PURPOSE: The purpose of this study was to compare the impact of uncertainties and interplay on 3-dimensional (3D) and 4D robustly optimized intensity modulated proton therapy (IMPT) plans for @entity2 in an exploratory methodology study. METHODS AND MATERIALS: IMPT plans were created for 11 nonrandomly selected @entity1149 ( @entity1149 ) cases: 3D robustly optimized plans on average CTs with internal gross @entity5 volume density overridden to irradiate internal target volume, and 4D robustly optimized plans on 4D computed tomography (CT) to irradiate clinical target volume (CTV). Regular fractionation (66  Gy [relative biological effectiveness; RBE] in 33 fractions) was considered. In 4D optimization, the CTV of individual phases received nonuniform doses to achieve a uniform cumulative dose. The @entity614 ( @entity614 ) measured the sensitivity of the dose to uncertainties, and the areas under the @entity614 curve (AUCs) were used to evaluate plan robustness. Dose evaluation software modeled time-dependent spot delivery to incorporate interplay effect with randomized starting phases of each field per fraction. Dose-volume histogram (DVH) indices comparing CTV coverage, homogeneity, and normal tissue sparing were evaluated using Wilcoxon signed rank test. RESULTS: 4D robust optimization plans led to smaller AUC for CTV (14.26 vs 18.61, respectively; P=.001), better CTV coverage (Gy [RBE]) (D95% CTV: 60.6 vs 55.2, respectively; P=.001), and better CTV homogeneity (D5%-D95% CTV: 10.3 vs 17.7, resspectively; P=.002) in the face of uncertainties. With interplay effect considered, 4D robust optimization produced plans with better target coverage (D95% CTV: 64.5 vs 63.8, respectively; P=.0068), comparable target homogeneity, and comparable normal tissue protection. The benefits from 4D robust optimization were most obvious for the 2 typical @entity5 @entity1 . CONCLUSIONS: Our exploratory methodology study showed that, compared to 3D robust optimization, 4D robust optimization produced significantly more robust and interplay-effect-resistant plans for targets with comparable dose distributions for normal tissues. A further study with a larger and more realistic @entity1 population is warranted to generalize the conclusions.

Exploratory Study of 4D versus 3D Robust Optimization in Intensity Modulated Proton Therapy for XXXX .

@entity1 :: ('9606', 'Species') :: ['patients', 'patient'] @entity5 :: ('MESH:D009369', 'Disease') :: ['tumor', 'stage III lung cancer'] @entity1149 :: ('MESH:D002289', 'Disease') :: ['NSCLC', 'non-small cell lung cancer'] @entity2 :: ('MESH:D008175', 'Disease') :: ['lung cancer'] @entity614 :: ('MESH:D011843', 'Disease') :: ['root-mean-square dose-volume histograms', 'RVH']
@entity2 :: (MESH:D008175,Disease) :: ['Lung Cancer']
