Pathways to Discovery - Summer 2018 - UChicago Medicine Comprehensive Cancer Center by UChicago Medicine Community Benefit Report

Pathways TO DISCOVERY

AT T H E FO R E F R O NT O F C A N CE R CARE AND DIS COVE RY

Cancer Up Close FEATURE STORIES 1

ERFECTING MRI AS A BREAST CANCER P SCREENING TOOL

MOLECULAR IMAGING PROBES THE EFFECTS OF NICOTINE AND SMOKING CESSATION THERAPIES

IMPROVING PROSTATE CANCER DIAGNOSIS WITH MRI RISK MAPS

IMAGING AND DEEP LEARNING IN PRECISION MEDICINE FOR CANCER

SUMMER 2018

Pathways TO DISCOVERY

AT THE FOREFRONT OF CANCER CARE AND D ISCOVERY

Summer 2018 E X E C U T I V E E D I TO R

Jane Kollmer SENIOR SCIENCE WRITER

Kathleen Goss, PhD CO N T R I B U T I N G W R I T E R S

Ashley Heher Jordan A. Porter-Woodruff E D I TO R I A L A DV I S O R S

Michelle Le Beau, PhD Marcy List, PhD P H O TO G R A P H Y

David Christopher Rob Hart Robert Kozloff Lab of Maryellen Giger, PhD Lab of William Green, PhD Lab of Gregory Karczmar, PhD Lab of Aytekin Oto, MD, MBA Jean Lachat Lorna Wong John Zich DESIGN

Pivot Design, Inc. PRINTING

G Thomas Partners LLC Pathways to Discovery is a publication of the University of Chicago Medicine Comprehensive Cancer Center. T H E U N I V E R S I T Y O F C H I C AG O M E D I C I N E CO M P R E H E N S I V E C A N C E R C E N T E R 5 8 41 S . M A RY L A N D AV E . MC1140, H212 C H I C AG O , I L 6 0 6 3 7 P H O N E 1 -7 7 3 -70 2- 6 1 8 0 FA X 1 -7 7 3 -70 2- 9 3 1 1 F E E D B AC K@ B S D . U C H I C AG O . E D U

From the Director Imaging touches every part of cancer, from understanding cancer biology at a molecular level to detecting the very earliest signs of cancer and guiding treatment. With continual advances in technology, our imaging experts are able to extract more information from images than ever before. Their research findings have led to better ways to detect and diagnose cancer, as well as monitor response to therapy. The stories in this Pathways to Discovery focus on the Comprehensive Cancer Centerâ&#x20AC;&#x2122;s strength in advanced imaging research. Our team of imaging experts apply functional and anatomic imaging to noninvasively study how cancer initiates, progresses, and spreads. The new insights they uncover improve cancer detection and treatment, bringing us closer to realizing our goal of precision medicine, where treatment is tailored to the individual patient. In this issue, you will also find examples of our most recent research breakthroughs, new faculty, member honors, and clinical trials. Thank you for your support, as always! Regards,

Michelle M. Le Beau, PhD Director, The University of Chicago Medicine Comprehensive Cancer Center; Arthur and Marian Edelstein Professor of Medicine

Perfecting MRI as a Breast Cancer Screening Tool Mammography is the most routinely used imaging tool to screen for breast cancer, but it is not the best option for the approximately 40 percent of women who have dense breasts. Dense breast tissue obscures small masses, making them difficult to detect by mammography. Women with dense breasts are at higher risk of missed diagnosis and, therefore, need additional imaging tests to rule out suspicious areas. Mammography also often does not find invasive cancers until they are fairly advanced. Although mammography finds many ductal carcinoma in situ (DCIS)—or early-stage tumors confined to the lining of the breast milk duct—it does not reliably discriminate between DCIS that is not clinically significant and DCIS that will progress to become invasive and life-threatening.

MRI and Breast Screening The use of magnetic resonance imaging, better known as MRI, for breast cancer screening offers significant advantages for women with dense breasts and/or with moderate to high risk for breast cancer. MRI is much more sensitive than mammography, meaning it can pick up even very small abnormalities, regardless of breast density or fatty tissue in the breast. Importantly, MRI can find invasive breast cancers in some women (especially women with dense breasts) years before they would be found by mammography. The earlier a breast cancer is diagnosed, the better the survival outcome. MRI also has very strong negative predictive value, meaning that women who receive negative

findings on MRI can be very confident that they do not have clinically significant breast cancer. Although MRI has many advantages, there are still several hurdles to overcome before its wide adoption for breast cancer screening. For instance, conventional MRIs are much too expensive for routine screening of millions of women. In addition, MRI can produce too many false positives—resulting in unnecessary stress for patients, unnecessary biopsies, and expense. There are now concerns about routine use of MRI contrast agents in a large population of women due to adverse effects. The University of Chicago Medicine Comprehensive Cancer Center has built an interdisciplinary group of researchers and clinicians who are developing innovative and translational solutions to these problems. The team includes radiologists, medical physicists, oncologists and an experienced, dedicated staff of technicians and clinical research coordinators. The group has made several major contributions to the use of MRI for breast cancer screening.

