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An expert-driven literature review of “negative” chemicals for developmental neurotoxicity (DNT) in vitro assay evaluation

To date, approximately 200 chemicals have been tested in US Environmental Protection Agency (EPA) or Organization for Economic Co-operation and Development (OECD) developmental neurotoxicity (DNT) guideline studies, leaving thousands of chemicals without traditional animal information on DNT hazard potential. To address this data gap, a battery of in vitro DNT new approach methodologies (NAMs) has been proposed. Evaluation of the performance of this battery will increase the confidence in its use to determine DNT chemical hazards. One approach to evaluate DNT NAM performance is to use a set of chemicals to evaluate sensitivity and specificity. Since a list of chemicals with potential evidence of in vivo DNT has been established, this study aims to develop a curated list of “negative” chemicals for inclusion in a “DNT NAM evaluation set”. A workflow, including a literature search followed by an expert-driven literature review, was used to systematically screen 39 chemicals for lack of DNT effect. Expert panel members evaluated the scientific robustness of relevant studies to inform chemical categorizations. Following review, the panel discussed each chemical and made categorical determinations of “Favorable”, “Not Favorable”, or “Indeterminate” reflecting acceptance, lack of suitability, or uncertainty given specific limitations and considerations, respectively. Further, the panel determined that 10, 22, and 7 chemicals met the criteria for “Favorable”, “Not Favorable”, and “Indeterminate”, for use as negatives in a DNT NAM evaluation set. Ultimately, this approach not only supports DNT NAM performance evaluation but also highlights challenges in identifying large numbers of negative DNT chemicals.

59 BASIC BIOLOGICAL SCIENCES↗

Categorizing An Explosive Device by its Nuclear Signature (Rev. 1)

This report documents a study to eliminate ambiguity in identifying a very low-yield nuclear detonation in the early stages of the response to such an event. The ambiguity arises from the very similar explosive and radiation effects produced by three categories of explosive devices: An explosively driven radiological dispersal device (RDD) or an accidental explosion in which radiologic material is scattered by chemical explosives. A failed nuclear device in which nuclear material, such as uranium or plutonium, has been scattered by conventional explosives. A nuclear device that, in addition to scattering nuclear material, produced a very low-yield from nuclear fission. The study found that the properties of fission products provide a ready solution to the problem. The radiation dose rate from fission products that were produced in a nearly instantaneous “fission event” decreases extremely rapidly over the first eight hours after that event, whereas nuclear materials and common radiological materials produce an essentially constant dose rate. This contrast provides an unequivocal fission product signature. The measurements required to utilize this signature can be made by first responders with radiation detectors already in the field, on time scales of an hour, although later confirmation using more capable detectors, including spectroscopic capability, is advised. The process of categorizing an explosives-related incident, both pre- and post-detonation, can be represented as a Decision Tree. The Decision Tree illustrates the use of already-fielded radiation detectors to categorize incidents as likely to involve only conventional explosives, an explosively driven RDD, or a nuclear device. The identification of an explosion as a fission event is extremely important to evacuation planners. It has been shown that delayed evacuation after sheltering in place for up to 24 hours after a fission event has the potential to reduce radiation exposure to the affected public and responders by a factor of ten. Traditional evidence collection after a nuclear detonation is likely to be similarly delayed, as the value and urgency of collection efforts must be weighed against radiation and other hazardous exposure of the collectors. The evidence that survives the immediate effects of a nuclear detonation will, in many cases, still be available for collection once radiation levels have diminished to acceptable levels. Certain classes of evidence, notably information stored on digital media, may significantly degrade from exposure to post-detonation radiation fields. Technical nuclear forensics collections will be performed in all events with nuclear yield. Modification of the high-yield collection strategy may be necessary for a very low-yield device.

