Correlation of Left Anterior Descending Coronary Artery Radiation Dose with Major Adverse Cardiac Events and Feasibility of Coronary Artery Sparing Treatment Planning in Lung Cancer

Abstract

<h3>Purpose/Objective(s)</h3> Radiation dose to the left anterior descending (LAD) coronary artery is associated with major adverse cardiac events (MACE) in patients with locally advanced non-small cell lung cancer (LA-NSCLC). However, the newly identified LAD metric (percent volume receiving 15 Gy [LAD V15Gy]) has not been independently validated and the extent to which modern radiotherapy (RT) planning techniques can reduce LAD V15Gy without exceeding dose tolerances to other critical organs at risk (OAR) remains uncertain. <h3>Materials/Methods</h3> This is a single institution retrospective study of 98 patients with LA-NSCLC treated with RT between 2005-2020. The LAD was manually delineated for each patient. MACE (unstable angina, myocardial infarction, heart failure, coronary revascularization, and cardiac death) cumulative incidence was estimated and Fine and Gray regressions were performed, adjusting for non-cardiac death as a competing risk. Patients who received LAD V15Gy ≥10% and experienced MACE were re-planned with volumetric-modulated arc therapy (VMAT) to optimize reduction of LAD V15Gy while maintaining target coverage and meeting standard OAR constraints. <h3>Results</h3> The median follow up was 23.2 months. The median age was 69 years, 30.6% of patients had pre-existing coronary heart disease (CHD) or a CHD risk-equivalent. The mean LAD V15Gy was 32% (standard deviation [SD] 27.8%). Ten patients developed at least one MACE, with a 2-year cumulative incidence of 10.2% (95% CI: 3.1-17.0%). Adjusting for pre-existing CHD there was an increased risk of MACE with LAD V15Gy (subdistribution hazard ratio 1.03; 95% CI 1.00-1.06; p=.034), with a significant interaction between LAD V15Gy and CHD (p=.005). Among the 10 patients who developed a MACE, 6 (60%) had an LAD V15Gy ≥ 10% (mean 52%, range 10-100%). The original planning techniques included: 3-dimensional conformal RT (3D-CRT; n=2), static intensity-modulated RT (IMRT; n=2), and VMAT (n=2). In 4 of these plans (n=2 IMRT, n=1 3D-CRT, n=1 VMAT), the re-planned LAD V15Gy was reduced to <10%, however all 6/6 plans achieved some degree of LAD V15Gy reduction (range, 9-100%). Specifically, optimization with LAD-sparing VMAT achieved a mean absolute decrease of 35.1% for LAD V15Gy (SD 32.4%) and 6.2 Gy mean heart dose (SD 10.9 Gy), with a concomitant mean increase of 0.8 Gy mean lung dose (SD 1.8 Gy), and mean lung V20Gy of 0.2% (SD 4.1%). All re-plans achieved similar target coverage and remained within national guideline OAR constraints. <h3>Conclusion</h3> LAD V15Gy is associated with an increased risk of MACE in this independent retrospective cohort. VMAT-based LAD-sparing RT plan optimization is feasible and can achieve meaningful reductions in LAD V15Gy with potentially clinically acceptable tradeoffs in lung dose. Together, these findings underscore the need for more aggressive LAD-sparing RT planning approaches.