Improving Diagnostic Accuracy Gregory Karczmar, PhD, professor of radiology and co-leader of the Comprehensive Cancer Center’s Advancing Imaging Program, and colleagues CANCER.UCHICAGO.EDU

Interdisciplinary Team of Researchers & Clinicians Radiologists

Medical Physicists

Oncologists

Hiroyuki Abe, PhD, professor of radiology

Maryellen Giger, PhD, A.N. Pritzker Professor of Radiology and Vice-Chair of Basic Science Research in the Department of Radiology

Olufunmilayo Olopade, MD, Walter L. Palmer Distinguished Service Professor of Medicine and Human Genetics, associate dean for global health, and director of the Center for Clinical Cancer Genetics

David Schacht, MD, MPH, associate professor of radiology and section chief for breast imaging Deepa Sheth, MD, assistant professor of radiology Kirti Kulkarni, MD, associate professor of radiology Aytekin Oto, MD, MBA, professor of radiology and surgery and co-leader of the Comprehensive Cancer Center’s Advanced Imaging program

Gregory Karczmar, PhD, professor of radiology and co-leader of the Comprehensive Cancer Center’s Advancing Imaging Program Milica Medved, PhD, associate professor of radiology Xiaobing Fan, PhD, professor of radiology

developed faster and more clinically useful ways to obtain MRI scans. MRI is traditionally performed by administering a chemical substance known as a contrast agent and acquiring image scans every 60 to 90 seconds, for up to 40 minutes. Although this method provides very detailed images, it does not adequately show the rate at which the contrast agent is being taken up by suspicious lesions, which is useful information in identifying cancer. In order to obtain this information, Karczmar’s group developed a new technique called ultrafast dynamic contrast-enhanced (DCE) MRI. The technique involves scanning the breasts on both sides every 2 to 4 seconds to accurately measure the activity of the contrast media, which can reveal the presence of breast cancer. Karczmar’s lab was among the three labs that first demonstrated advantages of performing this type of MRI for breast cancer. They are also pioneering unique ways of analyzing this new type of data and have received a patent for novel quantitative parameters derived from ultrafast DCE-MRI that have potential to significantly increase diagnostic accuracy.

Reducing Time of Scan The researchers also found a way to make ultrafast DCE-MRI even more effective by integrating it 2

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Jane Churpek, MD, assistant professor of medicine, co-director of the Comprehensive Cancer Risk and Prevention Program Iris Romero, MD, MS, associate professor of obstetrics/ gynecology, dean for diversity and inclusion Suzanne Conzen, MD, professor of medicine

with abbreviated MRI. Abbreviated MRI is a 5to 10-minute scan that aims to reduce costs and increase convenience and efficiency compared to conventional scans by skipping unnecessary acquisitions. Adding ultrafast DCE-MRI into abbreviated MRI screening can achieve effective results in 10 minutes or less. “Compared to conventional MRI, this has potential to substantially reduce costs,” said Karczmar.

Reducing Contrast Agents Contrast materials are injected into a patient before imaging to help radiologists distinguish normal from abnormal areas. Although these materials are relatively safe, some patients may have adverse reactions. To address these concerns, Karczmar and colleagues have developed techniques that require only 15% to 25% of a standard dose of contrast agent without loss of diagnostic accuracy. They have been able to show that lower doses of contrast agent have potential advantages for the detection of cancer, while reducing costs and concerns about adverse effects. They have also developed an innovative MR method for detecting cancer without contrast media.

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This method, referred to as “high spectral and spatial resolution imaging” (HiSS) detects invasive breast cancer as reliably as conventional methods. 25

“Breast cancer screening without injection of contrast media would reduce costs, increase compliance with screening, and make it possible to perform MRI screening outside of hospitals, for example, in local malls and doctor’s offices,” Karczmar said.

A Greater Role for MRI As a technology that can detect early breast cancer regardless of breast density, MRI is playing a greater role in breast cancer management, especially with new ways to make it faster, more convenient, and less expensive. Many of the MRI methods newly developed by UChicago researchers are being used in routine clinical practice at UChicago Medicine. Additionally, Karczmar and his team are sharing these advancements with other institutions both locally and nationally through participation in a national multicenter clinical trial.

As a next step, Karczmar and colleagues are looking at new ways to use MRI to improve diagnosis of DCIS. Much of the support for this research comes from funds provided by the University of Chicago Cancer Research Foundation (UCCRF) and its Women’s Board.

0 MRI scans with malignant (a,b) and benign (c,d) breast lesions indicated by white arrows show that the areas that ‘light up’ soonest after the administration of contrast are malignancies.

Bringing Breast Cancer Screening to the Community African-American women are at highest risk of dying from breast cancers. Breast cancer screening is therefore crucial for women from underserved populations. Expense and convenience are critical factors for the underserved community on the South Side of Chicago. The University of Chicago team is partnering with local organizations such as the Metropolitan Chicago Breast Cancer Task Force to increase recruitment to clinical trials of new MRI screening methods. “It’s important to improve community outreach so that members of the surrounding community can benefit from the new breast MRI methods being developed,” said Karen Kim, MD, professor of medicine and director of the University of Chicago Medicine Comprehensive Cancer Center Office of Community Engagement and Cancer Disparities. “If we can catch more cancers earlier, fewer women will die from breast cancer.”

