U T S O U T H W E S T E R N THE TARGET News from the Department of Radiation Oncology VOLUME 5, SPRING 2014 Vocal cord cancer meets CyberKnife In a global first, a team of doctors at UT Southwestern seeks to preserve voice quality for cancer patients while shortening treatment time using the CyberKnife robotic radiosurgery tool. Stephen Wiley of Terrell, Texas, was the first patient treated with CyberKnife for early-stage lesions of the glottic larynx. Stephen Wiley What s Inside 1-3 CYBERKNIFE FOR VOCAL CORD CANCER 4 DEPARTMENT NEWS 6 CLINICAL TRIALS LISTING 7 TRIAL FOCUS
Page 1 story Vocal cord cancer meets CyberKnife Stephen Wiley, 59, is a central Texas trucker and rancher who in 15 years never once took off work from being sick. His job requires him to be talking on the radio constantly with his company s dispatch center. Last fall, he noticed that his voice would be hoarse when he woke up in the early hours of the morning to get to work at 4:30 a.m. but would be better an hour or two later. But one day, instead of improving over the course of the day, it just got worse. By evening, my super - visors couldn t understand what I was saying on the radio, recalls Mr. Wiley. I had to go home. A string of referrals led him to UT Southwestern s otolaryngology clinic, where he was diagnosed with an early-stage cancerous lesion of the right vocal cord. Coincidently, two young UT Southwestern physicians had recently collaborated on a new approach to treat vocal cord cancer with the CyberKnife robotic radiosurgery tool. While the CyberKnife is FDA-approved to treat many different sites of cancer in the body, it has yet to be systematically explored in a clinical trial for vocal cord cancer. Baran Sumer, M.D., a surgical oncologist, and Susie Chen, M.D., a radiation oncologist, both thought that CyberKnife might prove to be an effective alternative to other well-established therapies such as conventional radiation, carbon dioxide endoscopic laser surgery, and hemilaryngectomy. Our goal is to maintain excellent disease control we already have high cure rates for early-stage laryngeal cancer, says Dr. Chen, but it may be possible to improve patient convenience and quality of life in terms of how their voice recovers afterward. Instead of giving daily radiation over a period of six weeks, CyberKnife is able to deliver a precise, powerful dose in just a few: three weeks in the first study group, then two, then one. Currently, some patients opt for surgery to remove cancerous lesions rather than submit to a protracted course of radiation therapy, despite the risk that their voice quality after surgery may not be as good as with radiation. Similar to the progression of surgery, which once removed the entire voice box but now treats only a single vocal cord, practitioners of radiation therapy have begun looking at reducing the field of radiation to target only the involved vocal cord, with one preliminary study from the Netherlands suggesting that advanced image guidance can significantly spare normal tissue from radiation. Says Dr. Sumer, We re going to remove lesions in a very targeted way similar to surgery but using radiation. The difficulty of targeting an area with so much inherent movement was solved with the placement of gold fiducials. Dr. Sumer helped plan the area to be removed, and Dr. Chen, a member of the Radiation Oncology head and neck team, took charge of the patient s radiation treatment. Mr. Wiley says he chose to be a part of the first study group because the three-week course of treatment would help him get back to work faster. But it wasn t just that, he adds. If I can do something that will help other people in the future, I want to do it. When he s finished with CyberKnife, he says, he looks forward to rejoining his family in rodeo competitions and horse training. UT Southwestern physicians, too, are looking forward to the initial results of the CyberKnife trial, which recently completed its first phase. The Department of Radiation Oncology has continuously led studies in the developing field of hypofractionated, image-guided radiotherapy, which uses complex planning and multiple delivery angles to deliver ablative doses of radiation in just