Results for “DOSES” — Page 60

DOE OSTI2016

TH-CD-202-08: Feasibility Study of Planning Phase Optimization Using Patient Geometry-Driven Information for Better Dose Sparing of Organ at Risks

Purpose: To propose a simple and effective cost value function to search optimal planning phase (gating window) and demonstrated its feasibility for respiratory correlated radiation therapy. Methods: We acquired 4DCT of 10 phases for 10 lung patients who have tumor located near OARs such as esophagus, heart, and spinal cord (i.e., central lung cancer patients). A simplified mathematical optimization function was established by using overlap volume histogram (OVH) between the target and organ at risk (OAR) at each phase and the tolerance dose of selected OARs to achieve surrounding OARs dose-sparing. For all patients and all phases, delineation of the target volume and selected OARs (esophagus, heart, and spinal cord) was performed (by one observer to avoid inter-observer variation), then cost values were calculated for all phases. After the breathing phases were ranked according to cost value function, the relationship between score and dose distribution at highest and lowest cost value phases were evaluated by comparing the mean/max dose. Results: A simplified mathematical cost value function showed noticeable difference from phase to phase, implying it is possible to find optimal phases for gating window. The lowest cost value which may result in lower mean/max dose to OARs was distributed at various phases for all patients. The mean doses of the OARs significantly decreased about 10% with statistical significance for all 3 OARs at the phase with the lowest cost value. Also, the max doses of the OARs were decreased about 2∼5% at the phase with the lowest cost value compared to the phase with the highest cost value. Conclusion: It is demonstrated that optimal phases (in dose distribution perspective) for gating window could exist differently through each patient and the proposed cost value function can be a useful tool for determining such phases without performing dose optimization calculations. This research was supported by the Mid-career Researcher Program through NRF funded by the Ministry of Science, ICT & Future Planning of Korea (NRF-2014R1A2A1A10050270) and by the Radiation Technology R&D program through the National Research Foundation of Korea funded by the Ministry of Science, ICT & Future Planning (No. 2013M2A2A7038291)

60 APPLIED LIFE SCIENCES↗

DOE OSTI2016

TH-E-209-00: Radiation Dose Monitoring and Protocol Management

Radiation dose monitoring solutions have opened up new opportunities for medical physicists to be more involved in modern clinical radiology practices. In particular, with the help of comprehensive radiation dose data, data-driven protocol management and informed case follow up are now feasible. Significant challenges remain however and the problems faced by medical physicists are highly heterogeneous. Imaging systems from multiple vendors and a wide range of vintages co-exist in the same department and employ data communication protocols that are not fully standardized or implemented making harmonization complex. Many different solutions for radiation dose monitoring have been implemented by imaging facilities over the past few years. Such systems are based on commercial software, home-grown IT solutions, manual PACS data dumping, etc., and diverse pathways can be used to bring the data to impact clinical practice. The speakers will share their experiences with creating or tailoring radiation dose monitoring/management systems and procedures over the past few years, which vary significantly in design and scope. Topics to cover: (1) fluoroscopic dose monitoring and high radiation event handling from a large academic hospital; (2) dose monitoring and protocol optimization in pediatric radiology; and (3) development of a home-grown IT solution and dose data analysis framework. Learning Objectives: Describe the scope and range of radiation dose monitoring and protocol management in a modern radiology practice Review examples of data available from a variety of systems and how it managed and conveyed. Reflect on the role of the physicist in radiation dose awareness.

60 APPLIED LIFE SCIENCES↗

DOE OSTI2016

TH-E-209-01: Fluoroscopic Dose Monitoring and Patient Follow-Up Program at Massachusetts General Hospital

Radiation dose monitoring solutions have opened up new opportunities for medical physicists to be more involved in modern clinical radiology practices. In particular, with the help of comprehensive radiation dose data, data-driven protocol management and informed case follow up are now feasible. Significant challenges remain however and the problems faced by medical physicists are highly heterogeneous. Imaging systems from multiple vendors and a wide range of vintages co-exist in the same department and employ data communication protocols that are not fully standardized or implemented making harmonization complex. Many different solutions for radiation dose monitoring have been implemented by imaging facilities over the past few years. Such systems are based on commercial software, home-grown IT solutions, manual PACS data dumping, etc., and diverse pathways can be used to bring the data to impact clinical practice. The speakers will share their experiences with creating or tailoring radiation dose monitoring/management systems and procedures over the past few years, which vary significantly in design and scope. Topics to cover: (1) fluoroscopic dose monitoring and high radiation event handling from a large academic hospital; (2) dose monitoring and protocol optimization in pediatric radiology; and (3) development of a home-grown IT solution and dose data analysis framework. Learning Objectives: Describe the scope and range of radiation dose monitoring and protocol management in a modern radiology practice Review examples of data available from a variety of systems and how it managed and conveyed. Reflect on the role of the physicist in radiation dose awareness.