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Molecular Imaging Probes the Effects of Nicotine and Smoking Cessation Therapies Tobacco is the leading cause of preventable death in the United States. Despite its link to disease, including cancer, millions of people still use tobacco worldwide. Researchers are interested in understanding the underlying mechanisms of nicotine, the major addictive chemical found in tobacco, in order to develop more effective strategies to overcome addiction. When nicotine enters the body, it binds to neuro transmitter receptors in the brain called nicotinic acetylcholine receptors (nAChRs) that in turn bind to the neurotransmitter acetylcholine (Ach). Varenicline, the smoking cessation drug known as Chantix, is understood to work by activating the pleasure-producing nAChRs, making fewer available targets for nicotine to bind to, thereby curbing nicotine’s effects. Prolonged exposure to nicotine, however, causes an increased number of binding sites, a process known as “upregulation” that is important in the craving and withdrawal effects seen in nicotine addiction. Because varenicline also has been observed to cause increased upregulation, scientists have been long puzzled about how varenicline works to reduce nicotine cravings. And because varenicline, the most effective drug of its kind, only stops smoking in about 30–40% of people who use it, more knowledge is needed to explain its relationship to nicotinic receptors. The laboratory of William Green, PhD, professor of neurobiology, made progress on this front when they discovered that varenicline gets trapped within cells’ acidic compartments called vesicles that contain nAChRs. Chronic nicotine exposure increases

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the numbers of vesicles, thereby increasing varenicline trapping in neurons. Nicotine, however, does not get trapped and rapidly escapes the vesicles. The slow release of the trapped varenicline from the vesicles reduces nAChR signaling caused by nicotine-induced upregulation. This discovery may provide a new paradigm for how varenicline works. It also leads to many other questions, such as, how can studying nAChRs’ interactions with molecules such as varenicline and nicotine be used to design more effective therapies? Novel molecular imaging approaches provide an opportunity to better understand these mechanisms at a molecular level.

Kidney Cells +ACID

DIFFERENCE

+NICOTINE

-NICOTINE

-ACID

Micrographs (or microsope images) of fluorescently tagged nicotinic receptors in kidney cells show that exposure to nicotine leads to increased number of acidic vesicles.

Green is collaborating with Chin-Tu Chen, PhD, associate professor of radiology, and Jogeshwar Mukherjee, PhD, professor of radiological sciences at the University of California–Irvine and former radiochemistry faculty member at UChicago in the 1990s, to develop positron emission tomography (PET) probes to image proteins in the brain that respond to nicotine. PET involves radioactive tracers that are injected into the body, allowing radiologists to visualize what is happening as the “glowing” molecules are processed. Building on their hypothesis that compounds with fast kinetics are trapped less in acidic vesicles and those with slow kinetics are trapped more, the researchers will be testing different PET probes in cells and brains in animals to find the optimal probe for studying nicotine receptors. Just like nicotine and varenicline, PET probes have different properties that affect how they bind to receptors.

Green and Chen anticipate that findings from their work may be applied to the work of Andrea King, PhD, and Harriet de Wit, PhD, both professors of psychiatry and behavioral neuroscience, who are studying human addiction to nicotine and the effects of smoking cessation therapy. This type of molecular imaging research would not be possible without the use of a particle accelerator known as a cyclotron. The University of Chicago re-established its cyclotron research facility in January 2017 after two decades without one, making it the only academic medical institution in Illinois with an operational cyclotron. Green and Chen’s project is the first one initiated and externally funded since the cyclotron’s arrival, opening the door for many other molecular imaging studies for cancer and other diseases.

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Improving Prostate Cancer Diagnosis with MRI Risk Maps Prostate cancer is the most common cancer among American men yet current diagnostic tools, including PSA (prostate-specific antigen) screening, cannot tell the difference between prostate tumors that are life threatening and those that are indolent, or slow growing. To spare patients from undergoing unnecessary, invasive prostate biopsies and aggressive therapy, as well as to reduce overall healthcare spending, the medical field needs better diagnosis methods. Toward that end, physicians and researchers at the University of Chicago Medicine are seeking new ways to arrive at a definitive diagnosis for prostate cancer. Experts are exploring the use of magnetic resonance imaging (MRI) as a non-invasive tool for imaging cancer in the prostate because of its high soft-tissue contrast and ability to view images in multiple planes. By providing highly detailed images of the prostate, MRI can provide unique functional and biologic information not available with other imaging technology. The co-leaders of the Comprehensive Cancer Centerâ&#x20AC;&#x2122;s Advancing Imaging Program, Aytekin

Histopathology

MRI

Oto, MD, MBA, professor â&#x20AC;&#x2039;of radiology and surgery, and Gregory Karczmar, PhD, professor of radiolÂogy, recently led a prospective study assessing whether their novel MRI technique can diagnose prostate cancer accurately. Oto, Karczmar, and colleagues obtained preoperative images from 22 patients with prostate cancer using hybrid multidimensional MR imaging, a new imaging technique that provides quantitative information on tissue composition. The patients then underwent surgery to remove their prostate, known as radical prostatectomy, and the extracted tissue was placed on slides, with the areas of the tumor marked by a pathologist. Cancer Risk Score 100

Gleason 3+4

Gleason 4+3

Diagnosis of prostate cancer through MRI and associated risk map for cancer presence compared to histopathology.

