Relative Biological Effectiveness Data Research Articles

Relative biological effectiveness of oxygen ion beams in the rat spinal cord: Dependence on linear energy transfer and dose and comparison with model predictions

Background and purposeIon beams exhibit an increased relative biological effectiveness (RBE) with respect to photons. This study determined the RBE of oxygen ion beams as a function of linear energy transfer (LET) and dose in the rat spinal cord. Materials and methodsThe spinal cord of rats was irradiated at four different positions of a 6 cm spread-out Bragg-peak (LET: 26, 66, 98 and 141 keV/µm) using increasing levels of single and split oxygen ion doses. Dose-response curves were established for the endpoint paresis grade II and based on ED50 (dose at 50 % effect probability), the RBE was determined and compared to model predictions. ResultsWhen LET increased from 26 to 98 keV/µm, ED50 decreased from 17.2 ± 0.3 Gy to 13.5 ± 0.4 Gy for single and from 21.7 ± 0.4 Gy to 15.5 ± 0.5 Gy for split doses, however, at 141 keV/µm, ED50 rose again to 15.8 ± 0.4 Gy and 17.2 ± 0.4 Gy, respectively. As a result, the RBE increased from 1.43 ± 0.05 to 1.82 ± 0.08 (single dose) and from 1.58 ± 0.04 to 2.21 ± 0.08 (split dose), respectively, before declining again to 1.56 ± 0.06 for single and 1.99 ± 0.06 for split doses at the highest LET. Deviations from RBE-predictions were model-dependent. ConclusionThis study established first RBE data for the late reacting central nervous system after single and split doses of oxygen ions. The data was used to validate the RBE-dependence on LET and dose of three RBE-models. This study extends the existing data base for protons, helium and carbon ions and provides important information for future patient treatments with oxygen ions.

Microdosimetry of a 62-MeV clinical proton beam with five detectors.

In proton therapy, most treatment planning systems (TPS) use a fixed relative biological effectiveness (RBE) of 1.1 all along the depth-dose profile. Innovative TPS are now investigated considering the variability of RBE with radiation quality. New TPS need an experimental verification in the quality assurance (QA) routine in clinics, but RBE data are usually obtained with radiobiological measurements that are time consuming and not suitable for daily QA. Microdosimetry is a useful tool based on physical measurements which can monitor the radiation quality. Several microdosimeters are available in different research institutions, which could potentially be used for the QA in TPS. In this study, the response functions of five detectors in the same 62-MeV proton Spread Out Bragg Peak is compared in terms of spectral distributions and their average values and microdosimetric RBE. Their different response function has been commented and must be considered in the clinical practice.

The Mayo Clinic Florida microdosimetric kinetic model of clonogenic survival: formalism and first benchmark against in vitro and in silico data

Objective. To develop a new model (Mayo Clinic Florida microdosimetric kinetic model, MCF MKM) capable of accurately describing the in vitro clonogenic survival at low and high linear energy transfer (LET) using single-event microdosimetric spectra in a single target. Methodology. The MCF MKM is based on the ‘post-processing average’ implementation of the non-Poisson microdosimetric kinetic model and includes a novel expression to compute the particle-specific quadratic-dependence of the cell survival with respect to dose (β of the linear-quadratic model). A new methodology to a priori calculate the mean radius of the MCF MKM subnuclear domains is also introduced. Lineal energy spectra were simulated with the Particle and Heavy Ion Transport code System (PHITS) for 1H, 4He, 12C, 20Ne, 40Ar, 56Fe, and 132Xe ions and used in combination with the MCF MKM to calculate the ion-specific LET-dependence of the relative biological effectiveness (RBE) for Chinese hamster lung fibroblasts (V79 cell line) and human salivary gland tumor cells (HSG cell line). The results were compared with in vitro data from the Particle Irradiation Data Ensemble (PIDE) and in silico results of different models. The possibility of performing experiment-specific predictions to explain the scatter in the in vitro RBE data was also investigated. Finally, a sensitivity analysis on the model parameters is also included. Main results. The RBE values predicted with the MCF MKM were found to be in good agreement with the in vitro data for all tested conditions. Though all MCF MKM model parameters were determined a priori, the accuracy of the MCF MKM was found to be comparable or superior to that of other models. The model parameters determined a priori were in good agreement with the ones obtained by fitting all available in vitro data. Significance. The MCF MKM will be considered for implementation in cancer radiotherapy treatment planning with accelerated ions.

