RBE Of Neutrons Research Articles

Estimate of the Deterministic Neutron RBE for Radiation-induced Pseudo-Pelger Huët Cell Formation.

Using archival peripheral blood slides from radiation accident patients, we have recently described the pseudo-Pelger Huët anomaly (PPHA) in neutrophils as a new radiation-induced biomarker, useful for dosimetry not only immediately after a radiation incident but also potentially helpful as a tool in retrospective dosimetry. In conjunction with the Radiation Accident Registry at the Radiation Emergency Assistance Center/Training Site (REAC/TS), the frequency of PPHA cells has been compared from selected patients in the Y-12 criticality accident in Oak Ridge, TN, in 1958 and from the patient in the 1971 60Co accident at the USAEC Comparative Animal Research Laboratory (CARL), also in Oak Ridge. Patients A, C, and D in the Y-12 accident are described as having an average dose of 2.53 ± 0.14 Gy gamma + 0.90 ± 0.05 Gy neutron, while the patient in the CARL event had 2.6 Gy gamma dose from event reconstruction. Since the average gamma energies are almost identical in these two cohorts, it is possible to estimate the deterministic neutron relative biological effectiveness (RBEd) for PPHA formation in a criticality event. The neutron RBEd calculated in this way is an average value over the neutron fission energy spectrum and is found to be 3.4 ± 0.6, in good agreement with the currently recommended value of 3 for acute neutron dose to red marrow.

Assessing the impact of different neutron RBEs on the all solid cancer radiation risks obtained from the Japanese A-bomb survivors data

Purpose Development of a model characterizing risk variation with RBE to investigate how the incidence risk for all solid cancers combined varies with higher neutron RBEs and different organ dose types. Material and methods The model is based on RERF data with separate neutron and gamma dose information. Results For both additive and multiplicative linear excess risks per unit organ averaged dose, a reduction of 50% in the risk coefficient per weighted dose arises when a neutron RBE of 110 is used instead of 10. Considering risk per unit liver dose, this reduction occurs for an RBE of 130 and for risks per unit colon dose for an RBE of 190. The change in the shape of the dose response curve when using higher neutron RBEs is evaluated. The curvature changed and became significantly negative for males at an RBE of 140 for colon dose, 100 for liver dose and 80 for organ averaged dose. For females this is the case at an RBE of 110, 80 and 60, respectively. Conclusions Uncertainties in neutron RBE values should be considered when radiation risks and the shape of dose responses are deduced from cancer risk data from the atomic bomb survivors.

Fast neutron energy based modelling of biological effectiveness with implications for proton and ion beams

A practical neutron energy dependent RBE model has been developed, based on the relationship between a mono-energetic neutron energy and its likely recoil proton energy. Essentially, the linear energy transfer (LET) values of the most appropriate recoil proton energies are then used to modify the linear quadratic model radiosensitivities (α and β) from their reference LET radiation values to provide the RBE estimates. Experimental neutron studies published by Hall (including some mono-energetic beams ranging from 0.2 to 15 MeV), Broerse, Berry, and data from the Clatterbridge and Detroit clinical neutron beams, which all contain some data from a spectrum of neutron energies, are used to derive single effective neutron energies (NEeff) for each spectral beam. These energies yield a recoil proton spectrum, but with an effective mean proton energy (being around 50% of NEeff). The fractional increase in LET is given by the recoil proton LET divided by the proton (LETU) value which provides the highest RBE. This ratio is then used to determine the change in the linear-quadratic model α and β parameters, from those of the reference radiation, to estimate the RBE. The predicted proton recoil RBE is then reasonably close to the experimental neutron RBE values found when taking into account the variation inherent in biological experiments. The work has some important consequences. The data of Hall et al (1975 Radiat. Res. 64 245–55) shows that the highest RBE values are found with neutron energies around 0.3–0.4 MeV, but this energy cannot possibly generate recoil proton energies which are higher, as necessary for a 0.68 MeV proton with a 30.5 keV μm−1 LETU (the LET value which provides the maximum obtainable RBE for a specified ion). For 0.4 MeV neutrons with proton recoil energies of around 0.2 MeV, the latter have a LET of around 62.88 keV μm−1. This could have an impact on proton beam RBE modelling. However, this is compensated by finding that the maximum radiosensitivity for mono-energetic neutrons was around 1.7 times larger than previously suggested from experimental ion beam studies, probably due to the necessary spreading out of Bragg peaks for ion beam experimental purposes, sampling errors and particle range considerations. This semi-empirical model can be used with minimal computer support and could have applications in ionic beams and in radioprotection.

