Uncertainties on Lung Doses from Inhaled Plutonium

Estimates of plutonium lung doses from urine bioassay are highly dependent on the rate of absorption from the lungs to blood assumed for the inhaled aerosol. Absorption occurs by dissolution of particles in lung fluid followed by uptake to blood. The latter may occur either rapidly or dissolved ions may first become temporarily bound within airway tissue. The presence of long-term binding can greatly increase lung doses, particularly if it occurs in the bronchial and bronchiolar regions. Analyses of autopsy data from Beagle dogs and USTUR Case 0269, obtained following exposure to plutonium nitrate, suggest that a small fraction of 0.2-1.1 and 0.4-0.7%, respectively, of plutonium becomes permanently bound within the lungs. The present work performs a further analysis using autopsy data of former plutonium workers of the Mayak Production Association to determine values of the bound fraction that are supported by these data. The results suggest a bound fraction value of 0-0.3%. The results also indicate that the Mayak worker population median values of the particle transport clearance parameters from the alveolar-interstitial region are largely consistent with expected values, but suggest the rate from the alveolar region to the interstitium may be lower than initially thought.

Finding a new drug which is both safe and efficient is an expensive and time-consuming endeavour. In particular, establishing the ‘dose-effect relationship’ – how beneficial a drug is at different dosages – can be challenging. Predicting this curve requires gathering experimental data by exposing and recording how cells respond to various levels of the drug. However, extreme values are often observed at low and high dosages, potentially introducing errors that are hard to correct in the prediction process. Yet, these extreme observations are sometimes genuine so researchers cannot just ignore them. To improve dose-effect estimation, Zhou, Liu, Fang et al. developed a new general-purpose approach. It uses advanced statistical modelling to account for extremes in lab data. This strategy outperformed other methods when dealing with these observations while also providing higher efficiency in data analysis with more uniform data in experiments. To facilitate implementation, Zhou, Liu, Fang et al. set up a user-friendly tool baptized ‘REAP’; this free online resource allows scientists without advanced statistical experience to harness the new approach and to perform dose-effect analysis more easily and accurately. This could boost research across many different disciplines that examine the effects of chemicals on cells.

The revised human respiratory tract model, published in Part 1 of the International Commission on Radiological Protection's (ICRP) report on Occupational Intakes of Radionuclides (OIR), includes a bound fraction, fb, to represent radionuclides that have become chemically bound in the lungs following dissolution of particulates in lung fluid. Bound radionuclides are not subject to particle transport clearance but can be absorbed to blood at a rate, sb. The occurrence of long-term binding of plutonium can greatly increase lung doses, particularly if it occurs in the bronchial and bronchiolar regions. However, there has been little evidence that currently supports the existence of a long-term bound state for plutonium. The present work describes the analysis of measurements of lung data obtained from a life span study of Beagle dogs that were exposed by inhalation to different concentrations of plutonium-239 (239Pu) nitrate aerosol at Pacific Northwest Laboratories, USA. The data have been analysed to assess whether a bound state was required to explain the data. A Bayesian approach was adopted for the analysis that accounts for uncertainties in model parameter values, including uncertainties in the rates of particle transport clearance. Furthermore, it performs the analysis using two different modelling hypotheses: a model based on the current ICRP human respiratory tract model and its treatment of alveolar particle transport clearance; and a model of particle transport clearance that is based on the updated model developed by ICRP to calculate dose coefficients for the OIR. The current model better represents clearance in dogs at early times (up to 1 year following intake) and the latter better represents retention at greater times (>5 years following intake). The results indicate that a long-term bound fraction of between 0.16 and 1.1%, with a mean value of between 0.24 and 0.8% (depending on the model) is required to explain the data.

ObjectivesThe study aims to assess the risk of lung cancer death associated with lung doses due to radon gas and its short-lived progeny (RnP), long-lived radionucleides (LLR) and external γ...

Retrospective estimation of heart and lung doses in pediatric patients treated with spinal irradiation

We present our seven-year experience of using moderate deep inspiration breath-hold (mDIBH) with an active breathing control (ABC) device for patients with early-stage breast cancer and dosimetric comparison to evaluate the benefit of mDIBH on the heart, lung, and liver.We retrospectively reviewed all patients with newly diagnosed breast cancer and having clinical stage Tis, I, or II disease treated between November 2010 and October 2017. Among the 369 patients included in this study, 107 patients were treated with mDIBH and 262 patients were treated with free breathing (FB). Dosimetric analysis was performed to compare dose distribution in the heart, lung, and liver between the two treatment groups. The chi-square test was used to compare the distribution of stage and tumor site between the two groups. The independent samples t-test was used to compare the remaining parameters between the two groups.For all 369 patients, there was a significantly lower ipsilateral lung V5 (relative volume receiving ≧5 Gy), ipsilateral lung V10, ipsilateral lung V20, mean ipsilateral lung dose, whole lung V5, whole lung V10, whole lung V20, mean whole lung dose, heart V10, heart V30, heart V40, and mean heart dose in the mDIBH group. For 184 patients with a left-sided breast tumor, significantly lower ipsilateral lung V5, ipsilateral lung V10, ipsilateral lung V20, mean ipsilateral lung dose, whole lung V10, whole lung V20, mean whole lung dose, heart V10, heart V30, heart V40, and mean heart dose were observed in the mDIBH group. For 185 patients with a right-sided breast tumor, significantly lower ipsilateral lung V5, ipsilateral lung V10, ipsilateral lung V20, mean ipsilateral lung dose, whole lung V5, whole lung V10, whole lung V20, mean whole lung dose, heart V10, heart V30, heart V40, mean heart dose, liver V30, and mean liver dose were observed in the mDIBH group.For early-stage breast cancer patients, mDIBH reduces not only the heart dose but also the lung and liver doses. The routine integration of mDIBH using an ABC device may decrease radiation-induced toxicity in the heart, lung, and liver.

