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Editorial Board

Claire AlmanzaAsaithamby Aroumougame, Ph.D.Damiana Chiavolini, Ph.D.Hak Choy, M.D., FASTRORyan DaughertyKajal DesaiNeil Desai, M.D., M.H.S.Jonathan Feinberg, Ph.D.Michael Folkert, M.D., Ph.D.Raquibul Hannan, M.D., Ph.D.Xun Jia, Ph.D.Steve Jiang, Ph.D.Nathan Kim, M.D., Ph.D.Karen PattersonArnold Pompos, Ph.D.Asal Rahimi, M.D., M.S.David Sher, M.D., M.P.H.Michael Story, Ph.D.Robert Timmerman, M.D., FASTRO, FACRKenneth Westover, M.D., Ph.D.Mary Whitmore

SECTION 1 UNPARALLELED CARE

A Patient Experience: Investing in Quality, Efficiency, and Safety 4Breast Care: Advanced, Personalized Approach 22For Marilyn Gibson, the Decision Was an Easy One 30Fighting Kidney Cancer 34Fighting Prostate Cancer 38Brachytherapy: Expert and Advanced Guided Therapy 42

SECTION 2 DIVISION RESEARCH HIGHLIGHTS

Artificial Intelligence Research Programs in Radiation Oncology 47Immunotherapy Research in Radiation Oncology 51New Discoveries in Radiation Oncology 55A Unique and World-Class Pre-Clinical Radiation Research Facility 58

SECTION 3 DEPARTMENT HIGHLIGHTS

Our Faculty: Groups by Division 60Faculty Recognition 68Education and Training 69Department Statistics 74Publications 76

TA B L E O F C O N T E N T S JA, Fischer ES, Janne PA, Scott DA, Westover KD, Gray NS. Potent and Selective Covalent Quinazoline Inhibitors of KRAS G12C. Cell Chem Biol. 2017;24(8):1005-16 e3. Epub 2017/08/07. doi: 10.1016/j.chembiol.2017.06.017. PubMed PMID: 28781124.

Zhang H, Ma J, Wang J, Moore W, Liang Z. Assessment of prior image induced nonlocal means regularization for low-dose CT reconstruction: Change in anatomy. Med Phys. 2017;44(9):e264-e78. Epub 2017/09/14. doi: 10.1002/mp.12378. PubMed PMID: 28901622; PMCID: PMC5613294.

Zhang H, Zeng D, Zhang H, Wang J, Liang Z, Ma J. Applications of nonlocal means algorithm in low-dose X-ray CT image processing and reconstruction: A review. Med Phys. 2017;44(3):1168-85. Epub 2017/03/18. doi: 10.1002/mp.12097. PubMed PMID: 28303644; PMCID: PMC5381744.

Zhang L, Nomie K, Zhang H, Bell T, Pham L, Kadri S, Segal J, Li S, Zhou S, Santos D, Richard S, Sharma S, Chen W, Oriabure O, Liu Y, Huang S, Guo H, Chen Z, Tao W, Li C, Wang J, Fang B, Wang J, Li L, Badillo M, Ahmed M, Thirumurthi S, Huang SY, Shao Y, Lam L, Yi Q, Wang YL, Wang M. B-Cell Lymphoma Patient-Derived Xenograft Models Enable Drug Discovery and Are a Platform for Personalized Therapy. Clin Cancer Res. 2017;23(15):4212-23. Epub 2017/03/30. doi: 10.1158/1078-0432.CCR-16-2703. PubMed PMID: 28348046; PMCID: PMC5540787.

Zhang T, Zhang Z, Li F, Hu Q, Liu H, Tang M, Ma W, Huang J, Songyang Z, Rong Y, Zhang S, Chen BP, Zhao Y. Looping-out mechanism for resolution of replicative stress at telomeres. EMBO Rep. 2017;18(8):1412-28. Epub 2017/06/16. doi: 10.15252/embr.201643866. PubMed PMID: 28615293; PMCID: PMC5538764.

Zhang Y, Tehrani JN, Wang J. A Biomechanical Modeling Guided CBCT Estimation Technique. IEEE Trans Med Imaging. 2017;36(2):641-52. Epub 2016/11/11. doi: 10.1109/TMI.2016.2623745. PubMed PMID: 27831866; PMCID: PMC5381525.

Zhao B, Maquilan G, Jiang S, Schwartz DL. Minimal mask immobilization with optical surface guidance for head and neck radiotherapy. J Appl Clin Med Phys. 2018;19(1):17-24. Epub 2017/11/10. doi: 10.1002/acm2.12211. PubMed PMID: 29119677; PMCID: PMC5768028.

Zhao C, Chen X, Ouyang L, Wang J, Jin M. Robust moving-blocker scatter correction for cone-beam computed tomography using multiple-view information. PLoS One. 2017;12(12):e0189620. Epub 2017/12/22. doi: 10.1371/journal.pone.0189620. PubMed PMID: 29267307; PMCID: PMC5739408.

Zhao C, Ouyang L, Wang J, Jin M, editors. Multi-view scatter estimation for moving blocker scatter correction of CBCT. 2016 IEEE Nuclear Science Symposium, Medical Imaging Conference and Room-Temperature Semiconductor Detector Workshop (NSS/MIC/RTSD); 2016 29 Oct.-6 Nov. 2016.

Zhao C, Zhong Y, Duan X, Zhang Y, Huang X, Wang J, Jin M. 4D cone-beam computed tomography (CBCT) using a moving blocker for simultaneous radiation dose reduction and scatter correction. Phys Med Biol. 2018;63(11):115007. Epub 2018/05/04. doi: 10.1088/1361-6560/aac229. PubMed PMID: 29722297; PMCID: PMC5995796.

Zhao C, Zhong Y, Wang J, Jin M, editors. Modified simultaneous motion estimation and image reconstruction (m-SMEIR) for 4D-CBCT. 2018 IEEE 15th International Symposium on Biomedical Imaging (ISBI 2018); 2018 4-7 April 2018.

Zhen X, Chen J, Zhong Z, Hrycushko B, Zhou L, Jiang S, Albuquerque K, Gu X. Deep convolutional neural network with transfer learning for rectum toxicity prediction in cervical cancer radiotherapy: a feasibility study. Phys Med Biol. 2017;62(21):8246-63. Epub 2017/09/16. doi: 10.1088/1361-6560/aa8d09. PubMed PMID: 28914611.

Zhen X, Zhao B, Wang Z, Timmerman R, Spangler A, Kim N, Rahimi A, Gu X. Comprehensive target geometric errors and margin assessment in stereotactic partial breast irradiation. Radiat Oncol. 2017;12(1):151. Epub 2017/09/13. doi: 10.1186/s13014-017-0889-6. PubMed PMID: 28893302; PMCID: PMC5594509.

Zhong Y, Kalantari F, Zhang Y, Shao Y, Wang J. Quantitative 4D-PET Reconstruction for Small Animal Using SMEIR-Reconstructed 4D-CBCT. IEEE Transactions on Radiation and Plasma Medical Sciences. 2018;2(4):300-6. doi: 10.1109/TRPMS.2018.2814342.

Zhou H, Zhang Z, Denney R, Williams JS, Gerberich J, Stojadinovic S, Saha D, Shelton JM, Mason RP. Tumor physiological changes during hypofractionated stereotactic body radiation therapy assessed using multi-parametric magnetic resonance imaging. Oncotarget. 2017;8(23):37464-77. Epub 2017/04/19. doi: 10.18632/oncotarget.16395. PubMed PMID: 28415581; PMCID: PMC5514922.

Zhou Y, Klages P, Tan J, Chi Y, Stojadinovic S, Yang M, Hrycushko B, Medin P, Pompos A, Jiang S, Albuquerque K, Jia X. Automated high-dose rate brachytherapy treatment planning for a single-channel vaginal cylinder applicator. Phys Med Biol. 2017;62(11):4361-74. Epub 2017/03/01. doi: 10.1088/1361-6560/aa637e. PubMed PMID: 28244879.

Zhou Z, Folkert M, Iyengar P, Westover K, Zhang Y, Choy H, Timmerman R, Jiang S, Wang J. Multi-objective radiomics model for predicting distant failure in lung SBRT. Phys Med Biol. 2017;62(11):4460-78. Epub 2017/05/10. doi: 10.1088/1361-6560/aa6ae5. PubMed PMID: 28480871.

M E S S A G E F R O M T H E C H A I R M A N

With great pleasure, I present the Department of Radiation Oncology’s 2018 Progress Report reflecting on our program priorities and highlights. The theme for this report is Defining Excellence in Every Aspect: Care. Education. Research. Innovation. Our Department’s vision is – and has been – to assemble exceptional faculty and leaders in the field of radiation oncology to advance innovative approaches in battling cancer. With more than 66 faculty and our combined expertise, we are fulfilling this vision and delivering on a mission to provide exceptional patient care, discover and develop our field, and educate our future clinicians and researchers.

Over the past 15 years, our patient volume has increased consistently year over year – leading to continued enhancement and expansions of our clinical space. We will share unique features and innovative approaches of our new clinical and academic building, which redefines how we work and manage our patients. As recognized leaders, our research is advancing many areas of the field, including stereotactic ablative radiotherapy (SAbR), immunotherapy, and personalized patient care through artificial intelligence (AI). In this report, we highlight some key areas of research and advancement in the fight against breast, kidney, and prostate cancer,

along with a unique brachytherapy program. Each day our team of clinical faculty and staff work collaboratively to ensure that patients receive efficient quality care and the highest levels of patient safety. Because of this dedicated team approach, our patients rank us at the highest level for satisfaction and service. I am grateful to lead this Department comprised of truly dedicated employees and proud to share our most recent work, patient stories, and training and education.

Hak Choy, M.D., FASTRO Chairman of Radiation Oncology

Dear friends and colleagues,

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Collaborative academic space

A Patient Experience: Investing in Quality, Efficiency, and Safety

One of the finest buildings on UT Southwestern’s campus is the William P. Clements Jr. University Hospital, Harold C. Simmons Comprehensive Cancer Center, Radiation Oncology Building. With three floors and 63,000 square feet of space, this structure is the largest individual facility for radiation oncology in North Texas. The facility was not only built with the vision of being state-of-the-art, but also structured with a futuristic design.

With its design, the building enhances the delivery of quality care, creates efficient patient management, promotes collaboration among caregivers, and ensures high levels of patient safety.

One unique aspect of the Radiation Oncology Building is that it enhances disease-site specialization in the treatment

of cancer patients. Each major disease site has its own dedicated area for its team. Our disease-oriented teams (DOTs) are:

• Breast• Central Nervous System• Gastrointestinal • Genitourinary• Gynecological• Head and Neck• Lung• Lymphoma• Melanoma and Sarcoma• Pediatrics

This framework is consistent with how the Department of Radiation Oncology treats cancer. Each physician specializes in the treatment of a particular cancer type, enabling individual specialists to bring familiarity and expertise to each patient

encounter. Each specialist also participates in larger disease-oriented teams within UT Southwestern’s Harold C. Simmons Comprehensive Cancer Center.

“The goal was to have the teams located close to each other; that’s how that section of the building was designed,” says Arnold Pompos, Ph.D., Associate Professor of Radiation Oncology and Chief Clinical Physicist. “Because of this, there is common interest to encourage efficient discussion, problem-solving, and communication.”

Each team consists of a lead physician, additional physicians, molecular biologists, radiation physicists, dosimetrists, clinical researchers, and administrative support. Most of the team is located within a pod just outside of the team lead physician’s office.

By Ryan Daugherty

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The Radiation Oncology Building is home to many technologically advanced machines for treating cancer, some of which are unique in North Texas and even the U.S. These include:

• Six multi-energy state-of-the-art linear accelerators equipped with MLC and on-board kV 2-D and 3-D image guidance (two TrueBeam and two VitalBeam by Varian; two Versa HD by Elekta)

• One robotic accelerator with in-room kV image guidance and real-time tracking (CyberKnife M6 - Accuray)

• One multi-slice wide-bore CT simulator capable of 4-D CT (Philips Brilliance)

• One mobile CT scanner on wheels (Brainlab Airo)

• One superficial treatment unit (Xstrahl 150)

• One breast cancer therapy-dedicated unit (GammaPod)

• One real-time optic patient tracking system (Vision RT)

• One in-room kV 2-D image guidance (Brainlab ExacTrack)

Among the unique treatment machines within the building are the CyberKnife and the GammaPod, an advanced technology designed to treat early stage breast cancer, which will be available to patients by the end of the year. UT Southwestern has more experience with the CyberKnife robotic radiosurgery system than any other center in Texas and offers the next generation, the CyberKnife M6. The M6 allows for checking

targeting accuracy while treatment is being administered in real time.

The building also houses six state-of-the-art linear accelerators: two TrueBeam, two VitalBeam, and two Versa HD accelerators. These machines offer a number of unique capabilities as they deliver beams with precision, efficiency, and speed six times faster than conventional treatment machines, substantially decreasing irradiation time for selected tumors. Each of the TrueBeams is equipped with a treatment couch, which allows doctors to match a tumor’s position to the therapy beam in six different directions. In addition, each machine delivers radiation as it rotates around the patient, sparing organs, and also enables CT scans while a patient is in treatment position.

Driving Innovation: Advanced Technology

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Although not housed in the building, the Gamma Knife Icon is the latest radiosurgery tool that allows a frameless treatment option for patients with brain cancer and metastases. This new technology, located at Zale Lipshy University Hospital, uses cone-beam computed tomography imaging to verify patient positioning prior to treatment and continuous monitoring to ensure treatment is delivered with submillimeter accuracy. The Gamma Knife Icon offers several advantages, including expanded treatment areas that include the eyes, face, and upper neck. The new Clements University Hospital expansion, set for 2020, will include two state-of-the-art Gamma Knife Surgery Suites.

In the Radiation Oncology Building, all the treatment machines are located on the first floor within seven treatment vaults. In a typical radiation oncology facility, treatment vaults are fairly large, because they need

to house and store many patient-specific immobilization and delivery devices for treatment. These vaults usually have one door through which both patients and additional treatment devices enter; this causes patient distractions and clogged treatment rooms. Collectively within the Department, an idea arose to make the footprint of the room smaller, but to add a storage corridor to the back of each room where devices could be stored in one universal area. This allows the device exchange and room setup to happen behind the scenes, so patients are presented a neat room for their radiation therapy.

One innovative machine in particular is the Airo CT, a mobile CT scanner. Unlike a normal cone-beam CT, which is mounted on the machine in the room, the Airo CT is on wheels and can be moved from room to room effectively and efficiently. Airo CT is mainly used in operating rooms, because it

is designed for surgeons. The Department is working on a project to adapt the Airo CT to radiation therapy, which is currently in a research phase, led by Yang Park, Ph.D., Assistant Professor. With this project, UT Southwestern becomes the first institution

in the U.S. to

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Technical corridorBrainlab Airo CT

to incorporate a CT scanner on wheels in a radiation oncology practice.

Another unique advancement in the Department involves 3-D printing. With high-energy X-ray irradiators, distributing a dose to fairly shallow and deep areas at the same time can be difficult. This problem arises in anatomical locations where surface contours are highly variable, such as with

breast or head and neck cancer. To achieve an adequate dose distribution to superficial tissues, clinicians often add “soft, tissue-like” material to the skin to shift the X-ray dose to the outer surface of the tumor. Historically, the materials used for this have been items like sheets of flexible rubber or wet gauze, which can vary in day-to-day treatment setup, leading to uncertainties in dose distribution over a treatment course and to patient discomfort.