An ion-independent phenomenological relative biological effectiveness (RBE) model for proton therapy

BackgroundA relative biological effectiveness (RBE) of 1.1 is used for proton therapy though clinical evidence of varying RBE was raised. Clinical studies on RBE variability have been conducted for decades for carbon radiation, which could advance the understanding of the clinical proton RBE given an ion-independent RBE model. In this work, such a model, linear and simple, using the beam quantity Q = Z2/E (Z = ion charge, E = kinetic energy per nucleon) was tested and compared to the commonly used, proton-specific and linear energy transfer (LET) based Wedenberg RBE model. Material and methodsThe Wedenberg and Q models, both predicting RBEmax and RBEmin (i.e., RBE at vanishing and very high dose, respectively), are compared in terms of ion-dependence and prediction power. An experimental in-vitro data ensemble covering 115 publications for various ions was used as dataset. ResultsThe model parameter of the Q model was observed to be similar for different ions (in contrast to LET). The Q model was trained without any prior knowledge of proton data. For proton RBE, the differences between experimental data and corresponding predictions of the Wedenberg or the Q model were highly comparable. ConclusionsA simple linear RBE model using Q instead of LET was proposed and tested to be able to predict proton RBE using model parameter trained based on only RBE data of other particles in a clinical proton energy range for a large in-vitro dataset. Adding (pre)clinical knowledge from carbon ion therapy may, therefore, reduce the dominating biological uncertainty in proton RBE modelling. This would translate in reduced RBE related uncertainty in proton therapy treatment planning.

Microdosimetric characterization of a clinical proton therapy beam: comparison between simulated lineal energy distributions in spherical water targets and experimental measurements with a silicon detector

Objective. Treatment planning based on computer simulations was proposed to account for the increased relative biological effectiveness (RBE) of proton radiotherapy beams near to the edges of the irradiated volume. Since silicon detectors could be used to validate the results of these simulations, it is important to explore the limitations of this comparison. Approach. Microdosimetric measurements with a MicroPlus Bridge V2 silicon detector (thickness = 10 μm) were performed along the Bragg peak of a clinical proton beam. The lineal energy distributions, the dose-mean values, and the RBE calculated with a biological weighting function were compared with PHITS simulations (microdosimetric target = 1 μm water sphere), and published clonogenic survival in vitro RBE data for the V79 cell line. The effect of the silicon-to-water conversion was also investigated by comparing three different methodologies (conversion based on a single value, novel bin-to-bin conversions based on SRIM and PSTAR). Main results. Mainly due to differences in the microdosimetric targets, the experimental dose-mean lineal energy and RBE values at the distal edge were respectively up to 53% and 28% lower than the simulated ones. Furthermore, the methodology chosen for the silicon-to-water conversion was proven to affect the dose-mean lineal energy and the RBE10 up to 32% and 11% respectively. The best methodology to compensate for this underestimation was the bin-to-bin silicon-to-water conversion based on PSTAR. Significance. This work represents the first comparison between PHITS-simulated lineal energy distributions in water targets and corresponding experimental spectra measured with silicon detectors. Furthermore, the effect of the silicon-to-water conversion on the RBE was explored for the first time. The proposed methodology based on the PSTAR bin-to-bin conversion appears to provide superior results with respect to commonly used single scaling factors and is recommended for future studies.

Biological Impact of Target Fragments on Proton Treatment Plans: An Analysis Based on the Current Cross-Section Data and a Full Mixed Field Approach.