a few treatment sessions. This trial is the first to systematically explore CyberKnife for vocal cord cancer in the clinical setting. In particular, the dose to the uninvolved vocal cord could be limited to less than 30 Gy with this setup, which has the potential to improve functional voice outcomes, says Dr. Chen. Through single cord targeting we hope to realize the same efficiency that has already been realized in the surgical field, providing our patients with more options and better outcomes. It may be possible to improve patient convenience and quality of life in terms of how their voice recovers. Baran Sumer, M.D. Susie Chen, M.D. 2 SPRING 2014 The Target 3
News Education and Research Seminar Series New faculty brings future of GPU processing to Rad Onc Steve Jiang, Ph.D., has joined the Department of Radiation Oncology as Professor, Vice Chairman, and Chief of the 61-person Division of Medical Physics and Engineering. Dr. Jiang and his team of researchers, which has regrouped at UT Southwestern, have earned renown in recent years as pioneers in the application of graphic processing unit (GPU) processors to the field of radiation medicine. A fellow of the American Association of Physicists in Medicine, Dr. Jiang earned his doctorate in radiation therapy physics at the Medical College of Ohio in Toledo and completed a postdoctoral fellowship at the Stanford University School of Medicine. As part of his distinguished academic career, he most recently led the development of the Center for Advanced Radiotherapy Technologies (CART) at the University of California, San Diego. He was one of the first to recognize that the GPU processors used by the video gaming industry could be adapted to speed up the time-consuming calculations used for imaging and planning radiation treatment. Like video games, radiation planning needs a lot of computing power, and these types of processors are as powerful as supercomputers were several years ago, says Dr. Jiang. They are also inexpensive because of the huge market for them and can be easily deployed in the clinic. Over the course of a few years, Dr. Jiang s group developed and published more than 40 papers on this topic, becoming the leading group in the world investigating how to adapt these processors to the medical field. In one paper, Dr. Jiang et al. showed how GPUs could be used to speed up a standard algorithm (known as Monte Carlo) dose calculation from 70 hours to about 10 seconds. Our hope is to not just make planning faster but to change the way we treat patients, Dr. Jiang says. For example, we could reoptimize our plans on a daily basis as the anatomy of the patient or the tumor volume changes during treatment. While Dr. Jiang will continue his GPU research here, he stresses that his main role will be as a facilitator to provide technical support, ideas, and grant assistance to other members of the physics team. He also has plans to embed the physics team in the clinic, so that physicists adapt their research closely to real-life problems and solutions. We have to work together as a team with the physicians, he says. Schwartz to lead head and neck team David Schwartz, M.D., has joined the clinical faculty in Radiation Oncology and will lead the department s focused head and neck team. A California native, Dr. Schwartz graduated from Stanford University and earned his medical degree at the David Geffen School of Medicine at UCLA. He completed his residency in radiation oncology at the University of Washington and the Fred Hutchinson Cancer Research Center, both in Seattle. His career in academic medicine was honed while serving on the faculty at M.D. Anderson Cancer Center in Houston. Dr. Schwartz has participated as lead investigator for a wide number of local and national clinic trials, has received funding from NIH, VA, industry, and foundation grants, and has published his research in more than 50 peer-reviewed articles in scientific journals. He also has served as a journal reviewer and editor and has lectured widely on topics related to cancer management and adaptive radiotherapy. His current interests include adapting mobile technology to improve the patient experience. Dr. Schwartz says he