Dose Uncertainty Research Articles

Frequentist model averaging for analysis of dose-response in epidemiologic studies with complex exposure uncertainty.

In epidemiologic studies, association estimates of an exposure with disease outcomes are often biased when the uncertainties of exposure are ignored. Consequently, corresponding confidence intervals (CIs) will not have correct coverage. This issue is particularly problematic when exposures must be reconstructed from physical measurements, for example, for environmental or occupational radiation doses that were received by a study population for which radiation doses cannot be measured directly. To incorporate complex uncertainties in reconstructed exposures, the two-dimensional Monte Carlo (2DMC) dose estimation method has been proposed and used in various dose reconstruction efforts. The 2DMC method generates multiple exposure realizations from dosimetry models that incorporate various sources of errors to reflect the uncertainty of the dose distribution as well as the uncertainties in individual doses in the exposed population. Traditional measurement-error model approaches, typically based on using mean doses in the dose-exposure analysis, do not fully account exposure uncertainties. A recently developed statistical approach that overcomes many of these limitations by analyzing multiple exposure realizations in relation to disease risk is Bayesian model averaging (BMA). The analytic advantage of the BMA is its ability to better accommodate complex exposure uncertainty in the risk estimation, but a practical. Drawback is its significant computational complexity. In this present paper, we propose a novel frequentist model averaging (FMA) approach which has all the analytical advantages of the BMA method but is much simpler to implement and computationally faster. We show in simulations that, like BMA, FMA yields 95% confidence intervals for association parameters that close to 95% coverage rate. In simulations, the FMA has shorter length of CIs than those of another frequentist approach, the corrected information matrix (CIM) method. We illustrate the similarities in performance of BMA and FMA from a study of exposures from radioactive fallout in Kazakhstan.

Deep learning based uncertainty prediction of deformable image registration for contour propagation and dose accumulation in online adaptive radiotherapy

Objective. Online adaptive radiotherapy aims to fully leverage the advantages of highly conformal therapy by reducing anatomical and set-up uncertainty, thereby alleviating the need for robust treatments. This requires extensive automation, among which is the use of deformable image registration (DIR) for contour propagation and dose accumulation. However, inconsistencies in DIR solutions between different algorithms have caused distrust, hampering its direct clinical use. This work aims to enable the clinical use of DIR by developing deep learning methods to predict DIR uncertainty and propagating it into clinically usable metrics. Approach. Supervised and unsupervised neural networks were trained to predict the Gaussian uncertainty of a given deformable vector field (DVF). Since both methods rely on different assumptions, their predictions differ and were further merged into a combined model. The resulting normally distributed DVFs can be directly sampled to propagate the uncertainty into contour and accumulated dose uncertainty. Main results. The unsupervised and combined models can accurately predict the uncertainty in the manually annotated landmarks on the DIRLAB dataset. Furthermore, for 5 patients with lung cancer, the propagation of the predicted DVF uncertainty into contour uncertainty yielded for both methods an expected calibration error of less than 3%. Additionally, the probabilisticly accumulated dose volume histograms (DVH) encompass well the accumulated proton therapy doses using 5 different DIR algorithms. It was additionally shown that the unsupervised model can be used for different DIR algorithms without the need for retraining. Significance. Our work presents first-of-a-kind deep learning methods to predict the uncertainty of the DIR process. The methods are fast, yield high-quality uncertainty estimates and are useable for different algorithms and applications. This allows clinics to use DIR uncertainty in their workflows without the need to change their DIR implementation.

Synthetic CT generation from MRI using 3D transformer-based denoising diffusion model.