Simple SummaryProton therapy is now an established external radiotherapy modality for cancer treatment. Clinical routine currently neglects the radiobiological impact of nuclear target fragments even if experimental evidences show a significant enhancement in cell-killing effect due to secondary particles. This paper quantifies the contribution of proton target fragments of different charge in different irradiation scenarios and compares the computationally predicted corrections to the overall biological dose with experimental data.Clinical routine in proton therapy currently neglects the radiobiological impact of nuclear target fragments generated by proton beams. This is partially due to the difficult characterization of the irradiation field. The detection of low energetic fragments, secondary protons and fragments, is in fact challenging due to their very short range. However, considering their low residual energy and therefore high LET, the possible contribution of such heavy particles to the overall biological effect could be not negligible. In this context, we performed a systematic analysis aimed at an explicit assessment of the RBE (relative biological effectiveness, i.e., the ratio of photon to proton physical dose needed to achieve the same biological effect) contribution of target fragments in the biological dose calculations of proton fields. The TOPAS Monte Carlo code has been used to characterize the radiation field, i.e., for the scoring of primary protons and fragments in an exemplary water target. TRiP98, in combination with LEM IV RBE tables, was then employed to evaluate the RBE with a mixed field approach accounting for fragments’ contributions. The results were compared with that obtained by considering only primary protons for the pristine beam and spread out Bragg peak (SOBP) irradiations, in order to estimate the relative weight of target fragments to the overall RBE. A sensitivity analysis of the secondary particles production cross-sections to the biological dose has been also carried out in this study. Finally, our modeling approach was applied to the analysis of a selection of cell survival and RBE data extracted from published in vitro studies. Our results indicate that, for high energy proton beams, the main contribution to the biological effect due to the secondary particles can be attributed to secondary protons, while the contribution of heavier fragments is mainly due to helium. The impact of target fragments on the biological dose is maximized in the entrance channels and for small values. When applied to the description of survival data, model predictions including all fragments allowed better agreement to experimental data at high energies, while a minor effect was observed in the peak region. An improved description was also obtained when including the fragments’ contribution to describe RBE data. Overall, this analysis indicates that a minor contribution can be expected to the overall RBE resulting from target fragments. However, considering the fragmentation effects can improve the agreement with experimental data for high energy proton beams.

Fractionated carbon ion irradiations of the rat spinal cord: comparison of the relative biological effectiveness with predictions of the local effect model

BackgroundTo determine the relative biological effectiveness (RBE) and α/β-values after fractionated carbon ion irradiations of the rat spinal cord with varying linear energy transfer (LET) to benchmark RBE-model calculations.Material and methodsThe rat spinal cord was irradiated with 6 fractions of carbon ions at 6 positions within a 6 cm spread-out Bragg-peak (SOBP, LET: 16–99 keV/μm). TD50-values (dose at 50% complication probability) were determined from dose-response curves for the endpoint radiation induced myelopathy (paresis grade II) within 300 days after irradiation. Based on TD50-values of 15 MV photons, RBE-values were calculated and adding previously published data, the LET and fractional dose-dependence of the RBE was used to benchmark the local effect model (LEM I and IV).ResultsAt six fractions, TD50-values decreased from 39.1 ± 0.4 Gy at 16 keV/μm to 17.5 ± 0.3 Gy at 99 keV/μm and the RBE increased accordingly from 1.46 ± 0.05 to 3.26 ± 0.13. Experimental α/β-ratios ranged from 6.9 ± 1.1 Gy to 44.3 ± 7.2 Gy and increased strongly with LET. Including all available data, comparison with model-predictions revealed that (i) LEM IV agrees better in the SOBP, while LEM I fits better in the entrance region, (ii) LEM IV describes the slope of the RBE within the SOBP better than LEM I, and (iii) in contrast to the strong LET-dependence, the RBE-deviations depend only weakly on fractionation within the measured range.ConclusionsThis study extends the available RBE data base to significantly lower fractional doses and performes detailed tests of the RBE-models LEM I and IV. In this comparison, LEM IV agrees better with the experimental data in the SOBP than LEM I. While this could support a model replacement in treatment planning, careful dosimetric analysis is required for the individual patient to evaluate potential clinical consequences.

