Technical Note: Treatment planning system (TPS) approximations matter - comparing intensity-modulated proton therapy (IMPT) plan quality and robustness between a commercial and an in-house developed TPS for nonsmall cell lung cancer (NSCLC).

Purpose Approximate dose calculation methods were used in the nominal dose distribution and the perturbed dose distributions due to uncertainties in a commercial treatment planning system (CTPS) for robust optimization in intensity-modulated proton therapy (IMPT). We aimed to investigate whether the approximations influence plan quality, robustness, and interplay effect of the resulting IMPT plans for the treatment of locally advanced lung cancer patients. Materials and methods Ten consecutively treated locally advanced nonsmall cell lung cancer (NSCLC) patients were selected. Two IMPT plans were created for each patient using our in-house developed TPS, named "Solo," and also the CTPS, EclipseTM (Varian Medical Systems, Palo Alto, CA, USA), respectively. The plans were designed to deliver prescription doses to internal target volumes (ITV) drawn by a physician on averaged four-dimensional computed tomography (4D-CT). Solo plans were imported back to CTPS, and recalculated in CTPS for fair comparison. Both plans were further verified for each patient by recalculating doses in the inhalation and exhalation phases to ensure that all plans met clinical requirements. Plan robustness was quantified on all phases using dose-volume-histograms (DVH) indices in the worst-case scenario. The interplay effect was evaluated for every plan using an in-house developed software, which randomized starting phases of each field per fraction and accumulated dose in the exhalation phase based on the patient's breathing motion pattern and the proton spot delivery in a time-dependent fashion. DVH indices were compared using Wilcoxon rank-sum test. Results Compared to the plans generated using CTPS on the averaged CT, Solo plans had significantly better target dose coverage and homogeneity (normalized by the prescription dose) in the worst-case scenario [ITV D95% : 98.04% vs 96.28%, Solo vs CTPS, P = 0.020; ITV D5% -D95% : 7.20% vs 9.03%, P = 0.049] while all DVH indices were comparable in the nominal scenario. On the inhalation phase, Solo plans had better target dose coverage and cord Dmax in the nominal scenario [ITV D95% : 99.36% vs 98.45%, Solo vs CTPS, P = 0.014; cord Dmax : 20.07 vs 23.71 Gy(RBE), P = 0.027] with better target coverage and cord Dmax in the worst-case scenario [ITV D95% : 97.89% vs 96.47%, Solo vs CTPS, P = 0.037; cord Dmax : 24.57 vs 28.14 Gy(RBE), P = 0.037]. On the exhalation phase, similar phenomena were observed in the nominal scenario [ITV D95% : 99.63% vs 98.87%, Solo vs CTPS, P = 0.037; cord Dmax : 19.67 vs 23.66 Gy(RBE), P = 0.039] and in the worst-case scenario [ITV D95% : 98.20% vs 96.74%, Solo vs CTPS, P = 0.027; cord Dmax : 23.47 vs 27.93 Gy(RBE), P = 0.027]. In terms of interplay effect, plans generated by Solo had significantly better target dose coverage and homogeneity, less hot spots, and lower esophageal Dmean , and cord Dmax [ITV D95% : 101.81% vs 98.68%, Solo vs CTPS, P = 0.002; ITV D5% -D95% : 2.94% vs 7.51%, P = 0.002; cord Dmax : 18.87 vs 22.29 Gy(RBE), P = 0.014]. Conclusions Solo-generated IMPT plans provide improved cord sparing, better target robustness in all considered phases, and reduced interplay effect compared with CTPS. Consequently, the approximation methods currently used in commercial TPS programs may have space for improvement in generating optimal IMPT plans for patient cases with locally advanced lung cancer.