BOSTON, September 28, 2026 — Patients preparing for pancreatic cancer surgery maintained better physical function and experienced less fatigue with five treatments of stereotactic body radiation therapy (SBRT) than with 28 treatments of conventional radiation therapy given with chemotherapy, according to a randomized phase 2 clinical trial. Rates of cancer remaining in the lymph nodes after preoperative treatment, the trial’s primary endpoint, did not differ significantly between the groups. Results will be presented today at the American Society for Radiation Oncology (ASTRO) Annual Meeting .
“For patients with pancreatic cancer who have already spent months receiving chemotherapy and are preparing for major surgery, reducing the amount of time spent in radiation treatment matters,” said William A. Hall, MD, principal investigator of the trial and professor and chair of radiation oncology at the Medical College of Wisconsin in Milwaukee. “Patients who received five sessions of radiation therapy had comparable tumor and surgical outcomes while maintaining better quality of life during treatment than those who came in for several weeks of chemoradiation.”
Pancreatic cancer can be difficult to control because it has a high risk of recurring near the original tumor and spreading elsewhere in the body. For selected patients whose disease has not spread to distant organs and may be removed surgically, treatment often begins with chemotherapy. Radiation therapy may be added before surgery to treat the tumor and nearby areas at risk for microscopic disease, although questions remain about which patients benefit most and which radiation therapy schedule is preferable.
Radiation therapy may be delivered through a conventional schedule over several weeks, or through SBRT, which delivers highly focused radiation doses in five or fewer treatments. Before this study, however, it had not previously been tested against a longer course of preoperative chemoradiation in a randomized trial.
The SOFT Preop study enrolled 102 patients with resectable, borderline resectable or selected locally advanced pancreatic adenocarcinoma. All patients had tolerated at least one month of chemotherapy, and most had received more than two months before joining the trial. There was no conclusive evidence that any patients had distant metastatic progression at the time of enrollment.
Trial participants were randomly assigned to receive either five treatments of SBRT or 28 treatments of conventionally fractionated radiation with concurrent chemotherapy. Both approaches treated the primary tumor and regional lymph nodes at high risk for cancer involvement, allowing researchers to compare the two radiation schedules across similar treatment areas. Surgery was planned four to six weeks after radiation therapy.
The trial’s primary endpoint was the proportion of patients with cancer remaining in their lymph nodes at the time of surgery. Residual lymph node involvement after preoperative treatment is associated with worse outcomes and provides an objective measure of treatment response.
Among the 83 patients who completed all planned treatment and underwent surgery, lymph nodes remained positive for cancer in 41% of the SBRT group and 38% of the chemoradiation group. The difference was not statistically significant. Researchers also found no significant differences in pathologic tumor response, complication rates or surgical margins.
“We designed the trial expecting that the longer course of chemoradiation therapy might produce more tumor downstaging before surgery, but that is not what we found,” Dr. Hall said. “The similar pathologic and surgical outcomes make us more confident that a carefully planned five-treatment approach can serve as a platform for future studies.”
Local or regional recurrence was uncommon during a median follow-up of approximately 3.4 years, occurring in six patients who received SBRT and two who received chemoradiation. Median progression-free survival was approximately 14 and 22 months, respectively. Median overall survival from study enrollment was 26 months with SBRT and 43 months with chemoradiation. Among patients who completed all therapy, including surgery (>80% of patients), median survival was 39.6 months with SBRT and 45.5 months with chemoradiation. At three years, 43% of patients in the SBRT group and 58% in the chemoradiation group were alive. None of the differences in recurrence, progression-free survival or overall survival were statistically significant, although the trial was not powered to detect survival differences.
Because patients entered the trial after receiving chemotherapy, the survival estimates do not include their first months of treatment after diagnosis. Dr. Hall said survival in both groups was favorable compared with historical outcomes, which may reflect the study design of enrolling patients who had tolerated an initial course of chemotherapy without clear distant progression.
The clearest difference between the treatment approaches emerged in patient-reported outcomes during the preoperative treatment period. Patients who received SBRT reported significantly better physical function and overall physical health, with less fatigue, compared with patients receiving chemoradiation therapy. The differences were no longer significant after surgery.
“The quality-of-life benefit was concentrated during radiation therapy, when one group was completing treatment in five visits and the other was coming in daily for several weeks,” Dr. Hall said. “For patients who are already spending a great deal of time receiving cancer care, shortening that part of treatment can make a meaningful difference in their day-to-day experience.”
As systemic therapies improve, durable control around the pancreas also may become increasingly important for patients who live longer. “If you want to cure these patients, they simply cannot recur locally,” Dr. Hall said. “If we can offer five total visits to radiation oncology that can prevent them from recurring locally and preserve a high quality of life, we owe it to this patient population to routinely include that option in treatment discussions.”
The findings should be interpreted in the context of the study’s design. This was a single-institution phase 2 trial conducted by an experienced multidisciplinary pancreatic cancer team. It was not designed to establish that SBRT and chemoradiation therapy provide equivalent cancer control, and larger multicenter studies are needed to determine whether the results can be reproduced in other settings. The SBRT regimen also included lower-dose treatment to regional lymph nodes, which differs significantly from some other pancreatic SBRT approaches that treat only the primary tumor. Dr. Hall noted that an approach including radiotherapy to regional nodes during a course of SBRT may provide a platform for future study.
“We still have many unanswered questions about radiation therapy before pancreatic cancer surgery, but this trial shows that a five-treatment option can better preserve quality of life during treatment when delivered by an experienced team,” Dr. Hall said. “The next step is to build on these findings in larger studies.”
ASTRO Expert Perspective
“For patients with pancreatic cancer receiving preoperative radiation, this randomized trial demonstrates that SBRT may be a safe and effective alternative to conventionally fractionated chemoradiation. SBRT did not increase surgical complications, an often-cited concern, and in fact led to better preserved quality of life during treatment without any significant differences in pathologic response, surgical complications or survival. These results show that researchers should continue to explore the role of SBRT in the preoperative setting,” said Daniel Chang, MD, FASTRO, ASTRO Pancreatic Cancer Guideline Chair and a radiation oncologist at the University of Michigan in Ann Arbor.
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