Results for “AWARD” — Page 56

DOE OSTI2015

MO-FG-BRA-09: Quantification of Nanoparticle Heating and Concentration for MR-Guided Laser Interstitial Thermal Therapy

Purpose: Nanoparticle Mediated Laser Interstitial Thermal Therapy (npLITT) is a technique that utilizes tumor localized optically activated nanoparticles to increase the conformality of laser ablation procedures. Temperatures in these procedures are dependent on the particle concentration which generally cannot be measured noninvasively prior to therapy. In this work we attempt to quantify particle concentration in vivo by estimating the increase in R2* relaxation induced by bifunctional magnetic resonance (MR)-visible gold-based nanoparticles (SPIO@Au) and relate it to the temperature increase observed during real time MR temperature imaging (MRTI) of laser ablation. Methods: SPIO@Au nanoparticles (90nm) were synthesized containing a silica-iron core (for MR visibility via R2*) and gold shell (for near-infrared absorption). High resolution R2* maps were acquired before and after injecting four different particle concentrations (saline,1e10, 5e10, and 10e10 particles/mL) into HN5 flank xenografts. Tumors were monitored using MRTI during treatment with an interstitial fiber. (1 watt, 808 nm, 3 minutes) Results: The maximum temperature within the tumors increased linearly with concentration of injected particles, reaching 34.0, 37.6, 45.8, and 55.4 {sup 0}C for saline, 1e10, 5e10 and 10e10 particles/mL injections, respectively (R2=.994). The highest temperatures occur at the injection site rather than the fiber, confirming that SPIO@Au nanoparticles are the primary absorber. The differences between the median R2* measured at the injection site and the rest of the tumor were −6, 134, 111, 156 s-1 for the saline,1e10,5e10 and 10e10 particles/mL injections, respectively. This R2* change is consistent with the measured relaxivity for the 1e10 particles/mL injection but does not maintain linearity at higher concentrations. Conclusion: Bifunctional SPIO@Au nanoparticles are a promising technology for providing noninvasive estimates of particle concentration via MRI and temperature increase in npLITT procedures. Future experiments will focus on lower, physiologically relevant particle concentrations and spin echo R2 mapping to better quantify the particle concentration. This research was supported by the National Institutes of Health and National Cancer Institute under Award Numbers TL1TR000369 and P30CA016672 and was conducted at the MD Anderson Center for Advanced Biomedical Imaging in-part with equipment support from General Electric Healthcare.

60 APPLIED LIFE SCIENCES↗

DOE OSTI2015

MO-F-CAMPUS-T-03: Verification of Range, SOBP Width, and Output for Passive-Scattering Proton Beams Using a Liquid Scintillator Detector

Purpose: Liquid scintillators have been shown to provide fast and high-resolution measurements of radiation beams. However, their linear energy transfer-dependent response (quenching) limits their use in proton beams. The purpose of this study was to develop a simple and fast method to verify the range, spread-out Bragg peak (SOBP) width, and output of a passive-scattering proton beam with a liquid scintillator detector, without the need for quenching correction. Methods: The light signal from a 20×20×20 cm3 liquid scintillator tank was collected with a CCD camera. Reproducible landmarks on the SOBP depth-light curve were identified which possessed a linear relationship with the beam range and SOBP width. The depth-light profiles for three beam energies (140, 160 and 180 MeV) with six SOBP widths at each energy were measured with the detector. Beam range and SOBP width calibration factors were obtained by comparing the depth-light curve landmarks with the nominal range and SOBP width for each beam setting. The daily output stability of the liquid scintillator detector was also studied by making eight repeated output measurements in a cobalt-60 beam over the course of two weeks. Results: The mean difference between the measured and nominal beam ranges was 0.6 mm (σ=0.2 mm), with a maximum difference of 0.9 mm. The mean difference between the measured and nominal SOBP widths was 0.1 mm (σ=1.8 mm), with a maximum difference of 4.0 mm. Finally an output variation of 0.14% was observed for 8 measurements performed over 2 weeks. Conclusion: A method has been developed to determine the range and SOBP width of a passive-scattering proton beam in a liquid scintillator without the need for quenching correction. In addition to providing rapid and accurate beam range and SOBP measurements, the detector is capable of measuring the output consistency with a high degree of precision. This project was supported in part by award number CA182450 from the National Cancer Institute.