To improve patient satisfaction and the efficiency of these treatments, a resident investigator in the Department, Tsuicheng “David” Chiu, Ph.D., proposed the use of 3-D printers to directly construct molds to cast silicone shapes that exactly match the curves or crevices of a patient’s anatomy, using their CT imaging as a guide. Not only do these castings improve the radiation dose distributions, they are far more tolerable for patients.

We are one of the pioneers for the usage of Airo CT for setup of patients and adaptive treatment planning.

– Dr. Arnold Pompos

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3-D model

The clinic in the Department of Radiation Oncology sees more than 180 patients a day. To organize the very busy clinic, Kenneth Westover, M.D., Ph.D., Associate Professor of Radiation Oncology and Director of Information and Innovation; Jun Tan, Ph.D.; David Sher, M.D., M.P.H., Associate Professor and Associate Director of Clinical Operations, and a number of others created a plan for the clinic’s workflow to be guided and monitored through a technology system to maximize the efficiency of the clinic. This system was implemented around two years ago.

“The important thing is maximizing efficiency and respecting patient times, and the idea of having a clinic guided and monitored through a system like this is the way to make it optimal,” says Dr. Sher.This technology was created through the use of touchscreen tablets, known around the Department as RO Pads, which are located outside of every office and clinic room in the building and include a number of efficiency-optimization features. Physicians, nurses, and other faculty can access the features of this homegrown technology system through the RO Pads themselves, mobile devices, or computer stations, which allow everyone in the clinic to see what is happening at any time in terms of where patients are in their visiting process.

To help organize patient flow, an installed feature in the RO Pads sends reminder times to physicians and nurses when they are running late. For example, if a physician has been with a patient for 20 minutes, they receive an automatic reminder page letting them know the amount of time they have spent in the room. According to Dr. Sher, this feature is temporary and is more of a simple attempt to maximize physician and nurse times.

The larger objective is to be savvier in arranging the clinic and minimizing waiting times, and to identify how long patients have been waiting and which patients should be seen next. Another idea is to use this system to dynamically arrange the schedule based on how long each patient takes during their routine visits. This includes compiling data for each patient’s visit and efficiently monitoring the order in which they should be seen.

Increasing Efficiency for Both Patient & Provider

Disease-oriented team clinical workroom

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Large radiation therapy practices, like that at UT Southwestern, face unique challenges given the large number of patients receiving therapy on consecutive days. Missed appointments or delays in treatment can cause ripple effects in daily schedules and can also result in missed opportunities to deliver radiation therapy fractions.

To understand factors that influence non-compliance and to improve patient compliance in attending their radiation therapy appointments, Drs. Westover and Tan led a study that used an automated text message program (SMS). They evaluated appointments between July 2016 and January 2017, when daily appointment time reminders were sent to patients treated at UT Southwestern.

Over the course of a year, patients were given the option of receiving text message reminders for their appointments, and of the roughly 3,500 patients treated during that period, 20 percent opted to receive SMS. In total, more than 37,000 radiation therapy appointments were analyzed. A number of factors potentially related to appointment attendance or tardiness were analyzed, including demographic factors, treatment time of day, distance from the patient’s home to the radiation facility, and treatment fraction number. Receipt of SMS significantly improved patient tardiness and no-show rates, particularly within the first few fractions of treatment.

Mobile Text – Connecting the Patient

A big component of the building is the artwork all around the space. From the moment people walk through the front doors they are presented with art. The building houses 20 original works plus more than 50 nature and landscape prints in patient exam rooms, corridors, and dressing areas. Courtney Crothers, Art Curator at UT Southwestern, is responsible for recommending art for clinical spaces all around campus, including those in the Radiation Oncology Building.

“The vision, in meeting with Dr. Choy, revolved around reflecting the advanced technology around the building,” says Ms. Crothers. “There are three features in total of the art program here – technology-based, meditative, and uplifting color; I think color is the strand that runs through everything and ties it all together.”

“Technology-based” describes Matthew Kluber’s Half-Day Closing, a digital painting located just outside the second-floor elevators. Kluber’s paintings merge the traditional painting surface with the animation of video. The visual source material resembles the narrow, colorful bands of data on a computer that signal a crash.

At a glance, it’s a simple painted canvas with solid lines and colors, but with a projection turned on, three layers of mesmerizing animations appear. The projection for the video was developed through gaming software, and the speed and duration of the projection is randomized, resulting in an ever-changing animation.

“We wanted something soft and engaging,” says Ms. Crothers. “It’s quiet and beautiful in color, and when someone is standing by the elevator it catches their eye.”

Tying It All Together with Art

Pediatric waiting area

On the building’s ground floor, just outside the seven treatment vaults, is a set of seven large abstract paintings, named Spiritual-bypass. The artist, John Pomara, is a cancer survivor who was treated at UT Southwestern. Here, Pomara’s work focuses on human healing and visually expresses technology as an exploration of the beauty and celebration of the human form beyond recognition into a blurred state of presence. The bottom halves of the abstract paintings are one solid color, which is meant to enhance the viewer’s experience into a metaphysical – almost spiritual – vista, like that of a Mark Rothko painting.

Each image is based on a painted human figure, which is altered using web tools or glitch mechanisms. The images are printed with a special heated ink process called UV printing, where the ink dries through a photomechanical process.

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Treatment corridor

Pomara’s inspiration for the development of these abstract paintings arose during the early stages of his own battle with prostate cancer. He remembers the anxiety and worry he felt during that time and wanting nothing more than for these seven pieces to simply be beautiful.

“I wanted to be engaging,” he says. “Mark Rothko talked about wanting to create this atmosphere where people could just walk into these works and be a part of them as a

human being, and I felt the same. I wanted them to be inviting and just pull you in with the beauty.”

Similarly, Adela Andea’s light installation art in the building was created to be engaging and to provide an uplifting presence. Ms. Andea is known for creating all-encompassing visuals and temporal experiences in the form of innovative light installations. The Department’s installations, named The

Hall of Mirrors, hang from the ceiling, where they can be experienced from underneath, providing a continuing flow from one formation to the other. They are strategically placed in the pediatric play area, according to Ms. Crothers.

“I was trying to find a piece of artwork that could connect with the rest of the building but also be playful at the same time,” she says. “To me they almost look like fireworks; they relate to everything else with the advanced technology and LED lighting, but are also playful enough so they can be interesting to children out there.”

Ms. Andea’s art is inspired by nature, natural versus artificial concepts, environmental issues, and technological advances. It contemplates positively the necessity of progress and technological advances and artistically blends the

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The vision, in meeting with Dr. Choy, revolved around reflecting the advanced technology around the building.

– Courtney Crothers

romantic notion of nature with the man-made aesthetic.

The purpose of the light installations is not just to encourage an emotional reaction, but also to encourage artistic observation by amplifying visually the idea of space and providing more depth and brightness to the area. The lights in the installation are warm, and the vibrant colors relay a positive message; in a way, they are a light therapy.

“I’m very honored to be a part of the collection,” Ms. Andea says. “I think it’s important to play a role in the culture of an institution, because it shapes the culture and the way artists are perceived. I think it would be fabulous to have even more art in hospitals and public places; the institution itself as a patron of the arts is shaping our culture.” Courtney Crothers

“A Hero is an ordinary individual who finds the strength to persevere and endure in spite of overwhelming obstacles.”

This powerful quote from the actor Christopher Reeve, whose wife battled lung cancer, sits on a wall just outside the building’s patient rooms. Just below it, mounted on the wall, is a set of orchestra chimes. This setup is known as the building’s Patient Celebration Wall.

Many hospitals have a way to celebrate a patient’s milestones, usually with a bell. Here, patients have the option of playing their own song or tune on these orchestra chimes as they celebrate with friends, family, and radiation oncology staff.

A big part of cancer care revolves around the treatments and technology, but a valuable asset to patients is the support they receive through their journey. The ringing of these chimes represents a patient reaching a new milestone on a long journey, and a chance to celebrate this special day.

Patient Celebration Wall

I was full of trepidation and a little overwhelmed as they handed me the mallet and said, ‘Ring the bells.’ I hit them softly at first, feeling a bit silly and self-conscious, but after some encouragement I struck them with everything I had. The sound was beautiful and strong, and made me feel exactly the same way. That melody indicated to me and everyone who could hear the chimes that I was finished. It filled me with hope and I felt so blessed to have completed that part of my journey.

– Mindy Gentile

On the last day I was so happy, proud, and excited that I had made it to the end of the treatment. Ringing the chimes was the ultimate reward for the accomplishment. I rang them loud and proud with my family and staff cheering me on!

– Patricia Collins

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This year marked the beginning of our Radiation Oncology Patient and Family Advisory Council, led by Dr. Sher and Claire Almanza, Director of Marketing. The initiative’s goal was to create a council composed of patients, families, clinicians, staff, and department leadership that would jointly discuss patient and family experiences and make suggestions to the program and leadership. The Council’s mission is to better understand the true patient experience and to continue to build a culture within the practice where every decision is made in the best interest of patients and their families.

The Council conducted its first meeting in August with discussions of a new building expansion. The group provided key perspectives on the patient experience, which will enhance planning and design efforts.

Together — Striving for Excellence in Patient Care:Radiation Oncology Patient and Family Advisory Council

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Patient and Family Advisory Council

CyberKnife M6

Breast Care: Advanced, Personalized Approach

UT Southwestern offers the most advanced technologies and techniques available for breast cancer diagnosis, screening, treatment, and research, which are not available at every hospital. In the Center for Breast Care, we have a team of physicians, surgeons, and medical oncologists who specialize solely in the treatment of breast cancer.

Our team, led by Asal Rahimi, M.D., M.S., Associate Professor of Radiation Oncology and Director of Clinical Research, offers state-of-the-art multidisciplinary care, including robust clinical research complemented by cutting-edge, laboratory-based basic/translational research programs. Current areas of investigation include development of targeted approaches to personalize radiation treatments based on molecular profile of

individual tumors and studying molecular determinants of radiation-induced immune response in breast tumors.

In addition, the Department has a breast-specific tumor board that brings together all specialists, including radiation oncologists, surgeons, medical oncologists, radiologists, pathologists, plastic surgeons, and genetic counselors, to devise the best treatment plans for individual patients.

Our Department’s breast cancer team offers a multitude of innovative radiation clinical trials. Particularly, our team has been pivotal in developing a stereotactic partial breast irradiation (S-PBI) program – one of the few departments in the world with this capability. S-PBI is essentially treating a very focused area where the tumor is located with little margin around the tumor,

all in a much shorter course. A typical course for PBI is 10 treatments, and there are different ways it can be delivered.

UT Southwestern is running a clinical trial that involves using a single dose of radiation, titled Phase I Dose Escalation Trial of Single Fraction. There have been trials revolving around a single dose of radiation intraoperatively; this requires a special machine that is not available at all centers, and shielding in the operating room. At UT Southwestern, the same concept is being applied with the use of a stereotactic robotic radiation machine, the CyberKnife, to treat the lumpectomy cavity, but after surgery.

“The advantage of doing S-PBI after the lumpectomy is complete rather than during surgery is that we’ll know if the margins

By Ryan Daugherty

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are clear and the status of the lymph nodes,” says Dr. Rahimi. “So, we’ll know if the patient is a good candidate for S-PBI before irradiating the breast as opposed to intraoperative radiation where you don’t have all the pathology information at the time of surgery.”

The benefit of giving radiation in one treatment for early-stage breast cancer, as opposed to six-and-a-half weeks of radiotherapy, is a great one, as women will save time and not have to invest hours driving back and forth to the clinic.

Another trial involves the use of the soon-to-be-available GammaPod. This is a Phase II trial evaluating stereotactic partial breast irradiation in five fractions for early-stage breast cancer patients. A previous trial involved this five-fraction treatment with

the CyberKnife; in that trial, five groups of women – 15 in each group – were treated with different dose levels.

Not every woman lives in a city where they have access to medical care or a radiation oncology location. Sometimes longer courses of radiation can be disruptive to the average person, so we’re trying to improve convenience, decrease toxicity, and maintain high local control and overall survival rates.

– Dr. Asal Rahimi

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Breast CyberKnife plan

UT Southwestern is set to add another dimension to the treatment of breast cancer care by becoming the first center in Texas and only the second in the world to offer the GammaPod, an advanced technology designed specifically to treat breast cancer. The first scheduled patient to be treated on the GammaPod will be in 2019. By using stereotactic radiotherapy techniques to deliver higher doses in one to five treatment fractions, the GammaPod will be able to reduce treatment time and potentially lower the toxicity of the treatment.

Breast-conserving therapy involves surgery followed by breast irradiation and is equivalent to mastectomy in breast cancer survival. A number of randomized trials have shown that breast irradiation substantially reduces the risk of local recurrence

and prevents the need for subsequent mastectomy.

Standard radiation treatment for breast cancer patients typically lasts four to six weeks; it can be inconvenient and can lead to fatigue, breast pain, and irritation, among other concerns. With the GammaPod’s beam delivery method, treatment can be administered in just one to five days.

The GammaPod’s setup for patients is quick and comfortable. Patient loaders are used while the patient lies on her chest, which helps to limit the dose to the heart and lungs. A motor-driven couch lifts and rotates the patient from standing to prone position; this enhances patient comfort and ensures geometric consistency between breast imaging and treatment.

To immobilize the breast cup and get the stereotactic localization of the target, vacuum-assisted breast immobilization is used. There are three sizes of outer cups and 28 sizes of single-use inner cups available for patients. The inner and outer cups are joined with a single-use silicone flange that adheres to the chest to provide an airtight seal.

After the breast cup is fitted and sealed with a pump, the patient is placed on the GammaPod table and then treated through a multisource Cobalt-60 stereotactic radiotherapy system. Thousands of beam angles are created as the system rotates continuously, allowing surrounding tissue to be spared. The entire process is done on the same day, and patients are able to go home once treatment is completed.

New Technology: GammaPod

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GammaPod. Image courtesy of Xcision.

UT Southwestern is home to the most comprehensive deep inspiration breath hold (DIBH)-based cardiac-sparing radiation treatment program in North Texas for patients with left-sided breast cancer. For this, we have two VisionRT surface image-guided systems dedicated for patients, as well as two Active Breathing Coordinator (ABC) machines that are used to monitor patients requiring breast or chest wall and lymph node treatments.

“Our cardiac-sparing program - I think we do it well, and we have more tools than other places. I think our process is very fluid - from the CT to treatment planning delivery. It’s all very smooth,” says Nathan Kim, M.D., Ph.D., Associate Professor of Radiation Oncology.

Like VisionRT, ABC monitors patients’

breathing. It provides the precision and reproducibility to the motion management approach of deep inspiration breath hold. With left breast treatment, a big challenge in radiation therapy is avoiding dose to the heart. By using DIBH with the Active Breathing Coordinator, the distance between

the chest wall and heart is expanded with lung volume, reducing the dose. Breath-hold treatments using ABC also provide the ability to reduce dose to other critical structures, such as the spinal cord, by increasing the distance between the tumor and critical structure.

Adding to the Precision: Deep Inspiration Breath Hold

Our cardiac-sparing program – I think we do it well, and we have more tools than other places. I think our process is very fluid - from the CT to treatment planning delivery. It’s all very smooth.

– Dr. Nathan Kim

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Patient with active breathing control

Breath hold planning image

Marilyn & Bob Gibson

For Marilyn Gibson, the Decision Was an Easy One

Marilyn Gibson, 82, of Arlington has lived in Texas for more than 45 years. She’s gone to her doctor annually for a standard mammogram and there have never been any worrisome signs – until this past March. She went for her routine checkup at UT Southwestern and everything had initially looked fine, but the very next day she was called back in. An additional mammogram and X-ray revealed a small tumor in her breast.

