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At least 91 records · Page 5

Deep Gaze Velocity Analysis During Mammographic Reading for Biometric Identification of Radiologists

Several studies have confirmed that the gaze velocity of the human eye can be utilized as a behavioral biometric or personalized biomarker. In this study, we leverage the local feature representation capacity of convolutional neural networks (CNNs) for eye gaze velocity analysis as the basis for biometric identification of radiologists performing breast cancer screening. Using gaze data collected from 10 radiologists reading 100 mammograms of various diagnoses, we compared the performance of a CNN-based classification algorithm with two deep learning classifiers, deep neural network and deep belief network, and a previously presented hidden Markov model classifier. The study showed that the CNN classifier is superior compared to alternative classification methods based on macro F1-scores derived from 10-fold cross-validation experiments. Our results further support the efficacy of eye gaze velocity as a biometric identifier of medical imaging experts.

59 BASIC BIOLOGICAL SCIENCES↗

Dynamic Contrast-Enhanced MRI of Cervical Cancers: Temporal Percentile Screening of Contrast Enhancement Identifies Parameters for Prediction of Chemoradioresistance

Purpose: To systematically screen the tumor contrast enhancement of locally advanced cervical cancers to assess the prognostic value of two descriptive parameters derived from dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI). Methods and Materials: This study included a prospectively collected cohort of 81 patients who underwent DCE-MRI with gadopentetate dimeglumine before chemoradiotherapy. The following descriptive DCE-MRI parameters were extracted voxel by voxel and presented as histograms for each time point in the dynamic series: normalized relative signal increase (nRSI) and normalized area under the curve (nAUC). The first to 100th percentiles of the histograms were included in a log-rank survival test, resulting in p value and relative risk maps of all percentile-time intervals for each DCE-MRI parameter. The maps were used to evaluate the robustness of the individual percentile-time pairs and to construct prognostic parameters. Clinical endpoints were locoregional control and progression-free survival. The study was approved by the institutional ethics committee. Results: The p value maps of nRSI and nAUC showed a large continuous region of percentile-time pairs that were significantly associated with locoregional control (p < 0.05). These parameters had prognostic impact independent of tumor stage, volume, and lymph node status on multivariate analysis. Only a small percentile-time interval of nRSI was associated with progression-free survival. Conclusions: The percentile-time screening identified DCE-MRI parameters that predict long-term locoregional control after chemoradiotherapy of cervical cancer.

62 RADIOLOGY AND NUCLEAR MEDICINE↗

Lung Cancer Cell Line Screen Links Fanconi Anemia/BRCA Pathway Defects to Increased Relative Biological Effectiveness of Proton Radiation

Purpose: Growing knowledge of genomic heterogeneity in cancer, especially when it results in altered DNA damage responses, requires re-examination of the generic relative biological effectiveness (RBE) of 1.1 of protons. Methods and Materials: For determination of cellular radiosensitivity, we irradiated 17 lung cancer cell lines at the mid-spread-out Bragg peak of a clinical proton beam (linear energy transfer, 2.5 keV/μm). For comparison, 250-kVp X rays and {sup 137}Cs γ-rays were used. To estimate the RBE of protons relative to {sup 60}Co (Co60eq), we assigned an RBE(Co60Eq) of 1.1 to X rays to correct the physical dose measured. Standard DNA repair foci assays were used to monitor damage responses. FANCD2 was depleted using RNA interference. Results: Five lung cancer cell lines (29.4%) exhibited reduced clonogenic survival after proton irradiation compared with X-irradiation with the same physical doses. This was confirmed in a 3-dimensional sphere assay. Corresponding proton RBE(Co60Eq) estimates were statistically significantly different from 1.1 (P≤.05): 1.31 to 1.77 (for a survival fraction of 0.5). In 3 of these lines, increased RBE was correlated with alterations in the Fanconi anemia (FA)/BRCA pathway of DNA repair. In Calu-6 cells, the data pointed toward an FA pathway defect, leading to a previously unreported persistence of proton-induced RAD51 foci. The FA/BRCA-defective cells displayed a 25% increase in the size of subnuclear 53BP1 foci 18 hours after proton irradiation. Conclusions: Our cell line screen has revealed variations in proton RBE that are partly due to FA/BRCA pathway defects, suggesting that the use of a generic RBE for cancers should be revisited. We propose that functional biomarkers, such as size of residual 53BP1 foci, may be used to identify cancers with increased sensitivity to proton radiation.

