Left Anterior Descending Coronary Artery-Optimized Knowledge-Based Radiotherapy Planning in Patients with Locally Advanced Non-Small Cell Lung Cancer

Abstract

The left anterior descending (LAD) coronary artery volume receiving 15 Gy (V15 Gy) has been associated with major adverse cardiac events and mortality in patients with locally advanced non-small cell lung cancer (LA-NSCLC) treated with radiotherapy (RT). However, coronary arteries are not routinely contoured as standard-of-care and there is limited data describing coronary-sparing planning techniques. Our objective was to evaluate whether LAD-sparing could be improved compared to real-world plans using a commercial knowledge-based planning (KBP) software without clinically unacceptable tradeoffs to other critical organs at risk (OAR). Retrospective replanning analysis was conducted on 31 RT plans developed for patients with LA-NSCLC. Each case was manually replanned with volumetric modulated arc radiotherapy (VMAT) optimized for LAD V15 Gy sparing with a prescription dose of 60 Gy. The resulting plans were used to create an LAD-optimized KBP model. The model included both KBP-generated objectives and additional point objectives to meet LAD (V15 Gy < 10%), lung (V5 Gy < 60%, V20 < 30%, mean < 17 Gy), heart (mean < 20 Gy), spinal cord (D0.03cc < 45 Gy), esophagus (V60 Gy < 17%, mean < 34 Gy), and planning target volume (PTV; D95% = 100%). The LAD-optimized model was deployed to replan 33 additional VMAT plans for LA-NSCLC with prescription dose 60 Gy, delivered between 2018 and 2022. Dose constraints or objectives were only unmet with KBP when not met in the original plan. Descriptive statistics were used to compare dosimetric parameters between original and LAD-optimized KBP plans. For the 33 plans identified for LAD-optimized KBP replanning, the original plans had a mean LAD V15 Gy of 17.9% (standard error [SE], 3.9%), while the LAD-optimized KBP plans had a significantly lower mean LAD V15 Gy of 5.9% (SE, 1.9%; p = 0.031). There was no significant difference in mean heart dose between the original and LAD-optimized KBP plans (8.4 Gy [SE 6.6 Gy] vs. 7.3 Gy [SE 5.8 Gy]; p = 0.48). Of these 33 KBP plans, 42% (n = 14) had mean reductions in LAD V15 Gy from 40.5% (SE 4.3%) to 10.5% (SE 3.5%; p = 0.0002), with 9/14 now able to meet < 10%, without affecting other critical OAR objectives (p > 0.5 for lungs, esophagus, spinal cord). 45% (n = 15) originally had an LAD V15 Gy < 1%, which were unchanged using KBP (p > 0.3). Four plans (12%) had higher LAD V15 Gy in the KBP vs. original plan (2/4 still meeting < 10%), due to the model prioritizing other OARs to a greater degree. Improvements in LAD-sparing was achievable in more than 40% of plans without apparent clinically significant tradeoffs in other critical OARs and without corresponding change in MHD. This result underscores the importance of standard implementation of LAD contouring and dose constraints, particularly given the discordance between whole heart and LAD dose exposure.