Phantom design and dosimetric characterization for multiple simultaneous cell irradiations with active pencil beam scanning

A new phantom was designed for in vitro studies on cell lines in horizontal particle beams. The phantom enables simultaneous irradiation at multiple positions along the beam path. The main purpose of this study was the detailed dosimetric characterization of the phantom which consists of various heterogeneous structures. The dosimetric measurements described here were performed under non-reference conditions. The experiment involved a CT scan of the phantom, dose calculations performed with the treatment planning system (TPS) RayStation employing both the Pencil Beam (PB) and Monte Carlo (MC) algorithms, and proton beam delivery. Two treatment plans reflecting the typical target location for head and neck cancer and prostate cancer treatment were created. Absorbed dose to water and dose homogeneity were experimentally assessed within the phantom along the Bragg curve with ionization chambers (ICs) and EBT3 films. LETd distributions were obtained from the TPS. Measured depth dose distributions were in good agreement with the Monte Carlo-based TPS data. Absorbed dose calculated with the PB algorithm was 4% higher than the absorbed dose measured with ICs at the deepest measurement point along the spread-out Bragg peak. Results of experiments using melanoma (SKMel) cell line are also presented. The study suggested a pronounced correlation between the relative biological effectiveness (RBE) and LETd, where higher LETd leads to elevated cell death and cell inactivation. Obtained RBE values ranged from 1.4 to 1.8 at the survival level of 10% (RBE10). It is concluded that dosimetric characterization of a phantom before its use for RBE experiments is essential, since a high dosimetric accuracy contributes to reliable RBE data and allows for a clearer differentiation between physical and biological uncertainties.

Using the Proton Energy Spectrum and Microdosimetry to Model Proton Relative Biological Effectiveness

We introduce a methodology to calculate the microdosimetric quantity dose-mean lineal energy for input into the microdosimetric kinetic model (MKM) to model the relative biological effectiveness (RBE) of proton irradiation experiments. The data from 7 individual proton RBE experiments were included in this study. In each experiment, the RBE at several points along the Bragg curve was measured. Monte Carlo simulations to calculate the lineal energy probability density function of 172 different proton energies were carried out with use of Geant4 DNA. We calculated the fluence-weighted lineal energy probability density function (fw(y)), based on the proton energy spectra calculated through Monte Carlo at each experimental depth, calculated the dose-mean lineal energy yD¯ for input into the MKM, and then computed the RBE. The radius of the domain (rd) was varied to reach the best agreement between the MKM-predicted RBE and experimental RBE. A generic RBE model as a function ofdose-averaged linear energy transfer (LETD) with 1 fitting parameter was presented and fit to the experimental RBE data as well to facilitate a comparison to the MKM. Both the MKM and LETD-based models modeled the RBE from experiments well. Values for rd were similar to those of other cell lines under proton irradiation that were modeled with the MKM. Analysis of the performance of each model revealed that neither model was clearly superior to the other. Our 3 key accomplishments include the following: (1) We developed a method that uses the proton energy spectra and lineal energy distributions of those protons to calculate dose-mean lineal energy. (2) We demonstrated that our application of the MKM provides theoretical validation of proton irradiation experiments that show that RBE is significantly greater than 1.1. (3) We showed that there is no clear evidence that the MKM is better than LETD-based RBE models.

