Patients preparing to undergo surgery for pancreatic adenocarcinoma who received stereotactic body radiation therapy (SBRT) appeared to have comparable pathologic and surgical outcomes while reporting better quality of life during treatment than those who received conventionally fractionated chemoradiation therapy. These findings were based on the phase II SOFT Preop study presented at the 2026 American Society for Radiation Oncology (ASTRO) Annual Meeting.1
Although neoadjuvant therapy is increasingly used in this clinical context, the optimal type and duration remain uncertain. Neoadjuvant radiation therapy may be delivered over several weeks or as SBRT in five or fewer treatments, but these two commonly used approaches had not previously been compared in a randomized trial, according to presenting author and principal investigator William A. Hall, MD, Professor and Chair of Radiation Oncology at the Medical College of Wisconsin in Milwaukee.
“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,” he commented in a news statement issued by ASTRO.
Study Details
“Our inclusion criteria were broad, as this was a single-institution study,” Dr. Hall said.
SOFT Preop enrolled 102 patients with resectable, borderline resectable, or locally advanced pancreatic ductal adenocarcinoma, an Eastern Cooperative Oncology Group performance status score of 0 to 2, no conclusive evidence of distant metastatic disease, and planned surgical resection. All patients had received and tolerated at least 1 month of neoadjuvant chemotherapy before enrollment, with 92% receiving more than 2 months.
Patients were randomly assigned in a 1:1 ratio to SBRT or conventional fractionated chemoradiation therapy. SBRT was delivered at 25 Gy in 5 fractions to regional nodes and 33 to 35 Gy in 5 fractions to the primary tumor without concurrent chemotherapy. Conventionally fractionated chemoradiation therapy was delivered at 50.4 Gy in 28 fractions to the primary tumor and regional nodes with weekly gemcitabine or capecitabine. Most SBRT treatments used 1.5-T adaptive MRI guidance to deliver guided radiation therapy, which, along with the inclusion of an intermediate- to low-risk prophylactic clinical target volume, Dr. Hall identified as a key distinction from prior neoadjuvant SBRT studies.
Surgery was planned for approximately 4 to 6 weeks after completion of radiation therapy.
Pathologic and Surgical Outcomes
The study’s primary endpoint was pathologic lymph node positivity, defined as at least one positive node, at surgical resection. “We designed the trial expecting that the longer course of chemoradiation therapy might produce more tumor downstaging before surgery,” Dr. Hall commented, “but that is not what we found.”
Of the 83 patients (SBRT: n = 41; conventional chemoradiation therapy: n = 42) who completed all planned treatment and underwent successful surgical resection, lymph node positivity was observed in 41% of the SBRT group and 38% of the conventional chemoradiation therapy group (P = .754), which Dr. Hall described as “a nearly identical number.” He also reported no between-arm differences in surgical complications or outcomes, including margin-negative surgical resection, which most patients achieved.
“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,” he said.
Local Control and Survival
Local and regional recurrences were “exceptionally rare” during a median follow-up among all enrolled patients of 3.4 years, Dr. Hall stated, occurring in eight patients (7.8%) overall, including six patients in the SBRT arm and two in the conventional chemoradiation therapy arm.
Median progression-free survival was not significantly different between SBRT vs conventional chemoradiation therapy (P = .96). Median overall survival was also not significantly different with SBRT vs conventional chemoradiation therapy (P = .639). Dr. Hall emphasized that this endpoint was measured from enrollment and may thus be 2 to 4 months longer from diagnosis. He also characterized overall survival in both arms as among some of the highest reported for patients enrolled prior to surgical resection—“a critical point” that may partly reflect the requirement that patients complete an initial course of chemotherapy before enrollment. However, he told The ASCO Post that these findings should be taken “with a bit of a grain of salt,” given that the study was not designed to detect survival differences and was limited by relatively early follow-up and a small population.
“That’s why we did multiple statistical comparisons, looking at any difference in overall survival between the arms, and I was actually surprised there was not,” he said. “Stay tuned. We’ll keep following these patients.”
Improved Quality of Life
The more apparent differences between the treatment approaches were seen in patient-reported outcomes during the preoperative period. Patient-reported quality of life was modestly better preserved with SBRT compared with conventional chemoradiation therapy, according to Dr. Hall, including physical function, global physical health, and fatigue (all P < .05).
“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,” he 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.”
Findings in Context
Daniel T. Chang, MD, FASTRO, ASTRO Pancreatic Cancer Guideline Chair and Professor and Chair of Radiation Oncology at the University of Michigan in Ann Arbor, noted that the findings support SBRT as an alternative to conventional chemoradiation therapy and its continued investigation in the preoperative setting. “SBRT did not increase surgical complications, an often-cited concern, and in fact led to better preserved quality of life during treatment…,” he said in a statement.
The findings should be interpreted with some caution considering the single-institution phase II design, which was not intended to establish equivalent cancer control between the approaches. Whether they will be reproducible in a phase III trial remains to be determined.