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Aytekin Oto, MD, MBA, professor of radiology and surgery, helps a patient prepare for a prostate MRI procedure.

The MR images were analyzed based on the three components that make up prostate tissue: the lumen, the epithelium, and the stroma. The researchers chose these parameters because they are clinically relevant; the presence of prostate cancer is often characterized by an increased volume of epithelium and a decreased volume of lumen. By obtaining quantitative measurements of the volumes of each tissue component, the researchers were able to create a map showing the tumor’s location in the prostate. By assigning values to the volumes of tissue composition, they were also able to predict the tumor’s aggressiveness. To evaluate how accurate these maps were, the researchers compared the MRI scans with the pathology slides of confirmed cancer and found that the results matched closely. The study findings, as reported in a research paper published in Radiology, conclude that prostate tissue components can be measured noninvasively by using hybrid multidimensional MR imaging and have the potential to improve the diagnosis of prostate cancer and determine its aggressiveness. “MRI has been used to guide biopsy in prostate cancer, but our goal is to be able to use MRI to

obtain diagnostic information about prostate cancer noninvasively,” Oto said. “We are excited by the idea of these risk maps serving as a ‘virtual biopsy’ that can help patients avoid needle biopsies and false negative test results in the future.” He adds that there is potential to translate the MRI technique for risk-mapping other cancers, such as breast and liver cancers, but more studies are needed to understand the tissue composition of other cancers. “We need to tailor our MR technique so that our patients don’t need to undergo unnecessary biopsies or treatment,” he said. References: Chatterjee et al., Radiology 287:864-73, 2018. Research support: National Institutes of Health (grants NIH R01 CA172801 and NIH 1S10OD018448-01), Philips Healthcare, and the University of Chicago Medicine Comprehensive Cancer Center. Patent - Karczmar GS, Oto A, Chatterjee A, Devaraj A. Non-invasive estimation of prostate tissue composition with compartmental analysis of Hybrid Multi-dimensional MRI. (Provisional patent application submitted—US Application #: 62563362)

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Imaging and Deep Learning in Precision Medicine for Cancer Medical images are routinely used to detect the presence of cancer. However, there may be more to these images than the human eye can see. Images contain data that can be collected, measured, and analyzed by computers. ABOVE: An analysis of breast cancer on MRI using computer-extracted data allows for a â&#x20AC;&#x153;virtualâ&#x20AC;? digital biopsy of the tumor that is both non-invasive and repeatable.

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Computer-aided detection (CADe), for example, uses quantitative image analysis methods to recognize patterns of breast cancer on mammograms that radiologists may miss. CADe is an artificial intelligence technology for cancer detection, initially for breast and lung images, which was developed and translated for ultimate clinical use by a team of medical physicists and radiologists at the University of Chicago in the 1980s. Today, more than 80 percent of screening mammograms are read by a computer as a “second reader.” In addition, multiple algorithms are being translated for the detection and follow-up of lung nodules on thoracic radiographs and computed tomography (CT) scans. Beyond detecting cancer, computers have proven useful in diagnosis. Computer-assisted diagnosis (CADx) aims to help physicians diagnose cancer accurately by analyzing the features of an image and estimating the likelihood that those features correspond to a specific disease state, such as a tumor being cancerous or not. Over the past few decades, advances in new computer technologies and image acquisition and analysis tools have enabled deeper learning from medical images than ever before possible. Imaging data are, therefore, increasingly valuable for many applications in cancer, including risk assessment, detection, diagnosis, prognosis, therapy response, and basic scientific research. UNLEASHING IMAGING’S POTENTIAL WITH RADIOMICS AND DEEP LEARNING Even with these tremendous advances, there is still great untapped potential to use information from medical images to support physician decisionmaking. In recent years, CAD has expanded to a broader field called radiomics, which involves the conversion of images into minable data. Obtaining radiomic data may involve computer segmentation of a tumor from its background followed by computer extraction of various tumor features, including size, shape, texture, and margins (morphology), as well as other features related to physiologic processes.

“By extracting imaging features and relating them, we are able to better understand the patterns that define cancer.” — MARYELLEN GIGER, PhD Giger and others are merging these image-based features through machine learning algorithms to yield tumor signatures. MINING IMAGING DATA FOR DISCOVERY Machine learning is dependent on large datasets of tumor images across diverse populations. The Cancer Imaging Archive (TCIA) is a National Cancer Institute-funded research effort to aggregate de-identified medical images of cancer and supporting data, such as patient outcomes, treatment details, genomics, pathology, and expert analyses. Giger and colleagues are leveraging this database, and others such as The Cancer Genome Atlas (TCGA), to make discoveries that translate to image-based biomarkers for use in the clinic.

Did You Know? If deep learning is not a familiar term, it’s because it is a subcategory of machine learning, which is a subcategory of artificial intelligence. It may sound like a new area, but the implementation of deep networks that allow computers to learn directly from image data have been around since the early 1990s. Now however, these algorithms are deeper, i.e., more complex, given the availability of more powerful computers.

