An extended photon isoeffective dose model accounting for the energy-dependent effectiveness of secondary charged particles in BNCT

Abstract

Background: The absorbed dose in Boron Neutron Capture Therapy (BNCT) arises from various radiation components, each contributing differently to the overall biological effect. These effects depend not only on the absorbed dose but also on the type and energy of the involved secondary charged particles. Current dosimetric models convert absorbed dose into an equivalent photon dose using radiation-specific weighting factors that account for some differences in radiation type. However, these models generally neglect the energy dependence of biological effectiveness.

Purpose: To evaluate the relevance of incorporating the energy dependence of secondary charged particles into BNCT dosimetry, and to assess its impact on dose calculations and clinical outcome estimations.

Methods: The photon isoeffective dose formalism was extended by reformulating the mathematical model for $D_{IsoE}$ in terms of the secondary particle fields rather than dose components in BNCT. Tissue-specific radiobiological (RB) parameters $\alpha$ and $\beta$ were introduced as functions of Linear Energy Transfer (LET), as predicted by the BIANCA biophysical model for normal skin and head and neck tumor tissues. Recoil proton spectra were analyzed at superficial and deep locations in tissues to evaluate their effectiveness relative to 583 keV protons from the ${}^{14}N$ (n,p) ${}^{14}C$ reaction. Four approaches to $D_{IsoE}$ , with varying levels of detail regarding energy and radiation fields representation, were evaluated across three scenarios. The analysis moved from a simplified geometry using a cylindrical phantom irradiated with epithermal neutrons, to progressively more realistic clinical scenarios, including a head and neck cancer treatment planning case and a retrospective study of a cutaneous melanoma case treated with BNCT at the RA-6 reactor in Argentina.

Results: Recoil protons were found to have lower ${\mathrm{RBE}}_{1\%}$ than 583 keV protons from ${}^{14}N$ (n,p) ${}^{14}C$ reactions, indicating that assuming equal effectiveness leads to overestimated doses in photon-equivalent units. In the phantom, detailed LET-based modeling proved essential in low-to-moderate boron concentration or superficial tissue scenarios, where simplified models showed deviations up to 30%. In contrast, boron-rich or deep tissue conditions tolerated simplifications with minimal loss of accuracy. In the head and neck case, simplified models led to skin overdoses up to 13%, increasing NTCP from negligible ( $\sim 0$ ) to high values ( $\sim 0.5$ ), thus raising the potential radiotoxicity risk. An apparent gain in TCP resulted from overestimating the required treatment time due to oversimplified modeling. In the retrospective melanoma case irradiated with the RA-6 mixed thermal-epithermal beam, simplified models underestimated the skin dose by 8% to 12%, potentially compromising dose-response interpretations.

Conclusions: Beyond treatment planning, accurate dose modeling is also key for outcome assessment and meaningful comparisons with photon radiotherapy. Incorporating detailed LET-dependent RB modeling is especially important in scenarios involving low-to-moderate boron concentration levels or superficial tissues, where recoil protons dominate the dose composition. In contrast, simplified models may be acceptable in boron-rich, high-LET contexts, particularly when constrained by limited radiobiological data or computational resources. These findings support the development of a flexible photon isoeffective dose formalism that can evolve alongside advances in BNCT technologies and RB data.

Keywords: BIANCA; BNCT; photon isoeffective dose.