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At least 217 records · Page 12

MO-FG-202-08: Real-Time Monte Carlo-Based Treatment Dose Reconstruction and Monitoring for Radiotherapy

Purpose: This proof-of-concept study is to develop a real-time Monte Carlo (MC) based treatment-dose reconstruction and monitoring system for radiotherapy, especially for the treatments with complicated delivery, to catch treatment delivery errors at the earliest possible opportunity and interrupt the treatment only when an unacceptable dosimetric deviation from our expectation occurs. Methods: First an offline scheme is launched to pre-calculate the expected dose from the treatment plan, used as ground truth for real-time monitoring later. Then an online scheme with three concurrent threads is launched while treatment delivering, to reconstruct and monitor the patient dose in a temporally resolved fashion in real-time. Thread T1 acquires machine status every 20 ms to calculate and accumulate fluence map (FM). Once our accumulation threshold is reached, T1 transfers the FM to T2 for dose reconstruction ad starts to accumulate a new FM. A GPU-based MC dose calculation is performed on T2 when MC dose engine is ready and a new FM is available. The reconstructed instantaneous dose is directed to T3 for dose accumulation and real-time visualization. Multiple dose metrics (e.g. maximum and mean dose for targets and organs) are calculated from the current accumulated dose and compared with the pre-calculated expected values. Once the discrepancies go beyond our tolerance, an error message will be send to interrupt the treatment delivery. Results: A VMAT Head-and-neck patient case was used to test the performance of our system. Real-time machine status acquisition was simulated here. The differences between the actual dose metrics and the expected ones were 0.06%–0.36%, indicating an accurate delivery. ∼10Hz frequency of dose reconstruction and monitoring was achieved, with 287.94s online computation time compared to 287.84s treatment delivery time. Conclusion: Our study has demonstrated the feasibility of computing a dose distribution in a temporally resolved fashion in real-time and quantitatively and dosimetrically monitoring the treatment delivery.

60 APPLIED LIFE SCIENCES↗

MO-FG-CAMPUS-TeP1-01: An Efficient Method of 3D Patient Dose Reconstruction Based On EPID Measurements for Pre-Treatment Patient Specific QA

Purpose: To demonstrate an efficient and clinically relevant patient specific QA method by reconstructing 3D patient dose from 2D EPID images for IMRT plans. Also to determine the usefulness of 2D QA metrics when assessing 3D patient dose deviations. Methods: Using the method developed by King et al (Med Phys 39(5),2839–2847), EPID images of IMRT fields were acquired in air and converted to dose at 10 cm depth (SAD setup) in a flat virtual water phantom. Each EPID measured dose map was then divided by the corresponding treatment planning system (TPS) dose map calculated with an identical setup, to derive a 2D “error matrix”. For each field, the error matrix was used to adjust the doses along the respective ray lines in the original patient 3D dose. All field doses were combined to derive a reconstructed 3D patient dose for quantitative analysis. A software tool was developed to efficiently implement the entire process and was tested with a variety of IMRT plans for 2D (virtual flat phantom) and 3D (in-patient) QA analysis. Results: The method was tested on 60 IMRT plans. The mean (± standard deviation) 2D gamma (2%,2mm) pass rate (2D-GPR) was 97.4±3.0% and the mean 2D gamma index (2D-GI) was 0.35±0.06. The 3D PTV mean dose deviation was 1.8±0.8%. The analysis showed very weak correlations between both the 2D-GPR and 2D-GI when compared with PTV mean dose deviations (R2=0.3561 and 0.3632 respectively). Conclusion: Our method efficiently calculates 3D patient dose from 2D EPID images, utilising all of the advantages of an EPID-based dosimetry system. In this study, the 2D QA metrics did not predict the 3D patient dose deviation. This tool allows reporting of the 3D volumetric dose parameters thus providing more clinically relevant patient specific QA.

