Methods and models of dose calculation

Abstract

Boron Neutron Capture Therapy is characterized by the interaction of a mixed radiation field with biological tissues. Thermal neutrons are captured in 10B, producing an alpha particle and a lithium ion, and in 14N, producing a proton. These charged particles have moderate to high ionization density values (164, 151 and 44 keV/m, respectively, averaged over track intersection segments with the cell), and short ranges in tissue (9, 5 and 11 μm, respectively). Epithermal neutrons thermalize in tissue mainly through elastic scattering in hydrogen, each losing on average half of its energy per collision and producing a recoil proton that deposits dose. Finally, neutrons are captured in hydrogen producing low-LET radiation: a 2.2 MeV gamma ray. Another source of low-LET radiation is the gamma rays present in the beam or produced in neutron interactions with surrounding materials: this structural component is unavoidable but kept as low as possible during design of the beam and collimator system. Dosimetry is thus characterized by the calculation of the absorbed dose due to the charged particles heavier than electrons (depositing all their energy locally) and the electrons set in motion by the sparsely ionizing photons. With sophisticated transport techniques the different contributions are tracked separately.Biological effects are the result of the action of ionizing radiation in living systems. These effects are directly related to absorbed dose. Therefore, a deep understanding of the spatial scale and geometry of the problem and of the methods to correctly calculate dose is essential to evaluate and optimize the clinical use of BNCT. Absorbed doses can be calculated using different strategies according to the physical situation, for example, assuming charged particle or electronic equilibrium, which makes calculation more straightforward. In preclinical models such as cell cultures or small animals, or in case of patients for dose calculation in skin, the equilibrium hypothesis may not be correct. It is thus necessary to apply more detailed simulations. Section 3 deals with this issue: the need to set-up the correct absorbed dose calculation in the different scenarios. Two approaches have been described: macroscopic and microscopic, separating the issue of dose calculation in different spatial scales and starting from different perspectives: the whole sample/tissue/patient or the single cell.Each of the BNCT radiation components have different biological effects: high and low-LET components produce different ionization density. High-LET radiation, densely ionizing, directly damages the DNA. Low-LET radiation, sparsely ionizing, mainly causes indirect damage by formation of free radicals. The fact that there is not a unique relationship between absorbed dose and induced biological effects, prompts the need for translation of BNCT doses into a reference radiation dose capable of predicting clinical effects. To this end, the clinical experience with photon therapy is used as a reference. Radiobiological experiments with cell cultures or animals irradiated with BNCT, with neutrons only and with photons, provide the fundamental information for models which aim to translate the BNCT absorbed dose into the dose of the reference radiation producing the same effect. With a BNCT dose in photon equivalent units, i.e., with a photon isoeffective dose, medical doctors can prescribe doses and predict the outcome of the therapy according to the clinical experience gained with photon radiotherapy. Different strategies conceived to translate BNCT dose into photon equivalent units are described in Section 4, highlighting the range of validity of the traditional and modern models and the equivalent dose unit recommended by IAEA-ICRU. To deliver a safe and effective BNCT treatment, it is necessary to calculate absorbed dose in the most precise way and to know how to relate this physical quantity to its effects in tumour and in normal tissues. The key ingredients are correct dose calculation, representative radiobiological data, and reliable models to translate mixed-field absorbed dose into photon-equivalent units. Recommendations presented in Sections 3 and 4 of this Chapter are thus particularly important: wrong assumptions in dose calculation and incorrect models may propagate significant errors in the determination of isoeffective dose in patients, leading to a bias in evaluating the relationship between clinical outcome and calculated dose.