Publications by authors named "Choonik Lee"

54 Publications

Fetal dose from proton pencil beam scanning craniospinal irradiation during pregnancy: a Monte Carlo study.

Phys Med Biol 2022 Jan 13. Epub 2022 Jan 13.

Radiation Epidemiology Branch, National Cancer Institute, 9609 Medical Center Dr, Bethesda, Maryland, 20850 , UNITED STATES.

Objective: We conducted a Monte Carlo study to comprehensively investigate the fetal dose resulting from proton pencil beam scanning (PBS) craniospinal irradiation (CSI) during pregnancy.

Approach: The gestational-age dependent pregnant phantom series developed at the University of Florida (UF) were converted into DICOM-RT format (CT images and structures) and imported into a treatment planning system (TPS) (Eclipse v15.6) commissioned to a IBA PBS nozzle. A proton PBS CSI plan (prescribed dose: 36 Gy) was created on the phantoms. The TOPAS MC code was used to simulate the proton PBS CSI on the phantoms, for which MC beam properties at the nozzle exit (spot size, spot divergence, mean energy, and energy spread) were matched to IBA PBS nozzle beam measurement data. We calculated mean absorbed doses for 28 organs and tissues and whole body of the fetus at eight gestational ages (8, 10, 15, 20, 25, 30, 35, and 38 weeks). For contextual purposes, the fetal organ/tissue doses from the treatment planning CT scan of the mother's head and torso were estimated using the National Cancer Institute dosimetry system for CT (NCICT, Version 3) considering a low-dose CT protocol (CTDIvol: 8.97 mGy).

Main Results: The majority of the fetal organ/tissue doses from the proton PBS CSI treatment fell within a range of 3 to 6 mGy. The fetal organ/tissue doses for the 38-week phantom showed the largest variation with the doses ranging from 2.9 mGy (adrenals) to 8.2 mGy (eye lenses) while the smallest variation ranging from 3.2 mGy (oesophagus) to 4.4 mGy (brain) was observed for the doses for the 20-week phantom. The fetal whole-body dose ranged from 3.7 mGy (25 weeks) to 5.8 mGy (8 weeks). Most of the fetal doses from the planning CT scan fell within a range of 7 to 13 mGy, approximately 2-to-9 times lower than the fetal dose equivalents of the proton PBS CSI treatment (assuming a quality factor of 7).

Significance: The fetal organ/tissue doses observed in the present work will be useful for one of the first clinically informative predictions on the magnitude of fetal dose during proton PBS CSI during pregnancy.
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http://dx.doi.org/10.1088/1361-6560/ac4b38DOI Listing
January 2022

Early HPV ctDNA Kinetics and Imaging Biomarkers Predict Therapeutic Response in p16+ Oropharyngeal Squamous Cell Carcinoma.

Clin Cancer Res 2021 Oct 26. Epub 2021 Oct 26.

Department of Otolaryngology Head and Neck Surgery, University of Michigan, Ann Arbor, Michigan.

Purpose: In locally advanced p16+ oropharyngeal squamous cell carcinoma (OPSCC), (i) to investigate kinetics of human papillomavirus (HPV) circulating tumor DNA (ctDNA) and association with tumor progression after chemoradiation, and (ii) to compare the predictive value of ctDNA to imaging biomarkers of MRI and FDG-PET.

Experimental Design: Serial blood samples were collected from patients with AJCC8 stage III OPSCC ( = 34) enrolled on a randomized trial: pretreatment; during chemoradiation at weeks 2, 4, and 7; and posttreatment. All patients also had dynamic-contrast-enhanced and diffusion-weighted MRI, as well as FDG-PET scans pre-chemoradiation and week 2 during chemoradiation. ctDNA values were analyzed for prediction of freedom from progression (FFP), and correlations with aggressive tumor subvolumes with low blood volume (TV) and low apparent diffusion coefficient (TV), and metabolic tumor volume (MTV) using Cox proportional hazards model and Spearman rank correlation.

Results: Low pretreatment ctDNA and an early increase in ctDNA at week 2 compared with baseline were significantly associated with superior FFP ( < 0.02 and < 0.05, respectively). At week 4 or 7, neither ctDNA counts nor clearance were significantly predictive of progression ( = 0.8). Pretreatment ctDNA values were significantly correlated with nodal TV, TV, and MTV pre-chemoradiation ( < 0.03), while the ctDNA values at week 2 were correlated with these imaging metrics in primary tumor. Multivariate analysis showed that ctDNA and the imaging metrics performed comparably to predict FFP.

Conclusions: Early ctDNA kinetics during definitive chemoradiation may predict therapy response in stage III OPSCC.
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http://dx.doi.org/10.1158/1078-0432.CCR-21-2338DOI Listing
October 2021

Application of an automatic segmentation method for evaluating cardiac structure doses received by breast radiotherapy patients.

Phys Imaging Radiat Oncol 2021 Jul 23;19:138-144. Epub 2021 Aug 23.

Division of Cancer Epidemiology and Genetics, National Cancer Institute, National Institutes of Health, Rockville, MD 20850, United States.

Background And Purpose: Quantifying radiation dose to cardiac substructures is important for research on the etiology and prevention of complications following radiotherapy; however, segmentation of substructures is challenging. In this study we demonstrate the application of our atlas-based automatic segmentation method to breast cancer radiotherapy plans for generating radiation doses in support of late effects research.

Material And Methods: We applied our segmentation method to contour heart substructures on the computed tomography (CT) images of 70 breast cancer patients who received external photon radiotherapy. Two cardiologists provided manual segmentation of the whole heart (WH), left/right atria, left/right ventricles, and left anterior descending artery (LAD). The automatically contours were compared with manual delineations to evaluate similarity in terms of geometry and dose.

Results: The mean Dice similarity coefficient between manual and automatic segmentations was 0.96 for the WH, 0.65 to 0.82 for the atria and ventricles, and 0.06 for the LAD. The mean average surface distance was 1.2 mm for the WH, 3.4 to 4.1 mm for the atria and ventricles, and 6.4 mm for the LAD. We found the dose to the cardiac substructures based on our automatic segmentation agrees with manual segmentation within expected observer variability. For left breast patients, the mean absolute difference in mean dose was 0.1 Gy for the WH, 0.2 to 0.7 Gy for the atria and ventricles, and 1.8 Gy for the LAD. For right breast patients, these values were 0.0 Gy, 0.1 to 0.4 Gy, and 0.4 Gy, respectively.

Conclusion: Our automatic segmentation method will facilitate the development of radiotherapy prescriptive criteria for mitigating cardiovascular complications.
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http://dx.doi.org/10.1016/j.phro.2021.08.005DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8397890PMC
July 2021

Early MRI Blood Volume Changes in Constrictor Muscles Correlate With Postradiation Dysphagia.

Int J Radiat Oncol Biol Phys 2021 06 24;110(2):566-573. Epub 2020 Dec 24.