60 APPLIED LIFE SCIENCES↗

TH-AB-207A-12: CT Lung Cancer Screening and the Effects of Further Dose Reduction On CAD Performance

Purpose: CT lung screening is already performed at low doses. In this study, we investigated the effects of further dose reduction on a lung-nodule CAD detection algorithm. Methods: The original raw CT data and images from 348 patients were obtained from our local database of National Lung Screening Trial (NLST) cases. 61 patients (17.5%) had at least one nodule reported on the NLST reader forms. All scans were acquired with fixed mAs (25 for standard-sized patients, 40 for large patients) on a 64-slice scanner (Sensation 64, Siemens Healthcare). All images were reconstructed with 1-mm slice thickness, B50 kernel. Based on a previously-published technique, we added noise to the raw data to simulate reduced-dose versions of each case at 50% and 25% of the original NLST dose (i.e. approximately 1.0 and 0.5 mGy CTDIvol). For each case at each dose level, a CAD detection algorithm was run and nodules greater than 4 mm in diameter were reported. These CAD results were compared to “truth”, defined as the approximate nodule centroids from the NLST forms. Sensitivities and false-positive rates (FPR) were calculated for each dose level, with a sub-analysis by nodule LungRADS category. Results: For larger category 4 nodules, median sensitivities were 100% at all three dose levels, and mean sensitivity decreased with dose. For the more challenging category 2 and 3 nodules, the dose dependence was less obvious. Overall, mean subject-level sensitivity varied from 38.5% at 100% dose to 40.4% at 50% dose, a difference of only 1.9%. However, median FPR quadrupled from 1 per case at 100% dose to 4 per case at 25% dose. Conclusions: Dose reduction affected nodule detectability differently depending on the LungRADS category, and FPR was very sensitive at sub-screening levels. Care should be taken to adapt CAD for the very challenging noise characteristics of screening. Funding support: NIH U01 CA181156; Disclosures (McNitt-Gray): Institutional research agreement, Siemens Healthcare; Past recipient, research grant support, Siemens Healthcare; Consultant, Toshiba America Medical Systems; Consultant, Samsung Electronics.

60 APPLIED LIFE SCIENCES↗

IDAC-Dose 2.1, an internal dosimetry program for diagnostic nuclear medicine based on the ICRP adult reference voxel phantoms

To date, the estimated radiation-absorbed dose to organs and tissues in patients undergoing diagnostic examinations in nuclear medicine is derived via calculations based on models of the human body and the biokinetic behaviour of the radiopharmaceutical. An internal dosimetry computer program, IDAC-Dose2.1, was developed based on the International Commission on Radiological Protection (ICRP)-specific absorbed fractions and computational framework of internal dose assessment given for reference adults in ICRP Publication 133. The program uses the radionuclide decay database of ICRP Publication 107 and considers 83 different source regions irradiating 47 target tissues, defining the effective dose as presented in ICRP Publications 60 and 103. The computer program was validated against another ICRP dosimetry program, Dose and Risk Calculation (DCAL), that employs the same computational framework in evaluation of occupational and environmental intakes of radionuclides. IDAC-Dose2.1 has a sub-module for absorbed dose calculations in spherical structures of different volumes and composition; this sub-module is intended for absorbed dose estimates in radiopharmaceutical therapy. For nine specific alpha emitters, the absorbed dose contribution from their decay products is also included in the committed absorbed dose calculations. The absorbed doses and effective dose of 131 I-iodide determined by IDAC-Dose2.1 were validated against the dosimetry program DCAL, showing identical results. IDAC-Dose2.1 was used to calculate absorbed doses for intravenously administered 18 F-FDG and orally administered 99m Tc-pertechnetate and 131 I-iodide, three frequently used radiopharmaceuticals. Using the tissue weighting factors from ICRP Publication 103, the effective dose per administered activity was estimated to be 0.016 mSv/MBq for 18 F-FDG, 0.014 mSv/MBq for 99m Tc-pertechnetate, and 16 mSv/MBq for 131 I-iodide. The internal dosimetry program IDAC-Dose2.1 was developed and applied to three radiopharmaceuticals for validation against DCAL and to generate improved absorbed dose estimations for diagnostic nuclear medicine using specific absorbed fraction values of the ICRP computational voxel phantoms. The sub-module for absorbed dose calculations in spherical structures 1 mm to 9 cm in diameter and different tissue composition was included to broaden the clinical usefulness of the program. The IDAC-Dose2.1 program is free software for research and available for download at http://www.idac-dose.org.