07 ISOTOPE AND RADIATION SOURCES↗

DOE OSTI2015

TU-AB-BRA-12: Impact of Image Registration Algorithms On the Prediction of Pathological Response with Radiomic Textures

Purpose: Tumor regions-of-interest (ROI) can be propagated from the pre-onto the post-treatment PET/CT images using image registration of their CT counterparts, providing an automatic way to compute texture features on longitudinal scans. This exploratory study assessed the impact of image registration algorithms on textures to predict pathological response. Methods: Forty-six esophageal cancer patients (1 tumor/patient) underwent PET/CT scans before and after chemoradiotherapy. Patients were classified into responders and non-responders after the surgery. Physician-defined tumor ROIs on pre-treatment PET were propagated onto the post-treatment PET using rigid and ten deformable registration algorithms. One co-occurrence, two run-length and size zone matrix textures were computed within all ROIs. The relative difference of each texture at different treatment time-points was used to predict the pathologic responders. Their predictive value was assessed using the area under the receiver-operating-characteristic curve (AUC). Propagated ROIs and texture quantification resulting from different algorithms were compared using overlap volume (OV) and coefficient of variation (CoV), respectively. Results: Tumor volumes were better captured by ROIs propagated by deformable rather than the rigid registration. The OV between rigidly and deformably propagated ROIs were 69%. The deformably propagated ROIs were found to be similar (OV∼80%) except for fast-demons (OV∼60%). Rigidly propagated ROIs with run-length matrix textures failed to significantly differentiate between responders and non-responders (AUC=0.65, p=0.07), while the differentiation was significant with other textures (AUC=0.69–0.72, p<0.03). Among the deformable algorithms, fast-demons was the least predictive (AUC=0.68–0.71, p<0.04). ROIs propagated by all other deformable algorithms with any texture significantly predicted pathologic responders (AUC=0.71–0.78, p<0.01) despite substantial variation in texture quantification (CoV>70%). Conclusion: Propagated ROIs using deformable registration for all textures can lead to accurate prediction of pathologic response, potentially expediting the temporal texture analysis process. However, rigid and fast-demons deformable algorithms are not recommended due to their inferior performance compared to other algorithms. The project was supported in part by a Kaye Scholar Award.

60 APPLIED LIFE SCIENCES↗

DOE OSTI2015

TU-AB-303-04: Characterizing CT-Derived Mass Change of Non-Tumor Pathology During Lung Radiotherapy

Purpose: Atelectasis and other commonly-observed non-tumor lung pathologies (NTPs) can change during thoracic radiotherapy altering normal anatomy and inducing large changes in tumor position. However, the characteristics of these changes are not well understood. This study investigates longitudinal NTP tissue mass change during radiotherapy. Methods: Delineation of corresponding atelectatic regions before and after re-aeration is challenging since it is difficult to detect atelectatic-region boundaries after re-aeration. Therefore, individual lobes were delineated and analyzed instead. A radiation oncologist contoured the tumor and individual lobes in the planning and mid-treatment CTs for 7 patients. Each lobe was eroded by 2–4 voxels, which was found to reduce effects of inadvertent chest wall in the lobe delineation but still preserve the mean density of the lobe. The mass of each lobe was calculated after removing the tumor region. The uninvolved lobes were used as controls. Results: Mean mass change for contralateral, ipsilateral without NTP, and NTP lobes were +2.1 (18.0) %, −9.4 (18.2) %, and −13.4 (40.1) %, respectively. For NTP lobes, the degree and direction of change depended on atelectasis resolution type (full or partial), with mean mass change for full resolution of −43.1 (16.2) % and +4.5 (40.1) % for partial. The standard deviation for NTP lobes is likely higher due to actual changes in mass as well as increased delineation variability in the presence of tumor and lung consolidation. Median mean density change was −46.4% for NTP lobes, showing significant difference from contralateral (p=8.2×10−{sup 4}) and NTP-free ipsilateral lobes (p=0.006). Conclusion: No noticeable mass change occurred for pathology-free lobes. As NTP fully resolved, mass of the lobe decreased. One possible explanation is that the release of retained fluid and infiltrate commonly associated with NTP accounts for the reduced mass. This work was supported by the National Cancer Institute of the National Institutes of Health under Award Number R01CA166119. The authors have no conflicts of interest.