Department of Radiation Oncology, University of Michigan, Ann Arbor, Michigan; Department of Radiology, University of Michigan, Ann Arbor, Michigan; Department of Biomedical Engineering, University of Michigan, Ann Arbor, Michigan.

Purpose: Predicting individual patient sensitivity to radiation therapy (RT) for tumor control or normal tissue toxicity is necessary to individualize treatment planning. In head and neck cancer, radiation doses are limited by many nearby critical structures, including structures involved in swallowing. Previous efforts showed that imaging parameters correlate with RT dose; here, we investigate the role of dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) blood volume (BV) changes in predicting dysphagia.

Methods And Materials: This study included 32 patients with locally advanced oropharyngeal squamous cell carcinoma treated with definitive chemoradiation on an institutional protocol incorporating baseline and early midtreatment DCE-MRI. BV maps of the pharyngeal constrictor muscles (PCM) were created, and BV increases midtreatment were correlated with the following parameters at 3 and 12 months post-RT: RT dose, Dynamic Imaging Grade of Swallowing Toxicity swallow score, aspiration frequency, European Organisation for Research and Treatment of Cancer HN35 patient-reported outcomes, physician-reported dysphagia, and feeding tube (FT) dependence.

Results: The mean BV to the PCMs increased from baseline to fraction 10, which was significant for the superior PCM (P = .006) and middle PCM (P < .001), with a trend in the inferior PCM where lower mean doses were seen (P = .077). The factors associated with FT dependence at 3 months included BV increases in the total PCM (correlation, 0.48; P = .006) and middle PCM (correlation, 0.50; P = .004). A post-RT increase in aspiration was associated with a BV increase in the superior PCM (correlation, 0.44; P = .013),and the increase in the total PCMs was marginally significant (correlation, 0.34; P = .06). The best-performing models of FT dependence (area under the receiver operating curve [AUC] = 0.84) and aspiration increases (AUC = 0.78) included BV increases as well as a mean RT dose to middle PCM.

Conclusions: Our results suggest that midtreatment BV increases derived from DCE-MRI are an early predictor of dysphagia. Further investigation of these promising imaging markers to assess individual patient sensitivity to treatment and the patient's subsequent risk of toxicities is warranted to improve personalization of RT planning.
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http://dx.doi.org/10.1016/j.ijrobp.2020.12.018DOI Listing
June 2021

A dose voxel kernel method for rapid reconstruction of out-of-field neutron dose of patients in pencil beam scanning (PBS) proton therapy.

Phys Med Biol 2020 08 27;65(17):175015. Epub 2020 Aug 27.

Division of Cancer Epidemiology and Genetics, National Cancer Institute, National Institutes of Health, Rockville, MD 20850, United States of America.

Monte Carlo (MC) radiation transport methods are used for dose calculation as 'gold standard.' However, the method is computationally time-consuming and thus impractical for normal tissue dose reconstructions for the large number of proton therapy patients required for epidemiologic investigations of late health effects. In the present study, we developed a new dose calculation method for the rapid reconstruction of out-of-field neutron dose to patients undergoing pencil beam scanning (PBS) proton therapy. The new dose calculation method is based on neutron dose voxel kernels (DVKs) generated by MC simulations of a proton pencil beam irradiating a water phantom (60 × 60 × 300 cm), which was conducted using a MC proton therapy simulation code, TOPAS. The DVKs were generated for 19 beam energies (from 70 to 250 MeV with the 10 MeV interval) and three range shifter thicknesses (1, 3, and 5 cm). An in-house program was written in C++ to superimpose the DVKs onto a patient CT images according to proton beam characteristics (energy, position, and direction) available in treatment plans. The DVK dose calculation method was tested by calculating organ/tissue-specific neutron doses of 1- and 5-year-old whole-body computational phantoms where intracranial and craniospinal irradiations were simulated. The DVK-based doses generally showed reasonable agreement with those calculated by direct MC simulations with a detailed PBS model that were previously published, with differences mostly less than 30% and 10% for the intracranial and craniospinal irradiations, respectively. The computation time of the DVK method for one patient ranged from 1 to 30 min on a single CPU core of a personal computer, demonstrating significant improvement over the direct MC dose calculation requiring several days on high-performance computing servers. Our DVK-based dose calculation method will be useful when dosimetry is needed for the large number of patients such as for epidemiologic or clinical research.
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http://dx.doi.org/10.1088/1361-6560/abaa5fDOI Listing
August 2020

Practice Patterns for the Treatment of Uveal Melanoma with Iodine-125 Plaque Brachytherapy: Ocular Oncology Study Consortium Report 5.

Ocul Oncol Pathol 2020 May 11;6(3):210-218. Epub 2019 Dec 11.

Department of Radiation Medicine, Oregon Health and Science University, Portland, Oregon, USA.

Background: Treatment planning for I-125 plaque therapy for uveal melanoma has advanced significantly since the Collaborative Ocular Melanoma Study trial, with more widely available image-guided planning and improved dosimetry.

Objective: We evaluated real-world practice patterns for I-125 plaque brachytherapy in the United States by studying practice patterns at centers that comprise the Ocular Oncology Study Consortium (OOSC).

Methods: The OOSC database and responses to a treatment practice survey were evaluated. The database contains treatment information from 9 institutions. Patients included in the database were treated between 2010 and 2014. The survey was conducted in 2018 and current treatment planning methods and prescriptions were queried.

Results: Examination of the OOSC database revealed that average doses to critical structures were highly consistent, with the exception of one institution. Survey responses indicated that most centers followed published guidelines regarding dose and prescription point. Dose rate ranged from 51 to 118 cGy/h. As of 2018, most institutions use pre-loaded plaques and fundus photographs and/or computed tomography or magnetic resonance imaging in planning.

Conclusions: While there were differences in dosimetric practices, overall agreement in plaque brachytherapy practices was high among OOSC institutions. Clinical margins and planning systems were similar among institutions, while prescription dose, dose rates, and dosimetry varied.
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http://dx.doi.org/10.1159/000504312DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7250354PMC
May 2020

Development and comprehensive commissioning of an automated brachytherapy plan checker.

Brachytherapy 2020 May - Jun;19(3):355-361. Epub 2020 Apr 2.

Department of Radiation Oncology, University of Michigan, Ann Arbor, MI. Electronic address:

Purpose: To present on the commissioning of an automated brachytherapy plan checker (BPC) for the evaluation of high-dose-rate brachytherapy treatment plans in support of standardized workflows and patient safety.

Methods And Materials: A BPC was developed using an applications programming interface in a commercial treatment planning system based on different inputs (e.g., regulations, professional society recommendations, and user feedback) and leveraged our experience with an in-house developed external beam plan checker. The BPC was commissioned using a comprehensive suite of test plans with known errors and anonymized clinical plans.