Late normal tissue response in the rat spinal cord after carbon ion irradiation

BackgroundThe present work summarizes the research activities on radiation-induced late effects in the rat spinal cord carried out within the “clinical research group ion beam therapy” funded by the German Research Foundation (DFG, KFO 214).Methods and materialsDose–response curves for the endpoint radiation-induced myelopathy were determined at 6 different positions (LET 16–99 keV/μm) within a 6 cm spread-out Bragg peak using either 1, 2 or 6 fractions of carbon ions. Based on the tolerance dose TD50 of carbon ions and photons, the relative biological effectiveness (RBE) was determined and compared with predictions of the local effect model (LEM I and IV). Within a longitudinal magnetic resonance imaging (MRI)-based study the temporal development of radiation-induced changes in the spinal cord was characterized. To test the protective potential of the ACE (angiotensin converting enzyme)-inhibitor ramipril™, an additional dose–response experiment was performed.ResultsThe RBE-values increased with LET and the increase was found to be larger for smaller fractional doses. Benchmarking the RBE-values as predicted by LEM I and LEM IV with the measured data revealed that LEM IV is more accurate in the high-LET, while LEM I is more accurate in the low-LET region. Characterization of the temporal development of radiation-induced changes with MRI demonstrated a shorter latency time for carbon ions, reflected on the histological level by an increased vessel perforation after carbon ion as compared to photon irradiations. For the ACE-inhibitor ramipril™, a mitigative rather than protective effect was found.ConclusionsThis comprehensive study established a large and consistent RBE data base for late effects in the rat spinal cord after carbon ion irradiation which will be further extended in ongoing studies. Using MRI, an extensive characterization of the temporal development of radiation-induced alterations was obtained. The reduced latency time for carbon ions is expected to originate from a dynamic interaction of various complex pathological processes. A dominant observation after carbon ion irradiation was an increase in vessel perforation preferentially in the white matter. To enable a targeted pharmacological intervention more details of the molecular pathways, responsible for the development of radiation-induced myelopathy are required.

Modeling in vivo relative biological effectiveness in particle therapy for clinically relevant endpoints

Background: The relative biological effectiveness (RBE) of particle therapy compared to photon radiotherapy is known to be variable but the exact dependencies are still subject to debate. In vitro data suggested that RBE is to a large extend independent of ion type if parametrized by the beam quality Q. This study analyzed the RBE dependence of pre-clinical data on late toxicity with an emphasis on the beam quality.Material and methods: Published pre-clinical RBE dose-response data of the spinal cord following one and two fractions of photon and carbon ion irradiation were compiled. The beam quality for each treatment condition was obtained from Monte Carlo simulations. The αp and βp parameters of the linear-quadratic (LQ) model for particle irradiation were determined from the pre-clinical data and was provided as a function of Q. An introduced model proposed αp to increase linearly with Q and βp to remain constant. RBE values predicted by the model were compared to the published data.Results: The αp parameter was highly correlated with Q (R2 = 0.96) with a linear slope of 0.019 Gy−1. No significant variation of βp with Q was found. RBE and Q were also highly correlated (R2 = 0.98) for one and two fractions. The (extrapolated) RBE at Q = 0 (theoretical photon limit) for one and two fractions was 1.22 and significantly larger than 1 (p = .004). The model reproduced the dependence of RBE on fractionation well.Conclusions: Fraction dose and beam quality Q were sufficient to describe the RBE variability for a late toxicity model within a carbon ion treatment field. Assuming the independence of the identified RBE parameters on the ion type might suggest the translation of variable (pre-) clinical RBE data from carbon ion to proton therapy.

Optimizing the modified microdosimetric kinetic model input parameters for proton and 4He ion beam therapy application

Models able to predict relative biological effectiveness (RBE) values are necessary for an accurate determination of the biological effect with proton and 4He ion beams. This is particularly important when including RBE calculations in treatment planning studies comparing biologically optimized proton and 4He ion beam plans. In this work, we have tailored the predictions of the modified microdosimetric kinetic model (MKM), which is clinically applied for carbon ion beam therapy in Japan, to reproduce RBE with proton and 4He ion beams. We have tuned the input parameters of the MKM, i.e. the domain and nucleus radii, reproducing an experimental database of initial RBE data for proton and He ion beams. The modified MKM, with the best fit parameters obtained, has been used to reproduce in vitro cell survival data in clinically-relevant scenarios. A satisfactory agreement has been found for the studied cell lines, A549 and RENCA, with the mean absolute survival variation between the data and predictions within 2% and 5% for proton and 4He ion beams, respectively. Moreover, a sensitivity study has been performed varying the domain and nucleus radii and the quadratic parameter of the photon response curve. The promising agreement found in this work for the studied clinical-like scenarios supports the usage of the modified MKM for treatment planning studies in proton and 4He ion beam therapy.

