Evaluating county-level lung cancer incidence from environmental radiation exposure, PM2.5, and other exposures with regression and machine learning models.

Characterizing the interplay between exposures shaping the human exposome is vital for uncovering the etiology of complex diseases. For example, cancer risk is modified by a range of multifactorial external environmental exposures. Environmental, socioeconomic, and lifestyle factors all shape lung cancer risk. However, epidemiological studies of radon aimed at identifying populations at high risk for lung cancer often fail to consider multiple exposures simultaneously. For example, moderating factors, such as PM2.5, may affect the transport of radon progeny to lung tissue. This ecological analysis leveraged a population-level dataset from the National Cancer Institute's Surveillance, Epidemiology, and End-Results data (2013-17) to simultaneously investigate the effect of multiple sources of low-dose radiation (gross [Formula: see text] activity and indoor radon) and PM2.5 on lung cancer incidence rates in the USA. County-level factors (environmental, sociodemographic, lifestyle) were controlled for, and Poisson regression and random forest models were used to assess the association between radon exposure and lung and bronchus cancer incidence rates. Tree-based machine learning (ML) method perform better than traditional regression: Poisson regression: 6.29/7.13 (mean absolute percentage error, MAPE), 12.70/12.77 (root mean square error, RMSE); Poisson random forest regression: 1.22/1.16 (MAPE), 8.01/8.15 (RMSE). The effect of PM2.5 increased with the concentration of environmental radon, thereby confirming findings from previous studies that investigated the possible synergistic effect of radon and PM2.5 on health outcomes. In summary, the results demonstrated (1) a need to consider multiple environmental exposures when assessing radon exposure's association with lung cancer risk, thereby highlighting (1) the importance of an exposomics framework and (2) that employing ML models may capture the complex interplay between environmental exposures and health, as in the case of indoor radon exposure and lung cancer incidence.

Radiation Protection Considerations for Cancer Patients with End-stage Renal Disease Receiving 131 I Treatment.

ABSTRACT: Differentiated thyroid cancer (DTC) is commonly treated first with a partial or complete thyroidectomy, followed by radioiodine (RAI) ablative therapy to eliminate remaining cancer cells. In such treatments, physical decay and urinary excretion are the primary means of 131 I. As such, patients with impaired urinary ability clearance, such as patients with end-stage renal disease (ESRD) whose urinary ability is impaired by dysfunction, can retain abnormally high activities of RAI, posing a concern to both the patient and those with whom the patient interacts. Additionally, ESRD patients are commonly administered dialysis therapy, wherein their blood is externally cycled through a dialyzer (hemodialysis) or filtered by instilling a dialysate fluid into the peritoneum (peritoneal dialysis) to filter uremic toxins from their blood that accumulate due to kidney dysfunction. These factors make determining release and dosing for ESRD patients receiving RAI therapy dependent on a plurality of variables. An evaluation of the current patient release guidelines, as given in US Nuclear Regulatory Commission (US NRC) Regulatory Guide 8.39 Rev. 1 for ESRD patients receiving RAI, has yet to be addressed. In this study, a biokinetic model for 131 I in ESRD patients receiving dialysis has been developed, improving on traditional two-compartment models, reflective of kinetics from multi-compartment models with updated transfer coefficients modified to reflect the different physiological functions of compartments. This updated biokinetic model was integrated with Monte Carlo radiation transport calculations using stylized computational hermaphroditic phantoms to calculate dose rate coefficients in exposure scenarios and compared with those of the point source models of NRC Reg Guide 8.39 Rev. 1 (and the proposed verbiage in Rev. 2). Results demonstrated that the baseline models of Rev. 1 and Rev. 2 overestimated the effective dose rate to an exposed individual for the majority of time post-administration, where both models overestimated the total dose to the maximally exposed individual. However, the application of several patient-specific modifying factors to the Rev. 2 model resulted in an overestimation by only a factor of 1.25, and in general, the results produced with the patient-specific modifications provide improved convergence with the dose rate coefficients computed in this study for ESRD patients.

Shielding Analysis of a Preclinical Bremsstrahlung X-ray FLASH Radiotherapy System within a Clinical Radiation Therapy Vault.

