Are we overestimating proton minibeam therapy effectiveness through physical dose metrics?

Purpose: The conventional implementation of proton spatially fractionated radiotherapy (SFRT) uses physical collimators with millimeter apertures to generate minibeams, creating alternating regions of high-dose peaks and low-dose valleys. Current evaluation of SFRT effectiveness predominantly relies on physical quantities, particularly the peak-to-valley dose ratio (PVDR). While high PVDR and low valley doses have been correlated with improved normal tissue sparing, this physical metric-based approach provides an incomplete picture of the treatment's biological impact. In this work, we aim to quantify biological dose for proton minibeams created using physical collimators and critically evaluate the adequacy of physical (PVDR Methods: Monte Carlo simulations using TOPAS were performed to model proton minibeam arrangements with 70 and 150 MeV monoenergetic beams, as well as a Spread-Out Bragg Peak (SOBP) configuration to represent clinically relevant dose delivery. We investigated the impact of multiple collimator configurations on PVDR: collimator thickness (6.35 cm), hole diameter (1-3 mm), center-to-center (c-t-c) distances (2, 3, 4 mm for 1 mm hole, 4, 6, 8 mm for 2 mm hole) and air gaps (5, 10, and 15 cm) between the collimator and water phantom. For each configuration, 3D dose and dose-averaged LET (LET Results: Our comprehensive analysis revealed significant differences between physical and biological PVDR metrics across various configurations. For both 70 and 150 MeV beams, PVDR Conclusions: The significant variations between PVDR