Magnetic resonance imaging (MRI)-based synthetic computed tomography (sCT) simplifies radiation therapy treatment planning by eliminating the need for CT simulation and error-prone image registration, ultimately reducing patient radiation dose and setup uncertainty. In this work, we propose a MRI-to-CT transformer-based improved denoising diffusion probabilistic model (MC-IDDPM) to translate MRI into high-quality sCT to facilitate radiation treatment planning. MC-IDDPM implements diffusion processes with a shifted-window transformer network to generate sCT from MRI. The proposed model consists of two processes: a forward process, which involves adding Gaussian noise to real CT scans to create noisy images, and a reverse process, in which a shifted-window transformer V-net (Swin-Vnet) denoises the noisy CT scans conditioned on the MRI from the same patient to produce noise-free CT scans. With an optimally trained Swin-Vnet, the reverse diffusion process was used to generate noise-free sCT scans matching MRI anatomy. We evaluated the proposed method by generating sCT from MRI on an institutional brain dataset and an institutional prostate dataset. Quantitative evaluations were conducted using several metrics, including Mean Absolute Error (MAE), Peak Signal-to-Noise Ratio (PSNR), Multi-scale Structure Similarity Index (SSIM), and Normalized Cross Correlation (NCC). Dosimetry analyses were also performed, including comparisons of mean dose and target dose coverages for 95% and 99%. MC-IDDPM generated brain sCTs with state-of-the-art quantitative results with MAE 48.825±21.491 HU, PSNR 26.491±2.814dB, SSIM 0.947±0.032, and NCC 0.976±0.019. For the prostate dataset: MAE 55.124±9.414 HU, PSNR 28.708±2.112dB, SSIM 0.878±0.040, and NCC 0.940±0.039. MC-IDDPM demonstrates a statistically significant improvement (with p<0.05) in most metrics when compared to competing networks, for both brain and prostate synthetic CT. Dosimetry analyses indicated that the target dose coverage differences by using CT and sCT were within±0.34%. We have developed and validated a novel approach for generating CT images from routine MRIs using a transformer-based improved DDPM. This model effectively captures the complex relationship between CT and MRI images, allowing for robust and high-quality synthetic CT images to be generated in a matter of minutes. This approach has the potential to greatly simplify the treatment planning process for radiation therapy by eliminating the need for additional CT scans, reducing the amount of time patients spend in treatment planning, and enhancing the accuracy of treatment delivery.

Economic evaluation in collaborative hospital drug evaluation reports

ObjectiveEconomic evaluation is a fundamental criterion when deciding a drug’s place in therapy. The MADRE method (Method for Assistance in making Decisions and Writing Drug Evaluation Reports) is widely used for drug evaluation. This method was developed by the GENESIS group of the Spanish Society of Hospital Pharmacy (SEFH), including economic evaluation. We intend to improve the economic aspects of this method. As for the direction to take, we have to first analyze our previous experiences with the current methodology and propose necessary improvements. MethodEconomic evaluation sections in collaboratively conducted drug evaluation reports (as the scientific society, SEFH) with the MADRE method were reviewed retrospectively. ResultsThirty-two reports were reviewed, 87.5% of them included an economic evaluation conducted by authors and 65.6% contained published economic evaluations. In 90.6% of the reports, a Budget impact analysis was conducted. The cost per life year gained or per Quality Adjusted Life Year gained was present in 14 reports. Twenty-three reports received public comments regarding the need to improve the economic aspect. Main difficulties: low quality evidence in the target population, no comparative studies with a relevant comparator, non-final outcomes evaluated, no quality of life data, no fixed drug price available, dosing uncertainty, and different prices for the same drug. ConclusionsProposed improvements: incorporating different forms of aid for non-drug costs, survival estimation and adapting published economic evaluations; establishing criteria for drug price selection, decision-making in conditions of uncertainty and poor quality evidence, dose calculation and cost-effectiveness thresholds depending on different situations.

Simulation-guided development of an optical calorimeter for high dose rate dosimetry.

Optical Calorimetry (OC) is based on interferometry and provides a direct measurement of spatially resolved absorbed dose to water by measuring refractive index changes induced by radiation. The purpose of this work was to optimize and characterize in software an OC system tailored for ultra-high dose rate applications and to build and test a prototype in a clinical environment.A radiation dosimeter using the principles of OC was designed in optical modelling software. Traditional image quality instruments, fencepost and contrast phantoms, were utilized both in software and experimentally in a lab environment to investigate noise reduction techniques and to test the spatial and dose resolution of the system. Absolute dose uncertainty was assessed by measurements in a clinical 6 MV Flattening Filter Free (FFF) photon beam with dose rates in the range 0.2-6Gy/s achieved via changing the distance from the source.Design improvements included: equalizing the pathlengths of the interferometer, isolating the system from external vibrations and controlling the system's internal temperature as well as application of mathematical noise reduction techniques. Simulations showed that these improvements should increase the spatial resolution from 22 to 35 lp/mm and achieve a minimum detectable dose of 0.2Gy, which was confirmed experimentally. In the FFF beam, the absolute dose uncertainty was dose rate dependent and decreased from 2.5 ± 0.8 to 2.5 ± 0.2Gy for dose rates of 0.2 and 6Gy/s, respectively.A radiation dosimeter utilizing the principles of OC was developed and constructed. Optical modelling software and image quality phantoms allowed for iterative testing and refinement. The refined OC system proved capable of measuring absorbed dose to water in a linac generated photon beam. Reduced uncertainty at higher dose rates indicates the potential for OC as a dosimetry system for high dose rate techniques such as microbeam and ultra-high dose-rate radiotherapy.

