Changes In Relative Biological Effectiveness Research Articles

Modelling of RBE differences in selected points within similar spread-out Bragg-peaks (SOBP) placed at superficial and deep water phantom locations in passively scattered beams but not in scanned pencil beams: A hypothesis

PurposeTo model relative biological effectiveness (RBE) differences found in two studies which used spread-out Bragg-peaks (SOBP) placed at (a) superficial depth and (b) at the maximum range depth. For pencil beam scanning (PBS), RBE at similar points within the SOBP did not change between the two extreme SOBP placement depths; in passively scattered beams (PSB), high RBE values (typically 1.2–1.3) were found within superficially- placed SOBP but reduced to lower values (1–1.07) at similar points within the extreme-depth positioned SOBP. The dose, LET (linear energy transfer) distributions along each SOBP were closely comparable regardless of placement depth, but significant changes in dose rate occurred with depth in the PSB beam. MethodsThe equations used allow α and β changes with falling dose rate (the converse to FLASH studies) in PSB, resulting in reduced α/β ratios, compatible with a reduction in micro-volumetric energy transfer (the product of Fluence and LET), with commensurate reductions in RBE. The experimental depth-distances, positions within SOBP, observed dose-rates and radiosensitivity ratios were used to estimate the changes in RBE. ResultsRBE values within a 5 % tolerance limit of the experimental results for PSB were found at the deepest SOBP placement. No RBE changes were predicted for PBS beams, as in the published results. ConclusionsEnhanced proton therapy toxicity might occur with PBS when compared with PSB for deeply positioned SOBP due to the maintenance of higher RBE. Scanned pencil beam users need to be vigilant about RBE and further research is indicated.

Impact of gadolinium concentration and cell oxygen levels on radiobiological characteristics of gadolinium neutron capture therapy technique in brain tumor treatment.

Neutron capture therapy (NCT) with various concentrations of gadolinium (157Gd) is one of the treatment modalities for glioblastoma (GBM) tumors. Current study aims to evaluate how variations of 157Gd concentration and cell oxygen levels can affect the relative biological effectiveness (RBE) of gadolinium neutron capture therapy (GdNCT) technique through a hybrid Monte Carlo (MC) simulation approach. At first, Snyder phantom including a spherical tumor was simulated by Geant4 MC code and relevant energy electron spectra to different 157Gd concentrations including 100, 250, 500, and 1000 ppm were calculated following the neutron irradiation of simulated phantom. Scored energy electron spectra were then imported to Monte Carlo damage simulation (MCDS) code to estimate RBE values (both RBESSB and RBEDSB) at different gadolinium concentrations and oxygen levels from 10 to 100%. The results indicate that variations of 157Gd can affect the energy spectrum of released secondary electrons including Auger electrons. Variation of gadolinium concentration from 100 to 1000 ppm in tumor region can change RBESSB and RBEDSB values by about 0.1% and 0.5%, respectively. Besides, maximum variations of 4.3% and 2% were calculated for RBEDSB and RBESSB when cell oxygen level changed from 10 to 100%. From the results, variations of considered gadolinium and oxygen concentrations during GdNCT can influence RBE values. Nevertheless, due to the not remarkable changes in the intensity of Auger electrons, a slight difference in RBE values would be expected at various 157Gd concentrations, although considerable RBE changes were calculated relevant to the oxygen alternations inside tumor tissue.

Technical note: Impact of beamline-specific particle energy spectra on clinical plans in carbon ion beam therapy.

