Risk estimation for fast neutrons with regard to solid cancer.

In the absence of epidemiological information on the effects of neutrons, their cancer mortality risk coefficient is currently taken as the product of two low-dose extrapolations: the nominal risk coefficient for photons and the presumed maximum relative biological effectiveness of neutrons. This approach is unnecessary. Since linearity in dose is assumed for neutrons at low to moderate effect levels, the risk coefficient can be derived in terms of the excess risk from epidemiological observations at an intermediate dose of gamma rays and an assumed value, R(1), of the neutron RBE relative to this reference dose of gamma rays. Application of this procedure to the A-bomb data requires accounting for the effect of the neutron dose component, which, according to the current dosimetry system, DS86, amounts on average to 11 mGy in the two cities at a total dose of 1 Gy. With R(1) tentatively set to 20 or 50, it is concluded that the neutrons have caused 18% or 35%, respectively, of the total effect at 1 Gy. The excess relative risk (ERR) for neutrons then lies between 8 per Gy and 16 per Gy. Translating these values into risk coefficients in terms of the effective dose, E, requires accounting for the gamma-ray component produced by the neutron field in the human body, which will require a separate analysis. The risk estimate for neutrons will remain essentially unaffected by the current reassessment of the neutron doses in Hiroshima, because the doses are unlikely to change much at the reference dose of 1 Gy.     

Oncogenic transformation by fractionated doses of neutrons

Oncogenic transformation was assayed after C3H 10T1/2 cells were irradiated with monoenergetic neutrons; cells were exposed to 0.23-, 0.35-, 0.45-, 5.9-, and 13.7-MeV neutrons given singly or in five equal fractions over 8 h. At the biologically effective neutron energy of 0.45 MeV, enhancement of transformation was evident with some small fractionated doses (below 1 Gy). When transformation was examined as a function of neutron energy at 0.5 Gy, enhancement was seen for cells exposed to three of the five energies (0.35, 0.45, and 5.9 MeV). Enhancement was greatest for cells irradiated with 5.9-MeV neutrons. Of the neutron energies examined, 5.9-MeV neutrons had the lowest dose-averaged lineal energy and linear energy transfer. This suggests that enhancement of transformation by fractionated low doses of neutrons may be radiation-quality dependent.     

Relative biological effectiveness and tolerance dose of fission neutrons in canine skin for a potential combination of neutron capture therapy and fast-neutron therapy

To investigate the potential efficacy of fission neutrons from a fast-neutron reactor for the treatment of radioresistant tumors, the relative biological effectiveness (RBE) and tolerance dose of fission neutrons in canine skin were determined. The forelimbs of 34 healthy mongrel dogs received a single dose of fission neutrons (5.6, 6.8, 8.2, 9.6 or 11 Gy) or 137Cs gamma rays (10, 15, 20, 25 or 30 Gy). Based on observations of radiodermatitis for each radiation, the single-fraction RBE of fission neutrons in the sixth month was calculated as approximately 3. The tolerance doses of fission neutrons and gamma rays, defined as the highest doses giving no moist desquamation on the irradiated skin in the recovery phase, were estimated as 7.6 Gy and 20 Gy, respectively. The tolerance dose of 7.6 Gy of fission neutrons included 5.0 Gy of fast neutrons possessing high anti-tumor effects and 1.4 x 10(12) n/cm2 of thermal neutrons, which could be applicable to neutron capture therapy (NCT). The combination of fast-neutron therapy and NCT using a fast-neutron reactor might be useful for the treatment of radioresistant tumors.     

Evaluation of the relative biological effectiveness of a clinical epithermal neutron beam using dog brain