Along with help from her daughter, Mrs. Gibson quickly moved forward and scheduled a visit with a cardio-oncologist to check her heart before surgeries could be scheduled. She mentions that from the very start, the process was smooth. Through that process, she would have a group of five other oncologists care for her, including Dr. Rahimi.

“I adore Dr. Rahimi,” says Mrs. Gibson. “She is so sweet, smart, and empathetic; I loved her from the very first meeting.”

Mrs. Gibson met with Dr. Rahimi after surgery to discuss the next step. Since there was no involvement with the lymph nodes, she qualified for radiation and would have a few options to choose from. Two of those options involved four to six weeks of daily radiation to the whole breast or partial breast radiation given twice a day for five days. The third option was a clinical trial delivering just one large dose of radiation to part of the breast. For Mrs. Gibson, the decision was an easy one – she would take the single dose of radiation.

“I just think it was a no-brainer, and that’s what I told Dr. Rahimi,” she says. “It’s all just amazing research, and even though

it’s a study, it’s been very successful based on the previous study. It was absolutely a godsend, and I can’t imagine getting that option and not going for it.”

This single treatment of radiation is being tested in a current clinical trial at UT Southwestern, led by Dr. Rahimi. The Phase I clinical trial is for early-stage breast cancer patients, stage 1 and particularly stage 2 if no lymph nodes are present and the tumor is a certain size. Treatment is administered with the CyberKnife, a stereotactic radiation machine that is mounted on a robotic arm and focuses multiple beams on the tumor.

A previously published trial, conducted at UT Southwestern, also used the CyberKnife, and involved five fractions of radiation as opposed to just one. The subjects in that study are still being followed, and the

By Ryan Daugherty

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results have been favorable to date. In the current, single-fraction trial, three groups of patients are being treated; each group receives a little higher dose of radiation.

“There have been trials in Europe looking at intraoperative radiation, which is essentially a single dose of radiation at the time of surgery. This requires a specialized radiation machine in the operating room,” says Dr. Rahimi. “We are trying to take this concept and make it more accessible to the

general radiation oncology public, as many institutions do not have access to these machines. There is also a benefit to knowing what the final pathology is, which is usually not available for several days after surgery, prior to delivering radiation.”

The entire treatment process takes around one hour, including setup of the CyberKnife and the other components of the treatment. The efficiency of the treatment was apparent to Mrs. Gibson and the minimal

length was a surprise, too. She even joked that she fell asleep twice while the team played Frank Sinatra for her. She notes that she was “blown away” by the technology and that the entire process couldn’t have been more pleasant.

It has only been a few months since Mrs. Gibson received the treatment, but overall she is doing great. So far she has experienced no pain, with her only downside being occasional fatigue from prescribed tamoxifen. Meanwhile, from this point, the trial will be running for nearly four-and-a-half more years. Over this time, Dr. Rahimi hopes not only to see the enrolled patients and the trial make progress, but to make the public more aware of other trials accessible to the community.

“It really is a gift that Mrs. Gibson is giving

I think it’s an opportunity – a wonderful experience. It’s so minimal, but the end result is so good.

– Marilyn Gibson

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to the medical field as well as to the community by participating in this trial,” says Dr. Rahimi. “Every couple of years our field continues to advance in different technologies, and we need to make sure we keep up with that from the treatment perspective. It wouldn’t be possible without patients like her.”

Mrs. Gibson will continue to come back for checkups every three months and while being healed is her primary interest, she shares a sentiment similar to Dr. Rahimi’s: She is proud to be a part of something that can potentially help women of all ages.

“I think it’s an opportunity – a wonderful experience,” she says. “It’s so minimal, but the end result is so good. If you’re not willing to do this sort of thing, then you just aren’t willing to make a contribution to anything.”

Dr. Rahimi & Marilyn Gibson

Fighting Kidney Cancer

UT Southwestern’s Kidney Cancer Program is composed of a multidisciplinary team that delivers advanced, evidence-based care for kidney cancer patients, as well as researchers who conduct a wide range of clinical trials aimed at improving the diagnosis and treatment of the disease.

“We are probably the center that has the largest number of enrolling SBRT kidney cancer clinical trials in the U.S. and probably even in the world,” says Raquibul Hannan, M.D., Ph.D., Associate

Professor of Radiation Oncology.

Several clinical trials are open and enrolling, including one that targets oligometastasic kidney cancer and another that combines immunotherapy with stereotactic body radiation therapy (SBRT) for metastatic kidney cancer.

Treating kidney cancer patients who have limited metastases with curative intent using SBRT, as opposed to systemic therapies, is a new treatment paradigm that is being evaluated in UT Southwestern’s Department of Radiation Oncology.

“This spares patients from the significant side effects of systemic therapy, impacting their quality of life at the cost of offering modest benefits of delaying cancer progression – all of this, only if they respond to the systemic therapy in the first place,” says Dr. Hannan. “On the other

hand, for selected patients, SBRT can offer a curative and non-invasive form of metastasectomy with virtually no impact on patients’ quality of life.”

UT Southwestern’s five-year survival rate across all kidney cancer stages are superior to national benchmarks, according to an analysis conducted by the Office of Health Systems Affairs. Three out of the four stages, including stage IV, show significant statistical differences; for stage IV patients, five-year survival rates are more than double national benchmarks – 25 percent vs. 11 percent.

By Ryan Daugherty

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“We are probably the center that has the largest number of enrolling SBRT kidney cancer clinical trials in the U.S. and probably even in the world.

– Dr. Raquibul Hannan

Angela Baas had suffered through poor health for years. She had been struggling with various discomforts, such as frequent bladder infections, blood in her urine, tinnitus, and extreme physical exhaustion, but her local physician didn’t seem concerned, as her blood tests were within normal ranges. When she had back pain, she was told to exercise. Even when she had a fever almost every night for two years, she was told it was probably just a virus. Eventually, her doctor even suggested that she try antidepressants because of her frequent complaints.

Making all the Difference

Mrs. Baas could eventually figure out what was wrong as she was told losing weight would help alleviate her complaints. After several failed diets prescribed by her doctor, she decided to pursue gastric sleeve surgery.

“I would have done anything to feel better at that point,” she says.

In the weeks leading up to the bariatric surgery, an ultrasound was recommended to check the health of her gallbladder – and a large tumor was found on her right kidney. The surgery was put on hold and she was immediately referred to a urologist to have both the tumor and

kidney surgically removed.

At first, the diagnosis was encouraging because the tumor appeared to be fully encapsulated. However, a later pathology report revealed the tumor had broken out of the encapsulation and started to travel up her renal vein. That initial relief of a good prognosis was overcome by the fear of increased risk of the cancer spreading.

Mrs. Baas was screened for metastasis with computer tomography (CT) scans at regular intervals after surgery. One year later, two small tumors were found on her

left lung. After undergoing three surgical biopsies in one month, it was revealed that the cancer from her kidney had metastasized and formed tumors on her lung – she had stage IV kidney cancer. She was told it was a type of cancer that could not be treated with success, or perhaps at all, and that it was terminal.

Devastated, Mrs. Baas went back to her hometown of Los Alamos, N.M., and discussed options with her local oncologist, who kept searching for medical studies that would offer some hope. A potentially good option was found at UT Southwestern Medical Center. This would be her next, and last, attempt at finding a successful treatment.

Specialists at UT Southwestern were studying SBRT combined with Interleukin-2 (IL-2) immunotherapy. Mrs. Baas made the trip to discuss the study with James Brugarolas, M.D., Ph.D., Director of the

The fact that I was treated like an individual and not just another patient made all the difference.

– Angela Baas

Kidney Cancer Program at Harold C. Simmons Comprehensive Cancer Center. During their conversation, Dr. Brugarolas determined that because of the tumors in her left lung, which were now large and aggressive, the study was not the best option. Instead, she was referred to Dr. Hannan to be considered for treatment of the lung tumors with SBRT alone.

Dr. Hannan discussed with Mrs. Baas that whatever therapy is chosen, whether it be chemotherapy, systemic therapy, or immunotherapy, the disease would typically be held back for a certain amount of time. Because she had only two metastases, and because this was the only site of cancer spread, treating both of these lesions with stereotactic radiation would be her best option to be cured.

Transient nausea and emotional stress were the most difficult aspects of the treatment,

Mrs. Baas said, but she emphasized the great support she received from the people she worked with, as well as from her family and friends. Also, she said, Dr. Hannan and one medical resident in particular showed extra care to keep her encouraged. Compared with previous hospitals she had visited, UT Southwestern stood out.

“The fact that I was treated like an individual and not just another patient made all the difference,” says Mrs. Baas. “That’s how it works at UT Southwestern; they carefully choose the treatment for each person according to their needs. My experience was very positive, which definitely built a strong trust between me and my doctors.”

Four years after her initial diagnosis, Mrs. Baas continues to return to UT Southwestern for regular follow-up appointments with Drs. Brugarolas and Hannan. In the past two years since her

treatment, she has had no evidence of disease, a remarkable feat, as the five-year survival rate for stage IV kidney cancer patients is only 10 percent.

Between appointments, she is enjoying life through multiple hobbies that include painting, quilting with friends, fishing with her husband, Brad, and walking with their two dogs. She has returned to work and recently welcomed her first grandchild - something she thought she would never have the opportunity to experience.

“I thought life had stopped at one point and I didn’t know what the future was going to hold, or if I had a future at all,” she says. “God has been so good to me and has answered so many prayers for healing. I have so much to look forward to and am very thankful for all my extremely knowledgeable and accomplished doctors at UT Southwestern. I highly recommend them.”

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Our dedicated genitourinary team, led by Dr. Hannan, is made up of experienced clinicians in the treatment of prostate cancer. A primary focus in our fight against prostate cancer is the use of stereotactic ablative approaches, an area in which Robert Timmerman, M.D., FASTRO, FACR, Professor and Medical Director of Radiation Oncology, is a true pioneer.

Dr. Timmerman was one of the first researchers to bring the specialized treatment techniques of stereotactic ablative radiotherapy (SAbR), previously used solely on the brain, to other tumors

located within the body. He has had a part in numerous trials that have applied SAbR to treat cancer in various areas, including the prostate. “We were amongst the first institutions to treat prostate cancer with SAbR and remain among a select few to do so in a step-wise manner using rigorous trials to optimize its effect and quality of life,” says Neil Desai, M.D., M.H.S., Assistant Professor of Radiation Oncology

UT Southwestern has conducted many clinical trials of SAbR involving the prostate. SAbR is a highly potent treatment and can produce significant side effects. Both were demonstrated in one of the first trials of SAbR in prostate cancer led by UT Southwestern, which produced an impressive 98.6% five-year biochemical control rate at the cost of a low-rate significant rectal toxicity. To address, a UTSW-led follow-up trial used SpaceOAR, a spacer gel between the prostate and rectum, to reduce the amount of radiation reaching the rectum. Since the success of that trial in minimizing rectal injury risk, UT

Southwestern has become a main training center for other institutions seeking to learn about the technique.

Based on this leadership in applying SAbR to prostate cancer, UT Southwestern was selected to lead an ongoing multicenter randomized trial, called POTEN-C. This trial combines modern MRI imaging, SpaceOAR’s ability to displace the rectum from the prostate target, and the precision of SAbR to diminish erectile dysfunction following treatment. According to Dr. Desai, who leads this trial, “Further success in this domain would be a crucial next step in our efforts to pair the high cure rates with SAbR with equally impressive reductions in the quality-of-life impact of treatment.”

Fighting Prostate CancerBy Ryan Daugherty

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We were amongst the first institutions to treat prostate cancer with SAbR and remain among a select few to do so in a step-wise manner using rigorous trials to optimize its effect and quality of life.

– Dr. Neil Desai

Jerry Smith, 76, of Preston Hollow in Dallas, grew up in West Texas on a cotton farm near Lubbock. He has lived an accomplished life, having been in the oil and gas, real estate, and financial businesses.

Honoring a Friend

In early 2016, Mr. Smith visited his local urologist for his annual exam. His PSA levels were higher than normal, so a biopsy was recommended. When the results were clear, he was told he had prostate cancer. Initially, there was no fear because it was a slow-growing type of cancer. He was also not worried about finding help, as the search for the right physicians didn’t take long; he immediately knew where he would go to be treated.

“Living in Dallas for as long as I have, you just know about UT Southwestern,” he says. “It was the reputation of the medical school that gave me the confidence, and that’s exactly where I wanted to be.”

Upon his arrival, he met Dr. Hannan, and learned about a clinical trial that would treat his cancer quickly and efficiently. The trial was for low-risk prostate cancer patients and involved SAbR and the SpaceOAR gel. The goal of the trial is to determine whether the gel reduces toxicity and other side effects to the rectum.

The current form of radiation for prostate cancer is 44 treatments given over nine days. However, the therapy in this trial is delivered in only five treatments, allowing patients to return to their normal lives quicker. Without hesitation, Mr. Smith wanted to be a part of the trial, particularly because of the shortened

radiation treatments.

In March 2016, he received the first of his five treatments. The entire process was smooth, according to Mr. Smith. And the professionalism from everyone – the physicians, nurses, and technicians – made it easier; he notes that “there was very little interruption of life, which is what [he] was looking for.” Within six months, his PSA levels had dropped; he had essentially been cured of his prostate cancer. In addition, he maintained his potency. Potency is a big problem with any form of treatment for prostate cancer patients, with nearly half experiencing decreasing quality of potency.

“I would definitely recommend UT Southwestern to anyone, because of the system and the fine people that work there,” Mr. Smith says. “I could have had the high number of treatments, or however many, at any place, but I’m grateful that this great institution is nearby and that it was a minimum inconvenience.”

It was the reputation of the medical school that gave me the confidence, and that’s exactly where I wanted to be.

– Jerry Smith

So far, the trial has been successful and is currently in the follow-up stage. The Department is in the process of publishing a manuscript, and the treatment is now being offered to the public.

“Because of Mr. Smith’s participation in the trial, and the other participants of course, we are now able to offer this to others as a standard of care,” says Dr. Hannan. “He should be very proud; this was something very noble of him to do.”

For Mr. Smith, aside from the blessing of Dr. Hannan and UT Southwestern, his life hasn’t changed much. He still enjoys being active and waking up every day and spending time with his wife, kids, and grandkids. And he looks forward to continuing a tradition of support for UT Southwestern that he began long before his prostate cancer diagnosis.

In 2001, Lucille “Lupe” Murchison, a Dallas arts patron, former co-owner of the Dallas Cowboys, and longtime friend of Mr.

Smith’s, passed away. Per Ms. Murchison’s request, Mr. Smith became the managing trustee of the Lupe Murchison Foundation. Since 2004, he and the foundation have given gifts of $500,000 per year to the Southwestern Medical Foundation in Ms. Murchison’s honor.

“Personally, it is very rewarding to lead a foundation that supports cancer research and treatment,” says Mr. Smith. “Lupe entrusted us to invest the money and disperse it wisely to good places such as UT Southwestern. It is great fun to give large sums of money to great charities in her honor.”

The foundation gave a $250,000 grant to Dr. Hannan for his research on prostate cancer and i-SAbR, an innovative treatment mechanism that combines immunotherapy and SAbR. His research seeks to increase the effect of both therapies by combining them in three phase II clinical trials currently being offered at UT Southwestern.

“It is very gratifying that our research efforts are supported,” says Dr. Hannan. “Knowing that our patients here appreciate the efforts we put in every day in improving the science and treatment for them is a motivation for me.”

It is very gratifying that our research efforts are supported.