PurposeThe Local Effect Model version one (LEM I) is applied clinically across Europe to quantify the relative biological effectiveness (RBE) of carbon ion beams. It requires the full particle fluence spectrum differential in energy in each voxel as input parameter. Treatment planning systems (TPSs) use beamline‐specific look‐up tables generated with Monte Carlo (MC) codes. In this study, the changes in RBE weighted dose were quantified using different levels of details in the simulation or different MC codes.MethodsThe particle fluence differential in energy was simulated with FLUKA and Geant4 at 500 depths in water in 1‐mm steps for 58 initial carbon ion energies (between 120.0 and 402.8 MeV/u). A dedicated beam model was applied, including the full description of the Nozzle using GATE‐RTionV1.0 (Geant4.10.03p03). In addition, two tables generated with FLUKA were compared. The starting points of the FLUKA simulations were phase space (PhS) files from, firstly, the Geant4 nozzle simulations, and secondly, a clinical beam model where an analytic approach was used to mimic the beamline. Treatment plans (TPs) were generated with RayStation 8B (RaySearch Laboratories AB, Sweden) for cubic targets in water and 10 clinical patient cases using the clinical beam model. Subsequently, the RBE weighted dose was re‐computed using the two other fluence tables (FLUKA PhS or Geant4).ResultsThe fluence spectra of the primary and secondary particles simulated with Geant4 and FLUKA generally agreed well for the primary particles. Differences were mainly observed for the secondary particles. Interchanging the two energy spectra (FLUKA vs. GEANT4) to calculate the RBE weighted dose distributions resulted in average deviations of less than 1% in the entrance up to the end of the target region, with a maximum local deviation at the distal edge of the target. In the fragment tail, larger discrepancies of up to 5% on average were found for deep‐seated targets. The patient and water phantom cases demonstrated similar results.ConclusionRBE weighted doses agreed well within all tested setups, confirming the clinical beam model provided by the TPS vendor. Furthermore, the results showed that the open source and generally available MC code Geant4 (in particular using GATE or GATE‐RTion) can also be used to generate basic beam data required for RBE calculation in carbon ion therapy.

Microdosimetric measurements as a tool to assess potential in-field and out-of-field toxicity regions in proton therapy

Relative biological effectiveness (RBE) variations are thought to be one of the primary causes of unexpected normal-tissue toxicities during tumor treatments with charged particles. Unlike carbon therapy, where treatment planning is optimized on the basis of the RBE-weighted dose, a constant RBE value of 1.1 is currently used in proton therapy. Assuming a uniform value can lead to under- or over-dosage, not just to the tumor but also to surrounding normal tissue. RBE changes have been linked with dose/fraction, the biological endpoint and beam properties. Understanding radiation quality and the associated RBE can improve the prediction of normal-tissue toxicities.In this study, we exploited microdosimetry for characterizing radiation quality in proton therapy in-field, and off-beam at 20 (beam edge), 50 (close out-of-field) and 100 (far out-of-field) mm from the beam center. We measured the lineal energy y spectra in a water phantom irradiated with 152 MeV protons, from which beam quality as well as the physical dose could be obtained. Taking advantage of the linear quadratic model and a modified version of the microdosimetric kinetic model, the microdosimetric data were combined with radiobiological parameters (α and β) of human salivary gland tumor cells for assessing cell survival RBE and RBE-weighted dose.The results indicate that if a dose of 60 Gy is delivered to the peak, the beam edge receives up to 6 Gy while the close and far out-of-field regions receive doses on the order of 10−3 Gy and 10−4 Gy, respectively. The RBE estimate in-beam shows large variations, ranging from 1.0 ± 0.2 at the entrance channel to 2.51 ± 0.15 at the tail. The beam edge follows a similar trend but the RBE calculated at the Bragg peak depth is 2.27 ± 0.17, i.e. twice the RBE in-beam (1.05 ± 0.15). Out-of-field, the estimated RBE is always significantly higher than 1.1 and increases with increasing lateral distance, reaching the overall highest value of 3.4 ± 0.3 at a depth of 206 mm and a lateral distance of 10 mm. The combination of RBE and dose into the biological dose points to the beam edge and the end-of-range in-beam as the areas with the highest risk of potential toxicities.