ABSTRACT: A preclinical radiotherapy system producing FLASH dose rates with 12 MV bremsstrahlung x rays is being developed at Stanford University and SLAC National Accelerator Laboratory. Because of the high expected workload of 6,800 Gy w -1 at the isocenter, an efficient shielding methodology is needed to protect operators and the public while the preclinical system is operated in a radiation therapy vault designed for 6 MV x rays. In this study, an analysis is performed to assess the shielding of the local treatment head and radiation vault using the Monte Carlo code FLUKA and the empirical methodology given in the National Council on Radiation Protection and Measurements Report 151. Two different treatment head shielding designs were created to compare single-layer and multilayer shielding methodologies using high-Z and low-Z materials. The multilayered shielding methodology produced designs with a 17% reduction in neutron fluence leaking from the treatment head compared to the single layered design of the same size, resulting in a decreased effective dose to operators and the public. The conservative assumptions used in the empirical methods can lead to over-shielding when treatment heads use polyethylene or multilayered shielding. High-Z/Low-Z multilayered shielding optimized via Monte Carlo is shown to be effective in the case of treatment head shielding and provide more effective shielding design for external beam radiotherapy systems that use 12 MV bremsstrahlung photons. Modifications to empirical methods used in the assessment of MV radiotherapy systems may be warranted to capture the effects of polyethylene in treatment head shielding.

Monte Carlo simulation of shielding designs for a cabinet form factor preclinical MV-energy photon FLASH radiotherapy system.

PURPOSE: A preclinical MV-energy photon FLASH radiotherapy system is being designed at Stanford and SLAC National Accelerator Laboratory. Because of the higher energy and dose rate compared to conventional kV-energy photon laboratory-scale irradiators, adequate shielding in a stand-alone cabinet form factor is more challenging to achieve. We present a Monte Carlo simulation of multilayered shielding for a compact self-shielding system without the need for a radiation therapy vault. METHODS: A multilayered shielding approach using multiple alternating layers of high-Z and low-Z materials is applied to the self-shielded cabinet to effectively mitigate the secondary radiation produced and to allow the device to be housed in a Controlled Radiation Area outside of a radiation vault. The multilayered shielding approach takes advantage of the properties of high-Z and low-Z radiation shielding materials such as density, cross-section, atomic number of the shielding elements, and products of radiation interactions within each layer. The Monte Carlo radiation transport code, FLUKA, is used to simulate the total effective dose produced by the operation. RESULTS: The multilayered shielding designs proposed and simulated produced effective dose rates significantly lower than monolayer designs with the same total material thickness at the regulatory boundary; this is accomplished through the manipulation of the locations where secondary radiation is produced and reactions due to material properties such as neutron back reflection in hydrogen. Borated polyethylene at 5 wt% significantly increased the shielding performance as compared to regular polyethylene, with the magnitude of the reduction depending upon the order of the shielding material. CONCLUSIONS: The multilayered shielding provides a path for shielding preclinical FLASH systems that deliver MV-energy bremsstrahlung photons. This approach promises to be more efficient with respect to the shielding material mass and space claim as compared to shielded vaults typically required for clinical radiation therapy with MV photons.

177Lu-PSMA Therapy for Metastatic Castration-Resistant Prostate Cancer: A Mini-Review of State-of-the-Art.

BACKGROUND: Prostate specific membrane antigen (PSMA) ligand labeled with Lutetium-177 (177Lu) is a promising therapeutic option for metastatic castration-resistant prostate cancer (mCRPC). Several prospective and retrospective studies as well as clinical trials are completed or underway. This has ultimately led to the approval of this therapy by the US Food and Drug Administration (FDA) on March 23 2022. Our work aims to present a mini-review of the most recent research performed and the potential future directions of 177Lu-PSMA-radioligand therapy (RLT) for mCRPC patients. MAIN BODY: For patients with mCRPCwho have met the eligibility criteria for 177Lu-PSMA RLT, numerous studies and trials are either ongoing or have been completed. The studies included in this review have reported overall biochemical response, defined as a prostate-specific antigen (PSA) decline of at least 50%, in at least 44% of patients with mCRPC. The median ranges of overall survival (OS) and radiographic progression-free survival (rPFS) were reported within 10.7-56 and 3.6-16 months, respectively. With data from several retrospective and prospective studies published, the safety of 177Lu-PSMA RLT in mCRPC has been confirmed and demonstrated by its low toxicity profile. Various studies have published pharmacokinetic/pharmacodynamic models to better understand the absorption, distribution, metabolism, and excretion of the RLT in this patient population. Findings have been published for 177Lu-PSMA RLT alone and in combination with other agents. We summarize their findings in our review. CONCLUSIONS: The efficacy of 177Lu-PSMA RLT for patients with mCRPC has been proven thus far with promising results: PSA response, OS and rPFS when used alone or in combination with other treatment options, relative to the standard treatment options alone. The low toxicity profile noted also proves the safety of 177Lu-PSMA RLT in these patients.