REAP-2: An interactive quantitative tool for robust and efficient dose-response curve estimation.

REAP-2 is an interactive dose-response curve estimation tool for Robust and Efficient Assessment of drug Potency. It provides user-friendly dose-response curve estimation for in vitro studies and conducts statistical testing for model comparisons with a redesigned user interface. We also make a major update of the underlying estimation method with penalized beta regression, which demonstrates great reliability and accuracy in dose estimation and uncertainty quantification. In this note, we describe the method and implementation of REAP-2 with a highlight on potency estimation and drug comparison.

Spot Scanning Proton Therapy for Pregnant Patients with Brain and Head and Neck Tumors

When radiotherapy is medically necessary, x-ray based treatments (XRT) have traditionally been used to treat pregnant patients. Treatment planning and delivery techniques may be modified to minimize dose to the fetus but results in less optimal plans due to avoiding posterior beams or arcs. Monte Carlo calculations and published case studies suggest spot scanning proton therapy (PRT) reduces the equivalent dose to the fetus by a factor of 10 compared to XRT and does not require modified treatment planning techniques. However, due to concern for dose uncertainties and neutron scatter with PRT, few centers have adopted PRT over XRT for pregnant patients. The purpose of this work is to perform a retrospective study on the pregnant patients previously treated at our institution with XRT to measure the equivalent dose that would be delivered to the fetus with spot scanning PRT compared to XRT. PRT plans were made for seven pregnant patients, 4 brain tumors and 3 head and neck tumors, who had received XRT. Due to the finite range of protons, the fetal exposure is dominated by neutrons and not the primary beam. Thus, no beam arrangement modifications were required to minimize fetal dose for PRT plans. Fetal dose measurements were performed with the patient plans using a Rando phantom and Wendi-2 (Thermo Scientific) meter placed at the phantom's abdomen. The Wendi-2 measures ambient dose equivalent, which accounts for the biological effect of the neutron energies. Measurements were made at various distances from isocenter to the center of the detector. The total dose equivalent from PRT at several out of field distances was compared to that from XRT. Patient specific measurements were used to determine the total fetal dose from each modality, accounting for the changing position of the fetus each week of the mother's treatment. The imaging dose for standard of practice imaging, including verification CT scans and daily alignment imaging, was also evaluated using a similar setup with a Fluke 451 dose meter. The average measured fetal equivalent dose for the brain plans was 0.4 mSv for PRT and 7 mSv for XRT. For the head and neck plans, it was 6 mSv for PRT and 90 mSv for XRT. The dose from PRT was consistently at least a factor of 10 less than the XRT plans. In addition, the PRT plans were preferred by the physicians when considering tumor coverage and other normal tissue sparing. Daily imaging added between 0.05 and 1.5 mSv to the total dose in the PRT treatments. This retrospective study showed that when treating brain or head and neck tumors in pregnant patients, the equivalent dose a fetus would receive with PRT is approximately a factor of 10 less than XRT without making any compromises in treatment planning. These results support changing the standard of practice to utilizing spot scanning PRT as the preferred method for treating pregnant patients with brain or head and neck tumors when available instead of XRT. We have brought this process to clinic at our center.

Heart Dose Uncertainty Caused by Heartbeat during Adjuvant Breast Radiotherapy

Adjuvant radiotherapy is a crucial treatment option for breast cancer. Owing to the long survival after treatment, heart toxicity has become a critical issue in those who receive radiotherapy. The heart dose is calculated using the computed tomography (CT) images acquired during simulation. The heart volume is quite different between the systolic and diastolic phases. This study used four-dimensional (4D) CT to capture the heart image and determine the ranges of the heart dose in different phases of the heart. Patients with left-sided breast cancer who underwent breast conservative surgery followed by adjuvant radiotherapy to the entire breast between January 2016 and December 2021 were identified. The three-dimensional (3D) CT and 4DCT datasets of the patients were acquired to evaluate the variation in the heart dose. The heart volume in each respiratory phase was depicted in a box plot along with the dice similarity coefficient (DCS). A total of 32 patients met the inclusion criteria. The DCS of the heart in each respiration phase was within the range of 0.91 to 0.95. Variations in the heart volume and morphology were not evident. However, these variations were not influenced by the respiratory cycle. The median relative variations in the 4DCT volume, mean dose, V20 (≥20 Gy), and V40 (40 Gy) were 6%, 14%, 19%, and 32%, respectively. All parameters showed significant variation between the maximum values in 4DCT and planning 3DCT. When parameters in planning 3DCT were compared to minimum values in 4DCT, the heart volume and V20 still showed significant differences, whereas the mean dose (p = .052) and V40 (p = .151) did not. We found that the median variation in the heart volume during the respiratory cycle was 6%, which led to a 14% variation in the mean heart dose, 19% in V20, and 32% in V40. Dose variation should not be ignored. A more precise method for estimating the heart dose during treatment should be investigated.