98 NUCLEAR DISARMAMENT, SAFEGUARDS, AND PHYSICAL P↗

Needs for integrated risk assessment to support optimal environmental management decisions - 15455

Cleaning up legacy waste from 50 years of nuclear weapons production and energy research still remains a challenge for the U.S. Department of Energy (DOE). The DOE environmental management program is currently forecasted to run through at least late 2060's with an estimated liability of $204 billion. Risks to human health of workers and the public, the ecological system, and nuclear safety of cleanup activities continue to drive the cost of DOE's cleanup programs. Currently, these risks are generally assessed and managed independently of each other. Except for DOE self-regulated on-site disposal activities of low-level radioactive waste, risks to human health and the environment are generally under the purview of U.S. Environmental Protection Agency and State regulatory agencies, while nuclear safety risks are regulated by DOE with oversight from the U.S. Nuclear Regulatory Commission and the Defense Nuclear Facilities Safety Board where appropriate. When managing health and environmental risks, the individual regulatory authorities often use an area-by-area (or unit-by-unit), contaminant-by-contaminant (chemical-by-chemical or radionuclide-by-radionuclide) approach, focusing on a single medium (soil, water, or air), a single source (e.g., a burial ground or a processing facility), and a single receptor (e.g, a groundwater well or a creek). This level of segregation in risk evaluations by risk category, geographical location, and operational unit, as well as the corresponding separation of regulatory authorities poses a significant challenge to reaching an optimal decision in prioritizing and managing cleanup activities. This management challenge adds another layer of complexity to large-scale cleanup effort at complex sites such as the Hanford site in eastern Washington. Therefore, to support a scientifically sound, operationally robust decision making process, there is a need for an integrated, holistic approach to risk assessment that addresses the combined effects of all major contributing factors. Previous studies have pointed out the need for integrated risk assessments that address multi-contaminant, multimedia, multi-pathway exposures, for the purposes of evaluating risks to human health and the environment. We believe that a comprehensive risk assessment should also take into nuclear safety risks that are associated with handling of nuclear material either retrieved from burial sites or to be decommissioned from nuclear facilities. Recent efforts, such as the Consortium for Risk Evaluation with Stakeholder Participation (CRESP)-led Hanford site-wide independent risk review that will categorize all types of risks at the Hanford site and the DOE complex-wide risk review mandated by the Fiscal Year 2014 Consolidated Appropriations Act ('Omnibus bill'), are beginning to more comprehensively address this need. This paper provides a categorization of various types of risks present at typical DOE sites, reviews the current risk assessment and management practices, and discusses the needs for integrating nuclear safety into performance and risk assessments for optimal cleanup decisions. (authors)

12 MANAGEMENT OF RADIOACTIVE AND NON-RADIOACTIVE W↗

Radiological Risk From Disused Radioactive Sealed Sources in Egypt - 19083

Sealed sources are radioactive nuclear substances encased in a sealed capsule or in a cover to which the substance is bonded, and are used for a variety of activities, such as medical, industrial, academic and research, as well as commercial applications. While most sources are of relatively low activity, there are many of medium or very high activity. In use radioactive sealed sources after time become disused sources according to several reasons like, if the source activity became less than the desired activity (unfit for the intended application), if the model of the instrument became old fashion and no longer uses, if the source had been damaged, and if the user company was shut down and no longer in business. In developing countries, thousands of radium needles, teletherapy sources, oil well logging neutron sources, and miscellaneous industrial radioactive gauges are annually collected as waste and stored in centralized waste facilities. Although these sources become disused, it still dangerous and the mismanagement of high activity sources is responsible for most of the radiological accidents that result in loss of life or disabling injuries. On the other hand, these sources may be a target for criminal acts in countries where final disposal options are unavailable. Egyptian Atomic Energy Authority (EAEA) represented in Hot Labs and Waste Management Center (HLWMC) is responsible by the national nuclear law (law No. 7 /2010) for management of all kinds of radioactive waste including disused radioactive sealed sources from all Egyptian territories. Categorization of disused sources is necessary to ensure that the controls and security measures that are applied to the sources are adequate with its radiological risk. The aim of this work is to use the international Atomic Energy Agency (IAEA) categorization system to provide a simple, logical system for grading disused radioactive sealed sources in Egypt as well as to update the inventory of such sources which already collected as waste in Egypt. The categorizations of radioactive sealed sources are based on their potential to cause harm to human health. This study revealed that nearly 980 sources have been defined in Egypt as disused sources with a total activity of 46100 Ci according to available data in July 2018. (author)

12 MANAGEMENT OF RADIOACTIVE AND NON-RADIOACTIVE W↗

Long-Term Management of Mercury at the Savannah River Site Liquid Waste System - 17364

