Microdosimetry in BNCT

Microdosimetry provides a powerful framework to interpret outcomes in cases where average quantities—such as absorbed dose or linear energy transfer (LET)—fail to adequately explain observed effects. Since its inception, microdosimetry has evolved into a robust discipline, offering biophysical models of radiation action and measurement techniques that are essential for quality control of radiation fields. Differences in acquired or calculated microdosimetric spectra are almost invariably linked to variations in the radiobiological properties of radiation fields. In boron neutron capture therapy (BNCT), the complexity of the radiation field extends beyond the conventional description of a mixed neutron–photon primary field. A fundamental challenge arises from the small number of secondary high-LET particles required to deliver therapeutic doses. For example, 1 Gy of macroscopic boron-10 absorbed dose corresponds to only three or four short-range reactions per cell. These “small numbers,” together with inherent Poisson fluctuations, generate broad energy deposition distributions. Consequently, even under a seemingly uniform KERMA distribution, individual cells may experience very different numbers of hits, and a non-negligible fraction of tumor cells may remain unaffected by boron capture reactions at therapeutic doses. Moreover, the short ranges—comparable to cellular sensitive structures—and the strong variations in energy deposition along particle tracks preclude the use of LET as a reliable descriptor of dose. Additional complexities, such as non-uniform boron distributions, further challenge the use of KERMA-based quantities to explain biological observations. This work reviews the stochastic aspects of BNCT within the conceptual and formal framework of microdosimetry, with particular emphasis on the impact of non-uniform boron microdistributions. Factors such as cell size and shape, as well as relative boron concentrations inside and outside the nucleus, are considered. To accurately predict the average boron doses received by cells, microscopic dose correction factors are required. These can be derived by considering the average three-dimensional model of the sensitive site, obtained through isotropic chord-length distribution sampling on histological images.