60 APPLIED LIFE SCIENCES↗

DOE OSTI2016

TH-E-209-02: Dose Monitoring and Protocol Optimization: The Pediatric Perspective

Radiation dose monitoring solutions have opened up new opportunities for medical physicists to be more involved in modern clinical radiology practices. In particular, with the help of comprehensive radiation dose data, data-driven protocol management and informed case follow up are now feasible. Significant challenges remain however and the problems faced by medical physicists are highly heterogeneous. Imaging systems from multiple vendors and a wide range of vintages co-exist in the same department and employ data communication protocols that are not fully standardized or implemented making harmonization complex. Many different solutions for radiation dose monitoring have been implemented by imaging facilities over the past few years. Such systems are based on commercial software, home-grown IT solutions, manual PACS data dumping, etc., and diverse pathways can be used to bring the data to impact clinical practice. The speakers will share their experiences with creating or tailoring radiation dose monitoring/management systems and procedures over the past few years, which vary significantly in design and scope. Topics to cover: (1) fluoroscopic dose monitoring and high radiation event handling from a large academic hospital; (2) dose monitoring and protocol optimization in pediatric radiology; and (3) development of a home-grown IT solution and dose data analysis framework. Learning Objectives: Describe the scope and range of radiation dose monitoring and protocol management in a modern radiology practice Review examples of data available from a variety of systems and how it managed and conveyed. Reflect on the role of the physicist in radiation dose awareness.

60 APPLIED LIFE SCIENCES↗

DOE OSTI2016

TH-E-209-03: Development of An In-House CT Dose Monitoring and Management System Based On Open-Source Software Resources -- Pearls and Pitfalls

Radiation dose monitoring solutions have opened up new opportunities for medical physicists to be more involved in modern clinical radiology practices. In particular, with the help of comprehensive radiation dose data, data-driven protocol management and informed case follow up are now feasible. Significant challenges remain however and the problems faced by medical physicists are highly heterogeneous. Imaging systems from multiple vendors and a wide range of vintages co-exist in the same department and employ data communication protocols that are not fully standardized or implemented making harmonization complex. Many different solutions for radiation dose monitoring have been implemented by imaging facilities over the past few years. Such systems are based on commercial software, home-grown IT solutions, manual PACS data dumping, etc., and diverse pathways can be used to bring the data to impact clinical practice. The speakers will share their experiences with creating or tailoring radiation dose monitoring/management systems and procedures over the past few years, which vary significantly in design and scope. Topics to cover: (1) fluoroscopic dose monitoring and high radiation event handling from a large academic hospital; (2) dose monitoring and protocol optimization in pediatric radiology; and (3) development of a home-grown IT solution and dose data analysis framework. Learning Objectives: Describe the scope and range of radiation dose monitoring and protocol management in a modern radiology practice Review examples of data available from a variety of systems and how it managed and conveyed. Reflect on the role of the physicist in radiation dose awareness.