Variation in Left Anterior Descending Coronary Artery Accumulated Dose Estimates during Breast Cancer Radiotherapy

Left anterior descending (LAD) coronary artery RT dose has been associated with the risk of coronary ischemic events in patients with breast cancer treated with radiotherapy (RT). However, consensus dose constraints commonly utilize mean heart dose, which has been shown to be an inadequate surrogate for LAD dose. Given the LAD is adjacent to the steep dose gradients of the left breast/chest wall, we hypothesize that variations in patient positioning or depth of breath hold may contribute to significant deviations in daily LAD dose exposure compared to predicted. Our objective was to investigate variations in accumulated LAD dose in patients with left-sided breast cancer treated with RT. Retrospective analysis of 10 consecutive patients with left-sided breast cancer treated between 2019-2022 with volumetric modulated arc therapy (VMAT) in the supine position. RT was delivered using daily cone beam computed tomography (CBCT) image guidance with deep-inspiratory breath hold technique and an optical surface monitoring system. Daily CBCT scans were individually registered to each planning CT based on daily positional changes. The LAD was manually segmented and transformed to each CBCT. Daily fractional dose was calculated (mean, volume receiving 15 Gy [V15 Gy], V30 Gy, and max) and summed to produce an accumulated dose which was compared to the predicted dose. Significant deviations in accumulated dose were defined as at least ±15% from predicted. The RT targets included breast/chest wall only (n = 1), supraclavicular nodes (n = 8), and/or internal mammary chain (n = 5). All plans were prescribed to 50 Gy in 25 fractions. The median predicted mean heart dose was 5.1 Gy. Overall, there were no significant differences between the median predicted vs. accumulated LAD doses: mean 10.4 vs. 10.2 Gy, V15 Gy 21% vs. 25%, V30 Gy 0% vs. 1%, max 24.5 vs 25.7 Gy (all p>.05). However, there was a subset of patients (n = 5, 50%) with significant deviations in accumulated vs. predicted dose (at least ±15%). For LAD mean, n = 2 had higher accumulated vs. predicted doses (16.6 vs. 11.6 Gy; 14.6 vs. 12.8 Gy), while n = 3 had lower (21.8 vs. 26.5 Gy; 2.7 vs. 4.2 Gy; 13.9 vs. 16.5 Gy). For LAD V15 Gy, n = 3 had higher accumulated vs. predicted doses (43 vs. 35%; 51% vs. 25%; 14% vs. 9%), while n = 2 had lower (49% vs. 61%; 37% vs. 56%). For LAD V30 Gy, n = 4 had higher accumulated vs. predicted doses (12% vs. 5%; 5% vs. 0%; 4% vs. 0%; 4% vs. 2%), while n = 1 had lower (32% vs. 44%). Daily setup differences, including the extent of inspiratory breath hold, may contribute to deviations in accumulated LAD dose (more than 15% of predicted) in approximately half of patients and were more pronounced in V15 and V30 Gy metrics. The potential for significant LAD dose uncertainty in a clinically meaningful subset of patients should be recognized and warrants further analysis in an expanded cohort.

