Impact of Interplay Effects on Spot Scanning Proton Therapy with Motion Mitigation Techniques for Lung Cancer: SFUD versus Robustly Optimized IMPT Plans Utilizing a Four-dimensional Dynamic Dose Simulation Tool

Abstract Background: The interaction between breathing motion and scanning beam causes interplay effects in spot-scanning proton therapy for lung cancer, resulting in compromised treatment quality. Therefore, in this study, we investigated the impact of the effects and clinical robustness of two types of spot-scanning proton therapy with motion mitigation techniques for locally advanced non-small cell lung cancer (NSCLC) by utilizing a new simulation tool (4DCT calculation). Methods: Three-field single-field uniform dose (SFUD) and robustly optimized intensity-modulated proton therapy (IMPT) plans, combined with gating and rescanning techniques, were created using a VQA treatment planning system for 15 patients with locally advanced NSCLC (70 GyRBE/35 fractions). In addition, gating windows of three or five phases around the end-of-expiration phase and two internal gross tumor volumes (iGTVs) were created, and a rescanning number of four was used. At first, the static dose (SD) was calculated using end-of-expiration computed tomography (CT). Then, the four-dimensional dynamic dose (4DDD) was calculated using the SD plans, 4D-CT images, and deformable image registration technique on the end-of-expiration CT. The target coverage (V98%, V100%), homogeneity index, and conformation number for the iGTVs and organ-at-risk (OAR) doses were calculated for the SD and 4DDD groups and compared between both treatment plans. Results: In the 3- and 5-phase SFUD, statistically significant differences between SD and 4DDD were observed for V100%, homogeneity, and conformity. In contrast, statistically significant differences were observed for V98%, V100%, and homogeneity in both the 3- and 5- phases of IMPT. The mean V98% and V100% in both 3-phase plans were within the clinical limits (>95%) when the interplay effects were considered; however, V100% decreased to 89.3% and 94.0% for the 5-phase SFUD and IMPT, respectively. Conclusions: The interplay effects had a limited impact on target coverage and OAR doses in SFUD and robustly optimized IMPT with 3-phase gating and rescanning for patients with locally advanced NSCLC. Furthermore, the target coverage deteriorated considerably as the gating window increased. This study demonstrated that robustly optimized IMPT is more robust than SFUD to the interplay effect in terms of target coverage with the prescription dose and homogeneity. Trial registration: None.