– Dr. Raquibul Hannan

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Brachytherapy: Expert and Advanced Guided Therapy

We are one of the few centers in North Texas to offer brachytherapy and the only center in North Texas to offer intraoperative brachytherapy. The William P. Clements Jr. University Hospital has an operating room dedicated to special brachytherapy cases as well as outpatient high-dose brachytherapy suites from our center.

Led by Michael Folkert, M.D., Ph.D., Assistant Professor of Radiation Oncology and Medical Residency Program Director, the brachytherapy program at UT Southwestern is the most comprehensive in North Texas. Alongside medical oncologists and cancer surgeons, our radiation oncologists use imaging to guide brachytherapy procedures to make treatment safer and more effective.

Our cancer specialists use brachytherapy to treat:

• Prostate cancer• Cervical cancer

• Endometrial (uterine) cancer• Eye cancer• Breast cancer• Liver cancer and liver metastases• Gallbladder/bile duct cancer• Brain tumors• Esophageal cancer• Colorectal cancer• Head and neck cancer• Skin cancer• Lung cancer

Based on the type of cancer and each patient’s situation, brachytherapy can be administered in different ways. In most cases, radioactive sources are placed in a space or cavity in the body – intracavitary – such as the rectum or uterus. Advanced and complex tumors are treated with interstitial brachytherapy, where the sources are placed directly inside the tumor.

Brachytherapy is given either with a high-dose rate or a low-dose rate, each having benefits for patients. With high-

dose-rate brachytherapy, patients receive a powerful radioactive source for a few minutes per treatment session, usually a few sessions over a few weeks. After each session the radioactive material is removed from the patient’s body. With low-dose brachytherapy, patients receive lower amounts of radiation for a longer period of time – over weeks to months – before the radioactive source is no longer active.

One other unique component of brachytherapy at UT Southwestern is the use of MRI image-guided brachytherapy, specifically for prostate and cervical cancer. Compared with the use of traditional planning methods, MRI-guided brachytherapy will improve clinical outcomes of patients with cervical and prostate cancer, according to several studies over the past decade. By using MRI-guided brachytherapy, a lower dose is delivered to normal structures, sparing patients from toxicities that can plague them for the rest of their lives.

By Ryan Daugherty

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Dr. Folkert in OR brachytherapy procedure

A Different View after Cancer

Maria Snead describes herself as a woman of faith. Throughout her life she has been involved in her local church and has expressed her faith to the fullest. But she recalls a time when she was practicing her faith at a minimum. Depressed and isolated, her life was spiraling downward. She hit rock-bottom when she found out that she had cervical cancer.

At the time she couldn’t foresee that her life would dramatically change for the better.

Back in her home of Garland, Mrs. Snead had begun experiencing abnormal vaginal bleeding. When the bleeding continued, she decided to visit a gynecologist to find out what was wrong with her. After multiple scans and tests she learned she had a tumor in her cervix. Devastated, she traveled to Monterrey, Mexico, where her sister, a doctor, would refer her to a local gynecologist.

At that appointment she was told that she needed a partial hysterectomy, and surgery

was attempted. However, with the type of cancer she had, surgical removal of the tumor would have caused it to spread throughout her body; she learned that instead, chemotherapy plus radiation was her best option. She decided to go back to the United States where she could get the best care possible.

“Before I started any treatment, I was so depressed,” she says. “I was so afraid and I thought I was going to die. I went to Parkland, where they told me UT

Southwestern was where I needed to go – that they had the best equipment and I would be placed with the best doctor.”At UTSW, Mrs. Snead would be treated by Kevin Albuquerque, M.D., FACR, Professor of Radiation Oncology and holder of the Ken Sharma Professorship in Radiation Oncology. When she met with Dr. Albuquerque, she learned she would receive the standard treatment for advanced cervical cancer – combined chemotherapy and radiation treatment to the pelvis – and, in her case, to the

By Ryan Daugherty

What we use over here at UT Southwestern is MRI to guide the brachytherapy, which is unique in Dallas.

– Dr. Kevin Albuquerque

abdomen and lymph nodes as well, where the cancer had spread. Following that would be brachytherapy.

“Brachytherapy is a form of highly focused radiation therapy that is delivered directly to the tumor,” says Dr. Albuquerque. “What we use over here at UT Southwestern is MRI to guide the brachytherapy, which is unique in Dallas.”

MRI imaging allows a very precise delineation of the cervical tumor and does not depend on 2-D points and space for a determined dose. Using this MRI-based technique has several advantages – it actually lowers the radiation dose to normal structures and spares patients from numerous toxicities.

First, Mrs. Snead was treated with external radiation using a special extended-field intensity-modulated radiation technique. Small dots, or tattoos, were placed around Mrs. Snead’s upper stomach and ribs to help radiation delivery setup. Internal radiation,

or brachytherapy, was the next step to consolidate the radiation effect.

After just two weeks of external radiation, Mrs. Snead received some very good news during one of her checkups. Her tumor had shrunk from 5 centimeters to 3 centimeters, which meant she would be able to take the next step and receive internal radiation – five treatments over a period of one month.

On March 5, 2014, Mrs. Snead received her last radiation treatment. Dr. Albuquerque explained that everything looked fine, but he wanted to wait for her PET scan. Not long

after, Mrs. Snead received the results of her PET scan and saw that she was cancer-free.

Currently a little over four years free of cancer, Mrs. Snead is living life to the fullest again alongside her husband, five children, and granddaughter. She continues to express her faith, more strongly, and is involved with her community as much as she can be. But, of course, the biggest blessing is being alive to do all these things, a testament to Dr. Albuquerque and UT Southwestern.

“For me it’s another chance to live,” she says. “I am so blessed that God allowed me to be treated here.”

Dr. Albuquerque & Maria Snead

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Innovations in delivering radiation treatment to patients with cancer are based on the most cutting-edge research. Our Department supports interlinked and integrated research tracks aimed at improving radiation therapy from every angle. Research in artificial intelligence, immunotherapy, imaging techniques, and novel therapeutic agents is a major part of how we are advancing radiation cancer care.

D I V I S I O N R E S E A R C H H I G H L I G H T S

Artificial Intelligence Research Programs in Radiation Oncology

Artificial intelligence (AI) has improved the ability of computers to learn and advance human-like tasks such as decision-making and problem-solving in medicine. Optimizing accuracy and efficiency is essential in radiation oncology because of the decisions that physicians and other clinical staff make, introducing error and variation. Implementing AI tools will minimize or eliminate problems encountered in the workflow of a radiation oncology clinic. Specifically, AI technology is improving cancer diagnosis, classification, delineation, and differentiation between tumors and sensitive healthy structures to improve radiation treatment for patients.

In 2017, Steve Jiang, Ph.D., Professor and Division Chief of Medical Physics and Engineering, established an initiative in our Department to address important medical problems through AI tools. The Medical Artificial Intelligence and Automation (MAIA) Lab and the Program of Excellence in Intelligence Medicine (PEIM) were designed to innovate, implement, and translate novel AI technologies to the clinical practice of cancer radiation therapy. The MAIA Lab is an internal program focused on AI research.

“Our AI-based algorithms are showing promise in improving the daily processes in the radiation oncology clinic,” says Dr. Jiang.

A team of prominent medical physicists from his Division is using sophisticated new tools to improve clinical workflow and patient treatment. Areas of medical application in cancer radiation therapy include radiomics to improve diagnosis and classification, better imaging techniques to predict metastasis development, more effective delineation of tumors and critical organs to advance clinical outcomes in patients, and novel tools to improve treatment quality.

Developing Automatic Parameter Tuning

Intelligent parameter tuning methods are designed to solve optimization problems in image reconstruction and treatment planning. “Optimization problems typically contain parameters that rule solution quality,” says Xun Jia, Ph.D., Associate Professor of Radiation Oncology. “In general, we adjust these parameters

manually in a trial-and-error fashion for best solution quality, delaying optimization and making optimization models difficult to use in the clinic.”

Dr. Jia’s team is developing deep reinforcement learning algorithms and approaches that can train a system to adjust parameters in an automatic, human-like manner.

“Our goal is to achieve similar or better quality in image reconstruction and treatment planning than that achieved with manually adjusted parameters,” he says.

By Damiana Chiavolini, Ph.D.

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Our goal is to achieve similar or better quality in image reconstruction and treatment planning than that achieved with manually adjusted parameters.

– Dr. Xun Jia

We will be able to better select patients who need systemic cancer therapy, and also reduce the risk of metastasis formation and adverse effects.

– Dr. Jing Wang

Delineating Tumors & Organs at Risk

Successful treatment planning in cancer radiation therapy depends on accurately delineating tumors and nearby sensitive organs, so that radiation therapy can be delivered safely and precisely. Delineation is still conducted manually by physicians with different levels of experience, generating variation in individual treatment plans. A team led by Xuejun Gu, Ph.D., Associate Professor of Radiation Oncology, is using AI technologies to develop automated delineation strategies.

“We are using a new AI model to segment brain tumor metastases and to better differentiate between tumors and healthy organs. For example, we try to irradiate brain metastases while sparing critical organs such as the brain stem and optical nerves,” says Dr. Gu.

Dr. Gu’s team is also developing AnatomyNet, a patient image database that will advance the field toward automatic delineation.

Predicting Treatment Outcome & Toxicity

Models that predict outcome and toxicity in cancer

treatment are currently preventing clinicians from developing accurate and personalized therapy options for individual patients. Jing Wang, Ph.D., Associate Professor of Radiation Oncology, is combining a so-called “multi-objective” radiomics model with AI algorithms to predict the development of metastases in patients with lung and cervical cancers. Also, Dr. Wang is focused on helping patients who are at high risk of developing toxicity caused by radiation treatment.

“We will be able to better select patients who need systemic cancer therapy, and also reduce the risk of metastasis formation and adverse effects. If we are successful, this will increase the length and quality of their life,” says Dr. Wang.

Detecting & Preventing Medical Errors

Reducing or eliminating errors in the complex and time-consuming treatment planning process (e.g., delineation, prescription) will increase accuracy and consistency of radiation delivery. This is also important to free up clinical staff time, allowing for a greater focus on patient care.

“In one of our projects we are developing SafetyNet, a platform that exploits AI to improve detecting errors in the radiation treatment of cancers, such as

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those of the head and neck,” says Weiguo Lu, Ph.D., Associate Professor of Radiation Oncology.

Developing a Treatment Planner

Dr. Jiang is also searching for solutions to increase and standardize treatment plan quality. Currently, treatment plan design depends on planners’ experience, effort, and ability to communicate with clinicians, making the process time-consuming and more prone to quality variations. This, in turn, may affect clinical outcomes such as mortality and hospital readmissions for patients across different centers and clinics. Dr. Jiang and Dan Nguyen, Ph.D., Assistant Professor of Radiation Oncology, are using AI tools to design a new planner that will assist dosimetrists in developing more efficient plans.

Developing Wearable Sensors & Location Tracking Systems

Dr. Jiang is applying AI tools to develop sensors that can be worn by patients undergoing radiation therapy to continuously monitor health data. These devices will help predict patient condition and activity, hospital admissions, and pain levels. Also, his team is designing Real-Time Location Systems, through Bluetooth Low Energy technology, which can locate patients and staff in the clinic to improve workflow and safety.

“The idea is to move toward ‘smart clinics,’ in which we will be able to process large sets of patient data using highly sophisticated AI technology,” says Dr. Jiang.

Improving Imaging

Current AI methods are also advancing disease imaging to improve treatment planning. The idea is to convert MRI to CT using AI methods for MRI-based radiotherapy treatment planning. MRI is more accurate and precise because it allows better differentiation between tumors and soft tissue, leading to better monitoring of treatment response and metastasis development. MRI is a safer imaging modality because it eliminates patient exposure to radiation. It is also more convenient because it reduces the number of appointments needed to evaluate the tumor site. Radiation Oncology

investigators involved in AI imaging projects include Dr. Jia; Dr. Wang; Amir Owrangi, Ph.D., Assistant Professor; and Ming Yang, Ph.D., Assistant Professor.

Founded in December 2017, PEIM promotes interdisciplinary collaborations in AI between researchers at UT Southwestern and other centers. Under the leadership of Dr. Jiang; Robert Timmerman, M.D., Professor and Co-Director for AI in Clinical Research; and Michael Story, Ph.D., Professor and Co-Director for AI in Biological Research, PEIM promotes research in precision medicine, diagnosis, treatment planning, medical imaging, quality assurance, and medical error detection. These collaborations are essential to developing and establishing AI technologies that will help solve medical problems. All PEIM members and collaborators have access to shared resources such as high-performance computing and database cores. Also, PEIM co-sponsors the AI in Medicine (AIM) Seminar Series with the Department of Bioinformatics and the Quantitative Biomedical Research Center at UT Southwestern, fostering interdisciplinary collaborations and community relations.

Through MAIA and PEIM, AI has great potential to advance the field of radiation oncology, leading to more effective and efficient clinical workflow and better treatment of patients with cancer.

Dr. Jiang holds the Barbara Crittenden Professorship in Cancer Research.

The idea is to move toward ‘smart clinics,’ in which we will be able to process large sets of patient data using highly sophisticated AI technology.

– Dr. Steve Jiang

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Immunotherapy Research in Radiation Oncology

Immunotherapy, which harnesses the immune system to attack tumor cells in the same way that it attacks foreign pathogens, holds great promise for advancing cancer treatment, especially when combined with radiation or chemotherapy. With support from across UT Southwestern and the surrounding community, researchers and clinicians in the Department of Radiation Oncology are collaborating to study the interactions between radiation and the immune system, from the molecular level to the clinic, to identify new therapeutic combinations to treat cancer more effectively.

By Jonathan Feinberg, Ph.D.

Molecular Biological Bases

Radiation therapy kills cancer cells mainly by damaging their DNA, which affects these cells’ ability to replicate and can lead to cell death. However, the DNA damage caused by radiation also sets in motion molecular factors that respond to this damage, as well as factors that activate and regulate the immune system. Developing new therapies that can exploit the immune response to radiation requires understanding the complex molecular interplay among these factors.

Asaithamby Aroumougame, Ph.D., Assistant Professor of Radiation Oncology, and his lab study the molecular factors that respond to and repair DNA damage caused by radiation and other genetic or environmental influences. Specifically, they focus on how these factors interact with, trigger, or suppress the immune system. Dr. Aroumougame and his team seek novel immunomodulatory drugs that can exploit DNA repair and DNA damage response factors within cancer cells to trigger immune signaling after irradiation and recruit immune cells to the tumor to kill cancer cells.

Directing the immune system to attack cancer cells but ignore normal, non-cancerous cells requires

identifying tumor-specific neoantigens, or antigens that form on certain cancer cells but not on normal cells, for immune cells to target. Dr. Aroumougame’s lab is currently investigating neoantigens specific to BRCA1-mutant breast cancer, in collaboration with Chao Xing, Ph.D., Associate Professor of Clinical Science, and Tao Wang, Ph.D., Assistant Professor of Clinical Science, to locate potential targets for new vaccines. “Our research will not only help us to develop novel vaccines against cancer-specific neoantigens but also redirect immune cells to the tumor microenvironment to eradicate metastatic cancer cells,” Dr. Aroumougame explains. Their research has great clinical potential not only to improve treatment for BRCA1-mutant breast cancer, but also to help prevent it through vaccination.

From the Lab to the Clinic

Different tumors respond to immunotherapy in different ways, and many tumors have evolved mechanisms that suppress immune responses to resist therapy. Understanding how the immune system and cancer cells interact is essential to developing new strategies to overcome this therapeutic resistance.