Maryellen Giger, PhD, A.N. Pritzker Professor of Radiology and Vice-Chair for Basic Science Research in the Department of Radiology, and a nationally recognized leader in the field of quantitative imaging, is at the forefront of radiomics. Identifying image-based features that characterize cancer is a primary goal of radiomics. Further,

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“Similar to how the genomics community approached the big biology of the Cancer Genome Project, the radiological community continues to conduct robust collection, annotation, analysis, and evaluation of images of large populations,” said Giger. “By extracting imaging features and relating them, we are able to better understand the patterns that define cancer.”

prognostic tools. The first step is to compare radiomic features with a biopsy and other tests that a patient may have to see which features correlate and complement one another. From this, researchers aim to learn not only where the cancer is, but more specifically what type of cancer it is and how it is behaving. They can then use that information to develop predictive models.

Giger was tasked by the National Cancer Institute to co-lead the TCGA Breast Phenotype Group in order to investigate and map relationships between computer-extracted quantitative MRI radiomic tumor features and various clinical, molecular, and genomic markers of prognosis and risk of recurrence, including gene expression profiles.

For example, if a certain feature on a tumor image correlates to a feature in common with a known genetic marker, that information could potentially help guide treatment decisions. The same principle applies in imaging to monitor treatment response and predict future risk of recurrence. This is what Giger describes as a “virtual digital biopsy,”—which is non-invasive, covers the entire tumor, and is reproducible, and it would add value and meaning to the information gained from biopsies and other tests. A virtual biopsy would not replace an actual biopsy, but rather it could be used when an actual biopsy is not practical, such as during screening or repeated assessments for response to therapy.

Among the many novel findings, the group discovered some highly specific imaging-genomics associations among invasive breast cancers, which may be potentially useful in imaging-based diagnoses that can inform the genetic progress of tumors and discovery of genetic mechanisms that regulate the development of tumor phenotypes. THE VIRTUAL DIGITAL BIOPSY Another major goal of radiomics and machine learning is to link image data with clinical, pathologic, and genomic data to create diagnostic or

Studies such as these are contributing to the goal of precision medicine in imaging, which is to personalize the screening and detection of early disease, and then give the right person the right treatment at the right time.

A Timeline of Commercialization & Innovation Maryellen Giger, PhD, has a track record of translating imaging research into clinical advances over the years.

1980s UChicago researchers pioneer the field of CAD, and develop image analysis methods for computer-aided detection (CADe) and computer-aided diagnosis (CADx)

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1993 R2 Technology is founded to commercialize CADe

1998 R2 Technology’s ImageChecker is the first CADe system approved by the FDA for screening mammography

Radiomics is the study of the relationships between features “seen” in medical images (as shown here) and the cancer’s biology in order to personalize screening, detection, and the assessment of treatment response more effectively.

2010

2006

Quantitative Insights is established through the University of Chicago New Venture Challenge and formed to commercialize CADx

Hologic acquires R2 Technology

2017 Quantitative Insights’ QuantX becomes the first FDA-cleared machine-learning driven system (CADx) to aid in cancer diagnosis.

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Research

Meet the Expert Maryellen Giger, PhD A.N. PRITZKER PROFESSOR OF RADIOLOGY

For more than 25 years, Maryellen Giger, PhD, has conducted research on computer-aided diagnosis and quantitative image analysis in the areas of breast cancer, lung cancer, and bone diseases. Her work has revolutionized the way medical images are used to help doctors detect and diagnose cancer in patients. She is also leading a movement to apply artificial intelligence to images to yield improved biomarkers of cancer, a key goal of precision medicine. diagnose disease (such as breast cancer). Along with my colleagues, we established the field of CAD—or computer-aided diagnosis. The research has flourished to include various disease types, various image interpretation tasks, and various imaging acquisition modalities, and now includes big data mining to yield more discoveries. What is the impact of your research? I have seen first-hand the impact of combining laboratory innovations with entrepreneurial expertise to transfer new knowledge into new applications for the public. After a decade of pioneering laboratory research at the University of Chicago, my colleagues and I worked in the 1990s with the University’s entrepreneurial center to translate and commercialize our computer-aided detection methods. R2 Technology, a start-up company, licensed the patents from the University and developed the first FDA-approved computer-aided detection system, which is now standard of care in breast cancer screening programs. R2 Technology was eventually acquired by a major women’s health company, and computer-aided detection is now mainstream.

Explain your research in simple terms in 2–5 sentences. My lab discovers new ways to use computers to enrich the information obtained from medical images so that radiologists can better find and

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Inspired by my prior experience, my lab, in 2009, and some business school students, formed the company Quantitative Insights to bring another laboratory invention to the public. The company’s product, QuantX, is an intuitive clinical interface that seamlessly merges our image analysis methods with the display of mammography, ultrasound, and MRI. It received FDA clearance last summer,