62 RADIOLOGY AND NUCLEAR MEDICINE↗

Screening for prostate cancer

Despite recent advances in both the survival and cure rates for many forms of cancer, unfortunately the same has not been true for prostate cancer. In fact, the age-adjusted death rate from prostate cancer has not significantly improved since 1949, and prostate cancer remains the most common cancer in American men, causing the second highest cancer mortality rate. Topics discussed include the following: serum testosterone levels; diagnosis; mortality statistics; prostate-sppecific antigen (PSA) tests; and the Occupational Medicine Services policy at LeRC.

Weirich, Stephen A.↗

Engineered bone marrow as a clinically relevant ex vivo model for primary bone cancer research and drug screening

Osteosarcoma (OS) is the most common primary malignant bone cancer in children and adolescents. While numerous other cancers now have promising therapeutic advances, treatment options for OS have remained unchanged since the advent of standard chemotherapeutics and offer less than a 25% 5-y survival rate for those with metastatic disease. This dearth of clinical progress underscores a lack of understanding of OS progression and necessitates the study of this disease in an innovative system. Here, we adapt a previously described engineered bone marrow (eBM) construct for use as a three-dimensional platform to study how microenvironmental and immune factors affect OS tumor progression. We form eBM by implanting acellular bone-forming materials in mice and explanting the cellularized constructs after 8 wk for study. We interrogate the influence of the anatomical implantation site on eBM tissue quality, test ex vivo stability under normoxic (5% O 2 ) and standard (21% O 2 ) culture conditions, culture OS cells within these constructs, and compare them to human OS samples. We show that eBM stably recapitulates the composition of native bone marrow. OS cells exhibit differential behavior dependent on metastatic potential when cultured in eBM, thus mimicking in vivo conditions. Furthermore, we highlight the clinical applicability of eBM as a drug-screening platform through doxorubicin treatment and show that eBM confers a protective effect on OS cells that parallel clinical responses. Combined, this work presents eBM as a cellular construct that mimics the complex bone marrow environment that is useful for mechanistic bone cancer research and drug screening.

59 BASIC BIOLOGICAL SCIENCES↗

WE-FG-201-00: High Impact Technologies for Low Resource Environments

Many low- and middle-income countries lack the resources and services to manage cancer, from screening and diagnosis to radiation therapy planning, treatment and quality assurance. The challenges in upgrading or introducing the needed services are enormous, and include severe shortages in equipment and trained staff. In this symposium, we will describe examples of technology and scientific research that have the potential to impact all these areas. These include: (1) the development of high-quality/low-cost colposcopes for cervical cancer screening, (2) the application of automated radiotherapy treatment planning to reduce staffing shortages, (3) the development of a novel radiotherapy treatment unit, and (4) utilizing a cloud-based infrastructure to facilitate collaboration and QA. Learning Objectives: Understand some of the issues in cancer care in low- resource environments, including shortages in staff and equipment, and inadequate physical infrastructure for advanced radiotherapy. Understand the challenges in developing and deploying diagnostic and treatment devices and services for low-resource environments. Understand some of the emerging technological solutions for cancer management in LMICs. NCI; L. Court, NIH, Varian, Elekta; I. Feain, Ilana Feain is founder and CTO of Nano-X Pty Ltd.

60 APPLIED LIFE SCIENCES↗

WE-FG-201-01: Patient Centric Technologies for Diagnosis of Breast and Cervical Cancer

Many low- and middle-income countries lack the resources and services to manage cancer, from screening and diagnosis to radiation therapy planning, treatment and quality assurance. The challenges in upgrading or introducing the needed services are enormous, and include severe shortages in equipment and trained staff. In this symposium, we will describe examples of technology and scientific research that have the potential to impact all these areas. These include: (1) the development of high-quality/low-cost colposcopes for cervical cancer screening, (2) the application of automated radiotherapy treatment planning to reduce staffing shortages, (3) the development of a novel radiotherapy treatment unit, and (4) utilizing a cloud-based infrastructure to facilitate collaboration and QA. Learning Objectives: Understand some of the issues in cancer care in low- resource environments, including shortages in staff and equipment, and inadequate physical infrastructure for advanced radiotherapy. Understand the challenges in developing and deploying diagnostic and treatment devices and services for low-resource environments. Understand some of the emerging technological solutions for cancer management in LMICs. NCI; L. Court, NIH, Varian, Elekta; I. Feain, Ilana Feain is founder and CTO of Nano-X Pty Ltd.