This investigation was designed to determine the relative biological effectiveness (RBE) of an epithermal neutron beam (FiR 1 beam) using the brains of dogs. The FiR 1 beam was developed for the treatment of patients with glioma using boron neutron capture therapy. Comparisons were made between the effects of whole-brain irradiation with epithermal neutrons and 6 MV photons. For irradiations with epithermal neutrons, three dose groups were used, 9.4 +/- 0.1, 10.2 +/- 0.1 and 11.5 +/- 0.2 Gy. These physical doses were given as a single exposure and are quoted at the 90% isodose. Four groups of five dogs were irradiated with single doses of 10, 12, 14 or 16 Gy of 6 MV photons to the 100% isodose. Different reference isodoses were used to obtain the most comparable dose distribution in the brain for the two different irradiation modalities. Sequential magnetic resonance images (MRI) were taken for 77-115 weeks after irradiation to detect changes in the brain. Dose-effect relationships were established for changes in the brain as detected either by MRI or by subsequent gross morphology and histology. The doses that caused a specified response in 50% of the animals (ED(50)) were calculated from these dose-effect curves for each end point, and these values were used to calculate the RBE values for the different end points. The RBE values for the FiR 1 beam, based on changes observed on MRI, were in the range 1.2-1.3. For microscopic and gross pathological lesions, the values were in the range 1.2-1.4. The corresponding RBE values for the MRI and pathological end points for the high-LET components (protons from nitrogen capture and recoil protons from fast neutrons) were in the ranges 3.5-4.0 and 3.4-4.4, respectively. This assumed a dose-rate reduction factor of 0.6 for the low-dose-rate gamma-ray component of this beam. Finally, a comparison was made between experimentally derived photon doses, for a specified end point, with calculated photon equivalent doses, which were obtained using the weighting factors for clinical studies on the epithermal neutron beam on the Brookhaven Medical Research Reactor (BNL) in New York. This indicated that the radiation-induced lesions seen in the present study were, on average, detected at a 12% lower photon dose than predicted by the use of the BNL clinical weighting factors. This indicates the need for caution in the extrapolation of results from one reactor-based epithermal neutron beam to another.     

A comparison of gamma and neutron irradiation on Raji cells: effects on DNA damage, repair, cell cycle distribution and lethality.

The Comet assay (microgel electrophoresis) was used to study DNA damage in Raji cells, a B-lymphoblastoid cell line, after treatment with different doses of neutrons (0.5 to 16 Gy) or gamma rays (1.4 to 44.8 Gy). A better growth recovery was observed in cells after gamma-ray treatments compared with neutron treatments. The relative biological effectiveness (RBE) of neutron in cell killing was determined to be 2.5. Initially, the number of damaged cells per unit dose was approximately the same after neutron and gamma-ray irradiation. One hour after treatment, however, the number of normal cells per unit dose was much lower for neutrons than for gamma rays, suggesting a more efficient initial repair for gamma rays. Twenty-four hours after treatment, the numbers of damaged cells per unit dose of neutrons or gamma rays were again at comparable level. Cell cycle kinetic studies showed a strong G2/M arrest at equivalent unit dose (neutrons up to 8 Gy; gamma rays up to 5.6 Gy), suggesting a period in cell cycle for DNA repair. However, only cells treated with low doses (up to 2 Gy) seemed to be capable of returning into normal cell cycle within 4 days. For the highest dose of neutrons, decline in the number of normal cells seen at already 3 days after treatment was deeper compared with equivalent unit doses of gamma rays. Our present results support different mechanisms of action by these two irradiations and suggest the generation of locally multiply damaged sites (LMDS) for high linear energy transfer (LET) radiation which are known to be repaired at lower efficiency.     

Neutron relative biological effectiveness for solid cancer incidence in the Japanese A-bomb survivors: an analysis considering the degree of independent effects from γ-ray and neutron absorbed doses with hierarchical partitioning

