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An interface between the FLUKA transport code and the BIANCA biophysical model to predict the biological effectiveness of hadrontherapy beams
Full text linkIn the context of cell death induced by ionizing radiation, the BIANCA biophysical model was used to produce tables of biological effectiveness, in terms of α and β parameters typical of the linear quadratic model for cell survival curves; the tables were produced for irradiation by protons, helium ions and carbon ions over a wide energy range and for two cell lines of different radiosensitivity. By using these values, the predictions of BIANCA were compared with experimental data of RBE, and good agreement was found. After this validation step, the FLUKA radiation transport code, which can produce physical dose profiles for typical hadrontherapy beams, could read the α and β tables; thanks to such an interface between FLUKA and BIANCA, probabilities of cell death were predicted along depth-dose profiles. An example of a carbon spread out Bragg peak is shown, highlighting the differences in the biological response of different cell lines and the possible importance of using more than one cell line in the context of treatment plan optimization
EP-1606: Calculating ion-induced cell death and chromosome damage by the BIANCA biophysical model
No full textEffects of ionizing radiation in biomolecules, cells and tissue/organs: basic mechanisms and applications for cancer therapy, medical imaging and radiation protection
No full textPredicting biological effects along hadrontherapy dose profiles by the BIANCA biophysical model
No full textThe BIANCA biophysical model of cell death and chromosome aberrations was further refined and applied to predict the biological effectiveness along Spread-Out Bragg Peaks used in hadrontherapy. The simulation outcomes were compared with in vitro survival data on protons, He-ions and C-ions over a wide LET range, and the particle- and LET-dependence of the DNA Cluster Lesions (CLs) yields used as input parameters was investigated. For each particle type, the CL yield was found to increase with LET in a linear-quadratic fashion; fitting the CL yields allowed to predict cell death and chromosome aberrations in principle at any depth along a longitudinal proton dose profile used at CNAO. A clear increase in effectiveness was found in the SOBP distal region, supporting the idea that, in some cases, the constant proton RBE usually applied in clinics may be a sub-optimal solution
Modelling the induction of cell death and chromosome damage by therapeutic protons
No full textA two-parameter biophysical model cal led BIANCA (BIophysical ANalysis of Cell death and chromosome Aberrations), which assumes a pivotal role for DNA cluster damage and for “lethal” chromosome aberrations, was applied to calculate cell death and chromosome aberrations for normal and radio-resistant cells along a 62-MeV eye melanoma proton beam. The yield of DNA “Cluster Lesions” and the probability for a chromosome fragment of not being rejoined with any partne r were adjustable parameters. In line with other works, the beam effectiveness at inducing both biological endpoints was found to increase with increasing depth, and high levels of damage were found also beyond the dose fall-off, due to the higher biological effectiveness of low-energy protons. This implies that assuming a constant RBE along the whole SOBP, as is currently done in clinical practice, may be sub-optimal, also implying a possible underestimation of normal tissue damage. Furthermore, the calculations suggested that for higher fractional doses, like those delivered in hypo-fractionation regimes, the relative increase in effectiven ess along the SOBP may be less pronounced than for lower fractional doses
Radiation Damage in Biomolecules and Cells 2.0
No full textIt is well known that ionizing radiation, when it hits living cells, causes a plethora of different damage types at different levels [...
First benchmarking of the BIANCA model for cell survival prediction in a clinical hadron therapy scenario
No full textIn the framework of RBE modelling for hadron therapy, the BIANCA biophysical model was extended to O-ions and was used to construct a radiobiological database describing the survival of V79 cells as a function of ion type (1 ⩽ Z ⩽ 8) and energy. This database allowed performing RBE predictions in very good agreement with experimental data. A method was then developed to construct analogous databases for different cell lines, starting from the V79 database as a reference. Following interface to the FLUKA Monte Carlo radiation transport code, BIANCA was then applied for the first time to predict cell survival in a typical patient treatment scenario, consisting of two opposing fields of range-equivalent protons or C-ions. The model predictions were found to be in good agreement with CHO cell survival data obtained at the Heidelberg ion-beam therapy (HIT) centre, as well as predictions performed by the local effect model (version LEM IV). This work shows that BIANCA can be used to predict cell survival and RBE not only for V79 and AG01522 cells, as shown previously, but also, in principle, for any cell line of interest. Furthermore, following interface to a transport code like FLUKA, BIANCA can provide predictions of 3D biological dose distributions for hadron therapy treatments, thus laying the foundations for future applications in clinics
Biophysical modelling of proximity effects in chromosome aberration production
Full text linkAlthough two chromosome breaks induced in proximity are known to have a higher probability of being (mis-)rejoined, several aspects of these “proximity effects” are still unclear. Herein, proximity effects in human lymphocytes and fibroblasts were investigated by the BIANCA biophysical model, describing the dependence of the rejoining probability on the break initial distance, r, either by an exponential function of the form exp(-r/r0), or by a Gaussian function of the form exp(-r2/22). The characteristic distance (r0 or was an adjustable parameter; the only other parameter was the yield of DNA “Cluster Lesions” (CLs), where a CL is defined as a critical damage producing two independent chromosome fragments. The comparison of the simulation outcomes with published experimental and theoretical works showed that an exponential function may describe proximity effects in both considered cell types, and possibly other cells. Since this exponential behavior has been found to be consistent with confined diffusion of break ends, this also suggests that, at the relatively short times required for chromosome aberration production, (confined) diffusion is preferable to other mechanisms. Furthermore, the results suggested that the ratio of dicentrics to centric rings (“F-ratio”) may be a better high-LET fingerprint in lymphocytes, whereas the ratio of acentric to centric rings (“G-ratio”) may be a better one in fibroblasts
A radiobiological database produced by the BIANCA model to predict the biological effectiveness of hadrontherapy beams
No full textThe BIANCA biophysical model was used to simulate cell survival curves by protons, He- and C-ions over a wide LET range and for several doses. Each simulated curve was then fitted by a linear-quadratic exponential function of the form S(D)=exp(-αD-βD2). This allowed to produce an almost continuous set of α and β values as a function of LET for each ion type. The same procedure was repeated for chromosome aberration dose-response curves, using the following fitting function: A(D)=αAD+βAD2. In the context of hadrontherapy, the tables of α and β (as well as αA and βA) were read by the FLUKA radiation transport code, which provides the necessary information about particle type, LET and absorbed dose, thus allowing fast computing of biological outputs in every position of a therapeutic dose profile. Some examples of the variation of the two considered biological quantities, i.e. probability of cell survival and chromosome aberrations, along Spread Out Bragg Peaks in water are reported as preliminary results
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