60 APPLIED LIFE SCIENCES↗

DOE OSTI2015

TU-AB-201-03: A Robot for the Automated Delivery of An Electromagnetic Tracking Sensor for the Localization of Brachytherapy Catheters

Purpose: To present a programmable robotic system for the accurate and fast deployment of an electromagnetic (EM) sensor for brachytherapy catheter localization. Methods: A robotic system for deployment of an EM sensor was designed and built. The system was programmed to increment the sensor position at specified time and space intervals. Sensor delivery accuracy was measured in a phantom using the localization of the EM sensor and tested in different environmental conditions. Accuracy was tested by measuring the distance between the physical locations reached by the sensor (measured by the EM tracker) and the intended programmed locations. Results: The system consisted of a stepper motor connected to drive wheels (that grip the cable to move the sensor) and a series of guides to connect to a brachytherapy transfer tube, all controlled by a programmable Arduino microprocessor. The total cost for parts was <$300. The positional accuracy of the sensor location was within 1 mm of the expected position provided by the motorized guide system. Acquisition speed to localize a brachytherapy catheter with 20 cm of active length was 10 seconds. The current design showed some cable slip and warping depending on environment temperature. Conclusion: The use of EM tracking for the localization of brachytherapy catheters has been previously demonstrated. Efficient data acquisition and artifact reduction requires fast and accurate deployment of an EM sensor in consistent, repeatable patterns, which cannot practically be achieved manually. The design of an inexpensive, programmable robot allowing for the precise deployment of stepping patterns was presented, and a prototype was built. Further engineering is necessary to ensure that the device provides efficient independent localization of brachytherapy catheters. This research was funded by the Kaye Family Award.

60 APPLIED LIFE SCIENCES↗

DOE OSTI2015

TU-CD-BRB-01: Normal Lung CT Texture Features Improve Predictive Models for Radiation Pneumonitis

Purpose: Existing normal tissue complication probability (NTCP) models for radiation pneumonitis (RP) traditionally rely on dosimetric and clinical data but are limited in terms of performance and generalizability. Extraction of pre-treatment image features provides a potential new category of data that can improve NTCP models for RP. We consider quantitative measures of total lung CT intensity and texture in a framework for prediction of RP. Methods: Available clinical and dosimetric data was collected for 198 NSCLC patients treated with definitive radiotherapy. Intensity- and texture-based image features were extracted from the T50 phase of the 4D-CT acquired for treatment planning. A total of 3888 features (15 clinical, 175 dosimetric, and 3698 image features) were gathered and considered candidate predictors for modeling of RP grade≥3. A baseline logistic regression model with mean lung dose (MLD) was first considered. Additionally, a least absolute shrinkage and selection operator (LASSO) logistic regression was applied to the set of clinical and dosimetric features, and subsequently to the full set of clinical, dosimetric, and image features. Model performance was assessed by comparing area under the curve (AUC). Results: A simple logistic fit of MLD was an inadequate model of the data (AUC∼0.5). Including clinical and dosimetric parameters within the framework of the LASSO resulted in improved performance (AUC=0.648). Analysis of the full cohort of clinical, dosimetric, and image features provided further and significant improvement in model performance (AUC=0.727). Conclusions: To achieve significant gains in predictive modeling of RP, new categories of data should be considered in addition to clinical and dosimetric features. We have successfully incorporated CT image features into a framework for modeling RP and have demonstrated improved predictive performance. Validation and further investigation of CT image features in the context of RP NTCP modeling is warranted. This work was supported by the Rosalie B. Hite Fellowship in Cancer research awarded to SPK.

60 APPLIED LIFE SCIENCES↗

DOE OSTI2015

TU-CD-303-02: Beyond Radiation Induced Double Strand Breaks - a New Horizon for Radiation Therapy Research

Recent advances in cancer research have shed new light on the complex processes of how therapeutic radiation initiates changes at cellular, tissue, and system levels that may lead to clinical effects. These new advances may transform the way we use radiation to combat certain types of cancers. For the past two decades many technological advancements in radiation therapy have been largely based on the hypothesis that direct radiation-induced DNA double strand breaks cause cell death and thus tumor control and normal tissue damage. However, new insights have elucidated that in addition to causing cellular DNA damage, localized therapeutic radiation also initiates cascades of complex downstream biological responses in tissue that extend far beyond where therapeutic radiation dose is directly deposited. For instance, studies show that irradiated dying tumor cells release tumor antigens that can lead the immune system to a systemic anti-cancer attack throughout the body of cancer patient; targeted irradiation to solid tumor also increases the migration of tumor cells already in bloodstream, the seeds of potential metastasis. Some of the new insights may explain the long ago discovered but still unexplained non-localized radiation effects (bystander effect and abscopal effect) and the efficacy of spatially fractionated radiation therapy (microbeam radiation therapy and GRID therapy) where many “hot” and “cold” spots are intentionally created throughout the treatment volume. Better understanding of the mechanisms behind the non-localized radiation effects creates tremendous opportunities to develop new and integrated cancer treatment strategies that are based on radiotherapy, immunology, and chemotherapy. However, in the multidisciplinary effort to advance new radiobiology, there are also tremendous challenges including a lack of multidisciplinary researchers and imaging technologies for the microscopic radiation-induced responses. A better grasp of the essence of these advances in cancer biology research will give medical physicists a new perspective in daily clinical physics practice and in future radiation therapy technological development. Furthermore, academic medical physics should continue to be an integral part of the multidisciplinary cancer research community, harnessing our newly acquired understanding of radiation effects, and developing novel cost-effective treatment strategies to better combat cancer. Learning Objectives: Understand that localized radiation can lead to non-localized secondary effects such as radiation-induced immune response, bystander effect, and abscopal effect. Understand that the non-localized radiation effects may be harnessed to improve cancer treatment. Learn examples of physics participation in multidisciplinary research to advance cancer biology. Recognize the challenges and possibilities of physics applications in cancer research. Chang: NIH 5RC2CA148487-02 and 1U54CA151652-01 Graves: IDEA award (19IB-0106) from the California Breast Cancer Research Program (CBCRP), and by NIH P01 CA67166.

