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TU-D-209-01: Dosimetry of Diagnostic Work Up Mammography

Purpose: To investigate patient average glandular dose (AGD) characteristics of diagnostic mammography. Methods: The techniques used to image 14420 patients who received diagnostic work up mammography from October 2008 to December 2014 at one academic hospital were retrospectively collected. The most common diagnostic views and the techniques used for each according to compressed breast thickness were determined. For all techniques, 1st half value layer and air kerma output per tube current-exposure time product were measured; then the incident air kerma for each acquisition was calculated. The values for normalized glandular dose (DgN) were obtained with a validated Monte Carlo simulation of mammographic acquisition. The mono-energetic DgN results were combined according to relative fluence using the TASMICS model to obtain DgN coefficients for each spectrum. The spectral DgN and calculated incident air kerma were used to estimate AGD of patients with breast thickness ranging from 2 to 8 cm. Results: The most common views utilized during diagnostic mammography were magnification craniocaudal (24%), magnification mediolateral (19%), spot craniocaudal (28%), and spot mediolateral oblique (24%). The AGD increased with increasing breast thickness for both the magnification and spot views. The AGD for a 5.5 cm thick breast was approximately 6.8 mGy and 2.2 mGy for the magnification and spot views, respectively. The AGD ranged from 3.6 mGy to 6.8 mGy for the magnification views and from 1.0 mGy to 3.1 mGy for spot views. The difference in AGD between the two magnification views or the two spot views was not significant. Conclusion: These results provide information on breast dose to which screening recalled women are exposed to. In addition to understanding the dose used for common clinical imaging tests, this data could be used when comparing use of mammography for diagnostic workup to other potential modalities, such as breast tomosynthesis and breast CT.

60 APPLIED LIFE SCIENCES↗

TU-FG-201-10: Quality Management of Accelerated Partial Breast Irradiation (APBI) Plans

Purpose: Since 2008, over 700 patients received high dose rate (HDR) APBI treatment at Virginia Hospital Center. The complexity involved in the planning process demonstrated a broad variation between patient geometry across all applicators, in relation to anatomical regions of interest. A quality management program instituting various metrics was implemented in March 2013 with the goal of ensuring an optimal plan is achieved for each patient. Methods: For each plan, an in-house complexity index, geometric conformity index, and plan quality index were defined. These indices were obtained for all patients treated. For patients treated after the implementation, the conformity index and quality index were maximized while other dosimetric limits, such as maximum skin and rib doses, were strictly kept. Subsequently, all evaluation parameters and applicator information were placed in a database for cross-evaluation with similar complexity. Results: Both the conformity and quality indices show good correlation with the complexity index. They decrease as complexity increases for all applicators. Multi lumen type balloon applicators demonstrate a minimal advantage over single lumen applicators in increasingly complex patient geometries, as compared to SAVI applicators which showed considerably greater advantage in these circumstances. After the implementation of the in-house planning protocol, there is a direct improvement of quality for SAVI plans. Conclusion: Due to their interstitial nature, SAVI devices show a better conformity in comparison to balloon-based devices regardless of the number of lumens, especially in complex cases. The quality management program focuses on optimizing indices by utilizing prior planning knowledge based on complexity levels. The database of indices assists in decision making and has subsequently aided in balancing the experience level among planners. This approach has made APBI planning more robust for patient care, with a measurable improvement in the plan quality.

60 APPLIED LIFE SCIENCES↗

TU-FG-201-12: Designing a Risk-Based Quality Assurance Program for a Newly Implemented Y-90 Microspheres Procedure

Purpose: To create a quality assurance program based upon a risk-based assessment of a newly implemented SirSpheres Y-90 procedure. Methods: A process map was created for a newly implemented SirSpheres procedure at a community hospital. The process map documented each step of this collaborative procedure, as well as the roles and responsibilities of each member. From the process map, different potential failure modes were determined as well as any current controls in place. From this list, a full failure mode and effects analysis (FMEA) was performed by grading each failure mode’s likelihood of occurrence, likelihood of detection, and potential severity. These numbers were then multiplied to compute the risk priority number (RPN) for each potential failure mode. Failure modes were then ranked based on their RPN. Additional controls were then added, with failure modes corresponding to the highest RPNs taking priority. Results: A process map was created that succinctly outlined each step in the SirSpheres procedure in its current implementation. From this, 72 potential failure modes were identified and ranked according to their associated RPN. Quality assurance controls and safety barriers were then added for failure modes associated with the highest risk being addressed first. Conclusion: A quality assurance program was created from a risk-based assessment of the SirSpheres process. Process mapping and FMEA were effective in identifying potential high-risk failure modes for this new procedure, which were prioritized for new quality assurance controls. TG 100 recommends the fault tree analysis methodology to design a comprehensive and effective QC/QM program, yet we found that by simply introducing additional safety barriers to address high RPN failure modes makes the whole process simpler and safer.