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making it the first computer-aided diagnosis platform incorporating machine learning for the evaluation of breast abnormalities. How did you become interested in a career as a medical physicist? During my undergraduate years at Illinois Benedictine College (USA), I was fortunate to receive summer jobs at Fermi National Accelerator Lab where I worked on the beam diagnostics team and in the neutron therapy facility. After college, I received a Rotary Fellowship to Exeter University in England and investigated digital signal analysis on electrocardiograms for my MSc in physics. These experiences led me to the field of medical physics, which I then pursued at the University of Chicago, earning a PhD in 1985. What is the most rewarding part of your job? My life of research and teaching is not just a job, not just a careerâ&#x20AC;&#x201D;it is my passion. The most rewarding experience for me is educating the next generation. I have mentored over 100 students, and I feel successful when my students become my colleagues. If you had one piece of advice for someone considering your field, what would it be? Identify your passion in medical physics whether it be research, education, and/or clinical, and make a difference. Who inspires you? Many people have inspired me! Professor Vernon Wynn, my MSc advisor, taught me the fun of research, noting that while research is 99.9% frustration, it is that 0.1% when you find or realize an advancement that makes it all so worthwhile. Professor Kunio Doi, my PhD advisor, taught me how to conduct research and how to become an independent investigator. Professor Chin-Tu Chen was my graduate school classmate and is now a colleague who often serves as my sounding board. What do you love about working at the University of Chicago? We are more multidisciplinary than ever, and being at the University has allowed for the growth and the ability to cross the hallway and to cross the campus in order to find collaborators. I really appreciate the team approach to big science. This is intentional as we need to make sure that there is a strong link from research to clinical, and clinical to research.

Research Highlights Taking Prostate Cancer Drug with Food Lowers Cost The drug abiraterone acetate is a standard of care for advanced metastatic castration-Â resistant prostate cancer, but it can be very expensive for patients (up to $11,000 per month). A Comprehensive Cancer Center team led by Russell Szmulewitz, MD, assistant professor of medicine, and Mark Ratain, MD, Leon O. Jacobson Professor of Medicine, compared the effectiveness of taking a low dose of abiraterone (250 mg) with a low-fat meal to the standard dosing (1,000 mg fasting) and found that the prostate-specific antigen (PSA) response and progression-free survival were not different between the groups. Because the lower dose would be associated with a lower cost of the drug, these findings suggest that prescribers, payers and patients should take this into consideration when making abiraterone treatment decisions and support additional studies to determine the long-term effectiveness of this regimen. Szmulewitz et al., J Clin Oncol 2018 36:1389-95, 2018.

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Research Highlights (continued) RNA Modifications Control Therapy Response and Resistance in Leukemia

Pioneering Nanomedicine Enhances Immunotherapy Radiation therapy has been a mainstay of local cancer control for more than a century, while immuÂÂnotherapy has revolutionized how cancer can be treated systemically by mobilizing the immune system throughout the body. A multidisciplinary team led by Wenbin Lin, PhD, James Frank Professor of Chemistry, and Ralph Weichselbaum, MD, Daniel K. Ludwig Distinguished Service Professor of Radiation and Cell Oncology, developed a combination approach involving nanoscale metalorganic framework-enabled radiotherapyradiodynamic therapy with immunotherapy checkpoint blockade to treat mouse models of breast and colorectal cancer. They found that by employing the advantages of both local radiotherapy and systemic immunotherapy tumor rejection, they could overcome some limitations of each approach individually. This therapeutic strategy is now being tested in phase I clinical trials, sponsored by RiMO Therapeutics, a startup biotechnology company launched by Lin with assistance from the Polsky Center for Entrepreneurship. Lu et al., Nature Biomed Eng 2018 Epub ahead of print

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Although drugs that target epigenetic modifications (changes to DNA and RNA that influence gene expression, but do not change the genetic sequence) are effective in some patients with blood cancers, many patients develop resistance. A research team led by Jason Cheng, MD, PhD, assistant professor of pathology, identified a novel mechanism by which this resistance develops in myelodysplastic syndrome and acute myeloid leukemia. They found that enzymes that control RNA epigenetic modifications, called methyltransferases, bind to specific factors that control the structure of chromatin (the 3D organization of DNA) to make cancer cells sensitive or resistant to epigenetic-modifying drugs. Not only does this study provide molecular insights into the treatment of leukemia, it also uncovers new tools, or biomarkers, that can be used to predict and reduce the risk of treatment resistance. Cheng et al., Nat Commun 9:1163, 2018.

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Clinical Trials As a NCI-designated Comprehensive Cancer Center and a lead site for the National Clinical Trials Network, we provide national leadership in developing clinical trials, which offer more options for patients. With more than 350 open therapeutic trials available, we enroll approximately 1,000 patients each year. For a full listing, visit clinicaltrials.uccrc.org.

Spotlight: Cellular Therapies for Hematological Malignancies Cellular therapies hold great potential to improve outcomes for patients with hematologic malignancies, including leukemia, lymphoma, and myeloma. The University of Chicago Medicine is a leader in providing leading-edge cellular therapies for blood cancers, such as CAR (Chimeric Antigen Receptor) T-cell therapy. The following clinical trials are currently enrolling patients. • A Phase I Multicenter Study of KITE-585, an Autologous Anti-BCMA CAR T-Cell Therapy, in Subjects with Relapsed/Refractory Multiple Myeloma, IRB17-1329 • A Phase III, Randomized, Open-Label Study Evaluating the Efficacy of Axicabtagene Ciloleucel versus Standard of Care Therapy in Subjects with Relapsed/Refractory Diffuse Large B Cell Lymphoma (ZUMA-7), IRB17-1212 • A Randomized Trial Comparing CD3/CD19 Depleted or CD3 Depleted/CD56 Selected Haploidentical Donor Natural Killer (NK) Cell Based Therapy for Adults With Acute Myelogenous Leukemia Who Have Failed 1 or 2 Induction Attempts, IRB16-1015 • A Phase I/II Multi-Center Study Evaluating the Safety and Efficacy of KTE-C19 in Adult Subjects