О некоторых методических вопросах исследования цитогенетических эффектов у пациентов со злокачественными новообразованиями при нейтронной терапии на циклотроне У-120

Purpose: To study dosimetric characteristics of neutron radiation field, to determine their role in the formation of the total cytogenetic effect in the patient’s body and to assess the cytogenetic dosimetry capabilities in improving the quality of NT. Material and methods: A therapeutic beam with the average neutron energy of ~6.3 MeV was obtained from the V-120 cyclotron. The radiation field of the beam was investigated with the help of two ionization chambers with different sensitivity to neutrons. Chamber with high and low sensitivities were made of polyethylene and graphite, respectively. To exclude the uncertainty associated with the change in beam intensity in time, a dosimeter monitor operating in the integral mode was used. Results: The dependence of the monitor factor on the irradiated area was measured. The distributions of the absorbed dose of neutrons and γ-radiation over the depth of the tissue-equivalent medium were found. The contribution of γ-radiation to the neutron dose was increased from ~10 % at the entry to the medium to ~30 % at a depth of 16 cm. Dose distributions of scattered neutron and γ-radiation in the plane of the end face of the forming device were obtained. The contribution of these radiations to the dose received by the patient’s body was estimated. This contribution was shown to be comparable with that from the therapeutic beam. The analysis of the influence of NT on the estimation of the frequency of chromosome aberrations in the blood of patients was carried out. Conclusion: The frequency of chromosome aberrations in the blood of patients was determined by the whole-body dose, including dose due to scattered radiation. When using equal focal doses, the cytogenetic effect was found to be dependent on the area of the irradiated field and the depth of the tumor in the patient’s body. The differences in the RBE of neutrons and γ-radiation as well as the instability of the therapeutic neutron beam intensity create uncertainties that do not allow for the necessary control over the doses using the cytogenetic dosimetry. Therefore, cytogenetic dosimetry should be combined with an effective instrument dosimetry method. The use of biodosimetry based on the assessment of the frequency of chromosome aberrations is promising for controlling the average whole-body dose, on which the overall radiation response of the body depends.

P11. - Assessment of out-of-field DNA damage and the impact of neutron RBE on secondary cancer risk in paediatric proton therapy

P11. - Assessment of out-of-field DNA damage and the impact of neutron RBE on secondary cancer risk in paediatric proton therapy

Оценка терапевтического фактора выигрыша в нейтронной терапии на основе линейно-квадратичной модели

Purpose: To study the dependencies of therapeutic gain factor (TGF) on dose of cyclotron-produced fast neutron beams using the linear-quadratic model (LQM) parameters characterizing radiation response in tumor and normal tissues.
 Material and methods: The TGF in neutron therapy was calculated as the ratio of the relative biological effectiveness of neutrons for tumor (RBE tumor) to relative biological effectiveness for normal tissue (RBE normal tissue). The LQM was used to calculate the dependencies of neutron RBE on the dose and therapeutic gain factor. We considered two cases: 1) neutron therapy for 3 types of tumors with different radiation response, where the same normal tissue was critical; 2) neutron therapy for the same tumor, when 3 types of normal tissues were taken as critical.
 Results: Based on calculations and analysis of published data, the dependencies of neutron RBE on dose for selected types of tumors and normal tissues were obtained. The following variants were considered: 1) RBE tumor > RBE normal tissue; 2) RBE tumor < RBE normal tissue, in both two variants, the dependen-
 cies in the therapeutic dose rate were convergent; 3) the dependencies of RBE tumor and RBE normal tissue on dose are crossed. The dependencies of TGF for neutron therapy on single boost doses and quantitative ratios between the LQM parameters characterizing radiation response of tumor and normal tissues were found. A multivariate ratio between the dependencies on dose of RBE tumor and RBE normal tissue was the cause of variety in the dependencies of TGF on dose. In the first case, the TGF increased with increasing (α/β)γ ratio and decreasing single dose, and the maximum value of TGF was equal to ~ 1.4. In the second case, TGF was < 1, i.e. the effectiveness of neutron therapy was lower than the effectiveness of gamma irradiation, but it was increased with higher single dose and lower radiosensitivity of normal tissue. In the third case, the dose at the intersection point (Di) was the boundary, and TGF was > 1 to the left of the boundary, and TPV was <1 to the right of the boundary, provided that D <Di, RBEtumor > OBEnormal tissue.
 Conclusion: The obtained results with known parameters of the LQM for tumor and normal tissues allowed us to make an appropriate choice between neutron and gamma- ray therapy in order to increase the effectiveness of treatment for cancer patients. It was shown that in the case of neutron therapy, the analysis of dependencies of TGF on dose allowed the optimal dose fractionation regimen to be selected.