Wen Jiang, M.D., Ph.D., Assistant Professor of Radiation Oncology, investigates how tumor cells evade detection and eradication by the body’s innate immune system. Specifically, his lab studies how cancer cells suppress phagocytosis, the process by which certain immune cells, such as dendritic cells, engulf foreign substances and present them to other

Our research will not only help us to develop novel vaccines against cancer-specific neoantigens but also redirect immune cells to the tumor microenvironment to eradicate metastatic cancer cells.

– Dr. Asaithamby Aroumougame

immune cells to initiate a systemic immune response throughout the body.

Understanding the mechanisms of immune suppression will help to develop new therapeutic approaches to overcome them. Currently, Dr. Jiang’s group is working with industry partners to develop agents that specifically target phagocytosis evasion in preparation for phase I clinical trials. They are also collaborating with Yang-Xin Fu, M.D., Ph.D., Professor of Pathology, and others to study how overcoming innate immune resistance can improve treatment outcomes in brain tumors.

Todd Aguilera, M.D., Ph.D., Assistant Professor of Radiation Oncology, and his lab study the genetic factors that influence whether immune responses are suppressed or activated in the tumor microenvironment in response to cancer therapies. Specifically, they seek to identify factors that allow pancreatic tumors to withstand or even hijack the immune response stimulated by radiation therapy. “In a number of cancers that are adapted to an inflammatory environment, the immune response is quite subdued after irradiation, and it can trigger a wound-healing response that supports tumor cell recovery within the tumor and the tumor microenvironment,” says Dr. Aguilera. “We actually need to add novel agents that help generate

productive anti-tumor responses to combat immune responses that help the tumor recover.” With funding support from a Distinguished Researcher Award given by UT Southwestern’s President’s Research Council, Dr. Aguilera’s lab is screening a library of millions of single-domain antibodies to identify molecules that can target factors that influence the immune response within the tumor microenvironment.

For patients with locally advanced pancreatic cancer, adding an immune agent after treatment with stereotactic ablative radiotherapy (SAbR) – which delivers a focused, powerful dose of radiation – could generate a systemic immune response to complement the superior local tumor control that SAbR provides. As the UT Southwestern site principal investigator for the multi-institution PanCRS phase III clinical trial, Dr. Aguilera is investigating whether SAbR improves

longer-term outcomes for patients with locally advanced pancreatic cancer when added to the standard of care chemotherapy regimen, FOLFIRINOX. Adding an immune active agent that uniquely couples with ablative radiation to generate anti-tumor immune responses could eradicate micro-metastatic disease – the microscopic, undetectable beginnings of metastasis – before it progresses. This could offer a compelling approach to improve long-term outcomes in patients with localized pancreatic cancer.

Immunotherapy and SAbR have been shown to synergize and enhance each other’s effects when administered concurrently. Raquibul Hannan, M.D., Ph.D., Associate Professor of Radiation Oncology, investigates this synergy to develop strategic therapeutic combinations that can treat cancer more effectively. In the lab, Dr. Hannan’s group

We actually need to add novel agents that help generate productive anti-tumor responses to combat immune responses that help the tumor recover.

– Dr. Todd Aguilera

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studies animal models of cancer to understand the molecular mechanisms of synergy between stereotactic radiation and immunotherapy. Dr. Hannan is a project leader on a recently-funded Multi-Investigator Research Award (MIRA), a prestigious, $6 million grant from the Cancer Prevention Research Institute of Texas that will fund a coordinated program of research studies. Together with Dr. Fu, the MIRA principal investigator, and Zhijian Chen, Ph.D., Professor of Molecular Biology, Dr. Hannan will study the molecular operation of the cGAS-STING pathway, which links the cellular response to DNA damage caused by radiation to the activation of the immune system. Understanding how this pathway functions will allow them to identify molecular targets for drugs or other agents to regulate and direct the immune response after radiation therapy.

Dr. Hannan’s pre-clinical laboratory studies inform his clinical research, including several ongoing clinical trials that apply and test combinations of SAbR and immunotherapy in patients. Dr. Hannan recently published a study in OncoImmunology, together with Robert Timmerman, M.D., Professor and Vice Chair of Radiation Oncology, and others, that reviews their experience treating patients at UT Southwestern with a combination of SAbR and immune checkpoint inhibitors. They compared patient outcomes and adverse side effects with historical reports

of patients treated only with immune checkpoint inhibitors. They found that adding SAbR does not significantly increase side effects and may improve patients’ response to treatment. These promising results suggest that combining SAbR and immune checkpoint inhibitors can provide safe and effective treatment and should be studied further.

Transforming Clinical Practice

Clinical radiation oncologists have long observed isolated, infrequent cases where radiation delivered to one tumor causes other, non-treated tumors to shrink or even disappear. This phenomenon, known as the abscopal effect, is believed to occur when targeted radiation therapy initiates an adaptive immune response that kills cancer cells elsewhere in the body.

Dr. Timmerman investigates the mechanisms of the abscopal effect to learn how to trigger it deliberately and consistently. “We are actively working to understand the mechanisms and processes involved in reliable immune response after radiation as well as test combination therapies in the clinic,” Dr. Timmerman explains. “We have put considerable resources in place for this investigation, including organizing teams to develop new therapeutic approaches, conducting new imaging investigations,

and testing strategies in clinical trials.” One such trial, the RADVAX Trial, led by Hans Hammers, M.D., Ph.D., Associate Professor of Internal Medicine, tests the safety and efficacy of combining SAbR with the immune checkpoint inhibitors Nivolumab and Ipilimumab in patients with kidney cancer.

Their findings are already influencing clinical practice at UT Southwestern. “We piggy-back stereotactic ablative treatments onto standard immunotherapy drug regimens if one or more tumors are symptomatic,” says Dr. Timmerman, “to ‘increase the bang for the buck’ of treatments that might otherwise be given independently.” These therapeutic combinations will be refined over time as laboratory and clinical research advances.

By investigating the molecular interactions between DNA damage response factors and the immune system, identifying novel agents that stimulate and direct the immune response after radiation, and testing new combinations of radiation and immunotherapy in clinical trials, the Department of Radiation Oncology is transforming cancer treatment to improve outcomes for patients with cancer.

Dr. Timmerman holds the Effie Marie Cain Distinguished Chair in Cancer Therapy Research.

Precise Imaging for Radiation Treatment of Liver Cancer

The frequency of liver cancer has increased over the years, leading to many deaths in the United States and worldwide. Stereotactic ablative radiotherapy (SAbR), also known as stereotactic body radiation therapy (SBRT), is potentially effective and safe for treating liver malignancies. SAbR is delivered to patients with the aid of cone-beam computed tomography (CBCT), a medical imaging technique where divergent X-rays form a cone. Nevertheless, respiratory motion and low contrast in CBCT do not allow clear imaging of tumors, indicating the need to improve image quality so that radiation treatment can be delivered more successfully to patients. Although image-contrast agents are used in diagnostic CT to better visualize tumors, their use in CBCT is only helpful in about 50 percent of patients because of poor image quality.

Xun Jia, Ph.D., Associate Professor of Radiation

Oncology, and his team are studying the applications of CBCT for image-guided radiation therapy. So far, they have examined how to improve image quality by overcoming difficulties associated with low contrast and motion. Also, they have evaluated methods that reduce patients’ exposure to radiation during treatment courses. Most recently, they have focused their attention on liver cancer.

In March 2018, Dr. Jia was awarded $2 million in NIH funds to develop a new version of CBCT that will allow more precise detection of tumors, facilitating SAbR treatment in patients with liver cancer. Because liver tumors cannot be seen clearly due to motion and poor CBCT quality, even with the aid of image-contrast agents, he and his team will develop a method that converts traditional CBCT to multi-energy motion-compensated CBCT. Because the new multi-energy CBCT is more sensitive than traditional CBCT, tumors will be visualized better with lower doses of the image-contrast agents. “CBCT image quality can be very poor without contrast,” says Dr. Jia. “So we need novel tools to improve it.”

“In addition to developing an image-guidance system that will enable us to see liver tumors better, we are also looking at increasing safety by reducing the amount of image-contrast agents that may be toxic for patients, especially considering that the agents will be used multiple times in a treatment course,” adds Dr. Jia.

Refining CBCT quality, accuracy, and safety is essential for improving the effectiveness of SAbR as a treatment modality for patients with liver cancer.

Novel Applications for a Promising New Drug

Almost all patients who receive combined radiation and chemotherapy to treat head and neck cancer experience oral mucositis, a painful inflammation of the mucous membranes inside the mouth. Patients who suffer from this debilitating side effect of radiotherapy can be hospitalized and their therapies interrupted, ultimately leading to worse treatment outcomes.

New Discoveries in Radiation Oncology By Damiana Chiavolini, Ph.D., and Jonathan Feinberg, Ph.D.

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GC4419, an investigational drug developed by Galera Therapeutics, is currently being evaluated in a phase III clinical trial as a radioprotective agent to reduce the incidence and severity of severe oral mucositis due to radiation therapy in patients being treated for head and neck cancer. This promising drug has received breakthrough therapy designation and fast track designation by the U.S. Food and Drug Administration.

Michael Story, Ph.D., Professor and Vice Chair of Radiation Oncology, and his lab have discovered another potential application for GC4419. Their pre-clinical studies have shown that GC4419 has a profound anti-tumor effect when combined with high-dose per fraction radiation, an unexpected finding for a drug designed to be a radioprotector.

This discovery has laid the groundwork for new pre-clinical studies and clinical trials to test the drug’s anti-tumor effects in various cancers. A clinical trial evaluating the combination of GC4419 and SBRT on pancreatic cancer is currently underway at UT MD Anderson Cancer Center in Houston. UT Southwestern will join this trial soon, with Todd Aguilera, M.D., Ph.D., Assistant Professor of Radiation Oncology, as

site principal investigator. With funding from a Small Business Innovation Research award, Dr. Story and Puneeth Iyengar, M.D., Ph.D., Assistant Professor of Radiation Oncology, are working with Galera on pre-clinical studies and a clinical trial that will test GC4419’s potential to improve SBRT for lung cancer by reducing side effects while increasing the radiation’s anti-tumor effect. And working with David Sher, M.D., M.P.H., Associate Professor of Radiation Oncology, Dr. Story has applied for an Individual Investigator Research Award for Clinical Translation from the Cancer Prevention Research Institute of Texas to study GC4419’s ability to sensitize head and neck cancer to SBRT while protecting normal tissues.

Through their cutting-edge research, Dr. Story’s team has expanded the possibilities for GC4419, revealing this already promising drug’s potential uses for treating cancer.

Space Radiation Risk Assessment

Astronauts on long-duration space missions are

exposed to radiation that humans don’t normally encounter on Earth. The National Aeronautics and Space Administration (NASA) invests in research that investigates the cancer risks that astronauts face as a result of this exposure.

In September 2018, Dr. Story’s lab was awarded research funding from NASA to study

sex differences in the risk for developing lung cancer after space radiation exposure. The NASA award will also provide funding for Dr. Story’s team to investigate GC4419 as a countermeasure to protect astronauts from the harmful effects of space radiation. Astronauts could take this drug daily or before an impending radiation exposure, such as a solar storm.

NASA also funds Sandeep Burma, Ph.D., Associate Professor of Radiation Oncology, and his lab to study the molecular mechanisms by which high-energy (HZE) particles in space radiation cause gliomas, a type of brain cancer that forms in the glial cells, in mouse models. Dr. Burma’s team has found that mammalian cells cannot repair much of the DNA damage inflicted by HZE particles, which results in a high rate of cellular transformation that leads to cancer.

These studies will advance the understanding of the health risks that astronauts face from prolonged exposure to space radiation and may identify new ways to lessen those risks.

New Targets for Cancer Therapy

Kenneth Westover, M.D., Ph.D., Associate Professor of Radiation Oncology, is studying the molecular machinery, such as proteins, that becomes dysfunctional in cancer. His lab’s studies

emphasize understanding how these proteins work and designing specific small molecule inhibitors that can be used to study and, in some cases, treat cancer. Historically, his lab has focused on the RAS and kinase protein families, which control diverse cellular processes such as cell division, growth, survival, migration, and metabolism, and are often mutated in cancer.

In January 2018, Dr. Westover’s team published a study in the prestigious journal Cell showing a new mechanism that regulates RAS function called dimerization. In dimerization, two RAS molecules interact to form a complex. “What became clear in our studies is that RAS needs to dimerize to efficiently pass signals in cells that cause the cancer state. However, dimerization can also change the sensitivity of cancer cells to certain targeted therapies. Dimerization is a potential target for cancer therapy and may also inform how we select certain therapies for cancer patients,” says Dr. Westover.

Dr. Story holds the David A. Pistenmaa, M.D., Ph.D.

Distinguished Chair in Radiation Oncology.

Dr. Hannan & student in lab

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Pre-clinical radiation research in cell or small animal models is essential for understanding the molecular biological effects of radiation and for developing new treatment strategies that involve radiation before testing them in clinical trials.

Unfortunately, many investigators do not have the training in radiation physics and radiobiology to conduct this research properly, which often results in experimental results that cannot be reproduced by other scientists. The U.S. Food and Drug Administration, the National Cancer Institute, and many prominent research journals have raised concerns that pre-clinical radiation research often calculates radiation doses inaccurately and calibrates irradiation devices improperly. Furthermore, many pre-clinical research facilities have not kept pace with the technologies currently used in clinical radiation therapy, which limits the clinical relevance of their research findings.

To address these limitations in pre-clinical radiation

research, the Cancer Prevention Research Institute of Texas (CPRIT) has awarded Michael Story, Ph.D., Professor and Vice Chair of Radiation Oncology, $3.7 million to establish a Pre-Clinical Radiation Core Facility (PCRCF) at UT Southwestern. Led by Dr. Story and co-Principal Investigator Xun Jia, Ph.D., Associate Professor, and managed by Debabrata Saha, Ph.D., Associate Professor, the PCRCF will provide investigators access to up-to-date technologies, including novel irradiators, as well as the expertise needed to perform accurate, clinically relevant radiation research on those devices. One reviewer of Dr. Story’s application called the PCRCF a “unique and world-class facility.”

The PCRCF will organize, consolidate, and administer existing resources at UT Southwestern within a single facility and add new devices as well. Available resources will include not only irradiators and imaging technologies, but also cell and animal models that have been developed for use in experiments involving

radiation. Investigators will be given proper training on PCRCF devices, as well as substantial sets of historical data on the cell and animal models. Radiation physicists will ensure that machines are calibrated properly and that radiation doses are calculated accurately. In addition to a complete description of the dosimetry plan for their experiments, investigators will be provided with the proper language for publication. In this way, the PCRCF will ensure that pre-clinical radiation experiments are performed correctly and their results are communicated clearly and accurately.

The PCRCF will be available not only to scientists at UT Southwestern, but to all CPRIT-funded investigators across the state of Texas. In this way, the facility will serve a broad community of cancer researchers.

By providing much-needed expertise and state-of-the-art facilities and technologies, the PCRCF will advance the pre-clinical research that forms the foundation for clinical radiation therapy.

A Unique and World-Class Pre-Clinical Radiation Research FacilityBy Jonathan Feinberg, Ph.D.

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D E P A R T M E N T H I G H L I G H T S

Our Faculty

CLINICAL

Hak Choy, M.D., FASTROChairman, ProfessorHolder of the Nancy B. & Jake L. Hamon Distinguished Chair in Therapeutic Oncology ResearchTrained: Ohio State University Hospital; UT Health Science Center at San Antonio

Dr. Choy treats lung cancer.