Investigating the Influence of Cardiac Substructure Dose on Survival of Lung Cancer Patients

Since RTOG 0617, the relationship between cardiac dose and overall survival for lung cancer patients (pts) is increasingly scrutinized. However, clinical cardiac substructure (CS) contours are typically lacking. In this study, we use deep learning (DL) to create accurate CS contours for a large lung cohort, and then investigate the influence of CS dose and delineation-induced dose uncertainty on overall survival. Retrospectively included are 2075 lung cancer pts (T stage 1-4 with median survival times of 49, 36, 19, and 16 months respectively, median [range] age 70 [36-95], 58% male), treated with radiotherapy (RT) between 2009 and 2019 in a single academic institution. Re-irradiated pts were excluded. Input for DL were 70 randomly selected pts, which had manual ground-truth CS contours created on their RT planning scan. The 70 pts were split between training, validation, and test set (50, 10, 10). The trained network was then used to create 13 CS contours for the remaining pts. The influence of delineation-induced dose uncertainty on survival was investigated, first, by dilating, and second, by eroding the DL-created contours using the mean surface distance (MSD) ± 2SD of MSD, as estimated from the test set. Significant variables from univariable cox regression (CR) were included in multivariable CR (MCR). Separate MCR's include dose to one CS or the whole heart and age, gender, and log(V95%) while stratifying for T-stage, and palliative treatment. V95% is the volume receiving 95% prescribed dose. Tumor laterality was insignificant in the univariable analysis. DL test output was deemed sufficient (median dice score > 0.80 and/or MSD < 2mm) for all CS but the ascending aorta, aortic valve, coronary sinus, and pulmonary veins. Max and mean dose to inferior vena cava were not significant. Table 1 shows significant CS dose parameters in MCR's for 1465 pts with complete data. Hazard ratios (HR) for max and mean dose parameters (per Gy [EQD2]) are only shown when significant for all three contour variations. Confidence intervals (CI) are based on the interval over the three contour variations. *, **, *** indicating p-values <0.05, <0.01, <0.001 respectively. Nearly all CS dose parameters were significantly associated with reduced overall survival in MCR even after accounting for delineation uncertainty. Additional analysis is required to find the most crucial CS by solving multicollinearity, whereafter dosimetric constraints can be investigated.

EPR-based uncertainty validation of the calculated external doses for population exposed in the urals region.

Tooth enamel Electron Paramagnetic Resonance (EPR) spectroscopy was used as a method for external dosimetry in the territories contaminated in the 1950s by PA 'Mayak' (Urals region) to validate the mean dose estimates predicted by the Techa River Dosimetry System (TRDS). The purpose of this study is to validate the uncertainties of TRDS doses. Ninety percent confidence intervals (90% confidence interval, CI) of dose estimated with both methods were compared for 220 people. All data were grouped according to the width of 90%CI, viz.: (1) 90%CI of EPR-based dose≤ 90%CI of TRDS prediction (38 cases); (2) 90%CI of EPR-based dose> 90%CI of TRDS prediction (182 cases). About 91% of 90%CIs overlap. In group 1, 100% cases overlap. In group 2, 80% of the cases were non-contradictive (the calculated 90%CI is completely within the measured one). Interval comparison of doses predicted retrospectively and estimated based on individual measurements are non-contradictory and demonstrate a good agreement.

End-to-end quality assurance for stereotactic radiotherapy with Fricke-Xylenol orange-Gelatin gel dosimeter and dual-wavelength cone-beam optical CT readout

PurposeThe end-to-end (E2E) quality assurance (QA) test is a unique tool for validating the treatment chain undergone by patients in external radiotherapy. It should be conducted in three dimensions (3D) to get accurate results. This study aims to implement these tests with Fricke-Xylenol orange-Gelatin (FXG) gel dosimeter and a newly developed dual-wavelength reading method on the Vista16™ optical Computed Tomography (CT) scanner (ModusQA) for three treatment techniques in stereotactic radiotherapy, on Novalis (Varian) and CyberKnife (Accuray) linear accelerators. MethodsThe tests were performed in head phantoms. Gel measurements were compared with planned dose distributions and measured by film and ion chamber measurements by plotting isodose curves and dose profiles, and by conducting a 3D local gamma-index analysis (2%/2mm criteria). ResultsGamma passing rates were higher than 95 %. Point dose differences between treatment planning and gel and ion chamber measurements at the isocenter were < 2.3 % for both treatments delivered on the Novalis accelerator, while this difference was higher than 4 % for the treatment delivered on the CyberKnife, highlighting a small overdosing of the tumor volume. A good agreement was observed between gel and film dose profiles. ConclusionsThis study presents the successful implementation of 3D E2E QA tests for stereotactic radiotherapy with FXG gel dosimetry and a dual-wavelength reading method on an optical CT scanner. This dosimetric method provides 3D absolute dose distributions in the 0.25 – 10 Gy dose range with a high spatial resolution and a dose uncertainty of around 2 % (k=1).

Dose estimates and their uncertainties for use in epidemiological studies of radiation-exposed populations in the Russian Southern Urals.