Low dose radiation risks for women surviving the a-bombs in Japan: generalized additive model.

BackgroundAnalyses of cancer mortality and incidence in Japanese A-bomb survivors have been used to estimate radiation risks, which are generally higher for women. Relative Risk (RR) is usually modelled as a linear function of dose. Extrapolation from data including high doses predicts small risks at low doses. Generalized Additive Models (GAMs) are flexible methods for modelling non-linear behaviour.MethodsGAMs are applied to cancer incidence in female low dose subcohorts, using anonymous public data for the 1958 – 1998 Life Span Study, to test for linearity, explore interactions, adjust for the skewed dose distribution, examine significance below 100 mGy, and estimate risks at 10 mGy.ResultsFor all solid cancer incidence, RR estimated from 0 – 100 mGy and 0 – 20 mGy subcohorts is significantly raised. The response tapers above 150 mGy. At low doses, RR increases with age-at-exposure and decreases with time-since-exposure, the preferred covariate. Using the empirical cumulative distribution of dose improves model fit, and capacity to detect non-linear responses. RR is elevated over wide ranges of covariate values. Results are stable under simulation, or when removing exceptional data cells, or adjusting neutron RBE. Estimates of Excess RR at 10 mGy using the cumulative dose distribution are 10 – 45 times higher than extrapolations from a linear model fitted to the full cohort. Below 100 mGy, quasipoisson models find significant effects for all solid, squamous, uterus, corpus, and thyroid cancers, and for respiratory cancers when age-at-exposure > 35 yrs. Results for the thyroid are compatible with studies of children treated for tinea capitis, and Chernobyl survivors. Results for the uterus are compatible with studies of UK nuclear workers and the Techa River cohort.ConclusionNon-linear models find large, significant cancer risks for Japanese women exposed to low dose radiation from the atomic bombings. The risks should be reflected in protection standards.Electronic supplementary materialThe online version of this article (doi:10.1186/s12940-016-0191-3) contains supplementary material, which is available to authorized users.

Neutrons in proton pencil beam scanning: parameterization of energy, quality factors and RBE

The biological effectiveness of neutrons produced during proton therapy in inducing cancer is unknown, but potentially large. In particular, since neutron biological effectiveness is energy dependent, it is necessary to estimate, besides the dose, also the energy spectra, in order to obtain quantities which could be a measure of the biological effectiveness and test current models and new approaches against epidemiological studies on cancer induction after proton therapy. For patients treated with proton pencil beam scanning, this work aims to predict the spatially localized neutron energies, the effective quality factor, the weighting factor according to ICRP, and two RBE values, the first obtained from the saturation corrected dose mean lineal energy and the second from DSB cluster induction.A proton pencil beam was Monte Carlo simulated using GEANT. Based on the simulated neutron spectra for three different proton beam energies a parameterization of energy, quality factors and RBE was calculated. The pencil beam algorithm used for treatment planning at PSI has been extended using the developed parameterizations in order to calculate the spatially localized neutron energy, quality factors and RBE for each treated patient.The parameterization represents the simple quantification of neutron energy in two energy bins and the quality factors and RBE with a satisfying precision up to 85 cm away from the proton pencil beam when compared to the results based on 3D Monte Carlo simulations. The root mean square error of the energy estimate between Monte Carlo simulation based results and the parameterization is 3.9%. For the quality factors and RBE estimates it is smaller than 0.9%. The model was successfully integrated into the PSI treatment planning system.It was found that the parameterizations for neutron energy, quality factors and RBE were independent of proton energy in the investigated energy range of interest for proton therapy. The pencil beam algorithm has been extended using the developed parameterizations in order to calculate the neutron energy, quality factor and RBE.