62 RADIOLOGY AND NUCLEAR MEDICINE↗

Connecting the Dots: Linking Environmental Justice Indicators to Daily Dose Model Estimates

Many different quantitative techniques have been developed to either assess Environmental Justice (EJ) issues or estimate exposure and dose for risk assessment. However, very few approaches have been applied to link EJ factors to exposure dose estimate and identify potential impacts of EJ factors on dose-related variables. The purpose of this study is to identify quantitative approaches that incorporate conventional risk assessment (RA) dose modeling and cumulative risk assessment (CRA) considerations of disproportionate environmental exposure. We apply the Average Daily Dose (ADD) model, which has been commonly used in RA, to better understand impacts of EJ indicators upon exposure dose estimates and dose-related variables, termed the Environmental-Justice-Average-Daily-Dose (EJ-ADD) approach. On the U.S. nationwide census tract-level, we defined and quantified two EJ indicators (poverty and race/ethnicity) using an EJ scoring method to examine their relation to census tract-level multi-chemical exposure dose estimates. Pollutant doses for each tract were calculated using the ADD model, and EJ scores were assigned to each tract based on poverty- or race-related population percentages. Single- and multiple-chemical ADD values were matched to the tract-level EJ scores to analyze disproportionate dose relationships and contributing EJ factors. We found that when both EJ indicators were examined simultaneously, ADD for all pollutants generally increased with larger EJ scores. To demonstrate the utility of using EJ-ADD on the local scale, we approximated ADD levels of lead via soil/dust ingestion for simulated communities with different EJ-related scenarios. The local-level simulation indicates a substantial difference in exposure-dose levels between wealthy and EJ communities. The application of the EJ-ADD approach can link EJ factors to exposure dose estimate and identify potential EJ impacts on dose-related variables.

54 ENVIRONMENTAL SCIENCES↗

Validation of Methodology to Simulate Gamma Doses from Historical Weapons Tests

The United States tested nuclear weapons in the atmosphere (aboveground) from 1945 until 1963, when the nation became a signatory to the Partial Test Ban Treaty. During those tests, gamma doses were often measured within kilometers of the point of detonation. Additional gamma dose measurements were made in and around the location of any personnel conducting the test, possibly with personal dosimeters. These gamma dose measurements have been declassified to provide the personnel involved with an estimate of the total dose they received while involved with the aboveground testing program. Several years ago, interest in these gamma doses was renewed by organizations that would need to provide the public with dose estimates in the event of a radiological or nuclear weapon terrorist attack on the United States. This work provides an initial validation of the computational methods used to simulate dose from a radiological or nuclear weapon. This initial work will focus on dose from gamma rays. The sources of gamma rays from a nuclear weapon include prompt fission gammas, gammas generated via neutron interactions (capture, inelastic scattering, and activation), and gammas produced by the decay of fission products. All of these gamma ray sources for a nuclear weapon are also potential sources of gammas from a radiological weapon. However, the sources of gamma rays from a radiological weapon depend on the material present in the device, and prompt fission gammas will mostly come from spontaneous fission instead of induced fission. This paper focuses on validation using gamma ray dose measurements from nuclear detonations, which is adequate to validate the requisite transport methodologies, source term generation, and cross sections needed to model gamma doses delivered by most radiological weapons. The 1961 report on Operation Plumbbob provides an overview of how the total gamma dose delivered by a nuclear weapon is broken down by the different sources specified above. The prompt fission gamma rays contribute about 5% of the total gamma dose. The gamma rays produced by neutron interactions usually deliver the largest portion of the total gamma dose, which is typically between 55% and 85% of the total. The remainder of the total gamma ray dose is attributed to decay of fission products.