Results: During commissioning, the BPC was successfully executed on a total of 87 test plans. Commissioning tests spanned a range of treatment sites and evaluated that pass and fail states were correct. Administration settings were changed in a nonclinical database to evaluate tests involving the source and afterloader. Clinical testing of the BPC was then performed in parallel with a manual review process before clinical implementation.

Conclusions: To commission the BPC for clinical use, a comprehensive suite of test plans was developed and used to ensure the BPC correctly detected and reported errors. A summary of the test plans is presented to help guide users developing similar automated tools. The BPC represents a process-improvement initiative designed to reduce errors and improve safety for brachytherapy patients. By using a comprehensive test suite for commissioning, tests are available for periodic quality assurance and after software upgrades.
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http://dx.doi.org/10.1016/j.brachy.2020.02.003DOI Listing
January 2021

Predictive Values of MRI and PET Derived Quantitative Parameters for Patterns of Failure in Both p16+ and p16- High Risk Head and Neck Cancer.

Front Oncol 2019 14;9:1118. Epub 2019 Nov 14.

Department of Radiation Oncology, University of Michigan, Ann Arbor, MI, United States.

FDG-PET adds to clinical factors, such tumor stage and p16 status, in predicting local (LF), regional (RF), and distant failure (DF) in poor prognosis locally advanced head and neck cancer (HNC) treated with chemoradiation. We hypothesized that MRI-based quantitative imaging (QI) metrics could add to clinical predictors of treatment failure more significantly than FDG-PET metrics. Fifty four patients with poor prognosis HNCs who were enrolled in an IRB approved prospective adaptive chemoradiotherapy trial were analyzed. MRI-derived gross tumor volume (GTV), blood volume (BV), and apparent diffusion coefficient (ADC) pre-treatment and mid-treatment (fraction 10), as well as pre-treatment FDG PET metrics, were analyzed in primary and individual nodal tumors. Cox proportional hazards models for prediction of LRF and DF free survival were used to test the additional value of QI metrics over dominant clinical predictors. The mean ADC pre-RT and its change rate mid-treatment were significantly higher and lower in p16- than p16+ primary tumors, respectively. A Cox model identified that high mean ADC pre-RT had a high hazard for LF and RF in p16- but not p16+ tumors ( = 0.015). Most interesting, persisting subvolumes of low BV (TV) in primary and nodal tumors mid-treatment had high-risk for DF ( < 0.05). Also, total nodal GTV mid-treatment, mean/max SUV of FDG in all nodal tumors, and total nodal TLG were predictive for DF ( < 0.05). When including clinical stage (T4/N3) and total nodal GTV in the model, all nodal PET parameters had a -value of >0.3, and only TV of primary tumors had a -value of 0.06. MRI-defined biomarkers, especially persisting subvolumes of low BV, add predictive value to clinical variables and compare favorably with FDG-PET imaging markers. MRI could be well-integrated into the radiation therapy workflow for treatment planning, response assessment, and adaptive therapy.
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http://dx.doi.org/10.3389/fonc.2019.01118DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6874128PMC
November 2019

Automatic segmentation of cardiac structures for breast cancer radiotherapy.

Phys Imaging Radiat Oncol 2019 Oct 5;12:44-48. Epub 2019 Dec 5.

Division of Cancer Epidemiology and Genetics, National Cancer Institute, National Institutes of Health, Rockville, MD 20850, USA.

Background And Purpose: We developed an automatic method to segment cardiac substructures given a radiotherapy planning CT images to support epidemiological studies or clinical trials looking at cardiac disease endpoints after radiotherapy.

Material And Methods: We used a most-similar atlas selection algorithm and 3D deformation combined with 30 detailed cardiac atlases. We cross-validated our method within the atlas library by evaluating geometric comparison metrics and by comparing cardiac doses for simulated breast radiotherapy between manual and automatic contours. We analyzed the impact of the number of cardiac atlas in the library and the use of manual guide points on the performance of our method.

Results: The Dice Similarity Coefficients from the cross-validation reached up to 97% (whole heart) and 80% (chambers). The Average Surface Distance for the coronary arteries was less than 10.3 mm on average, with the best agreement (7.3 mm) in the left anterior descending artery (LAD). The dose comparison for simulated breast radiotherapy showed differences less than 0.06 Gy for the whole heart and atria, and 0.3 Gy for the ventricles. For the coronary arteries, the dose differences were 2.3 Gy (LAD) and 0.3 Gy (other arteries). The sensitivity analysis showed no notable improvement beyond ten atlases and the manual guide points does not significantly improve performance.

Conclusion: We developed an automated method to contour cardiac substructures for radiotherapy CTs. When combined with accurate dose calculation techniques, our method should be useful for cardiac dose reconstruction of a large number of patients in epidemiological studies or clinical trials.
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http://dx.doi.org/10.1016/j.phro.2019.11.007DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7807574PMC
October 2019

A feasibility study to reduce misclassification error in occupational dose estimates for epidemiological studies using body size-dependent computational phantoms.

IEEE Trans Radiat Plasma Med Sci 2019 Jan 15;3(1):83-88. Epub 2018 Jun 15.

Division of Cancer Epidemiology and Genetics, National Cancer Institute, National Institutes of Health, Rockville, MD 20850.

In the epidemiological study on the health effects of participants in the United States Radiologic Technologists (USRT) study, organ dosimetry was performed based on surveys and literature reviews. To convert dosimeter readings to organ doses, organ dose coefficients were adopted. However, the existing dose coefficients were derived from computational human phantoms with ICRP reference height and weight not accounting for the variation in body size. We first calculated preliminary body size-dependent organ dose coefficients using selected body size-dependent phantoms combined with Monte Carlo radiation transport method. We then tested the accuracy of these body-size dependent coefficients against the ICRP 74 reference size coefficients in comparison with five individual-specific organ dose coefficients computed from computed tomography (CT) image-based anatomical models of five adult males with different body sizes also using Monte Carlo methods. The reference size dose coefficients overall underestimate the patient-specific dose coefficients by up to 51%. Body size-dependent phantoms overall provided more accurate organ dose coefficients for the five patients. In case of the esophagus, the dose underestimation of 51% in the comparison with the reference phantom was reduced to 7%. The results confirm that potential dosimetric misclassification caused by using reference size phantom-based dose coefficients can be resolved by using the body size-dependent dose coefficients.
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http://dx.doi.org/10.1109/TRPMS.2018.2847227DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6879178PMC
January 2019

A Monte Carlo model for organ dose reconstruction of patients in pencil beam scanning (PBS) proton therapy for epidemiologic studies of late effects.

J Radiol Prot 2020 Mar 11;40(1):225-242. Epub 2019 Sep 11.

Division of Cancer Epidemiology and Genetics, National Cancer Institute, National Institutes of Health, Rockville, MD 20850, United States of America.