Mercury in the Savannah River Site Liquid Waste System (LWS) originated from decades of canyon processing where it was used as a catalyst for dissolving the aluminum cladding of reactor fuel. Approximately 60 metric tons of mercury (Hg) is currently present throughout the LWS. Mercury has long been a consideration in the LWS, from both hazard and processing perspectives. In February 2015, a Mercury Program Team (MPT) was established at the request of the Department of Energy to 'take an integrated, system-wide approach to evaluating the movement, monitoring, and collection of mercury through the entire Liquid Waste System/Facilities.... The key objective of the Mercury Program Team was to evaluate mercury in the LWS and develop a comprehensive action plan for long term management and removal of mercury. After completion of Phase I and II, a comprehensive action plan for long-term management and removal of mercury was developed and recommendations for actions are categorized under three broad categories - Plant Operations, Technology Development, and Sampling and Monitoring. The resolution of these Action Items will provide long term management and removal of mercury through the LWS. (authors)

12 MANAGEMENT OF RADIOACTIVE AND NON-RADIOACTIVE W↗

Role of Adjuvant Chemotherapy in ypT0-2N0 Patients Treated with Preoperative Chemoradiation Therapy and Radical Resection for Rectal Cancer

Objective: To explore the role of adjuvant chemotherapy for patients with ypT0-2N0 rectal cancer treated by preoperative chemoradiation therapy (PCRT) and radical resection. Patients and Methods: A national consortium of 10 institutions was formed, and patients with ypT0-2N0 mid- and low-rectal cancer after PCRT and radical resection from 2004 to 2009 were included. Patients were categorized into 2 groups according to receipt of additional adjuvant chemotherapy: Adj CTx (+) versus Adj CTx (−). Propensity scores were calculated and used to perform matched and adjusted analyses comparing relapse-free survival (RFS) between treatment groups while controlling for potential confounding. Results: A total of 1016 patients, who met the selection criteria, were evaluated. Of these, 106 (10.4%) did not receive adjuvant chemotherapy. There was no overall improvement in 5-year RFS as a result of adjuvant chemotherapy [91.6% for Adj CTx (+) vs 87.5% for Adj CTx (−), P=.18]. There were no differences in 5-year local recurrence and distant metastasis rate between the 2 groups. In patients who show moderate, minimal, or no regression in tumor regression grade, however, possible association of adjuvant chemotherapy with RFS would be considered (hazard ratio 0.35; 95% confidence interval 0.14-0.88; P=.03). Cox regression analysis after propensity score matching failed to show that addition of adjuvant chemotherapy was associated with improved RFS (hazard ratio 0.81; 95% confidence interval 0.39-1.70; P=.58). Conclusions: Adjuvant chemotherapy seemed to not influence the RFS of patients with ypT0-2N0 rectal cancer after PCRT followed by radical resection. Thus, the addition of adjuvant chemotherapy needs to be weighed against its oncologic benefits.

62 RADIOLOGY AND NUCLEAR MEDICINE↗

Reduced Incidence of Cardiac Arrhythmias in Walkers and Runners

Walking is purported to reduce the risk of atrial fibrillation by 48%, whereas jogging is purported to increase its risk by 53%, suggesting a strong anti-arrhythmic benefit of walking over running. The purpose of these analyses is to compare incident self-reported physician-diagnosed cardiac arrhythmia to baseline energy expenditure (metabolic equivalent hours per day, METhr/d) from walking, running and other exercise. Proportional hazards analysis of 14,734 walkers and 32,073 runners. There were 1,060 incident cardiac arrhythmias (412 walkers, 648 runners) during 6.2 years of follow-up. The risk for incident cardiac arrhythmias declined 4.4% per baseline METhr/d walked by the walkers, or running in the runners (P = 0.0001). Specifically, the risk declined 14.2% (hazard ratio: 0.858) for 1.8 to 3.6 METhr/d, 26.5% for 3.6 to 5.4 METhr/d, and 31.7% for $5.4 METhr/d, relative to ,1.8 METhr/d. The risk reduction per METhr/d was significantly greater for walking than running (P,0.01), but only because walkers were at 34% greater risk than runners who fell below contemporary physical activity guideline recommendations; otherwise the walkers and runners had similar risks for cardiac arrhythmias. Cardiac arrhythmias were unrelated to walking and running intensity, and unrelated to marathon participation and performance. The risk for cardiac arrhythmias was similar in walkers and runners who expended comparable METhr/d during structured exercise. We found no significant risk increase for self-reported cardiac arrhythmias associated with running distance, exercise intensity, or marathon participation. Rhythm abnormalities were based on self-report, precluding definitive categorization of the nature of the rhythm disturbance. However, even if the runners’ arrhythmias include sinus bradycardia due to running itself, there was no increase in arrhythmias with greater running distance.