60 APPLIED LIFE SCIENCES↗

WE-FG-201-02: Automated Treatment Planning for Low-Resource Settings

Many low- and middle-income countries lack the resources and services to manage cancer, from screening and diagnosis to radiation therapy planning, treatment and quality assurance. The challenges in upgrading or introducing the needed services are enormous, and include severe shortages in equipment and trained staff. In this symposium, we will describe examples of technology and scientific research that have the potential to impact all these areas. These include: (1) the development of high-quality/low-cost colposcopes for cervical cancer screening, (2) the application of automated radiotherapy treatment planning to reduce staffing shortages, (3) the development of a novel radiotherapy treatment unit, and (4) utilizing a cloud-based infrastructure to facilitate collaboration and QA. Learning Objectives: Understand some of the issues in cancer care in low- resource environments, including shortages in staff and equipment, and inadequate physical infrastructure for advanced radiotherapy. Understand the challenges in developing and deploying diagnostic and treatment devices and services for low-resource environments. Understand some of the emerging technological solutions for cancer management in LMICs. NCI; L. Court, NIH, Varian, Elekta; I. Feain, Ilana Feain is founder and CTO of Nano-X Pty Ltd.

60 APPLIED LIFE SCIENCES↗

WE-FG-201-03: Lean Innovation Transforming Global Access to Best Practice Radiotherapy Treatment

Many low- and middle-income countries lack the resources and services to manage cancer, from screening and diagnosis to radiation therapy planning, treatment and quality assurance. The challenges in upgrading or introducing the needed services are enormous, and include severe shortages in equipment and trained staff. In this symposium, we will describe examples of technology and scientific research that have the potential to impact all these areas. These include: (1) the development of high-quality/low-cost colposcopes for cervical cancer screening, (2) the application of automated radiotherapy treatment planning to reduce staffing shortages, (3) the development of a novel radiotherapy treatment unit, and (4) utilizing a cloud-based infrastructure to facilitate collaboration and QA. Learning Objectives: Understand some of the issues in cancer care in low- resource environments, including shortages in staff and equipment, and inadequate physical infrastructure for advanced radiotherapy. Understand the challenges in developing and deploying diagnostic and treatment devices and services for low-resource environments. Understand some of the emerging technological solutions for cancer management in LMICs. NCI; L. Court, NIH, Varian, Elekta; I. Feain, Ilana Feain is founder and CTO of Nano-X Pty Ltd.

60 APPLIED LIFE SCIENCES↗

WE-FG-201-04: Cloud-Based Collaboration for Radiotherapy Clinical Trials, Research and Training

Many low- and middle-income countries lack the resources and services to manage cancer, from screening and diagnosis to radiation therapy planning, treatment and quality assurance. The challenges in upgrading or introducing the needed services are enormous, and include severe shortages in equipment and trained staff. In this symposium, we will describe examples of technology and scientific research that have the potential to impact all these areas. These include: (1) the development of high-quality/low-cost colposcopes for cervical cancer screening, (2) the application of automated radiotherapy treatment planning to reduce staffing shortages, (3) the development of a novel radiotherapy treatment unit, and (4) utilizing a cloud-based infrastructure to facilitate collaboration and QA. Learning Objectives: Understand some of the issues in cancer care in low- resource environments, including shortages in staff and equipment, and inadequate physical infrastructure for advanced radiotherapy. Understand the challenges in developing and deploying diagnostic and treatment devices and services for low-resource environments. Understand some of the emerging technological solutions for cancer management in LMICs. NCI; L. Court, NIH, Varian, Elekta; I. Feain, Ilana Feain is founder and CTO of Nano-X Pty Ltd.

