353 NSCLC patients treated to a median of 3x18 Gy were included in this study. Cone beam CTs (CBCTs) were acquired prior to each fraction for patient positioning. RIRFs were diagnosed on follow-up (FU) CT scans acquired at 4 months post SBRT, every 6 months for 2 years and annually until year 5. Ribs outside the CBCT field-of-view were not considered (5338 ribs, 63%).
Each fraction’s dose distribution was approximated by shifting the planned dose to the daily tumor location followed by conversion to biologically equivalent dose (EQD2) with α/β=3 Gy. The total delivered dose was estimated by deforming each corrected fraction dose onto the planning anatomy (using CBCT-to-planning CT deformable image registration) and accumulating all fractions.
Ribs were automatically segmented using atlas based segmentation. A dose volume histogram was computed per rib, and dosimetric parameters D
x (dose to volume x; range 0-50%) extracted. NTCP models for both planned and delivered dose were built by maximizing the likelihood to correctly classify fracture, optimizing TD
50 (dose with 50% toxicity risk) and m (steepness of the curve) for all D
x. The best dosimetric RIRF predictor for each dose distribution and the best NTCP model were selected using Akaike weights (relative likelihoods). Differences between model parameters were tested for significance using the log likelihood ratio test by applying the TD
50 and m from the 2 distributions jointly or separately to the delivered dose.