60 APPLIED LIFE SCIENCES↗

DOE OSTI2016

Approaches to reducing photon dose calculation errors near metal implants

Purpose: Dose calculation errors near metal implants are caused by limitations of the dose calculation algorithm in modeling tissue/metal interface effects as well as density assignment errors caused by imaging artifacts. The purpose of this study was to investigate two strategies for reducing dose calculation errors near metal implants: implementation of metal-based energy deposition kernels in the convolution/superposition (C/S) dose calculation method and use of metal artifact reduction methods for computed tomography (CT) imaging. Methods: Both error reduction strategies were investigated using a simple geometric slab phantom with a rectangular metal insert (composed of titanium or Cerrobend), as well as two anthropomorphic phantoms (one with spinal hardware and one with dental fillings), designed to mimic relevant clinical scenarios. To assess the dosimetric impact of metal kernels, the authors implemented titanium and silver kernels in a commercial collapsed cone C/S algorithm. To assess the impact of CT metal artifact reduction methods, the authors performed dose calculations using baseline imaging techniques (uncorrected 120 kVp imaging) and three commercial metal artifact reduction methods: Philips Healthcare’s O-MAR, GE Healthcare’s monochromatic gemstone spectral imaging (GSI) using dual-energy CT, and GSI with metal artifact reduction software (MARS) applied. For the simple geometric phantom, radiochromic film was used to measure dose upstream and downstream of metal inserts. For the anthropomorphic phantoms, ion chambers and radiochromic film were used to quantify the benefit of the error reduction strategies. Results: Metal kernels did not universally improve accuracy but rather resulted in better accuracy upstream of metal implants and decreased accuracy directly downstream. For the clinical cases (spinal hardware and dental fillings), metal kernels had very little impact on the dose calculation accuracy (<1.0%). Of the commercial CT artifact reduction methods investigated, the authors found that O-MAR was the most consistent method, resulting in either improved dose calculation accuracy (dental case) or little impact on calculation accuracy (spine case). GSI was unsuccessful at reducing the severe artifacts caused by dental fillings and had very little impact on calculation accuracy. GSI with MARS on the other hand gave mixed results, sometimes introducing metal distortion and increasing calculation errors (titanium rectangular implant and titanium spinal hardware) but other times very successfully reducing artifacts (Cerrobend rectangular implant and dental fillings). Conclusions: Though successful at improving dose calculation accuracy upstream of metal implants, metal kernels were not found to substantially improve accuracy for clinical cases. Of the commercial artifact reduction methods investigated, O-MAR was found to be the most consistent candidate for all-purpose CT simulation imaging. The MARS algorithm for GSI should be used with caution for titanium implants, larger implants, and implants located near heterogeneities as it can distort the size and shape of implants and increase calculation errors.

60 APPLIED LIFE SCIENCES↗

DOE OSTI2016

Low dose radiation risks for women surviving the a-bombs in Japan: generalized additive model

Background: Analyses of cancer mortality and incidence in Japanese A-bomb survivors have been used to estimate radiation risks, which are generally higher for women. Relative Risk (RR) is usually modelled as a linear function of dose. Extrapolation from data including high doses predicts small risks at low doses. Generalized Additive Models (GAMs) are flexible methods for modelling non-linear behaviour. Methods: GAMs are applied to cancer incidence in female low dose subcohorts, using anonymous public data for the 1958 – 1998 Life Span Study, to test for linearity, explore interactions, adjust for the skewed dose distribution, examine significance below 100 mGy, and estimate risks at 10 mGy. Results: For all solid cancer incidence, RR estimated from 0 – 100 mGy and 0 – 20 mGy subcohorts is significantly raised. The response tapers above 150 mGy. At low doses, RR increases with age-at-exposure and decreases with time-since-exposure, the preferred covariate. Using the empirical cumulative distribution of dose improves model fit, and capacity to detect non-linear responses. RR is elevated over wide ranges of covariate values. Results are stable under simulation, or when removing exceptional data cells, or adjusting neutron RBE. Estimates of Excess RR at 10 mGy using the cumulative dose distribution are 10 – 45 times higher than extrapolations from a linear model fitted to the full cohort. Below 100 mGy, quasipoisson models find significant effects for all solid, squamous, uterus, corpus, and thyroid cancers, and for respiratory cancers when age-at-exposure > 35 yrs. Results for the thyroid are compatible with studies of children treated for tinea capitis, and Chernobyl survivors. Results for the uterus are compatible with studies of UK nuclear workers and the Techa River cohort. Conclusion: Non-linear models find large, significant cancer risks for Japanese women exposed to low dose radiation from the atomic bombings. The risks should be reflected in protection standards.