Clinical Management of End-Stage Renal Disease Patients on Dialysis Receiving Radioactive Iodine Treatment.

PURPOSE: Radioactive iodine (RAI) is used to treat thyroid cancer patients with a clear paradigm for most patients. End-stage renal disease (ESRD) patients pose several challenges when undergoing RAI treatment, primarily due to the lack of renal clearance. We retrospectively report our experience with RAI treatment in a cohort of patients with ESRD and provide a set of recommendations on aspects such as the need for adjusted dose activity, balancing scheduling between RAI therapy and dialysis, and radiation safety precautions. PATIENTS AND METHODS: In this study, we report on 5 patients (6 cases), with ESRD on dialysis, treated with RAI for thyroid cancer. Retention measurements to determine individual biological clearance of RAI from the patient's body before and after dialysis sessions were assessed using external exposure dose rates measured at 1 m. RESULTS: Delayed biological clearance of RAI, after the first hemodialysis session, resulted in a longer RAI effective half-life as a consequence of longer retention periods, consistent with observations reported in scientific literature. To achieve a much closer radiation exposure compared with a nondialysis patient, one would recommend administering ~20%-30% of the dose activity normally administered to a thyroid cancer patient based on their medical history, histopathology, and uptake with the appropriate dialysis schedule. CONCLUSIONS: Special precautions should be taken with the administration of RAI in ESRD patients by adjusting the prescribed dose activity, dialysis sessions, and paying special attention to wastes. Pooling data from multiple centers may be useful to build a consensus and substantiated recommendations.

Dose Coefficient Calculation for Use in Dosimetry Assessment of a Fission-Based Weapon.

In the event of a fission-based weapon or improvised nuclear device (IND) detonation, dose coefficients can be harnessed to provide dose assessments for defense, emergency preparedness, and consequence management, as well as to prospectively inform the assessment of radiation biomarkers and development of medical prophylaxis countermeasures for defense and homeland security stakeholders and decision-makers. Although dose coefficients have previously been calculated for this group, they would apply specifically to the studied population, the 1945 Japanese cohort, after which their anthropomorphic computational phantoms were modeled. For this reason, applications to other populations may be limited, and instead, an assessment of a more standardized population is desired. We employed a series of computational human phantoms representing international reference individuals: UF/NCI voxel phantom series containing newborn, 1-, 5-, 10-, 15-, and 35-year-old males and females. Irradiation of the phantoms was simulated using the Monte Carlo N-Particle transport code to determine organ dose coefficients under four idealized irradiation geometries at three distances from the detonation hypocenter at Hiroshima and Nagasaki using DS02 free-in-air prompt neutron and photon fluence spectra. Through these simulations, age-specific dose coefficients were determined for individual organs. Various articulated PIMAL stylized phantoms were simulated as well to estimate the effect of body posture on dose coefficients and determine the effect of posture on dosimetric estimation and reconstruction. Results additionally demonstrate that 137Cs and the Watt fission spectra are not ideal general surrogate sources for fission weapons, which may be considered for experimental testing of medical countermeasures. Supplementary data provided tabulates the compilation of organ dose-rate coefficients in this study.

Specific absorbed fractions for a revised series of the UF/NCI pediatric reference phantoms: internal electron sources.

