Photon minibeam-based LATTICE radiotherapy for small and medium-sized tumors: A dosimetric planning study

Lattice radiotherapy (LRT) is a spatially fractionated technique that delivers three-dimensional high-dose vertices within tumors. However, conventional LRT is constrained by geometric limitations when applied to small and medium-sized tumor volumes, primarily due to the large beam sizes that restrict optimal lattice pattern formation.

This study aims to investigate a photon minibeam-based LATTICE radiotherapy (mini-LRT) approach designed to overcome the geometric limitations of conventional LRT and enable effective spatially fractionated treatment for small and medium-sized tumors adjacent to critical organs.

Three brain cases and three lung cases, with clinical target volumes ranging from 12.34 cc to 40.88 cc, were presented for treatment planning comparison between conventional LRT and mini-LRT. A multi-collimator delivery strategy employing shifted slit patterns was implemented to achieve complementary spatial coverage. Dose calculation and optimization were performed using Monte Carlo simulations and solved via an iterative convex relaxation algorithm. Reference stereotactic body radiation therapy (SBRT) plans were generated for all six cases, and setup-error robustness analysis was performed for two representative cases using nominal and shifted dose-influence matrix scenarios.

Mini-LRT produced denser lattice structures in all cases, generating 5-11 vertices compared to only 1-3 vertices achievable with conventional LRT. Vertex diameters were reduced from 15.0 mm to 3.0-4.0 mm, and vertex-to-vertex distances decreased from 25.0 mm to 12.5 mm. The lattice volume ratio ranged from 0.68% to 1.07% with mini-LRT. Organs at risk (OARs) dose reductions were observed in the evaluated cases, including reduced mean dose to brainstem, heart, and esophageal. Furthermore, mini-LRT achieved a higher peak-to-valley dose ratio (PVDR) ranging from 2.19 to 2.94, compared to 1.75-2.34 for conventional LRT. Reference SBRT plans achieved clinical target volume (CTV) D₉₅ = 50 Gy in all cases but showed elevated D_0.03cc to adjacent OARs in selected anatomically constrained cases. In the representative robustness analysis, worst-case setup-error scenarios showed modest PVDR degradation.

This proof-of-concept dosimetric planning study suggests that photon minibeam-based LATTICE radiotherapy can generate compact spatially fractionated dose distributions in selected small and medium-sized tumors. Compared with conventional LRT, mini-LRT increased vertex density, reduced lattice volume ratio, and improved OAR sparing in the evaluated cases. Additional experimental validation, motion assessment, and larger patient studies are required before clinical translation.