Chapter 1

Predicting the risk of radiation-induced lung injury using a biophysical parameter

Purpose: To investigate the radiation dose for pediatric high pitch cardiac CTA Methods: A total of 14 cases were included in this study, with mean age of 6.2 years (ranges from 2 months to 15 years). Cardiac CTA was performed using a dual-source CT system (Definition Flash, Siemens). Tube voltage (70, 80 and 100kV) was chosen based on patient weight. All patients were scanned using a high-pitch spiral mode (pitch ranges from 2.5 to 3) with tube current modulation technique (CareDose4D, Siemens). For each case, the three dimensional dose distributions were calculated using a Monte Carlo software package (IMPACT-MC, CT Image GmbH). Scanning parameters of each exam, including tube voltage, tube current, beamshaping filters, beam collimation, were defined in the Monte Carlo calculation. Tube current profile along projection angles was obtained from projection data of each tube, which included data within the over-scanning range along z direction. The volume of lungs was segmented out with CT images (3DSlicer). Lung doses of all patients were calculated and compared with CTDIvol, DLP, and SSDE. Results: The average (range) of CTDIvol, DLP and SSDE of all patients was 1.19 mGy (0.58 to 3.12mGy), 31.54 mGy*cm (12.56 to 99 mGy*cm), 2.26 mGy (1.19 to 6.24 mGy), respectively. Radiation dose to the lungs ranged from 0.83 to 4.18 mGy. Lung doses correlated with CTDIvol, DLP and SSDE with correlation coefficients(k) at 0.98, 0.93, and 0.99. However, for the cases with CTDIvol less than 1mGy, only SSDE preserved a strong correlation with lung doses (k=0.83), while much weaker correlations were found for CTDIvol (k=0.29) and DLP (k=-0.47). Conclusion: Lung doses to pediatric patients during Cardiac CTA were estimated. SSDE showed the most robust correlation with lung doses in contrast to CTDIvol and DLP.

Development and comparison in uncertainty assessment based Bayesian modularization method in hydrological modeling

Previous studies have investigated the dose-response relationship between external beam radiotherapy (EBRT) and leukemia by reconstructing the mean active bone marrow (ABM) dose as part of the exposure assessment. However, no prior study has leveraged electronic medical records (EMR) to reconstruct ABM dose and dose-volume in an EBRT patient population. To support future studies on the relationship between radiation exposure and adverse health effects among EBRT patients, we demonstrate methods to retrospectively calculate ABM dose and dose-volume metrics in a large patient cohort using EMR. We retrieved complete EMR for 639 individuals (five pediatric and 634 adult) from a retrospective cohort of cancer patients treated with photon radiotherapy between 2003 and 2011, covering a wide range of treatment sites and target volumes. Using a previously published methodology by our group, bone site contours were derived for each patient treatment session via three-dimensional skeletal registration with a habitus-matched computational phantom. Segmentation accuracy was assessed analytically and by visual inspection of the patient-phantom skeletal overlap. ABM dose and dose-volume metrics were computed using the derived skeletal segmentation and the dose distribution calculated by the treatment planning system. Analytically and visually acceptable skeletal segmentation was achieved for 478 patients (three pediatric, 475 adult). Across all treatment sessions, pelvic irradiation resulted in the highest mean ABM dose per prescribed dose (distribution 25th-75th percentile: 0.1820-0.2870Gy/Gy_Rx, n=183), while intracranial irradiation produced the lowest among the categorized field types (0.0030-0.0391Gy/Gy_Rx, n=37). Dose-volume analyses indicated that the mean ABM dose estimate provides a limited characterization of the ABM dose distribution, with most patients having a 99th percentile dose to marrow volume that was at least one order of magnitude higher than the mean dose estimate. This study presents a scalable EMR-based approach for reconstructing ABM dose and dose-volume metrics in EBRT patients. By capturing clinically relevant dose heterogeneity, we have estimated a more informative exposure variable than mean ABM dose for studies on the role of radiotherapy in leukemogenesis and other adverse health effects. Future work will improve the generalizability of these methods for certain treatment regions and pediatric populations.

