Systematic parameter selection of carbon ion lattice radiation therapy: balancing RBE-weighted dose and LETd distributions

OBJECTIVE: Carbon ion lattice radiation therapy (CLRT) lacks systematic parameter selection strategies. This study aimed to develop an automated lattice placement system for CLRT and to elucidate the impact of irradiation strategies, lattice structures, vertex diameters, and gaps on RBE-weighted dose (RWD) and dose-averaged linear energy transfer (LETd) distributions. APPROACH: A proprietary MATLAB-based automated lattice placement system was applied to 15 bulky tumors using single-field optimization to mitigate range uncertainties. Two irradiation strategies, lattice-only and lattice combined with a uniform background dose to the clinical treatment volume (lattice+CTV), were investigated. Lattice configurations included body-centered cubic and hexagonal close-packed structures, with diameters of 10, 15, and 20 mm and vertex gaps of 15, 20, 25, and 30 mm. Plan quality was assessed using the evaluation metrics of spatially fractionated radiation therapy, gross tumor volume, and organs at risk (OARs). Generalized estimating equations (GEEs) were employed to quantify the relative contribution of each parameter. Moreover, a multi-criteria decision framework integrating the technique for order of preference by similarity and a significance-based winning vote was constructed to identify recommended parameter configurations across varying clinical priorities. MAIN RESULTS: GEE regression indicated that the interaction between the irradiation strategy and gap (26.86%), the main effect of the irradiation strategy (17.55%), and the gap (16.88%) were the primary contributors to variations in RWD and LETd distributions. Conversely, the lattice structure had a minimal effect (<2.5%). In both strategies, a 10 mm vertex diameter demonstrated the most favorable performance. However, the recommended gap diverged significantly. For the lattice-only strategy, a 20 mm gap emerged as the recommended configuration, achieving target coverage while minimizing OAR doses. In contrast, for the lattice+CTV strategy, the addition of a background RWD rendered a 30 mm gap the recommended choice. SIGNIFICANCE: The proposed automated lattice placement system and irradiation-strategy-specific parameter selection strategy provide a robust quantitative foundation for enhancing the clinical adaptability and efficacy of CLRT.