SU‐F‐T‐128: Dose‐Volume Constraints for Particle Therapy Treatment Planning

Purpose:Determine equivalent Organ at Risk (OAR) tolerance dose (TD) constraints for MV x‐rays and particle therapy.Methods:Equivalent TD estimates for MV x‐rays are determined from an isoeffect, regression‐analysis of published and in‐house constraints for various fractionation schedules (n fractions). The analysis yields an estimate of (α/β) for an OAR. To determine equivalent particle therapy constraints, the MV x‐ray TD(n) values are divided by the RBE for DSB induction (RBEDSB) or cell survival (RBES). Estimates of (RBEDSB) are computed using the Monte Carlo Damage Simulation, and estimates of RBES are computed using the Repair‐Misrepair‐Fixation (RMF) model. A research build of the RayStation™ treatment planning system implementing the above model is used to estimate (RBEDSB) for OARs of interest in 16 proton therapy patient plans (head and neck, thorax, prostate and brain).Results:The analysis gives an (α/β) estimate of about 20 Gy for the trachea and heart and 2–4 Gy for the esophagus, spine, and brachial plexus. Extrapolation of MV x‐ray constraints (n = 1) to fast neutrons using RBEDSB = 2.7 are in excellent agreement with clinical experience (n = 10 to 20). When conventional (n > 30) x‐ray treatments are used as the reference radiation, fast neutron RBE increased to a maximum of 6. For comparison to a constant RBE of 1.1, the RayStation™ analysis gave estimates of proton RBEDSB from 1.03 to 1.33 for OARs of interest.Conclusion:The presented system of models is a convenient formalism to synthesize from multiple sources of information a set of self‐consistent plan constraints for MV x‐ray and hadron therapy treatments. Estimates of RBEDSB from the RayStation™ analysis differ substantially from 1.1 and vary among patients and treatment sites. A treatment planning system that incorporates patient and anatomy‐specific corrections in proton RBE would create opportunities to increase the therapeutic ratio.The research build of the RayStation used in the study was made available to the University of Washington free of charge. RaySearch Laboratories did not provide any monetary support for the reported studies.

Эффективность фракционированного воздействия γ-излучения и быстрых нейтронов на саркому М-1

The effectiveness of fractionated exposure to gamma- and neutron radiation in their separate and combined use on the growth and functional morphology of mutant p53 sarcoma M-1 in rats was studied. Investigation techniques included immunostaining of PCNA and mutant p53 expressing cells, determination of mitotic activity and apoptotic death of tumor cells, as well as computer analysis of microscopic images. The antitumor efficacy of different types of radiation is shown to be determined by different levels of apoptosis induction, reduced proliferation and cellularity. Neutron radiation of the impulse generator has a marked damaging effect on the vasculature and the development of tumor necrosis. Fractionated irradiation at equal daily doses led to the decrease in the relative effectiveness of radio-inactivation of tumor cells. After 9 fractions of irradiation, the calculated value of the RBE of fast neutrons normalized to the input dose of 1 Gy by the coefficient of tumor growth inhibition, a reduced proliferative activity of PCNA and induced apoptosis of tumor cells was 3.4, 3.7 and 3.1, respectively. In the mode of daily superfractionation with splitting the dose in two fractions, the effectiveness of the combined exposure corresponded to the additive effect of gamma- and neutron radiation with a tendency toward synergism. There are reasons to believe that high resistance of sarcoma M-1 to the ionizing radiation impact is due not only to a fraction of hypoxic cells, but also the mutant status of p53 gene.