Significant efforts such as the Pediatric Proton/Photon Consortium Registry (PPCR) involving multiple proton therapy centers have been made to conduct collaborative studies evaluating outcomes following proton therapy. As a groundwork dosimetry effort for the late effect investigation, we developed a Monte Carlo (MC) model of proton pencil beam scanning (PBS) to estimate organ/tissue doses of pediatric patients at the Maryland Proton Treatment Center (MPTC), one of the proton centers involved in the PPCR. The MC beam modeling was performed using the TOPAS (TOol for PArticle Simulation) MC code and commissioned to match measurement data within 1% for range, and 0.3 mm for spot sizes. The established MC model was then tested by calculating organ/tissue doses for sample intracranial and craniospinal irradiations on whole-body pediatric computational human phantoms. The simulated dose distributions were compared with the treatment planning system dose distributions, showing the 3 mm/3% gamma index passing rates of 94%-99%, validating our simulations with the MC model. The calculated organ/tissue doses per prescribed doses for the craniospinal irradiations (1 mGy Gy to 1 Gy Gy) were generally much higher than those for the intracranial irradiations (2.1 μGy Gy to 0.1 Gy Gy), which is due to the larger field coverage of the craniospinal irradiations. The largest difference was observed at the adrenal dose, i.e. ∼3000 times. In addition, the calculated organ/tissue doses were compared with those calculated with a simplified MC model, showing that the beam properties (i.e. spot size, spot divergence, mean energy, and energy spread) do not significantly influence dose calculations despite the limited irradiation cases. This implies that the use of the MC model commissioned to the MPTC measurement data might be dosimetrically acceptable for patient dose reconstructions at other proton centers particularly when their measurement data are unavailable. The developed MC model will be used to reconstruct organ/tissue doses for MPTC pediatric patients collected in the PPCR.
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http://dx.doi.org/10.1088/1361-6498/ab437dDOI Listing
March 2020

Conversion of computational human phantoms into DICOM-RT for normal tissue dose assessment in radiotherapy patients.

Phys Med Biol 2019 07 5;64(13):13NT02. Epub 2019 Jul 5.

Division of Cancer Epidemiology and Genetics, National Cancer Institute, National Institutes of Health, Rockville, MD 20850, United States of America.

Radiotherapy (RT) treatment planning systems (TPS) are designed for the fast calculation of dose to the tumor bed and nearby organs at risk using x-ray computed tomography (CT) images. However, CT images for a patient are typically available for only a small portion of the body, and in some cases, such as for retrospective epidemiological studies, no images may be available at all. When dose to organs that lie out-of-scan must be estimated, a convenient alternative for the unknown patient anatomy is to use a matching whole-body computational phantom as a surrogate. The purpose of the current work is to connect such computational phantoms to commercial RT TPS for retrospective organ dose estimation. A custom software with graphical user interface (GUI), called the DICOM-RT Generator, was developed in MATLAB to convert voxel computational phantoms into the digital imaging and communications in medicine radiotherapy (DICOM-RT) format, compatible with commercial TPS. DICOM CT image sets for the phantoms are created via a density-to-Hounsfield unit (HU) conversion curve. Accompanying structure sets containing the organ contours are automatically generated by tracing binary masks of user-specified organs on each phantom CT slice. The software was tested on a library of body size-dependent phantoms, the International Commission on Radiological Protection reference phantoms, and a canine voxel phantom, taking only a few minutes per conversion. The resulting DICOM-RT files were tested on several commercial TPS. As an example application, a library of converted phantoms was used to estimate organ doses for members of the National Wilms Tumor Study (NWTS) cohort. The converted phantom library, in DICOM format, and a standalone MATLAB-compiled executable of the DICOM-RT Generator are available for others to use for research purposes (http://ncidose.cancer.gov).
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http://dx.doi.org/10.1088/1361-6560/ab2670DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6612588PMC
July 2019

Functional Adaptation in Radiation Therapy.

Semin Radiat Oncol 2019 Jul;29(3):236-244

Department of Radiation Oncology, University of Michigan, Ann Arbor, MI.

The promise of adaptive therapy to improve outcomes in radiation oncology has been an area of interest and research in the community for many years. One of the sources of data that can be used to drive adaptive therapy is functional information about the tumor or normal tissues. This avenue of adaptation includes many potential sources of data including global markers and functional imaging. Global markers can be assessments derived from blood measurements, patient functional testing, and circulating tumor material and functional imaging data comprises spatial physiological information from various imaging studies such as positron emission tomography, magnetic resonance imaging, and single photon emission computed tomography. The goal of functional adaptation is to use these functional data to adapt radiation therapy to improve patient outcomes. While functional adaptation holds a lot of promise, there are challenges such as quantifying and minimizing uncertainties, streamlining clinical implementation, determining the ideal way to incorporate information within treatment plan optimization, and proving the clinical benefit through trials. This paper will discuss the types of functional information currently being used for adaptation, highlight several areas where functional adaptation has been studied, and introduce some of the barriers to more widespread clinical implementation.
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http://dx.doi.org/10.1016/j.semradonc.2019.02.006DOI Listing
July 2019

Real-Time Quantitative Assessment of Accuracy and Precision of Blood Volume Derived from DCE-MRI in Individual Patients During a Clinical Trial.

Tomography 2019 03;5(1):61-67

Departments of Radiation Oncology.

Accuracy and precision of quantitative imaging (QI) metrics should be assessed in real time in each patient during a clinical trial to support QI-based decision-making. We developed a framework for real-time quantitative assessment of QI metrics and evaluated accuracy and precision of dynamic contrast-enhanced (DCE)-magnetic resonance imaging (MRI)-derived blood volume (BV) in a clinical trial for head and neck cancers. Patients underwent DCE-MRI before and after 2 weeks of radiation therapy (2wkRT). A mean as a reference value and a repeatability coefficient (RC) of BV values established from patients in cerebellum volumes of interest (VOIs), which were normal and affected little by therapy, served as accuracy and precision measurements. The BV maps of a new patient were called accurate and precise if the values in cerebellum VOIs and the difference between the 2 scans agreed with the respective mean and RC with 95% confidence. The new data could be used to update reference values. Otherwise, the data were flagged for further evaluation before use in the trial. BV maps from 62 patients enrolled on the trial were evaluated. Mean BV values were 2.21 (±0.14) mL/100 g pre-RT and 2.22 (±0.17) mL/100 g at 2wkRT; relative RC was 15.9%. The BV maps from 3 patients were identified to be inaccurate and imprecise before use in the clinical trial. Our framework of real-time quantitative assessment of QI metrics during a clinical trial can be translated to different QI metrics and organ-sites for supporting QI-based decision-making that warrants success of a clinical trial.
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http://dx.doi.org/10.18383/j.tom.2018.00029DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6403042PMC
March 2019

Predictive Models to Determine Clinically Relevant Deviations in Delivered Dose for Head and Neck Cancer.

Pract Radiat Oncol 2019 Jul - Aug;9(4):e422-e431. Epub 2019 Mar 2.