60 APPLIED LIFE SCIENCES↗

DOE OSTI2014

Low Dose Radiation-Induced Epigenetic Changes in an Animal Model (Final Report)

This project sought mechanistic understanding of the epigenetic response of tissues as well as the consequences of those responses, when induced by low dose irradiation in a well-established model system (mouse). Based on solid and extensive preliminary data we investigated the molecular epigenetic mechanisms of in vivo radiation responses, particularly – effects of low, occupationally relevant radiation exposures on the genome stability and adaptive response in mammalian tissues and organisms. We accumulated evidence that low dose irradiation altered epigenetic profiles and impacted radiation target organs of the exposed animals. The main long-term goal was to dissect the epigenetic basis of induction of the low dose radiation-induced genome instability and adaptive response and the specific fundamental roles of epigenetic changes (i.e. DNA methylation, histone modifications and miRNAs) in their generation. We hypothesized that changes in global and regional DNA methylation, global histone modifications and regulatory microRNAs played pivotal roles in the generation and maintenance low-dose radiation-induced genome instability and adaptive response. We predicted that epigenetic changes influenced the levels of genetic rearrangements (transposone reactivation). We hypothesized that epigenetic responses from low dose irradiation were dependent on exposure regimes, and would be greatest when organisms are exposed in a protracted/fractionated manner: fractionated exposures > acute exposures. We anticipated that the epigenetic responses were correlated with the gene expression levels. Our immediate objectives were: • To investigate the exact nature of the global and locus-specific DNA methylation changes in the LDR exposed cells and tissues and dissect their roles in adaptive response • To investigate the roles of histone modifications in the low dose radiation effects and adaptive response • To dissect the roles of regulatory microRNAs and their targets in low dose radiation effects and adaptive response • To correlate the levels of epigenetic changes with genetic rearrangement levels and gene expression patterns. In sum, we determined the precise global and locus-specific DNA methylation patterns in the LDR-exposed cells and tissues of mice, and to correlated DNA methylation changes with the gene expression patterns and manifestations of genome instability. We also determined the alterations of global histone modification pattern in the LDR exposed tissues. Additionally, we established the nature of microRNAome changes in the LDR exposed tissue. In this study we for the first time found that LDR exposure caused profound tissue-specific epigenetic changes in the exposed tissues. We established that LDR exposure affect methylation of repetitive elements in the murine genome, causes changes in histone methylation, acetylation and phosphorylation. Importantly, we found that LDR causes profound and persistent effects on small RNA profiles and gene expression, and that miRNAs are excellent biomarkers of LDR exposure. Furthermore, we extended our analysis and studied LDR effects in rat tissues and human tissues and cell lines. There we also analyzed LDR-induced gene expression, DNA methylation and miRNA changes. Our datasets laid foundation for several new research projects aimed to understand molecular underpinnings of low dose radiation responses, and biological repercussions of low dose radiation effects and radiation carcinogenesis.

59 BASIC BIOLOGICAL SCIENCES↗

DOE OSTI2014

Estimates of Internal Dose Resulting from I-131 Patients in Hotels - Paper 147

U.S. Nuclear Regulatory Commission Regulatory Guide 8.39 provides the following estimate to the maximum internal committed effective dose, CED{sub i}, to an individual from a released patient having received radionuclide therapy: CED{sub i} = 10{sup -5} Q{sub adm} DCF where Q{sub adm} = activity administered to the patient (Bq), DCF = ingestion dose coefficient (Sv/Bq). Since many released patients stay in a hotel for a day or two after administration of the I-131, an effort was made to provide reasonable estimates of internal committed effective dose to a housekeeper at a hotel. Reasonable exposure scenarios are presented herein with the resulting doses. The value 10{sup -6} from a health physics 'rule of thumb' for intake in workplace environments, and explored by Brodsky, was multiplied by a factor of 10 to account for the most highly exposed individual and to add a degree of conservatism to the evaluation. The ingestion dose coefficient was used since it was felt that the maximum internal intake would either be via the skin or mouth. The scenarios investigated to date and presented herein show rather low potential doses of hotel housekeepers due to internal contamination. The internal doses are conservative since they assume the immediate release and placement of the patient in the hotel or household. The existing Reg. Guide 8.39 internal dose estimate appears to be very conservative and are very low in comparison to external gamma ray dose due to released patients. (authors)

61 RADIATION PROTECTION AND DOSIMETRY↗

DOE OSTI2011

Health-Related Quality of Life After Single-Fraction High-Dose-Rate Brachytherapy and Hypofractionated External Beam Radiotherapy for Prostate Cancer