RBE of thermal neutrons for induction of chromosome aberrations in human lymphocytes

The induction of chromosome aberrations in human lymphocytes irradiated in vitro with slow neutrons was examined to assess the maximum low-dose RBE (RBE(M)) relative to (60)Co γ-rays. For the blood irradiations, cold neutron beam available at the prompt gamma activation analysis facility at the Munich research reactor FRM II was used. The given flux of cold neutrons can be converted into a thermally equivalent one. Since blood was taken from the same donor whose blood had been used for previous irradiation experiments using widely varying neutron energies, the greatest possible accuracy was available for such an estimation of the RBE(M) avoiding the inter-individual variations or differences in methodology usually associated with inter-laboratory comparisons. The magnitude of the coefficient α of the linear dose-response relationship (α=0.400±0.018Gy(-1)) and the derived RBE(M) of 36.4±13.3 obtained for the production of dicentrics by thermal neutrons confirm our earlier observations of a strong decrease in α and RBE(M) with decreasing neutron energy lower than 0.385MeV (RBE(M)=94.4±38.9). The magnitude of the presently estimated RBE(M) of thermal neutrons is-with some restrictions-not significantly different to previously reported RBE(M) values of two laboratories.

Assessment of cancer risk from neutron exposure – The ANDANTE project

The ANDANTE project began in January 2012 as a spin-off of results of an earlier Euratom project, ALLEGRO, designed to address the problems of medium- and long-term risks following radiotherapy. ANDANTE will investigate the relative risk of induction of cancer from exposure to neutrons compared to photons. The project will focus on three specific cancers that may be detected as second malignant neoplasms following paediatric radiotherapy: salivary gland, thyroid gland, and breast tissue. Stem cells from each of the types of tissue will be exposed to well characterised beams of both neutrons and photons. Biological markers of possible tumorigenesis will be used to develop RBE models for neutrons. The experimental beams will be measured in terms of fluence and energy spectra in order to provide date for a track structure model, which will be developed to simulate the exact experimental conditions and to explore the relationships between exposure parameters and response. The RBE model will be utilized in the assessment of follow-up data from paediatric photon radiotherapy patients. The out-of-beam mixed photon-neutron fields generated during proton therapy will be measured in phantoms, and an analytic algorithm will be developed for reconstructing the fields distant from the treatment site using data available from clinical records. One of the aims of the project is a critical analysis of the potential power of a multi-centre cohort of paediatric patients to give confidence in the neutron risk estimates in radiotherapy patients.This paper focuses on the challenges in the ANDANTE project posed by the need to know detailed neutron, photon, and charged particle fluences and energy spectra in order to determine the neutron RBE as a function of dose and energy.

A two-mutation model of radiation-induced acute myeloid leukemia using historical mouse data

From studies of the atomic bomb survivors, it is well known that ionizing radiation causes several forms of leukemia. However, since the specific mechanism behind this process remains largely unknown, it is difficult to extrapolate carcinogenic effects at acute high-dose exposures to risk estimates for the chronic low-dose exposures that are important for radiation protection purposes. Recently, it has become clear that the induction of acute myeloid leukemia (AML) in CBA/H mice takes place through two key steps, both involving the Sfpi1 gene. A similar mechanism may play a role in human radiation-induced AML. In the present paper, a two-mutation carcinogenesis model is applied to model AML in several data sets of X-ray- and neutron-exposed CBA/H mice. The models obtained provide good fits to the data. A comparison between the predictions for neutron-induced and X-ray-induced AML yields an RBE for neutrons of approximately 3. The model used is considered to be a first step toward a model for human radiation-induced AML, which could be used to estimate risks of exposure to low doses.

Effects of low doses by different types of radiation on the waxy locus in barley and maize

The mutation frequency in the pollen character waxy of barley and maize was investigated after different irradiations. Altogether 17 experimental series are presented, 8 of which have been published earlier. The experiments indicate that the RBE of fast neutrons is lower than 3. It seems probable that lower doses are more mutagenic than higher ones per dose unit.