Department of Imaging Physics, The University of Texas MD Anderson Cancer Center, Houston, Texas.

Purpose: This study aimed to improve the understanding of deviations between planned and accumulated doses and to establish metrics to predict clinically significant dosimetric deviations midway through treatment to evaluate the potential need to re-plan during fractionated radiation therapy (RT).

Methods And Materials: A total of 100 patients with head and neck cancer were retrospectively evaluated. Contours were mapped from the planning computed tomography (CT) scan to each fraction cone beam CT via deformable image registration. The dose was calculated on each cone beam CT and evaluated based on the mapped contours. The mean dose at each fraction was averaged to approximate the accumulated dose for structures with mean dose constraints, and the daily maximum dose was summed to approximate the accumulated dose for structures with maximum dose constraints. A threshold deviation value was calculated to predict for patients needing midtreatment re-planning. This predictive model was applied to 52 patients treated at a separate institution.

Results: Dose was accumulated on 10 organs over 100 patients. To generate a threshold deviation that predicted the need to re-plan with 100% sensitivity, the submandibular glands required re-planning if the delivered dose was at least 3.5 Gy higher than planned by fraction 15. This model predicts the need to re-plan the submandibular glands with 98.7% specificity. In the independent evaluation cohort, this model predicts the need to re-plan the submandibular glands with 100% sensitivity and 98.0% specificity. The oral cavity, intermediate clinical target volume, left parotid, and inferior constrictor patient groups each had 1 patient who exceeded the threshold deviation by the end of RT. By fraction 15 of 30 to 35 total fractions, the left parotid gland, inferior constrictor, and intermediate clinical target volume had a dose deviation of 3.1 Gy, 5.9 Gy, and 4.8 Gy, respectively. When a deformable image registration failure was observed, the dose deviation exceeded the threshold for at least 1 organ, demonstrating that an automated deformable image registration-based dose assessment process could be developed with user evaluation for cases that result in dose deviations.

Conclusions: A midtreatment threshold deviation was determined to predict the need to replan for the submandibular glands by fraction 15 of 30 to 35 total fractions of RT.
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http://dx.doi.org/10.1016/j.prro.2019.02.014DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6592740PMC
December 2019

Dosimetric impact of interfractional organs at risk variation during high-dose rate interstitial brachytherapy for gynecologic malignancies.

Med Dosim 2019 Autumn;44(3):239-244. Epub 2018 Oct 15.

Department of Radiation Oncology, University of Michigan, Ann Arbor, MI, USA. Electronic address:

We sought to develop a framework for the identification and management of patients at risk for organs at risk (OARs) overdosing due to interfractional anatomic variation during high-dose rate interstitial brachytherapy for gynecologic malignancies. We analyzed 40 high-dose rate interstitial brachytherapy fractions from 10 patients. Planned OAR doses were compared to delivered doses, which were calculated from computed tomography scans obtained prior to each treatment fraction. Doses were converted to equivalent doses in 2 Gy fractions (EQD2) and doses to the most exposed 2 cm (D) were reviewed. Patients were risk-stratified by identifying dose thresholds corresponding to a 10% or lower risk of receiving an OAR dose exceeding the corresponding planning constraint. For each OAR, 30% to 62.5% of patients received total doses greater than planned, although the magnitude of these differences was <4 Gy in over 75% of cases. Using EMBRACE II guidelines, one patient who had met the planning constraint for bladder and one for small bowel were found to have received doses exceeding the recommended limits. We next calculated thresholds for estimating the risk of OAR overdosing in individual patients and developed a framework based on these thresholds to direct time- and resource-intensive imaging and replanning efforts toward patients who are most likely to derive benefit. In summary, differential OAR dosing due to interfractional anatomic variation is common but likely rarely clinically meaningful. The proposed framework could decrease toxicity and maximize clinical efficiency.
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http://dx.doi.org/10.1016/j.meddos.2018.09.001DOI Listing
February 2020

Comparison of normal tissue dose calculation methods for epidemiological studies of radiotherapy patients.

J Radiol Prot 2018 Jun 11;38(2):775-792. Epub 2018 Apr 11.

Division of Cancer Epidemiology and Genetics, National Cancer Institute, National Institutes of Health, Rockville, MD 20850, United States of America.

Radiation dosimetry is an essential input for epidemiological studies of radiotherapy patients aimed at quantifying the dose-response relationship of late-term morbidity and mortality. Individualised organ dose must be estimated for all tissues of interest located in-field, near-field, or out-of-field. Whereas conventional measurement approaches are limited to points in water or anthropomorphic phantoms, computational approaches using patient images or human phantoms offer greater flexibility and can provide more detailed three-dimensional dose information. In the current study, we systematically compared four different dose calculation algorithms so that dosimetrists and epidemiologists can better understand the advantages and limitations of the various approaches at their disposal. The four dose calculations algorithms considered were as follows: the (1) Analytical Anisotropic Algorithm (AAA) and (2) Acuros XB algorithm (Acuros XB), as implemented in the Eclipse treatment planning system (TPS); (3) a Monte Carlo radiation transport code, EGSnrc; and (4) an accelerated Monte Carlo code, the x-ray Voxel Monte Carlo (XVMC). The four algorithms were compared in terms of their accuracy and appropriateness in the context of dose reconstruction for epidemiological investigations. Accuracy in peripheral dose was evaluated first by benchmarking the calculated dose profiles against measurements in a homogeneous water phantom. Additional simulations in a heterogeneous cylinder phantom evaluated the performance of the algorithms in the presence of tissue heterogeneity. In general, we found that the algorithms contained within the commercial TPS (AAA and Acuros XB) were fast and accurate in-field or near-field, but not acceptable out-of-field. Therefore, the TPS is best suited for epidemiological studies involving large cohorts and where the organs of interest are located in-field or partially in-field. The EGSnrc and XVMC codes showed excellent agreement with measurements both in-field and out-of-field. The EGSnrc code was the most accurate dosimetry approach, but was too slow to be used for large-scale epidemiological cohorts. The XVMC code showed similar accuracy to EGSnrc, but was significantly faster, and thus epidemiological applications seem feasible, especially when the organs of interest reside far away from the field edge.
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http://dx.doi.org/10.1088/1361-6498/aabd4fDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6007019PMC
June 2018

A Novel Method to Extend a Partial-Body CT for the Reconstruction of Dose to Organs beyond the Scan Range.

Radiat Res 2018 06 4;189(6):618-626. Epub 2018 Apr 4.

a   Division of Cancer Epidemiology and Genetics, National Cancer Institute, National Institutes of Health, Rockville, Maryland 20850.