In both the International Commission on Radiological Protection (ICRP) and Medical Internal Radiation Dose (MIRD) schemata of internal dosimetry, the S-value is defined as the absorbed dose to a target organ per nuclear decay of the radionuclide in a source organ. Its computation requires data on the energies and yields of all radiation emissions from radionuclide decay, the mass of the target organ, and the value of the absorbed fraction-the fraction of particle energy emitted in the source organ that is deposited in the target organ. The specific absorbed fraction (SAF) is given as the ratio of the absorbed fraction and the target mass. Historically, in the early development of both schemata, computational simplifications were made to the absorbed fraction in considering both organ self-dose ([Formula: see text]) and organ cross-dose ([Formula: see text]). In particular, the value of the absorbed fraction was set to unity for all 'non-penetrating' particle emissions (electrons and alpha particles) such that they contributed only to organ self-dose. As radiation transport codes for charged particles became more widely available, it became increasingly possible to abandon this distinction and to explicitly consider the transport of internally emitted electrons in a manner analogous to that for photons. In this present study, we report on an extensive series of electron SAFs computed in a revised series of the UF/NCI pediatric phantoms. A total of 28 electron energies-0-10 MeV-along a logarithmic energy grid are provided in electronic annexes, where 0 keV is associated with limiting values of the SAF. Electron SAFs were computed independently for collisional energy losses (SAFCEL) and radiation energy losses (SAFREL) to the target organ. A methodology was employed in which values of SAFREL were compiled by first assembling organ-specific and electron energy-specific bremsstrahlung x-ray spectra, and then using these x-ray spectra to re-weight a previously established monoenergetic database of photon SAFs for all phantoms and source-target combinations. Age-dependent trends in the electron SAF were demonstrated for the majority of the source-target organ pairs, and were consistent to values given for the ICRP adult phantoms. In selected cases, however, anticipated age-dependent trends were not seen, and were attributed to anatomical differences in relative organ positioning at specific phantom ages. Both the electron SAFs of this study, and the photon SAFs from our companion study, are presently being used by ICRP Committee 2 in its upcoming pediatric extension to ICRP Publication 133.

Specific absorbed fractions for a revised series of the UF/NCI pediatric reference phantoms: internal photon sources.

Assessment of radiation absorbed dose to internal organs of the body from the intake of radionuclides, or in the medical setting through the injection of radiopharmaceuticals, is generally performed based upon reference biokinetic models or patient imaging data, respectively. Biokinetic models estimate the time course of activity localized to source organs. The time-integration of these organ activity profiles are then scaled by the radionuclide S-value, which defines the absorbed dose to a target tissue per nuclear transformation in various source tissues. S-values are computed using established nuclear decay information (particle energies and yields), and a parameter termed the specific absorbed fraction (SAF). The SAF is the ratio of the absorbed fraction-fraction of particle energy emitted in the source tissue that is deposited in the target tissue-and the target organ mass. While values of the SAF may be computed using patient-specific or individual-specific anatomic models, they have been more widely available through the use of computational reference phantoms. In this study, we report on an extensive series of photon SAFs computed in a revised series of the University of Florida and the National Cancer Institute pediatric reference phantoms which have been modified to conform to the specifications embodied in the ICRP reference adult phantoms of Publication 110 (e.g. organs modeled, organ ID numbers, blood contribution to elemental compositions). Following phantom anatomical revisions, photon radiation transport simulations were performed using MCNPX v2.7 in each of the ten phantoms of the series-male and female newborn, 1 year old, 5 year old, 10 year old, and 15 year old-for 60 different tissues serving as source and/or target regions. A total of 25 photon energies were considered from 10 keV to 10 MeV along a logarithm energy grid. Detailed analyses were conducted of the relative statistical errors in the Monte Carlo target tissue energy deposition tallies at low photon energies and over all energies for source-target combinations at large intra-organ separation distances. Based on these analyses, various data smoothing algorithms were employed, including multi-point weighted data smoothing, and log-log interpolation at low energies (1 keV and 5 keV) using limiting SAF values based upon target organ mass to bound the interpolation interval. The final dataset is provided in a series of ten electronic supplemental files in MS Excel format. The results of this study were further used as the basis for assessing the radiative component of internal electron source SAFs as described in our companion paper (Schwarz et al 2021) for this same pediatric phantom series.

Stylized versus voxel phantoms: a juxtaposition of organ depth distributions.