Robert Timmerman, M.D., FASTRO, FACRVice Chairman, Professor and Medical DirectorHolder of the Effie Marie Cain Distinguished Chair in Cancer Therapy ResearchTrained: Johns Hopkins Hospital

Dr. Timmerman primarily treats adults and children with brain tumors and vascular malformations.

Todd Aguilera, M.D., Ph.D.Assistant ProfessorTrained: UC San Diego School of Medicine

Dr. Aguilera treats gastrointestinal cancer.

Kevin Albuquerque, M.D., FACRProfessor Director of Quality Improvement/Quality Assurance Holder of the Ken Sharma Professorship in Radiation OncologyTrained: University Hospital of Brooklyn

Dr. Albuquerque treats gynecologic cancers and melanoma.

Prasanna Alluri, M.D., Ph.D. Assistant ProfessorTrained: University of Minnesota

Dr. Alluri treats breast cancer.

Tu Dan, M.D.Assistant ProfessorTrained: Sidney Kimmel Medical College at Thomas Jefferson University

Dr. Dan treats adult and pediatric central nervous system diseases.

Neil Desai, M.D., M.H.S.Assistant ProfessorAwarded the Dedman Family Scholar in Clinical CareTrained: Memorial Sloan Kettering Cancer Center

Dr. Desai treats genitourinary diseases and lymphoma.

Michael Folkert, M.D., Ph.D.Assistant Professor and Residency Program DirectorTrained: Memorial Sloan Kettering Cancer Center

Dr. Folkert treats gastrointestinal malignancies and many other disease sites with brachytherapy.

Aurelie Garant, M.D.Assistant ProfessorTrained: McGill University

Dr. Garant treats genitourinary and gastrointestinal malignancies.

Groups by Division

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Raquibul Hannan, M.D., Ph.D.Associate ProfessorTrained: Albert Einstein College of Medicine

Dr. Hannan treats genitourinary malignancies.

Puneeth Iyengar, M.D., Ph.D.Assistant ProfessorTrained: UT MD Anderson Cancer Center

Dr. Iyengar treats lung cancer.

Wen Jiang, M.D., Ph.D.Assistant ProfessorTrained: UT MD Anderson Cancer Center

Dr. Jiang treats central nervous system tumors.

Nathan Kim, M.D., Ph.D.Associate ProfessorTrained: Vanderbilt University Medical Center

Dr. Kim treats breast cancer.

Kiran Kumar, M.D. Assistant ProfessorTrained: Stanford University

Dr. Kumar treats lymphomas and pediatric malignancies.

Lucien Nedzi, M.D.Associate ProfessorTrained: Harvard Medical School

Dr. Nedzi treats central nervous system malignancies.

Asal Rahimi, M.D., M.S.Associate Professor and Director of Clinical ResearchTrained: University of Virginia

Dr. Rahimi treats breast cancer.

Nina Sanford, M.D.Assistant ProfessorTrained: Harvard Radiation Oncology Program

Dr. Sanford treats gastrointestinal malignancies.

Jennifer Shah, M.D.Assistant Professor and Associate Director of Medical Residency ProgramTrained: Stanford University

Dr. Shah treats head and neck malignancies and lymphoma.

David Sher, M.D., M.P.H.Associate ProfessorTrained: Harvard Radiation Oncology Program

Dr. Sher treats head and neck cancer.

Ann Spangler, M.D.Associate ProfessorTrained: Shands Hospital at the University of Florida

Dr. Spangler treats breast cancer.

Zabi Wardak, M.D.Assistant ProfessorTrained: UT Southwestern Medical Center

Dr. Wardak treats adult and pediatric central nervous system diseases.

Kenneth Westover, M.D., Ph.D.Associate Professor and Director of Clinical Innovation and Information SystemsTrained: Harvard Radiation Oncology Program

Dr. Westover treats lung cancer.

MOLECULAR RADIATION BIOLOGY

Michael Story, Ph.D.Vice Chairman, ProfessorDirector, Division of Molecular Radiation BiologyTrained: Colorado State University

Research Interests:• Biomarkers of radiotherapeutic response in head

and neck cancer• Carcinogenic risk from charged particle exposure

in space• Charged particle radiotherapy

Asaithamby Aroumougame, Ph.D.Assistant ProfessorTrained: Banaras Hindu University

Research Interests:• DNA damage response signaling in carcinogenesis• DNA repair factors in immune response and

immunotherapy• DNA replication in tumorigenesis

Sandeep Burma, Ph.D.Associate ProfessorTrained: National Institute of Immunology (India)

Research Interests:• Sensing, signaling, and repair of DNA double-

strand breaks• Genetic basis of glioblastoma radioresistance• Genetic events underlying transformation of

radiation-induced gliomagenesis

Benjamin Chen, Ph.D.Associate ProfessorTrained: Ohio State University

Research Interests:• Genomic instability and cancer development• Radiation biology and DNA damage repair• Tissue stem cells

David Chen, Ph.D.ProfessorTrained: University of Missouri

Research Interests:• DNA damage responses induced by HZE particles

in human cells• Pathway choice of DNA double-strand break repair• The role of DNA-PK in double-strand break repair

Anthony Davis, Ph.D.Assistant ProfessorTrained: UT Southwestern Medical Center

Research Interests:• Basic radiation biology• Cellular response to DNA damage• Intrinsic and tumor/cancer radioresponses

Lianghao Ding, Ph.D.Assistant ProfessorTrained: Tohoku University

Research Interests:• DNA damage response induced by heavy particles• Functional genomics of radiation toxicity• Role of microRNA in head and neck cancer

Liya Gu, Ph.D.ProfessorTrained: Wayne State University

Research Interests:• Mismatch repair• Genome instability• Cancer metabolism

Qihuang Jin, Ph.D.InstructorTrained: Chinese Academy of Sciences

Research Interests:• Relationship between DNA mismatch repair and

immunotherapy• Role of DNA mismatch repair and

neurodegenerative disease• Epigenetic regulation of DNA repair

Guo-Min Li, Ph.D.ProfessorTrained: Wayne State University

Research Interests:• Mechanistic studies of DNA mismatch repair• Targeting DNA repair factors for cancer therapy• Mechanisms regulating chromosome stability

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Yu-Fen Lin, Ph.D.InstructorTrained: National Taiwan University

Research Interests:• DNA-PK in ATR-signaling pathway• Role of T2609 phosphorylation cluster on the

S-phase checkpoint response

Huiming Lu, Ph.D.InstructorTrained: Zhejiang University

Research Interests:• Molecular mechanisms of DNA double-strand

break repair• Targeting key players of DNA double-strand break

repair for potential cancer therapy

Bipasha Mukherjee, Ph.D.Assistant ProfessorTrained: National Institute of Immunology (India)

Research Interests:• DNA damage and repair• Heavy particle radiobiology• Radioresistance of glioblastoma

Shibani Mukherjee, Ph.D.Assistant ProfessorTrained: Lawrence Berkeley National Laboratory

Research Interests:• DNA damage response signaling in immune

signaling and cancer immunotherapy• Role of Werner syndrome protein in cardiovascular disease

Janice Ortega, Ph.D.InstructorTrained: University of Kentucky

Research Interests:• Mismatch repair in cancer initiation and

progression• Mismatch repair activity in DNA damage response• Characterization of PCNA phosphorylation in cancer

Laurentiu Pop, M.D.InstructorTrained: University of Medicine and Pharmacy of Craiova

Research Interests:• Investigating tumor escape mechanisms• Developing immunotherapy for cancer

Vinesh Puliyappadamba, Ph.D.InstructorTrained: University of Kerala

Research Interests:• Radiosensitization of glioma using novel ATR inhibitors• Study of the mechanism of radiation resistance in glioma• DNA damage and DNA repair mechanism in glioma

Debabrata Saha, Ph.D.Associate ProfessorTrained: University of Calcutta

Research Interests:• Role of cycloxygenase-2 in radiation and

chemoresistance• Role of small-molecule inhibitors as

radiosensitizers

Janapriya Saha, Ph.D.InstructorTrained: University of Duisburg-Essen

Research Interests:• DNA double-strand break signaling and repair• Space/HZE particle radiation-induced DNA

damage and response

Nashir Udden, Ph.D.InstructorTrained: University of Dhaka

Research Interests:• Biomarkers for breast cancer, colorectal cancer,

and hepatocellular carcinoma• Gut microbiome in regulating the efficacy of anti-

cancer therapy• Radiation-mediated immunity and tumor

regression

MEDICAL PHYSICS AND ENGINEERING

Steve Jiang, Ph.D.Vice Chair Professor and Division ChiefTrained: Medical College of Ohio-Toledo

Research Interests:• Artificial intelligence in medicine• GPU and cloud-based automated treatment

planning• Online replanning for adaptive radiotherapy

Chuxiong Ding, Ph.D.Associate ProfessorTrained: Tsinghua University

Research Interests:• Image-guided radiotherapy• Stereotactic radiation therapy

Xuejun Gu, Ph.D.Associate ProfessorTrained: Columbia University

Research Interests:• Online adaptive radiotherapy• Pediatric radiation oncology with movie-induced

sedation effect

Brian Hrycushko, Ph.D.Assistant ProfessorTrained: UT Health Science Center at San Antonio

Research Interests:• Normal tissue tolerance• Stereotactic radiotherapy• Brachytherapy

Xun Jia, Ph.D.Associate ProfessorTrained: Peking University

Research Interests:• 3-D/4-D computed tomography reconstruction• Monte Carlo particle transport simulation for

radiotherapy• GPU-based high-performance computing

radiotherapy

Mu-Han Lin, Ph.D.Assistant ProfessorTrained: National Tsing Hua University

Research Interests:• 3-D/4-D patient dose reconstruction and validation• Clinical implementation of novel treatment technologies• Stereotactic radiotherapy

Weiguo Lu, Ph.D.Associate ProfessorTrained: University of Wisconsin-Madison

Research Interests:• Next-generation treatment planning• High performance (GPU) computing• Adaptive radiotherapy

Sarah McGuire, Ph.D.Associate ProfessorTrained: Duke University

Research Interests:• Functional imaging for radiation therapy treatment

planning and response assessment

Paul Medin, Ph.D.Professor and Medical Physics Residency Program Director

Research Interests:• Stereotactic delivery technology and research• Tissue tolerance in high-dose, single-fraction delivery

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Dan Nguyen, Ph.D.Assistant ProfessorTrained: University of California, Los Angeles

Research Interests:• Radiation therapy treatment planning• Artificial intelligence applications to medicine• Optimization techniques and algorithms

Amir Owrangi, Ph.D.Assistant ProfessorTrained: University of Western Ontario

Research Interests:• MRI-guided radiation therapy• Brachytherapy• Adaptive radiation therapy

Yang Park, Ph.D.Assistant ProfessorTrained: Harvard Radiation Oncology Program

Research Interests:• Cone-beam computed tomography• Motion management• Open source software

Arnold Pompos, Ph.D.Associate Professor and Chief Clinical PhysicistTrained: Indiana University - Purdue University Indianapolis

Research Interests:• Heavy particle interactions• Microdosimetry• Monte Carlo simulations

Robert Reynolds, Ph.D.Assistant ProfessorTrained: Georgia Institute of Technology

Research Interests:• Quality assurance and management• Novel treatment delivery• Stereotactic radiotherapy

Yiping Shao, Ph.D.ProfessorTrained: Kent State University

Research Interests:• Nuclear imaging technology and application for

molecular imaging and radiotherapy

Chenyang Shen, Ph.D.InstructorTrained: Hong Kong Baptist University

Research Interests:• Medical image processing• Machine learning• Optimization techniques and algorithms

Strahinja Stojadinovic, Ph.D.Associate ProfessorTrained: University of Belgrade

Research Interests:• Intensity-modulated radiation therapy quality assurance• Preclinical radiotherapy delivery technologies• Stereotactic radiotherapy

Guanglin Tang, Ph.D.InstructorTrained: Texas A&M University

Research Interests:• Real-time location system• Smart hospitals• Imaging processing

Jing Wang, Ph.D.Associate ProfessorTrained: University of Science and Technology of China

Research Interests:• Cone-beam computed tomography• Image-guided radiation therapy• Medical imaging processing

Rongfang Wang, Ph.D.Visiting InstructorTrained: Xidian University

Research Interests:• Medical image processing• Deep learning• Optimization techniques and algorithms

Yulong Yan, Ph.D.Associate Professor and Computational Physics DirectorTrained: Nanjing University

Research Interests:• Novel treatment-planning technologies• Clinic-oriented applications• DICOM

Ming Yang, Ph.D.Assistant ProfessorTrained: University of Texas Health Science Center at Houston

Research Interests:• Proton dose calculation and optimization• Dual-energy computed tomography

You Zhang, Ph.D.Assistant ProfessorTrained: Duke University

Research Interests:• 3-D/4-D image reconstruction• Biomechanical modeling• Motion management in radiotherapy

Bo Zhao, Ph.D.Assistant ProfessorTrained: State University of New York at Stony Brook

Research Interests:• Image-guided radiation therapy• Stereotactic body radiation therapy

Yuncheng Zhong, Ph.D.InstructorTrained: Peking University

Research Interests:• Computer simulation and system integration of

cone-beam computed tomography and positron emission tomography

• Image reconstruction

Zhiguo Zhou, Ph.D.InstructorTrained: Xidian University

Research Interests:• Radiomics• Treatment outcome prediction• Medical image analysis

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Faculty RecognitionWhether through clinical care, research, or education, many of our faculty have recently been recognized for their

commitment and contributions to the field of radiation oncology.

Todd Aguilera, M.D., Ph.D. • CPRIT Recruitment of First-Time, Tenure-

Track Faculty Member Award, 2017• President’s Research Council

Distinguished Researchers Award, 2018

Kevin Albuquerque, M.D., FACR • Ken Sharma Professorship in

Radiation Oncology, 2017• Fellow of American College of

Radiology, 2018

Hak Choy, M.D., FASTRO• Fellow of American Society for

Radiation Oncology, 2017

Neil Desai, M.D., M.H.S.• Dedman Family Scholar in Clinical

Care, 2016

Xun Jia, Ph.D.• American Association of Physicists

in Medicine John Laughlin Young Scientist Award, 2017

Wen Jiang, M.D., Ph.D. • CPRIT Recruitment of First-Time,

Tenure-Track Faculty Member Award, 2018

Paul Medin, Ph.D.• Fellow of American Association of

Physicists in Medicine, 2017

Guo-Min Li, Ph.D.• CPRIT Established Investigator

Recruitment Award, 2017• UT Rising Star Investigator Award, 2017• Reece A. Overcash Jr. Distinguished Chair

for Research on Colon Cancer, 2017• Fellow of American Association for

the Advancement of Science, 2018

Jennifer Shah, M.D. • Eugene P. Frenkel Endowed Scholar

in Clinical Medicine, 2018

Robert Timmerman, M.D., FASTRO, FACR

• Fellow of American College of Radiology, 2017

• Fellow of American Society for Radiation Oncology, 2018

Yulong Yan, Ph.D. • Fellow of American Association of

Physicists in Medicine, 2018

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Education & Training

Radiation Oncology Residency Programs

We offer two accredited residency programs, a Medical Residency Program and Medical Physics Residency Program – both of which are among the top of radiation oncology training and research programs in the country.

As part of the larger Department that includes physicians, physicists, dosimetrists, molecular biology researchers, and various clinical and administrative staff, residents are part of the NCI-designated Harold C. Simmons Comprehensive Cancer Center that is accredited by the Joint Commission and the American College of Radiology. Our Department cares for approximately 200 patients each day, covering all disease types and including pediatric patients.

Our Medical Residency Program is a four-year program, accredited by the ACGME since 2005, open to applicants who have completed their first postgraduate year. In addition to receiving clinical training, each resident trains in physics and radiation biology, as well as biostatistics and clinical trial design.

