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Volumetric Modulated Arc Therapy for Primary Lung Cancer: the Benefit and
Limitations of Including Contralateral Esophagus and Left Anterior Descending Coronary
Artery as Substructure Organs at Risk
Kerry Shroyer RT (R)(T)(CT), Ryan Monago RT(R)(MR)(T), Nishele Lenards, PhD, CMD,
RT(R)(T), FAAMD; Ashley Hunzeker, MS, CMD, Matt Tobler, CMD, R.T.(T) FAAMD
Medical Dosimetry Program at the University of Wisconsin-La Crosse, WI

Introduction
Volumetric modulated arc therapy (VMAT) is an external beam radiation therapy
technique used for curative non-small cell lung cancers (NSCLC) that allows conformal dose
distribution and critical organ sparing.1 One of the primary advantages of VMAT planning is the
ability to spare healthy organs that would otherwise be at risk from other planning techniques.
Volumetric modulated arc therapy lung planning objectives often include whole-organ
constraints such as contralateral lung or heart, but it is not common practice to include the left
anterior descending coronary artery (LAD) and contralateral esophagus (CE) specifically as dose
limiting structures despite clinical research indicating that exceeding dose to these structures can
lead to severe patient complications and morbidity.
The coronary arteries including the LAD originate in the base of the heart. 3 Radiation
dose to the base of the heart is associated with non-cancer deaths for patients with NSCLC. 2
Fifteen Gy to 10% or more of the LAD has been associated with an increase in major adverse
cardiac events.4 When considering substructures of the heart, the LAD has the highest
association with adverse outcomes independent from other factors such as cardiac disease
history. Research by Atkins et al4 suggests that the current use of mean dose as the primary
constraint of the heart is limited in value because it does not account for dose distribution across
specific areas of the heart. McWilliam et al4 suggests that contouring and sparing substructures in
the base of the heart rather than the whole heart for dose constraints could lead to better patient
outcomes.
The CE is the esophageal wall region contralateral to the disease and is another structure
not commonly used as an organ at risk (OAR). Al-Halabi et al5 found it is possible to limit total
esophagus cross-section dose for patients with NSCLC receiving intensity modulated radiation
therapy (IMRT) treatments. By reducing the median volume of the CE receiving 45.0 Gy (V 45 )
and 55.0 Gy (V 55 ) to 2.5 cubic centimeters (cc) and 0.5 cc respectively, patients were spared of
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grade 3 esophagitis which can cause hospital admittance and necessitate a feeding tube. 5-7
Reduction in preventable radiation induced complications could reduce interruptions in patient
treatment courses. Based on previous studies, it can be assumed that considering the CE as a
separate, additional structure rather than the serial organ esophagus, can reduce grade 3
esophagitis as a patient complication.
Literature suggests that careful avoidance of the CE and LAD can lead to better clinical
outcomes for patients The problem is that these structures are not routinely included as standard
avoidance structures for VMAT planning for NSCLC. The purpose of this retrospective planning
study was to determine whether prescription target volume goals could be maintained while
limiting dose to the CE and LAD for VMAT lung planning. Researchers tested the hypotheses
that VMAT lung plans will meet prescription planning tumor volume (PTV) goals while
reducing dose to the LAD to V 15 <10% (H1A) and reducing dose to the CE to V 55 Gy<0.5cc
(H2A), V 45 Gy<2.5cc (H3A), and D.03cc<60Gy (H4A) as proposed by previous clinical studies.4,5
Methods and Materials
Patient Selection and Setup
Patients selected for this study were previously treated with VMAT plans for primary
lung cancer of various non-small cell histologies. Prescription dose was at least 59.4Gy, 1.8-2.0
Gy per fraction. The patients included had left-side disease or right-side disease with a PTV
within 2.0 cm lateral to the esophagus. Patients were all simulated headfirst, supine, with arms
raised. All patients were scanned with four-dimensional computed tomography (4DCT), 2mm
CT slice thickness, and planned on the average phase series.
Contours
In addition to the previously contoured structures for traditional lung metrics such as
whole hear and, total lung minus ITV, the LAD and CE were contoured on each patient. The
LAD was contoured as an independent structure from the heart and a 1.0 mm planning organ at
risk volume (PRV) structure was created for optimization. The CE was created following the
Kamran et al8 guidelines utilized in their phase 1 nonrandomized clinical trial. First, the gross
tumor volume (GTV) created by the physician was examined in the contouring window. The
contralateral esophagus was drawn with a brush tool by contouring the half of the esophagus
distal to the disease on all axial slices where the GTV was present. Per Al Halabi et al5
guidelines, the contralateral esophagus should not be within 5.0 mm of the internal target volume
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(ITV) edge. All the cases utilized in this planning study had 5mm expansions on the ITV to
create the PTV. Thus, to make the contralateral esophagus, the drawn contour was edited using
the crop tool to remove any overlap of the CE and the PTV.
Treatment Planning
All plans were created using Varian Eclipse version 16.1, 6 MV, and arc geometry was
kept from the original patient treatment so that any changes to dose metrics could be specifically
linked to the addition of new structure constraints. Plans were calculated using AcurosXB16101
algorithm. All plans were created for the same linear accelerator – Varian TrueBeam with 1.0cm
multi-leaf collimator (MLC) width for the outer 10cm section of MLC and 0.5cm width MLC for
the inner 20cm section. Clinical constraints were unchanged from the previous patient plan other
than the addition of LAD and CE objectives. Optimization goals were adjusted within planning
to address constraints that were exceeding limitations. The Varian optimization tool “avoid
entry” was used for LAD goals. Plans were designed to have a monitor unit (MU) ratio below
4.0. Evaluation of newly optimized plans assessed whether the retrospective plan still met OAR
constraints compared to the previous plan, whether prescription goals still met, and whether the
new plan met the new LAD and CE goals.
