Author: Daniel A. Alexander, Jeffrey D. Bradley, Steven J. Feigenberg, Cole Friedes, Casey Hollawell, William Levin, Maksym Sharma, Boon-Keng Kevin Teo, Ying Xiao, Nikhil Yegya-Raman, Jennifer Wei Zou 👨🔬
Affiliation: Department of Radiation Oncology and Applied Sciences, Department of Radiation Oncology, University of Pennsylvania, University of Pennsylvania 🌍
Purpose: To investigate lung function changes following definitive chemoradiation dose using CT-derived measurements in patients with locally advanced NSCLC at 6-months post-treatment compared to pre-treatment.
Methods: Consecutive patients who were treated with definitive radiation (60-to-70Gy at 200cGy/fx, IMRT[n=6] or Proton-RT[n=7]) with concurrent chemotherapy were enrolled on an IRB approved prospective trial. Each patient underwent Dual-energy (DE) and 4D-CT imaging prior to radiation and 6-months post-RT. All CT data was obtained using Siemens SOMATOM-Drive (Siemens-Medical-Solutions, Malvern, PA). The DE and 4D-CT datasets were used to generate the pre‐RT and post‐RT perfusion and ventilation maps. Perfusion-Blood-Volume (PBV) was obtained from DECT with contrast by quantifying the contrast agent per voxel, while ventilation maps were generated by registering the inhale-phase to the exhale-phase image and computing the Jacobian determinant of the resulting transformation. The voxel‐wise ventilation change between pre‐RT and post‐RT PBV and Jacobian-maps were investigated as a function of dose. Perfusion and ventilation data were processed using MIM v7.3.2 (MIM-Software-Inc., Beachwood, OH). Statistical analysis was performed using GraphPad-PRISM v10.4.1 (GraphPad-Software, San Diego, CA).
Results: We evaluated CT-derived lung function changes after 6-months of lung-RT (n=13, Male/Female=7/6) and observed the most significant change in perfusion and ventilation at >30Gy(ΔHU=-4.41±6.55) and >50Gy(ΔJacobian=-0.048±0.055) dose, respectively. Using segmental-linear-regression we identified a potential breakpoint of >20Gy for differential perfusion loss (Slope#1:-0.147[95%CI:-0.323,0.029] and Slope#2:0.018[95%CI:-0.106,0.141]) and ventilation loss (Slope#1:-0.0024[95%CI:-0.0041,-0.0006] and Slope#2:-0.0006[95%CI:-0.0019,0.0006]), respectively.
Conclusion: Substantial perfusion and ventilation changes were seen in lung cancer patients treated with definitive chemoradiation 6-months post-RT treatment. Overall, there were greater perfusion changes as opposed to ventilation. We showed that perfusion and ventilation decreased with increasing dose delivered, indicating a potential breakpoint dose of >20Gy that may be used during treatment planning. This is important because using CT-derived lung function has the advantage of routine accessibility and is currently investigated in functional lung avoidance studies.