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 study provides evidence of a more effective approach with biological insights for treating one of the most aggressive and lethal forms of cancer.
Pancreatic ductal adenocarcinoma (PDAC) poses a significant treatment challenge because, even after chemotherapy and surgery, tumors frequently recur, often at the original site. “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,” said study leader Dr. Todd Aguilera, Assistant Professor of Radiation Oncology at UT Southwestern.
Study Insights and Methodology
The retrospective study analyzed 181 patients treated for pancreatic cancer at UT Southwestern and Parkland Health between 2012 and 2023. These patients underwent neoadjuvant chemotherapy, aimed at shrinking the tumor before surgery, and either received or did not receive SAbR. Using RNA sequencing, researchers examined molecular changes in tumor tissue among 43 of these patients to understand the biological effects of SAbR.
Despite having more advanced disease initially, patients treated with SAbR exhibited better treatment responses and notably improved local control, or prevention of recurrence at the original site, particularly when arterial involvement was present. However, overall survival rates remained similar between the groups.
“This matters because local tumor regrowth causes significant suffering for patients,” Dr. Aguilera emphasized. “As systemic therapies continue to improve, the burden of local recurrence becomes even more prominent—and more important to address.”
Immune System Stimulation and Future Directions
The research also found evidence that SAbR stimulated the immune system, increasing cancer-fighting lymphocytes in SAbR-treated tumors. “While further study is needed, it’s possible that there is potential in combining high-dose ablative radiation with immunotherapies,” Dr. Aguilera noted. “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.”
This study builds upon previous research conducted in the Aguilera Lab, focusing on how radiation alters 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 explained.
Collaborative Efforts and Patient Involvement
Dr. Aguilera highlighted the importance of collaboration and patient involvement in advancing cancer treatment. “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,” he said. “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.”
More information: Peter Q. Leung et al, Presurgical Ablative Radiation Is Associated with Local Control and Immune Response in Pancreatic Cancer, Clinical Cancer Research (2025). DOI: 10.1158/1078-0432.CCR-24-3582
As the medical community continues to explore the potential of combining radiation with other therapies, this study marks a promising step towards improving outcomes for pancreatic cancer patients. The research underscores the importance of innovative approaches and collaborative efforts in the ongoing battle against this formidable disease.