Assessment of RBE-Weighted Dose Models for Carbon Ion Therapy Toward Modernization of Clinical Practice at HIT: In Vitro, in Vivo, and in Patients

Present-day treatment planning in carbon ion therapy is conducted with assumptions for a limited number of tissue types and models for effective dose. Here, we comprehensively assess relative biological effectiveness (RBE) in carbon ion therapy and associated models toward the modernization of current clinical practice in effective dose calculation. Using 2 human (A549, H460) and 2 mouse (B16, Renca) tumor cell lines, clonogenic cell survival assay was performed for examination of changes in RBE along the full range of clinical-like spread-out Bragg peak (SOBP) fields. Prediction power of the local effect model (LEM1 and LEM4) and the modified microdosimetric kinetic model (mMKM) was assessed. Experimentation and analysis were carried out in the frame of a multidimensional end point study for clinically relevant ranges of physical dose (D), dose-averaged linear energy transfer (LETd), and base-line photon radio-sensitivity (α/β)x. Additionally, predictions were compared against previously reported RBE measurements invivo and surveyed in patient cases. RBE model prediction performance varied among the investigated perspectives, with mMKM prediction exhibiting superior agreement with measurements both invitro and invivo across the 3 investigated end points. LEM1 and LEM4 performed their best in the highest LET conditions but yielded overestimations and underestimations in low/midrange LET conditions, respectively, as demonstrated by comparison with measurements. Additionally, the analysis of patient treatment plans revealed substantial variability across the investigated models (±20%-30% uncertainty), largely dependent on the selected model and absolute values for input tissue parameters αx and βx. RBE dependencies invitro, invivo, and in silico were investigated with respect to various clinically relevant end points in the context of tumor-specific tissue radio-sensitivity assignment and accurate RBE modeling. Discovered model trends and performances advocate upgrading current treatment planning schemes in carbon ion therapy and call for verification via clinical outcome analysis with large patient cohorts.

Estimations of relative biological effectiveness of secondary fragments in carbon ion irradiation of water using CR-39 plastic detector and microdosimetric kinetic model.

To estimate relative biological effectiveness (RBE) ascribed to secondary fragments in a lateral distribution of carbon ion irradiation. The RBE was estimated with the microdosimetric kinetic (MK) model and measured linear energy transfer (LET) obtained with CR-39 plastic detectors. A water phantom was irradiated by a 12 C pencil beam with energy of 380MeV/u at the Gunma University Heavy Ion Medical Center (GHMC), and CR-39 detectors were exposed to secondary fragments. Because CR-39 was insensitive to low LET, we conducted Monte Carlo simulations with Geant4 to calculate low LET particles. The spectra of low LET particleswere combined with experimental spectra to calculate RBE. To estimate accuracy of RBE, we calculated RBE by changing yield of low LET particles by±10% and±40%. At a small angle, maximum RBE by secondary fragments was 1.3 for 10% survival fractions. RBE values of fragments gradually decreased as the angle became larger. The shape of the LET spectra in the simulation reproduced the experimental spectra, but there was a discrepancy between the simulation and experiment for the relative yield of fragments. When the yield of low LET particles was changed by±40%, the change in RBE was smaller than 10%. An RBE of 1.3 was expected for secondary fragments emitted at a small angle. Although, we observed a discrepancy in the relative yield of secondary fragments between simulation and experiment, precision of RBE was not so sensitive to the yield of low LET particles.

Dosimetric accuracy and radiobiological implications of ion computed tomography for proton therapy treatment planning