It has generally been assumed that the neutron and γ-ray absorbed doses in the data from the life span study (LSS) of the Japanese A-bomb survivors are too highly correlated for an independent separation of the all solid cancer risks due to neutrons and due to γ-rays. However, with the release of the most recent data for all solid cancer incidence and the increased statistical power over previous datasets, it is instructive to consider alternatives to the usual approaches. Simple excess relative risk (ERR) models for radiation-induced solid cancer incidence fitted to the LSS epidemiological data have been applied with neutron and γ-ray absorbed doses as separate explanatory covariables. A simple evaluation of the degree of independent effects from γ-ray and neutron absorbed doses on the all solid cancer risk with the hierarchical partitioning (HP) technique is presented here. The degree of multi-collinearity between the γ-ray and neutron absorbed doses has also been considered. The results show that, whereas the partial correlation between the neutron and γ-ray colon absorbed doses may be considered to be high at 0.74, this value is just below the level beyond which remedial action, such as adding the doses together, is usually recommended. The resulting variance inflation factor is 2.2. Applying HP indicates that just under half of the drop in deviance resulting from adding the γ-ray and neutron absorbed doses to the baseline risk model comes from the joint effects of the neutrons and γ-rays—leaving a substantial proportion of this deviance drop accounted for by individual effects of the neutrons and γ-rays. The average ERR/Gy γ-ray absorbed dose and the ERR/Gy neutron absorbed dose that have been obtained here directly for the first time, agree well with previous indirect estimates. The average relative biological effectiveness (RBE) of neutrons relative to γ-rays, calculated directly from fit parameters to the all solid cancer ERR model with both colon absorbed dose covariables, is 65 (95 %CI: 11; 170). Therefore, although the 95 % CI is quite wide, reference to the colon doses with a neutron weighting of 10 may not be optimal as the basis for the determination of all solid cancer risks. Further investigations into the neutron RBE are required, ideally based on the LSS data with organ-specific neutron and γ-ray absorbed doses for all organs rather than the RBE weighted absorbed doses currently provided. The HP method is also suggested for use in other epidemiological cohort analyses that involve correlated explanatory covariables.     

Cancer risk estimates from the combined Japanese A-bomb and Hodgkin cohorts for doses relevant to radiotherapy

Most information on the dose–response of radiation-induced cancer is derived from data on the A-bomb survivors who were exposed to γ-rays and neutrons. Since, for radiation protection purposes, the dose span of main interest is between 0 and 1 Gy, the analysis of the A-bomb survivors is usually focused on this range. However, estimates of cancer risk for doses above 1 Gy are becoming more important for radiotherapy patients and for long-term manned missions in space research. Therefore in this work, emphasis is placed on doses relevant for radiotherapy with respect to radiation-induced solid cancer. The analysis of the A-bomb survivor’s data was extended by including two extra high-dose categories (4–6 Sv and 6–13 Sv) and by an attempted combination with cancer data on patients receiving radiotherapy for Hodgkin’s disease. In addition, since there are some recent indications for a high neutron dose contribution, the data were fitted separately for three different values for the relative biological effectiveness (RBE) of the neutrons (10, 35 and 100) and a variable RBE as a function of dose. The data were fitted using a linear, a linear-exponential and a plateau-dose–response relationship. Best agreement was found for the plateau model with a dose-varying RBE. It can be concluded that for doses above 1 Gy there is a tendency for a nonlinear dose–response curve. In addition, there is evidence of a neutron RBE greater than 10 for the A-bomb survivor data. Many problems and uncertainties are involved in combing these two datasets. However, since very little is currently known about the shape of dose–response relationships for radiation-induced cancer in the radiotherapy dose range, this approach could be regarded as a first attempt to acquire more information on this area. The work presented here also provides the first direct evidence that the bending over of the solid cancer excess risk dose response curve for the A-bomb survivors, generally observed above 2 Gy, is due to cell killing effects.     

Relative biological effectiveness measurements using murine lethality and survival of intestinal and hematopoietic stem cells after fermilab neutrons compared to JANUS reactor neutrons and 60Co gamma rays

The relative biological effectiveness (RBE) of the 25-MeV (average energy) neutron beam at the Fermi National Accelerator Laboratory was measured using murine bone marrow (LD50/30) and gut (LD50/6) lethality and killing of hematopoietic colony forming units (CFU-S) or intestinal clonogenic cells (ICC). The reference radiation was 60Co gamma rays. The LD50/30 and LD50/6 for mice exposed to the Fermilab neutron beam were 6.6 and 8.7 Gy, respectively, intermediate between those of JANUS neutrons and 60Co gamma rays. The D0 values for CFU-S and ICC were 47 cGy and 1.05 Gy, respectively, also intermediate between the lowest values found for JANUS neutrons and the highest values found after 60Co gamma rays. The split-dose survival ratios for CFU-S at intervals of 1-6 hr between doses were essentially 1.0 for both neutron sources, while the corresponding split-dose survival ratio for 60Co gamma rays was consistantly above 1, reaching a maximum of 1.7 with a 1-hr interval between doses. The 3-hr split-dose survival ratios for ICC were 1.0 for JANUS neutrons, 1.85 for Fermilab neutrons, and 6.5 for 60Co gamma rays. The RBE estimates for LD50/30 were 1.5 and 2.3 for Fermilab and JANUS neutrons, respectively. Based on LD50/6, the RBEs were 1.9 (Fermilab) and 3.0 (JANUS). The RBEs for CFU-S D0 were 1.4 (Fermilab) and 1.9 (JANUS) and for jejunal microcolony D0 1.4 (Fermilab) and 2.8 (JANUS).     