60 APPLIED LIFE SCIENCES↗

TU-FG-BRB-06: A Prompt Gamma-Ray Spectroscopy System for Clinical Studies of in Vivo Proton Range Verification

Purpose: We present a new system to perform prompt gamma-ray spectroscopy during proton pencil-beam scanning treatments, which enables in vivo verification of the proton range. This system will be used for the first clinical studies of this technology. Methods: After successful pre-clinical testing of prompt gamma-ray spectroscopy, a full scale system for clinical studies is now being assembled. Prompt gamma-rays will be detected during patient treatment using an array of 8 detector modules arranged behind a tungsten collimator. Each detector module consists of a lanthanum(III) bromide scintillator, a photomultiplier tube, and custom electronics for stable high voltage supply and signal amplification. A new real-time data acquisition and control system samples the signals from the detectors with analog-to-digital converters, analyses events of interest, and communicates with the beam delivery systems. The timing of the detected events was synchronized to the cyclotron radiofrequency and the pencil-beam delivery. Range verification is performed by matching measured energy- and timeresolved gamma-ray spectra to nuclear reaction models based on the clinical treatment plan. Experiments in phantoms were performed using clinical beams in order to assess the performance of the systems. Results: The experiments showed reliable real-time analysis of more than 10 million detector events per second. The individual detector modules acquired accurate energy- and time-resolved gamma-ray measurements at a rate of 1 million events per second, which is typical for beams delivered with a clinical dose rate. The data acquisition system successfully tracked the delivery of the scanned pencil-beams to determine the location of range deviations within the treatment field. Conclusion: A clinical system for proton range verification using prompt gamma-ray spectroscopy has been designed and is being prepared for use during patient treatments. We anticipate to start a first clinical study in the near future. This work was supported by the Federal Share of program income earned by Massachusetts; General Hospital on C06-CA059267, Proton Therapy Research and Treatment Center.

60 APPLIED LIFE SCIENCES↗

TU-E-TOUR-I-00: Exhibit Hall Guided Tours-Dosimters for QC in Diagnostic Imaging (Tuesday)

Tour Leader: Xia Jiang, Ohio State University, Columbus, OH Tour Guides: Xia Jiang, Ohio State University, Columbus, OH Kevin Little, The University of Chicago, Chicago, IL Christina Sammet, Lurie Children’s Hospital of Chicago, Chicago, IL Participating Vendors: IBA PTW - New York Radcal Corporation RTI Electronics, Inc. Exhibit Hall Guided Tours is a new program launching this year at the Annual Meeting. The Guided Tours are designed to enhance the interaction between meeting attendees and exhibitors. This year’s Imaging Guided Tours are organized around the theme of dosimeters for quality control in diagnostic imaging. Tours will begin with an introduction and background given by Dr. Xia Jiang, the Tour Leader. The introduction will cover the types and properties of different radiation dosimeters used for quality assurance in clinical radiology. Attendees will then break into smaller groups, each lead by an AAPM-member Tour Guide. The tour groups will visit the exhibit booths of vendors who provide appropriate dosimeters, and a vendor representative will give a presentation to the group about their particular product(s). The vendor representatives as well as the Tour Guides will be available to answer questions. Outline: Types and properties of radiation detectors and dosimeters Ionization chamber dosimeters Solid state dosimeters Dosimeter calibration: Primary and secondary standards dosimetry laboratories Instruments for measuring tube voltage and exposure time Vendor presentations will likely cover features and innovations of different dosimeter systems, as well as their practical use. Learning Objectives: Understand the types and properties of different instrumentations used for quality control in diagnostic imaging. Understand the process of dosimeter calibration. Gain familiarity with the latest commercial dosimeter systems from different vendors.