Epidemiological investigation is an important approach to assessing the risk of late effects after radiotherapy, and organ dosimetry is a crucial part of such analysis. Computed tomography (CT) images, if available, can be a valuable resource for individualizing the dosimetry, because they describe the specific anatomy of the patient. However, CT images acquired for radiation treatment planning purposes cover only a portion of the body near the target volume, whereas for epidemiology, the interest lies in the more distant normal tissues, which may be located outside the scan range. To address this challenge, we developed a novel method, called the Anatomically Predictive Extension (APE), to extend a partial-body CT image stack using images of a computational human phantom matched to the patient based on their height and weight. To test our method, we created five APE phantoms from chest and abdominal images extracted from the chest-abdomen-pelvis (CAP) CT scans of five patients. Organ doses were calculated for simple chest and prostate irradiations that were planned on the reference computational phantom (assumed patient geometry if no CT images are available), APE phantoms (patient-phantom hybrid given a partial-body patient CT) and full patient CAP CT scans (ground truth). The APE phantoms and patient CAP CT scans resulted in nearly identical dosimetry for those organs that were fully included in the partial-body CT used to construct the APE. The calculated doses to these same organs in the reference phantoms differed by up to 20% and 52% for the chest and prostate cases, respectively. For organs outside the scan coverage, the reference phantom showed, on average, dose differences of 31% (chest case) and 41% (prostate case). For the APE phantoms, these values were 26% (chest) and 17% (prostate). The APE method combines patient and phantom images to improve organ dosimetry both inside and outside the scan range. We intend to use the APE method for estimating dose for organs peripheral to the treatment fields; however, this method is quite generalizable with many potential applications.
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http://dx.doi.org/10.1667/RR14999.1DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6384816PMC
June 2018

Adaptive Boost Target Definition in High-Risk Head and Neck Cancer Based on Multi-imaging Risk Biomarkers.

Int J Radiat Oncol Biol Phys 2018 11 21;102(4):969-977. Epub 2017 Dec 21.

Department of Radiation Oncology, University of Michigan, Ann Arbor, Michigan; Department of Radiology, University of Michigan, Ann Arbor, Michigan; Department of Biomedical Engineering, University of Michigan, Ann Arbor, Michigan. Electronic address:

Purpose: Positron emission tomography with F-deoxyglucose (FDG), dynamic contrast-enhanced magnetic resonance imaging (MRI), and diffusion-weighted MRI each identify unique risk factors for treatment outcomes in head and neck cancer (HNC). Clinical trials in HNC largely rely on a single imaging modality to define targets for boosting. This study aimed to investigate the spatial correspondence of FDG uptake, perfusion, and the apparent diffusion coefficient (ADC) in HNC and their response to chemoradiation therapy (CRT) and to determine the implications of this overlap or lack thereof for adaptive boosting.

Methods And Materials: Forty patients with HNC enrolled in a clinical trial underwent FDG positron emission tomography-computed tomography before CRT and underwent dynamic contrast-enhanced and diffusion-weighted MRI scans before and during CRT. The gross tumor volume (GTV) of the primary tumor was contoured on post-gadolinium T1-weighted images. Tumor subvolumes with high FDG uptake, low blood volume (BV), and low ADC were created by using previously established thresholds. Spatial correspondences between subvolumes were analyzed using the Dice coefficient, and those between each pair of image parameters at voxel level were analyzed by Spearman rank correlation coefficients.

Results: Prior to CRT, the median subvolumes of high FDG, low BV, and low ADC relative to the primary GTV were 20%, 21%, and 45%, respectively. Spearman correlation coefficients between BV and ADC varied from -0.47 to 0.22; between BV and FDG, from -0.08 to 0.59; and between ADC and FDG, from -0.68 to 0.25. Dice coefficients between subvolumes of FDG and BV, FDG and ADC, and BV and ADC were 10%, 46%, and 15%, respectively. The union of the 3 parameters was 64% of the GTV. The union of the subvolumes of BV and ADC was 56% of the GTV before CRT but was reduced significantly by 57% after 10 fractions of radiation therapy.

Conclusions: High FDG uptake, low BV, and low ADC as imaging risk biomarkers of HNC identify largely distinct tumor characteristics. A single imaging modality may not define the boosting target adequately.
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http://dx.doi.org/10.1016/j.ijrobp.2017.12.269DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6013352PMC
November 2018

State of dose prescription and compliance to international standard (ICRU-83) in intensity modulated radiation therapy among academic institutions.

Pract Radiat Oncol 2017 Mar - Apr;7(2):e145-e155. Epub 2016 Nov 13.

Department of Radiation Oncology, University of Pennsylvania, Philadelphia, Pennsylvania.

Purpose: The purpose of this study was to evaluate dose prescription and recording compliance to international standard (International Commission on Radiation Units & Measurements [ICRU]-83) in patients treated with intensity modulated radiation therapy (IMRT) among academic institutions.

Methods And Materials: Ten institutions participated in this study to collect IMRT data to evaluate compliance to ICRU-83. Under institutional review board clearance, data from 5094 patients-including treatment site, technique, planner, physician, prescribed dose, target volume, monitor units, planning system, and dose calculation algorithm-were collected anonymously. The dose-volume histogram of each patient, as well as dose points, doses delivered to 100% (D), 98% (D), 95% (D), 50% (D), and 2% (D), of sites was collected and sent to a central location for analysis. Homogeneity index (HI) as a measure of the steepness of target and is a measure of the shape of the dose-volume histogram was calculated for every patient and analyzed.

Results: In general, ICRU recommendations for naming the target, reporting dose prescription, and achieving desired levels of dose to target were relatively poor. The nomenclature for the target in the dose prescription had large variations, having every permutation of name and number contrary to ICRU recommendations. There was statistically significant variability in D D, and HI among institutions, tumor site, and technique with P values < .01. Nearly 95% of patients had D higher than 100% (103.5 ± 6.9) of prescribed dose and varied among institutions. On the other hand, D was close to 100% (97.1 ± 9.4) of prescribed dose. Liver and lung sites had a higher D compared with other sites. Pelvic sites had a lower variability indicated by HI (0.13 ± 1.21). Variability in D is 101.2 ± 8.5, 103.4 ± 6.8, 103.4 ± 8.2, and 109.5 ± 11.5 for IMRT, tomotherapy, volume modulated arc therapy, and stereotactic body radiation therapy with IMRT, respectively.

Conclusions: Nearly 95% of patient treatments deviated from the ICRU-83 recommended D prescription dose delivery. This variability is significant (P < .01) in terms of treatment site, technique, and institution. To reduce dosimetric and associated radiation outcome variability, dose prescription in every clinical trial should be unified with international guidelines.
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http://dx.doi.org/10.1016/j.prro.2016.11.003DOI Listing
March 2017

Improving treatment plan evaluation with automation.

J Appl Clin Med Phys 2016 11 8;17(6):16-31. Epub 2016 Nov 8.

University of Michigan.