60 APPLIED LIFE SCIENCES↗

DOE OSTI2015

TU-CD-303-03: Localized Radiation Can Induce Systemic Anti-Cancer Immune and Non-Immune Responses and How We Might Utilize It

Recent advances in cancer research have shed new light on the complex processes of how therapeutic radiation initiates changes at cellular, tissue, and system levels that may lead to clinical effects. These new advances may transform the way we use radiation to combat certain types of cancers. For the past two decades many technological advancements in radiation therapy have been largely based on the hypothesis that direct radiation-induced DNA double strand breaks cause cell death and thus tumor control and normal tissue damage. However, new insights have elucidated that in addition to causing cellular DNA damage, localized therapeutic radiation also initiates cascades of complex downstream biological responses in tissue that extend far beyond where therapeutic radiation dose is directly deposited. For instance, studies show that irradiated dying tumor cells release tumor antigens that can lead the immune system to a systemic anti-cancer attack throughout the body of cancer patient; targeted irradiation to solid tumor also increases the migration of tumor cells already in bloodstream, the seeds of potential metastasis. Some of the new insights may explain the long ago discovered but still unexplained non-localized radiation effects (bystander effect and abscopal effect) and the efficacy of spatially fractionated radiation therapy (microbeam radiation therapy and GRID therapy) where many “hot” and “cold” spots are intentionally created throughout the treatment volume. Better understanding of the mechanisms behind the non-localized radiation effects creates tremendous opportunities to develop new and integrated cancer treatment strategies that are based on radiotherapy, immunology, and chemotherapy. However, in the multidisciplinary effort to advance new radiobiology, there are also tremendous challenges including a lack of multidisciplinary researchers and imaging technologies for the microscopic radiation-induced responses. A better grasp of the essence of these advances in cancer biology research will give medical physicists a new perspective in daily clinical physics practice and in future radiation therapy technological development. Furthermore, academic medical physics should continue to be an integral part of the multidisciplinary cancer research community, harnessing our newly acquired understanding of radiation effects, and developing novel cost-effective treatment strategies to better combat cancer. Learning Objectives: Understand that localized radiation can lead to non-localized secondary effects such as radiation-induced immune response, bystander effect, and abscopal effect. Understand that the non-localized radiation effects may be harnessed to improve cancer treatment. Learn examples of physics participation in multidisciplinary research to advance cancer biology. Recognize the challenges and possibilities of physics applications in cancer research. Chang: NIH 5RC2CA148487-02 and 1U54CA151652-01 Graves: IDEA award (19IB-0106) from the California Breast Cancer Research Program (CBCRP), and by NIH P01 CA67166.

60 APPLIED LIFE SCIENCES↗

DOE OSTI2015

TU-CD-303-04: Radiation-Induced Long Distance Tumor Cell Migration Into and Out of the Radiation Field and Its Clinical Implication

