Background Esophageal carcinoma is the eighth most common cancer in the world. Volumetric‐modulated arc therapy (VMAT) is widely used to treat distal esophageal carcinoma due to high conformality to the target and good sparing of organs at risk (OAR). It is not clear if small‐spot intensity‐modulated proton therapy (IMPT) demonstrates a dosimetric advantage over VMAT. In this study, we compared dosimetric performance of VMAT and small‐spot IMPT for distal esophageal carcinoma in terms of plan quality, plan robustness, and interplay effects. Methods 35 distal esophageal carcinoma patients were retrospectively reviewed; 19 patients received small‐spot IMPT and the remaining 16 of them received VMAT. Both plans were generated by delivering prescription doses to clinical target volumes (CTVs) on phase‐averaged 4D‐CT's. The dose‐volume‐histogram (DVH) band method was used to quantify plan robustness. Software was developed to evaluate interplay effects with randomized starting phases for each field per fraction. DVH indices were compared using Wilcoxon rank‐sum test. For fair comparison, all the treatment plans were normalized to have the same CTVhigh D95% in the nominal scenario relative to the prescription dose. Results In the nominal scenario, small‐spot IMPT delivered statistically significantly lower liver Dmean and V30Gy[RBE], lung Dmean, heart Dmean compared with VMAT. CTVhigh dose homogeneity and protection of other OARs were comparable between the two treatments. In terms of plan robustness, the IMPT and VMAT plans were comparable for kidney V18Gy[RBE], liver V30Gy[RBE], stomach V45Gy[RBE], lung Dmean, V5Gy[RBE], and V20Gy[RBE], cord Dmax and D0.03boldcboldm3, liver Dmean, heart V20Gy[RBE], and V30Gy[RBE], but IMPT was significantly worse for CTVhigh D95%, D2boldcboldm3, and D5%‐D95%, CTVlow D95%, heart Dmean, and V40Gy[RBE], requiring careful and experienced adjustments during the planning process and robustness considerations. The small‐spot IMPT plans still met the standard clinical requirements after interplay effects were considered. Conclusions Small‐spot IMPT decreases doses to heart, liver, and total lung compared to VMAT as well as achieves clinically acceptable plan robustness. Our study supports the use of small‐spot IMPT for the treatment of distal esophageal carcinoma.

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, Eclipse TM (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 D 95% : 98.04% vs 96.28%, Solo vs CTPS, P = 0.020; ITV D 5% -D 95% : 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 D max in the nominal scenario [ITV D 95% : 99.36% vs 98.45%, Solo vs CTPS, P = 0.014; cord D max : 20.07 vs 23.71 Gy (RBE), P = 0.027] with better target coverage and cord D max in the worst-case scenario [ITV D 95% : 97.89% vs 96.47%, Solo vs CTPS, P = 0.037; cord D max : 24.57 vs 28.14 Gy(RBE), P = 0.037]. On the exhalation phase, similar phenomena were observed in the nominal scenario [ITV D 95% : 99.63% vs 98.87%, Solo vs CTPS, P = 0.037; cord D max : 19.67 vs 23.66 Gy(RBE), P = 0.039] and in the worst-case scenario [ITV D 95% : 98.20% vs 96.74%, Solo vs CTPS, P = 0.027; cord D max : 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 D mean , and cord D max [ITV D 95% : 101.81% vs 98.68%, Solo vs CTPS, P = 0.002; ITV D 5% -D 95% : 2.94% vs 7.51%, P = 0.002; cord D max : 18.87 vs 22.29 Gy(RBE), P = 0.014]. C...

Purpose To compare the dosimetric performances of small‐spot three‐dimensional (3D) and four‐dimensional (4D) robustly optimized intensity‐modulated proton (IMPT) plans in the presence of uncertainties and interplay effect simultaneously for distal esophageal carcinoma. Method and Materials Thirteen (13) patients were selected and re‐planned with small‐spot (σ ~ 2–6 mm) 3D and 4D robust optimization in IMPT, respectively. The internal clinical target volumes (CTVhigh3d, CTVlow3d) were used in 3D robust optimization. Different CTVs (CTVhigh4d, CTVlow4d) were generated by subtracting an inner margin of the motion amplitudes in three cardinal directions from the internal CTVs and used in 4D robust optimization. All patients were prescribed the same dose to CTVs (50 Gy[RBE] for CTVhigh3d/CTVhigh4d and 45 Gy[RBE] for CTVlow3d/CTVlow4d). Dose–volume histogram (DVH) indices were calculated to assess plan quality. Comprehensive plan robustness evaluations that consisted of 300 perturbed scenarios (10 different motion patterns to consider irregular motion (sampled from a Gaussian distribution) and 30 different uncertainties scenarios (sampled from a 4D uniform distribution) combined), were performed to quantify robustness to uncertainties and interplay effect simultaneously. Wilcoxon signed‐rank test was used for statistical analysis. Results Compared to 3D robustly optimized plans, 4D robustly optimized plans had statistically improved target coverage and better sparing of lungs and heart (heart Dmean, P = 0.001; heart V30Gy[RBE], P = 0.001) in the nominal scenario. 4D robustly optimized plans had better robustness in target dose coverage (CTVhigh4d V100%, P = 0.002) and the protection of lungs and heart (heart Dmean, P = 0.001; heart V30Gy[RBE], P = 0.001) when uncertainties and interplay effect were considered simultaneously. Conclusions Even with small spots in IMPT, 4D robust optimization outperformed 3D robust optimization in terms of normal tissue protection and robustness to uncertainties and interplay effect simultaneously. Our findings support the use of 4D robust optimization to treat distal esophageal carcinoma with small spots in IMPT.