61 RADIATION PROTECTION AND DOSIMETRY↗

A Systematic Assessment of US Food and Drug Administration Dosing Recommendations For Drug Development Programs Amenable to Response‐Guided Titration

A key goal in drug development is optimized dosing for patients. Interactions between drug developers and regulatory scientists throughout development are important for the optimization of dosing and serve as a forum to discuss approaches for optimal dosing, such as precision or individualized dosing. To date, there has not been a systematic assessment of the advice provided by the US Food and Drug Administration (FDA) to drug developers from an individualized dosing perspective. Here, we reviewed FDA recommendations on dose selection for efficacy trials at end‐of‐phase meetings between the FDA and drug developers for 76 new molecular entities approved between 2013 and 2017 that are considered amenable for an individualized dosing method, response‐guided titration. Forty FDA dosing recommendations were identified as specific to dose selection and design of the respective efficacy trials and subsequently: (i) characterized based on if they were supportive of individualized dosing and (ii) compared with dosing regimens used in efficacy trials and labeling at approval to evaluate if FDA recommendations were implemented. Of these 40 recommendations for efficacy trials, 35 (88%) were considered supportive of individualized dosing. Eighteen of these 40 recommendations (45%) were incorporated into efficacy trials and 11 (28%) were incorporated into labeling. This research suggests that early FDA‐sponsor interactions can support the study of doses in efficacy trials that may lead to individualized dosing strategies in labeling.

Wang, Lingshan↗

Comparison and calibration of dose delivered by 137 Cs and x-ray irradiators in mice

Objective. The Office of Radiological Security, U.S. Department of Energy's National Nuclear Security Administration, is implementing a radiological risk reduction program which seeks to minimize or eliminate the use of high activity radiological sources, including 137 Cs, by replacing them with non-radioisotopic technologies, such as x-ray irradiators. The main goal of this paper is to evaluate the equivalence of the dose delivered by gamma- and x-ray irradiators in mice using experimental measurements and Monte Carlo simulations. We also propose a novel biophantom as an in situ dose calibration method. Approach. We irradiated mouse carcasses and 3D-printed mouse biophantoms in a 137 Cs irradiator (Mark I-68) and an x-ray irradiator (X-Rad320) at three voltages (160 kVp, 225 kVp and 320 kVp) and measured the delivered radiation dose. A Geant4-based Monte Carlo model was developed and validated to provide a comprehensive picture of gamma- and x-ray irradiation in mice. Main Results. Our Monte Carlo model predicts a uniform dose delivered in soft-tissue for all the explored irradiation programs and in agreement with the absolute dose measurements. Our Monte Carlo model shows an energy-dependent difference between dose in bone and in soft tissue that decreases as photon energy increases. Dose rate depends on irradiator and photon energy. We observed a deviation of the measured dose from the target value of up to –9% for the Mark I-68, and up to 35% for the X-Rad320. The dose measured in the 3D-printed phantoms are equivalent to that in the carcasses within 6% uncertainty. Significance. Our results suggest that 320 kVp irradiation is a good candidate to substitute 137 Cs irradiation barring a few caveats. There is a significant difference between measured and targeted doses for x-ray irradiation that suggests a strong need for in situ calibration, which can be achieved with 3D-printed mouse biophantoms. A dose correction is necessary for bone doses, which can be provided by a Monte Carlo calculation. Lastly, the biological implications of the differences in dose rates and dose per photon for the different irradiation methods should be carefully assessed for each small-animal irradiation experiment.

62 RADIOLOGY AND NUCLEAR MEDICINE↗

Pediatric dosing for locally acting drugs in submissions to the U.S. Food and Drug Administration between 2002 and 2020

Abstract Deriving pediatric doses for locally acting drugs (LADs) presents a unique challenge because limited systemic exposure hinders commonly used approaches such as pharmacokinetic matching to adults. This study systematically evaluated drug development practices used for pediatric dose selection of LADs approved by the U.S. Food and Drug Administration from 2002 to 2020. The three study objectives were: (1) to determine the dose selection approach for the labeled pediatric dose, (2) to examine the studied pediatric dose(s), and (3) to evaluate the characteristics of the pediatric clinical programs used to support the labeled pediatric dose. A total of 187 pediatric submissions were characterized for the labeled and studied pediatric doses of LADs. The pediatric dose was predominantly labeled as a flat dose (91%) and at a single‐dose level (67%) similar to adults. The majority (68.4%) of the submissions had the same labeled dose for pediatrics and adults. Independent pharmacodynamic/efficacy studies in pediatric patients commonly (64.2%) provided supportive evidence for the labeled pediatric dose. Inhalation, nasal, and injectable submissions had the highest number of clinical trials, lowest usage of an extrapolation of efficacy approach, and utilized diverse approaches in selecting the studied pediatric doses. This article highlights approaches for LAD dosing in pediatric patients and can be used to inform drug development of these products in the pediatric population.