The goal of this work is to evaluate the effectiveness of Plan-Checker Tool (PCT) which was created to improve first-time plan quality, reduce patient delays, increase the efficiency of our electronic workflow, and standardize and automate the phys-ics plan review in the treatment planning system (TPS). PCT uses an application programming interface to check and compare data from the TPS and treatment management system (TMS). PCT includes a comprehensive checklist of automated and manual checks that are documented when performed by the user as part of a plan readiness check for treatment. Prior to and during PCT development, errors identified during the physics review and causes of patient treatment start delays were tracked to prioritize which checks should be automated. Nineteen of 33checklist items were automated, with data extracted with PCT. There was a 60% reduction in the number of patient delays in the six months after PCT release. PCT was suc-cessfully implemented for use on all external beam treatment plans in our clinic. While the number of errors found during the physics check did not decrease, automation of checks increased visibility of errors during the physics check, which led to decreased patient delays. The methods used here can be applied to any TMS and TPS that allows queries of the database.
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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5378447PMC
http://dx.doi.org/10.1120/jacmp.v17i6.6322DOI Listing
November 2016

Revisiting fetal dose during radiation therapy: evaluating treatment techniques and a custom shield.

J Appl Clin Med Phys 2016 09 8;17(5):34-46. Epub 2016 Sep 8.

University of Michigan.

To create a comprehensive dataset of peripheral dose (PD) measurements from a new generation of linear accelerators with and without the presence of a newly designed fetal shield, PD measurements were performed to evaluate the effects of depth, field size, distance from the field edge, collimator angle, and beam modi-fiers for common treatment protocols and modalities. A custom fetal lead shield was designed and made for our department that allows external beam treatments from multiple angles while minimizing the need to adjust the shield during patient treatments. PD measurements were acquired for a comprehensive series of static fields on a stack of Solid Water. Additionally, PDs from various clinically relevant treatment scenarios for pregnant patients were measured using an anthropomorphic phantom that was abutted to a stack of Solid Water. As expected, the PD decreased as the distance from the field edge increased and the field size decreased. On aver-age, a PD reduction was observed when a 90° collimator rotation was applied and/or when the tertiary MLCs and jaws defined the field aperture. However, the effect of the collimator rotation (90° versus 0°) in PD reduction was not found to be clini-cally significant when the tertiary MLCs were used to define the field aperture. In the presence of both the MLCs and the fetal shield, the PD was reduced by 58% at a distance of 10 cm from the field edge. The newly designed fetal shield may effectively reduce fetal dose and is relatively easy to setup. Due to its design, we are able to use a broad range of treatment techniques and beam angles. We believe the acquired comprehensive PD dataset collected with and without the fetal shield will be useful for treatment teams to estimate fetal dose and help guide decisions on treat-ment techniques without the need to perform pretreatment phantom measurements.
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http://dx.doi.org/10.1120/jacmp.v17i5.6135DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5874082PMC
September 2016

Methods for Reducing Normal Tissue Complication Probabilities in Oropharyngeal Cancer: Dose Reduction or Planning Target Volume Elimination.

Int J Radiat Oncol Biol Phys 2016 11;96(3):645-52

Department of Radiation Oncology, University of Michigan, Ann Arbor, Michigan. Electronic address:

Purpose: Strategies to reduce the toxicities of head and neck radiation (ie, dysphagia [difficulty swallowing] and xerostomia [dry mouth]) are currently underway. However, the predicted benefit of dose and planning target volume (PTV) reduction strategies is unknown. The purpose of the present study was to compare the normal tissue complication probabilities (NTCP) for swallowing and salivary structures in standard plans (70 Gy [P70]), dose-reduced plans (60 Gy [P60]), and plans eliminating the PTV margin.

Methods And Materials: A total of 38 oropharyngeal cancer (OPC) plans were analyzed. Standard organ-sparing volumetric modulated arc therapy plans (P70) were created and then modified by eliminating the PTVs and treating the clinical tumor volumes (CTVs) only (C70) or maintaining the PTV but reducing the dose to 60 Gy (P60). NTCP dose models for the pharyngeal constrictors, glottis/supraglottic larynx, parotid glands (PGs), and submandibular glands (SMGs) were analyzed. The minimal clinically important benefit was defined as a mean change in NTCP of >5%. The P70 NTCP thresholds and overlap percentages of the organs at risk with the PTVs (56-59 Gy, vPTV56) were evaluated to identify the predictors for NTCP improvement.

Results: With the P60 plans, only the ipsilateral PG (iPG) benefited (23.9% vs 16.2%; P<.01). With the C70 plans, only the iPG (23.9% vs 17.5%; P<.01) and contralateral SMG (cSMG) (NTCP 32.1% vs 22.9%; P<.01) benefited. An iPG NTCP threshold of 20% and 30% predicted NTCP benefits for the P60 and C70 plans, respectively (P<.001). A cSMG NTCP threshold of 30% predicted for an NTCP benefit with the C70 plans (P<.001). Furthermore, for the iPG, a vPTV56 >13% predicted benefit with P60 (P<.001) and C70 (P=.002). For the cSMG, a vPTV56 >22% predicted benefit with C70 (P<.01).

Conclusions: PTV elimination and dose-reduction lowered the NTCP of the iPG, and PTV elimination lowered the NTCP of the cSMG. NTCP thresholds and the percentage of overlap of the PTV with organs at risk can predict which patients will benefit and inform future clinical trial design.
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http://dx.doi.org/10.1016/j.ijrobp.2016.06.2456DOI Listing
November 2016

Failure mode and effects analysis in a dual-product microsphere brachytherapy environment.

Pract Radiat Oncol 2016 Nov - Dec;6(6):e299-e306. Epub 2016 Mar 16.

Department of Radiation Oncology, University of Michigan Hospitals, Ann Arbor, Michigan.

Purpose: We performed a failure mode and effects analysis (FMEA) during the addition of a new microspheres product into our existing microsphere brachytherapy program to identify areas for safety improvements.

Methods And Materials: A diverse group of team members from the microsphere program participated in the project to create a process map, identify and score failure modes, and discuss programmatic changes to address the highest ranking items. We developed custom severity ranking scales for staff- and institution-related failure modes to encompass possible risks that may exist outside of patient-based effects.

Results: Between both types of microsphere products, 173 failure mode/effect pairs were identified: 90 for patients, 35 for staff, and 48 for the institution. The SIR-Spheres program was ranked separately from the TheraSphere program because of significant differences in workflow during dose calculation, preparation, and delivery. High-ranking failure modes in each category were addressed with programmatic changes.

Conclusions: The FMEA aided in identifying potential risk factors in our microsphere program and allowed a theoretically safer and more efficient design of the workflow and quality assurance for both our new SIR-Spheres program and our existing TheraSphere program. As new guidelines are made available, and our experience with the SIR-Spheres program increases, we will update the FMEA as an efficient starting point for future improvements.
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http://dx.doi.org/10.1016/j.prro.2016.03.003DOI Listing
March 2017

SafetyNet: Streamlining and Automating QA in radiotherapy.

