IDC in their phantom
study. However, the authors used VMAT technique and
evaluated the results according to application of an air
cavity correction option simultaneously with the intermediate
dose option. Li et al.[] examined the effect
of the IDC module on PTV and OAR using the IMRT
technique for 11 lung cancer patients. They found that
the HI and CI value of 0.12±0.04 and 0.59±0.11 and
0.08±0.03 and 0.69±0.10 for plans optimized with and
without IDC module, respectively. In addition, Dmax of
the spinal cord was found to be 29.10±10.49 Gy and
31.39±9.71 Gy for plans optimized with and without
IDC module, respectively. These results show positive
parallelism with our study.
When the results of our study were evaluated, the
use of the IDC module in the AAA algorithm improved
HI and CI in the plans of patients with abdominal and
thoracic EC patients. Some of the critical organ doses
improved. In abdominal esophagus cancer irradiations,
lung-PTV (V5), lung-PTV (Dmean), liver (Dmean),
kidney (Dmean), kidney (V23), and kidney (V28) doses are
improved, while in thoracic esophagus cancer irradiations,
lung-PTV (V20), heart (V30), spinal cord (Dmax),
and spinal cord (D1cc) doses were reduced.
Conclusion
As a result of this study, it has been observed that the
use of the IDC module during VMAT optimization for
abdominal and thoracic esophagus cancer patients increased
the quality of the plan and provided a slight
improvement in critical organ doses.
Peer-review: Externally peer-reviewed.
Conflict of Interest: All authors declared no conflict of interest.
Ethics Committee Approval: The study was approved
by the Istanbul University Istanbul Faculty of Medicine
Ethics Committee (No: E-29624016-050.99-6125, Date:
06/01/2021).
Financial Support: This study has received no financial
support.
Authorship contributions: Concept - Y.E., H.B.B.; Design
- Y.E., C.K.A., Ş.K., H.B.B.; Supervision - H.B.B.; Funding -
Ş.K., C.K.A.; Materials - Y.E., Ş.K., C.K.A.; Data collection
and/or processing - Y.E., C.K.A., Ş.K.; Data analysis and/or
interpretation - Y.E., H.B.B.; Literature search - Y.E., C.K.A.,
Ş.K., H.B.B.; Writing - Y.E.; Critical review - H.B.B.
References
Kato H, Nakajima M. Treatments for esophageal cancer:
a review. Gen Thorac Cardiovasc Surg 2013;61(6):330?5.
Shi HY, Liu ML, Zhu SC, Shen WB. Pathological characteristics
of esophageal cancer. Oncology Letters
2014;8(2):533-8.
Kollarova H, Machova L, Horakova D, Janoutova G,
Janout V. Epidemiology of esophageal cancer--an
overview article. Biomed Pap Med Fac Univ Palacky
Olomouc Czech Repub 2007;151(1):17-20.
Yildirim M, Kaya V, Yildiz M, Demirpence O, Gunduz
S, Dilli UD. Esophageal cancer, gastric cancer and the
use of pesticides in the southwestern of Turkey. Asian
Pac J Cancer Prev 2014;15(6):2821-3.
Ychou M, Boige V, Pignon JP, Conroy T, Bouché O, Lebreton
G, et al. Perioperative chemotherapy compared
with surgery alone for resectable gastroesophageal
adenocarcinoma: an FNCLCC and FFCD multicenter
phase III trial. J Clin Oncol 2011;29(13):1715-21.
Deng W, Lin SH. Advances in radiotherapy for
esophageal cancer. Ann Transl Med 2018;6(4):79.
Allehyani SH, Sharyan HA, Tolba AR, Hassan RA.
3DCRT versus RapidArc in terms of Iso-dose distribution,
Dose Volume Histogram (DVH) and organs
at risk for esophageal cancer (EC) dosimetric study.
AJCEM 2017;5(4):123-33.
Van Benthuysen L, Hales L, Podgorsak MB. Volumetric
modulated arc therapy vs. IMRT for the treatment of
distal esophageal cancer. Med Dosim 2011;36(4):404-9.
Kim YL, Chung JB, Kang SH. Dosimetric and radiobiological
evaluation of dose volume optimizer (DVO)
and progressive resolution optimizer (PRO) algorithm
against photon optimizer on IMRT and VMAT plan
for prostate cancer. Medical Physics 2018;29(4):106-14.
Klippel N, Schmücking M, Terribilini D, Geretschläger
A, Aebersold DM, Manser P. Improved VMAT planning
for head and neck tumors with an advanced optimization
algorithm. Z Med Phys 2015;25(4):333?40.
Li Y, Rodrigues A, Li T, Yuan L, Yin FF, Wu QJ. Impact
of dose calculation accuracy during optimization
on lung IMRT plan quality. J Appl Clin Med Phys
2015;16(1):5137.
Park BD, Kim TG, Kim JE. Dosimetric impact of intermediate
dose calculation for optimization convergence
error. Oncotarget 2016;7(25):37589-98.
International Commission on Radiation Units and
Measurements. Prescribing, recording, and reporting
photon-beam intensity-modulated radiation therapy
(IMRT). Journal of the ICRU 2010;10(1):Report 83.
Bentzen SM, Constine LS, Deasy JO, Eisbruch A, Jackson
A, Marks LB, et al. Quantitative analyses of normal
tissue effects in the clinic (QUANTEC): an introduction
to the scientific issues. Int J Radiat Oncol Biol
Phys 2010;76(3 Suppl):S3-9.
Paddick I. A simple scoring ratio to index the conformity
of radiosurgical treatment plans. Technical
note. J Neurosurg 2000;93 Suppl 3:219-22.
Nakamura JL, Verhey LJ, Smith V, Petti PL, Lamborn
KR, Larson DA, et al. Dose conformity of gamma
knife radiosurgery and risk factors for complications.
Int J Radiat Oncol Biol Phys 2001;51(5):1313-9.
van Hagen P, Hulshof MC, van Lanschot JJ, Steyerberg
EW, van Berge Henegouwen MI, Wijnhoven BP,
et al; CROSS Group. Preoperative chemoradiotherapy
for esophageal or junctional cancer. N Engl J Med
2012;366(22):2074-84.
Fenkell L, Kaminsky I, Breen S, Huang S, Van Prooijen
M, Ringash J. Dosimetric comparison of IMRT
vs. 3D conformal radiotherapy in the treatment of
cancer of the cervical esophagus. Radiother Oncol
2008;89(3):287-91.
Ma P, Wang X, Xu Y, Dai J, Wang L. Applying the
technique of volume-modulated arc radiotherapy to
upper esophageal carcinoma. J Appl Clin Med Phys
2014;15(3):4732.
Akbas U, Koksal C, Kesen ND, Kaval G, Karaman S,
Dağoğlu N, et al. Dosimetric impact of intermediate
dose calculation on heterogeneous region radiotherapy
planning. Physica Media 2018;52(suppl 1):99-187.
Kan MW, Leung LH, Yu PK. The performance of the
progressive resolution optimizer (PRO) for RapidArc
planning in targets with low-density media. J Appl
Clin Med Phys 2013;14(6):4382.