The origin of neutron biological effectiveness as a function of energy.

The understanding of the impact of radiation quality in early and late responses of biological targets to ionizing radiation exposure necessarily grounds on the results of mechanistic studies starting from physical interactions. This is particularly true when, already at the physical stage, the radiation field is mixed, as it is the case for neutron exposure. Neutron Relative Biological Effectiveness (RBE) is energy dependent, maximal for energies ~1 MeV, varying significantly among different experiments. The aim of this work is to shed light on neutron biological effectiveness as a function of field characteristics, with a comprehensive modeling approach: this brings together transport calculations of neutrons through matter (with the code PHITS) and the predictive power of the biophysical track structure code PARTRAC in terms of DNA damage evaluation. Two different energy dependent neutron RBE models are proposed: the first is phenomenological and based only on the characterization of linear energy transfer on a microscopic scale; the second is purely ab-initio and based on the induction of complex DNA damage. Results for the two models are compared and found in good qualitative agreement with current standards for radiation protection factors, which are agreed upon on the basis of RBE data.

SU‐G‐TeP3‐01: A New Approach for Calculating Variable Relative Biological Effectiveness in IMPT Optimization

Purpose:To investigate the impact of a new approach for calculating relative biological effectiveness (RBE) in intensity‐modulated proton therapy (IMPT) optimization on RBE‐weighted dose distributions. This approach includes the nonlinear RBE for the high linear energy transfer (LET) region, which was revealed by recent experiments at our institution. In addition, this approach utilizes RBE data as a function of LET without using dose‐averaged LET in calculating RBE values.Methods:We used a two‐piece function for calculating RBE from LET. Within the Bragg peak, RBE is linearly correlated to LET. Beyond the Bragg peak, we use a nonlinear (quadratic) RBE function of LET based on our experimental. The IMPT optimization was devised to incorporate variable RBE by maximizing biological effect (based on the Linear Quadratic model) in tumor and minimizing biological effect in normal tissues. Three glioblastoma patients were retrospectively selected from our institution in this study. For each patient, three optimized IMPT plans were created based on three RBE resolutions, i.e., fixed RBE of 1.1 (RBE‐1.1), variable RBE based on linear RBE and LET relationship (RBE‐L), and variable RBE based on linear and quadratic relationship (RBE‐LQ). The RBE weighted dose distributions of each optimized plan were evaluated in terms of different RBE values, i.e., RBE‐1.1, RBE‐L and RBE‐LQ.Results:The RBE weighted doses recalculated from RBE‐1.1 based optimized plans demonstrated an increasing pattern from using RBE‐1.1, RBE‐L to RBE‐LQ consistently for all three patients. The variable RBE (RBE‐L and RBE‐LQ) weighted dose distributions recalculated from RBE‐L and RBE‐LQ based optimization were more homogenous within the targets and better spared in the critical structures than the ones recalculated from RBE‐1.1 based optimization.Conclusion:We implemented a new approach for RBE calculation and optimization and demonstrated potential benefits of improving tumor coverage and normal sparing in IMPT planning.

Direct evaluation of radiobiological parameters from clinical data in the case of ion beam therapy: an alternative approach to the relative biological effectiveness

The relative biological effectiveness (RBE) concept is commonly used in treatment planning for ion beam therapy. Whether models based on in vitro/in vivo RBE data can be used to predict human response to treatments is an open issue. In this work an alternative method, based on an effective radiobiological parameterization directly derived from clinical data, is presented. The method has been applied to the analysis of prostate cancer trials with protons and carbon ions.Prostate cancer trials with proton and carbon ion beams reporting 5 year-local control (LC5) and grade 2 (G2) or higher genitourinary toxicity rates (TOX) were selected from literature to test the method. Treatment simulations were performed on a representative subset of patients to produce dose and linear energy transfer distribution, which were used as explicative physical variables for the radiobiological modelling. Two models were taken into consideration: the microdosimetric kinetic model (MKM) and a linear model (LM). The radiobiological parameters of the LM and MKM were obtained by coupling them with the tumor control probability and normal tissue complication probability models to fit the LC5 and TOX data through likelihood maximization. The model ranking was based on the Akaike information criterion.Results showed large confidence intervals due to the limited variety of available treatment schedules. RBE values, such as RBE = 1.1 for protons in the treated volume, were derived as a by-product of the method, showing a consistency with current approaches. Carbon ion RBE values were also derived, showing lower values than those assumed for the original treatment planning in the target region, whereas higher values were found in the bladder. Most importantly, this work shows the possibility to infer the radiobiological parametrization for proton and carbon ion treatment directly from clinical data.