61 RADIATION PROTECTION AND DOSIMETRY↗

WE-A-201-00: Anne and Donald Herbert Distinguished Lectureship On Modern Statistical Modeling

Chris Marshall: Memorial Introduction Donald Edmonds Herbert Jr., or Don to his colleagues and friends, exemplified the “big tent” vision of medical physics, specializing in Applied Statistics and Dynamical Systems theory. He saw, more clearly than most, that “Making models is the difference between doing science and just fooling around [ref Woodworth, 2004]”. Don developed an interest in chemistry at school by “reading a book” - a recurring theme in his story. He was awarded a Westinghouse Science scholarship and attended the Carnegie Institute of Technology (later Carnegie Mellon University) where his interest turned to physics and led to a BS in Physics after transfer to Northwestern University. After (voluntary) service in the Navy he earned his MS in Physics from the University of Oklahoma, which led him to Johns Hopkins University in Baltimore to pursue a PhD. The early death of his wife led him to take a salaried position in the Physics Department of Colorado College in Colorado Springs so as to better care for their young daughter. There, a chance invitation from Dr. Juan del Regato to teach physics to residents at the Penrose Cancer Hospital introduced him to Medical Physics, and he decided to enter the field. He received his PhD from the University of London (UK) under Prof. Joseph Rotblat, where I first met him, and where he taught himself statistics. He returned to Penrose as a clinical medical physicist, also largely self-taught. In 1975 he formalized an evolving interest in statistical analysis as Professor of Radiology and Head of the Division of Physics and Statistics at the College of Medicine of the University of South Alabama in Mobile, AL where he remained for the rest of his career. He also served as the first Director of their Bio-Statistics and Epidemiology Core Unit working in part on a sickle-cell disease. After retirement he remained active as Professor Emeritus. Don served for several years as a consultant to the Nuclear Regulatory Commission and may be remembered for his critique of the National Academy of Sciences BEIR III report (stating that their methodology “imposes a Delphic quality to the .. risk estimates”.) This led to his appointment as a member of the BEIR V committee. Don presented refresher courses at the AAPM, ASTRO and RSNA meetings and was active in the AAPM as a member or chair of several committees. He was the principal author of AAPM Report 43, which is essentially a critique of established clinical studies prior to 1992. He was co-editor of the Proceedings of many symposia on Time, Dose and Fractionation held in Madison, Wisconsin. He received the AAPM lifetime Achievement award in 2004. Don’s second wife of 46 years, Ann, predeceased him and he is survived by daughters Hillary and Emily, son John and two grandsons. Don was a true gentleman with a unique and erudite writing style illuminated by pithy quotations. If he had a fault it was, perhaps, that he did not realize how much smarter he was than the rest of us. This presentation draws heavily on a biography and video interview in the History and Heritage section of the AAPM website. The quote is his own. Andrzej Niemierko: Statistical modeling plays an essential role in modern medicine for quantitative evaluation of the effect of treatment. This session will feature an overview of statistical modeling techniques used for analyzing the many types of research data and an exploration of recent advances in new statistical modeling methodologies. Learning Objectives: To learn basics of statistical modeling methodology. To discuss statistical models that are frequently used in radiation oncology To discuss advanced modern statistical modeling methods and applications.