gravitated toward the treatment of head and neck cancers during his first professional position at the VA Hospital in Seattle. The majority of cancers we treated had to do with cigarette smoking, recalls Dr. Schwartz. What I quickly figured out is that head and neck cancer is unique in its impact on human functions that we mostly take completely for granted. He continues, Think of all the things that you do with your face, mouth, and throat the basic things we need to do to connect with others and to be human. Eating with friends, talking with family, hearing and seeing the world around you, the appearance of your face these are things that define who you are, your place in the world, and your relationships with others. Your entire self-worth can be stripped away if you lose these elemental functions, either from the cancer itself or, tragically, by the treatments we use to cure the cancer. The reason I chose to be in academic medicine is to have the opportunity to find ways to lessen the impact on these functions so that patients can continue being themselves and have a good quality of life once their treatment is complete. My goal is to discover better ways to cure cancer and to guide patients toward a full recovery. Seminars sponsored by the Department of Radiation Oncology are free and open to attend for any interested professionals engaged in the field, including physicians, physicists, radiation therapists, biologists, and students. Please RSVP to 214-645-2265 or RadOncLectures@utsouthwestern.edu. Lectures are held in the W.A. Monty and Tex Moncrief Radiation Oncology Building on the UT Southwestern campus. Radiation Oncology Residency Program Visiting Professor Lecture Medical Physics and Engineering Research Seminar Series Molecular Radiation Biology Lecture March April Speaker: Mark Glover, Ph.D. From: University of Alberta, Canada Date: Tuesday, April 15 Talk Title: Development of Small- Molecule Inhibitors of the DNA Damage Response Speaker: David Sher, M.D., M.P.H. From: Rush University, Chicago, IL Date: Friday, April 25 Topic: Cost-Effectiveness in Medicine Speaker: Charles Limoli, Ph.D. Speaker: Sandra Demaria, M.D. From: University of California, From: New York University Irvine School of Medicine, NYU Date: Tuesday, March 11 Langone Medical Center Alexandria Center for Life Talk Title: CNS Dysfunction Caused Science B Cancer Therapy: Causes, Date: Tuesday, May 13 Consequences and Stem Cell-Based Remedies Talk Title: Partnership of Radiotherapy and Immunotherapy: Speaker: Xun Jia, Ph.D. A New Paradigm in Cancer From: UT Southwestern Treatment Date: Friday, March 14 4 5 p.m. Speaker: Quynh-Thu Le, M.D. Talk Title: Monte Carlo Particle From: Stanford University, Transport Simulations for Stanford, CA Radiotherapy Date: Friday, May 29 Speaker: Michael J. Zelefsky, M.D. Topic: Head and Neck From: Memorial Sloan-Kettering, Malignancies New York, NY Date: Thursday, March 27 Talk Title: Optimizing the Outcomes for High-Risk Prostate Cancer with Radiotherapy: Can We do Better? Topic: Genitourinary Malignancies 4 SPRING 2014 The Target 5 May
Clinical Trials Trial focus: Ixempra + SBRT Recent faculty publications BRAIN RTOG 6913 Phase I/II trial of concurrent RAD001 (everolimus) with temozolomide/radiation followed by adjuvant RAD001/temozolomide in newly diagnosed glioblastoma 072012-094 A prospective, multicenter trial of NovoTTF-100A together with temozolomide compared to temozolomide alone in patients with newly diagnosed GBM 052012-050/MID-897 A randomized, double-blind, phase II, dose-ranging study to evaluate the safety and efficacy of veliparib and whole brain radiation therapy versus placebo and whole brain radiation therapy in subjects with brain metastases from non-small cell lung cancer 042011-075 Interstitial radioactive iodine implants for the treatment of pan-invasive pituitary macroadenomas 042011-050 Phase II trial of hippocampal-avoiding whole brain irradiation with simultaneous integrated boost for treatment of brain metastases E3F05 Phase III study of radiation therapy with or without temozolomide for symptomatic or progressive low-grade gliomas BREAST 102012-020 A phase II trial of ixabepilone and stereotactic body radiation