UT Southwestern researchers found that patients who had high-dose radiation with chemotherapy before surgery to remove pancreatic tumors showed better response to treatment than those who were not treated with radiation. (Photo credit: Getty Images)
DALLAS – July 02, 2025 – Adding targeted radiation to chemotherapy prior to surgery may offer better control of pancreatic tumors – potentially reducing the rate of recurrence after treatment, according to a new study from UT Southwestern Medical Center. Published in Clinical Cancer Research, the novel study offers evidence of a more effective approach with biological insights for treating one of the most aggressive and lethal forms of cancer.
Todd Aguilera, M.D., Ph.D., is Assistant Professor of Radiation Oncology and a member of the Experimental Therapeutics Research Program at the Harold C. Simmons Comprehensive Cancer Center at UT Southwestern.
“Pancreatic ductal adenocarcinoma (PDAC) is extremely difficult to treat because even after chemotherapy and surgery, tumors often grow back, many times at the original site,” said study leader Todd Aguilera, M.D., Ph.D., Assistant Professor of Radiation Oncology and a member of the Experimental Therapeutics Research Program at the Harold C. Simmons Comprehensive Cancer Center at UT Southwestern. “Our findings suggest stereotactic ablative radiotherapy (SAbR), which delivers high-dose radiation with minimal toxicity, may improve clinical outcomes for patients with PDAC by lowering the risk of recurrence – especially in cancers that invade or encase major arteries.”
The retrospective study compared 181 patients who were treated for pancreatic cancer at UT Southwestern and Parkland Health between 2012 and 2023 using neoadjuvant chemotherapy – designed to shrink the tumor prior to surgery – and either received or didn’t receive SAbR. Using RNA sequencing, the researchers examined molecular changes in tumor tissue among 43 of those patients to understand the biological effects of SAbR.
Despite having more advanced disease at the outset, patients treated with SAbR had better treatment response and notably improved local control, or prevention of recurrence at the original site – particularly when arterial involvement was present — but similar overall survival rates. “This matters because local tumor regrowth causes significant suffering for patients,” Dr. Aguilera said. “As systemic therapies continue to improve, the burden of local recurrence becomes even more prominent – and more important to address.”
The researchers, including first author and M.D./Ph.D. student researcher Peter Q. Leung, also found evidence that SAbR stimulated the immune system, increasing cancer-fighting lymphocytes in SAbR-treated tumors.
UT Southwestern M.D./Ph.D. student researcher Peter Q. Leung is the study’s first author.
“While further study is needed, it’s possible that there is potential in combining high-dose ablative radiation with immunotherapies,” Dr. Aguilera said. “That could open up new areas to enhance antitumor immunity and ultimately improve cure rates for pancreatic patients, which today stand only at around 30% for those who undergo surgery.”
The research builds upon previous studies conducted in the Aguilera Lab, which focus on understanding how radiation changes the tumor microenvironment.
“With high-resolution tools like single-cell RNA sequencing and multiplexed immunofluorescence, we are now investigating how each patient’s tumor responds at the cellular and molecular level and using that insight to develop smarter, more targeted treatments,” Dr. Aguilera said. “Detailed tissue analyses like those conducted here at UT Southwestern are critical for uncovering new therapeutic directions. This kind of work is only possible at a center like ours, where an interdisciplinary team collaborates closely to tailor the right treatment path for each patient. It also depends on the incredible commitment of our patients, who empower us to learn from every case. And none of it happens without dedicated trainees like Mr. Leung and the rest of our team, who take on critical parts of the effort.”
Dr. Aguilera is a Cancer Prevention and Research Institute of Texas (CPRIT) Scholar in Cancer Research, a National Cancer Institute (NCI) Cancer Moonshot Scholar, and a Damon Runyon Clinical Investigator.
Other UTSW researchers who contributed to the study are Herbert J. Zeh III, M.D., Chair and Professor of Surgery; Adam C. Yopp, M.D., Professor of Surgery and Chief of the Division of Surgical Oncology; John C. Mansour, M.D., Professor of Surgery; Song Zhang, Ph.D., Professor in the Peter O’Donnell Jr. School of Public Health; Cheryl M. Lewis, Ph.D., Associate Professor in the Simmons Cancer Center and of Pathology; Patricio M. Polanco, M.D., Associate Professor of Surgery, Director of Robotic Surgery Training, co-Director of the Pancreatic Cancer Program, and co-Director of the Pancreatic Cancer Prevention Clinic; Nina N. Sanford, M.D., Associate Professor of Radiation Oncology and Chief of Gastrointestinal Radiation Oncology Service; Syed Kazmi, M.D., Associate Professor of Internal Medicine in the Division of Hematology and Oncology; Matthew R. Porembka, M.D., Associate Professor of Surgery; Megan Wachsmann, M.D., Assistant Professor of Pathology; Zhikai Chi, M.D., Ph.D., Assistant Professor of Pathology; Salwan Al Mutar, M.D., Assistant Professor of Internal Medicine in the Division of Hematology and Oncology; David Hsieh, M.D., Assistant Professor of Internal Medicine in the Division of Hematology and Oncology; Eslam A. Elghonaimy, Ph.D., Instructor of Radiation Oncology; Muhammad S. Beg, M.D., Adjunct Associate Professor of Internal Medicine in the Division of Hematology and Oncology; Ahmed M. Elamir, M.D., Clinical Fellow in Radiation Oncology; Neha Barrows, B.S., Research Assistant II in Radiation Oncology; Hollis Notgrass, M.S., Lead Pathologist Assistant; Ethan Johnson, Clinical Research Coordinator; Cassandra Hamilton, B.S., Senior Regulatory Analyst; and Samy Castillo-Flores, M.D., and Ricardo E. Nunez Rocha, M.D., postdoctoral researchers.
Drs. Zeh, Yopp, Mansour, Zhang, Lewis, Polanco, Sanford, Kazmi, Porembka, Wachsmann, Chi, Al Mutar, and Hsieh are all members of Simmons Cancer Center.
The study was funded by a Simmons Cancer Center Translational Cancer Research Pilot Grant; CPRIT (RR170051); the Carroll Shelby Foundation; the UT Southwestern Disease Oriented Scholars Program; and an NCI Cancer Center Support Grant (P30CA142543).
About UT Southwestern Medical Center
UT Southwestern, one of the nation’s premier academic medical centers, integrates pioneering biomedical research with exceptional clinical care and education. The institution’s faculty members have received six Nobel Prizes and include 25 members of the National Academy of Sciences, 23 members of the National Academy of Medicine, and 14 Howard Hughes Medical Institute Investigators. The full-time faculty of more than 3,200 is responsible for groundbreaking medical advances and is committed to translating science-driven research quickly to new clinical treatments. UT Southwestern physicians provide care in more than 80 specialties to more than 140,000 hospitalized patients, more than 360,000 emergency room cases, and oversee nearly 5.1 million outpatient visits a year.
About Parkland Health
Parkland Health is one of the largest public hospital systems in the country. Premier services at the state-of-the-art Parkland Memorial Hospital include the Level I Rees-Jones Trauma Center, the only burn center in North Texas verified by the American Burn Association for adult and pediatric patients, and a Level III Neonatal Intensive Care Unit. The system also includes two on-campus outpatient clinics – the Ron J. Anderson, MD Clinic and the Moody Outpatient Center, as well as more than 30 community-based clinics and numerous outreach and education programs. By cultivating its diversity, inclusion, and health equity efforts, Parkland enriches the health and wellness of the communities it serves. For more information, visit parklandhealth.org.