60 APPLIED LIFE SCIENCES↗

A Novel Assay for Profiling GBM Cancer Model Heterogeneity and Drug Screening

Accurate patient-derived models of cancer are needed for profiling the disease and for testing therapeutics. These models must not only be accurate, but also suitable for high-throughput screening and analysis. Here we compare two derivative cancer models, microtumors and spheroids, to the gold standard model of patient-derived orthotopic xenografts (PDX) in glioblastoma multiforme (GBM). To compare these models, we constructed a custom NanoString panel of 350 genes relevant to GBM biology. This custom assay includes 16 GBM-specific gene signatures including a novel GBM subtyping signature. We profiled 11 GBM-PDX with matched orthotopic cells, derived microtumors, and derived spheroids using the custom NanoString assay. In parallel, these derivative models underwent drug sensitivity screening. We found that expression of certain genes were dependent on the cancer model while others were model-independent. These model-independent genes can be used in profiling tumor-specific biology and in gauging therapeutic response. It remains to be seen whether or not cancer model-specific genes may be directly or indirectly, through changes to tumor microenvironment, manipulated to improve the concordance of in vitro derivative models with in vivo models yielding better prediction of therapeutic response.

Stackhouse, Christian T. (ORCID:0000000266601963)↗

Automated assessment of bilateral breast volume asymmetry as a breast cancer biomarker during mammographic screening

The biological concept of bilateral symmetry as a marker of developmental stability and good health is well established. Although most individuals deviate slightly from perfect symmetry, humans are essentially considered bilaterally symmetrical. Consequently, increased fluctuating asymmetry of paired structures could be an indicator of disease. There are several published studies linking bilateral breast size asymmetry with increased breast cancer risk. These studies were based on radiologists manual measurements of breast size from mammographic images. We aim to develop a computerized technique to assess fluctuating breast volume asymmetry in screening mammograms and investigate whether it correlates with the presence of breast cancer. Using a large database of screening mammograms with known ground truth we applied automated breast region segmentation and automated breast size measurements in CC and MLO views using three well established methods. All three methods confirmed that indeed patients with breast cancer have statistically significantly higher fluctuating asymmetry of their breast volumes. However, statistically significant difference between patients with cancer and benign lesions was observed only for the MLO views. The study suggests that automated assessment of global bilateral asymmetry could serve as a breast cancer risk biomarker for women undergoing mammographic screening. Such biomarker could be used to alert radiologists or computer-assisted detection (CAD) systems to exercise increased vigilance if higher than normal cancer risk is suspected.

Williams, Alex C↗

Occurrence of Breast Cancer After Chest Wall Irradiation for Pediatric Cancer, as Detected by a Multimodal Screening Program

Purpose: To assess the occurrence of breast cancer (BC) after exposure to ionizing radiation for pediatric cancer, by means of a multimodal screening program. Patients and Methods: We identified 86 patients who had received chest wall radiation therapy for pediatric cancer. Clinical breast examination (CBE), ultrasound (US), and mammography (MX) were performed yearly. Magnetic resonance imaging (MRI) was added as of October 2007. We calculated the risk of developing BC by radiation therapy dose, patient age, and menarche before or after primary treatment. Results: Eleven women developed a BC from July 2002-February 2010. The sensitivity of the screening methods was 36% for CBE, 73% for MX, 55% for US, and 100% for MRI; the specificity was 91%, 99%, 95%, and 80% for CBE, MX, US, and MRI, respectively. The annual BC detection rate was 2.9%. The median age at BC diagnosis was 33 years. Although age had no influence, menarche before as opposed to after radiation therapy correlated significantly with BC (P=.027): the annual BC detection rate in the former subgroup was 5.3%. Conclusions: Mammography proved more sensitive and specific in our cohort of young women than CBE or US. Magnetic resonance imaging proved 100% sensitive (but this preliminary finding needs to be confirmed). Our cohort of patients carries a 10-fold BC risk at an age more than 20 years younger than in the general population.