59 BASIC BIOLOGICAL SCIENCES↗

Sodium silicate treatment for uranium (vi) bearing groundwater systems at f/h area at savannah river site - 15709

The Savannah River Site (SRS) was one of the most significant manufacturing facilities during the Cold War era for producing nuclear materials. At the end of the Cold War, the Site's mission changed to support the environmental restoration of the Site due to over six decades of research, development, and production of nuclear weapons. Currently SRS is a major hazardous waste management facility responsible for nuclear materials storage, and remediation of contaminated soil and groundwater from radionuclides. This research focuses on controlling the mobilization of the contaminants, specifically uranium (VI) located in groundwater plumes at the Site's F/H Area Seepage Basin, where approximately 1.8 billion gallons of hazardous waste were deposited. Objective: To evaluate the potential use of sodium silicate for uranium removal from the aqueous phase, as well as to restore the pH of the treatment zone. Adding sodium silicate increases the pH of the treatment zone and uranium precipitation is achieved, therefore immobilizing the contaminant. Through a series of experiments the optimal concentration of sodium silicate was investigated. Part 1: An experiment was conducted in order to determine the effect of sodium silicate on the pH of a solution containing Savannah River Site soil and synthetic groundwater replicated after the Site's natural groundwater composition. Each sample was spiked with the appropriate volume from the sodium silicate stock solution in order to achieve final desired sodium silicate concentrations of 10, 20, 40,50,60,70, and 80 parts per million. The samples were placed on a platform shaker for three days during which pH readings were collected in regular intervals to determine which silicate concentration produced a pH in the neutral range (6 > pH < 8). Part 2: A sequential experiment was conducted specifically using 40 and 50 ppm of sodium silicate with Savannah River Site soil, synthetic groundwater, and 0.5 ppm of uranium (VI), in order to investigate the removal of uranium in the aqueous phase via precipitation. Samples were extracted and categorized into a filtered and non-filtered control group. Each sample was diluted 1:20 with 1% nitric acid and analyzed using the Kinetic Phosphorescence Analyzer (KPA) in order to measure uranium concentrations in the supernatant. By measuring the concentration of uranium in the supernatant the percent removal is obtained for the comparison between the filtered and non-filtered samples, revealing the amount of uranium precipitation that occurred for each silicate concentration. Results: A sodium silicate concentration of between 40-50 ppm proved ideal for achieving uranium precipitation and creating a circum-neutral pH environment in the aqueous phase. 50 ppm achieved the larger percent of uranium precipitation with a range of 30-50% removal for the filtered samples and between 60-95% removal for the non-filtered samples. A large difference between the removal of filtered and non- filtered samples from the same day was observed for both sodium silicate concentrations tested, indicating that there is a considerable amount of uranium species retained in the filter. The addition of sodium silicate proved effective in the removal of uranium precipitation from the aqueous phase. Future work: Determine potential re-solubilization of uranium concentrations; Examine mineralogy and surface morphology of dried precipitate using XRD and SEM/EDS.