Research & Experimental Medicine↗

Improving Dose-Optimization Processes Used in Oncology Drug Development to Minimize Toxicity and Maximize Benefit to Patients

This review highlights strategies to integrate dose optimization into premarketing drug development and discusses the underlying statistical principles. Poor dose optimization can have negative consequences for patients, most commonly because of toxicity, including poor quality of life, reduced effectiveness because of inability of patients to stay on current therapy or receive subsequent therapy because of toxicities, and difficulty in developing combination regimens. We reviewed US Food and Drug Administration initial approvals (2019-2021) of small molecules and antibody-drug conjugates for oncologic indications to determine the proportion with a recommended dosage at the maximum tolerated dose or the maximal administered dose, to characterize the use of randomized evaluations of multiple dosages in dose selection, to describe the frequency of dose modifications at the recommended dosage, and to identify case examples that highlight key principles for premarket dose optimization during drug development. Herein, we highlight major principles for dose optimization and review examples of recent US Food and Drug Administration approvals that illustrate how investigation of dose- and exposure-response relationships and use of randomized dose trials can support dose optimization. Although there has been some progress, dose optimization through randomized dose evaluation in oncology trials is not routinely conducted. Dose optimization is essential to ensure that patients receive therapies which maximize efficacy while minimizing toxicity.

Oncology↗

Chromosomal Aberrations in DNA Repair Defective Cell Lines: Comparisons of Dose Rate and Radiation Quality

Chromosome aberration yields were assessed in DNA double-strand break repair (DSB) deficient cells after acute doses of gamma-rays or high-LET iron nuclei, or low dose-rate (0.018 Gy/hr) gamma-rays. We studied several cell lines including fibroblasts deficient in ATM (product of the gene that is mutated in ataxia telangiectasia patients) or NBS (product of the gene mutated in the Nijmegen breakage syndrome), and gliomablastoma cells that are proficient or lacking in DNA-dependent protein kinase, DNA-PK activity. Chromosomes were analyzed using the fluorescence in-situ hybridization (FISH) chromosome painting method in cells at the first division post-irradiation and chromosome aberrations were identified as either simple exchanges (translocations and dicentrics) or complex exchanges (involving >2 breaks in 2 or more chromosomes). Gamma radiation induced higher yields of both simple and complex exchanges in the DSB repair defective cells than in the normal cells. The quadratic dose-response terms for both chromosome exchange types were significantly higher for the ATM and NBS defective lines than for normal fibroblasts. However, the linear dose-response term was significantly higher only for simple exchanges in the NBS cells. Large increases in the quadratic dose response terms indicate the important roles of ATM and NBS in chromatin modifications that facilitate correct DSB repair and minimize aberration formation. Differences in the response of AT and NBS deficient cells at lower doses suggests important questions about the applicability of observations of radiation sensitivity at high dose to low dose exposures. For all iron nuclei irradiated cells, regression models preferred purely linear and quadratic dose responses for simple and complex exchanges, respectively. All the DNA repair defective cell lines had lower Relative biological effectiveness (RBE) values than normal cells, the lowest being for the DNA-PK-deficient cells, which was near unity. To further investigate the sensitivity differences for low and low high doses, we performed chronic low dose-rate irradiation, and have begun studies with ATM and Nibrin inhibitors and siRNA knockout of these proteins. Results support the conclusion that for the endpoint of simple chromosomal aberrations (translocation or dicentrics), the increased radiation sensitivity of AT cells found at high doses (>1 Gy) does not carry over to low doses or doserates, while NBS cells show increased sensitivity for both high and low dose exposures.

