Sparing Functional Lung Using Optimized Volumetric Modulated Arc Therapy in Thoracic Radiation for Locally Advanced Non-Small Cell Lung Cancer

Abstract

Chemoradiation (CRT) followed by maintenance durvalumab is the standard of care for locally advanced non-small cell lung cancer (NSCLC) but is limited by toxicity to normal lung tissue from radiotherapy and immunotherapy1. Many lung cancer patients have heterogeneous lung function as a result of the tumor and/or pre-existing co-morbidities2. We proposed Volumetric Modulated Arc Therapy (VMAT) could be used to spare the functional parts of the lung (FL) without exceeding organs at risk (OARs) constraints or compromising tumor coverage.Functional lung volumes were retrospectively contoured using 4D-CT ventilation maps for 32 patients with stage III NSCLC treated with CRT and maintenance durvalumab at a single institution from September 2017- October 2019. Functional lung volumes were created from 4D-CT data using methodology previously described3,4. Studies have shown 4D-CT ventilation maps generated from the changes in the density of lungs during the respiratory cycle correlate with pulmonary function tests and ventilation-perfusion imaging5. New VMAT plans were generated to spare the FL while also maintaining adequate planning target volume (PTV) coverage and without exceeding dose constraints to the OARs. The dosimetric values of the original plans were compared to the dosimetric values of the optimized plans using paired t-test or paired Wilcox rank-sum test as appropriate. Specifically, the PTV D95, heart mean, esophagus mean, spinal cord Dmax, as well as the FL mean, FL V5, FL V10, FL V20, and FL V30 were compared.Optimized plans had statically significant lower FL mean dose, FL V5, FL V10, FL V20, and FL V30 (all P values < 0.001). Numerically, the mean dose to the heart, mean dose to the esophagus, and spinal cord Dmax were lower in the optimized plan as compared to the original plan, though only the esophageal dose was statistically significant (P < 0.001). When comparing the PTV D95, the median for both plans were the same (60 Gy), though statistically lower (P = 0.032) in the optimized plan (range, 57-66.15) as compared to the original plan (range, 57-67.27). However, both plans provided adequate PTV coverage.We demonstrated the ability to optimize VMAT plans to avoid functional parts of the lung while maintaining adequate PTV coverage and meeting OAR constraints for locally advanced NSCLC. VMAT plans optimized to avoid functional lung can be created with minimal extra cost or change in treatment planning workflow as 4D-CT acquisition at time of simulation is standard practice, which is advantageous compared to other functional lung avoidance techniques, i.e., single photon emission computerized tomography (SPECT). Given already compromised lung function and risk of pulmonary toxicities from treatment, this work highlights a personalized approach to radiation treatment planning.