For external irradiation, the variability in organ dose estimation found between computational phantom generations arises particularly from the differences in organ positioning. This work represents the first effort to quantify the differences in organ depth below the body surface between a stylized and voxel phantom series. Herein, the revised Oak Ridge National Laboratory stylized phantom series and the University of Florida/National Cancer Institute voxel phantom series were compared. Both series include whole-body models of the newborn; the 1-, 5-, 10-, and 15-year-old; and the adult human. Organ depths from eight different directions applicable to external irradiation geometries were computed: antero-posterior, postero-anterior, left and right lateral, rotational, isotropic, cranial and caudal directions. Organ depths in the stylized phantoms were computed using a ray-tracing technique available through Monte Carlo radiation transport simulations in MCNP6. Organ depths in the voxel phantom were found using phantom matrix manipulation. Resultant organ depths for both series were plotted as distributions; available are twenty-four organs and two bone tissue distributions for each of six phantom ages and in each of the eight directional geometries. Quantitative data descriptors (e.g. mean and median depths) were also tabulated. For demonstration purposes, a literature review of relevant stylized versus voxel comparison works was performed to explore where the quantification of organ depth differences can provide further insight or evidence to study conclusions. The entire dataset of organ depth distributions and their data descriptors can be found in online supplementary files.

Organ and detriment-weighted dose rate coefficients for exposure to radionuclide-contaminated soil considering body morphometries that differ from reference conditions: adults and children.

The system of protection established by the International Commission on Radiological Protection (ICRP) provides a robust framework for ionizing radiation exposure justification, optimization, and dose limitation. The system is built upon fundamental concepts of a reference person, defined in ICRP Publication 89, and the radiation protection quantity effective dose, defined in ICRP Publication 103. For external exposures to radionuclide-contaminated soil, values of the organ dose rate coefficient (Gy/s per Bq/m2) and effective dose rate coefficient (Sv/s per Bq/m2) have been computed by several authors and national laboratories using ICRP-compliant reference phantoms-both stylized and voxelized. These coefficients are of great value in post-accident exposure assessments as seen in Japan following the 2011 Fukushima Daiichi nuclear power station disaster. Questions arise, however, among the general public regarding the accuracy of organ and effective dose estimates based upon reference phantom methodologies, especially for those individuals with height and/or total body mass that differ modestly or even substantially from the nearest age-matched reference person. In this pilot study, this issue is explored through use of the extended 351-member UF/NCI hybrid phantom library in which values of organ and detriment-weighted dose rate coefficients are computed for sex/height/mass-specific phantoms, and systematically compared to their values of the effective dose rate coefficient computed using corresponding reference phantoms. Results are given for monoenergetic photons, and then for some 33 different radionuclides, with all dose rate coefficient data provided in a series of electronic annexes. For environmentally relevant radionuclides such as 89Sr, 90Sr, 137Cs, and 131I, percent differences between the detriment-weighted dose rate coefficient computed using non-reference and the effective dose rate coefficient computed using reference phantoms vary only ± 5% for young children approximated by the reference 1-year-old phantom. With increased body size and age, the range of percent differences in these two quantities increases to + 7% to - 14% for the reference 5-year-old, to + 10% to - 27% for the reference 10-year-old, to + 33% to - 31% for the reference 15-year-old, and to + 15% to - 40% for male and female adults.

Monitoring and Dose Assessment for Children Following a Radiation Emergency-Part II: Calibration Factors for Thyroid Monitoring.

Past radiological and nuclear accidents have demonstrated that monitoring a large number of children following a radiological and nuclear emergency can be challenging, in accommodating their needs as well as adapting monitoring protocols and applying age-specific biokinetics to account for various ages and body sizes. This paper presents the derived calibration factors for thyroid monitoring of children of all ages recommended by the International Commission on Radiological Protection using four selected detectors at given times following a short-term (acute) intake of I by inhalation. These calibration factors were derived by Monte Carlo simulations using the models of various detectors and pediatric voxel phantoms. A collection of lookup tables is presented in this paper which may be directly used as a quick reference by emergency response personnel or technical experts performing thyroid monitoring and assessment without doing time-consuming calculations.

Synopsis of the Oak Ridge Radiation Protection Research Needs Workshop.