60 APPLIED LIFE SCIENCES↗

WE-A-201-01: Memorial Introduction

Chris Marshall: Memorial Introduction Donald Edmonds Herbert Jr., or Don to his colleagues and friends, exemplified the “big tent” vision of medical physics, specializing in Applied Statistics and Dynamical Systems theory. He saw, more clearly than most, that “Making models is the difference between doing science and just fooling around [ref Woodworth, 2004]”. Don developed an interest in chemistry at school by “reading a book” - a recurring theme in his story. He was awarded a Westinghouse Science scholarship and attended the Carnegie Institute of Technology (later Carnegie Mellon University) where his interest turned to physics and led to a BS in Physics after transfer to Northwestern University. After (voluntary) service in the Navy he earned his MS in Physics from the University of Oklahoma, which led him to Johns Hopkins University in Baltimore to pursue a PhD. The early death of his wife led him to take a salaried position in the Physics Department of Colorado College in Colorado Springs so as to better care for their young daughter. There, a chance invitation from Dr. Juan del Regato to teach physics to residents at the Penrose Cancer Hospital introduced him to Medical Physics, and he decided to enter the field. He received his PhD from the University of London (UK) under Prof. Joseph Rotblat, where I first met him, and where he taught himself statistics. He returned to Penrose as a clinical medical physicist, also largely self-taught. In 1975 he formalized an evolving interest in statistical analysis as Professor of Radiology and Head of the Division of Physics and Statistics at the College of Medicine of the University of South Alabama in Mobile, AL where he remained for the rest of his career. He also served as the first Director of their Bio-Statistics and Epidemiology Core Unit working in part on a sickle-cell disease. After retirement he remained active as Professor Emeritus. Don served for several years as a consultant to the Nuclear Regulatory Commission and may be remembered for his critique of the National Academy of Sciences BEIR III report (stating that their methodology “imposes a Delphic quality to the .. risk estimates”.) This led to his appointment as a member of the BEIR V committee. Don presented refresher courses at the AAPM, ASTRO and RSNA meetings and was active in the AAPM as a member or chair of several committees. He was the principal author of AAPM Report 43, which is essentially a critique of established clinical studies prior to 1992. He was co-editor of the Proceedings of many symposia on Time, Dose and Fractionation held in Madison, Wisconsin. He received the AAPM lifetime Achievement award in 2004. Don’s second wife of 46 years, Ann, predeceased him and he is survived by daughters Hillary and Emily, son John and two grandsons. Don was a true gentleman with a unique and erudite writing style illuminated by pithy quotations. If he had a fault it was, perhaps, that he did not realize how much smarter he was than the rest of us. This presentation draws heavily on a biography and video interview in the History and Heritage section of the AAPM website. The quote is his own. Andrzej Niemierko: Statistical modeling plays an essential role in modern medicine for quantitative evaluation of the effect of treatment. This session will feature an overview of statistical modeling techniques used for analyzing the many types of research data and an exploration of recent advances in new statistical modeling methodologies. Learning Objectives: To learn basics of statistical modeling methodology. To discuss statistical models that are frequently used in radiation oncology To discuss advanced modern statistical modeling methods and applications.

60 APPLIED LIFE SCIENCES↗

WE-A-201-02: Modern Statistical Modeling

Chris Marshall: Memorial Introduction Donald Edmonds Herbert Jr., or Don to his colleagues and friends, exemplified the “big tent” vision of medical physics, specializing in Applied Statistics and Dynamical Systems theory. He saw, more clearly than most, that “Making models is the difference between doing science and just fooling around [ref Woodworth, 2004]”. Don developed an interest in chemistry at school by “reading a book” - a recurring theme in his story. He was awarded a Westinghouse Science scholarship and attended the Carnegie Institute of Technology (later Carnegie Mellon University) where his interest turned to physics and led to a BS in Physics after transfer to Northwestern University. After (voluntary) service in the Navy he earned his MS in Physics from the University of Oklahoma, which led him to Johns Hopkins University in Baltimore to pursue a PhD. The early death of his wife led him to take a salaried position in the Physics Department of Colorado College in Colorado Springs so as to better care for their young daughter. There, a chance invitation from Dr. Juan del Regato to teach physics to residents at the Penrose Cancer Hospital introduced him to Medical Physics, and he decided to enter the field. He received his PhD from the University of London (UK) under Prof. Joseph Rotblat, where I first met him, and where he taught himself statistics. He returned to Penrose as a clinical medical physicist, also largely self-taught. In 1975 he formalized an evolving interest in statistical analysis as Professor of Radiology and Head of the Division of Physics and Statistics at the College of Medicine of the University of South Alabama in Mobile, AL where he remained for the rest of his career. He also served as the first Director of their Bio-Statistics and Epidemiology Core Unit working in part on a sickle-cell disease. After retirement he remained active as Professor Emeritus. Don served for several years as a consultant to the Nuclear Regulatory Commission and may be remembered for his critique of the National Academy of Sciences BEIR III report (stating that their methodology “imposes a Delphic quality to the .. risk estimates”.) This led to his appointment as a member of the BEIR V committee. Don presented refresher courses at the AAPM, ASTRO and RSNA meetings and was active in the AAPM as a member or chair of several committees. He was the principal author of AAPM Report 43, which is essentially a critique of established clinical studies prior to 1992. He was co-editor of the Proceedings of many symposia on Time, Dose and Fractionation held in Madison, Wisconsin. He received the AAPM lifetime Achievement award in 2004. Don’s second wife of 46 years, Ann, predeceased him and he is survived by daughters Hillary and Emily, son John and two grandsons. Don was a true gentleman with a unique and erudite writing style illuminated by pithy quotations. If he had a fault it was, perhaps, that he did not realize how much smarter he was than the rest of us. This presentation draws heavily on a biography and video interview in the History and Heritage section of the AAPM website. The quote is his own. Andrzej Niemierko: Statistical modeling plays an essential role in modern medicine for quantitative evaluation of the effect of treatment. This session will feature an overview of statistical modeling techniques used for analyzing the many types of research data and an exploration of recent advances in new statistical modeling methodologies. Learning Objectives: To learn basics of statistical modeling methodology. To discuss statistical models that are frequently used in radiation oncology To discuss advanced modern statistical modeling methods and applications.