Recent advances in cancer research have shed new light on the complex processes of how therapeutic radiation initiates changes at cellular, tissue, and system levels that may lead to clinical effects. These new advances may transform the way we use radiation to combat certain types of cancers. For the past two decades many technological advancements in radiation therapy have been largely based on the hypothesis that direct radiation-induced DNA double strand breaks cause cell death and thus tumor control and normal tissue damage. However, new insights have elucidated that in addition to causing cellular DNA damage, localized therapeutic radiation also initiates cascades of complex downstream biological responses in tissue that extend far beyond where therapeutic radiation dose is directly deposited. For instance, studies show that irradiated dying tumor cells release tumor antigens that can lead the immune system to a systemic anti-cancer attack throughout the body of cancer patient; targeted irradiation to solid tumor also increases the migration of tumor cells already in bloodstream, the seeds of potential metastasis. Some of the new insights may explain the long ago discovered but still unexplained non-localized radiation effects (bystander effect and abscopal effect) and the efficacy of spatially fractionated radiation therapy (microbeam radiation therapy and GRID therapy) where many “hot” and “cold” spots are intentionally created throughout the treatment volume. Better understanding of the mechanisms behind the non-localized radiation effects creates tremendous opportunities to develop new and integrated cancer treatment strategies that are based on radiotherapy, immunology, and chemotherapy. However, in the multidisciplinary effort to advance new radiobiology, there are also tremendous challenges including a lack of multidisciplinary researchers and imaging technologies for the microscopic radiation-induced responses. A better grasp of the essence of these advances in cancer biology research will give medical physicists a new perspective in daily clinical physics practice and in future radiation therapy technological development. Furthermore, academic medical physics should continue to be an integral part of the multidisciplinary cancer research community, harnessing our newly acquired understanding of radiation effects, and developing novel cost-effective treatment strategies to better combat cancer. Learning Objectives: Understand that localized radiation can lead to non-localized secondary effects such as radiation-induced immune response, bystander effect, and abscopal effect. Understand that the non-localized radiation effects may be harnessed to improve cancer treatment. Learn examples of physics participation in multidisciplinary research to advance cancer biology. Recognize the challenges and possibilities of physics applications in cancer research. Chang: NIH 5RC2CA148487-02 and 1U54CA151652-01 Graves: IDEA award (19IB-0106) from the California Breast Cancer Research Program (CBCRP), and by NIH P01 CA67166.

60 APPLIED LIFE SCIENCES↗

DOE OSTI2015

TU-CD-303-05: Unveiling Tumor Heterogeneity by Molecular Imaging

Recent advances in cancer research have shed new light on the complex processes of how therapeutic radiation initiates changes at cellular, tissue, and system levels that may lead to clinical effects. These new advances may transform the way we use radiation to combat certain types of cancers. For the past two decades many technological advancements in radiation therapy have been largely based on the hypothesis that direct radiation-induced DNA double strand breaks cause cell death and thus tumor control and normal tissue damage. However, new insights have elucidated that in addition to causing cellular DNA damage, localized therapeutic radiation also initiates cascades of complex downstream biological responses in tissue that extend far beyond where therapeutic radiation dose is directly deposited. For instance, studies show that irradiated dying tumor cells release tumor antigens that can lead the immune system to a systemic anti-cancer attack throughout the body of cancer patient; targeted irradiation to solid tumor also increases the migration of tumor cells already in bloodstream, the seeds of potential metastasis. Some of the new insights may explain the long ago discovered but still unexplained non-localized radiation effects (bystander effect and abscopal effect) and the efficacy of spatially fractionated radiation therapy (microbeam radiation therapy and GRID therapy) where many “hot” and “cold” spots are intentionally created throughout the treatment volume. Better understanding of the mechanisms behind the non-localized radiation effects creates tremendous opportunities to develop new and integrated cancer treatment strategies that are based on radiotherapy, immunology, and chemotherapy. However, in the multidisciplinary effort to advance new radiobiology, there are also tremendous challenges including a lack of multidisciplinary researchers and imaging technologies for the microscopic radiation-induced responses. A better grasp of the essence of these advances in cancer biology research will give medical physicists a new perspective in daily clinical physics practice and in future radiation therapy technological development. Furthermore, academic medical physics should continue to be an integral part of the multidisciplinary cancer research community, harnessing our newly acquired understanding of radiation effects, and developing novel cost-effective treatment strategies to better combat cancer. Learning Objectives: Understand that localized radiation can lead to non-localized secondary effects such as radiation-induced immune response, bystander effect, and abscopal effect. Understand that the non-localized radiation effects may be harnessed to improve cancer treatment. Learn examples of physics participation in multidisciplinary research to advance cancer biology. Recognize the challenges and possibilities of physics applications in cancer research. Chang: NIH 5RC2CA148487-02 and 1U54CA151652-01 Graves: IDEA award (19IB-0106) from the California Breast Cancer Research Program (CBCRP), and by NIH P01 CA67166.