Permanent and temporary implantation of I-125 brachytherapy sources has become an official method for the treatment of different cancers. In this technique, it is essential to determine dose distribution around the brachytherapy source to choose the optimal treatment plan. In this study, the dosimetric parameters for a new interstitial brachytherapy source I-125 (IrSeed-125) were calculated with GATE/GEANT4 Monte Carlo code. Dose rate constant, radial dose function and 2D anisotropy function were calculated inside a water phantom (based on the recommendations of TG-43U1 protocol), and inside several tissue phantoms around the IrSeed-125 capsule. Acquired results were compared with MCNP simulation and experimental data. The dose rate constant of IrSeed-125 in the water phantom was about 1.038 cGy·h−1U−1 that shows good consistency with the experimental data. The radial dose function at 0.5, 0.9, 1.8, 3 and 7 cm radial distances were obtained as 1.095, 1.019, 0.826, 0.605, and 0.188, respectively. The results of the IrSeed-125 is not only in good agreement with those calculated by other simulation with MCNP code but also are closer to the experimental results. Discrepancies in the estimation of dose around IrSeed-125 capsule in the muscle and fat tissue phantoms are greater than the breast and lung phantoms in comparison with the water phantom. Results show that GATE/GEANT4 Monte Carlo code produces accurate results for dosimetric parameters of the IrSeed-125 LDR brachytherapy source with choosing the appropriate physics list. There are some differences in the dose calculation in the tissue phantoms in comparison with water phantom, especially in long distances from the source center, which may cause errors in the estimation of dose around brachytherapy sources that are not taken account by the TG43-U1 formalism.

Retrospective dose estimation, particularly dose reconstruction that supports epidemiological investigations of health risk, relies on various strategies that include models of physical processes and exposure conditions with detail ranging from simple to complex. Quantification of dose uncertainty is an essential component of assessments for health risk studies since, as is well understood, it is impossible to retrospectively determine the true dose for each person. To address uncertainty in dose estimation, numerical simulation tools have become commonplace and there is now an increased understanding about the needs and what is required for models used to estimate cohort doses (in the absence of direct measurement) to evaluate dose response. It now appears that for dose-response algorithms to derive the best, unbiased estimate of health risk, we need to understand the type, magnitude and interrelationships of the uncertainties of model assumptions, parameters and input data used in the associated dose estimation models. Heretofore, uncertainty analysis of dose estimates did not always properly distinguish between categories of errors, e.g., uncertainty that is specific to each subject (i.e., unshared error), and uncertainty of doses from a lack of understanding and knowledge about parameter values that are shared to varying degrees by numbers of subsets of the cohort. While mathematical propagation of errors by Monte Carlo simulation methods has been used for years to estimate the uncertainty of an individual subject's dose, it was almost always conducted without consideration of dependencies between subjects. In retrospect, these types of simple analyses are not suitable for studies with complex dose models, particularly when important input data are missing or otherwise not available. The dose estimation strategy presented here is a simulation method that corrects the previous deficiencies of analytical or simple Monte Carlo error propagation methods and is termed, due to its capability to maintain separation between shared and unshared errors, the two-dimensional Monte Carlo (2DMC) procedure. Simply put, the 2DMC method simulates alternative, possibly true, sets (or vectors) of doses for an entire cohort rather than a single set that emerges when each individual's dose is estimated independently from other subjects. Moreover, estimated doses within each simulated vector maintain proper inter-relationships such that the estimated doses for members of a cohort subgroup that share common lifestyle attributes and sources of uncertainty are properly correlated. The 2DMC procedure simulates inter-individual variability of possibly true doses within each dose vector and captures the influence of uncertainty in the values of dosimetric parameters across multiple realizations of possibly true vectors of cohort doses. The primary characteristic of the 2DMC approach, as well as its strength, are defined by the proper separation between uncertainties shared by members of the entire cohort or members of defined cohort subsets, and uncertainties that are individual-specific and therefore unshared.

The purpose of this study is to develop a total body irradiation technique that does not require additional devices or sophisticated processes to overcome the space limitation of a small treatment room. The technique aims to deliver a uniform dose to the entire body while keeping the lung dose within the tolerance level. The technique treats the patient lying on the floor anteriorly and posteriorly. For each AP/PA treatment, two complementary fields with dynamic field edges are matched over an overlapped region defined by the marks on the body surface. A compensator, a spoiler, and lung shielding blocks were used during the treatment. Moreover, electron beams were used to further boost the chest wall around the lungs. The technique was validated in a RANDO phantom using GAFCHROMIC films. Dose ratios at different body sites along the midline ranged from 0.945 to 1.076. The dose variation in the AP direction ranged from 96.0% to 104.6%. The dose distribution in the overlapped region ranged from 98.5% to 102.8%. Lateral dose profiles at abdomen and head revealed 109.8% and 111.7% high doses, respectively, at the body edges. The results confirmed that the technique is capable of delivering a uniform dose distribution to the midline of the body in a small treatment room while keeping the lung dose within the tolerance level.

ID: 188 Monte Carlo simulation of “out-of-field” distributions in a pediatric phantom in external radiotherapy – Couch top impact