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Volumetric modulated arc therapy for primary lung cancer; the benefit and limitations of
including contralateral esophagus (CE) and left anterior descending coronary artery
(LAD) as substructure organs at risk (OAR).

Kerry Shroyer R.T. (R)(T)(CT), Ryan Monago R.T. (R)(MR)(T), Nishele Lenards, PhD, CMD,
R.T. (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

I. Abstract
II. Introduction
A. P1: Explain volumetric modulated arc therapy (VMAT) benefits for non-small cell
lung cancer (NSCLC) treatment and organs at risk (OAR). Mention current
research findings regarding radiation dose limitations to contralateral esophagus
and left anterior descending artery.
B. P2: Left anterior descending artery (LAD) OAR (Reference: Atkins et al,1
McWilliam et al,2 Stam et al,3 Wennstig et al,4 Bergom et al5)
C. P3: Contralateral esophagus (CE) OAR (Reference: Al-halabi et al,6 Kamran et
al,7 Ma et al8)
D. P4: Summarize introduction points:
1. Problem: While clinical research has shown that exceeding dose to
structures such as the LAD and contralateral esophagus region can lead
to severe patient complications and morbidity, many volumetric
modulated arc (VMAT) lung plans do not include these as contoured
avoidance structures.
2. Purpose: The purpose of this retrospective study was to determine if
PTV prescription goals could be maintained while limiting dose to the
CE and LAD utilizing the defined dose constraints of this study.
3. Hypotheses: Researchers tested the hypotheses that VMAT lung plans
will meet prescription planned tumor volume (PTV) goals while
reducing dose to the LAD to V15<10% (H1A) and reducing dose to the
CE to V55Gy<0.5cc (H2A), V45Gy<2.5cc (H3A), and D.03cc<60Gy
(H4A) as proposed by previous clinical studies.4,5
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III. Materials and Methods

A. Patient selection and setup
1. P1: Patient population
1. Retrospective study: choose patients treated with VMAT plans
2. Dose: at least 59.4Gy, 1.8-2Gy/fx
3. Left sided disease (and right side if certain criteria met)
a. Right side criteria: tumor volume within 2cm laterally of
esophagus.
2. P2: Simulation and procedure
1. Sim setup
a. Patients were simulated HFS, arms raised
2. All patients were scanned with 4DCT, treatment plan created on
average phase 0-90 series.
B. Contours
1. LAD
1. The LAD was contoured as an independent structure from the heart
and a 1.0mm planning risk volume (PRV) structure was created for
optimization
2. CE:
1. The CE was created following the Kamran et al8 guidelines utilized
in their phase 1 nonrandomized clinical trial
2. If esophagus and PTV were within 2cm superiorly/inferiorly and
5cm laterally, CE contoured
a. GTV was examined in contouring. CE was drawn by
contouring half of the esophagus that is distal to the GTV
on all slices that contain GTV. Kamran et al. research
guidelines state that the CE should not be within 5.0mm of
the internal target volume (ITV) edge. All cases in this
study had a 5.0mm expansion on the ITV to create the PTV.
Thus, to make the CE contour, the drawn half of the
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esophagus was edited to remove any overlap of the CE and

the PTV.
C. Treatment planning
1. PI: Planning details
a. Varian Eclipse Version 16.1
b. 6MV
c. Partial Arcs: Angles used from original plans
d. AcurosXB16101 algorithm used to evaluated plans
e. All retrospective cases planned using the same linear
accelerator (Varian TrueBeam)
i. Couch insert for all plans: AcurosXB-13.5
f. Approved clinical protocol for primary lung utilized and
added LAD and CE constraints.
2. PII: Optimization & Plan Evaluation
a. All retrospective plans used clinical protocol as goals for
optimization
b. Varian optimization tool Avoid Entry for LAD
c. Does retrospective plan meet all OAR constraints?
d. Does retrospective plan meet prescription goals?
e. Does retrospective plan meet new structure goals?
D. Plan comparison
1. Comparison of the retrospective plan vs. the original plan on specific
metrics:
1. PTV coverage
a. % Volume receiving 100% of prescription dose
2. Global dose max goal
a. 0.03cc<110%
3. LAD
4. CE
5. Heart mean
a. Ideal constraint: Dmean < 2000cGy
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2. Clinical goals:
1. Esophagus_CE:
a. D0.3cc < 6000cGy
b. V45Gy < 2.5cc
c. V55Gy < 0.5cc
2. LAD:
a. V15Gy <10%
E. Statistical Analysis
1. PI. Explanation of statistical test: sign test with p-value
a. Recommended .10 as threshold for P value due to
experimental state of study
F.
IV. Results
A. PII. LAD dose data and reoptimization changes (H1A)
1. Sign test LAD: P<.10, Z value was 2.828 (Statistically significant)
(Figure ___, Table___)
2. Mean dose changes and standard deviation data
3. LAD V15Gy constraint = Fail to reject null hypothesis
B. PIII. Contralateral Esophagus dose data and reoptimization changes (H2A, H3A,
H4A)
1. Sign Test V55Gy: P <.10 (Statistically significant) (Figure___, Table ___)
2. Sign Test V45Gy: P <.10 (Statistically significant) (Figure ___, Table___)
3. Sign Test D0.3cc P > .10 (Statistically insignificant) Mention that there
was no statistically useful change due to reoptimization goals (Table
___)
4. Mean dose changes and standard deviation data (1-3)
5. CE V55Gy constraint = Fail to reject null hypothesis
6. CE V45Gy constraint = Fail to reject null hypothesis
7. CE Dmax = Fail to reject null hypothesis
C. PIV. Changes to OAR values
1. Mean dose changes and standard deviation: Heart mean
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2. Mean dose changes and standard deviation: Global Max Dose .03cc
3. Mean dose changes and standard deviation: Lung-ITV mean dose
4. Mean dose changes and standard deviation: Lung-ITV V20Gy
5. Mean dose changes and standard deviation: Lung-ITV V5Gy
1. Lung-ITV V5Gy P<.10 (Significant change) Increase in low dose
to volume of lung with reoptimization
D. P V. PTV Coverage maintenance
1. Mean dose changes and standard deviation: V100% prescription dose
2. Plans maintained OAR goals (Table____)
3. Sign test PTV Coverage: P > .10 (Statistically insignificant)
1. Coverage thus maintained effectively
4. Global Dose max mean values and standard deviation
1. Original plans
2. New plans
V. Discussion
A. PI: Summary of dosimetric findings after applying new LAD and CE constraints
B. P2: Whole study comparison of PTV coverage with and without new CE and
LAD constraints
C. P3: Discuss how to incorporate these constraints with commonly used protocols
(review current RTOG protocols)
VI. Conclusion
A. PI: Summary of LAD and CE related morbidities and the research about sparing
these organs
B. PII: Summary of problem and purpose of this research
1. Problem: While clinical research has shown that exceeding dose to
structures such as the LAD and contralateral esophagus region can lead
to severe patient complications and morbidity, many volumetric
modulated arc (VMAT) lung plans do not include these as contoured
avoidance structures.
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2. Purpose: The purpose of this retrospective study was to determine if