60 APPLIED LIFE SCIENCES↗

DOE OSTI2015

TU-EF-210-00: Therapeutic Strategies and Image Guidance

The use of therapeutic ultrasound to provide targeted therapy is an active research area that has a broad application scope. The invited talks in this session will address currently implemented strategies and protocols for both hyperthermia and ablation applications using therapeutic ultrasound. The role of both ultrasound and MRI in the monitoring and assessment of these therapies will be explored in both pre-clinical and clinical applications. Katherine Ferrara: High Intensity Focused Ultrasound, Drug Delivery, and Immunotherapy Rajiv Chopra: Translating Localized Doxorubicin Delivery to Pediatric Oncology using MRI-guided HIFU Elisa Konofagou: Real-time Ablation Monitoring and Lesion Quantification using Harmonic Motion Imaging Keyvan Farahani: AAPM Task Groups in Interventional Ultrasound Imaging and Therapy Learning Objectives: Understand the role of ultrasound in localized drug delivery and the effects of immunotherapy when used in conjunction with ultrasound therapy. Understand potential targeted drug delivery clinical applications including pediatric oncology. Understand the technical requirements for performing targeted drug delivery. Understand how radiation-force approaches can be used to both monitor and assess high intensity focused ultrasound ablation therapy. Understand the role of AAPM task groups in ultrasound imaging and therapies. Chopra: Funding from Cancer Prevention and Research Initiative of Texas (CPRIT), Award R1308 Evelyn and M.R. Hudson Foundation; Research Support from Research Contract with Philips Healthcare; COI are Co-founder of FUS Instruments Inc Ferrara: Supported by NIH, UCDavis and California (CIRM and BHCE) Farahani: In-kind research support from Philips Healthcare.

60 APPLIED LIFE SCIENCES↗

DOE OSTI2015

TU-EF-210-01: HIFU, Drug Delivery, and Immunotherapy

The use of therapeutic ultrasound to provide targeted therapy is an active research area that has a broad application scope. The invited talks in this session will address currently implemented strategies and protocols for both hyperthermia and ablation applications using therapeutic ultrasound. The role of both ultrasound and MRI in the monitoring and assessment of these therapies will be explored in both pre-clinical and clinical applications. Katherine Ferrara: High Intensity Focused Ultrasound, Drug Delivery, and Immunotherapy Rajiv Chopra: Translating Localized Doxorubicin Delivery to Pediatric Oncology using MRI-guided HIFU Elisa Konofagou: Real-time Ablation Monitoring and Lesion Quantification using Harmonic Motion Imaging Keyvan Farahani: AAPM Task Groups in Interventional Ultrasound Imaging and Therapy Learning Objectives: Understand the role of ultrasound in localized drug delivery and the effects of immunotherapy when used in conjunction with ultrasound therapy. Understand potential targeted drug delivery clinical applications including pediatric oncology. Understand the technical requirements for performing targeted drug delivery. Understand how radiation-force approaches can be used to both monitor and assess high intensity focused ultrasound ablation therapy. Understand the role of AAPM task groups in ultrasound imaging and therapies. Chopra: Funding from Cancer Prevention and Research Initiative of Texas (CPRIT), Award R1308 Evelyn and M.R. Hudson Foundation; Research Support from Research Contract with Philips Healthcare; COI are Co-founder of FUS Instruments Inc Ferrara: Supported by NIH, UCDavis and California (CIRM and BHCE) Farahani: In-kind research support from Philips Healthcare.

60 APPLIED LIFE SCIENCES↗

DOE OSTI2015

TU-EF-210-02: MRg Hyperthermia

The use of therapeutic ultrasound to provide targeted therapy is an active research area that has a broad application scope. The invited talks in this session will address currently implemented strategies and protocols for both hyperthermia and ablation applications using therapeutic ultrasound. The role of both ultrasound and MRI in the monitoring and assessment of these therapies will be explored in both pre-clinical and clinical applications. Katherine Ferrara: High Intensity Focused Ultrasound, Drug Delivery, and Immunotherapy Rajiv Chopra: Translating Localized Doxorubicin Delivery to Pediatric Oncology using MRI-guided HIFU Elisa Konofagou: Real-time Ablation Monitoring and Lesion Quantification using Harmonic Motion Imaging Keyvan Farahani: AAPM Task Groups in Interventional Ultrasound Imaging and Therapy Learning Objectives: Understand the role of ultrasound in localized drug delivery and the effects of immunotherapy when used in conjunction with ultrasound therapy. Understand potential targeted drug delivery clinical applications including pediatric oncology. Understand the technical requirements for performing targeted drug delivery. Understand how radiation-force approaches can be used to both monitor and assess high intensity focused ultrasound ablation therapy. Understand the role of AAPM task groups in ultrasound imaging and therapies. Chopra: Funding from Cancer Prevention and Research Initiative of Texas (CPRIT), Award R1308 Evelyn and M.R. Hudson Foundation; Research Support from Research Contract with Philips Healthcare; COI are Co-founder of FUS Instruments Inc Ferrara: Supported by NIH, UCDavis and California (CIRM and BHCE) Farahani: In-kind research support from Philips Healthcare.