Our Medical Physics Residency Program is a three-year program, accredited by CAMPEP, that integrates two years of full-time clinical training and one year of research in medical physics. Residents have uniquely diverse clinical training with access to state-of-the-art technology from nearly every major vendor in the profession and hands-on experience with a full complement of special procedures.

Many of our residents have received awards and special recognition for their work in radiation oncology.

Medical Residents’ Awards

Osama Mohamad, M.D. • International Symposium on Ion Therapy, Travel

Award, 11/2018. Dr. Mohamad was invited to give a talk at this year’s annual workshop in Saga, Japan. His talk was entitled “Second Malignant Neoplasm After Carbon Ion Therapy.”

Dat Vo, M.D., Ph.D.• American College of Radiation Oncology Resident

Seed Grant, 9/2017. Dr. Vo was given the award for

his work in Dr. Story’s lab, where he studied the role of miR-125a-5p as a tumor suppressor miRNA in head and neck cancer and as a marker of poor prognosis. ACR awards only two seed grants annually to fund small but important projects.

Ryan Jones, M.D. • James M. Moorefield, MD, Economics Fellowship,

2017. This award, sponsored by the American College of Radiology Economics & Health Policy Department, offers radiology residents direct exposure to ACR’s economics activities. Each year, two residents are sponsored by ACR and one is sponsored by the Texas Radiological Society (TRS). Dr. Jones was supported by TRS.

Yuanyuan (Faith) Zhang, M.D., Ph.D.• B. Leonard Holman Research Pathway by the

American Board of Radiology, 2018. The Holman Pathway is awarded to an exceptional trainee with both strong clinical abilities and a background in research. Dr. Zhang’s overall research interest was to identify metabolic predictors of tumor sensitivity to radiation and immunotherapy and to develop small-molecule therapeutics targeting the

The Department of Radiation Oncology is committed to providing comprehensive and advanced educational programs to the next generation of medical professionals, as well as professionals already practicing.

Resident in OR brachytherapy procedure

metabolic microenvironment to enhance tumor kill and mitigate normal tissue toxicities.

Physics Residents’ Awards

CURRENT RESIDENTS

Tsuicheng “David” Chiu, Ph.D. • BestinPhysics(JointImagingTherapy),AAPM2016

David Parsons, Ph.D. • BestPoster,SWAAPM2018YoungInvestigator:D.Parsons,T.Chiu,R.Chopra,W.Lu,S.JiangandX.Gu.“DevelopmentofaRoboticPrototypeUltrasoundTomographySystemforImageGuidedProneBreastSBRT.”

• BookPrizeforBiologyandTechnology,CARO2017(poster):M.N.Ha,D.Parsons,O.Piccolo,N.Melong,A.Detappe,O.Tillement,R.I.Berbeco,J.N.BermanandJ.L.Robar.“AnInVivoModeltoStudytheUseofNanoparticlesasaRadiosensitizerinRadiationBeamsGeneratedFromaLowZTarget.”

AlfonsoRodriguez,Ph.D.• YoungInvestigator’sSymposium,thirdplaceinoralpresentation,SWAAPM2017.“RadiomicsT2-WeightedMRIGeometricalandTextureFeaturesTrainedClassificationModelsUsingMachineLearning.”Dr.Rodriguez’sresearchinvolvedusingT2fat-saturatedimagestopredictmalignancyoftumors.

ZhenTian,Ph.D.• Invitedspeaker,SAMTherapyScientificSymposiumonMicroscopicMonteCarloSimulationsforRadiobiologyModeling:AdvancesandChallenges,AAPM2017.“gMicroMC:AcceleratingMicroscopicMonteCarloSimulationUsingRapidParallelProcessingPlatforms.”

2018GRADUATINGRESIDENTS

RezaTaleei,Ph.D.• IntegratedCourseinBiology,PhysicsinRadiationOncology,Detroit2018

• AAPMExpandingHorizonfor2017,MICROS17inItaly• ABSawardfor2017,HDRLDRProstateWorkshop,

Chicago• RRSfor2015,61stRadiationResearchSocietyAnnualMeeting,Weston

• PTCOG(ParticleTherapyCo-OperativeGroup)for2016,55thPTCOG,Prague,CzechRepublic

• InternationalWorkshoponRadiationDamagetoDNAfor2016,14thInternationalWorkshopofRadiationDamagetoDNA,Melbourne,Australia

YouZhang,Ph.D.•ABSScholarshipforHDR/LDRProstateBrachytherapyWorkshop,2017

• Top10%Performerforthe2017QA&DosimetrySymposiumTG244HeadandNeckTreatmentPlanningCompetition(scored13thoutof238submissions),2017

• Basic/TranslationalScienceAbstractAward,ASTROAnnualMeeting,2016

• JohnR.CameronYoungInvestigatorCompetitionFinalists(10outof391),AAPMAnnualMeeting,2016

• Firstprizeforresidents,SouthTexasChapter-HealthPhysicsSocietyMeeting,2016

Molecular Radiation Biology Division - Graduate Program

TheCancerBiologyGraduateProgramofferstrain-ingforstudentsinterestedinpursuingaresearchca-reer investigating the molecules, mechanisms, and pathwaysinvolvedinthedevelopmentofcancer.Theprogramisflexibleandallowsstudentstofocusontheirspecificinterests.

Inthelastfewyears,theDivisionofMolecularRadi-ationBiologyhasgraduatedfivePh.D.’s,including:

• Cristel Camacho, Ph.D.,thesis:GeneticEventsUnderlyingRadiation-InducedGliomagenesis.CurrentlyatSt.JudeChildren’sResearchHospital.

• Carlos Gil del Alcazar, Ph.D.,thesis:TargetingDNADouble-StrandBreaksRepairtoPotentiateRadio-andChemo-therapyofGlioblastoma.CurrentlyatDana-FarberCancerInstitute.

• Molly Catherine Hardebeck, Ph.D.,thesis:NovelInsightsintoDNADouble-StrandBreakRepairanditsCancerImplications.CurrentlyatEliLillyandCo.

• Mariya IIcheva, Ph.D.,thesis:ModulatingDNADamageResponsesforImprovedBreastCancerTherapy.CurrentlyatMedpace.

• Brian McEllin, Ph.D.,thesis:DissectingMolecular

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Mechanisms of Radioresistance Using In Vitro and In Vivo Brain Tumor Model Systems. Currently at Swedish Hospital and Health Care.

• Pavlina Todorova, Ph.D., thesis: Mechanistic Analysis of Radiation-Induced Gliomagenesis. Currently at Memorial Sloan Kettering Cancer Center.

Master of Radiation Therapy Training Program

Inadditiontoourresidencies,weofferseveralothereducational programs, including the Master of Radia-tionTherapyTraining(RTT)Program,whichisthefirstradiation therapy master’s program in the nation.

Crucial to training and education is hands-on learning, including the technology we use on a daily basis. As part of the master’s therapy program,

students can participate in a cutting-edge simulation lab. VERT, a virtual environment of a radiotherapy treatmentroom,istheflightsimulatorforLinacs:everythingyoucandoonarealLinac,youcandowith VERT.

Gamma Knife Icon Training Program

The primary focus of the Gamma Knife Icon course is to educate new Icon users and serve as an introduction for professionals who need to be trained for Gamma Knife. The course includes hands-on training in pro-cedures done at UTSW that include both frame- and mask-basedworkflows.Theemphasisisonframelesscapabilities and expanded utilization in the form of frac-tionated, distributed, and staged treatments.

CyberKnife Training Program

The CyberKnife Training Program is designed for physicians who have primary roles in evaluating and approvingtreatmentplansandconfirmingpatientsetup and alignment in CyberKnife treatment. During the course, physicians develop an understanding of a variety of aspects of CyberKnife treatment, includ-ing patient selection, simulation, treatment planning, beam delivery with robot tracking technologies, and diseasesubsite-specificapplications.Thecoursecurriculum blends instruction on treatment planning/evaluation and treatment delivery with hands-on labs.

SBRT Training Program

The primary focus of this two-day CME course is to help oncology professionals in academic, communi-ty, and private centers learn about the proper imple-mentationofaviableandeffectiveSBRTtreatmentpractice. The emphasis is on contemporary ablation of tumors in the body including the evolution of SBRT from its roots in image-guided 3-D confor-mal therapy and radiosurgery. The course presents unique challenges of SBRT beyond conventional radiotherapy and IMRT including new program con-siderations, physics and dosimetry requirements, guidelines for conducting proper treatment, and billing compliance.

Research Collaboration through PEIM and MAIA

PEIM (Program of Excellence in Intelligence Med-icine)andMAIA(MedicalArtificialIntelligenceandAutomation) were established by Dr. Jiang to solve clinical and biomedical research problems using artificialintelligence(AI)technology.TheMAIALabdevelops and applies innovative AI tools to improve aspects of cancer radiation therapy. PEIM serves as a collaborative education resource to promote AI research in precision medicine, diagnosis, medical errordetection,qualityassurance,andrelatedfields.

Dr. Pavlina Todorova

Image courtesy of Vertual Ltd.

VERT virtual environment

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FY 04 FY 05 FY 06 FY 07 FY 08 FY 09 FY 10 FY 11 FY 12 FY 13 FY 14 FY 15 FY 16 FY 17 FY 18 FY 19

Radiation Oncology New Patient Volume 2003-2018

$0

$2,000,000

$4,000,000

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$12,000,000

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FY08 FY09 FY10 FY11 FY12 FY13 FY14 FY15 FY16 FY17 FY18

NIH & Other Fed Endowments Clinical Trials Private/Industry grants State (CPRIT)

Department Statistics

Radiation Oncology New Patient Volume 2003-2018Since 2014, we have an exceptional steady cumulative growth of greater than 50%.

Total Annual Department Research ExpenditureThe desire of our researchers to go beyond and advance the field of radiation oncology are hallmarks of our program.

Total:Federal:State: Other:

$ 82.6 M$ 33.2 M$ 34.4 M$ 15 M

Total Active Research Funding

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4

4

3

2

1

$5,667,309

$4,000,000

$1,084,617

$561,420

$558,761

$15,051,766$20,309,182

$30,418,075

Foundations

CPRIT

# R01

# R21

NASA

# P/K Grant

State

DOD

Annual Accrual for Therapeutic Trials

We are leaders in multi-institutional studies fo-cused on stereotactic ablative radiotherapy (SAbR), also known as stereotactic body radiation therapy (SBRT). Robert Timmerman, M.D., head of our clin-ical division, is a pioneer in SAbR and continues to display his expertise in the field through our ongoing research. Four of our key clinical trials include:

NRG-LU002 Led by Puneeth Iyengar, M.D., Ph.D., Assistant Pro-fessor of Radiation Oncology, this randomized phase II/III trial is studying how local radiotherapy in the form of SBRT (radiation) may help systemic therapy (including immunotherapy) improve overall survival of patients with metastatic non-small cell lung cancer (NSCLC) (stage 4).

JOLT (STABLEMATES TRIAL)JoLT is a randomized phase III study of sublobar resection versus stereotactic ablative radiotherapy in high-risk patients with stage I non-small cell lung cancer. Led by Dr. Timmerman and Hiran Chrish Fernando, M.D., of Boston Medical Center, the study has a primary goal of testing the hypothesis that the three-year overall survival in high-risk operable pa-tients with stage I NSCLC is greater in patients who undergo SAbR as compared to standard sublobal resection. Patients are pre-randomized before giving consent in this trial.

POTEN-C UT Southwestern is leading the first clinical trial us-ing SAbR to preserve sexual potency after prostate cancer. The Prostate Oncologic Therapy While Ensuring Neurovascular Conservation (POTEN-C) clinical trial is a national, multicenter trial, led by UT Southwest-ern cancer specialist Neil Desai, M.D., M.H.S., Assis-tant Professor of Radiation Oncology. The POTEN-C trial combines SAbR with a new technique that aims to lower the dose of radiation to nerves and vessels

involved in sexual function, with the goal of reducing patients’ risk for erectile dysfunction.

PHASE I DOSE ESCALATION TRIAL OF SINGLE FRACTIONThis trial involves using a single fraction of adju-vant stereotactic body partial breast irradiation for early-stage breast cancer on the unique CyberKnife system. Led by Asal Rahimi, M.D., M.S., Associate Professor of Radiation Oncology, the study aims to reduce toxicity, maintain or improve breast cosme-sis, and improve convenience for patients.

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Dr. Desai & Kevin Stanfield

PublicationsTotalling over 190 publications from 2017 - 2018. Abugharib A, Jackson WC, Tumati V, Dess RT, Lee JY, Zhao SG, Soliman M, Zumsteg ZS, Mehra R, Feng FY, Morgan TM, Desai N, Spratt DE. Very Early Salvage Radiotherapy Improves Distant Metastasis-Free Survival. J Urol. 2017;197(3 Pt 1):662-8. Epub 2016/09/11. doi: 10.1016/j.juro.2016.08.106. PubMed PMID: 27614333.

Aguilera TA, Giaccia AJ. Molecular Pathways: Oncologic Pathways and Their Role in T-cell Exclusion and Immune Evasion-A New Role for the AXL Receptor Tyrosine Kinase. Clin Cancer Res. 2017;23(12):2928-33. Epub 2017/03/16. doi: 10.1158/1078-0432.CCR-17-0189. PubMed PMID: 28289089; PMCID: PMC5474155.

Albuquerque K, Folkert M, Mayadev J, Christie A, Liotta MR, Nagel C, Sevak P, Harkenrider MM, Lea JS, Hanna RK, Small WC, Jr., Miller DS, Xie XJ, Potkul RK, Elshaikh MA. Adjuvant External Radiation Impacts Outcome of Pelvis-limited Stage III Endometrial Carcinoma: A Multi-institutional Study. Am J Clin Oncol. 2018;41(8):792-6. Epub 2017/02/23. doi: 10.1097/COC.0000000000000371. PubMed PMID: 28225446.

Albuquerque K, Rodgers K, Spangler A, Rahimi A, Willett D. Electronic Medical Record-Based Radiation Oncology Toxicity Recording Instrument Aids Benchmarking and Quality Improvement in the Clinic. J Oncol Pract. 2018;14(3):e186-e93. Epub 2018/02/15. doi: 10.1200/JOP.2017.025163. PubMed PMID: 29443646.

Ambrogio C, Kohler J, Zhou ZW, Wang H, Paranal R, Li J, Capelletti M, Caffarra C, Li S, Lv Q, Gondi S, Hunter JC, Lu J, Chiarle R, Santamaria D, Westover KD, Janne PA. KRAS Dimerization Impacts MEK Inhibitor Sensitivity and Oncogenic Activity of Mutant KRAS. Cell. 2018;172(4):857-68 e15. Epub 2018/01/18. doi: 10.1016/j.cell.2017.12.020. PubMed PMID: 29336889.

Awan MJ, Nedzi L, Wang D, Tumati V, Sumer B, Xie XJ, Smith I, Truelson J, Hughes R, Myers LL, Lavertu P, Wong S, Yao M. Final results of a multi-institutional phase II trial of reirradiation with concurrent weekly cisplatin and cetuximab for recurrent or

second primary squamous cell carcinoma of the head and neck. Ann Oncol. 2018;29(4):998-1003. Epub 2018/01/19. doi: 10.1093/annonc/mdy018. PubMed PMID: 29346519.

Azoulay M, Shah J, Pollom E, Soltys SG. New Hypofractionation Radiation Strategies for Glioblastoma. Curr Oncol Rep. 2017;19(9):58. Epub 2017/07/25. doi: 10.1007/s11912-017-0616-3. PubMed PMID: 28735440.