PTV prescription goals could be maintained while limiting dose to the
CE and LAD utilizing the defined dose constraints of this study.
C. PIII: Summary of results from retrospective plans
D. Limitations
1. 10 patient retrospective study
2. Data collected from singular clinical site (only one TPS and algorithm)
3. Limitations from inclusion criteria vs. all patients
E. Future Research
1. Larger and more expansive set of patient data
2. More clinical sites, other TPS and algorithms
3. More variety in tumor location (i.e. different inclusional criteria)
VII. Acknowledgements
A. PI. Acknowledgement will be included for Douglas Baumann from the UW La
Crosse statistics department at the end of the manuscript.
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References
1. Atkins KM, Chaunzwa TL, Lamba N, et al. Association of left anterior descending
coronary artery radiation dose with major adverse cardiac events and mortality in patients
with non–small cell lung cancer. JAMA Oncol. 2021;7(2):206–219.
http://doi.org/10.1001/jamaoncol.2020.6332
2. McWilliam A, Kennedy J, Hodgson C, Vasquez Osorio E, Faivre-Finn C, van Herk M.
Radiation dose to heart base linked with poorer survival in lung cancer patients. Eur J
Cancer. 2017;85:106-113. http://dx.doi.org/10.1016/j.ejca.2017.07.053
3. Stam B, Peulen H, Guckenberger M, et al. Dose to heart substructures is associated with
non-cancer death after SBRT in stage I-II NSCLC patients. Radiother Oncol.
2017;123(3):370-375. http://dx.doi.org/10.1016/j.radonc.2017.04.017
4. Wennstig AK, Garmo H, Isacsson U, et al. The relationship between radiation doses to
coronary arteries and location of coronary stenosis requiring intervention in breast cancer
survivors. Radiat Oncol. 2019;14(1):40. http://dx.doi.org/10.1186/s13014-019-1242-z
5. Bergom C, Bradley JA, Ng AK, et al. Past, present, and future of radiation-induced
cardiotoxicity: refinements in targeting, surveillance, and risk stratification. JACC
CardioOncol. 2021;3(3):343-359. http://dx.doi.org/10.1016/j.jaccao.2021.06.007
6. Al-Halabi H, Paetzold P, Sharp GC, Olsen C, Willers H. A contralateral esophagus-
sparing technique to limit severe esophagitis associated with concurrent high-dose
radiation and chemotherapy in patients with thoracic malignancies. Int J Radiat Oncol
Biol Phys. 2015;92(4):803-810. http://dx.doi.org/10.1016/j.ijrobp.2015.03.018
7. Kamran SC, Yeap BY, Ulysse CA, et al. Assessment of a contralateral esophagus–
sparing technique in locally advanced lung cancer treated with high-dose chemoradiation:
a phase 1 nonrandomized clinical trial. JAMA Oncol. 2021;7(6):910–914.
http://dx.doi.org/10.1001/jamaoncol.2021.0281
8. Ma L, Qiu B, Li Q, et al. An esophagus-sparing technique to limit radiation esophagitis in
locally advanced non-small cell lung cancer treated by simultaneous integrated boost
intensity-modulated radiotherapy and concurrent chemotherapy. Radiat Oncol.
2018;13(1):130. https://doi.org/10.1186/s13014-018-1073-3
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9. Chang, J. Intensity-modulated radiotherapy, not 3D conformal, is the preferred technique

for treating locally advanced lung cancer. Semin Radiat Oncol. 2015; 25(2) 110-116.
https://doi.org/10.1016/j.semradonc.2014.11.004