Regional lung avoidance by CT numbers to reduce radiation-induced lung damage risk in non-small-cell lung cancer: a simulation study

Background: Selective avoidance aims at sparing functional lung regions. Here, we preferentially direct radiation to irreversibly nonfunctional lung areas based on planning CT imaging to reduce functional lung damage. Materials and methods: For 12 stage I-IV NSCLC patients, 5 lung substructures were segmented on the planning CT, combining voxels =-600HU (Level 1 to 5). Two VMAT plans were optimized: a reference plan blinded from substructures and a selective avoidance plan (AV) imposing gradually stricter constraints on Level 1-5, based on previously validated associations between lung subvolume baseline density and density increase (Delta HU) after treatment. Characteristics of treatment plans were evaluated, including subvolumes, dose, and predicted Delta HU (with reported 95% CI reflecting prediction model uncertainty). Results: Segmented substructures were on average 477 cc, 1157 cc, 484 cc, 69 cc, and 123 cc (Level 1-5). AV plans could spare Level 3-5, e.g., mean dose decrease of 3.5 Gy (range 0.6 Gy; 6.0 Gy) for Level 5, p001. This significantly reduced the average lung mass with predicted Delta HU>20HU by 12.5 g (95% CI: 5.4-16.9) and 27.1 g (95% CI: 10.2-32.9) for a median and upper 10th percentile patient susceptibility for damage simulation, respectively. Conclusions: Lung damage avoidance based on CT density is feasible and easy to implement. A biomarker providing a reliable selection of patients with high susceptibility for lung damage will be crucial to show the clinical relevance of this avoidance planning strategy.