Microdosimetry on a Mini-Reactor UTR-KINKI for Educational Uses and Biological Researches

Microdosimetry study has been carried out at the education and research mini-reactor of Kinki University (UTR-KINKI) using a tissue equivalent gas proportional counter (TEPC). The microdosimetric single event spectra for 0.5, 1, 2, 3 and 5 microm site sizes were obtained in the lineal energy range from 1 to 1000 keV/microm. Neutron and gamma-ray fractional doses were estimated from the single event spectra. The neutron dose fraction was varied from 35 to 55% for 0.5 to 5 microm site size. The averaged lineal energy, y(D), for each site size was likewise estimated and found to be dependent on the site size. The averaged lineal energy for neutron was slightly larger than that of the fission neutrons from (252)Cf, and the averaged lineal energy for gamma-ray had similar site-size-dependence of 25 keV gamma-rays and 250 kV X-rays. Relative biological effectiveness was found to be 4.1 +/- 0.13 for UTR-KINKI using Tilikidis's 2 Gy-response function. The estimated RBE for UTR-KINKI neutrons is quite close to the previous biological experimental value of 4.3 +/- 0.6 for micronucleated cells in gill cell of Medaka and 4.6 +/- 0.5 for induction of lymphocyte apoptosis in the thymus of ICR mice.

Variations in the Radiosensitivity of T-lymphocytes of different Individuals to a Therapeutic Neutron Beam

Purpose: Variations in the radiosensitivty of different tumours pertain to the potential for therapeutic gain for treatment with high energy neutrons. In this work the radiosensitivities of T-lymphocytes of different individuals to the clinical neutron beam at iThemba LABS were measured. The objective of this investigation was to establish if a relationship between neutron RBE and resistance to conventional gamma radiation could be determined. Materials and Methods: Peripheral blood samples were collected from five healthy donors. Whole blood was exposed to different doses of 60Co gamma rays (1-5 Gy) and p(66)/Be neutrons (0.5-2.5 Gy). One sample per donor was not exposed to radiation and served as a control. From each sample, lymphocytes were separated and cultured to induce micronuclei in cytokinesis-blocked cells. The micronuclei yield and nucleation index were assessed using fluorescent microscopy. Radiosensitiviies and RBE values were calculated from the fitted dose response micronuclei frequency data. Results: Dose limiting RBE values for the clinical neutron beam were found to range from 1.8 to 11.2 with a mean value of 6.5 ± 3.4. A clear reduction in neutron RBE is noted for donors with lymphocytes more sensitive to gamma rays (p = 0.05, R2 = 0.9). Conclusion: The correlation between neutron RBE and cellular radioresistance to photons suggests a potential for therapeutic gain for some patients treated with the high energy neutron beam at iThemba LABS.

Lung Cancer Risk in Mice: Analysis of Fractionation Effects and Neutron RBE with a Biologically Motivated Model

Data from Argonne National Laboratory on lung cancer in 15,975 mice with acute and fractionated exposures to gamma rays and neutrons are analyzed with a biologically motivated model with two rate-limiting steps and clonal expansion. Fractionation effects and effects of radiation quality can be explained well by the estimated kinetic parameters. Both an initiating and a promoting action of neutrons and gamma rays are suggested. While for gamma rays the initiating event is described well with a linear dose-rate dependence, for neutrons a nonlinear term is needed, with less effectiveness at higher dose rates. For the initiating event, the neutron RBE compared to gamma rays is about 10 when the dose rate during each fraction is low. For higher dose rates this RBE decreases strongly. The estimated lifetime relative risk for radiation-induced lung cancers from 1 Gy of acute gamma-ray exposure at an age of 110 days is 1.27 for male mice and 1.53 for female mice. For doses less than 1 Gy, the effectiveness of fractionated exposure to gamma rays compared to acute exposure is between 0.4 and 0.7 in both sexes. For lifetime relative risk, the RBE from acute neutrons at low doses is estimated at about 10 relative to acute gamma-ray exposure. It decreases strongly with dose. For fractionated neutrons, it is lower, down to about 4 for male mice.

