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Comparison of IMRT, VMAT, and 3D-CRT Treatment Techniques to Minimize Risk of

Radiation Induced Esophagitis for Mediastinal NSCLC: A Case Study
Authors: Brittany Check BS, R.T.(T), Jennifer Kouri BS, R.T.(T), Benjamin Lemieux BS, R.T.
(T), Nishele Lenards, MS, CMD, R.T.(R)(T), FAAMD, Ashley Hunzeker, MS, CMD
Abstract:
Introduction: This study aimed to compare esophageal dose using three radiotherapy techniques
for mediastinal non-small cell lung cancer (NSCLC) while analyzing adequate tumor coverage
and limited critical structures dose.
Case Description: The presentation of bulky, mediastinal lung tumors are commonly associated
with NSCLC. The treatment of mediastinal lung cancer presents challenges due to the close
proximity of many sensitive critical structures. Depending on the tumor proximity to the
esophagus and target dose, patients who undergo chemoradiation for mediastinal disease may
present with esophagitis at some point during the course of treatment. Rose et al9 suggested dosevolume criteria that correlate with the incidence of esophagitis. In this study, a plan comparison
of 3 different treatment techniques was conducted on 7 patients diagnosed with NSCLC of the
mediastinum. Intensity modulated radiation therapy (IMRT), volume modulated arc therapy
(VMAT), and 3D conformal radiation therapy (3D-CRT) were compared to analyze significant
dose-volume criteria for the esophagus while maintaining adequate target coverage.
Conclusion: Each plan was evaluated for esophageal dose using a dose-volume analysis. The
volume of the esophagus that received 30 Gy (V30), 35 Gy (V35), 40 Gy (V40), 50 Gy (V50), and
60 Gy (V60) were compared for each treatment technique. The mean dose was also compared to
demonstrate the overall effectiveness of the different treatment techniques on the dose
distribution to the organ. The lowest esophageal mean doses were observed in the VMAT and
IMRT plans at 2068.9 cGy and 2126 cGy, respectively. The 3D-CRT mean esophageal dose was
2491.6 cGy. The total patient average of the dose-volume analysis showed that the VMAT and
IMRT plans were nearly identical except for the V60, which was 8.13% and 12.4%, respectively.
The 3D-CRT average V60 was 17.7%. This study showed there are advantages to using inverse
planning techniques such as VMAT and IMRT for sparing the esophagus and an advantage of
using VMAT to better control higher doses to smaller volumes of esophagus.
Key Words: NSCLC, esophagitis, IMRT, VMAT, 3D-CRT

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Introduction
Lifestyles associated with tobacco use, unhealthy diet, and inactivity increase the risk of
lung cancer; the most common malignancy in both males and females worldwide. Lung cancer is
the leading cause of cancer mortality with unfavorable survival rates after 5 years.1 In 2012, 1 in
every 5 cancer related deaths were linked to lung cancer.2 Of all lung cancers, 85% are
histologically defined as NSCLC.
The standard of treatment care for NSCLC requires a high dose of radiation, preferably
with chemotherapy, for local long-term control. It is generally acceptable to deliver 60 to 75 Gy
at 1.8 to 2.0 Gy per fraction over 6 to 7 weeks for NSCLC.1 Doses of 64 Gy showed greater
locoregional control compared to patients receiving less than 64 Gy. If escalated another 10 Gy,
locoregional control improved by 36.4%.4 Although this high dose regimen increases probability
of eliminating disease, the high dose to the primary disease and involved lymph nodes increase
toxicities to the surrounding critical structures as well. Since the target volume coverage takes
priority over the surrounding tissue toxicities, many mediastinal structures develop adverse side
effects.
A substantial volume of the esophagus can be located within the desired target volume in
mediastinal NSCLC radiotherapy cases. Excessive esophageal radiation exposure results in
esophagitis. The incidence of acute esophagitis varies from 1.3% with radiation alone to 14% to
52% with concurrent chemoradiation therapy.4 After receiving 18 to 30 Gy over a 2 to 3 week
period, symptoms of dysphagia, heartburn, and chest pain can occur. If the esophagus receives
more than 55 Gy delivered to 32% of the volume, the risk and severity of esophagitis escalates.1,4
Possible late responses from severe esophagitis include esophageal stricture in need of
intermittent surgical dilatation, intravenous hydration, or feeding tube placement. Although death
from radiation-induced esophagitis is seldom, quality of life during and after completion of
treatment can result in clinical and social impairment.5
Bradley et al7 demonstrated dosimetric parameters correlated to the incidence of
esophagitis. Research reveals a high degree of variability regarding the number of patients, the
diagnosis and stage of the patients, the presence or absence of chemotherapy and surgery, and the
prescribed radiation dose. However, patterns among the studies related specific dosimetric
parameters to the rate of esophagitis. For example, the V50 and V60 were the most common
indicative factors of esophagitis.6,7 There does not appear to be a specific comparison of