Ion computed tomography (iCT) represents a potential replacement for x-ray CT (xCT) in ion therapy treatment planning to reduce range uncertainties, inherent in the semi-empirical conversion of xCT information into relative stopping power (RSP). In this work, we aim to quantify the increase in dosimetric accuracy associated with using proton-, helium- and carbon-CT compared to conventional xCT for clinical scenarios in proton therapy. Three cases imaged with active beam-delivery using an ideal single-particle-tracking detector were investigated using FLUKA Monte-Carlo (MC) simulations. The RSP accuracy of the iCTs was evaluated against the ground truth at similar physical dose. Next, the resulting dosimetric accuracy was investigated by using the RSP images as a patient model in proton therapy treatment planning, in comparison to common uncertainties associated with xCT. Finally, changes in relative biological effectiveness (RBE) with iCT particle type/spectrum were investigated by incorporating the repair-misrepair-fixation (RMF) model into FLUKA, to enable first insights on the associated biological imaging dose. Helium-CT provided the lowest overall RSP error, whereas carbon-CT offered the highest accuracy for bone and proton-CT for soft tissue. For a single field, the average relative proton beam-range variation was −1.00%, +0.09%, −0.08% and −0.35% for xCT, proton-, helium- and carbon-CT, respectively. Using a 0.5%/0.5mm gamma-evaluation, all iCTs offered comparable accuracy with a better than 99% passing rate, compared to 83% for xCT. The RMF model predictions for RBE for cell death relative to a diagnostic xCT spectrum were 0.82–0.85, 0.85–0.89 and 0.97–1.03 for proton-, helium-, and carbon-CT, respectively. The corresponding RBE for DNA double-strand break induction was generally below one. iCT offers great clinical potential for proton therapy treatment planning by providing superior dose calculation accuracy as well as lower physical and potentially biological dose exposure compared to xCT. For the investigated dose level and ideal detector, proton-CT and helium-CT yielded the best performance.

Establishment of a New Three-Dimensional Dose Evaluation Method Considering Variable Relative Biological Effectiveness and Dose Fractionation in Proton Therapy Combined with High-Dose-Rate Brachytherapy.

Purpose:The purpose of this study is to evaluate the influence of variable relative biological effectiveness (RBE) of proton beam and dose fractionation has on dose distribution and to establish a new three-dimensional dose evaluation method for proton therapy combined with high-dose-rate (HDR) brachytherapy.Materials and Methods:To evaluate the influence of variable RBE and dose fractionation on dose distribution in proton beam therapy, the depth-dose distribution of proton therapy was compared with clinical dose, RBE-weighted dose, and equivalent dose in 2 Gy fractions using a linear-quadratic-linear model (EQD2LQL). The clinical dose was calculated by multiplying the physical dose by RBE of 1.1. The RBE-weighted dose is a biological dose that takes into account RBE variation calculated by microdosimetric kinetic model implemented in Monte Carlo code. The EQD2LQL is a biological dose that makes the RBE-weighted dose equivalent to 2 Gy using a linear-quadratic-linear (LQL) model. Finally, we evaluated the three-dimensional dose by taking into account RBE variation and LQL model for proton therapy combined with HDR brachytherapy.Results:The RBE-weighted dose increased at the distal of the spread-out Bragg peak (SOBP). With the difference in the dose fractionation taken into account, the EQD2LQL at the distal of the SOBP increased more than the RBE-weighted dose. In proton therapy combined with HDR brachytherapy, a divergence of 103% or more was observed between the conventional dose estimation method and the dose estimation method we propose.Conclusions:Our dose evaluation method can evaluate the EQD2LQL considering RBE changes in the dose distribution.

The potential impact of ultrathin filter design on dosimetry and relative biological effectiveness in modern image-guided small animal irradiators.

Modern image-guided small animal irradiators like the Xstrahl Small Animal Radiation Research Platform (SARRP) are designed with ultrathin 0.15 mm Cu filters, which compared with more heavily filtrated traditional cabinet-style biological irradiators, produce X-ray spectra weighted toward lower energies, impacting the dosimetric properties and the relative biological effectiveness (RBE). This study quantifies the effect of ultrathin filter design on relative depth dose profiles, absolute dose output, and RBE using Monte Carlo techniques. The percent depth-dose and absolute dose output are calculated using kVDoseCalc and EGSnrc, respectively, while a tally based on the induction of double-strand breaks as a function of electron spectra invoked in PENELOPE is used to estimate the RBE. The RBE increases by >2.4% in the ultrathin filter design compared to a traditional irradiator. Furthermore, minute variations in filter thickness have notable effects on the dosimetric properties of the X-ray beam, increasing the percent depth dose (at 2 cm in water) by + 0.4%/0.01 mm Cu and decreasing absolute dose (at 2 cm depth in water) by -1.8%/0.01 mm Cu for the SARRP. These results show that modern image-guided irradiators are quite sensitive to small manufacturing variations in filter thickness, and show a small change in RBE compared to traditional X-ray irradiators. We quantify the consequences of ultrathin filter design in modern image-guided biological irradiators on relative and absolute dose, and RBE. Our results show these to be small, but not insignificant, suggesting laboratories transitioning between irradiators should carefully design their radiobiological experiments.