J Appl Clin Med Phys 2016 01 8;17(1):387-395. Epub 2016 Jan 8.

University of Michigan.

Proper quality assurance (QA) of the radiotherapy process can be time-consuming and expensive. Many QA efforts, such as data export and import, are inefficient when done by humans. Additionally, humans can be unreliable, lose attention, and fail to complete critical steps that are required for smooth operations. In our group we have sought to break down the QA tasks into separate steps and to automate those steps that are better done by software running autonomously or at the instigation of a human. A team of medical physicists and software engineers worked together to identify opportunities to streamline and automate QA. Development efforts follow a formal cycle of writing software requirements, developing software, testing and commissioning. The clinical release process is separated into clinical evaluation testing, training, and finally clinical release. We have improved six processes related to QA and safety. Steps that were previously performed by humans have been automated or streamlined to increase first-time quality, reduce time spent by humans doing low-level tasks, and expedite QA tests. Much of the gains were had by automating data transfer, implementing computer-based checking and automation of systems with an event-driven framework. These coordinated efforts by software engineers and clinical physicists have resulted in speed improvements in expediting patient-sensitive QA tests.
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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5345488PMC
http://dx.doi.org/10.1120/jacmp.v17i1.5920DOI Listing
January 2016

Development of a brachytherapy audit checklist tool.

Brachytherapy 2015 Nov-Dec;14(6):963-9. Epub 2015 Oct 2.

Department of Radiation Oncology, University of Michigan, Ann Arbor, MI; Department of Radiation Oncology, Veterans Affairs Ann Arbor Healthcare System, Ann Arbor, MI.

Purpose: To develop a brachytherapy audit checklist that could be used to prepare for Nuclear Regulatory Commission or agreement state inspections, to aid in readiness for a practice accreditation visit, or to be used as an annual internal audit tool.

Methods And Materials: Six board-certified medical physicists and one radiation oncologist conducted a thorough review of brachytherapy-related literature and practice guidelines published by professional organizations and federal regulations. The team members worked at two facilities that are part of a large, academic health care center. Checklist items were given a score based on their judged importance. Four clinical sites performed an audit of their program using the checklist. The sites were asked to score each item based on a defined severity scale for their noncompliance, and final audit scores were tallied by summing the products of importance score and severity score for each item.

Results: The final audit checklist, which is available online, contains 83 items. The audit scores from the beta sites ranged from 17 to 71 (out of 690) and identified a total of 7-16 noncompliance items. The total time to conduct the audit ranged from 1.5 to 5 hours.

Conclusions: A comprehensive audit checklist was developed which can be implemented by any facility that wishes to perform a program audit in support of their own brachytherapy program. The checklist is designed to allow users to identify areas of noncompliance and to prioritize how these items are addressed to minimize deviations from nationally-recognized standards.
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http://dx.doi.org/10.1016/j.brachy.2015.08.001DOI Listing
July 2016

Reconstruction of organ dose for external radiotherapy patients in retrospective epidemiologic studies.

Phys Med Biol 2015 Mar 26;60(6):2309-24. Epub 2015 Feb 26.

Department of Radiation Oncology, University of Michigan, Ann Arbor, MI 48109, USA.

Organ dose estimation for retrospective epidemiological studies of late effects in radiotherapy patients involves two challenges: radiological images to represent patient anatomy are not usually available for patient cohorts who were treated years ago, and efficient dose reconstruction methods for large-scale patient cohorts are not well established. In the current study, we developed methods to reconstruct organ doses for radiotherapy patients by using a series of computational human phantoms coupled with a commercial treatment planning system (TPS) and a radiotherapy-dedicated Monte Carlo transport code, and performed illustrative dose calculations. First, we developed methods to convert the anatomy and organ contours of the pediatric and adult hybrid computational phantom series to Digital Imaging and Communications in Medicine (DICOM)-image and DICOM-structure files, respectively. The resulting DICOM files were imported to a commercial TPS for simulating radiotherapy and dose calculation for in-field organs. The conversion process was validated by comparing electron densities relative to water and organ volumes between the hybrid phantoms and the DICOM files imported in TPS, which showed agreements within 0.1 and 2%, respectively. Second, we developed a procedure to transfer DICOM-RT files generated from the TPS directly to a Monte Carlo transport code, x-ray Voxel Monte Carlo (XVMC) for more accurate dose calculations. Third, to illustrate the performance of the established methods, we simulated a whole brain treatment for the 10 year-old male phantom and a prostate treatment for the adult male phantom. Radiation doses to selected organs were calculated using the TPS and XVMC, and compared to each other. Organ average doses from the two methods matched within 7%, whereas maximum and minimum point doses differed up to 45%. The dosimetry methods and procedures established in this study will be useful for the reconstruction of organ dose to support retrospective epidemiological studies of late effects in radiotherapy patients.
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http://dx.doi.org/10.1088/0031-9155/60/6/2309DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4422070PMC
March 2015

Regression rate of posterior uveal melanomas following iodine-125 plaque radiotherapy.

Middle East Afr J Ophthalmol 2015 Jan-Mar;22(1):103-7

Department of Ophthalmology and Visual Sciences, W.K. Kellogg Eye Center, Michigan, USA ; Department of Epidemiology, School of Public Health, Michigan, USA.

Aim: To characterize the regression rate of posterior uveal melanoma following radioactive iodine-125 (I-125) plaque.

Materials And Methods: We retrospectively analyzed 95 patients with posterior uveal melanoma who were treated with only radioactive I-125 plaque and had more than 3 years follow-up. All patients were treated with plaque radiotherapy using tumor dose of 85 Gy at the tumor apex, following COMS protocol. Regression rate was assessed with standardized A-scan ultrasonography. Associations with tumor regression were evaluated by means of mixed linear regression modeling.

Results: Mean decrease in the tumor thickness (% original thickness) at 12, 24, and 36 months after radiotherapy for melanomas < 3 mm in thickness was 29%, 38%, and 45%, for melanoma 3-8 mm in thickness was 32%, 44%, and 59%, and for melanoma more than 8 mm in thickness was 52%, 62%, and 68%, respectively. With a doubling of follow-up time (0.5-1 year, or 1-2 years of follow-up from treatment), tumors < 3 mm in thickness at treatment showed a 0.5 mm decrease in tumor thickness, whereas melanomas 3-8 mm showed a 1 mm decrease, and melanomas >8 mm showed a 1.7 mm decrease. Uveal melanomas that developed systemic metastasis showed an additional 0.4 mm decrease with a doubling of follow-up time from treatment, compared with those that did not develop metastasis (P = 0.050).

Conclusions: Posterior uveal melanomas with higher initial thickness show steeper and more reduction in tumor thickness following radioactive I-125 plaque. After the initial phases, the regression curve became similar for tumors with different thicknesses.
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http://dx.doi.org/10.4103/0974-9233.148358DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4302463PMC
April 2015
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