A Mathematical Radiobiological Model (MRM) to Predict Complex DNA Damage and Cell Survival for Ionizing Particle Radiations of Varying Quality

Predicting radiobiological effects is important in different areas of basic or clinical applications using ionizing radiation (IR); for example, towards optimizing radiation protection or radiation therapy protocols. In this case, we utilized as a basis the ‘MultiScale Approach (MSA)’ model and developed an integrated mathematical radiobiological model (MRM) with several modifications and improvements. Based on this new adaptation of the MSA model, we have predicted cell-specific levels of initial complex DNA damage and cell survival for irradiation with 11Β, 12C, 14Ν, 16Ο, 20Νe, 40Αr, 28Si and 56Fe ions by using only three input parameters (particle’s LET and two cell-specific parameters: the cross sectional area of each cell nucleus and its genome size). The model-predicted survival curves are in good agreement with the experimental ones. The particle Relative Biological Effectiveness (RBE) and Oxygen Enhancement Ratio (OER) are also calculated in a very satisfactory way. The proposed integrated MRM model (within current limitations) can be a useful tool for the assessment of radiation biological damage for ions used in hadron-beam radiation therapy or radiation protection purposes.

Further development of spinal cord retreatment dose estimation: including radiotherapy with protons and light ions

A new graphical user interface (GUI) was developed to aid in the assessment of changes in the radiation tolerance of spinal cord/similar central nervous system tissues with time between two treatment courses. The GUI allows any combination of photons, protons (or ions) to be used as the initial, or retreatment, course. Allowances for clinical circumstances, of reduced tolerance, can also be made. The radiobiological model was published previously and has been incorporated with additional checks and safety features, to be as conservative as possible. The proton option includes use of a fixed RBE of 1.1 (set as the default), or a variable RBE, the latter depending on the proton linear energy transfer (LET) for organs at risk. This second LET-based approach can also be used for ions, by changing the LET parameters. GUI screenshots are used to show the input and output parameters for clinical situations used in worked examples from previous publications, where the proton and ion treatments required additional ‘longhand’ calculations. The results from the GUI are in agreement with previously published calculations, but the results are now rapidly available without tedious and error-prone manual computations. The software outputs provide a maximum dose limit boundary, which should not be exceeded. Clinicians may also choose a lower number of treatment fractions, whilst using the same dose per fraction (or conversely a lower dose per fraction but with the same number of fractions) in order to achieve the intended clinical benefit. The new GUI will allow rational estimations of time related radiation tolerance changes in the spinal cord and similar central nervous tissues (optic chiasm, brainstem), which can be used to guide the choice of retreatment dose fractionation schedules.

Mechanistic Modeling of the Relative Biological Effectiveness of Boron Neutron Capture Therapy

Accurate dosimetry and determination of the biological effectiveness of boron neutron capture therapy (BNCT) is challenging because of the mix of different types and energies of radiation at the cellular and subcellular levels. In this paper, we present a computational, multiscale system of models to better assess the relative biological effectiveness (RBE) and compound biological effectiveness (CBE) of several neutron sources as applied to BNCT using boronophenylalanine (BPA) and a potential monoclonal antibody (mAb) that targets HER-2-positive cells with Trastuzumab. The multiscale model is tested against published in vitro and in vivo measurements of cell survival with and without boron. The combined dosimetric and radiobiological model includes an analytical formulation that accounts for the type of neutron source, the tissue- or cancer-specific dose–response characteristics, and the microdistribution of boron. Tests of the model against results from published experiments with and without boron show good agreement between modeled and experimentally determined cell survival for neutrons alone and in combination with boron. The system of models developed in this work is potentially useful as an aid for the optimization and individualization of BNCT for HER-2-positive cancers, as well as other cancers, that can be targeted with mAb or a conventional BPA compound.