Purpose: To investigate the change in health-related quality of life for men after high-dose-rate brachytherapy and external beam radiotherapy for prostate cancer and the factors associated with this change. Methods and Materials: Eligible patients had clinically localized intermediate-risk prostate cancer. The patients received high-dose-rate brachytherapy as a single 15-Gy implant, followed by external beam radiotherapy to 37.5 Gy in 15 fractions. The patients were monitored prospectively for toxicity (Common Terminology Criteria for Adverse Events, version 3.0) and health-related quality of life (Expanded Prostate Cancer Index Composite [EPIC]). The proportion of patients developing a clinically significant difference in the EPIC domain score (minimally important difference of >0.5 standard deviation) was determined and correlated with the baseline clinical and dosimetric factors. The study accrued 125 patients, with a median follow-up of 24 months. Results: By 24 months, 23% had Grade 2 urinary toxicity and only 5% had Grade 2 bowel toxicity, with no Grade 3 toxicity. The proportion of patients reporting a significant decrease in EPIC urinary, bowel, sexual, and hormonal domain scores was 53%, 51%, 45%, and 40% at 12 months and 57%, 65%, 51%, and 30% at 24 months, respectively. The proportion with a >1 standard deviation decrease in the EPIC urinary, bowel, sexual, and hormonal domain scores was 38%, 36%, 24%, and 20% at 12 months and 46%, 48%, 19%, and 8% at 24 months, respectively. On multivariate analysis, the dose to 10% of the urethra was associated with a decreasing EPIC urinary domain score (p = .0089) and, less strongly (p = .0312) with a decreasing hormonal domain score. No association was found between the prostate volume, bladder dose, or high-dose volume and urinary health-related quality of life. A high baseline International Index of Erectile Function score was associated (p = .0019) with a decreasing sexual domain score. The optimal maximal dose to 10% of the urethra cutpoint for urinary health-related quality of life was 120% of the prescription dose. Conclusion: EPIC was a more sensitive tool for detecting the effects on function and bother than were the generic toxicity scales. The urethral dose had the strongest association with a deteriorating urinary quality of life.

62 RADIOLOGY AND NUCLEAR MEDICINE↗

DOE OSTI2012

Dose Effect Relationship for Late Side Effects of the Rectum and Urinary Bladder in Magnetic Resonance Image-Guided Adaptive Cervix Cancer Brachytherapy

Purpose: To establish dose-response relationships for late side effects of the rectum and bladder in cervix cancer patients after magnetic resonance image-guided adaptive brachytherapy (IGABT). Methods and Materials: A cohort of 141 patients was treated with 45 to 50.4 Gy with or without cisplatin plus 4 fractions of 7 Gy IGABT. Doses for the most exposed 2, 1, and 0.1-cm{sup 3} (D{sub 2cc}, D{sub 1cc}, D{sub 0.1cc}) volumes of the rectum and bladder were converted into the equivalent dose in 2 Gy fractions (EQD2), using a linear quadratic model ({alpha}/{beta} = 3 Gy). Late side effects were prospectively assessed (using late effects in normal tissues subjective, objective, management and analytic [LENT SOMA]) scales. Dose-response relationships were determined by logit analyses. Results: Eleven patients developed rectal side effects, and 23 patients had urinary side effects. A significant dose effect was found for all rectal dose-volume histogram (DVH) parameters for patients with side effect grades of 1 to 4 but was only significant for D{sub 2cc} and D{sub 1cc} for grades {>=}2. The ED10 values for D{sub 2cc} were 73 Gy for grades 1 to 4 and 78 Gy for grades 2 to 4 rectal morbidity. For bladder side effects, a significant dose effect was shown for all DVH parameters for complication grades {>=}2; the respective ED10 was 101 Gy. Conclusions: Well-defined dose-response curves could be established for D{sub 2cc} in the rectum and the urinary bladder.

