The role of SSDL in quality assurance in radiotherapy

This paper describes the role of the Polish Secondary Standard Dosimetry Laboratory (SSDL) in quality assurance in radiotherapy by means of providing calibration of ionisation chambers, TLD postal dosimetry audits and end-to-end audits for radiation therapy. A historical review of the methods and results are presented. The influence of the SSDL in Warsaw on radiation protection of patients in Poland is discussed. The International Atomic Energy Agency together with World Health Organisation (IAEA/WHO), through its network of SSDLs around the world, propagates newly developed methods for calibration and auditing. Suitable high quality equipment was provided by the IAEA, as well as special materials and technical support to the SSDL in Warsaw. The activity of the SSDL and the services provided for Polish radiotherapy centres have resulted in a reduction of discrepancies between planned doses and doses delivered to patients. The newly tested IAEA methods of end-to-end on-site dosimetry audits allow for monitoring and improving the quality of IMRT in Poland. The traceability of standards used for the calibration of therapy level dosimeters from Polish radiotherapy centres is assured by the IAEA dosimetry laboratory. The consistency of methods performed in the Polish SSDL with the ISO:17025 norm is supervised by the Polish Centre for Accreditation – a member of International Laboratory Accreditation Cooperation (ILAC), for calibration and testing. Due to the rapid technological development of radiotherapy, special attention has to be paid to newly developed methods for dosimetry auditing and institutions which provide services for assuring radiation safety of patients.     

Dosimetry of low-energy neutrons using low-pressure proportional counters

Measurements in nearly monoenergetic beams of 144, 24.5, and 2 keV neutrons and of thermal neutrons have been performed with low-pressure proportional counters. The suitability of a tissue-equivalent proportional counter (TEPC) for dosimetry of low-energy neutrons has been investigated. In contrast to higher neutron energies, the modification of the primary radiation field by the detector wall and the contribution of secondaries produced in the gas are significant. These effects have been investigated by additional measurements with a carbon-walled proportional counter. The various physical processes of neutron interaction with wall and gas of the TEPC have been analyzed, and absorbed dose, kerma, and kerma contributions from the various processes are presented. In addition, dose contributions from contaminating neutrons and photons have been obtained for the calibration fields used. The results have been related to neutron fluence. The comparison with tabulated kerma factors shows excellent agreement, indicating the suitability of the TEPC method for dosimetry of low-energy neutrons.     

Absorbed doses in tissue-equivalent spheres above radioactive sources in soil

Doses due to external exposure of terrestrial biota are assessed using differential air kerma from radioactive sources in soil and energy-dependent ‘absorbed dose-per-air kerma’ conversion factors computed for spherical tissue-equivalent bodies. The presented approach allows computing average whole body absorbed dose for terrestrial organisms with body masses from 1 mg to 1,000 kg located at heights from 10 cm to 500 m above ground. Radioactive sources in soil emitting photons with energies from 10 keV to 10 MeV have been considered. Interpolation of the computed quantities over source energy, body mass, and height above ground results in plausible estimates of whole body average absorbed doses for non-human terrestrial biota from gamma-radiation emitted by any radionuclides in contaminated terrain.     

Allowance for random dose estimation errors in atomic bomb survivor studies: a revision

Allowing for imprecision of radiation dose estimates for A-bomb survivors followed up by the Radiation Effects Research Foundation can be improved through recent statistical methodology. Since the entire RERF dosimetry system has recently been revised, it is timely to reconsider this. We have found that the dosimetry revision itself does not warrant changes in these methods but that the new methodology does. In addition to assumptions regarding the form and magnitude of dose estimation errors, previous and current methods involve the apparent distribution of true doses in the cohort. New formulas give results conveniently and explicitly in terms of these inputs. Further, it is now possible to use assumptions about two components of the dose errors, referred to in the statistical literature as "classical" and "Berkson-type". There are indirect statistical indications, involving non-cancer biological effects, that errors may be somewhat larger than assumed before, in line with recommendations made here. Inevitably, methods must rely on uncertain assumptions about the magnitude of dose errors, and it is comforting to find that, within the range of plausibility, eventual cancer risk estimates are not very sensitive to these.     