Sensitivity of SP cell line of melanoma B16 to low- and high-ionizing radiation

Cancer stem cells (CSC) found in multiple tumor types and cancer cell lines were shown to be more resistant to low-LET radiation in comparison to other cancer cells. Therefore, CSC are supposed to determine the long-term effect of cancer therapy. Research into the CSC sensitivity to high-LET radiation is of great interest because of the advances in hadron therapy. The aim of this investigation is to compare CSC and other cancer cell sensitivity to the low- (60Co gamma-rays) and high-LET (neutron) radiation. To identify CSC, we used the low cytometry-based side population (SP) technique based on the CSC capacity to produce the efflux of the vital dye Hoechst 33342. SP and non SP cells were sorted and exposed to gamma and neutron radiation at doses of 1-10 Gy and 0.1-4.7 Gy, correspondingly. We applied the colony-formation test to examine the SP and non SP survival rate after irradiation. It was shown that the sensitivity of SP to gamma-irradiation was lower than that of other cells: D0 average values (+/- SE) made up 2.3 +/- 0.3 Gy and 1.4 +/- 0.2 Gy, correspondingly (p = 0.047). The survival rate of SP and non SP did not differ after neutron irradiation. The values of relative biological effectiveness of neutron radiation relative to gamma-radiation at the D10 level were 2.6 for SP and 2.1 for other cells. The obtained results justify for the first time a high efficiency of application of neutrons in radiotherapy from the point of view of CSC elimination.     

First results of a randomized clinical trial of fast neutrons compared with X or gamma rays in treatment of advanced tumours of the head and neck. Report to the Medical Research Council.

Results of the first randomized clinical trial to compare the effects of fast neutrons and those of x or gamma rays (photons) in treating patients with advanced tumours of the head and neck are reported. In 37 out of 52 patients treated with neutrons and 16 out of 50 treated with photons the local tumour completely regressed; the tumour later recurred in nine of the 16 photon patients but in none of the 37 neutron patients. The advantages to the neutron-treated patients were seen in tumours of well and poorly differentiated histology and in each site. Complications after treatment did not differ significantly between the groups. Despite these substantial differences in local control of the tumour there were no significant differences in mortality between the series. A detailed study of the effective doses and the response of tumours and normal tissue in each series indicated that the improved results from neutron therapy were due to differences in the biological quality of the beam and not to the rather higher average effective dose in the neutron series. To assess the long-term effects of neutron treatment patients in earlier stages of disease and with smaller tumours should be included in the next phase of the trial.     

Out-of-field doses from secondary radiation produced in proton therapy and the associated risk of radiation-induced cancer from a brain tumor treatment

PurposeTo determine out-of-field doses produced in proton pencil beam scanning (PBS) therapy using Monte Carlo simulations and to estimate the associated risk of radiation-induced second cancer from a brain tumor treatment.MethodsSimulations of out-of-field absorbed doses were performed with MCNP6 and benchmarked against measurements with tissue-equivalent proportional counters (TEPC) for three irradiation setups: two irradiations of a water phantom using proton energies of 78–147 MeV and 177–223 MeV, and one brain tumor irradiation of a whole-body phantom. Out-of-field absorbed and equivalent doses to organs in a whole-body phantom following a brain tumor treatment were subsequently simulated and used to estimate the risk of radiation-induced cancer. Additionally, the contribution of absorbed dose originating from radiation produced in the nozzle was calculated from simulations.ResultsOut-of-field absorbed doses to the TEPC ranged from 0.4 to 135 µGy/Gy. The average deviation between simulations and measurements of the water phantom irradiations was about 17%. The absorbed dose contribution from radiation produced in the nozzle ranged between 0 and 70% of the total dose; the contribution was however small in absolute terms. The absorbed and equivalent doses to the organs ranged between 0.2 and 60 µGy/Gy and 0.5–151 µSv/Gy. The estimated lifetime risk of radiation-induced second cancer was approximately 0.01%.ConclusionsThe agreement of out-of-field absorbed doses between measurements and simulations was good given the sources of uncertainties. Calculations of out-of-field organ doses following a brain tumor treatment indicated that proton PBS therapy of brain tumors is associated with a low risk of radiation-induced cancer.     

