Decrease In Relative Biological Effectiveness Research Articles

Radiobiological effects of the interruption time with Monte Carlo Simulation on multiple fields in photon beams.

PurposeThe interruption time is the irradiation interruption that occurs at sites and operations such as the gantry, collimator, couch rotation, and patient setup within the field in radiotherapy. However, the radiobiological effect of prolonging the treatment time by the interruption time for tumor cells is little evaluated. We investigated the effect of the interruption time on the radiobiological effectiveness with photon beams based on a modified microdosimetric kinetic (mMK) model.MethodsThe dose‐mean lineal energy yD (keV/µm) of 6‐MV photon beams was calculated by the particle and heavy ion transport system (PHITS). We set the absorbed dose to 2 or 8 Gy, and the interruption time (τ) was set to 1, 3, 5, 10, 30, and 60 min. The biological parameters such as α0, β0, and DNA repair constant rate (a + c) values were acquired from a human non‐small‐cell lung cancer cell line (NCI‐H460) for the mMK model. We used two‐field and four‐field irradiation with a constant dose rate (3 Gy/min); the photon beams were paused for interruption time τ. We calculated the relative biological effectiveness (RBE) to evaluate the interruption time's effect compared with no interrupted as a reference.ResultsThe yD of 6‐MV photon beams was 2.32 (keV/µm), and there was little effect by changing the water depth (standard deviation was 0.01). The RBE with four‐field irradiation for 8 Gy was decreased to 0.997, 0.975, 0.900, and 0.836 τ = 1, 10, 30, 60 min, respectively. In addition, the RBE was affected by the repair constant rate (a + c) value, the greater the decrease in RBE with the longer the interruption time when the (a + c) value was large.ConclusionThe ~10‐min interruption of 6‐MV photon beams did not significantly impact the radiobiological effectiveness, since the RBE decrease was <3%. Nevertheless, the RBE's effect on tumor cells was decreased about 30% by increasing the 60 min interruption time at 8 Gy with four‐field irradiation. It is thus necessary to make the interruption time as short as possible.

RBE variation in prostate carcinoma cells in active scanning proton beams: In-vitro measurements in comparison with phenomenological models.

In-vitro radiobiological studies are essential for modelling the relative biological effectiveness (RBE) in proton therapy. The purpose of this study was to experimentally determine the RBE values in proton beams along the beam path for human prostate carcinoma cells (Du-145). RBE-dose and RBE-LETd (dose-averaged linear energy transfer) dependencies were investigated and three phenomenological RBE models, i.e. McNamara, Rørvik and Wilkens were benchmarked for this cell line. Cells were placed at multiple positions along the beam path, employing an in-house developed solid phantom. The experimental setup reflected the clinical prostate treatment scenario in terms of field size, depth, and required proton energies (127.2-180.1MeV) and the physical doses from 0.5 to 6Gy were delivered. The reference irradiation was performed with 200kV X-ray beams. Respective (α/β) values were determined using the linear quadratic model and LETd was derived from the treatment planning system at the exact location of cells. Independent of the cell survival level, all experimental RBE values were consistently higher in the target than the generic clinical RBE value of 1.1; with the lowest RBE value of 1.28 obtained at the beginning of the SOBP. A systematic RBE decrease with increasing dose was observed for the investigated dose range. The RBE values from all three applied models were considerably smaller than the experimental values. A clear increase of experimental RBE values with LETd parameter suggests that proton LET must be taken into consideration for this low (α/β) tissue.

A Monte Carlo approach to the microdosimetric kinetic model to account for dose rate time structure effects in ion beam therapy with application in treatment planning simulations.