62 RADIOLOGY AND NUCLEAR MEDICINE↗

DOE OSTI2014

Quantifying the Combined Effect of Radiation Therapy and Hyperthermia in Terms of Equivalent Dose Distributions

Purpose: To develop a method to quantify the therapeutic effect of radiosensitization by hyperthermia; to this end, a numerical method was proposed to convert radiation therapy dose distributions with hyperthermia to equivalent dose distributions without hyperthermia. Methods and Materials: Clinical intensity modulated radiation therapy plans were created for 15 prostate cancer cases. To simulate a clinically relevant heterogeneous temperature distribution, hyperthermia treatment planning was performed for heating with the AMC-8 system. The temperature-dependent parameters α (Gy{sup −1}) and β (Gy{sup −2}) of the linear–quadratic model for prostate cancer were estimated from the literature. No thermal enhancement was assumed for normal tissue. The intensity modulated radiation therapy plans and temperature distributions were exported to our in-house-developed radiation therapy treatment planning system, APlan, and equivalent dose distributions without hyperthermia were calculated voxel by voxel using the linear–quadratic model. Results: The planned average tumor temperatures T90, T50, and T10 in the planning target volume were 40.5°C, 41.6°C, and 42.4°C, respectively. The planned minimum, mean, and maximum radiation therapy doses were 62.9 Gy, 76.0 Gy, and 81.0 Gy, respectively. Adding hyperthermia yielded an equivalent dose distribution with an extended 95% isodose level. The equivalent minimum, mean, and maximum doses reflecting the radiosensitization by hyperthermia were 70.3 Gy, 86.3 Gy, and 93.6 Gy, respectively, for a linear increase of α with temperature. This can be considered similar to a dose escalation with a substantial increase in tumor control probability for high-risk prostate carcinoma. Conclusion: A model to quantify the effect of combined radiation therapy and hyperthermia in terms of equivalent dose distributions was presented. This model is particularly instructive to estimate the potential effects of interaction from different treatment modalities.

62 RADIOLOGY AND NUCLEAR MEDICINE↗

DOE OSTI2015

Study of dose calculation on breast brachytherapy using prism TPS

PRISM is one of non-commercial Treatment Planning System (TPS) and is developed at the University of Washington. In Indonesia, many cancer hospitals use expensive commercial TPS. This study aims to investigate Prism TPS which been applied to the dose distribution of brachytherapy by taking into account the effect of source position and inhomogeneities. The results will be applicable for clinical Treatment Planning System. Dose calculation has been implemented for water phantom and CT scan images of breast cancer using point source and line source. This study used point source and line source and divided into two cases. On the first case, Ir-192 seed source is located at the center of treatment volume. On the second case, the source position is gradually changed. The dose calculation of every case performed on a homogeneous and inhomogeneous phantom with dimension 20 × 20 × 20 cm{sup 3}. The inhomogeneous phantom has inhomogeneities volume 2 × 2 × 2 cm{sup 3}. The results of dose calculations using PRISM TPS were compared to literature data. From the calculation of PRISM TPS, dose rates show good agreement with Plato TPS and other study as published by Ramdhani. No deviations greater than ±4% for all case. Dose calculation in inhomogeneous and homogenous cases show similar result. This results indicate that Prism TPS is good in dose calculation of brachytherapy but not sensitive for inhomogeneities. Thus, the dose calculation parameters developed in this study were found to be applicable for clinical treatment planning of brachytherapy.

62 RADIOLOGY AND NUCLEAR MEDICINE↗

DOE OSTI2012

Determining the effects of microsphere and surrounding material composition on {sup 90}Y dose kernels using egsnrc and mcnp5

