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Working Title

A Comparison of Volumetric Modulated Arc Radiotherapy Techniques to Evaluate Left Anterior

Descending Artery Dose Sparing in Left Non-Small Cell Lung Tumor Patients

Problem Statement

The problem is that there is an increased risk for major adverse cardiac events and coronary heart

disease for medial, left-sided upper lobe lung VMAT patients when the volume of the LAD

receiving 15 Gy exceeds 10%.

Purpose Statement

The purpose of this study is to compare dose to the LAD in VMAT plans optimized with and

without an LAD PRV in medial, left-sided, upper lobe non-small cell lung patients to evaluate

dose sparing of the LAD while maintaining 95% coverage of the prescribed PTV dose.

Hypotheses Statements

H1A: The research hypothesis is that VMAT plans optimized with an LAD PRV will meet V15

Gy < 10% dose constraint while maintaining 95% coverage of the prescribed PTV dose.

H10: The null hypothesis is that VMAT plans optimized with an LAD PRV will not meet V15

Gy < 10% dose constraint while maintaining 95% coverage of the prescribed PTV dose.

Summary

Volumetric modulated arc therapy (VMAT) is a type of radiation therapy that delivers a

precise dose of radiation to a tumor while minimizing exposure to nearby normal tissues. VMAT
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uses inverse planning to recognize provided dose constraints to create the most optimal plan that

best meets tumor coverage, while minimizing dose to surrounding OAR. For this reason, VMAT

is a common technique used to treat non-small cell lung cancer (NSCLC), which accounts for

about 81% of all lung cancer cases.1

An important consideration in VMAT planning for NSCLC is the potential impact of

radiation exposure to the left anterior descending artery (LAD), a major coronary artery that

supplies blood to the heart. In particular, the volume of the LAD receiving 15 Gy or more has

been identified as a predictor of cardiac events after radiation therapy. 2 Emerging evidence

suggests that increasing dose to the LAD correlates with an increased risk of major adverse

cardiac events (MACE) and coronary heart disease (CHD) in left-sided NSCLC patients. Despite

evidence that the V15 Gy ≥10% to the LAD predicts an almost 10% increase in risk of a cardiac

events occurring, it has not been followed systematically in instances of lung cancer. 2,3 Once

previously thought to be a side effect that occurs many years after radiation treatment, recent

evidence suggests that the onset of CHD develops an average of 20 months after radiation

treatment in NSCLC patients without prior history of heart disease. 3-5 This suggests the need to

evaluate planning techniques that could reduce dose to the LAD while effectively targeting

tumors in NSCLC patients treated with VMAT.

One common technique utilized during VMAT optimization is the use of a planning

organ at risk volume (PRV). This technique involves creating an expansion structure of an OAR

and is intended to ensure that minimizing dose to an OAR is prioritized during optimization.

Prioritizing this expansion can further reduce dose to the LAD as it provides another structure

that the optimizer must consider. Utilizing a PRV has the additional benefit of reducing dose in
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that it accounts for potential day-to-day variations in patient positioning, respiration, and other

factors that can negatively impact the accuracy of radiation delivery.

The proximity of the LAD to the left lung puts this structure at risk of receiving excessive

radiation during treatment for NSCLC. As treatment continues to improve and patients continue

to live longer after treatment, there is an increased need to investigate planning techniques that

reduce the risk of causing new diseases shortly after the conclusion of treatment. 4,6 Current

planning techniques mainly rely on constraint metrics related to the mean heart dose (MHD);

however, recent evidence has shown that MHD is an inadequate predictor of dose to cardiac

substructures and future incidence of cardiotoxicities. 7 The problem is that there is an increased

risk for major adverse cardiac events and coronary heart disease for medial, left-sided upper lobe

lung VMAT patients when the volume of the LAD receiving 15 Gy exceeds 10%. Therefore, the

purpose of this study is to compare the dose to the LAD in VMAT plans optimized with and

without an LAD PRV in patients with non-small cell lung cancer located in the medial, left-

sided, upper lobe. Researchers tested the hypothesis that VMAT plans optimized with an LAD

PRV will meet the V15 Gy < 10% dose constraint while maintaining 95% coverage of the

prescribed PTV dose.

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References

1. Wakelee HA, Chang ET, Gomez SL, et al. Lung cancer incidence in never smokers. J Clin

Oncol. 2007;25(5):472-478. https://doi.org/10.1200/JCO.2006.07.2983

2. 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.

https://doi.org/10.1001/jamaoncol.2020.6332

3. Reshko LB, Kalman NS, Hugo GD, Weiss E. Cardiac radiation dose distribution, cardiac

events and mortality in early-stage lung cancer treated with stereotactic body radiation

therapy (SBRT). J Thorac Dis. 2018;10(4):2346-2356. http://doi.org/10.21037/jtd.201

4. Atkins KM, Bhupendra R, Tafadzwa CL, et al. Cardiac radiation dose, cardiac disease, and

mortality in patients with lung cancer. J Am Coll Cardiol. 2019;73(23):2976-2978.

https://doi.org/10.1016/j.jacc.2019.03.500

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after conventional-dose chemoradiation therapy for inoperable NSCLC. J Thorac Oncol.

2018;13(10):1508-1518. https://doi.org/10.1016/j.jtho.2018.05.028

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treatment on population mortality. New Engl J Med. 2020;383:640-649.

https://doi.org/10.1056/NEJMoa1916623

7. Atkins KM, Bitterman DS, Chaunzwa TL, et al. Mean heart dose is an inadequate surrogate

for left anterior descending coronary artery dose and the risk of major adverse cardiac events

in lung cancer radiation therapy. Int J Radiat Oncol Biol Phys. 2021;110(5):1473-1479.

https://doi.org/10.1016/j.ijrobp.2021.03.005