As systemic therapies improve, Dr. Hall suggested that durable local control may become increasingly important for patients who live longer. “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,” he said.
“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 concluded. “The next step is to build on these findings in larger studies.”
DISCLOSURE: Dr. Hall has received grant or research support and reimbursement for travel-related expenses from Elekta; compensation or payment from Aktis Oncology and Sonoptima; and copyright, patent, license, or royalty interests, ownership equity, and stock options with Sonoptima. He also serves as Vice Chair of the Clinical Steering Committee for the MR-Linac Consortium. Dr. Chang reported no conflicts of interest.
REFERENCE
1. Hall WA, Tsai S, Banerjee A, et al: A randomized, phase II clinical trial of stereotactic body radiation therapy or conventionally fractionated concurrent chemotherapy and radiation therapy preoperatively for pancreatic adenocarcinoma, the SOFT Preop study. 2026 ASTRO Annual Meeting. Abstract LBA 08. Presented September 29, 2026.
The SOFT Power of Neoadjuvant SBRT for Pancreatic Cancer
Neoadjuvant therapy for pancreatic cancer has several potential benefits. For patients with early resectable disease, it can address micrometastatic disease and identify patients who develop early metastatic progression. For patients with borderline resectable disease, it can facilitate an R0 resection. For those with locally advanced disease, it can convert patients to resectable. Neoadjuvant radiation plays an important role by treating the primary tumor and regional lymph nodes to improve pathologic response, sterilize potential surgical margins, and reduce the risk of local-regional recurrence. The PREOPANC trial showed that preoperative chemoradiation with gemcitabine and 15-fraction hypofractionated radiation improved R0 resection rates, local-regional control, and overall survival compared to upfront surgery and adjuvant chemotherapy in patients with resectable and borderline resectable disease.2 In the CONKO-007 trial, adding radiation to neoadjuvant chemotherapy for locally advanced diseases improved the R0 rate in those who underwent surgery and reduced the local-regional recurrence rate.3
The SOFT Preop trial by Hall et al. is the first to compare two neoadjuvant radiation schedules, conventionally fractionated chemoradiation and stereotactic body radiotherapy (SBRT). Patients with resectable, borderline resectable disease, or locally advanced disease were randomized after at least 1 month of chemotherapy, predominantly FOLFIRINOX, to concurrent chemoradiation (50.4 Gy/28 fractions) or SBRT (25 Gy/5 fractions to elective nodes and 33-40 Gy in 5 fractions to the primary without concurrent chemotherapy). It should be noted that while SBRT historically treated gross disease only, elective nodal irradiation to a lower dose of25 Gy in 5 fractions has become a newer paradigm, which the SOFT Preop trial incorporated.
The chemoradiation schedule used in the standard arm is the historical standard considered safe and within normal tissue tolerance but not necessarily optimal. SBRT is considered more biologically effective, delivering higher doses in fewer fractions, and indeed, several published series demonstrated superior local-regional control. The SOFT Preop trial showed no difference in the primary endpoint, pathologic node positivity rate (41% SBRT vs 38% chemoradiation, P = .754). There was also no difference in progression-free survival, overall survival, or surgical complication rate. Most importantly, patient-reported physical function and global physical health were all better preserved with SBRT (P < .05) during the radiation period, attributable to a better side-effect profile and more convenient treatment schedule.
There are caveats to these results. It is a relatively small phase II trial that was not powered to look at differences in overall survival and other clinical outcomes. There were numerically more deaths, surgical complications, and local-regional recurrence in the SBRT arm, but none reached statistical significance. The trial also does not compare these regimens to chemotherapy alone.
Overall, these results support SBRT as an option in the neoadjuvant setting. While it had similar outcomes to standard chemoradiation, the benefit of quality of life preservation and patient convenience are underappreciated “softer” endpoints that make SBRT a preferred modality for centers with the requisite technology and expertise. ν
DISCLOSURE: Dr. Chang reported no conflicts of interest.
REFERENCES
1. Versteijne E, van Dam JL, et al: Neoadjuvant chemoradiotherapy versus upfront surgery for resectable and borderline resectable pancreatic cancer. J Clin Oncol 40:1220-1230, 2022.
2. Fietkau R, et al: Benefit of chemoradiotherapy vs chemotherapy after induction therapy for conversion of unresectable to resectable pancreatic cancer. J Clin Oncol43:3266-3278, 2025.
3. Hall WA, Tsai S, Banerjee A, et al: A randomized, phase II clinical trial of stereotactic body radiation therapy or conventionally fractionated concurrent chemotherapy and radiation therapy preoperatively for pancreatic adenocarcinoma, the SOFT Preop study. 2026 ASTRO Annual Meeting. Abstract LBA 08. Presented September 29, 2026.
Dr. Chang is with the Department of Radiation Oncology at the Rogel Cancer Center, University of Michigan, in Ann Arbor.