60 APPLIED LIFE SCIENCES↗

WE-FG-BRB-02: Spatial Mapping of the RBE of Scanned Particle Beams

The physical pattern of energy deposition and the enhanced relative biological effectiveness (RBE) of protons and carbon ions compared to photons offer unique and not fully understood or exploited opportunities to improve the efficacy of radiation therapy. Variations in RBE within a pristine or spread out Bragg peak and between particle types may be exploited to enhance cell killing in target regions without a corresponding increase in damage to normal tissue structures. In addition, the decreased sensitivity of hypoxic tumors to photon-based therapies may be partially overcome through the use of more densely ionizing radiations. These and other differences between particle and photon beams may be used to generate biologically optimized treatments that reduce normal tissue complications. In this symposium, speakers will examine the impact of the RBE of charged particles on measurable biological endpoints, treatment plan optimization, and the prediction or retrospective assessment of treatment outcomes. In particular, an AAPM task group was formed to critically examine the evidence for a spatially-variant RBE in proton therapy. Current knowledge of proton RBE variation with respect to dose, biological endpoint, and physics parameters will be reviewed. Further, the clinical relevance of these variations will be discussed. Recent work focused on improving simulations of radiation physics and biological response in proton and carbon ion therapy will also be presented. Finally, relevant biology research and areas of research needs will be highlighted, including the dependence of RBE on genetic factors including status of DNA repair pathways, the sensitivity of cancer stem-like cells to charged particles, the role of charged particles in hypoxic tumors, and the importance of fractionation effects. In addition to the physical advantages of protons and more massive ions over photons, the future application of biologically optimized treatment plans and their potential to provide higher levels of local tumor control and improved normal tissue sparing will be discussed. Learning Objectives: To assess whether the current practice of a constant RBE of 1.1 should be revised or maintained in proton therapy and to evaluate the potential clinical consequences of delivering RBE-weighted dose distributions based on variable RBE To review current research on biological models used to predict the increased biological effectiveness of proton and carbon ions to help move towards a practical understanding and implementation of biological optimization in particle therapy To discuss potential differences in biological mechanisms between photons and charged particles (light and heavy ions) that could impact clinical cancer therapy H. Paganetti, NCI U19 CA21239D. Grosshans, Our research is supported by the NCIK. Held, Funding Support: National Cancer Institute of the National Institutes of Health, USA, under Award Number R21CA182259 and Federal Share of Program Income Earned by Massachusetts General Hospital on C06CA059267, Proton Therapy Research and Treatment Center.