Bai T, Yan H, Jia X, Jiang S, Wang G, Mou X. Z-Index Parameterization for Volumetric CT Image Reconstruction via 3-D Dictionary Learning. IEEE Trans Med Imaging. 2017;36(12):2466-78. Epub 2017/10/06. doi: 10.1109/TMI.2017.2759819. PubMed PMID: 28981411; PMCID: PMC5732496.

Bai T, Yan H, Ouyang L, Staub D, Wang J, Jia X, Jiang SB, Mou X. Data correlation based noise level estimation for cone beam projection data. J Xray Sci Technol. 2017;25(6):907-26. Epub 2017/07/13. doi: 10.3233/XST-17266. PubMed PMID: 28697578; PMCID: PMC5714667.

Beg MS, Gupta A, Sher D, Ali S, Khan S, Gao A, Stewart T, Ahn C, Berry J, Mortensen EM. Impact of Concurrent Medication Use on Pancreatic Cancer Survival-SEER-Medicare Analysis. Am J Clin Oncol. 2018;41(8):766-71. Epub 2017/01/13. doi: 10.1097/COC.0000000000000359. PubMed PMID: 28079594; PMCID: PMC5503814.

Bhattacharya S, Asaithamby A. Repurposing DNA repair factors to eradicate tumor cells upon radiotherapy. Translational Cancer Research. 2017:S822-S39.

Bhattacharya S, Srinivasan K, Abdisalaam S, Su F, Raj P, Dozmorov I, Mishra R, Wakeland EK, Ghose S, Mukherjee S, Asaithamby A. RAD51 interconnects between DNA replication, DNA repair and immunity. Nucleic Acids Research. 2017;45(8):4590-605. doi: 10.1093/nar/gkx126.

Brown TJ, Sher DJ, Nedzi LA, Hughes RS, Beg MS, Mull J, Sarode VR, Khan SA. Cutaneous adnexal adenocarcinoma with exquisite sensitivity to trastuzumab. Head Neck. 2017;39(5):E69-E71. Epub 2017/02/23. doi: 10.1002/hed.24682. PubMed PMID: 28225558.

Cartwright IM, Su C, Haskins JS, Salinas VA, Sunada S, Yu H,

Uesaka M, Hirakawa H, Chen DJ, Fujimori A, Kato TA. DNA Repair Deficient Chinese Hamster Ovary Cells Exhibiting Differential Sensitivity to Charged Particle Radiation under Aerobic and Hypoxic Conditions. Int J Mol Sci. 2018;19(8). Epub 2018/08/01. doi: 10.3390/ijms19082228. PubMed PMID: 30061540; PMCID: PMC6121575.

Chang J, Lin MH, Lu W, Chen M, Jiang S. Convolution-based modified Clarkson integration (CMCI) for electron cutout factor calculation. J Appl Clin Med Phys. 2018;19(2):128-36. Epub 2018/02/06. doi: 10.1002/acm2.12267. PubMed PMID: 29396894; PMCID: PMC5849839.

Chang J, Tian Z, Lu W, Gu X, Chen M, Jiang SB. A novel geometry-dosimetry label fusion method in multi-atlas segmentation for radiotherapy: a proof-of-concept study. Phys Med Biol. 2017;62(9):3656-67. Epub 2017/04/06. doi: 10.1088/1361-6560/aa5ed9. PubMed PMID: 28379850.

Chang MT, Penson A, Desai NB, Socci ND, Shen R, Seshan VE, Kundra R, Abeshouse A, Viale A, Cha EK, Hao X, Reuter VE, Rudin CM, Bochner BH, Rosenberg JE, Bajorin DF, Schultz N, Berger MF, Iyer G, Solit DB, Al-Ahmadie HA, Taylor BS. Small-Cell Carcinomas of the Bladder and Lung Are Characterized by a Convergent but Distinct Pathogenesis. Clin Cancer Res. 2018;24(8):1965-73. Epub 2017/11/29. doi: 10.1158/1078-0432.CCR-17-2655. PubMed PMID: 29180607; PMCID: PMC5965261.

Chen B, Xiang K, Gong Z, Wang J, Tan S. Statistical Iterative CBCT Reconstruction Based on Neural Network. IEEE Trans Med Imaging. 2018;37(6):1511-21. Epub 2018/06/06. doi: 10.1109/TMI.2018.2829896. PubMed PMID: 29870378; PMCID: PMC6002810.

Chen H, Zhong Z, Yang Y, Chen J, Zhou L, Zhen X, Gu X. Internal Motion Estimation by Internal-external Motion Modeling for Lung Cancer Radiotherapy. Sci Rep. 2018;8(1):3677. Epub 2018/03/01. doi: 10.1038/s41598-018-22023-3. PubMed PMID: 29487330; PMCID: PMC5829085.

Chen J, Chen H, Zhong Z, Wang Z, Hrycushko B, Zhou L, Jiang S, Albuquerque K, Gu X, Zhen X. Investigating rectal toxicity associated dosimetric features with deformable accumulated rectal surface dose maps for cervical cancer radiotherapy. Radiat Oncol. 2018;13(1):125. Epub 2018/07/08. doi: 10.1186/s13014-018-

1068-0. PubMed PMID: 29980214; PMCID: PMC6035458.Chen L, Shen C, Zhou Z, Maquilan G, Thomas K, Folkert MR, Albuquerque K, Wang J. Accurate segmenting of cervical tumors in PET imaging based on similarity between adjacent slices. Comput Biol Med. 2018;97:30-6. Epub 2018/04/24. doi: 10.1016/j.compbiomed.2018.04.009. PubMed PMID: 29684783; PMCID: PMC5970095.

Chen X, Ouyang L, Yan H, Jia X, Li B, Lyu Q, Zhang Y, Wang J. Optimization of the geometry and speed of a moving blocker system for cone-beam computed tomography scatter correction. Med Phys. 2017;44(9):e215-e29. Epub 2017/09/14. doi: 10.1002/mp.12326. PubMed PMID: 28901608; PMCID: PMC5619659.

Chi Y, Rezaeian NH, Shen C, Zhou Y, Lu W, Yang M, Hannan R, Jia X. A new method to reconstruct intra-fractional prostate motion in volumetric modulated arc therapy. Phys Med Biol. 2017;62(13):5509-30. Epub 2017/06/14. doi: 10.1088/1361-6560/aa6e37. PubMed PMID: 28609300; PMCID: PMC5729029.

Chiu T, Tan J, Brenner M, Gu X, Yang M, Westover K, Strom T, Sher D, Jiang S, Zhao B. Three-dimensional printer-aided casting of soft, custom silicone boluses (SCSBs) for head and neck radiation therapy. Pract Radiat Oncol. 2018;8(3):e167-e74. Epub 2018/02/18. doi: 10.1016/j.prro.2017.11.001. PubMed PMID: 29452869.

Chiu TD, Arai TJ, Campbell Iii J, Jiang SB, Mason RP, Stojadinovic S. MR-CBCT image-guided system for radiotherapy of orthotopic rat prostate tumors. PLoS One. 2018;13(5):e0198065. Epub 2018/05/31. doi: 10.1371/journal.pone.0198065. PubMed PMID: 29847586; PMCID: PMC5976174.

Chiu TD, Parsons D, Zhang Y, Hrycushko B, Zhao B, Chopra R, Kim N, Spangler A, Rahimi A, Timmerman R, Jiang SB, Lu W, Gu X. Prototype volumetric ultrasound tomography image guidance system for prone stereotactic partial breast irradiation: proof-of-concept. Phys Med Biol. 2018;63(5):055004. Epub 2018/02/07. doi: 10.1088/1361-6560/aaad1f. PubMed PMID: 29405123.

Chun SG, Hu C, Choy H, Komaki RU, Timmerman RD, Schild SE, Bogart JA, Dobelbower MC, Bosch W, Galvin JM, Kavadi VS, Narayan S, Iyengar P, Robinson CG, Wynn RB, Raben A, Augspurger ME, MacRae RM, Paulus R, Bradley JD. Impact of Intensity-Modulated Radiation Therapy Technique for

Locally Advanced Non-Small-Cell Lung Cancer: A Secondary Analysis of the NRG Oncology RTOG 0617 Randomized Clinical Trial. J Clin Oncol. 2017;35(1):56-62. Epub 2016/12/31. doi: 10.1200/JCO.2016.69.1378. PubMed PMID: 28034064; PMCID: PMC5455690.

Cremonesi M, Garibaldi C, Timmerman R, Ferrari M, Ronchi S, Grana CM, Travaini L, Gilardi L, Starzynska A, Ciardo D, Orecchia R, Jereczek-Fossa BA, Leonardi MC. Interim (18)F-FDG-PET/CT during chemo-radiotherapy in the management of oesophageal cancer patients. A systematic review. Radiother Oncol. 2017;125(2):200-12. Epub 2017/10/17. doi: 10.1016/j.radonc.2017.09.022. PubMed PMID: 29029833.

Cremonesi M, Gilardi L, Ferrari ME, Piperno G, Travaini LL, Timmerman R, Botta F, Baroni G, Grana CM, Ronchi S, Ciardo D, Jereczek-Fossa BA, Garibaldi C, Orecchia R. Role of interim (18)F-FDG-PET/CT for the early prediction of clinical outcomes of Non-Small Cell Lung Cancer (NSCLC) during radiotherapy or chemo-radiotherapy. A systematic review. Eur J Nucl Med Mol Imaging. 2017;44(11):1915-27. Epub 2017/07/07. doi: 10.1007/s00259-017-3762-9. PubMed PMID: 28681192.

Dan T, Williams NL. Management of Stage I Lung Cancer with Stereotactic Ablative Radiation Therapy. Surg Oncol Clin N Am. 2017;26(3):393-403. Epub 2017/06/04. doi: 10.1016/j.soc.2017.01.005. PubMed PMID: 28576179.

Dan TD, Eldredge-Hindy HB, Hoffman-Censits J, Lin J, Kelly WK, Gomella LG, Lallas CD, Trabulsi EJ, Hurwitz MD, Dicker AP, Den RB. Hematologic Toxicity of Concurrent Administration of Radium-223 and Next-generation Antiandrogen Therapies. Am J Clin Oncol. 2017;40(4):342-7. Epub 2015/02/28. doi: 10.1097/COC.0000000000000181. PubMed PMID: 25723740; PMCID: PMC4549230.

Davis AJ, Wang SY, Chen DJ, Chen BPC. Imaging of Fluorescently Tagged ATM Kinase at the Sites of DNA Double Strand Breaks. Methods Mol Biol. 2017;1599:277-85. Epub 2017/05/10. doi: 10.1007/978-1-4939-6955-5_20. PubMed PMID: 28477126; PMCID: PMC6085091.

Deng Y, Wang ZV, Gordillo R, Zhu Y, Ali A, Zhang C, Wang X, Shao M, Zhang Z, Iyengar P, Gupta RK, Horton JD, Hill JA, Scherer PE. Adipocyte Xbp1s overexpression drives uridine

production and reduces obesity. Mol Metab. 2018;11:1-17. Epub 2018/03/20. doi: 10.1016/j.molmet.2018.02.013. PubMed PMID: 29551634; PMCID: PMC6001360.

Derek Stensby J, Fox MG, Kwon MS, Caycedo FJ, Rahimi A. Primary synovial chondromatosis of the subtalar joint: case report and review of the literature. Skeletal Radiol. 2018;47(3):391-6. Epub 2017/09/22. doi: 10.1007/s00256-017-2775-6. PubMed PMID: 28932921.

Desai NB, Laine AM, Timmerman RD. Stereotactic ablative body radiotherapy (SAbR) for oligometastatic cancer. Br J Radiol. 2017;90(1070):20160500. Epub 2016/12/23. doi: 10.1259/bjr.20160500. PubMed PMID: 28008774; PMCID: PMC5685107.

Despres P, Jia X. A review of GPU-based medical image reconstruction. Phys Med. 2017;42:76-92. Epub 2017/11/28. doi: 10.1016/j.ejmp.2017.07.024. PubMed PMID: 29173924.

Dess RT, Hartman HE, Aghdam N, Jackson WC, Soni PD, Abugharib AE, Suy S, Desai NB, Zumsteg ZS, Mehra R, Morgan TM, Feng FY, Hamstra DA, Schipper MJ, Collins SP, Spratt DE. Erectile function after stereotactic body radiotherapy for localized prostate cancer. BJU Int. 2018;121(1):61-8. Epub 2017/07/16. doi: 10.1111/bju.13962. PubMed PMID: 28710895.

Ding C, Chun SG, Sumer BD, Nedzi LA, Abdulrahman RE, Yordy JS, Lee P, Hrycushko B, Solberg TD, Ahn C, Timmerman RD, Schwartz DL. Phantom-to-clinic development of hypofractionated stereotactic body radiotherapy for early-stage glottic laryngeal cancer. Med Dosim. 2017;42(2):90-6. Epub 2017/04/26. doi: 10.1016/j.meddos.2017.01.004. PubMed PMID: 28438431.

Ding C, Hrycushko B, Whitworth L, Li X, Nedzi L, Weprin B, Abdulrahman R, Welch B, Jiang SB, Wardak Z, Timmerman RD. Multistage stereotactic radiosurgery for large cerebral arteriovenous malformations using the Gamma Knife platform. Med Phys. 2017;44(10):5010-9. Epub 2017/07/07. doi: 10.1002/mp.12455. PubMed PMID: 28681423; PMCID: PMC5646226.

Ding C, Saw CB, Timmerman RD. Cyberknife stereotactic radiosurgery and radiation therapy treatment planning system. Med Dosim. 2018;43(2):129-40. Epub 2018/04/02. doi: 10.1016/j.meddos.2018.02.006. PubMed PMID: 29605528.

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Folkert MR, Setton J, Apte AP, Grkovski M, Young RJ, Schoder H, Thorstad WL, Lee NY, Deasy JO, Oh JH. Predictive modeling of outcomes following definitive chemoradiotherapy for oropharyngeal cancer based on FDG-PET image characteristics. Phys Med Biol. 2017;62(13):5327-43. Epub 2017/06/13. doi: 10.1088/1361-6560/aa73cc. PubMed PMID: 28604368; PMCID: PMC5729737.

Gerelchuluun A, Maeda J, Manabe E, Brents CA, Sakae T, Fujimori A, Chen DJ, Tsuboi K, Kato TA. Histone Deacetylase Inhibitor Induced Radiation Sensitization Effects on Human Cancer Cells after Photon and Hadron Radiation Exposure. Int J Mol Sci. 2018;19(2). Epub 2018/02/08. doi: 10.3390/ijms19020496. PubMed PMID: 29414878; PMCID: PMC5855718.

Goel R, Moore W, Sumer B, Khan S, Sher D, Subramaniam RM. Clinical Practice in PET/CT for the Management of Head and Neck Squamous Cell Cancer. AJR Am J Roentgenol. 2017;209(2):289-303. Epub 2017/07/22. doi: 10.2214/AJR.17.18301. PubMed PMID: 28731808.

Gong H, Li B, Jia X, Cao G. Physics Model-Based Scatter Correction in Multi-Source Interior Computed Tomography. IEEE Trans Med Imaging. 2018;37(2):349-60. Epub 2017/08/23. doi: 10.1109/TMI.2017.2741259. PubMed PMID: 28829306.

Gong H, Yan H, Jia X, Li B, Wang G, Cao G. X-ray scatter correction for multi-source interior computed tomography. Med Phys. 2017;44(1):71-83. Epub 2017/01/20. doi: 10.1002/mp.12022. PubMed PMID: 28102959.

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