CT-Based Lung Function Worsening In Patients with NSCLC Treated Using Photon Versus Proton Radiotherapy
Abstract
Purpose
To evaluate CT-derived longitudinal changes in regional lung function following definitive treatment with photon versus proton radiotherapy in patients with locally advanced non-small cell lung cancer (LA-NSCLC).
Methods
We enrolled patients on an IRB-approved clinical trial of functional lung imaging. All patients were diagnosed with LA-NSCLC, and received definitive, conventionally fractionated concurrent chemoradiation (RT) with or without consolidation immunotherapy (60-70Gy in 2Gy fractions; Photon[n=12] and Proton[n=10]). Functional imaging was not used for planning purposes on this study. All patients underwent contrast-enhanced dual-energy (DE) and 4DCT scans prior to radiation and 6-months post-RT per protocol. Perfusion-Blood-Volume (PBV) was derived from DECT by quantifying iodine contrast per voxel, while ventilation maps were generated by registering inhale-phase to exhale-phase images and computing the Jacobian determinant of the resulting transformation. Perfusion and ventilation data were processed using MIM-Maestro v7.3.2. Statistical analysis performed using GraphPad-PRISM v10.4.1.
Results
We evaluated CT-derived lung function changes after 6-months of photon or proton-RT in 22 patients (Male/Female=11/11). There were no significant differences in baseline ventilation and perfusion measurements between proton and photon groups. There were significant differences in regional ventilation between baseline and 6-months for patients treated with photons (for regions receiving doses: >30Gy[p=0.02], >40Gy[p=0.01], >50Gy[p=0.04]), but no statistically significant regional worsening for those treated with protons. Whole lung perfusion changes were significantly different between patients treated with photon (ΔHU=-1.2±0.6) and proton-RT (ΔHU=-5.1±2.6). Within each treatment group, no significant longitudinal changes in regional lung perfusion were observed between baseline and 6-months. However, at 6-months, patients treated with photons demonstrated significantly different regional perfusion compared with patients receiving proton-RT in lung regions receiving >5Gy and >10Gy doses.
Conclusion
CT-derived functional imaging reveals dose-dependent ventilation loss after photon, but not proton radiotherapy, suggesting superior lung function preservation with protons. Future work will correlate longitudinal functional imaging biomarkers with patient outcomes.