60 APPLIED LIFE SCIENCES↗

DOE OSTI2015

TU-EF-210-03: Real-Time Ablation Monitoring and Lesion Quantification Using Harmonic Motion Imaging

The use of therapeutic ultrasound to provide targeted therapy is an active research area that has a broad application scope. The invited talks in this session will address currently implemented strategies and protocols for both hyperthermia and ablation applications using therapeutic ultrasound. The role of both ultrasound and MRI in the monitoring and assessment of these therapies will be explored in both pre-clinical and clinical applications. Katherine Ferrara: High Intensity Focused Ultrasound, Drug Delivery, and Immunotherapy Rajiv Chopra: Translating Localized Doxorubicin Delivery to Pediatric Oncology using MRI-guided HIFU Elisa Konofagou: Real-time Ablation Monitoring and Lesion Quantification using Harmonic Motion Imaging Keyvan Farahani: AAPM Task Groups in Interventional Ultrasound Imaging and Therapy Learning Objectives: Understand the role of ultrasound in localized drug delivery and the effects of immunotherapy when used in conjunction with ultrasound therapy. Understand potential targeted drug delivery clinical applications including pediatric oncology. Understand the technical requirements for performing targeted drug delivery. Understand how radiation-force approaches can be used to both monitor and assess high intensity focused ultrasound ablation therapy. Understand the role of AAPM task groups in ultrasound imaging and therapies. Chopra: Funding from Cancer Prevention and Research Initiative of Texas (CPRIT), Award R1308 Evelyn and M.R. Hudson Foundation; Research Support from Research Contract with Philips Healthcare; COI are Co-founder of FUS Instruments Inc Ferrara: Supported by NIH, UCDavis and California (CIRM and BHCE) Farahani: In-kind research support from Philips Healthcare.

60 APPLIED LIFE SCIENCES↗

DOE OSTI2015

TU-EF-210-04: AAPM Task Groups in Interventional Ultrasound Imaging and Therapy

The use of therapeutic ultrasound to provide targeted therapy is an active research area that has a broad application scope. The invited talks in this session will address currently implemented strategies and protocols for both hyperthermia and ablation applications using therapeutic ultrasound. The role of both ultrasound and MRI in the monitoring and assessment of these therapies will be explored in both pre-clinical and clinical applications. Katherine Ferrara: High Intensity Focused Ultrasound, Drug Delivery, and Immunotherapy Rajiv Chopra: Translating Localized Doxorubicin Delivery to Pediatric Oncology using MRI-guided HIFU Elisa Konofagou: Real-time Ablation Monitoring and Lesion Quantification using Harmonic Motion Imaging Keyvan Farahani: AAPM Task Groups in Interventional Ultrasound Imaging and Therapy Learning Objectives: Understand the role of ultrasound in localized drug delivery and the effects of immunotherapy when used in conjunction with ultrasound therapy. Understand potential targeted drug delivery clinical applications including pediatric oncology. Understand the technical requirements for performing targeted drug delivery. Understand how radiation-force approaches can be used to both monitor and assess high intensity focused ultrasound ablation therapy. Understand the role of AAPM task groups in ultrasound imaging and therapies. Chopra: Funding from Cancer Prevention and Research Initiative of Texas (CPRIT), Award R1308 Evelyn and M.R. Hudson Foundation; Research Support from Research Contract with Philips Healthcare; COI are Co-founder of FUS Instruments Inc Ferrara: Supported by NIH, UCDavis and California (CIRM and BHCE) Farahani: In-kind research support from Philips Healthcare.

60 APPLIED LIFE SCIENCES↗

DOE OSTI2015

TU-G-BRD-05: Results From Multi-Institutional Measurements with An Anthropomorphic Spine Phantom