SU‐E‐T‐10: A Computational Model for the Estimation of Biological Dose in a Clinical Proton Beam

Purpose: The variability of relative biological effectiveness (RBE) of a proton beam with spatial distribution is well known. It is dependent on the proton beam characteristics, type of tissue and biological indices. A computational model based on a proton spectrum and LET is used for the estimation of the biological dose. Methods: The depth dose curve of the pristine beam is divided into two regions: the proximal region from the surface to the Bragg peak and the distal region beyond the peak. Knowing the beam energy at the surface in the proximal region, and using the published energy‐range tables, we estimated the effective proton energy at any depth proximal to the Bragg peak. Based on the energy, the LET and RBE is estimated. In the distal region, we assume that the effective beam energy changes monotonically from the value calculated at the peak to the final energy of about 3MeV at the 3% dose level on the distal edge. Applying the calculated RBE factor to the measured depth dose profile we obtain the biological dose in the pristine beam. The method can easily be applied to modulated beams. Results: Our computation model shows that it is possible to predict the biological dose for any combination of beam energy, and for SOBP size based on the available RBE data. Our results showed that the biological dose for a SOBP has finite slope rising to higher values close to distal edge of the peak. Conclusions: A computational model provides an unique tool to estimate the biological dose in any combination of beam energy and SOBP size. If the RBE vs LET data for a tissue is know our computational approach could provide the biological dose accurately in a clinical beam.

Doses and risks from tritiated water and environmental organically bound tritium

This short review provides an explanation of the calculation and use of the ICRPprotection quantities, equivalent and effective dose, including the simplifications introducedby using radiation and tissue weighting factors. It discusses the dose coefficients (Sv Bq−1 intake) provided by ICRP for intakes of tritiated water (HTO) and organically boundtritium (OBT) and considers uncertainties in the human and animal data on which theyare based, including information on the relative biological effectiveness (RBE) oftritium beta particles compared to gamma and x-rays. The review also addressesthe specific issue of dose coefficients for ingestion of OBT in Cardiff Bay fish.A distinction is drawn between the adequacy of the ICRP calculation of effective dose to areference person for the purposes of planning and regulatory control, and the calculation ofbest estimates of dose and risk to individuals. ICRP will continue to use a radiationweighting factor of 1 for all low LET radiations in the calculation of effective dose,but specific RBE data should be used in risk estimates. Uncertainties in dosecoefficients are small for HTO but greater for OBT. The generic consideration of OBTprovided by ICRP may not be appropriate for specific organic forms such as OBT infish.

Effect of edema, relative biological effectiveness, and dose heterogeneity on prostate brachytherapya)