Many residents of the Russian Southern Urals were exposed to radioactive environmental pollution created by the operations of the Mayak Production Association in the mid- 20th century. There were two major releases: the discharge of about 1x1017 Bq of liquid waste into the Techa River between 1949 and 1959; and the atmospheric release of 7.4 * 1016 Bq as a result an explosion in the radioactive waste-storage facility in 1957. The releases into the Techa River resulted in the exposure of more than 30,000 people who lived in riverside villages between 1950 and 1961. The 1957 accident contaminated a larger area with the highest exposure levels in an area that is called the East Urals Radioactive Trace (EURT). Current epidemiologic studies of the exposed populations are based on dose estimates obtained using a Monte-Carlo dosimetry system (TRDS-2016MC) that provides multiple realizations of the annual doses for each cohort member. These dose realizations provide a central estimate of the individual dose and information on the uncertainty of these dose estimates. In addition, the correlation of individual annual doses over realizations provides important information on shared uncertainties that can be used to assess the impact of shared dose uncertainties on risk estimate uncertainty.This paper considers dose uncertainties in the TRDS-2016MC. Individual doses from external and internal radiation sources were reconstructed for 48,036 people based on environmental contamination patterns, residential histories, individual 90Sr body-burden measurements and dietary intakes. Dietary intake of 90Sr resulted in doses accumulated in active bone marrow (or simply, marrow) that were an order of magnitude greater than those in soft tissues. About 84% of the marrow dose and 50% of the stomach dose was associated with internal exposures. The lognormal distribution is well-fitted to the individual dose realizations, which, therefore, could be expressed and easily operated in terms of geometric mean (GM) and geometric standard deviation (GSD). Cohort average GM for marrow and stomach cumulative doses are 0.21 and 0.03 Gy, respectively. Cohort average dose uncertainties in terms of GSD are as follows: for marrow it is 2.93 (90%CI: 2.02-4.34); for stomach and the other non-calcified tissues it is 2.32 (90% CI: 1.78-2.9).

Preliminary dosimetric characterization of EDBreast gel

Purpose. EDBreast gel is an alternative Fricke gel dosimeter, read by Magnetic Resonance Imaging, in which sucrose is added to lower diffusion effects. This paper aims at determining the dosimetric characteristics of this dosimeter. Methods. The characterization has been performed in high energy photon beams. The dose-response of the gel has been evaluated as well as its detection limit, its fading effects, the reproducibility of its response and its stability over time. Its energy and dose-rate dependence has been investigated, and the overall dose uncertainty budget established. Once characterized, the dosimetry method has been applied to a simple reference irradiation case in a 6 MV photon beam, with the measurement of the lateral dose profile of a 2 × 2 cm2 field. The results have been compared with microDiamond measurements. Results. In addition to its low diffusivity, the gel presents a high sensitivity, no dose-rate dependence considering values ranging from 0.66 to 0.79 and an energy response comparable to ionization chambers. However, its non-linear dose-response induces a high uncertainty on the measured dose (8 % () at 20 Gy) and reproducibility issues. The profile measurements displayed discrepancies compared to the microDiamond due to diffusion effects. The appropriate spatial resolution was estimated using the diffusion coefficient. Conclusion. EDBreast gel dosimeter presents interesting characteristics for applications in clinics, but the linearity of its dose-response should be improved to lower the uncertainties and to enhance the reproducibility.

ПРОГНОЗ РАДИАЦИОННЫХ РИСКОВ РАКА ЩИТОВИДНОЙ ЖЕЛЕЗЫ СРЕДИ НАСЕЛЕНИЯ РАЙОНОВ БРЯНСКОЙ ОБЛАСТИ, ЗАГРЯЗНЕННЫХ ВСЛЕДСТВИЕ АВАРИИ НА ЧЕРНОБЫЛЬСКОЙ АЭС, С УЧЕТОМ НЕОПРЕДЕЛЕННОСТЕЙ ОЦЕНОК МОДЕЛЕЙ РИСКА