60 APPLIED LIFE SCIENCES↗

WE-FG-BRB-03: Challenges and Opportunities for Implementing Biological Optimization in Particle Therapy

The physical pattern of energy deposition and the enhanced relative biological effectiveness (RBE) of protons and carbon ions compared to photons offer unique and not fully understood or exploited opportunities to improve the efficacy of radiation therapy. Variations in RBE within a pristine or spread out Bragg peak and between particle types may be exploited to enhance cell killing in target regions without a corresponding increase in damage to normal tissue structures. In addition, the decreased sensitivity of hypoxic tumors to photon-based therapies may be partially overcome through the use of more densely ionizing radiations. These and other differences between particle and photon beams may be used to generate biologically optimized treatments that reduce normal tissue complications. In this symposium, speakers will examine the impact of the RBE of charged particles on measurable biological endpoints, treatment plan optimization, and the prediction or retrospective assessment of treatment outcomes. In particular, an AAPM task group was formed to critically examine the evidence for a spatially-variant RBE in proton therapy. Current knowledge of proton RBE variation with respect to dose, biological endpoint, and physics parameters will be reviewed. Further, the clinical relevance of these variations will be discussed. Recent work focused on improving simulations of radiation physics and biological response in proton and carbon ion therapy will also be presented. Finally, relevant biology research and areas of research needs will be highlighted, including the dependence of RBE on genetic factors including status of DNA repair pathways, the sensitivity of cancer stem-like cells to charged particles, the role of charged particles in hypoxic tumors, and the importance of fractionation effects. In addition to the physical advantages of protons and more massive ions over photons, the future application of biologically optimized treatment plans and their potential to provide higher levels of local tumor control and improved normal tissue sparing will be discussed. Learning Objectives: To assess whether the current practice of a constant RBE of 1.1 should be revised or maintained in proton therapy and to evaluate the potential clinical consequences of delivering RBE-weighted dose distributions based on variable RBE To review current research on biological models used to predict the increased biological effectiveness of proton and carbon ions to help move towards a practical understanding and implementation of biological optimization in particle therapy To discuss potential differences in biological mechanisms between photons and charged particles (light and heavy ions) that could impact clinical cancer therapy H. Paganetti, NCI U19 CA21239D. Grosshans, Our research is supported by the NCIK. Held, Funding Support: National Cancer Institute of the National Institutes of Health, USA, under Award Number R21CA182259 and Federal Share of Program Income Earned by Massachusetts General Hospital on C06CA059267, Proton Therapy Research and Treatment Center.

60 APPLIED LIFE SCIENCES↗

WE-FG-BRB-04: RBEs for Human Lung Cancer Cells Exposed to Protons and Heavier Ions: Implications for Clinical Use of Charged Particles in Cancer Therapy

The physical pattern of energy deposition and the enhanced relative biological effectiveness (RBE) of protons and carbon ions compared to photons offer unique and not fully understood or exploited opportunities to improve the efficacy of radiation therapy. Variations in RBE within a pristine or spread out Bragg peak and between particle types may be exploited to enhance cell killing in target regions without a corresponding increase in damage to normal tissue structures. In addition, the decreased sensitivity of hypoxic tumors to photon-based therapies may be partially overcome through the use of more densely ionizing radiations. These and other differences between particle and photon beams may be used to generate biologically optimized treatments that reduce normal tissue complications. In this symposium, speakers will examine the impact of the RBE of charged particles on measurable biological endpoints, treatment plan optimization, and the prediction or retrospective assessment of treatment outcomes. In particular, an AAPM task group was formed to critically examine the evidence for a spatially-variant RBE in proton therapy. Current knowledge of proton RBE variation with respect to dose, biological endpoint, and physics parameters will be reviewed. Further, the clinical relevance of these variations will be discussed. Recent work focused on improving simulations of radiation physics and biological response in proton and carbon ion therapy will also be presented. Finally, relevant biology research and areas of research needs will be highlighted, including the dependence of RBE on genetic factors including status of DNA repair pathways, the sensitivity of cancer stem-like cells to charged particles, the role of charged particles in hypoxic tumors, and the importance of fractionation effects. In addition to the physical advantages of protons and more massive ions over photons, the future application of biologically optimized treatment plans and their potential to provide higher levels of local tumor control and improved normal tissue sparing will be discussed. Learning Objectives: To assess whether the current practice of a constant RBE of 1.1 should be revised or maintained in proton therapy and to evaluate the potential clinical consequences of delivering RBE-weighted dose distributions based on variable RBE To review current research on biological models used to predict the increased biological effectiveness of proton and carbon ions to help move towards a practical understanding and implementation of biological optimization in particle therapy To discuss potential differences in biological mechanisms between photons and charged particles (light and heavy ions) that could impact clinical cancer therapy H. Paganetti, NCI U19 CA21239D. Grosshans, Our research is supported by the NCIK. Held, Funding Support: National Cancer Institute of the National Institutes of Health, USA, under Award Number R21CA182259 and Federal Share of Program Income Earned by Massachusetts General Hospital on C06CA059267, Proton Therapy Research and Treatment Center.