12 MANAGEMENT OF RADIOACTIVE AND NON-RADIOACTIVE W↗

Secondary Breast Cancer Risk by Radiation Volume in Women With Hodgkin Lymphoma

Purpose: To determine whether the risk of secondary breast cancer (SBC) is reduced in women with Hodgkin lymphoma (HL) treated with smaller field radiation therapy (SFRT) versus mantle field radiation therapy (MRT). Methods and Materials: We used the BC Cancer Agency (BCCA) Lymphoid Cancer Database to identify female patients treated for HL between January 1961 and December 2009. Radiation therapy volumes were categorized as MRT or SFRT, which included involved field, involved site, or involved nodal radiation therapy. SBC risk estimates were compared using competing risk analysis and Fine and Gray multivariable model: MRT ± chemotherapy, SFRT ± chemotherapy, or chemotherapy-only. Results: Of 734 eligible patients, 75% of the living patients have been followed up for more than 10 years, SBC has developed in 54, and 15 have died of breast cancer. The 20-year estimated risks (competing risk cumulative incidence) for SBC differed significantly: MRT 7.5% (95% confidence interval [CI] 4.4%-11.5%), SFRT 3.1% (95% CI 1.0%-7.7%), and chemotherapy-only 2.2% (95% CI 1.0%-4.8%) (P=.01). Using a Fine and Gray model to control for death and patients lost to follow-up, MRT was associated with a higher risk of SBC (hazard ratio [HR] = 2.9; 95% CI 1.4%-6.0%; P=.004) compared with chemotherapy-only and with SFRT (HR = 3.3; 95% CI 1.3%-8.4%; P=.01). SFRT was not associated with a greater risk of SBC compared with chemotherapy-only (HR = 0.87; 95% CI 0.28%-2.66%; P=.80). Conclusion: This study confirms that large-volume MRT is associated with a markedly increased risk of SBC; however, more modern small-volume RT is not associated with a greater risk of SBC than chemotherapy alone.

62 RADIOLOGY AND NUCLEAR MEDICINE↗

Is Androgen Deprivation Therapy Necessary in All Intermediate-Risk Prostate Cancer Patients Treated in the Dose Escalation Era?

Purpose: The benefit of adding androgen deprivation therapy (ADT) to dose-escalated radiation therapy (RT) for men with intermediate-risk prostate cancer is unclear; therefore, we assessed the impact of adding ADT to dose-escalated RT on freedom from failure (FFF). Methods: Three groups of men treated with intensity modulated RT or 3-dimensional conformal RT (75.6-78 Gy) from 1993-2008 for prostate cancer were categorized as (1) 326 intermediate-risk patients treated with RT alone, (2) 218 intermediate-risk patients treated with RT and ≤6 months of ADT, and (3) 274 low-risk patients treated with definitive RT. Median follow-up was 58 months. Recursive partitioning analysis based on FFF using Gleason score (GS), T stage, and pretreatment PSA concentration was applied to the intermediate-risk patients treated with RT alone. The Kaplan-Meier method was used to estimate 5-year FFF. Results: Based on recursive partitioning analysis, intermediate-risk patients treated with RT alone were divided into 3 prognostic groups: (1) 188 favorable patients: GS 6, ≤T2b or GS 3+4, ≤T1c; (2) 71 marginal patients: GS 3+4, T2a-b; and (3) 68 unfavorable patients: GS 4+3 or T2c disease. Hazard ratios (HR) for recurrence in each group were 1.0, 2.1, and 4.6, respectively. When intermediate-risk patients treated with RT alone were compared to intermediate-risk patients treated with RT and ADT, the greatest benefit from ADT was seen for the unfavorable intermediate-risk patients (FFF, 74% vs 94%, respectively; P=.005). Favorable intermediate-risk patients had no significant benefit from the addition of ADT to RT (FFF, 94% vs 95%, respectively; P=.85), and FFF for favorable intermediate-risk patients treated with RT alone approached that of low-risk patients treated with RT alone (98%). Conclusions: Patients with favorable intermediate-risk prostate cancer did not benefit from the addition of ADT to dose-escalated RT, and their FFF was nearly as good as patients with low-risk disease. In patients with GS 4+3 or T2c disease, the addition of ADT to dose-escalated RT did improve FFF.