Dose–response relationship of dicentric chromosomes in human lymphocytes obtained for the fission neutron therapy facility MEDAPP at the research reactor FRM II

The biological effectiveness of neutrons from the neutron therapy facility MEDAPP (mean neutron energy 1.9 MeV) at the new research reactor FRM II at Garching, Germany, has been analyzed, at different depths in a polyethylene phantom. Whole blood samples were exposed to the MEDAPP beam in special irradiation chambers to total doses of 0.14–3.52 Gy at 2-cm depth, and 0.18–3.04 Gy at 6-cm depth of the phantom. The neutron and γ-ray absorbed dose rates were measured to be 0.55 Gy min⁻¹ and 0.27 Gy min⁻¹ at 2-cm depth, while they were 0.28 and 0.25 Gy min⁻¹ at 6-cm depth. Although the irradiation conditions at the MEDAPP beam and the RENT beam of the former FRM I research reactor were not identical, neutrons from both facilities gave a similar linear-quadratic dose–response relationship for dicentric chromosomes at a depth of 2 cm. Different dose–response curves for dicentrics were obtained for the MEDAPP beam at 2 and 6 cm depth, suggesting a significantly lower biological effectiveness of the radiation with increasing depth. No obvious differences in the dose–response curves for dicentric chromosomes estimated under interactive or additive prediction between neutrons or γ-rays and the experimentally obtained dose–response curves could be determined. Relative to ⁶⁰Co γ-rays, the values for the relative biological effectiveness at the MEDAPP beam decrease from 5.9 at 0.14 Gy to 1.6 at 3.52 Gy at 2-cm depth, and from 4.1 at 0.18 Gy to 1.5 at 3.04 Gy at 6-cm depth. Using the best possible conditions of consistency, i.e., using blood samples from the same donor and the same measurement techniques for about two decades, avoiding the inter-individual variations in sensitivity or the differences in methodology usually associated with inter-laboratory comparisons, a linear-quadratic dose–response relationship for the mixed neutron and γ-ray MEDAPP field as well as for its fission neutron part was obtained. Therefore, the debate on whether the fission-neutron induced yield of dicentric chromosomes increases linearly with dose remains open.     

Thyroid cancer after exposure to external radiation: a pooled analysis of seven studies

The thyroid gland of children is especially vulnerable to the carcinogenic action of ionizing radiation. To provide insights into various modifying influences on risk, seven major studies with organ doses to individual subjects were evaluated. Five cohort studies (atomic bomb survivors, children treated for tinea capitis, two studies of children irradiated for enlarged tonsils, and infants irradiated for an enlarged thymus gland) and two case-control studies (patients with cervical cancer and childhood cancer) were studied. The combined studies include almost 120,000 people (approximately 58,000 exposed to a wide range of doses and 61,000 nonexposed subjects), nearly 700 thyroid cancers and 3,000,000 person years of follow-up. For persons exposed to radiation before age 15 years, linearity best described the dose response, even down to 0.10 Gy. At the highest doses (>10 Gy), associated with cancer therapy, there appeared to be a decrease or leveling of risk. For childhood exposures, the pooled excess relative risk per Gy (ERR/Gy) was 7.7 (95% CI = 2.1, 28.7) and the excess absolute risk per 10(4) PY Gy (EAR/10(4) PY Gy) was 4.4 (95% CI = 1.9, 10.1). The attributable risk percent (AR%) at 1 Gy was 88%. However, these summary estimates were affected strongly by age at exposure even within this limited age range. The ERR was greater (P = 0.07) for females than males, but the findings from the individual studies were not consistent. The EAR was higher among women, reflecting their higher rate of naturally occurring thyroid cancer. The distribution of ERR over time followed neither a simple multiplicative nor an additive pattern in relation to background occurrence. Only two cases were seen within 5 years of exposure. The ERR began to decline about 30 years after exposure but was still elevated at 40 years. Risk also decreased significantly with increasing age at exposure, with little risk apparent after age 20 years. Based on limited data, there was a suggestion that spreading dose over time (from a few days to >1 year) may lower risk, possibly due to the opportunity for cellular repair mechanisms to operate. The thyroid gland in children has one of the highest risk coefficients of any organ and is the only tissue with convincing evidence for risk at about 0.10 Gy.     