therapy (SBRT) for patients with triple negative metastatic breast cancer 092012-058 Randomized, double-blind, vehicle-controlled pilot study of the efficacy and safety of HylaCare in the treatment of acute skin changes in patients undergoing external beam radiotherapy for tumors of the breast 072010-015 A phase I study of CyberKnife partial breast irradiation (PBI) for early-stage breast cancer RTOG 1005 A phase III trial of accelerated whole breast irradiation with hypofractionation plus concurrent boost versus standard whole breast irradiation plus sequential boost for early-stage breast cancer GASTROINTESTINAL 032012-025 Phosphatidylserine-targeting antibody bavituximab in combination with capecitabine and radiation therapy for the treatment of stage II and III rectal adenocarcinoma GENITOURINARY 12013-041 A phase II trial of high dose IL-2 and stereotactic ablative body radiation (SABR) for patients with metastatic clear cell renal cell cancer (mrcc) 102012-026 Phase II trial of sipuleucel-t and stereotactic ablative body radiation (SABR) for patients with metastatic castrate-resistant prostate cancer (mcrpc) RTOG 0815 A phase III prospective randomized trial of dose-escalated radiotherapy with or without shortterm androgen deprivation therapy for patients with intermediate-risk prostate cancer RTOG 0534 A phase III trial of short-term androgen deprivation with pelvic lymph node or prostate bed only radiotherapy (SPPORT) in prostate cancer patients with a rising PSA after radical prostatectomy RTOG 1115 Phase III trial of dose-escalated radiation therapy and standard androgen deprivation therapy (ADT) with a GnRH agonist vs. dose-escalated radiation therapy and enhanced ADT with a GnRH agonist and TAK-700 for men with high-risk prostate cancer GYNECOLOGIC RTOG 1203 A randomized phase III study of standard vs. IMRT pelvic radiation for postoperative treatment of endometrial and cervical cancer (TIME-C) GOG 0274/RTOG 1174 A phase III trial of adjuvant chemotherapy following chemoradiation as primary treatment for locally advanced cervical cancer compared to chemoradiation alone: The Outback Trial (ANZGOG 0902/ GOG 0274/RTOG 1174) GOG-0263 Randomized phase III clinical trial of adjuvant radiation vs. chemoradiation in intermediate-risk, stage I/ IIA cervical cancer treated with initial radical hysterectomy and pelvic lymphadenectomy GOG 279 A phase II trial evaluating cisplatin and gemcitabine concurrent with intensity-modulated radiation therapy (IMRT) in the treatment of locally advanced squamous cell carcinoma of the vulva GOG 0258 A randomized phase III trial of cisplatin and tumor volume directed irradiation followed by carboplatin and paclitaxel vs. carboplatin and paclitaxel for optimally debulked, advanced endometrial carcinoma GOG 0724 Phase III randomized study of concurrent chemotherapy and pelvic radiation therapy with or without adjuvant chemotherapy in high-risk patients with earlystage cervical carcinoma following radical hysterectomy HEAD AND NECK New 062013-052 A phase I CyberKnife accelerated hemilarynx stereotactic radiotherapy study for early-stage glottic larynx cancer RTOG 1216 Randomized phase II/III trial of surgery and postoperative radiation delivered with concurrent cisplatin versus docetaxel versus docetaxel and cetuximab for high-risk squamous cell cancer of the head and neck RTOG 3501 A phase II randomized, double blind, placebo-controlled study of lapatinib (Tykerb ) for non-hpv locally advanced head and neck cancer with concurrent chemoradiation RTOG 0920 A phase III study of postoperative radiation therapy (IMRT) /- cetuximab for locally advanced resected head and neck cancer RTOG 1008 A randomized phase II study of adjuvant concurrent radiation and chemotherapy versus radiation alone in resected high-risk malignant salivary gland tumors Small Cell Lung Cancer LUNG CALGB 30610/RTOG 0538 A phase III comparison of thoracic radiotherapy regimes with cisplatin and etoposide in limited small cell lung cancer RTOG 0937 Randomized phase II study comparing prophylactic cranial irradiation alone to prophylactic cranial irradiation and consolidative extracranial irradiation for extensive disease small cell lung cancer (ED-SCLC) Non-Small Cell Lung Cancer New RTOG 1306 A randomized phase II study of individualized combined modality therapy for stage III non-small cell lung cancer (NSCLC) 062012-53 A randomized phase I/II study of nabpaclitaxel, or paclitaxel, plus carboplatin with concurrent radiation therapy followed by consolidation in patients with favorable prognosis inoperable stage IIIA/B NSCLC 052011-093 Phase III randomized study of standard versus accelerated hypofractionated image-guided radiation therapy (IGRT) in patients with stage II-III non-small cell lung cancer and poor performance status SPINE 072010-134 A phase II study of stereotactic body radiation therapy and vertebroplasty for localized spine metastasis RTOG 0631 A phase II/III study of image-guided radiosurgery/sbrt for localized spine metastasis For more information, please contact Clinical Research Manager Jean Wu at 214-633-1753 or jean.wu@utsouthwestern.edu. Asal Rahimi, M.D., trial leader Triple negative breast cancer affects about 15 percent of people with breast cancer and can be difficult to treat. It is not responsive to hormone and HER-2 -directed therapies and can develop resistance to standard chemotherapy. Ixabepilone (trade name Ixempra) was approved by the FDA in 2007 to treat breast cancer and has been found to maintain activity in breast cancer cells with multidrug resistance. For patients with triple negative breast cancer whose cancer has spread after chemotherapy, ixabepilone has been successfully tested in clinical trials. UT Southwestern is the first medical institution to combine ixabepilone with a radiation delivery technique pioneered here called stereotactic body radiation therapy. SBRT is highly effective in treating local sites of metastatic disease. This study aims to discover whether a combination of SBRT and ixabepilone improves progression-free survival for patients with triple negative breast cancer. Eligible patients must: Have biopsy-proven, metastatic, triple negative breast cancer with fewer than 6 sites of disease; Been previously treated with a course of standard chemotherapy, including an anthracycline, a taxane and a capecitabine. Iyengar P, Westover K, Timmerman RD. Stereotactic ablative radiotherapy (SABR) for non-small cell lung cancer. Semin Respir Crit Care Med. 2013 Dec;34(6):845-54. Liu G, Stevens JB, Horne SD, Abdallah BY, Ye KJ, Bremer SW, Ye CJ, Chen DJ, Heng HH. Genome chaos: Survival strategy during crisis. Cell Cycle. 2013 Dec 3;13(4). [Epub ahead of print] Ding C, Solberg TD, Hrycushko BA, Medin P, Whitworth L, Timmerman RD. Multi-staged robotic stereotactic radiosurgery for large cerebral arteriovenous malformations. Radiother Oncol. 2013 Dec;109(3):452-456. Yopp AC, Mansour JC, Beg MS, Arenas J, Trimmer C, Reddick M, Pedrosa I, Khatri G, Yakoo T, Meyer JJ, et al. Establishment of a multidisciplinary hepatocellular carcinoma clinic is associated with improved clinical outcome. Ann Surg Oncol. 2013 Dec 7. [Epub ahead of print] Meng T, Soliman AT, Shu M-L, Yang Y, Chen S-C, Iyengar SS, Yordy JS, Iyengar P. Wavelet analysis in current cancer genome research: A survey. IEEE/ACM Trans Comput Biol Bioinform. 2013 Dec;10. Desrosiers M, DeWerd L, Deye J, Lindsay P, Murphy MK, Mitch M, Macchiarini F, Stojadinovic S, Stone H. The importance of dosimetry standardization in radiobiology. J Res Natl Inst Standards Techn. 2013 Dec 30;118. 6 SPRING 2014 The Target 7
Department of Radiation Oncology 5801 Forest Park Rd. PRESORTED NON PROFIT US POSTAGE PAID TWMS Department of Radiation Oncology at UT Southwestern Physicians who would like to make a referral may call the Department s main clinic number at 214-645-8525 or UT Southwestern s physician referral line at 214-645-8300 (toll-free 866-645-5455) for adult patients, or 877-445-1234 for pediatric patients. W.A. Monty and Tex Moncrief Radiation Oncology Building 5801 Forest Park Rd. Annette Simmons Stereotactic Treatment Center UT Southwestern University Hospital Zale Lipshy 5151 Harry Hines Blvd. Visit us on the Web Patient care: utswmedicine.org/radonc Education & research: utsouthwestern.edu facebook.com/utswradiationoncology Harold C. Simmons Comprehensive Cancer Center Radiation Oncology 2001 Inwood Rd.