Targeted alpha therapy with 212Pb or 225Ac: Change in RBE from daughter migration

Targeted α-therapy (TAT) could be delivered early to patients who are at a high-risk for developing brain metastases, targeting the areas of the vasculature where tumor cells are penetrating into the brain. We have utilized a Monte Carlo model representing brain vasculature to calculate physical dose and DNA damage from the α-emitters 225Ac and 212Pb. The micron-scale dose distributions from all radioactive decay products were modeled in Geant4, including the eV-scale interactions using the Geant4-DNA models. These interactions were then superimposed on an atomic-scale DNA model to estimate strand break yields. In addition to 225Ac having a higher dose per decay than 212Pb, it also has a double strand break yield per decay that is 4.7 ± 0.5 times that of 212Pb. However, the efficacy of both nuclides depends on retaining the daughter nuclei at the target location in the brain vasculature. The relative biological effectiveness (RBE) of 225Ac and 212Pb are similar when the entire decay chains are included, with maxima of 2.7 ± 0.6 and 2.5 ± 0.5 (respectively), and RBE values of about 2 to a depth of 80 μm. If the initial daughter is lost, the RBE of 212Pb is completely reduced to 1 or lower and the RBE of 225Ac is approximately 2 only for the first 40 μm.

The Radiobiology of Proton Therapy: Challenges and Opportunities Around Relative Biological Effectiveness

With the current UK expansion of proton therapy there is a great opportunity for clinical oncologists to develop a translational interest in the associated scientific base and clinical results. In particular, the underpinning controversy regarding the conversion of photon dose to proton dose by the relative biological effectiveness (RBE) must be understood, including its important implications. At the present time, the proton prescribed dose includes an RBE of 1.1 regardless of tissue, tumour and dose fractionation. A body of data has emerged against this pragmatic approach, including a critique of the existing evidence base, due to choice of dose, use of only acute-reacting in vivo assays, analysis methods and the reference radiations used to determine the RBE. Modelling systems, based on the best available scientific evidence, and which include the clinically useful biological effective dose (BED) concept, have also been developed to estimate proton RBEs for different dose and linear energy transfer (LET) values. The latter reflect ionisation density, which progressively increases along each proton track. Late-reacting tissues, such as the brain, where α/β = 2 Gy, show a higher RBE than 1.1 at a low dose per fraction (1.2–1.8 Gy) at LET values used to cover conventional target volumes and can be much higher. RBE changes with tissue depth seem to vary depending on the method of beam delivery used. To reduce unexpected toxicity, which does occasionally follow proton therapy, a more rational approach to RBE allocation, using a variable RBE that depends on dose per fraction and the tissue and tumour radiobiological characteristics such as α/β, is proposed.

Biological and dosimetric characterisation of spatially fractionated proton minibeams

The biological effectiveness of proton beams varies with depth, spot size and lateral distance from the beam central axis. The aim of this work is to incorporate proton relative biological effectiveness (RBE) and equivalent uniform dose (EUD) considerations into comparisons of broad beam and highly modulated proton minibeams. A Monte Carlo model of a small animal proton beamline is presented. Dose and variable RBE is calculated on a per-voxel basis for a range of energies (30–109 MeV). For an open beam, the RBE values at the beam entrance ranged from 1.02–1.04, at the Bragg peak (BP) from 1.3 to 1.6, and at the distal end of the BP from 1.4 to 2.0. For a 50 MeV proton beam, a minibeam collimator designed to produce uniform dose at the depth of the BP peak, had minimal impact on the open beam RBE values at depth. RBE changes were observed near the surface when the collimator was placed flush with the irradiated object, due to a higher neutron contribution derived from proton interactions with the collimator. For proton minibeams, the relative mean RBE weighted entrance dose (RWD) was ~25% lower than the physical mean dose. A strong dependency of the EUD with fraction size was observed. For 20 Gy fractions, the EUD varied widely depending on the radiosensitivity of the cells. For radiosensitive cells, the difference was up to ~50% in mean dose and ~40% in mean RWD and the EUD trended towards the valley dose rather than the mean dose. For comparative studies of uniform dose with spatially fractionated proton minibeams, EUD derived from a per-voxel RWD distribution is recommended for biological assessments of reproductive cell survival and related endpoints.