Purpose: To analyze the results from an anthropomorphic spine phantom used for credentialing institutions for National Cancer Institute (NCI) sponsored clinical trial. Methods: An anthropomorphic phantom that contains left and right lungs, a heart, an esophagus, spinal cord, bony material and a PTV was sent to institutions wishing to be credentialed for NCI trials. The PTV holds 4 TLD and radiochromic film in the axial and sagittal planes. The heart holds one TLD. Institutions created IMRT plans to cover ≥90% of the PTV with 6 Gy and limit the cord dose to <0.35cc receiving 3.75 Gy and <1.2cc receiving 2.63 Gy. They were instructed to treat the phantom as they would a patient, including making plan specific IMRT/SBRT QA measurements before treatment. The TLD results in the PTV were required to be within ±7% of the plan dose. A gamma calculation was performed using the film results and the submitted DICOM plan. ≥85% of the analyzed region was required to pass a 5%/3 mm criteria. Results: 176 institutions irradiated the spine phantom for a total of 255 results. The pass rate was 73% (187 irradiations) overall. 44 irradiations failed only the gamma criteria, 2 failed only the dose criteria and 22 failed both. The most used planning systems were Eclipse (116) and Pinnacle (52) and they had pass rates of 76% and 71%, respectively. The AAA algorithm had a pass rate of 77% while superposition type algorithms had a 71% pass rate. The average TLD measurement to institution calculation ratio was 0.99 (0.04 std dev.). The average percent pixels passing the gamma criteria for films was 89% (12% std dev.) Conclusion: Results show that this phantom is an important part of credentialing and that we have room for improvement in IMRT/SBRT spine treatments. This work was supported by PHS CA180803 and CA037422 awarded by NCI, DHHS.

60 APPLIED LIFE SCIENCES↗

DOE OSTI2015

TU-G-BRB-00: Clinical Trials in Proton and Particle Therapy

Proton therapy, in particular, and ion therapy, just beginning, are becoming an increasing focus of attention in clinical radiation oncology and medical physics. Both modalities have been criticized of lacking convincing evidence from randomized trials proving their efficacy, justifying the higher costs involved in these therapies. This session will provide an overview of the current status of clinical trials in proton therapy, including recent developments in ion therapy. As alluded to in the introductory talk by Dr. Schulte, opinions are diverging widely as to the usefulness and need for clinical trials in particle therapy and the challenge of equipoise. The lectures will highlight some of the challenges that surround clinical trials in particle therapy. One, presented by Dr. Choy from UT Southwestern, is that new technology and even different types of particles such as helium and carbon ions are introduced into this environment, increasing the phase space of clinical variables. The other is the issue of medical physics quality assurance with physical phantoms, presented by Mrs. Taylor from IROC Houston, which is more challenging because 3D and 4D image guidance and active delivery techniques are in relatively early stages of development. The role of digital phantoms in developing clinical treatment planning protocols and as a QA tool will also be highlighted by Dr. Lee from NCI. The symposium will be rounded off by a panel discussion among the Symposium speakers, arguing pro or con the need and readiness for clinical trials in proton and ion therapy. Learning Objectives: To get an update on the current status of clinical trials allowing or mandating proton therapy. Learn about the status of planned clinical trials in the U.S. and worldwide involving ion therapy. Discuss the challenges in the design and QA of clinical trials in particle therapy. Learn about existing and future physical and computational anthropomorphic phantoms for charged particle clinical trial development and support. Research reported in this presentation is supported by the National Cancer Institute of the National; Institutes of Health under Award Number P20CA183640.

60 APPLIED LIFE SCIENCES↗

DOE OSTI2015

TU-G-BRB-01: Topic Introduction: Do We Need Clinical Trials in Particle Therapy and How Can Medical Physics Support Them?

Proton therapy, in particular, and ion therapy, just beginning, are becoming an increasing focus of attention in clinical radiation oncology and medical physics. Both modalities have been criticized of lacking convincing evidence from randomized trials proving their efficacy, justifying the higher costs involved in these therapies. This session will provide an overview of the current status of clinical trials in proton therapy, including recent developments in ion therapy. As alluded to in the introductory talk by Dr. Schulte, opinions are diverging widely as to the usefulness and need for clinical trials in particle therapy and the challenge of equipoise. The lectures will highlight some of the challenges that surround clinical trials in particle therapy. One, presented by Dr. Choy from UT Southwestern, is that new technology and even different types of particles such as helium and carbon ions are introduced into this environment, increasing the phase space of clinical variables. The other is the issue of medical physics quality assurance with physical phantoms, presented by Mrs. Taylor from IROC Houston, which is more challenging because 3D and 4D image guidance and active delivery techniques are in relatively early stages of development. The role of digital phantoms in developing clinical treatment planning protocols and as a QA tool will also be highlighted by Dr. Lee from NCI. The symposium will be rounded off by a panel discussion among the Symposium speakers, arguing pro or con the need and readiness for clinical trials in proton and ion therapy. Learning Objectives: To get an update on the current status of clinical trials allowing or mandating proton therapy. Learn about the status of planned clinical trials in the U.S. and worldwide involving ion therapy. Discuss the challenges in the design and QA of clinical trials in particle therapy. Learn about existing and future physical and computational anthropomorphic phantoms for charged particle clinical trial development and support. Research reported in this presentation is supported by the National Cancer Institute of the National; Institutes of Health under Award Number P20CA183640.

60 APPLIED LIFE SCIENCES↗