62 RADIOLOGY AND NUCLEAR MEDICINE↗

Cancer epidemiology update, following the 2011 IARC evaluation of radiofrequency electromagnetic fields (Monograph 102)

Highlights: • Increased risk of brain, vestibular nerve and salivary gland tumors are associated with mobile phone use. • Nine studies (2011–2017) report increased risk of brain cancer from mobile phone use. • Four case-control studies (3 in 2013, 1 in 2014) report increased risk of vestibular nerve tumors. • Concern for other cancers: breast (male & female), testis, leukemia, and thyroid. • Based on the evidence reviewed it is our opinion that IARC's current categorization of RFR as a possible human carcinogen (Group 2B) should be upgraded to Carcinogenic to Humans (Group 1). Epidemiology studies (case-control, cohort, time trend and case studies) published since the International Agency for Research on Cancer (IARC) 2011 categorization of radiofrequency radiation (RFR) from mobile phones and other wireless devices as a possible human carcinogen (Group 2B) are reviewed and summarized. Glioma is an important human cancer found to be associated with RFR in 9 case-control studies conducted in Sweden and France, as well as in some other countries. Increasing glioma incidence trends have been reported in the UK and other countries. Non-malignant endpoints linked include acoustic neuroma (vestibular Schwannoma) and meningioma. Because they allow more detailed consideration of exposure, case-control studies can be superior to cohort studies or other methods in evaluating potential risks for brain cancer. When considered with recent animal experimental evidence, the recent epidemiological studies strengthen and support the conclusion that RFR should be categorized as carcinogenic to humans (IARC Group 1). Opportunistic epidemiological studies are proposed that can be carried out through cross-sectional analyses of high, medium, and low mobile phone users with respect to hearing, vision, memory, reaction time, and other indicators that can easily be assessed through standardized computer-based tests. As exposure data are not uniformly available, billing records should be used whenever available to corroborate reported exposures.

63 RADIATION, THERMAL, AND OTHER ENVIRON. POLLUTAN↗

ASMT-783246, Assessment Report for Department 635 Analysis of Fiscal Year 2021 ES&H Events

This assessment analyzes Environment, Safety, and Health (ES&H) occurrences and Non-Occurrence Trackable Events (NOTEs) from fiscal year (FY) 2021. For this report, assessors used three primary methods for categorizing occurrence and NOTE data: issue categorization, DOE reporting criteria groups, and DOE cause codes. The FY 2021 Q1 occurrence and NOTE total was the lowest since this type of analysis began in FY 2018 Q4, following a downward trend from the FY 2019 Q3 high point. The FY 2021 Q2 occurrence and NOTE total was nearly double the FY 2021 Q1 total; occurrence totals declined slightly in Q3 and Q4, while NOTE totals remained the same. NOTEs in each of the final three quarters were more than double the amount from Q1. This assessment resulted in one observation. As COVID-19 vaccination rates increase and COVID 19 impacts on operations decrease, the number of workers on-site and the amount of activity-level work will increase. With these changes, focused attention on the following areas related to work planning and controls may reduce the probability of future events, hazard identification and analysis, compliance with standards, formality of operations, and job scoping.

99 GENERAL AND MISCELLANEOUS↗

Brachial Plexopathy in Apical Non-Small Cell Lung Cancer Treated With Definitive Radiation: Dosimetric Analysis and Clinical Implications

Purpose: Data are limited on the clinical significance of brachial plexopathy in patients with apical non-small cell lung cancers (NSCLC) treated with definitive radiation therapy. We report the rates of radiation-induced brachial plexopathy (RIBP) and tumor-related brachial plexopathy (TRBP) and associated dosimetric parameters in apical NSCLC patients. Methods and Materials: Charts of NSCLC patients with primary upper lobe or superiorly located nodal disease who received {>=}50 Gy of definitive conventionally fractionated radiation or chemoradiation were retrospectively reviewed for evidence of brachial plexopathy and categorized as RIBP, TRBP, or trauma-related. Dosimetric data were gathered on ipsilateral brachial plexuses (IBP) contoured according to Radiation Therapy Oncology Group atlas guidelines. Results: Eighty patients were identified with a median follow-up and survival time of 17.2 and 17.7 months, respectively. The median prescribed dose was 66.6 Gy (range, 50.4-84.0), and 71% of patients received concurrent chemotherapy. RIBP occurred in 5 patients with an estimated 3-year rate of 12% when accounting for competing risk of death. Seven patients developed TRBP (estimated 3-year rate of 13%), comprising 24% of patients who developed locoregional failures. Grade 3 brachial plexopathy was more common in patients who experienced TRBP than RIBP (57% vs 20%). No patient who received {<=}78 Gy to the IBP developed RIBP. On multivariable competing risk analysis, IBP V76 receiving {>=}1 cc, and primary tumor failure had the highest hazard ratios for developing RIBP and TRBP, respectively. Conclusions: RIBP is a relatively uncommon complication in patients with apical NSCLC tumors receiving definitive doses of radiation, while patients who develop primary tumor failures are at high risk for developing morbid TRBP. These findings suggest that the importance of primary tumor control with adequate doses of radiation outweigh the risk of RIBP in this population of patients.