Relative biological effectiveness in a proton spread-out Bragg peak formed by pencil beam scanning mode.

In recent years, there is an increased interest in using scanning modes in proton therapy, due to the more conformal dose distributions, thanks to the spot-weighted dose delivery. The dose rate in each spot is however much higher than the dose rate when using passive irradiation modes, which could affect the cell response. The purpose of this work was to investigate how the relative biological effectiveness changes along the spread-out Bragg peak created by protons delivered by the pencil beam scanning mode. Cell survival and micronuclei formation were investigated in four positions along the spread-out Bragg peak for various doses. Monte Carlo simulations were used to estimate the dose-averaged linear energy transfer values in the irradiation positions. The cell survival was found to decrease the deeper the sample was placed in the spread-out Bragg peak, which corresponds to the higher linear energy transfer values found using Monte Carlo simulations. The micronuclei frequencies indicate more complex cell injuries at that distal position compared to the proximal part of the spread-out Bragg peak. The relative biological effectiveness determined in this study varies significantly and systematically from 1.1, which is recommended value by the International Commission on Radiation Units, in all the studied positions. In the distal position of spread-out Bragg peak the relative biological effectiveness values were found to be 2.05 ± 0.44, 1.85 ± 0.42, 1.53 ± 0.38 for survival levels 90, 50 and 10%, respectively.

RBE of kV CBCT radiation determined by Monte Carlo DNA damage simulations

Due to the higher LET of kilovoltage (kV) radiation, there is potential for an increase in relative biological effectiveness (RBE) of absorbed doses of radiation from kV cone beam computed tomography (CBCT) sources in reference to megavoltage or Co-60 doses. This work develops a method for accurately coupling a Monte Carlo (MC) radiation transport code (PENELOPE) with the damage simulation (MCDS) to predict relative numbers of DNA double strand breaks (DSBs). The MCDS accounts for slowing down of electrons and delta ray production within the cell nucleus; however, determining the spectrum of electrons incident on the cell nucleus from photons interacting in a larger region of tissue is not trivial. PENELOPE simulations were conducted with a novel tally algorithm invoked where electrons incident on a detection material were tracked and both the incident energy and the final deposited dose were recorded. The DSB yield predicted by a set of MCDS runs of monoenergetic electrons was then looked up in a table and weighted by the specific energy of the incident electron. Our results indicate that the RBE for DSB induction is 1.1 for diagnostic x-rays with energies from 80 to 125 kVp. We found no significant change in RBE with depth or filtration. The predicted absolute DSB yields are about three times lower for cells irradiated under anoxic conditions than the yield in cells irradiated under normoxic (5%) or fully aerobic (100%) conditions. However, oxygen concentration has a negligible (±0.02) effect on the RBE of kV CBCT x-rays.