Purpose: Forecasting the lifetime attributable radiation risk of incidence with malignant neoplasm (MN) of the thyroid gland and identifying groups of increased radiation risk (HR) for the population of the Bryansk region currently (at the beginning of 2023) living in six areas most contaminated with radionuclides after the accident at Chernobyl NPP, based on a conservative approach, taking into account dose uncertainty factors and parameters of mathematical risk models. Material and methods: The mathematical model of the radiation risk of thyroid cancer is the model recommended by the International Commission on Radiological Protection (ICRP). The uncertainty assessment of radiation risks was carried out by simulation modeling, i.e. by multiple calculation of random realizations of the risk using the normal or log-normal distribution of all parameters involved in the calculation of this risk. Based on a set of random realizations, 95 % confidence limits of risks were estimated. The Unified Federal Database of the National Radiation and Epidemiological Register (NRER) containing reconstructed absorbed doses in the thyroid gland in the population was used as the initial data for the calculation. Results: At the beginning of 2023, the group of 37–40-year-old women is characterized by the maximum radiation risks of thyroid cancer. According to conservative estimates (according to the upper 95 % confidence limits of radiation risk assessments), up to 19.9 % of people from this group may experience the development of radiation-induced thyroid cancer in the future, and for 37-year-old women this proportion can be up to 30.0 %. The greatest risk is predicted for people living in the Krasnogorsk district of the Bryansk region. Radiation-induced thyroid cancer can develop in 40.1 % of individuals from this group. Radiation risks of thyroid cancer in men are up to 10 times lower than in women. For 74.5 % of the population of the entire studied cohort, it is predicted that the maximum individual risk of 5.0×10-5, established by NRB-99/2009 for the population under normal operation of ionizing radiation sources, will be exceeded. Conclusions: At present (since 2023 and for life), the population of the most polluted districts of the Bryansk region continues to be at a high risk of developing radiation-induced thyroid cancers. Women at the age of 0–3 years at the time of exposure (in 1986) should be allocated to the maximum risk group. The results of this work can be used in the preparation of recommendations by health authorities to improve medical monitoring of exposed citizens.

Clinical evaluation of 4D dynamic dose for thoracic tumor stereotactic body radiation therapy with variable parameters

ObjectiveTo evaluate the dose uncertainty in stereotactic body radiation therapy induced by respiratory motion using a 4D dynamic dose (4DDD) reconstruction method. MethodsA retrospective analysis was conducted on five lung cancer patients who received static intensity-modulated radiation therapy. The 4DDD was constructed using beam delivery log files, four-dimensional computed tomography (4DCT) scans, and treatment plans. To evaluate the impact of respiratory motion, 4DDD calculations were performed with 10 starting phases for each field. A total of 270 field doses were simulated and calculated. The differences between the cumulative volume histogram in whole-course treatment and the field doses' gamma passing rate (GPR) were compared. The correlations between plan complexity metrics and the dose deviation caused by respiratory motion were evaluated independently. The phase distributions of 398 subfields were calculated and evaluated for the influence of dose rate and breathing frequency. ResultsThe GPRs of all fields were different among various starting phases, with the highest range from 62.20% to 76.87% for 2 mm/3% GPR. The deviation of mean point dose was (5.42 ​± ​5.21) %, and the deviation in the mean dose and D98% within the internal gross tumor volume were (0.97 ​± ​0.71) % and (0.77 ​± ​0.53) %, respectively. There was a significant correlation between the beam aperture-to-volume (BA2V) ratio and the average 2 mm/2% GPR (R ​= 0.601, P ​< ​0.01). Lower dose rates led to a more homogeneous distribution of phases among subfields (t ​= ​44.100, P ​< ​0.001). ConclusionsDifferent beam starting phases had a limited impact on the overall treatment evaluation. However, the respiratory motion could be observed to induce dose deviations using the 4DDD reconstruction model, particularly for fields with small BA2V.

The Effect of Historical Data-Based Informative Prior on Benchmark Dose Estimation of Toxicogenomics.

High-throughput toxicogenomics as an advanced toolbox of Tox21 plays an increasingly important role in facilitating the toxicity assessment of environmental chemicals. However, toxicogenomic dose-response analyses are typically challenged by limited data, which may result in significant uncertainties in parameter and benchmark dose (BMD) estimation. Integrating historical data via prior distribution using a Bayesian method is a useful but not-well-studied strategy. The objective of this study is to evaluate the effectiveness of informative priors in genomic dose-response modeling and BMD estimation. Specifically, we aim to identify plausible informative priors and evaluate their effects on BMD estimates at both gene and pathway levels. A general informative prior and eight time-specific (from 3 h to 29 d) informative priors for seven commonly used continuous dose-response models were derived. Results suggest that the derived informative priors are sensitive to the specific data sets used for elicitation. Real data-based simulations indicate that BMD estimation with the time-specific informative priors can achieve increased or equivalent accuracy, significantly decreased uncertainty, and a slightly enhanced correlation with the points of departure estimated from apical end points than the counterparts with noninformative priors. Overall, our study systematically examined the effects of historical data-based informative priors on BMD estimates, highlighting the benefits of plausible information priors in advancing the practice of toxicogenomics.