62 RADIOLOGY AND NUCLEAR MEDICINE↗

WE-D-207-01: Background and Clinical Implementation of a Screening Program

In the United States, Lung Cancer is responsible for more cancer deaths than the next four cancers combined. In addition, the 5 year survival rate for lung cancer patients has not improved over the past 40 to 50 years. To combat this deadly disease, in 2002 the National Cancer Institute launched a very large Randomized Control Trial called the National Lung Screening Trial (NLST). This trial would randomize subjects who had substantial risk of lung cancer (due to age and smoking history) into either a Chest X-ray arm or a low dose CT arm. In November 2010, the National Cancer Institute announced that the NLST had demonstrated 20% fewer lung cancer deaths among those who were screened with low-dose CT than with chest X-ray. In December 2013, the US Preventive Services Task Force recommended the use of Lung Cancer Screening using low dose CT and a little over a year later (Feb. 2015), CMS announced that Medicare would also cover Lung Cancer Screening using low dose CT. Thus private and public insurers are required to provide Lung Cancer Screening programs using CT to the appropriate population(s). The purpose of this Symposium is to inform medical physicists and prepare them to support the implementation of Lung Screening programs. This Symposium will focus on the clinical aspects of lung cancer screening, requirements of a screening registry for systematically capturing and tracking screening patients and results (such as required Medicare data elements) as well as the role of the medical physicist in screening programs, including the development of low dose CT screening protocols. Learning Objectives: To understand the clinical basis and clinical components of a lung cancer screening program, including eligibility criteria and other requirements. To understand the data collection requirements, workflow, and informatics infrastructure needed to support the tracking and reporting components of a screening program. To understand the role of the medical physicist in implementing Lung Cancer Screening protocols for CT, including utilizing resources such as the AAPM Protocols and the ACR Designated Lung Screening Center program. UCLA Department of Radiology has an Institutional research agreement with Siemens Healthcare; Dr. McNitt-Gray has been a recipient of Research Support from Siemens Healthcare in the past. Dr. Aberle has been a Member of Advisory Boards for the LUNGevity Foundation (2011-present) and Siemens Medical Solutions. (2013)

60 APPLIED LIFE SCIENCES↗

WE-D-207-03: CT Protocols for Screening and the ACR Designated Lung Screening Program

In the United States, Lung Cancer is responsible for more cancer deaths than the next four cancers combined. In addition, the 5 year survival rate for lung cancer patients has not improved over the past 40 to 50 years. To combat this deadly disease, in 2002 the National Cancer Institute launched a very large Randomized Control Trial called the National Lung Screening Trial (NLST). This trial would randomize subjects who had substantial risk of lung cancer (due to age and smoking history) into either a Chest X-ray arm or a low dose CT arm. In November 2010, the National Cancer Institute announced that the NLST had demonstrated 20% fewer lung cancer deaths among those who were screened with low-dose CT than with chest X-ray. In December 2013, the US Preventive Services Task Force recommended the use of Lung Cancer Screening using low dose CT and a little over a year later (Feb. 2015), CMS announced that Medicare would also cover Lung Cancer Screening using low dose CT. Thus private and public insurers are required to provide Lung Cancer Screening programs using CT to the appropriate population(s). The purpose of this Symposium is to inform medical physicists and prepare them to support the implementation of Lung Screening programs. This Symposium will focus on the clinical aspects of lung cancer screening, requirements of a screening registry for systematically capturing and tracking screening patients and results (such as required Medicare data elements) as well as the role of the medical physicist in screening programs, including the development of low dose CT screening protocols. Learning Objectives: To understand the clinical basis and clinical components of a lung cancer screening program, including eligibility criteria and other requirements. To understand the data collection requirements, workflow, and informatics infrastructure needed to support the tracking and reporting components of a screening program. To understand the role of the medical physicist in implementing Lung Cancer Screening protocols for CT, including utilizing resources such as the AAPM Protocols and the ACR Designated Lung Screening Center program. UCLA Department of Radiology has an Institutional research agreement with Siemens Healthcare; Dr. McNitt-Gray has been a recipient of Research Support from Siemens Healthcare in the past. Dr. Aberle has been a Member of Advisory Boards for the LUNGevity Foundation (2011-present) and Siemens Medical Solutions. (2013)

60 APPLIED LIFE SCIENCES↗