George, K. A.↗

Pencil Beam Algorithms Are Unsuitable for Proton Dose Calculations in Lung

Purpose: To compare analytic and Monte Carlo–based algorithms for proton dose calculations in the lung, benchmarked against anthropomorphic lung phantom measurements. Methods and Materials: A heterogeneous anthropomorphic moving lung phantom has been irradiated at numerous proton therapy centers. At 5 centers the treatment plan could be calculated with both an analytic and Monte Carlo algorithm. The doses calculated in the treatment plans were compared with the doses delivered to the phantoms, which were measured using thermoluminescent dosimeters and film. Point doses were compared, as were planar doses using a gamma analysis. Results: The analytic algorithms overestimated the dose to the center of the target by an average of 7.2%, whereas the Monte Carlo algorithms were within 1.6% of the physical measurements on average. In some regions of the target volume, the analytic algorithm calculations differed from the measurement by up to 31% in the internal gross target volume (iGTV) (46% in the planning target volume), over-predicting the dose. All comparisons showed a region of at least 15% dose discrepancy within the iGTV between the analytic calculation and the measured dose. The Monte Carlo algorithm recalculations showed dramatically improved agreement with the measured doses, showing mean agreement within 4% for all cases and a maximum difference of 12% within the iGTV. Conclusions: Analytic algorithms often do a poor job predicting proton dose in lung tumors, over-predicting the dose to the target by up to 46%, and should not be used unless extensive validation counters the consistent results of the present study. Monte Carlo algorithms showed dramatically improved agreement with physical measurements and should be implemented to better reflect actual delivered dose distributions.

62 RADIOLOGY AND NUCLEAR MEDICINE↗

Reconstructing Hanford worker external doses from photons for epidemiology

The accurate reconstruction of external photon doses is essential for credible radiation epidemiology. This article presents the methodology used to derive dose estimates for 37 012 Hanford Site workers included in the Million Person Study. The approach employs historical dose records from the Hanford Radiation Exposure database and a previous epidemiology study. Bias correction factors specific to dosimeter type and period of use were applied and missing annual doses were estimated using a hierarchical nearby method to estimate deep dose equivalent for each worker. For early years with limited detection sensitivity, missed doses were quantified based on expected time-period-specific, low-dose statistical distributions. The revised dose estimates resulted in lower median and mean career doses than unadjusted data, while increasing the number of person-years with nonzero dose. Sensitivity analyses assessed the influence of bias in dosimetry measurements, missed doses and gap years on dose estimates. Differences in cumulative dose estimates between unadjusted and revised annual estimates are most prominent in the early operational years due to the highest bias during that time period.

dose reconstruction↗

SU-D-BRC-03: Development and Validation of an Online 2D Dose Verification System for Daily Patient Plan Delivery Accuracy Check

Purpose: All plan verification systems for particle therapy are designed to do plan verification before treatment. However, the actual dose distributions during patient treatment are not known. This study develops an online 2D dose verification tool to check the daily dose delivery accuracy. Methods: A Siemens particle treatment system with a modulated scanning spot beam is used in our center. In order to do online dose verification, we made a program to reconstruct the delivered 2D dose distributions based on the daily treatment log files and depth dose distributions. In the log files we can get the focus size, position and particle number for each spot. A gamma analysis is used to compare the reconstructed dose distributions with the dose distributions from the TPS to assess the daily dose delivery accuracy. To verify the dose reconstruction algorithm, we compared the reconstructed dose distributions to dose distributions measured using PTW 729XDR ion chamber matrix for 13 real patient plans. Then we analyzed 100 treatment beams (58 carbon and 42 proton) for prostate, lung, ACC, NPC and chordoma patients. Results: For algorithm verification, the gamma passing rate was 97.95% for the 3%/3mm and 92.36% for the 2%/2mm criteria. For patient treatment analysis,the results were 97.7%±1.1% and 91.7%±2.5% for carbon and 89.9%±4.8% and 79.7%±7.7% for proton using 3%/3mm and 2%/2mm criteria, respectively. The reason for the lower passing rate for the proton beam is that the focus size deviations were larger than for the carbon beam. The average focus size deviations were −14.27% and −6.73% for proton and −5.26% and −0.93% for carbon in the x and y direction respectively. Conclusion: The verification software meets our requirements to check for daily dose delivery discrepancies. Such tools can enhance the current treatment plan and delivery verification processes and improve safety of clinical treatments.