with Relapsed/Refractory B-precursor Acute Lymphoblastic Leukemia (r/r ALL), IRB15-1147 • A Phase II Multicenter Study Evaluating the Efficacy of KTE-C19 in Subjects with Relapsed/ Refractory Mantle Cell Lymphoma (r/r MCL), IRB15-1146 • A Multicenter, Open-Label, Expanded Access Study Of Axicabtagene Ciloleucel For The Treatment Of Relapsed/Refractory Large B-Cell Lymphoma, IRB17-0781 • PROTECT: A Phase I, Non-Randomized, OpenLabel/Phase II, Randomized, Blinded Study of ProTmune™ (EX Vivo Programmed Mobilized Peripheral Blood Cells) versus Non-Programmed Mobilized Peripheral Blood Cells for Allogeneic Hematopoietic Cell Transplantation in Adult Subjects with Hematologic Malignancies, IRB16-1796 • A Phase I Open-Label Dose-Escalation Study to Evaluate the Safety of Intramuscular Injections of PLX-R18 in Subjects with Incomplete Hematopoietic Recovery Following Hematopoietic Cell Transplantation, IRB16-1437 • An Open-Label Phase 1/2 Study of JCARH125, BCMA targeted Chimeric Antigen Receptor (CAR) T Cells, in Subjects with Relapsed or Refractory Multiple Myeloma, IRB17-1426

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Research

Breast Surgery Consults Now Available in the Community Setting To make it more convenient for patients living in Chicago’s south and southwest suburbs to access highly skilled and compassionate surgeons near home, UChicago Medicine now offers breast surgery consults at facilities in Orland Park and New Lenox. Fellowshiptrained female breast surgeons Jean Bao, MD, assistant professor of surgery, and Jennifer Tseng, MD, assistant professor of surgery, will help patients at the UChicago Medicine Center for Advanced Care at Orland Park and the University of Chicago Medicine Comprehensive Cancer Center at Silver Cross Hospital understand their treatment options.

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Hyde Park

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Upcoming Events AU G

The Changing Face of Oral Cancer

OCT

19–20

5th Head and Neck Cancer Symposium for the Advanced Practitioner

AUGUST 10, 2018 The University of Chicago Gleacher Center 450 N. Cityfront Plaza Dr. Chicago, IL 60611

OCTOBER 19–20, 2018 Embassy Suites Chicago Downtown Magnificent Mile 511 N. Columbus Dr. Chicago, IL 60611

To register, visit uchospitals.edu/oralcancer2018

To register, visit https://bit.ly/2GWNRdC

PATHWAYS TO DISCOVERY SUMMER 2018

News

All of Us Research Program Launches The University of Chicago, as part of the Illinois Precision Medicine Consortium, helped launch the All of Us Research Program, a large-scale national effort to enroll one million people in a study on the lifestyle, environmental, and genetic factors that influence health. The study aims to accelerate medical breakthroughs by helping researchers find patterns that may reveal how to better prevent and treat diseases. All of Us kicked off at public launch events across the country, including Chicago, in early May. Visit https://www.joinallofus.org to sign up.

NCI Renews Cancer Center Designation as Comprehensive The National Cancer Institute (NCI) has renewed the University of Chicago Medicine’s designation as a comprehensive cancer center, a prestigious distinction that the federal agency grants to recognize an institution’s excellence in research. Only two cancer centers in Illinois and 49 in the country carry comprehensive status. This is the third consecutive time the Cancer Center has received a five-year “comprehensive” designation since 2008.

A Cancer Center Designated by the National Cancer Institute

CHICAGO PLAYS HOST TO TWO MAJOR NATIONAL CANCER MEETINGS

At the Chicago launch event, Senator Dick Durbin (D-IL) chats with Habibul Ahsan, MD, Louis Block Distinguished Service Professor of Public Health Sciences, Medicine, and Human Genetics, and director of the University of Chicago Institute for Population and Precision Health, who is leading UChicago’s All of Us effort.

Most of the country’s cancer researchers and physicians came to Chicago this year as both the American Association for Cancer Research (AACR) and the American Society of Clinical Oncology (ASCO) held their annual meetings at McCormick Place in Chicago. The themes of the two meetings revolved around translating new discoveries into treatments that directly improve patient care. The 2018 AACR meeting, held in April, focused on the theme “Driving Innovative Cancer Science to Patient Care,” while ASCO’s 2018 meeting in June was titled, “Delivering Discoveries: Expanding the Reach of Precision Medicine.” Faculty and trainees from the University of Chicago were well- represented at both conferences with oral and poster presentations. CANCER.UCHICAGO.EDU

News

Hospital leaders and employees wave blue ribbons and dance in honor of colorectal cancer awareness.