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.     

Radiation-related posterior lenticular opacities in Hiroshima and Nagasaki atomic bomb survivors based on the DS86 dosimetry system

This paper investigates the quantitative relationship of ionizing radiation to the occurrence of posterior lenticular opacities among the survivors of the atomic bombings of Hiroshima and Nagasaki suggested by the DS86 dosimetry system. DS86 doses are available for 1983 (93.4%) of the 2124 atomic bomb survivors analyzed in 1982. The DS86 kerma neutron component for Hiroshima survivors is much smaller than its comparable T65DR component, but still 4.2-fold higher (0.38 Gy at 6 Gy) than that in Nagasaki (0.09 Gy at 6 Gy). Thus, if the eye is especially sensitive to neutrons, there may yet be some useful information on their effects, particularly in Hiroshima. The dose-response relationship has been evaluated as a function of the separately estimated gamma-ray and neutron doses. Among several different dose-response models without and with two thresholds, we have selected as the best model the one with the smallest x2 or the largest log likelihood value associated with the goodness of fit. The best fit is a linear gamma-linear neutron relationship which assumes different thresholds for the two types of radiation. Both gamma and neutron regression coefficients for the best fitting model are positive and highly significant for the estimated DS86 eye organ dose.     

Neutron versus Á-ray risk estimates

While it is recognized that neutrons contributed to the excess cancer incidence and mortality among the atomic bomb survivors in Hiroshima, there is no possibility to deduce the magnitude of this contribution from the data. This remains true even if the neutron doses in the dosimetry system DS86 are corrected upwards in line with recent neutron activation measurements. In spite of this fact, important information can be obtained in the form of an inverse relation of the risk coefficients for γ-rays and neutrons. Such an interrelation must apply because the observed excess incidence or mortality is made up of a γ-ray and a neutron component; increased attribution to neutrons decreases the attribution to photons. Computations with the uncorrected and the corrected DS86 are performed for the mortality and the incidence of solid tumors combined. They refer to doses up to 2 Gy and employ the constant relative risk model and a linear-quadratic dose dependence with variable ratio – the neutron relative biological effectiveness (RBE) at low doses – of the linear component for neutrons and γ-rays. In line with past analyses, no quadratic component is obtained with the uncorrected DS86, but it is seen, even in these calculations, that the assumption of increased neutron RBEs does not translate into proportional increases of the risk coefficients of neutrons, because it leads to substantially reduced risk estimates for γ-rays. Calculations with the corrected dosimetry bring out this reciprocity even more clearly. High values of the neutron RBE reduce – in line with recent suggestions by Rossi and Zaider – the risk estimates for γ-rays substantially. Even a purely quadratic dose relation for γ-rays is consistent with the data; it requires no major increase of the nominal risk coefficients for neutrons over the currently assumed values. The cancer data from Hiroshima can still provide `prudent' risk estimates for photons, but with the corrected DS86, they do not prove that there is a linear component in the dose dependence for photons. Received: 20 January 1997 / Accepted in revised form: 14 March 1997     

Nonlinear survival curves for cells of solid tumors after large doses of fast neutrons and gamma rays.

We have previously proposed that survival curves for cells of murine NFSa fibrosarcomas after exposure to fast neutrons might demonstrate curvature when the neutron doses reach a level high enough to cure the fibrosarcomas. We report here that this is the case. Murine NFSa fibrosarcomas growing in the hind legs of syngeneic mice were exposed to either gamma rays or fast neutrons. The tumors were removed and retransplanted into fresh recipients to obtain 50% tumor cell doses, from which the dose-cell survival relationship was constructed. Survival curves showed continuous bending down to 10(-7), and were well fitted using the linear-quadratic model. The alpha and beta values for neutrons were larger than those for gamma rays. When the surviving fractions at experimental TCD50 doses were calculated using these values, comparable figures were obtained for neutrons and gamma rays. The RBEs for neutrons were comparable for the TCD50 and TD50 assays. Neutron RBE was independent of dose within a range of 5-28 Gy. The capacity of the tumors to repair the damage caused by large doses of neutrons was identical to that for small doses of neutrons, indicating that cells retained the capacity to repair neutron damage irrespective of the size of the dose.     