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treatment planning techniques relating the ability to limit the dose-volume levels that are
correlated to esophagitis.
Many treatment techniques have been developed to help avoid excessive dose to critical
structures throughout the body. For example, IMRT and VMAT have been essential in creating
precise conformal treatment plans. These inverse treatment planning techniques allow the
creation of volumetric avoidances, in turn, manipulating radiation dose away from critical
structures and providing greater conformity with possible escalated dose to the delineated target
volume.1,8 Unlike standard 3D-CRT, IMRT and VMAT allow for dose escalation to the primary
tumor to increase locoregional control and improved therapeutic ratio.8
The aim of this study was to compare three different radiotherapy treatment techniques
for 7 patients with mediastinal NSCLC while analyzing adequate tumor coverage and limited
critical structure dose with an emphasis on esophageal dose sparing.
Case Description
Patient Selection & Setup
A total of 7 locally advanced NSCLC patients with mediastinal lesions were evaluated
(Table 1). Patients most commonly presented with chest pain, cough, and difficulty breathing. All
patients underwent a CT simulation scan for radiation therapy treatment. The patients were
positioned supine, head to gantry on the CT simulator couch. For reproducibility, the patients
were immobilized on a wingboard and Vac-Lok with both arms extended above their head and
hands placed holding the T-bar or pegs. Large knee sponges were utilized to aid in comfort. A 3point setup was marked with tattoo ink or paint markers on the chest for laser positioning prior to
daily treatment. Three of the 7 patients were scanned with 4D technique to evaluate the need for
respiratory gating. In 4 of the patients, physicians placed the simulation isocenter on planning CT
scans. The other 3 patients had radiopaque references markers placed and the isocenter was set
during treatment planning.
Target Delineation
After simulation, the CT scans were imported to MIM software or Eclipse Treatment
Planning System (TPS) for fusion. Diagnostic PET-CT scans and CT images were fused together
to facilitate in the delineation of the gross tumor volume (GTV). The GTV consisted of the
primary tumor and metastatic lymphadenopathy, as seen metabolically highlighted on the PETCT. A margin was placed around the GTV to define the clinical target volume (CTV). The CTV

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encompassed sub-clinical disease unspecified on the imaging modality. To define all possible
geometrical variations and inaccuracies, a margin of 1 cm was placed around the CTV to
delineate the planning target volume (PTV). The expansion of the target volumes incorporated
presumed microscopic extension and respiratory motion. Depending upon physician preference,
the GTV was not expanded into a CTV, only a PTV. To evaluate and record dose attenuated by
the organs at risk (OR) during treatment, the medical dosimetrists contoured the right and left
lung, the total lung minus the PTV, heart, carina, and spinal cord. The liver and brachial plexus
were also contoured on some patients. Contours were drawn according to the Radiation Therapy
Oncology Group (RTOG) 1106 Thoracic Atlas. To account for uncertainties, the spinal cord was
expanded with a margin of 0.5 cm to create a planning organ at risk volume (PRV) for some
patients. The esophagus was contoured from the cricoid to the gastroesophageal junction.
Treatment Planning
To evaluate the dose to the esophagus, 3 different radiotherapy planning techniques were
created per patient case. The goal of the treatment planning was to create the most optimal plan
per patient case while trying to minimize esophageal dose. As a result, the fields were
customized per patient case. Each case was prescribed a total dose of 60 Gy in 30 fractions to the
PTV. To achieve coverage, all plans were normalized to isocenter or a calculation point so that
100% of the dose was received to 95% of the target volume. Only 6 MV beam energies were
used for treatment planning. Heterogeneity corrections were applied to all the plans. Calculations
were completed with the analytical anisotropic algorithm (AAA) implemented in Eclipse TPS.
The beam arrangement for IMRT plans was chosen to optimally cover the PTV while
limiting OR doses. Between 5 and 7 fields were used depending on the location of the tumor and
OR (Table 2). In 5 of the 7 cases, 7 evenly distributed fields were used to avoid parallel opposed
fields sharing the same fluence map. Post-process structures were created prior to optimization
for IMRT plans. Objectives were set for the PTV or PTV optimization structures to receive 100%
or more of the prescribed dose. Objectives were also set to PTV structures to prevent doses 3-4%
higher than the prescription. A 1 cm ring was created surrounding the PTV with a 0 to 2 mm gap
between the ring and the PTV. An upper objective was set for the ring structure to reduce high
doses outside the PTV. For structures that overlapped the PTV, such as the heart in some cases,
an avoidance structure was created after cropping the structure 0.5 cm away from the PTV.