Hi'CT: a pixel sensor-based device for ion tomography

Carbon ions, commonly referred to as particle therapy, have become increasingly popular in the last decade. Accurately predicting the range of ions in tissues is important for the precise delivery of doses in heavy-ion radiotherapy. Range uncertainty is currently the largest contributor to dose uncertainty in normal tissues, leading to the use of safety margins in treatment planning. One potential method is the direct relative stopping measurement (RSP) with ions. Heavy-ion CT (Hi′CT), a compact segmented full digital tomography detector using monolithic active pixel sensors, was designed and evaluated using a 430 MeV/u high-energy carbon ion pencil beam in Geant4. The precise position of the individual carbon ion track can be recorded and reconstructed using a 30 μm × 30 μm small pixel pitch size. Two types of customized image reconstruction algorithms were developed, and their performances were evaluated using three different modules of CATPHAN 600-series phantoms. The RSP measurement accuracy of the tracking algorithm for different types of materials in the CTP404 module was less than 1%. In terms of spatial resolution, the tracking algorithm could achieve a 20% modulation transfer function normalization value of CTP528 imaging results at 5 lp/cm, which is significantly better than that of the fast imaging algorithm (3 lp/cm). The density resolution obtained using the tracking algorithm of the customized CTP515 was approximately 10.5%. In conclusion, a compact digital Hi'CT system was designed, and its nominal performance was evaluated in a simulation. The RSP resolution and image quality provide potential feasibility for scanning most parts of an adult body or pediatric patient, particularly for head and neck tumor treatment.

Assessment of uncertainties in threshold doses for tissue reactions following acute external radiation exposure.

The study aimed to estimate threshold doses and their uncertainties for some human health effects after short-term high dose-rate radiation exposure by quantile technique and the effective dose threshold technique based on distribution functions. The relative uncertainty (U) of the threshold dose was estimated using the error propagation technique. The quantile technique provided statistically significant estimates of threshold doses for acute radiation syndrome onset (0.44±0.12Gy, U=143%) and lethality (1.84±0.44Gy, U=117%) but relative uncertainties were high. The effective threshold dose technique provided statistically significant and more precise threshold dose estimates for acute radiation syndrome onset (0.73±0.02Gy, U=18%) and lethality (6.83±0.08Gy, U=36%), as well as agranulocytosis (3.51±0.03Gy, U=16%) and vomiting onset in the prodromal period (1.54±0.02Gy, U=16%). Threshold doses estimated for the change in the peripheral blood neutrophil and leukocyte counts during the first days after short-term high dose-rate radiation exposure were not statistically significant.

A real-world assessment of the robustness of gel dosimetry

The purpose of this multi-institutional study was to evaluate the robustness of a transported gel dosimeter. Six vials were filled with a normoxic N-vinylpyrrolidone-based polymer gel dosimeter containing inorganic salt as a sensitizer (iVIPET), manufactured by Triangle Products (Kashiwa, Japan). Three vials were sent to the home institution (National Cancer Center Hospital East, Chiba, Japan) and three to an external institution. At each institution, vials received a dose of 0, 5, or 10 Gy using a 10 MV X-ray beam. After irradiation, the gel in the vial was imaged using a 3 T MRI scanner, and an R2 (spin–spin relaxation rate) map was created. The dose–R2 relationship was then analyzed using linear regression and the dose uncertainty computed. Thirty-four institutions participated in the study from July 2020 to July 2021. At the home institution, dose uncertainties were constant throughout the year (95% confidence interval [mean ± 1.96σ]: 3.3 ± 2.1% at 5 Gy and 4.0 ± 2.5% at 10 Gy). The ratio of the dose uncertainties measured at the external institutions and home institution was 1.1 ± 0.4 at 5 Gy (r = 0.88) and 1.0 ± 0.3 at 10 Gy (r = 0.81). Dose uncertainties were approximately 4% within 4 d of transportation but exceeded 10% when the gels were irradiated 7 d after fabrication. Temperature variations during transportation resulted in negligible uncertainties in absorbed dose; however, extended transportation times may increase dose uncertainty. Thus, polymer gel dosimeters should be used within 2–4 d of fabrication.