UChicago Medicine Employees Shake Their Booties for Colon Cancer Awareness In late March, “Shake your Booty” brought together University of Chicago Medicine (UCM) employees and hospital leaders to have fun, listen to music, walk through a giant colon, and more importantly booty shake to raise awareness for colorectal cancer, a common disease that is preventable through screening. Among UCM employees, the colorectal cancer screening rate is less than 40%, 18

PATHWAYS TO DISCOVERY SUMMER 2018

which is lower than hospitals that care for uninsured patient populations. “Shake your Booty” was the launch of a new pilot program to support colorectal cancer screening for hospital employees. A total of 61 UCM employees signed pledge cards and 28 employees signed up to receive colorectal cancer screening.

News

UCHICAGO MEDICINE PARTNERS WITH PROFESSIONAL BASKETBALL

Holly Benjamin, MD, sports medicine specialist; Stephanie Dolson, Sky center; and Sharon O’Keefe, UChicago Medicine president, celebrate new partnership.

The WNBA’s Chicago Sky and UChicago Medicine have agreed to a multiyear partnership that names the academic health system as the official medical provider and a major sponsor of the team. Under the partnership, UChicago Medicine will utilize the Chicago Sky’s marketing platforms to provide public education about numerous community wellness topics, including nutrition and physical fitness.

New Faculty For more information about our new faculty, visit uchospitals.edu/physicians.

UChicago Medicine Receives Highest Honor for Nursing Excellence

Yasmin Asvat, PhD, assistant professor of psychiatry and behavioral neuroscience, specializes in the psychological care of cancer patients, cancer survivors, and their caregivers. Her research examines quality of life and resilience in cancer patients and survivors, and evaluates interventions to promote improved physical and psychological well-being in this population.

Jagoda Jasielec, MD, assistant professor of medicine, specializes in the care of patients with benign and malignant hematologic diseases, especially patients with multiple myeloma. Her clinical research is also focused on multiple myeloma.

The University of Chicago Medicine received the prestigious Magnet Recognition® Program designation, Magnet Recognition status, the gold standard for nursing excellence and high-quality patient care, from the American Nurses Credentialing Center. The distinction was granted April 26 after a lengthy and rigorous review process. (Above) UChicago Medicine President Sharon O’Keefe; Debra Albert, Sr. VP Patient Care Services and Chief Nursing Officer; and Kenneth Polonsky, MD, Dean and Executive Vice President for Medical Affairs at the University of Chicago, toast with sparkling grape juice.

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News

LEVEL 1 ADULT TRAUMA CENTER OPENS With the May 1 launch of Level 1 adult trauma services, UChicago Medicine now offers the highest level of care for life-threatening injuries. To be considered a Level 1 trauma center, a hospital must have the resources and staffing needed to provide comprehensive, specialized care for patients who suffer a traumatic injury from such causes as motor vehicle crashes, gunshot wounds, burns, and falls.

A Celebration for Cancer Survivors On Saturday, May 5, cancer survivors and their caregivers came together at UChicago Medicine for “Survive. Thrive. Celebrate.”—a celebration of survivorship. They spent the morning networking with fellow patients and advocacy groups, and

they heard educational sessions from leading UChicago Medicine faculty and staff who discussed topics such as nutrition and wellness, life after cancer, and what’s ahead in clinical cancer research.

Cancer survivors and caregivers hold up a banner filled with messages of hope and encouragement for those going through cancer treatment.

PATHWAYS TO DISCOVERY SUMMER 2018

News

Faculty Awards and Honors

Ralph Weichselbaum, MD, Daniel K. Ludwig Distinguished Service Professor of Radiation and Cellular Oncology, Chair of the Department of Radiation and Cellular Oncology, and co-director of the Ludwig Center for Metastasis Research, is the recipient of the 2018 American Society of Clinical Oncology’s David A. Karnofsky Memorial Award and Lecture for outstanding contributions to cancer research, diagnosis, and/or treatment.

Daniel A. Arber, MD, has been named the first Donald West and Mary Elizabeth King Professor in the Department of Pathology. Arber is chair of the Department of Pathology and an authority on the diagnosis, classification and molecular genetics of blood cancers. His research focuses on molecular genetics and immunophenotypic changes in blood cancers.

Habib Ahsan, MD, MMedSc, Louis Block Distinguished Service Professor of Public Health Sciences, Medicine and Human Genetics, has been appointed as Dean of Population and Precision Health in the Biological Sciences Division and the inaugural director of a newly established Institute for Population and Precision Health.

Bana Jabri, MD, PhD, has been named the Sarah and Harold Lincoln Thompson Professor in the Department of Medicine and the College. Jabri, vice chair for research in the Department of Medicine and director of research at the University of Chicago Celiac Disease Center, is a gastroenterologist and an expert in human immunology.

Other Headlines from The Forefront Visit www.uchicagomedicine.org/cancer for these stories and more… • Revolutionary laser procedure treats early vocal cord cancer without harming healthy tissue

• Sex joins tobacco and alcohol as a cause of head and neck cancer

• Surgical robot can reduce pain from pancreatic cancer surgery

Melody Swartz, PhD, William B. Ogden Professor of Molecular Engineering, was elected to the American Academy of Arts and Sciences, one of the nation’s most prestigious honorary societies.

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Pathways Summer '16 FIN.indd 4

A Cancer Center Designated by the National Cancer Institute

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