Organ doses from radiation therapy in atomic bomb survivors

Previous surveys of radiation therapy among the Life Span Study (LSS) population at the Radiation Effects Research Foundation (RERF) revealed that 1,670 (1.4%) of the LSS participants received radiation treatments before 1984. The data on therapeutic radiation doses are indispensable for studying the relationship between radiation treatments and subsequent cancer occurrences. In this study, the radiation treatments were reproduced experimentally to determine the scattered radiation doses. The experiments were conducted using a female human phantom and various radiation sources, including a medium-voltage X-ray machine and a (60)Co gamma-ray source. Doses were measured using thermoluminescence dosimetry and ionization chambers. Radiation doses were determined for the salivary glands, thyroid gland, breast, lung, stomach, colon, ovary and active bone marrow. The results have been used for documenting the organ doses received by patients in previous surveys. The contribution of therapeutic irradiation to the occurrence of chromosome aberrations was studied using data on doses to active bone marrow from both radiation treatments and atomic bomb exposures in 26 RERF Adult Health Study participants. The results suggest that radiation treatments contributed to a large part of their frequencies of stable-type chromosome aberrations. The therapeutic radiation doses determined in the present study are available for investigating the effects of therapeutic irradiation on the subsequent primary cancers among atomic bomb survivors who received radiation treatments.     

Alanine radicals,part 3: properties of the components contributing to the EPR spectrum of X-irradiated alanine dosimeters

The amino acid l-alpha-alanine has attracted considerable interest for use in radiation dosimetry and has been formally accepted as a secondary standard for high-dose and transfer dosimetry. Recent results have shown that the alanine EPR spectrum consists of contributions from three different radicals. A set of benchmark spectra describing the essential spectral features of these three radical components was used for reconstructions of the experimental spectra. In the present work, these basis spectra have been used to investigate the differential effects of variations in radiation doses and microwave power, as well as the dependence upon temperature annealing and UV illumination. The results presented here, based solely on relatively low-energy (60-80 keV) X rays, indicate that the three components behave very similarly with respect to radiation dose at room temperature. However, with respect to the thermal annealing/fading behavior and microwave power saturation properties, the three species behave significantly differently. It is concluded that even if it is now realized that three different radicals contribute to the composite EPR alanine spectrum, this has a minor impact on the established protocols for present-day applications (high-dose) of EPR/alanine dosimetry. However, some care should be exercised when e.g. constructing calibration curves, since fading and power saturation behavior may vary over the dose range in question. New results from UV-illumination experiments suggest a possible procedure for experimental spectral separation of the EPR signals due to the three radicals.     

In situ biological dose mapping estimates the radiation burden delivered to 'spared' tissue between synchrotron X-ray microbeam radiotherapy tracks

Microbeam radiation therapy (MRT) using high doses of synchrotron X-rays can destroy tumours in animal models whilst causing little damage to normal tissues. Determining the spatial distribution of radiation doses delivered during MRT at a microscopic scale is a major challenge. Film and semiconductor dosimetry as well as Monte Carlo methods struggle to provide accurate estimates of dose profiles and peak-to-valley dose ratios at the position of the targeted and traversed tissues whose biological responses determine treatment outcome. The purpose of this study was to utilise γ-H2AX immunostaining as a biodosimetric tool that enables in situ biological dose mapping within an irradiated tissue to provide direct biological evidence for the scale of the radiation burden to 'spared' tissue regions between MRT tracks. Γ-H2AX analysis allowed microbeams to be traced and DNA damage foci to be quantified in valleys between beams following MRT treatment of fibroblast cultures and murine skin where foci yields per unit dose were approximately five-fold lower than in fibroblast cultures. Foci levels in cells located in valleys were compared with calibration curves using known broadbeam synchrotron X-ray doses to generate spatial dose profiles and calculate peak-to-valley dose ratios of 30-40 for cell cultures and approximately 60 for murine skin, consistent with the range obtained with conventional dosimetry methods. This biological dose mapping approach could find several applications both in optimising MRT or other radiotherapeutic treatments and in estimating localised doses following accidental radiation exposure using skin punch biopsies.     

The effect of dose rate on radiation-induced neoplastic transformation in vitro by low doses of low-LET radiation

The dependence of the incidence of radiation-induced cancer on the dose rate of the radiation exposure is a question of considerable importance to the estimation of risk of cancer induction by low-dose-rate radiation. Currently a dose and dose-rate effectiveness factor (DDREF) is used to convert high-dose-rate risk estimates to low dose rates. In this study, the end point of neoplastic transformation in vitro has been used to explore this question. It has been shown previously that for low doses of low-LET radiation delivered at high dose rates, there is a suppression of neoplastic transformation frequency at doses less than around 100 mGy. In the present study, dose-response curves up to a total dose of 1000 mGy have been generated for photons from (125)I decay (approximately 30 keV) delivered at doses rates of 0.19, 0.47, 0.91 and 1.9 mGy/min. The results indicate that at dose rates of 1.9 and 0.91 mGy/min the slope of the induction curve is about 1.5 times less than that measured at high dose rate in previous studies with a similar quality of radiation (28 kVp mammographic energy X rays). In the dose region of 0 to 100 mGy, the data were equally well fitted by a threshold or linear no-threshold model. At dose rates of 0.19 and 0.47 mGy/min there was no induction of transformation even at doses up to 1000 mGy, and there was evidence for a possible suppressive effect. These results show that for this in vitro end point the DDREF is very dependent on dose rate and at very low doses and dose rates approaches infinity. The relative risks for the in vitro data compare well with those from epidemiological studies of breast cancer induction by low- and high-dose-rate radiation.     