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During optimization, higher priority was given to the PTV structures than OR objectives. Normal
tissue objective parameters were set depending on the needs of each case.
Like IMRT plans, post-process structures were created prior to optimization for VMAT
plans. Arc geometry varied depending on the location of the tumor and surrounding critical
structures. Stop and start angles are shown in Table 2. The optimization objectives were set in a
similar manner as the IMRT objectives. Normal tissue objectives were established per patient
case.
No additional contouring was needed for 3D-CRT planning. A block margin of 0.5 cm to
1.3 cm was placed around the PTV for proper coverage. The majority of the cases were planned
with 3 fields consisting of an anterior, posterior, and lateral beam. Less weighting was given to
the lateral field. A coplanar beam arrangement of 5 to 6 beams was used for 3 of the 7 patients.
Table 2 displays the beam orientation used for planning. Wedges and segmented fields were
utilized when necessary to achieve a homogeneous dose distribution.
Plan Analysis & Evaluation
Esophageal dose comparisons were made from a dose-volume analysis for each of the 3
treatment planning techniques (Figure 3 and Table 3). Focus was placed on the volume of the
esophagus receiving 30 to 60 Gy since evidence suggests that these parameters may influence the
rate and grade of radiation-induced esophagitis. The most common predictive factors were found
to be the V50 and the V606,7,9. The V30,V35, and V40 were also found to be correlated with
esophagitis.6,9,10 The mean was also compared to demonstrate overall differences in esophagus
dose for each technique. In the 7 patients studied, the mean V50 was 31.4%, 20.3%, and 20.2%,
for 3D-CRT, IMRT, and VMAT, respectively. Therefore, VMAT resulted in similar outcome as
IMRT, and a 35.7% decrease in the volume of esophagus irradiated with 50 Gy compared to 3DCRT. The mean V60 was 17.7%, 12.4%, and 8.1% for 3D-CRT, IMRT, and VMAT, respectively.
Similarly, VMAT resulted in 34.7% decrease compared to IMRT, and a 54.2% decrease
compared to 3D-CRT. Isodose comparison and dose volume histogram (DVH) comparison for
one patient can be seen in Figures 1 and 2.
Slight variation was observed between the isodose distributions for IMRT and VMAT,
though both differed from 3D-CRT. The challenge during 3D-CRT planning was minimizing the
maximum dose to a tolerable level. Since the tumors were bulky in size more beams were needed
for coverage. It was observed that more beams increased the volume of healthy lung tissue

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receiving radiation. While the esophagus cannot be removed from a mediastinal treatment field,
the dose can be altered depending upon which treatment technique is used.
An important difference between both IMRT and VMAT in comparison to 3D-CRT is the
target dose conformity. Often times, mediastinal NSCLC PTVs may include or abut a portion of
the esophagus. By increasing the conformity of the prescription dose by using IMRT or VMAT, a
lower volume of the esophagus receives a high dose. Although increasing the number of beams
or arcs helps to achieve conformity, it may also increase the spread of low dose to a greater
volume of the body.
Conclusion
Currently, the standard of care for NSCLC requires a dose of 60 to 75 Gy which can
cause troublesome side effects for patients. The esophagus is often in close proximity or included
in the PTV for patients with mediastinal NSCLC resulting in esophagitis which significantly
affects quality of life. To reduce the side effects to the esophagus, doses should be monitored and
minimized during the treatment planning process. Studies suggest that esophageal dose-volumes
most closely linked to esophagitis are the V50 and V60.6,7 This case study was conducted to
evaluate the influence of treatment planning techniques on the esophageal dose-volume
parameters associated with esophagitis.
In this case study of 7 patients, the volume of esophagus receiving 30 Gy to 60 Gy for
IMRT, VMAT, and 3D-CRT was evaluated. The IMRT and VMAT plans produced the most
favorable results with esophagus dose-volumes lower than that of 3D-CRT. The most substantial
difference in esophageal volume between IMRT, VMAT, and 3D-CRT was seen in doses 40 Gy
to 60 Gy. Bradley et al7 demonstrated that IMRT, when compared to 3D-CRT, had a significant
advantage to shape dose distributions around critical tissues and decrease toxicity to the
esophagus allowing for dose escalation; however, the study did not include VMAT. In the current
case study, it is evident through isodose plan comparison that superior dose conformity and
homogeneity appear to contribute to the relative sparing of the esophagus in IMRT and VMAT
plans. To a smaller degree, VMAT appeared to reduce the volume of esophagus treated more
effectively than IMRT. The significance of this study was to demonstrate how treatment planning
techniques affect the meaningful esophagus dose in plans that reduce the risk of esophagitis and
increase the patient quality of life.