Advanced ion beam therapeutic techniques, such as hypofractionation, respiratory gating, or laser-based pulsed beams, have dose rate time structures which are substantially different from those found in conventional approaches. The biological impact of the time structure is mediated through the β parameter in the linear quadratic (LQ) model. The aim of this study was to assess the impact of changes in the value of the β parameter on the treatment outcomes, also accounting for noninstantaneous intrafraction dose delivery or fractionation and comparing the effects of using different primary ions. An original formulation of the microdosimetric kinetic model (MKM) is used (named MCt-MKM), in which a Monte Carlo (MC) approach was introduced to account for the stochastic spatio-temporal correlations characteristic of the irradiations and the cellular repair kinetics. A modified version of the kinetic equations, validated on experimental cell survival invitro data, was also introduced. The model, trained on the HSG cells, was used to evaluate the relative biological effectiveness (RBE) for treatments with acute and protracted fractions. Exemplary cases of prostate cancer irradiated with different ion beams were evaluated to assess the impact of the temporal effects. The LQ parameters for a range of cell lines (V79, HSG, and T1) and ion species (H, He, C, and Ne) were evaluated and compared with the experimental data available in the literature, with good results. Notably, in contrast to the original MKM formulation, the MCt-MKM explicitly predicts an ion and LET-dependent β compatible with observations. The data from a split-dose experiment were used to experimentally determine the value of the parameter related to the cellular repair kinetics. Concerning the clinical case considered, an RBE decrease was observed, depending on the dose, ion, and LET, exceeding up to 3% of the acute value in the case of a protraction in the delivery of 10min. The intercomparison between different ions shows that the clinical optimality is strongly dependent on a complex interplay between the different physical and biological quantities considered. The present study provides a framework for exploiting the temporal effects of dose delivery. The results show the possibility of optimizing the treatment outcomes accounting for the correlation between the specific dose rate time structure and the spatial characteristic of the LET distribution, depending on the ion type used.

A phenomenological relative biological effectiveness (RBE) model for proton therapy based on all published in vitro cell survival data

Proton therapy treatments are currently planned and delivered using the assumption that the proton relative biological effectiveness (RBE) relative to photons is 1.1. This assumption ignores strong experimental evidence that suggests the RBE varies along the treatment field, i.e. with linear energy transfer (LET) and with tissue type. A recent review study collected over 70 experimental reports on proton RBE, providing a comprehensive dataset for predicting RBE for cell survival. Using this dataset we developed a model to predict proton RBE based on dose, dose average LET (LETd) and the ratio of the linear-quadratic model parameters for the reference radiation (α/β)x, as the tissue specific parameter.The proposed RBE model is based on the linear quadratic model and was derived from a nonlinear regression fit to 287 experimental data points. The proposed model predicts that the RBE increases with increasing LETd and decreases with increasing (α/β)x. This agrees with previous theoretical predictions on the relationship between RBE, LETd and (α/β)x. The model additionally predicts a decrease in RBE with increasing dose and shows a relationship between both α and β with LETd. Our proposed phenomenological RBE model is derived using the most comprehensive collection of proton RBE experimental data to date. Previously published phenomenological models, based on a limited data set, may have to be revised.

SU‐F‐BRD‐13: A Phenomenological Relative Biological Effectiveness (RBE) Model for Proton Therapy Based On All Published in Vitro Cell Survival Data

Purpose:Proton therapy treatments are currently planned and delivered using the assumption that the proton relative biological effectiveness (RBE) relative to photons is 1.1. This assumption ignores strong experimental evidence that suggests the RBE varies. A recent review study (Paganetti 2014), collected over 72 experimental reports on proton RBE, providing a comprehensive dataset for predicting proton RBE. Using this dataset we develop a model to predict RBE based on dose, linear energy transfer (LET) and the tissue specific parameter (α/β)x.Methods:The relationship of the RBE on dose, dose average LET (LETd) and (α/β)x was explored using 290 experimental data points. The RBE was calculated for each experimental point for doses ranging from 1 to 10 Gy. An RBE model, based on the linear‐quadratic model, was derived using a nonlinear regression fit to the experimental data.Results:The proposed RBE model predicts that the RBE increases with LET and decreases with (α/β)x. The model additionally predicts a decrease in RBE with increasing dose for low (α/β)x values (&lt; 3 Gy). However the model predicts an increase in RBE with increasing dose for large (α/β)x (&gt; 4 Gy). Previous phenomenological models were based on a small subset of experimental data and deviate significantly from our findings.Conclusion:The proposed RBE model is derived using the most comprehensive collection of proton RBE experimental data to date. The model agrees with previous theoretical predictions on the relationship between RBE, LETd and (α/β)x and also makes predictions on the relationship between RBE and dose. The proposed model shows a relationship between α and LETd but no significant relationship between β and LETd. Previously published phenomenological models based on a limited data set might have to be revised.

