Cell survival comparison of proton, helium, and carbon ion interlaced minibeams in water phantom simulations

Radiotherapy is a key in cancer treatment, with particle therapy providing better tumor targeting and sparing healthy tissues. Particle Minibeam Radiotherapy (PMBT) integrates the advantages of spatial fractionation into particle radiotherapy by employing submillimeter-sized beams, thus improving the therapeutic ratio by reducing side effects. Former simulation studies have shown that interlaced proton minibeams from opposing directions in Single Energy Distal-Edge (1E) mode better protect normal tissue compared to the conventional spread-out Bragg peak (SOBP) mode.

Helium and carbon ion minibeams may be an alternative to enhance the protection of healthy tissue, especially in deeper regions, due to less angular spread. This in silico study evaluates the potential for normal tissue sparing while preserving the same cell survival in the tumor in case of proton, helium and carbon minibeams in 1E mode.

Simulations were performed using TOPAS (Tool for Particle Simulation) by applying single-energy interlaced minibeams (beam size σ = 0.2 mm) from two opposing directions in a 250 mm-thick water phantom, assuming a 50 mm-thick tumor at the center. For the comparative analysis, cell survival rates were calculated across the whole phantom using the saturation-corrected Microdosimetric Kinetic Model (MKM-z*) implemented through MONAS (Microdosimetry-based modeling for RBE assessment). As a dose constraint, the minimum dose in the tumor was selected to ensure a maximum of 10% cell survival within the tumor. The sparing of healthy tissues was estimated using the Linear Quadratic (LQ) model, considering variable Relative Biological Effectiveness (RBE) via MONAS.

The findings show that helium and carbon minibeams offer enhanced protection of the normal tissues only ∼ 1-2 mm close to the tumor borders, while protons achieve an overall better sparing in the rest of the phantom for the 1E mode, when looking purely at the cell survival.

Although protons achieved the highest mean cell survival in normal tissue, the actual sparing effect is strongly influenced by beam size and valley dose, with helium and carbon ions showing enhanced confinement of damage near the tumor edge. These findings highlight the need for the implementation of more anatomically accurate phantoms with more concise biological data as a basis.