Radiation protection is foundational to harnessing the societal benefits of radiation in nuclear energy, security, and medicine applications. Significant challenges in radiation protection remain unaddressed for the nuclear fuel cycle, nuclear medicine, emergency response, national defense, and space exploration, as the United States is lacking a coherent research strategy prioritizing radiation protection mission needs and gaps in scientific knowledge to meet these needs. Research and development in the field of radiation protection calls for cooperation among governmental agencies, emergency responders, research organizations, and the academic community. Amidst atrophying national expertise in radiation protection, the Radiation Protection Research Needs Workshop was spearheaded by the Oak Ridge Associated Universities, Oak Ridge National Laboratory, and the Health Physics Society. This workshop facilitated critical dialogue among radiation stakeholders in the governmental and scientific communities, including national laboratories, academic institutions, and industry partners. The workshop featured presentations representing 12 federal agencies and breakout sessions involving the identification of scientific drivers by subject matter experts in each of the following areas: new fuel cycles/reactors, dosimetry, medical physics, instrumentation and operations, decontamination and decommissioning, space radiation, national defense, emergency response, environmental modeling, and low-dose effects. The goal of this workshop was to seek stakeholder input toward the development of a national strategic research agenda in the field of radiation protection. Consequently, the Health Physics Society has established a Special Task Force on Health Physics Research Needs, tasked with the prioritization of scientific drivers in radiation protection for the development of a national strategic research agenda.

Age-dependent comparison of monoenergetic photon organ and effective dose coefficients for pediatric stylized and voxel phantoms submerged in air.

Dose rate coefficients computed using the University of Florida-National Cancer Institute pediatric series of voxel phantoms were compared with values computed using the Oak Ridge National Laboratory pediatric stylized phantoms in an air submersion exposure geometry. Simulations were conducted comparing phantoms classified within five ages: newborn, 1-year-old, 5-year-old, 10-year-old, and 15-year-old for both male and female sexes. This is a continuation of previous work comparing monoenergetic photon organ dose rate coefficients, as defined by ICRP Publication 103, for the male and female adult phantoms. With both the male and female data computed for each pediatric phantom age, effective dose rate coefficients and ratios were computed for voxel and stylized phantoms. Organ dose rate coefficients for the pediatric phantoms and ratios of organ dose rates for the voxel and stylized phantoms are provided for eight monoenergetic photon energies ranging from 30 keV to 5 MeV. Analysis of the contribution of the organs to effective dose is also provided. Comparison of effective dose rates between the voxel and stylized phantoms was within 5% between 500 keV and 5 MeV and within 10% between 70 keV and 5 MeV for phantoms >1-year-old. Stylized newborn effective dose rates were consistently ~20% higher than the voxel counterpart, over all energies.

Critical Issues in Radiation Protection Knowledge Management for Preserving Radiation Protection Research and Development Capabilities.

As a hub of domestic radiation protection capabilities, Oak Ridge National Laboratory's Center for Radiation Protection Knowledge has a mandate to develop and actuate a formal knowledge management (KM) effort. This KM approach exceeds recruitment and training efforts but focuses on formalized strategies for knowledge transfer from outgoing subject matter experts in radiation protection to incoming generations. It is envisioned that such an effort will provide one avenue for preserving domestic capabilities to support stakeholder needs in the federal government and the nuclear industry while continuing to lead and innovate in research and development on a global scale. However, in the absence of broader coordination within the United States, preservation of radiation protection knowledge continues to be in jeopardy in the absence of a dedicated KM effort.

Assessment of the Point-Source Method for Estimating Dose Rates to Members of the Public from Exposure to Patients with 131I Thyroid Treatment.

The U.S. Nuclear Regulatory Commission (USNRC) initiated a contract with Oak Ridge National Laboratory (ORNL) to calculate radiation dose rates to members of the public that may result from exposure to patients recently administered iodine-131 (131I) as part of medical therapy. The main purpose was to compare dose rate estimates based on a point source and target with values derived from more realistic simulations of a human source and target. The latter simulations considered the time-dependent distribution of 131I in the patient and attenuation of emitted photons by the patient's tissues. The external dose rate estimates were derived using Monte Carlo methods and two representations of the Phantom with Movable Arms and Legs (PIMAL), previously developed by ORNL and the USNRC, to model the patient and a nearby member of the public. Dose rates to tissues and effective dose rates were calculated for distances ranging from 10 cm to 300 cm between the phantoms. Dose rates estimated from these simulations are compared to estimates based on the point-source method, as well as to results of previous studies that estimated exposure from 131I patients. The point-source method overestimates dose rates to members of the public in very close proximity to an 131I patient but is a broadly accurate method of dose rate estimation at separation distances of 300 cm or more at times closer to administration.