62 RADIOLOGY AND NUCLEAR MEDICINE↗

Impact of Preoperative Skeletal Muscle Mass and Nutritional Status on Short-and Long-Term Outcomes After Esophagectomy for Esophageal Cancer: A Retrospective Observational Study

Background: Preoperative muscle volume and body mass index (BMI) are associated with postoperative outcomes. Because esophagectomy for esophageal cancer (EC) is associated with high morbidity and because EC has a poor prognosis, this study investigated the association of preoperative skeletal muscle mass and nutritional status with postoperative outcomes. Methods: The study analyzed 483 patients who underwent esophagectomy from 2009 to 2012. The cross-sectional area of the psoas muscle index (PMI) was measured at the third lumbar vertebral level using computed tomography. Clavien–Dindo classifications were used to analyze postoperative complications. Because skeletal muscle mass varies according to sex, all analyses were performed accordingly (390 males, 93 females). Results: For male patients, BMI was a significant multivariate factor, and PMI, a univariate factor, predicted postoperative complications and overall survival (OS). Using a preoperative nutritional and muscular (PNM) score derived from BMI and PMI results (patients were allocated 1 point if their BMI was < 18.5 kg/m{sup 2} and 1 point if their PMI was < 600 mm{sup 2}/m{sup 2}, for a possible maximum total of 2 points), male patients were categorized as high risk (score 2), moderate risk (score 1), or low risk (score 0). In the low-risk group, anastomotic leakage was significantly less (p = 0.01), and the 3-year OS was significantly better (p < 0.01). On the other hand, in female patients, neither BMI nor PMI was a significant factor for postoperative outcomes. Conclusions: For male patients, the PNM score is a promising tool for predicting postoperative outcomes and identifying patients requiring preoperative nutritional intervention and rehabilitation.

62 RADIOLOGY AND NUCLEAR MEDICINE↗

The Accordion Sign in the Transplant Ureter: Ramifications During Balloon Dilation of Strictures

PurposeThis study was designed to demonstrate the accordion sign within the transplant ureter and evaluate its ramifications during balloon dilation of strictures.MethodsA retrospective electronic chart and imaging review included demographic characteristics, procedure reports, and complications of 28 renal transplant patients having ureteral strictures treated with percutaneous balloon dilation reported in our transplant nephrology database during an 8-year period. The accordion sign was deemed present or absent on the basis of an imaging review and was defined as present when a tortuous ureter became kinked and irregular when foreshortened after placement of a wire or a catheter. Procedure-related urine leaks were categorized as occurring at the stricture if within 2 cm; otherwise, they were considered away from the stricture.ResultsThe accordion sign was associated with a significantly greater occurrence of leaks away from the stricture (P = 0.001) but not at the stricture (P = 0.34).ConclusionsThe accordion sign is an important consideration when performing balloon dilation procedures on transplant ureteral strictures, given the increased risk of leak away from the stricture. Its presence should prompt additional care during wire and catheter manipulations.