60 APPLIED LIFE SCIENCES↗

SU-G-IeP3-13: Real-Time Patient and Staff Dose Monitoring in Fluoroscopy Guided Interventions

Purpose: Interventional radiology procedures involve the use of X-rays, which can pose a large radiation burden on both patients and staff. Although some reports on radiation dose are available, most studies focus on limited types of procedures and only report patient dose. In our cathlabs a dedicated real-time patient and staff monitoring system was installed in November 2015. The aim of this study was to investigate the patient and staff dose exposure for different types of interventions. Methods: Radiologists involved in fluoroscopy guided interventional radiology procedures wore personal dose meters (PDM, DoseAware, Philips) on their lead-apron that measured the personal dose equivalent Hp(10), a measure for the effective dose (E). Furthermore, reference PDMs were installed in the C-arms of the fluoroscopy system (Allura XPer, Philips). Patient dose-area-product (DAP) and PDM doses were retrieved from the monitoring system (DoseWise, Philips) for each procedure. A total of 399 procedures performed between November 2015 and February 2016 were analyzed with respect to the type of intervention. Interventions were grouped by anatomy and radiologist position. Results: The mean DAP for the different types of interventions ranged from 2.86±2.96 Gycm{sup 2} (percutaneous gastrostomy) to 147±178 Gycm{sup 2} (aortic repair procedures). The radiologist dose (E) ranged from 5.39±7.38 µSv (cerebral interventions) to 84.7±106 µSv (abdominal interventions) and strongly correlated with DAP (R{sup 2}=0.83). The E normalized to DAP showed that the relative radiologist dose was higher for interventions in larger body parts (e.g. abdomen) compared to smaller body parts (e.g. head). Conclusion: Using a real-time dose monitoring system we were able to assess the staff and patient dose revealing that the relative staff dose strongly depended on the type of procedure and patient anatomy. This could be explained by the position of the radiologist with respect to the patient and X-ray tube. To facilitate this study L Vergoossen received a scholarship from Philips Medical Systems.

60 APPLIED LIFE SCIENCES↗

Influence of neutron cross-section resonances on organ/tissue equivalent and effective dose coefficients for the ICRP voxel phantoms

The materials which compose the ICRP Voxel phantoms used in the computation of conversion coefficients involve neutron interaction cross-sections that have resonances at specific energies. Depending on the energy bin structure used in the computations, these cross-section resonances may occur at energies that fall between energies at which dose coefficients are computed, thus their effects may not be completely accounted for in the reported coefficients. Here In this study, a highly refined energy grid that closely follows the resonance structure in the phantom material cross-sections was identified and used to calculate dose coefficients. Both the equivalent organ/tissue doses for male and female voxel phantoms were computed as well as their summation to obtain the effective dose coefficients. The used refined energy grid tracks very closely the cross-sections in the vicinity of the resonances. The resulting refined energy grid coefficients are compared to coefficients for the coarser energy grid used in ICRP Publication 116. Additionally, reference spectra have been folded with both the fine and coarse sets of conversion coefficients. The resulting total effective doses for these reference spectra are used to assess the adequacy of the dose coefficients calculated on the original ICRP 116 energy grid. The dose coefficients were similarly computed for the local skin dose on the trunk of the body using the ICRU Report 95 phantom. The overall impact of the resonances on the organ/tissue equivalent dose, the effective dose, and the local skin dose are presented and discussed. In general, it was found that resonances can impact neutron dose coefficients, but in most cases the wide range of neutron energies encountered minimized this effect. The impact of resonances was further limited when computing effective dose due to organ/tissue summing and sex-averaging. For the neutron fields studied here, the impact was below 5%.