SU‐E‐T‐581: On the Value of LET as a Radiation Quality Descriptor for RBE

Purpose:To investigate the relationship between linear energy transfer (LET) and relative biological effectiveness (RBE) for protons and light ions, and the corresponding role of LET as a descriptor of radiation quality of hadron therapy.Methods:Monte Carlo (MC) proton and light ion (He, Li, C) tracks with LET &lt; 30 eV nm‐1 were generated in an event‐by‐event mode. They were overlaid on a cell nucleus model containing 6×109 nucleotide base pairs using an isotropic irradiation procedure that provides electronic equilibrium. Strand breaks (sbs) were scored in the DNA sugar‐phosphate groups and further sub‐classified into single or double sbs (ssbs or dsbs). Distributions of ssbs and dsbs for 2 Gy fractions were calculated to estimate RBE for the induction of initial dsbs with reference to 60Co. Additionally, sbs were classified based on their complexity (i.e. the number of sbs in each cluster).Results:An increase in LET for light ions of the same atomic number or a decrease in atomic number for ions of the same LET resulted in a lower kinetic energy of emitted secondary electrons. The clustering of DNA damage was more pronounced as reflected by the increase in proton RBE from ∼ 1.75 to 4 for LET values of 7 to 28 eV nm‐1. A significant RBE decrease between protons, He, Li and C ions of the same LET was also noticed as function of the atomic number. Significant differences in ssbs and dsbs complexities were also seen for particles with the same LET, potentially supporting a clustering‐based radiation quality descriptor.Conclusion:The LET‐RBE relationships were simulated for proton and light ions and exhibited expected trends, including different RBEs for particles with the same LET but different atomic numbers. A complexity based radiation quality descriptor may allow better differentiation of RBE between radiation fields of similar LET.We would like to acknowledge support from the Fonds de recherche du Quebec Sante (FRQS), from the CREATE Medical Physics Research Training Network grant (number 432290) of NSERC, support from NSERC under grants RGPIN 397711‐11 and RGPIN‐2014‐06475 and support from CIHR under grants MOP‐114910, MOP‐136774 and MOP‐102550.

Effectiveness of fission neutrons versus gamma radiation for inducing somatic mutations in presoaked seeds of maize

This study was conducted to determine the effectiveness of fission neutrons versus 60Co γ-radiation for inducing somatic mutations in germinating maize embryos. Seeds heterozygous for the yg 2 locus were soaked for 96 h at 20°C prior to irradiation with various doses of either 60Co γ-radiation or fission neutrons. Mitotic index and cytophotometric studies of the shoot (excluding the coleoptile and first 3 leaves) revealed that 33.2, 16.4, 39.5, and 6.1% of the cells were in G 1, S, G 2, and M stages of the cell cycle, respectively. The frequency of yg 2 sectors, as scored in leaves 4 and 5, increased with increasing dose of both radiations. Mutagenic effectiveness, as measured by sectors per rad, increased with increasing dose of γ-radiation but decreased with increasing dose of fission neutrons. This phenomenon resulted in a decrease in relative biological effectiveness (RBE) of fission neutrons with increasing sector frequency. The high mutation frequency, especially at low neutron doses, indicates a potential value of the test system for monitoring genetic effects of low radiation doses and other mutagenic agents.