Induction of chromosome aberrations in G0 human lymphocytes by low doses of ionizing radiations of different quality

Human peripheral blood lymphocytes from two donors were exposed to low doses (0.05 to 2.0 Gy) of gamma rays, X rays, or fast neutrons of different energies. Chromosome aberrations were analyzed in metaphase of first-division cells after a culture time of 45-46 hr. At this time, less than 5% of the cells were found in second division. Different dose-response relationships were fitted to the data by using a maximum likelihood method; best fits for radiation-induced dicentric aberrations were obtained with the linear-quadratic law for all radiations. The linear component of this equation predominated, however, for neutrons in the range of doses studied, and the frequency of dicentrics induced by d(16)+Be neutrons up to 1.0 Gy could also be described by a linear relationship. The relative biological efficiency (RBE) of X rays and d(16)+Be, d(33)+Be, and d(50)+Be neutrons compared to 60Co gamma rays in the low dose range was calculated from the dose-effect relationships for the dicentrics produced. The RBE increased with decreasing neutron dose and with decreasing neutron energy from d(50)+Be to d(16)-+Be neutrons. The limiting RBE at low doses (RBEo) was calculated to be about 1.5 for X rays and 14.0, 6.2, and 4.7 for the d(16)+Be, d(33)+Be, and d(50)+Be neutrons, respectively.     

The impact of treatment parameter variation on secondary neutron spectra in high-energy electron beam radiotherapy

High-energy electron treatment procedures in radiotherapy pose a potential iatrogenic cancer risk as well as a critical health risk to patients with cardiac implantable electronic devices due to the generation of secondary neutrons in the linac head, the treatment room, and the patient. It may be argued that the neutron production from photons is well characterized, but the same is not true for electrons. Therefore, to assess the risk involved in an electron treatment, one must determine the neutron flux spectrum generated by the treatment procedure. The neutron spectrum depends on the treatment parameters used and therefore it is crucial to study its dependence on these parameters. In this work, eight experiments were devised to analyze how eight electron treatment parameters impacted the neutron spectrum. The parameters we considered were the electron beam energy, location of measurement, cutout size, collimator size, applicator size, collimator angle, choice of treatment room, and the presence or absence of a solid water phantom. For each experiment, we used a Nested Neutron Spectrometer™ (NNS) to measure the neutron flux spectra for multiple settings of the treatment parameter of interest. The resulting spectra were plotted and compared. We found that the electron beam energy and the location of measurement had the most impact on the neutron flux spectra, while the other parameters had a smaller or insignificant impact. This report may serve as a reference tool for medical physicists to help estimate the risk associated with a particular high-energy electron treatment procedure.     

Influence of beam incidence and irradiation parameters on stray neutron doses to healthy organs of pediatric patients treated for an intracranial tumor with passive scattering proton therapy

PurposeIn scattering proton therapy, the beam incidence, i.e. the patient’s orientation with respect to the beam axis, can significantly influence stray neutron doses although it is almost not documented in the literature.MethodsMCNPX calculations were carried out to estimate stray neutron doses to 25 healthy organs of a 10-year-old female phantom treated for an intracranial tumor. Two beam incidences were considered in this article, namely a superior (SUP) field and a right lateral (RLAT) field. For both fields, a parametric study was performed varying proton beam energy, modulation width, collimator aperture and thickness, compensator thickness and air gap size.ResultsUsing a standard beam line configuration for a craniopharyngioma treatment, neutron absorbed doses per therapeutic dose of 63 μGy Gy⁻¹ and 149 μGy Gy⁻¹ were found at the heart for the SUP and the RLAT fields, respectively. This dose discrepancy was explained by the different patient’s orientations leading to changes in the distance between organs and the final collimator where external neutrons are mainly produced. Moreover, investigations on neutron spectral fluence at the heart showed that the number of neutrons was 2.5 times higher for the RLAT field compared against the SUP field. Finally, the influence of some irradiation parameters on neutron doses was found to be different according to the beam incidence.ConclusionBeam incidence was thus found to induce large variations in stray neutron doses, proving that this parameter could be optimized to enhance the radiation protection of the patient.