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Description
Proton therapy treatment planning traditionally assumes a constant Relative Biological Effectiveness (RBE) of 1.1. However, growing evidence shows that proton RBE varies with depth, generally increasing toward the distal region of the Spread-Out Bragg Peak (SOBP). This variation is linked to changes in microscopic energy deposition as protons slow down in tissue, potentially leading to underestimation of the biological dose to healthy tissues if not properly accounted for. Microdosimetry provides an experimental framework to characterize stochastic energy deposition at small scales and to identify physical parameters correlated with biological response.
This work reviews recent microdosimetric studies using two complementary detector systems: a pixelated silicon telescope for microdosimetric measurements and an avalanche-confinement tissue-equivalent proportional counter (TEPC) capable of probing nanometric dimensions.
The silicon telescope consists of micrometric ΔE silicon pixels coupled to a residual-energy E stage. Each pixel functions as an individual microdosimeter, while the E stage provides particle energy information, enabling discrimination and tissue-equivalence corrections. Measurements performed along a 148 MeV modulated proton beam across the SOBP showed increasing high lineal-energy contributions toward the distal region, consistent with proton slowing down. A double-exponential extrapolation method was applied to overcome low-energy detection thresholds. Using Loncol’s biological weighting function, the estimated RBE increased from about 1.0 at beam entrance to approximately 1.25 within the SOBP and up to 1.6 in the distal fall-off region.
Complementary measurements with an avalanche-confinement TEPC at a 62 MeV proton beam line simulated site sizes from 0.5 μm down to 35 nm. Nanometric spectra exhibited marked shape changes and trends in dose-mean lineal energy closely resembling RBE profiles, suggesting a strong link between nanometric energy deposition and biological effectiveness.
Overall, these results confirm the depth dependence of proton RBE and support the development of physically based variable-RBE models grounded in multi-scale microdosimetric measurements.