New models for evaluation of radiation-induced lifetime cancer risk and its uncertainty employed in the UNSCEAR 2006 report

Generalized relative and absolute risk models are fitted to the latest Japanese atomic bomb survivor solid cancer and leukemia mortality data (through 2000), with the latest (DS02) dosimetry, by classical (regression calibration) and Bayesian techniques, taking account of errors in dose estimates and other uncertainties. Linear-quadratic and linear-quadratic-exponential models are fitted and used to assess risks for contemporary populations of China, Japan, Puerto Rico, the U.S. and the UK. Many of these models are the same as or very similar to models used in the UNSCEAR 2006 report. For a test dose of 0.1 Sv, the solid cancer mortality for a UK population using the generalized linear-quadratic relative risk model is estimated as 5.4% Sv(-1) [90% Bayesian credible interval (BCI) 3.1, 8.0]. At 0.1 Sv, leukemia mortality for a UK population using the generalized linear-quadratic relative risk model is estimated as 0.50% Sv(-1) (90% BCI 0.11, 0.97). Risk estimates varied little between populations; at 0.1 Sv the central estimates ranged from 3.7 to 5.4% Sv(-1) for solid cancers and from 0.4 to 0.6% Sv(-1) for leukemia. Analyses using regression calibration techniques yield central estimates of risk very similar to those for the Bayesian approach. The central estimates of population risk were similar for the generalized absolute risk model and the relative risk model. Linear-quadratic-exponential models predict lower risks (at least at low test doses) and appear to fit as well, although for other (theoretical) reasons we favor the simpler linear-quadratic models.     

Radiation dose verification of an X-ray based blood irradiator using EBT3 radiochromic films calibrated using Gamma Knife machine

AimBlood irradiators (BI) initial acceptance testing and routine annual dosimetry checks require radiation dose measurements in order to comply with regulatory requirements.BackgroundTraditionally thermo-luminescence dosimeters (TLD) have been used to measure the dose. The EBT3 film is reported to be a better dosimeter for low energy X-rays than its predecessors EBT2 and EBT. To the best of our knowledge, the use of EBT3 films to perform dosimetry on X-ray based BI has not been reported yet.Materials and methodsWe performed routine radiation dosimetry checks using EBT3 films on a new X-ray based BI and compared the results with TLD dosimetry. Calibration films were irradiated with radiation beam from a Co-60 Gamma Knife (GK) radiosurgery machine and, alternatively, using an Ir-192 high dose rate (HDR) brachytherapy device. The films were calibrated to cover a wide dose range from 1 to 40 Gy. Such a wide dose range has not been reported yet in BI film dosimetry.ResultsWe obtained a relative difference of about 6.6% between doses measured using TLD and those measured using EBT3 films. Both irradiation methods using GK or HDR were found to be adequate for the calibration of the EBT3 Gafchromic films.ConclusionsWe recommend the use of EBT3 films in routine X-ray based BI dosimetry checks. The presented method takes advantage of available radiotherapy equipment that can be efficiently used for EBT3 films calibration. The method is fast, reproducible and saves valuable medical physicist's time.     

Shared uncertainty in measurement error problems, with application to Nevada Test Site fallout data

In radiation epidemiology, it is often necessary to use mathematical models in the absence of direct measurements of individual doses. When complex models are used as surrogates for direct measurements to estimate individual doses that occurred almost 50 years ago, dose estimates will be associated with considerable error, this error being a mixture of (a) classical measurement error due to individual data such as diet histories and (b) Berkson measurement error associated with various aspects of the dosimetry system. In the Nevada Test Site(NTS) Thyroid Disease Study, the Berkson measurement errors are correlated within strata. This article concerns the development of statistical methods for inference about risk of radiation dose on thyroid disease, methods that account for the complex error structure inherence in the problem. Bayesian methods using Markov chain Monte Carlo and Monte-Carlo expectation-maximization methods are described, with both sharing a key Metropolis-Hastings step. Regression calibration is also considered, but we show that regression calibration does not use the correlation structure of the Berkson errors. Our methods are applied to the NTS Study, where we find a strong dose-response relationship between dose and thyroiditis. We conclude that full consideration of mixtures of Berkson and classical uncertainties in reconstructed individual doses are important for quantifying the dose response and its credibility/confidence interval. Using regression calibration and expectation values for individual doses can lead to a substantial underestimation of the excess relative risk per gray and its 95% confidence intervals.     