Purpose: Recent advances in the imaging of {sup 90}Y using positron emission tomography (PET) and improved uncertainty in the branching ratio for the internal pair production component of {sup 90}Y decay allow for a more accurate determination of the activity distribution of {sup 90}Y microspheres within a patient. This improved activity distribution can be convolved with the dose kernel of {sup 90}Y to calculate the dose distribution within a patient. This work investigates the effects of microsphere and surrounding material composition on {sup 90}Y dose kernels using egsnrc and mcnp5 and compares the results of these two transport codes. Methods: Monte Carlo simulations were performed with egsnrc and mcnp5 to calculate the dose rate at multiple radial distances around various {sup 90}Y sources. Point source simulations were completed with mcnp5 to determine the optimal electron transport settings for this work. After determining the optimal settings, point source simulations were completed using egsnrc (user code edknrc) and mcnp5 in water and liver [as defined by the International Commission on Radiation Units and Measurements (ICRU) Report 44]. The results were compared to ICRU Report 72 reference data. Point source simulations were also completed in water with a density of 1.06 g{center_dot}cm{sup -3} to evaluate the effect of the density of the surrounding material. Glass and resin microsphere simulations were performed with average and maximum diameter and density values (based on values given in the literature) in water and in liver. The results were compared to point source simulation results using the same transport code and in the same surrounding material. All simulations had statistical uncertainties less than 1%. Results: The optimal transport settings in mcnp5 for this work included using the energy-and step-specific algorithm (DBCN 17J 2) and ESTEP set to 10. These settings were used for all subsequent simulations with mcnp5. The point source simulations in water for both egsnrc and mcnp5 were found to agree within 2% of the ICRU 72 reference data over the investigated range. Point source simulations in liver had large differences relative to ICRU 72, approaching -60% near the maximum range of {sup 90}Y. These differences are mostly attributed to the difference in density between water (1.0 g{center_dot}cm{sup -3}) and liver (1.06 g{center_dot}cm{sup -3}). Glass and resin microsphere simulations showed a slight decrease in the dose rate near the maximum range of {sup 90}Y relative to the point source simulations. The largest relative differences were approximately -4.2% and -2.8% for the glass and resin microspheres, respectively. Agreement between the egsnrc and mcnp5 simulations results was generally good. Conclusions: The presence of the microsphere material causes slight differences in the {sup 90}Y dose kernel compared to those calculated with point sources. Large differences were seen between simulations in water and those in liver. For the most accurate calculation of the dose distribution, the density of the patient's liver should be accounted for in the calculation of the dose kernel. Lastly, due to the need to determine the optimal transport settings with mcnp5, electron transport with this code should be used with caution.

61 RADIATION PROTECTION AND DOSIMETRY↗

DOE OSTI2015

TU-F-CAMPUS-J-05: Fast Volumetric MRI On An MRI-Linac Enables On-Line QA On Dose Deposition in the Patient

Purpose: The introduction of the MRI-linac in radiotherapy brings MRI-guided treatment with daily plan adaptions within reach. This paradigm demands on-line QA. With its ability to perform continuous volumetric imaging in an outstanding soft-tissue contrast, the MRI- linac promises to elucidate the dose deposition process during a treatment session. Here we study for a prostate case how dynamic MRI combined with linac machine parameters and a fast dose-engine can be used for on-line dose accumulation. Methods: Prostate imaging was performed in healthy volunteer on a 1.5T MR-scanner (Philips, Best, NL) according to a clinical MR-sim protocol, followed by 10min of dynamic imaging (FLASH, 4s/volume, FOV 40×40×12cm{sup 3}, voxels 3×3×3mm{sup 3}, TR/TE/α=3.5ms/1.7ms/5°). An experienced radiation oncologist made delineations, considering the prostate CTV. Planning was performed on a two-compartment pseudoCT (air/water density) according to clinical constraints (77Gy in PTV) using a Monte-Carlo (MC) based TPS that accounts for magnetic fields. Delivery of one fraction (2.2Gy) was simulated on an emulator for the Axesse linac (Elekta, Stockholm, SE). Machine parameters (MLC settings, gantry angle, dose rate, etc.) were recorded at 25Hz. These were re-grouped per dynamic volume and fed into the MC-engine to calculate a dose delivered for each of the dynamics. Deformations derived from non-rigid registration of each dynamic against the first allowed dose accumulation on a common reference grid. Results: The DVH parameters on the PTV compared to the optimized plan showed little changes. Local deformations however resulted in local deviations, primarily around the air/rectum interface. This clearly indicates the potential of intra-fraction adaptations based on the accumulated dose. Application in each fraction helps to track the influence of plan adaptations to the eventual dose distribution. Calculation times were about twice the delivery time. Conclusion: The current Result paves the way to perform on-line treatment delivery QA on the MRI-linac in the near future.