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In addition to esophagitis, minimizing healthy lung, heart, or spinal cord dose may be
most important depending on each patients situation and comorbidities when selecting a
treatment technique for NSCLC. Using IMRT or VMAT may also have potential drawbacks such
as spreading low dose over high volumes of healthy tissue, and potentially using a greater
quantity of monitor units (MU). Limitations of this study include the small number of patients
studied and the utilization of dose-volume data correlated to esophagitis rather than biological
effect or actual patient outcomes. Further studies are needed to investigate the esophageal dose
differences in 3D-CRT, IMRT, and VMAT for a larger population of patients or using different
optimization methods.

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References
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Ying X, Wasik M, Michalski D, et al. Comparison of three IMRT inverse planning

techniques that allow for partial esophagus sparing in patients receiving thoracic radiation
therapy for lung cancer. Med Dosim. 2004;29(3):210-216.
http://dx.doi.org/10.1016/j.meddos.2004.03.019
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Ramesh R, Rosinzweig KE, Venkatraman E. et al. Improved local control with
higher doses of radiation in large-volume stage III non-small-cell lung cancer. Int J Radiat
Oncol Biol Phys. 2014;60(3):741-747. http://doi:10.1016/j.ijrobp.2004.04.013
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Soffer E, Mitros F, Doornbos J, et al. Morphology and pathology of radiationinduced esophagitis: Double-blind study of naproxen vs placebo for prevention of radiation
injury. Dig Dis Sci. 1994;39(3):655-660. http://dx.doi.org/10.1007/BF02088356
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Cartier L, Auberdiac P, Khodri M, et al. Correlation of dosimetric parameters
obtained with the analytical anisotropic algorithm and toxicity of chest chemoradiation in
lung carcinoma. Med Dosim. 2011;37(2):152-156.
http://dx.doi.org/10.1016/j.meddos.2011.06.004
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Zhang Z, Xu J, Zhou T, et al. Risk factors of radiation-induced acute esophagitis
in non- small cell lung cancer patients treated with concomitant chemoradiotherapy. Radiat
Oncol. 2014;9(1):1-15. http://dx.doi.org/10.1186/1748-717X-9-54
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Bradley J, Deasy J, Bentzen S, et al. Dosimetric correlates for acute esophagitis in
patients treated with radiotherapy for lung carcinoma. Int J Radiat Oncol Biol Phys.
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Benthuysen L, Hales L, Podgorsak M. Volumetric modulated arc therapy vs.
IMRT for the treatment of distal esophageal cancer. Med Dosim. 2011; 36(4):404-409.
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dose-volume parameters in the prediction of esophagitis in thoracic radiotherapy. Radiat
Oncol. 2009;91(3):282-287. http://dx.doi.org/10.1016/j.radonc.2008.09.010
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Figures

Figure 1. Isodose comparison showing the PTV and esophagus for 3D-CRT (left), IMRT
(middle), and VMAT (right) plans for one patient.

Figure 2. Comparison DVH for the PTV and esophagus for one patient.

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Figure 3. Percentage of Esophagus Volume Receiving Dose

Tables

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Table 1. Patient Demographic Information

Table 2. Beam Angles (Degrees) For Each Treatment Technique

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Table 3. Percentage of Esophagus Volume Receiving Dose