Plan Comparison
The retrospective plans were compared to the patient’s original treatment plans by
evaluating specific metrics. First, PTV coverage was compared based on what percentage of the
volume was receiving 100% of prescription dose. The coverage goal was 100% of prescription
dose to 95% of the PTV. The overall hotspot within the plan was also evaluated using 0.03cc
volume with a goal of 0.03cc < 110%. Next, dose to the LAD and CE was compared. The
optimization goal for the LAD was that the volume of 15Gy (V 15 Gy) was 10% or less. The goals
for the CE were that 0.3cc of the structure received less than 6000cGy, the V 45 Gy was less than
2.5cc, and the V 55 Gy was less than 0.5cc. The heart mean dose was also evaluated, with an ideal
constraint of <2000cGy mean dose.
Statistical Analysis
To determine the significance of change in CE and LAD dose outcomes after re-
optimization with the aforementioned dose constraints, the previous values were compared to the
new reported values using a statistical sign-test. The sign test assigned a p-value and p-value to
each set of analyzed data. A p-value <0.10 is considered significant.
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Results
LAD V15Gy ≤ 10%
Initially, 8 of the 10 plans were failing the LAD V15Gy ≤ 10% goal. The range of values
for this constraint were between 0% and 69% with a mean value of 34% and a standard deviation
of 24%. After re-optimization, all 10 plans met this constraint with a new range of 0% to 9%
with a mean value of 4% and a standard deviation of 4%. The sign test determined the p-value of
this constraint to be 0.002, indicating it was statistically significant.
CE V55 Gy < 0.5cc
Of the 10 retrospective plans, 4 were initially failing the CE V 55 Gy goal of <0.5cc. Of the
6 passing plans, 5 had a value of 0 for this category. After re-optimization, all 10 retrospective
plans were under 0.5cc for this category. Initially, the plans ranged from 0.0cc to 1.53cc
receiving 55Gy, with a mean value of 0.439cc and a standard deviation of 0.571. After re-
optimization, the range of volume receiving 55Gy was 0.0cc to 0.49cc with a mean of 0.091cc
and standard deviation of 0.157. The sign test determined the p-value of this constraint to be
0.013, indicating it was a statistically significant change.
CE V45 Gy < 2.5cc
Initially, only 1 plan was failing the new V 45 Gy < 2.5cc constraint at 6.71cc. The range of
V45 Gy initially was between 0.0cc to 6.71cc with a mean value of 1.362cc and standard deviation
of 2.039. After re-optimization, all plans met the V 45 Gy constraint with a range of 0.0cc to
1.76cc with a mean value of 0.645cc and standard deviation of 0.703. The sign test determined
the p-value of this constraint to be 0.007, indicating it was a statistically significant change.
While 9 of the plans were meeting this constraint initially with 4 plans at 0.0cc, the 1 plan that
exceeded this metric was reduced from 6.71cc to 1.11 cc.
CE D0.03cc <60Gy
Initially, 2 of the 10 plans did not meet the goal of CE D0.03cc < 60Gy. The range for
this constraint was 25.6Gy to 60.8Gy with a mean value of 47.42Gy and a standard deviation
value of 15.22. After re-optimization, all 10 plans met this constraint, with a range from 24Gy to
59.4Gy, a mean value of 46.7Gy, and a standard deviation value of 12.21. The sign test
determined the p-value of this constraint to be 0.102, indicating this was not a statistically
significant change.
Maintenance of PTV coverage
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Of the initial plans, 9 were meeting the goal of V100%≥95%, meaning that 100% of the
prescription dose encompassed at least 95% of the PTV. One plan, patient 3, was not meeting
this constraint at only 91.5%. After re-optimization with these 3 new CE and LAD dose
constraints, all plans maintained their coverage goals, and patient 3 did not receive any less
prescription dose coverage than the original plan. The ability to meet the LAD V15Gy≤10%
(H1A), CE V45Gy < 2.5cc (H3A), CE V55Gy <0.5cc (H2A), and CE 0.03cc < 60Gy (H4A) goals
while maintaining PTV prescription goals rejected the researcher’s null hypotheses.
Significant changes to existing OAR constraints as a result of re-optimization
In addition to the new CE and LAD goals, the original OAR goals were re-evaluated to
determine any changes that could be linked directly to the addition of the new LAD and CE
constraints. Heart mean, global max dose, total lung minus ITV mean dose, total lung minus ITV
V20 Gy, and total lung minus ITV V 5 Gy were all compared to determine significant changes. The
initial range of heart mean dose was between 0.74Gy to 19.9Gy. After re-optimization, the heart
mean dose ranged from 2.4Gy to 19.9Gy. Six plans had a reduction in heart mean dose, while 4
plans had an increase. The sign test determined this was not statistically significant with a p-
value of 0.382.
The global max dose goal of V0.03cc receiving <110% was initially met in 8 of the 10
plans and met in 10 of the 10 plans after re-optimization. The p-value for the change in global
dose max was 0.5, indicating it was not statistically significant. It can be assumed based on these
results that adding the CE and LAD constraints did not significantly change the global max dose
to the plan. The total lung minus ITV mean dose saw an insignificant change with a sign test p-
value = 0.103. The total lung minus ITV V 20 Gy also saw statistically insignificant change with a
sign test p-value of 0.264. The total lung minus ITV V 5 Gy volume, however, had significant
change with a p-value of 0.006. In 9 of the 10 plans, there was an increase in V 5 Gy to the total
lung minus ITV.
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