Mitigation of the Interplay Effects of Combining 4D Robust With Layer Repainting Techniques in Proton-Based SBRT for Patients With Early-Stage Non-small Cell Lung Cancer

OBJECTIVE: The objective of this study was to evaluate the interplay effects in proton-based stereotactic body radiotherapy (SBRT) using 4D robust optimization combined with iso-energy layer repainting techniques for non-small cell lung cancer (NSCLC). MATERIALS AND METHODS: Twelve patients with early-stage NSCLC who underwent 4DCT were retrospectively selected. A robust CTV-based 4D plan was generated for each based on commercial Treatment planning system (TPS), considering patient setup errors, range uncertainties, and organ motion. The 4D static dose (4DSD) and 4D dynamic dose (4DDD) were calculated using a hybrid deformable algorithm and simulated proton delivery system. An index [Formula: see text] was developed to quantitatively evaluate the interplay effects. The interplay effects of the 4D robust plan and multiple iso-energy layers (3, 4, 5, 6, and 7) of the robust repainting 4D plan were calculated based on [Formula: see text] to select the optimal times for layer repainting. RESULTS: Due to the interplay effects, the mean target values D(2) and D(5) increased to 1.28 and 1.01%, and the target values D(98) and D(95) decreased to 2.01 and 1.77%, respectively, for the 4D Robust SBRT plan. After multiple iso-energy repainting times, the interplay effects of the target values D(98) and D(95) tended to migrate, from 2.01 to 0.92% in target value D(98) and from 1.77 to 0.89% in target value D(95), respectively. Moreover, a positive linear correlation was observed between the optimal interplay effect mitigation and target range of motion. CONCLUSION: In proton-based 4D Robust SBRT, the interplay effects degraded the target dose distribution but were mitigated using iso-energy layer repainting techniques. However, there was no significant correlation between the number of repainting layers and improvements in the dose distributions. The optimal layer repainting times based on the interplay effect index were ascertained according to the patient characteristics.