60 APPLIED LIFE SCIENCES↗

WE-FG-BRB-00: The Challenges of Predicting RBE Effects in Particle Therapy and Opportunities for Improving Cancer Therapy

The physical pattern of energy deposition and the enhanced relative biological effectiveness (RBE) of protons and carbon ions compared to photons offer unique and not fully understood or exploited opportunities to improve the efficacy of radiation therapy. Variations in RBE within a pristine or spread out Bragg peak and between particle types may be exploited to enhance cell killing in target regions without a corresponding increase in damage to normal tissue structures. In addition, the decreased sensitivity of hypoxic tumors to photon-based therapies may be partially overcome through the use of more densely ionizing radiations. These and other differences between particle and photon beams may be used to generate biologically optimized treatments that reduce normal tissue complications. In this symposium, speakers will examine the impact of the RBE of charged particles on measurable biological endpoints, treatment plan optimization, and the prediction or retrospective assessment of treatment outcomes. In particular, an AAPM task group was formed to critically examine the evidence for a spatially-variant RBE in proton therapy. Current knowledge of proton RBE variation with respect to dose, biological endpoint, and physics parameters will be reviewed. Further, the clinical relevance of these variations will be discussed. Recent work focused on improving simulations of radiation physics and biological response in proton and carbon ion therapy will also be presented. Finally, relevant biology research and areas of research needs will be highlighted, including the dependence of RBE on genetic factors including status of DNA repair pathways, the sensitivity of cancer stem-like cells to charged particles, the role of charged particles in hypoxic tumors, and the importance of fractionation effects. In addition to the physical advantages of protons and more massive ions over photons, the future application of biologically optimized treatment plans and their potential to provide higher levels of local tumor control and improved normal tissue sparing will be discussed. Learning Objectives: To assess whether the current practice of a constant RBE of 1.1 should be revised or maintained in proton therapy and to evaluate the potential clinical consequences of delivering RBE-weighted dose distributions based on variable RBE To review current research on biological models used to predict the increased biological effectiveness of proton and carbon ions to help move towards a practical understanding and implementation of biological optimization in particle therapy To discuss potential differences in biological mechanisms between photons and charged particles (light and heavy ions) that could impact clinical cancer therapy H. Paganetti, NCI U19 CA21239D. Grosshans, Our research is supported by the NCIK. Held, Funding Support: National Cancer Institute of the National Institutes of Health, USA, under Award Number R21CA182259 and Federal Share of Program Income Earned by Massachusetts General Hospital on C06CA059267, Proton Therapy Research and Treatment Center.

60 APPLIED LIFE SCIENCES↗

WE-FG-BRB-01: Clinical Significance of RBE Variations in Proton Therapy

The physical pattern of energy deposition and the enhanced relative biological effectiveness (RBE) of protons and carbon ions compared to photons offer unique and not fully understood or exploited opportunities to improve the efficacy of radiation therapy. Variations in RBE within a pristine or spread out Bragg peak and between particle types may be exploited to enhance cell killing in target regions without a corresponding increase in damage to normal tissue structures. In addition, the decreased sensitivity of hypoxic tumors to photon-based therapies may be partially overcome through the use of more densely ionizing radiations. These and other differences between particle and photon beams may be used to generate biologically optimized treatments that reduce normal tissue complications. In this symposium, speakers will examine the impact of the RBE of charged particles on measurable biological endpoints, treatment plan optimization, and the prediction or retrospective assessment of treatment outcomes. In particular, an AAPM task group was formed to critically examine the evidence for a spatially-variant RBE in proton therapy. Current knowledge of proton RBE variation with respect to dose, biological endpoint, and physics parameters will be reviewed. Further, the clinical relevance of these variations will be discussed. Recent work focused on improving simulations of radiation physics and biological response in proton and carbon ion therapy will also be presented. Finally, relevant biology research and areas of research needs will be highlighted, including the dependence of RBE on genetic factors including status of DNA repair pathways, the sensitivity of cancer stem-like cells to charged particles, the role of charged particles in hypoxic tumors, and the importance of fractionation effects. In addition to the physical advantages of protons and more massive ions over photons, the future application of biologically optimized treatment plans and their potential to provide higher levels of local tumor control and improved normal tissue sparing will be discussed. Learning Objectives: To assess whether the current practice of a constant RBE of 1.1 should be revised or maintained in proton therapy and to evaluate the potential clinical consequences of delivering RBE-weighted dose distributions based on variable RBE To review current research on biological models used to predict the increased biological effectiveness of proton and carbon ions to help move towards a practical understanding and implementation of biological optimization in particle therapy To discuss potential differences in biological mechanisms between photons and charged particles (light and heavy ions) that could impact clinical cancer therapy H. Paganetti, NCI U19 CA21239D. Grosshans, Our research is supported by the NCIK. Held, Funding Support: National Cancer Institute of the National Institutes of Health, USA, under Award Number R21CA182259 and Federal Share of Program Income Earned by Massachusetts General Hospital on C06CA059267, Proton Therapy Research and Treatment Center.