Out-of-field organ doses and associated risk of cancer development following radiation therapy with photons

Innovations in cancer treatment have contributed to the improved survival rate of these patients. Radiotherapy is one of the main options for cancer management nowadays. High doses of ionizing radiation are usually delivered to the tumor site with high energy photon beams. However, the therapeutic radiation exposure may lead to second cancer induction. Moreover, the introduction of intensity-modulated radiation therapy over the last decades has increased the radiation dose to out-of-field organs compared to that from conventional irradiation. The increased organ doses might result in elevated probabilities for developing secondary malignancies to critical organs outside the treatment volume. The organ-specific dosimetry is considered necessary for the theoretical second cancer risk assessment and the proper analysis of data derived from epidemiological reports. This study reviews the methods employed for the measurement and calculation of out-of-field organ doses from exposure to photons and/or neutrons. The strengths and weaknesses of these dosimetric approaches are described in detail. This is followed by a review of the epidemiological data associated with out-of-field cancer risks. Previously published theoretical cancer risk estimates for adult and pediatric patients undergoing radiotherapy with conventional and advanced techniques are presented. The methodology for the theoretical prediction of the probability of carcinogenesis to out-of-field sites and the limitations of this approach are discussed. The article also focuses on the factors affecting the magnitude of the probability for developing radiotherapy-induced malignancies. The restriction of out-of-field doses and risks through the use of different types of shielding equipment is presented.     

Biological dosimetry by the triage dicentric chromosome assay: potential implications for treatment of acute radiation syndrome in radiological mass casualties

Biological dosimetry is an essential tool for estimating radiation dose. The dicentric chromosome assay (DCA) is currently the tool of choice. Because the assay is labor-intensive and time-consuming, strategies are needed to increase throughput for use in radiation mass casualty incidents. One such strategy is to truncate metaphase spread analysis for triage dose estimates by scoring 50 or fewer metaphases, compared to a routine analysis of 500 to 1000 metaphases, and to increase throughput using a large group of scorers in a biodosimetry network. Previously, the National Institutes for Allergies and Infectious Diseases (NIAID) and the Armed Forces Radiobiology Research Institute (AFRRI) sponsored a double-blinded interlaboratory comparison among five established international cytogenetic biodosimetry laboratories to determine the variability in calibration curves and in dose measurements in unknown, irradiated samples. In the present study, we further analyzed the published data from this previous study to investigate how the number of metaphase spreads influences dose prediction accuracy and how this information could be of value in the triage and management of people at risk for the acute radiation syndrome (ARS). Although, as expected, accuracy decreased with lower numbers of metaphase spreads analyzed, predicted doses by the laboratories were in good agreement and were judged to be adequate to guide diagnosis and treatment of ARS. These results demonstrate that for rapid triage, a network of cytogenetic biodosimetry laboratories can accurately assess doses even with a lower number of scored metaphases.     

Thyroid cancer following scalp irradiation: a reanalysis accounting for uncertainty in dosimetry

In the 1940s and 1950s, over 20,000 children in Israel were treated for tinea capitis (scalp ringworm) by irradiation to induce epilation. Follow-up studies showed that the radiation exposure was associated with the development of malignant thyroid neoplasms. Despite this clear evidence of an effect, the magnitude of the dose-response relationship is much less clear because of probable errors in individual estimates of dose to the thyroid gland. Such errors have the potential to bias dose-response estimation, a potential that was not widely appreciated at the time of the original analyses. We revisit this issue, describing in detail how errors in dosimetry might occur, and we develop a new dose-response model that takes the uncertainties of the dosimetry into account. Our model for the uncertainty in dosimetry is a complex and new variant of the classical multiplicative Berkson error model, having components of classical multiplicative measurement error as well as missing data. Analysis of the tinea capitis data suggests that measurement error in the dosimetry has only a negligible effect on dose-response estimation and inference as well as on the modifying effect of age at exposure.     