Clinical Consequences of Relative Biological Effectiveness (RBE) Variations in Proton Radiotherapy of the Prostate, Brain, and Liver

The large range of (α/β)x-rays values reported for prostate (1.2Gy-5.0Gy), brain (10Gy-15Gy) and liver (13Gy-17Gy) imply that the proton RBE for these tissues could differ from the commonly used value of 1.1. Our aim was to evaluate the impact of this uncertainty on the RBE-weighted total dose (RWTD) to normal and tumor tissues when proton doses are delivered using standard or hypofractionated isoeffective regimes. RWTD distributions for five prostate, brain and liver patients were calculated using an in-house developed RBE model as a function of dose, Linear Energy Transfer (LET) and (α/β)x-rays. Variation on the DVH for the GTV and the organs-at-risk due to changes of (α/β)x-rays or fractionation regime were calculated and the RWTD received by 10% and 90% of the organ volume reported. The goodness of the plan, bearing the uncertainties, was then evaluated compared to the delivered plan with assumed RBE = 1.1. Table 1 summaries values of RWTD10 and RWTD90 when RBE is assumed to be equal to 1.1 and when RBE changes with the specified values of (α/β)x-rays. Standard fractionated regimes assuming an RBE varying with (α/β)x-rays provide RWTD10 values in organs-at-risk always smaller than those obtained in the case RBE = 1.1 except for the case of the chiasm, brainstem and the optical nerves. However, in hypofractionated regimes, the total doses received by normal tissues when RBE = 1.1 are in all cases larger than in the case of a variable RBE. The results show that, except for the case of prostate, large variations of (α/β)x-rays are not accompanied by large variations of RBE and, in standard fractionation regimes, the RWTD values derived from RBE = 1.1 or a variable RBE do not differ substantially. However, this difference increases in hypofractionated regimes, with a clear advantage for the case of a flexible RBE as in this case the RWTD delivered to the normal tissues is substantially smaller than in the case of RBE = 1.1. The results show that the use of a variable RBE with dose, LET and (α/β) x-rays would help to optimize the dose delivered to the target. The consideration of RBE variations could also influence the comparison of proton and photon treatments in clinical trials.Tabled 1GTV (1.2Gy< α/β <5.0Gy) Prescribed Dose (Standard Fractionation): 78.3GyANT RECTUM (2.5Gy< α/β <5.0Gy)BLADDER (3.0Gy< α/β <7.0Gy)GTV (10Gy< α/β <15Gy) Prescribed Dose (Standard Fractionation): 52.1GyCHIASM (1.5Gy< α/β <3.9Gy)BRAINSTEM (1.5Gy< α/β <3.9Gy)LT OPTICAL NERVE (1.5Gy< α/β <3.9Gy)RT OPTICAL NERVE (1.5Gy< α/β <3.9Gy)GTV (13Gy< α/β <17Gy) Prescribed Dose (Standard Fractionation): 60.2GyLUNG (1.6Gy< α/β <6.9Gy)HEALTHY LIVER (1.5Gy< α/β <3.0Gy)n = 3RWTD10RBE≠1.136 - 4931 - 3229.6 - 29.831.8 - 32.530.9 - 31.530.1 - 30.823.7 - 24.522.7 - 23.530.9 - 31.314.6 - 14.811.6 - 11.8RBE = 1.135.533.932.433.733.632.525.5824.532.415.812.3RWTD90RBE≠1.135 - 478 - 90.129.9 - 30.630 - 30.60.040.090.0929.2 - 29.60.010RBE = 1.134.59.10.1232.332.60.030.080.0830.60.010n = 10RWTD10RBE≠1.157 - 8049 - 5046 - 4752 - 5451 - 5350 - 5239 - 4137.7 - 39.848.6 - 49.423.1 - 23.518.6 - 19.8RBE = 1.155.552.950.555.154.853.041.839.950.524.619.2RWTD90RBE≠1.156 - 7713 - 140.2049 - 5149 - 510.050.160.1945.8 - 46.70.010.01RBE = 1.153.814.10.2052.853.20.050.150.1747.60.010.01Standard FractionationRWTD10RBE≠1.194 - 13979 - 8274.9 - 77.256 - 5955 - 5954 - 5843 - 4841 - 4665 - 6631.1 - 31.625 - 26.7RBE = 1.188.2684.280.457.957.755.843.94267.532.925.6RWTD90RBE≠1.191 - 13322 - 240.31 - 0.3454 - 5753.5 - 57.50.160.160.1661 - 620.010.01RBE = 1.185.720.70.3255.555.90.070.150.1663.70.010.01PROSTATE RWTD [Gy(RBE)]BRAIN RWTD [Gy(RBE)]LIVER RWTD [Gy(RBE)] Open table in a new tab