Many factors influence response in low-dose-rate (LDR) brachytherapy of prostate cancer. Among them, edema, relative biological effectiveness (RBE), and dose heterogeneity have not been fully modeled previously. In this work, the generalized linear-quadratic (LQ) model, extended to account for the effects of edema, RBE, and dose heterogeneity, was used to assess these factors and their combination effect. Published clinical data have shown that prostate edema after seed implant has a magnitude (ratio of post- to preimplant volume) of 1.3-2.0 and resolves exponentially with a half-life of 4-25 days over the duration of the implant dose delivery. Based on these parameters and a representative dose-volume histogram (DVH), we investigated the influence of edema on the implant dose distribution. The LQ parameters (alpha=0.15 Gy(-1) and alpha/beta=3.1 Gy) determined in earlier studies were used to calculate the equivalent uniform dose in 2 Gy fractions (EUD2) with respect to three effects: edema, RBE, and dose heterogeneity for 125I and 103Pd implants. The EUD2 analysis shows a negative effect of edema and dose heterogeneity on tumor cell killing because the prostate edema degrades the dose coverage to tumor target. For the representative DVH, the V100 (volume covered by 100% of prescription dose) decreases from 93% to 91% and 86%, and the D90 (dose covering 90% of target volume) decrease from 107% to 102% and 94% of prescription dose for 125I and 103Pd implants, respectively. Conversely, the RBE effect of LDR brachytherapy [versus external-beam radiotherapy (EBRT) and high-dose-rate (HDR) brachytherapy] enhances dose effect on tumor cell kill. In order to balance the negative effects of edema and dose heterogeneity, the RBE of prostate brachytherapy was determined to be approximately 1.2-1.4 for 125I and 1.3-1.6 for 103Pd implants. These RBE values are consistent with the RBE data published in the literature. These results may explain why in earlier modeling studies, when the effects of edema, dose heterogeneity, and RBE were all ignored simultaneously, prostate LDR brachytherapy was reported to show an overall similar dose effect as EBRT and HDR brachytherapy, which are independent of edema and RBE effects and have a better dose coverage.

An estimation of the relative biological effectiveness of 50 MV bremsstrahlung beams by microdosimetric techniques

An efficient algorithm has been developed to estimate the relative biological effectiveness (RBE) from experimental RBE data and measured single-event energy deposition spectra. As benchmarks for the calculations well established RBE data for crypt cell survival and associated microdosimetric distributions from a number of therapeutic high- and low-LET beams was used. As a by-product of the calculations the RBE for this system was determined for the lineal energy range 0.1 - 5000 keV in very good agreement with experimental data. These data have been applied to estimate the biological effectiveness of therapeutic high-energy bremsstrahlung beams characterized by microdosimetric measurements with a wall-less proportional counter. The absorbed dose component due to photoneutrons and charged particles from photonuclear reactions in scanned 50 MV bremsstrahlung beams was measured to be about 2% of the total absorbed dose. The RBE of 50 MV scanned bremsstrahlung beams was estimated to be 1.09 for jejunum crypt cell survival as the biological endpoint at absorbed doses of the order of 10 Gy, in fair agreement with reported results based on radiobiological experiments. The RBE is fairly independent of the bremsstrahlung target used. Using the estimated increase in the RBE of neutrons compared to photons for absorbed dose levels applied in clinical fractionation schedules increases the RBE further to 1.13 at absorbed doses per fraction of the order of 2 Gy.

The Relative Biological Effectiveness of 670 MeV/A Neon as a Function of Depth in Water for a Tissue Model

Linear energy transfer (LET infinity) spectra of identified charge fragments and primaries, produced by nuclear interactions of 670 MeV/A neon in water, were measured along the unmodulated Bragg curve of the neon beam. The relative biological effectiveness (RBE) values for spermatogonial cell killing, as reported on the basis of weight loss assay of mouse testes irradiated with beams of approximately constant single LET infinity, were summed over the particle LET infinity spectra to obtain an effective RBE for each charged-particle species, as a function of water absorber thickness. The resultant values of effective RBE were combined to obtain an effective RBE for the mixed radiation field. The RBE calculated in this way was compared with experimental RBEs obtained for spermatogonial cell killing in the mixed radiation field produced by neon ions traversing a thick water absorber. Discrepancies of 10-40% were observed between the calculated RBE and the RBE measured in the mixed radiation field. Part of this discrepancy can be attributed to undetected low-Z fragments, whose contribution is not included in the calculation, leading to an overestimated value for the calculated RBE. On the other hand, calculated values 10% greater than the measured RBE are explained as track structure effects due to the higher radial ionization density near neon tracks relative to the ionization density near the silicon tracks used to fit the RBE vs LET infinity data.