62 RADIOLOGY AND NUCLEAR MEDICINE↗

Research to Develop Flood Barrier Testing Strategies for Nuclear Power Plants

The U.S. Nuclear Regulatory Commission has developed regulations regarding the siting and design of nuclear power plants (NPPs) that are aimed at addressing various natural hazards, including flooding. Flood barriers are designed to prevent water from entering NPP areas containing structures, systems, and components (SSCs) important to safety. The barriers are used at NPPs along with drains, sumps, pumps, valves, plugs, and site grading as part of the plant flood protection features that protect SSCs from experiencing external or internal flooding and mitigate the effects of flooding on NPP operations. The performance of flood protection features, including flood barriers at NPPs, has been an ongoing concern. Domestic and international operational experience provides clear indications that flood barrier performance has significant safety implications, especially for aging NPPs. The observed deficiencies show that flood barriers should be designed and installed properly, then adequately tested, inspected, and maintained in order to ensure that they perform their intended functions during flooding events. Here, this paper reviews available information related to flood barriers employed at U.S. NPPs and provides an overview and categorization of NPP flood barriers. It identifies potential domestic and international flood barrier testing facilities, including operating and decommissioned U.S. NPPs. Finally, this paper presents the technical and logistical considerations that should be made when developing specific testing strategies and protocols for flood barriers, such as the selection of flood barriers, test locations, testing approach, performance criteria, and testing parameters.

21 SPECIFIC NUCLEAR REACTORS AND ASSOCIATED PLANTS↗

Inferring Atmospheric Release Characteristics in a Large Computer Experiment using Bayesian Adaptive Splines

An atmospheric release of hazardous material, whether accidental or intentional, can be catastrophic for those in the path of the plume. Predicting the path of a plume based on characteristics of the release (location, amount and duration) and meteorological conditions is an active research area highly relevant for emergency and long-term response to these releases. As a result, researchers have developed particle dispersion simulators to provide plume path predictions that incorporate release characteristics and meteorological conditions. However, since release characteristics and meteorological conditions are often unknown, the inverse problem is of great interest, that is, based on all the observations of the plume so far, what can be inferred about the release characteristics? This is the question we seek to answer using plume observations from a controlled release at the Diablo Canyon Nuclear Power Plant in Central California. With access to a large number of evaluations of a computationally expensive particle dispersion simulator that includes continuous and categorical inputs and spatio-temporal output, building a fast statistical surrogate model (or emulator) presents many statistical challenges, but is an essential tool for inverse modeling and sensitivity analysis. We achieve accurate emulation using Bayesian adaptive splines to model weights on empirical orthogonal functions. Here, we use this emulator as well as appropriately identifiable simulator discrepancy and observational error models to calibrate the simulator, thus finding a posterior distribution of characteristics of the release. Since the release was controlled, these characteristics are known, making it possible to compare our findings to the truth.

54 ENVIRONMENTAL SCIENCES↗

Trigeminal Neuralgia Treated With Stereotactic Radiosurgery: The Effect of Dose Escalation on Pain Control and Treatment Outcomes

Purpose: To analyze the effect of dose escalation on treatment outcome in patients undergoing stereotactic radiosurgery (SRS) for trigeminal neuralgia (TN). Methods and Materials: A retrospective review was performed of 870 patients who underwent SRS for a diagnosis of TN from 2 institutions. Patients were typically treated using a single 4-mm isocenter placed at the trigeminal nerve dorsal root entry zone. Patients were divided into groups based on treatment doses: ≤82 Gy (352 patients), 83 to 86 Gy (85 patients), and ≥90 Gy (433 patients). Pain response was classified using a categorical scoring system, with fair or poor pain control representing treatment failure. Treatment-related facial numbness was classified using the Barrow Neurological Institute scale. Log-rank tests were performed to test differences in time to pain failure or development of facial numbness for patients treated with different doses. Results: Median age at first pain onset was 63 years, median age at time of SRS was 71 years, and median follow-up was 36.5 months from the time of SRS. A majority of patients (827, 95%) were clinically diagnosed with typical TN. The 4-year rate of excellent to good pain relief was 87% (95% confidence interval 84%-90%). The 4-year rate of pain response was 79%, 82%, and 92% in patients treated to ≤82 Gy, 83 to 86 Gy, and ≥90 Gy, respectively. Patients treated to doses ≤82 Gy had an increased risk of pain failure after SRS, compared with patients treated to ≥90 Gy (hazard ratio 2.0, P=.0007). Rates of treatment-related facial numbness were similar among patients treated to doses ≥83 Gy. Nine patients (1%) were diagnosed with anesthesia dolorosa. Conclusions: Dose escalation for TN to doses >82 Gy is associated with an improvement in response to treatment and duration of pain relief. Patients treated at these doses, however, should be counseled about the increased risk of treatment-related facial numbness.

62 RADIOLOGY AND NUCLEAR MEDICINE↗