Early and late injuries in mouse rectum after fractionated X-ray and neutron irradiation

Purpose: to assess mouse rectum tolerance to fractionated X-ray and neutron irradiation. Materials and methods: doses per fraction ranged between 0.25 and 35 Gy for X-rays, 0.05 and 12 Gy for neutrons. Neutron top-up doses were added when the fractionated irradiation was given in fractions less than 2 Gy of X-rays or 0.35 Gy of neutrons in order to bring the damage into the detectable range. The early endpoints were the nadir of weight loss occurring within the first 2–3 weeks following irradiation and lethality by 2 months. The late endpoints were the peak of weight reached at maturity of the mice, the proportion of short feces in the daily fecal output at 10 months and lethality by 12 months. The linear-quadratic (LQ) model was fitted to the data (direct “one-step” analysis) and the estimated parameters were used to calculate relative biological effectiveness (RBE) values. Results: alpha/beta ratio estimates were for X-rays: 19.9 Gy [95% confidence limits: 15.2, 27.0] for weight nadir, 13.4 Gy [9.3, 19.5] for early lethality, 6.4 Gy [3.6, 11.0] for peak weight, and 6.9 Gy [4.2, 10.8] for late lethality, for neutrons: 19.9 Gy [9.5, 61.0] for peak weight. The fecal-deformity data were poorly fitted by the LQ model. The RBE was slightly higher for acute endpoints than for the late ones when X-ray fraction sizes were equal to or larger than 10 Gy. However, the change in RBE with decreasing X-ray dose per fraction was much steeper for the late endpoints, so that it became equal to or even higher than for acute reactions at doses per fraction of 5 Gy or less. Conclusion: Our results were consistent with those obtained from previously published studies using the same experimental system but larger doses per fraction.

Microdosimetric single‐event spectra for megavoltage electrons

Experimental techniques have been developed for obtaining single-event microdosimetric spectra from hospital based linear accelerators. Therapeutic electrons of 12, 15, 18, and 20 MeV from Clinic 18 and 20 accelerators have been produced at ultralow dose rates. Details of the experimental methods have been described previously by the authors. Single-event lineal energy spectra for these beams, as measured by a Rossi chamber differ significantly from cobalt-60 both in shape and dose average lineal energy (yd) which, depending on electron energy, can be 20-40% lower. The spectral peaks for electrons are greatly enhanced compared to cobalt. The yd for electrons also differs from previously reported values for 10-15 MV photon beams. These differences are less pronounced than for differences with cobalt. Spectral peaks and shapes correlate well with the actual electron stopping powers in tissue. The theory of dual radiation action predicts changes in relative biological effectiveness at low doses for megavoltage photon and electrons. Although at clinical doses the predicted differences are not statistically significant.

Changes in relative biological effectiveness with depth of neutron beams

(1) The point at issue in my letter (Hall, 1989), and the paper on which it was a comment (Hornsey et al, 1988), was the biological consequences of the difference in neutron spectra characteristic of the reactions involving protons on beryllium versus deuterons on beryllium; 14 MeV D–T neutrons are quite different. They can hardly be regarded as high-energy neutrons, and are nominally monoenergetic except for scattered neutrons from the collimator, and a large γ-ray component.

Changes in relative biological effectiveness with depth of neutron beams

In his letter on this subject in the August issue of the British Journal of Radiology (Hall, 1989), Professor E. J. Hall suggests that “the change of RBE [relative biological effectiveness] with depth is generally not seen for high energy neutron beams…where the neutron spectrum produced has a single peak”.

Changes in relative biological effectiveness with depth of neutron beams

The comments of Professor Hall are both interesting and pertinent, and indicate that if we are to assess the biological and medical effects of neutrons accurately, we should measure relative biological effectiveness changes with depth not only prior to using a new neutron beam but whenever changes in target construction are made or new beam colimation is introduced.