60 APPLIED LIFE SCIENCES↗

TH-AB-BRA-12: Experimental Results From the First High-Field Inline MRI-Linac

Purpose: The pursuit of real-time image guided radiotherapy using optimal tissue contrast has seen the development of several hybrid MRI-treatment systems, high field and low field, and inline and perpendicular configurations. As part of a new MRI-Linac program, an MRI scanner was integrated with a linear accelerator to enable investigations of a coupled inline MRI-Linac system. This work describes our experimental results from the first high-field inline MRI-Linac. Methods: A 1.5 Tesla magnet (Sonata, Siemens) was located in a purpose built RF cage enabling shielding from and close proximity to a linear accelerator with inline orientation. A portable linear accelerator (Linatron, Varian) was installed together with a multi-leaf collimator (Millennium, Varian) to provide dynamic field collimation and the whole assembly built onto a stainless-steel rail system. A series of MRI-Linac experiments was performed to investigate: (1) image quality with beam on measured using a macropodine (kangaroo) ex vivo phantom; (2) the noise as a function of beam state measured using a 6-channel surface coil array and; (3) electron focusing measured using GafChromic film. Results: (1) The macropodine phantom image quality with the beam on was almost identical to that with the beam off. (2) Noise measured with a surface RF coil produced a 25% elevation of background noise when the radiation beam was on. (3) Film measurements demonstrated electron focusing occurring at the center of the radiation field. Conclusion: The first high-field MRI-Linac has been built and experimentally characterized. This system has allowed us to establish the efficacy of a high field in-line MRI-Linac and study a number of the technical challenges and solutions. Supported by the Australian National Health and Medical Research Council, the Australian Research Council, the Australian Cancer Research Foundation and the Health and Hospitals Fund.

60 APPLIED LIFE SCIENCES↗

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↗

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↗

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↗

Poster - 30: Use of a Hazard-Risk Analysis for development of a new eye immobilization tool for treatment of choroidal melanoma

Purpose: Our treatment for choroidal melanoma utilizes the GTC frame. The patient looks at a small LED to stabilize target position. The LED is attached to a metal arm attached to the GTC frame. A camera on the arm allows therapists to monitor patient compliance. To move to mask-based immobilization we need a new LED/camera attachment mechanism. We used a Hazard-Risk Analysis (HRA) to guide the design of the new tool. Method: A pre-clinical model was built with input from therapy and machine shop personnel. It consisted of an aluminum frame placed in aluminum guide posts attached to the couch top. Further development was guided by the Department of Defense Standard Practice - System Safety hazard risk analysis technique. Results: An Orfit mask was selected because it allowed access to indexes on the couch top which assist with setup reproducibility. The first HRA table was created considering mechanical failure modes of the device. Discussions with operators and manufacturers identified other failure modes and solutions. HRA directed the design towards a safe clinical device. Conclusion: A new immobilization tool has been designed using hazard-risk analysis which resulted in an easier-to-use and safer tool compared to the initial design. The remaining risks are all low probability events and not dissimilar from those currently faced with the GTC setup. Given the gains in ease of use for therapists and patients as well as the lower costs for the hospital, we will implement this new tool.

60 APPLIED LIFE SCIENCES↗