60 APPLIED LIFE SCIENCES↗

DOE OSTI2016

SU-F-T-70: A High Dose Rate Total Skin Electron Irradiation Technique with A Specific Inter-Film Variation Correction Method for Very Large Electron Beam Fields

Purpose: Rotational total skin electron irradiation (RTSEI) is used in the treatment of cutaneous T-cell lymphoma. Due to inter-film uniformity variations the dosimetry measurement of a large electron beam of a very low energy is challenging. This work provides a method to improve the accuracy of flatness and symmetry for a very large treatment field of low electron energy used in dual beam RTSEI. Methods: RTSEI is delivered by dual angles field a gantry of ±20 degrees of 270 to cover the upper and the lower halves of the patient body with acceptable beam uniformity. The field size is in the order of 230cm in vertical height and 120 cm in horizontal width and beam energy is a degraded 6 MeV (6 mm of PMMA spoiler). We utilized parallel plate chambers, Gafchromic films and OSLDs as a measuring devices for absolute dose, B-Factor, stationary and rotational percent depth dose and beam uniformity. To reduce inter-film dosimetric variation we introduced a new specific correction method to analyze beam uniformity. This correction method uses some image processing techniques combining film value before and after radiation dose to compensate the inter-variation dose response differences among films. Results: Stationary and rotational depth of dose demonstrated that the Rp is 2 cm for rotational and the maximum dose is shifted toward the surface (3mm). The dosimetry for the phantom showed that dose uniformity reduced to 3.01% for the vertical flatness and 2.35% for horizontal flatness after correction thus achieving better flatness and uniformity. The absolute dose readings of calibrated films after our correction matched with the readings from OSLD. Conclusion: The proposed correction method for Gafchromic films will be a useful tool to correct inter-film dosimetric variation for the future clinical film dosimetry verification in very large fields, allowing the optimizations of other parameters.

60 APPLIED LIFE SCIENCES↗

DOE OSTI2020

Application of physiologically based pharmacokinetic modeling for sertraline dosing recommendations in pregnancy

Pregnancy is a period of significant change that impacts physiological and metabolic status leading to alterations in the disposition of drugs. Uncertainty in drug dosing in pregnancy can lead to suboptimal therapy, which can contribute to disease exacerbation. A few studies show there are increased dosing requirements for antidepressants in late pregnancy; however, the quantitative data to guide dose adjustments are sparse. We aimed to develop a physiologically based pharmacokinetic (PBPK) model that allows gestational-age dependent prediction of sertraline dosing in pregnancy. A minimal physiological model with defined gut, liver, plasma, and lumped placental-fetal compartments was constructed using the ordinary differential equation solver package, ‘mrgsolve’, in R. We extracted data from the literature to parameterize the model, including sertraline physicochemical properties, in vitro metabolism studies, disposition in nonpregnant women, and physiological changes during pregnancy. The model predicted the pharmacokinetic parameters from a clinical study with eight subjects for the second trimester and six subjects for the third trimester. Based on the model, gestational-dependent changes in physiology and metabolism account for increased clearance of sertraline (up to 143% at 40 weeks gestational age), potentially leading to under-dosing of pregnant women when nonpregnancy doses are used. The PBPK model was converted to a prototype web-based interactive dosing tool to demonstrate how the output of a PBPK model may translate into optimal sertraline dosing in pregnancy. Quantitative prediction of drug exposure using PBPK modeling in pregnancy will support clinically appropriate dosing and increase the therapeutic benefit for pregnant women.

60 APPLIED LIFE SCIENCES↗

DOE OSTI2022

Ultra-high dose rate FLASH irradiator at the radiological research accelerator facility

The Radiological Research Accelerator Facility has modified a decommissioned Varian Clinac to deliver ultra-high dose rates: operating in 9 MeV electron mode ( FLASH mode), samples can be irradiated at a Source-Surface Distance (SSD) of 20 cm at average dose rates of up to 600 Gy/s (3.3 Gy per 0.13 µs pulse, 180 pulses per second). In this mode multiple pulses are required for most irradiations. By modulating pulse repetition rate and irradiating at SSD = 171 cm, dose rates below 1 Gy/min can be achieved, allowing comparison of FLASH and conventional irradiations with the same beam. Operating in 6 MV photon mode, with the conversion target removed ( SuperFLASH mode), samples are irradiated at higher dose rates (0.2–150 Gy per 5 µs pulse, 360 pulses per second) and most irradiations can be performed with a single very high dose rate pulse. In both modes we have seen the expected inverse relation between dose rate and irradiated area, with the highest dose rates obtained for beams with a FWHM of about 2 cm and ± 10% uniformity over 1 cm diameter. As an example of operation of the ultra-high dose rate FLASH irradiator, we present dose rate dependence of dicentric chromosome yields.

43 PARTICLE ACCELERATORS↗