Cell killing, nuclear damage and apoptosis in Chinese hamster V79 cells after irradiation with heavy-ion beams of (16)O, (12)C and (7)Li

Chinese hamster V79 cells were exposed to high LET (linear energy transfer) (16)O-beam (625keV/mum) radiation in the dose range of 0-9.83Gy. Cell survival, micronuclei (MN), chromosomal aberrations (CA) and induction of apoptosis were studied as a follow up of our earlier study on high LET radiations ((7)Li-beam of 60keV/mum and (12)C-beam of 295keV/mum) as well as (60)Co gamma-rays. Dose dependent decline in surviving fraction was noticed along with the increase of MN frequency, CA frequency as well as percentage of apoptosis as detected by nuclear fragmentation assay. The relative intensity of DNA ladder, which is a useful marker for the determination of the extent of apoptosis induction, was also increased in a dose dependent manner. Additionally, expression of tyrosine kinase lck-1 gene, which plays an important role in response to ionizing radiation induced apoptosis, was increased with the increase of radiation doses and also with incubation time. The present study showed that all the high LET radiations were generally more effective in cell killing and inflicting other cytogenetic damages than that of low LET gamma-rays. The dose response curves revealed that (7)Li-beam was most effective in cell killing as well as inducing other nuclear damages followed by (12)C, (16)O and (60)Co gamma-rays, in that order. The result of this study may have some application in biological dosimetry for assessment of genotoxicity in heavy ion exposed subjects and in determining suitable doses for radiotherapy in cancer patients where various species of heavy ions are now being generally used.     

Investigating centering,scan length,and arm position impact on radiation dose across 4 countries from 4 continents during pandemic: Mitigating key radioprotection issues

PurposeOptimization of CT scan practices can help achieve and maintain optimal radiation protection. The aim was to assess centering, scan length, and positioning of patients undergoing chest CT for suspected or known COVID-19 pneumonia and to investigate their effect on associated radiation doses.MethodsWith respective approvals from institutional review boards, we compiled CT imaging and radiation dose data from four hospitals belonging to four countries (Brazil, Iran, Italy, and USA) on 400 adult patients who underwent chest CT for suspected or known COVID-19 pneumonia between April 2020 and August 2020. We recorded patient demographics and volume CT dose index (CTDI_vol) and dose length product (DLP). From thin-section CT images of each patient, we estimated the scan length and recorded the first and last vertebral bodies at the scan start and end locations. Patient mis-centering and arm position were recorded. Data were analyzed with analysis of variance (ANOVA).ResultsThe extent and frequency of patient mis-centering did not differ across the four CT facilities (>0.09). The frequency of patients scanned with arms by their side (11–40% relative to those with arms up) had greater mis-centering and higher CTDI_vol and DLP at 2/4 facilities (p = 0.027–0.05). Despite lack of variations in effective diameters (p = 0.14), there were significantly variations in scan lengths, CTDI_vol and DLP across the four facilities (p < 0.001).ConclusionsMis-centering, over-scanning, and arms by the side are frequent issues with use of chest CT in COVID-19 pneumonia and are associated with higher radiation doses.     

The cytogenetic effects of low doses of accelerated charged particles in human blood lymphocytes in vitro

The aim of the investigation was the study of cytogenetic effects in human blood lymphocytes of low doses of ionizing radiation in vitro. The analysis of unstable chromosome aberrations in human lymphocytes after irradiation by the accelerated ions 12C with the energy 500 MeV/nucleon and LET 10.7 keV/microm was carried out. Blood samples were irradiated on Nuclotron of the High Energy Laboratory of the Joint Institute for Nuclear Research. The doses of irradiation were in the range from 0.05 up to 1.0 Gy. Was shown that the frequency of unstable chromosome aberrations depends from the dose of ionizing radiation and can be described by linear function. At the doses 0.25-0.50 Gy the dose-independent curve was obtained for dicentrics and centric rings. The frequencies of dicentrics and centric rings as markers of the radiation action were slightly different for different donors that could be explained by different radiosensitivity. Using the calibration curve obtained earlier for gamma-rays coefficients of relative biological efficiency of accelerated 12C with the energy 500 MeV/nucleon were defined: they varied from 1.0 at the doses (0.5-1.0 Gy) up to 3.2 at the lower doses (0.05-0.25 Gy).     

Thermoluminescence dosimetry of gamma rays from the atomic bomb at Hiroshima using the predose technique

Thermoluminescence dosimetry measurements of gamma rays produced by the atomic bomb in Hiroshima were made by the predose technique using eight ceramic samples collected from five buildings located at distances between 1271 and 2051 m from the hypocenter. The results of our measurements are compared to both the newer dose estimates (Dosimetry System 1986) and older dose estimates (Tentative 1965 Doses) for survivors of the Hiroshima atomic bomb. In comparison with the older estimates, our results are larger by a factor of 2.3 at 1271 m and 3.9 at 2051 m. Our results and the newer estimates for Hiroshima differ by a factor of only 1.14 +/- 0.16 on the average.