36 MATERIALS SCIENCE↗

Stereotactic Body Radiation Therapy Boost After Concurrent Chemoradiation for Locally Advanced Non-Small Cell Lung Cancer: A Phase 1 Dose Escalation Study

Purpose: Stereotactic body radiation therapy (SBRT) boost to primary and nodal disease after chemoradiation has potential to improve outcomes for advanced non-small cell lung cancer (NSCLC). A dose escalation study was initiated to evaluate the maximum tolerated dose (MTD). Methods and Materials: Eligible patients received chemoradiation to a dose of 50.4 Gy in 28 fractions and had primary and nodal volumes appropriate for SBRT boost (<120 cc and <60 cc, respectively). SBRT was delivered in 2 fractions after chemoradiation. Dose was escalated from 16 to 28 Gy in 2 Gy/fraction increments, resulting in 4 dose cohorts. MTD was defined when ≥2 of 6 patients per cohort experienced any treatment-related grade 3 to 5 toxicity within 4 weeks of treatment or the maximum dose was reached. Late toxicity, disease control, and survival were also evaluated. Results: Twelve patients (3 per dose level) underwent treatment. All treatment plans met predetermined dose-volume constraints. The mean age was 64 years. Most patients had stage III disease (92%) and were medically inoperable (92%). The maximum dose level was reached with no grade 3 to 5 acute toxicities. At a median follow-up time of 16 months, 1-year local-regional control (LRC) was 78%. LRC was 50% at <24 Gy and 100% at ≥24 Gy (P=.02). Overall survival at 1 year was 67%. Late toxicity (grade 3-5) was seen in only 1 patient who experienced fatal bronchopulmonary hemorrhage (grade 5). There were no predetermined dose constraints for the proximal bronchial-vascular tree (PBV) in this study. This patient's 4-cc PBV dose was substantially higher than that received by other patients in all 4 cohorts and was associated with the toxicity observed: 20.3 Gy (P<.05) and 73.5 Gy (P=.07) for SBRT boost and total treatment, respectively. Conclusions: SBRT boost to both primary and nodal disease after chemoradiation is feasible and well tolerated. Local control rates are encouraging, especially at doses ≥24 Gy in 2 fractions. Toxicity at the PBV is a concern but potentially can be avoided with strict dose-volume constraints.

62 RADIOLOGY AND NUCLEAR MEDICINE↗

MPS dose reconstruction for internal emitters: some site-specific issues and approaches

Background: As part of the Million Person Study (MPS), dose reconstructions for internal emitters have been performed for several U.S. facilities where large quantities of radionuclides were handled. The main challenges and dominant sources of potential error in retrospective dose estimates for internally exposed workers have been found to vary from site to site. Here in this paper, we discuss some important issues encountered in dose reconstructions performed for selected MPS sites and the approaches used to address those issues. The focus is on some foundational components of retrospective dose assessments that have received little attention in the literature. Methods: The discussion is built around illustrative exposure data and dose reconstructions for workers at selected facilities addressed in the MPS. Related findings at some non-MPS sites are also discussed. Results: Each of the following items has been found to be a major source of potential error in reconstructed tissue doses for some MPS sites: identification of all dosimetrically important internal emitters; the time pattern of intake; the mode(s) of intake; reliability of bioassay measurements; application of surrogate (coworker) information in lieu of, or in conjunction with, worker-specific monitoring data; the chemical and physical forms of inhaled radionuclide; and the relation of air monitoring data to actual intake. Conclusions: (1) Much of the dose reconstruction effort for internal emitters should be devoted to development of best feasible exposure scenarios. (2) Coworker data should be used to assign exposure scenarios or dose estimates to workers with missing exposure data only if there is compelling evidence of similar coworker exposure. (3) Bioassay data for some radionuclides and periods of operation at MPS sites are of questionable reliability due to sizable uncertainties associated with contamination, recovery, or background issues. (4) Dose estimates derived solely from air monitoring data should be treated as highly uncertain values in the absence of site-specific information demonstrating that the data are reasonably predictive of intake. (5) For intakes known or assumed to be via inhalation, the uncertainty in lung dose typically is much greater than the uncertainty in dose to systemic tissues, when dose estimates are based on urinary excretion data. (6) The lung dose estimate often can be improved through development of site-specific respiratory absorption parameter values. (7) There is generally insufficient site-specific information to justify development of site-specific systemic models.

61 RADIATION PROTECTION AND DOSIMETRY↗