INDICATIONS OF THE NEUTRON EFFECT CONTRIBUTION IN THE SOLID CANCER DATA OF THE A-BOMB SURVIVORS

Risk estimates for radiation-induced cancer are primarily based on the follow-up of the Japanese A-bomb survivors. Their exposures were due to gamma rays and neutrons, and, currently--with the assumed low RBE = 10 of neutrons and reference to the colon dose--the late radiation effects are almost fully attributed to the gamma rays. Solid cancer risk estimates for different organ sites are assessed here, and an inconspicuous but statistically highly significant trend of larger values is found for the organs closer to the body surface; i.e., the organs with less body shielding and, therefore, with larger neutron dose-fractions. Underestimation of the RBE of neutrons can explain this apparent correlation. The trend of ERR/Gy vs. depth ceases to be statistically significant for RBE values close to 100. The suggestion of high RBE values and the corresponding reduction of gamma-ray risk estimates is found to be in line with log-likelihood computations in terms of AMFIT, which provide for the solid cancer mortality of the A-bomb survivors the minimum deviance for RBE = 100 with a 95% confidence lower limit of 25. The present assessment had to use the data made publicly available by RERF. In this form they contain city-, sex-, age-, and dose-categories, but--instead of a separate neutron-dose category--only the mean neutron dose for each data cell. The tentative conclusions that are here obtained should, therefore, be examined by a more definitive analysis, either in terms of grouped data with a separate classification of neutron doses or, ideally, in terms of person by person calculations to be performed at RERF with individually estimated neutron doses.

Estimation of relative biological effectiveness of 6 and 22 MeV neutrons and 137Cs γ-rays based on the analysis of chromosome aberrations in human peripheral blood lymphocytes

Summary Aim This investigation presents the estimation of cytogenetic injury in human peripheral blood lymphocytes and its dependence on the dose and quality of ionizing radiation applied in radiotherapy of cancer patients with the purpose of calculating RBE values for different radiation sources in the dose range under study. Materials/Methods Cytogenetic dosimetry was carried out at an exposure of human lymphocyte cultures to 137 Cs and 60 Co therapeutic sources and neutrons with average energies of 6 and 22 MeV. Results Increase in dose reduces RBE values of 137 Cs γ-irradiation, which in the range of doses investigated (0.3–5.0 Gy) vary between 3.5–1.3, respectively. Thus the difference in RBE values can be most accurately determined in the 0.5–2.0 Gy dose interval usually used in radiotherapy. Comparative estimation of fast neutron RBE values showed that 6 MeV neutrons give significantly higher yields of chromosome aberrations as compared with 22 Mev neutrons. It was shown that cytogenetic effectiveness has a tendency to decrease with the increase in the depth of the water phantom. The largest effect was observed at the depth of up to 6 cm. Conclusions The results of our pre-clinical studies indicate that radiation-induced effects simultaneously depend on different irradiation parameters such as dose, energy and the depth of the irradiated biological object, which should be taken into account in radiotherapy of cancer patients.

Cancer risk estimates for gamma-rays with regard to organ-specific doses

Part I of this study presented an analysis of the solid cancer mortality data for 1950-1997 from the Japanese life-span study of the A-bomb survivors to assess the cancer risk for gamma-rays in terms of the organ-specific dose for all solid cancers combined. Compared to earlier analyses, considerably more curvature in the dose-effect relation is indicated by these computations, which now suggests a dose and dose-rate effectiveness factor of about 2. The computations are extended here in order to explore the site-specific solid cancer risks for various organs. A computational method has been developed whereby the site-specific cancer risks are all simultaneously computed with global age and gender effect modifiers. This provides a more parsimonious representation with fewer parameters and avoids the large relative standard errors which would otherwise result. The sensitivity of site-specific risks to the choices of the neutron RBE is examined. The site-specific risk estimates are quite sensitive to the neutron RBE for the least shielded organs such as the breast, bladder and oesophagus. For the deeper lying organs, such as the gallbladder, pancreas and uterus, the impact of the neutrons is much lower. With an assumed neutron RBE of 35, which is in line with results on low neutron doses in major past studies on rodents and which corresponds approximately to the current ICRP radiation weighting factor for neutrons, the neutrons appear to contribute about 40% of the observed excess cancer risk in the breast, i.e. the organ that is closest to the body surface. However, this neutron contribution fraction is only about 10% for deeper lying organs, such as the colon.