Phase II SOFT Preop Trial Compares Radiation Schedules for Pancreatic Cancer Surgery
Data from the phase II SOFT Preop study, showcased at the 2026 American Society for Radiation Oncology (ASTRO) Annual Meeting, revealed that pancreatic cancer patients who underwent stereotactic body radiation therapy (SBRT) before surgery maintained better quality of life during therapy and achieved comparable pathologic results relative to peers treated with conventionally fractionated chemoradiation therapy. Neoadjuvant therapy is increasingly used for pancreatic adenocarcinoma, but clinical uncertainty has persisted regarding the optimal type and duration of radiation delivered prior to major operations.
William Hall, MD, of the Medical College of Wisconsin in Milwaukee, served as presenting author and principal investigator for the trial. He noted that reducing the time spent in radiation therapy is particularly critical for patients who have already endured months of chemotherapy before facing surgery. The single-institution study enrolled 102 patients diagnosed with resectable, borderline resectable, or locally advanced pancreatic ductal adenocarcinoma.
Randomized Patients Receive SBRT or Conventional Chemoradiation
Investigators randomized the cohort in a 1:1 ratio to receive either SBRT or conventional fractionated chemoradiation therapy.
The SBRT regimen delivered 33-40 Gy to the primary tumor with 25 Gy to elective nodes in five fractions without concurrent chemotherapy. Conversely, conventional chemoradiation delivered 50.4 Gy in 28 fractions to the primary tumor and regional nodes alongside weekly gemcitabine or capecitabine. Most SBRT treatments utilized 1.5-T adaptive MRI guidance, paired with a prophylactic clinical target volume, which Dr. Hall distinguished from previous neoadjuvant SBRT evaluations. Surgery was scheduled approximately four to six weeks following the completion of radiation therapy.
Surgical Resection Rates and Lymph Node Positivity Match Across Arms
The primary endpoint of the trial focused on pathologic lymph node positivity, defined as at least one positive node identified during surgical resection. Out of 102 enrolled patients, 83 successfully completed all planned treatment and underwent surgical resection, comprising 41 patients in the SBRT arm and 42 patients in the conventional chemoradiation arm. Lymph node positivity occurred in 41% of the SBRT group and 38% of the conventional chemoradiation group, reflecting a nearly identical distribution with a P-value of .754.
Dr. Hall stated that investigators originally anticipated the longer course of chemoradiation would yield greater tumor downstaging before surgery, but the data disproved that hypothesis. Analysis revealed no between-arm differences regarding surgical complications, margin-negative resections, or overall surgical outcomes. Daniel Chang, MD, FASTRO, ASTRO Pancreatic Cancer Guideline Chair and Professor and Chair of Radiation Oncology at the University of Michigan in Ann Arbor, observed that SBRT did not elevate surgical complications—a primary worry historically raised by physicians—while bolstering support for its ongoing evaluation in the preoperative setting.
Survival Rates and Preoperative Patient-Reported Quality of Life
Local and regional recurrences remained exceptionally rare during a median follow-up of 3.4 years across all enrolled patients, occurring in a total of eight individuals, which included six patients in the SBRT arm and two in the conventional chemoradiation arm. Median progression-free survival showed no significant difference between the two approaches, with a P-value of .96, and median overall survival also demonstrated no statistically significant difference, with a P-value of .639. Median overall survival measured from enrollment was numerically shorter with SBRT at 26 months compared with 43 months for conventional chemoradiation, though the gap narrowed to 39.6 months versus 45.5 months when evaluated strictly among patients who completed treatment. Three-year overall survival stood at 42.6% for the SBRT cohort and 57.5% for the conventional chemoradiation cohort.
The most pronounced differences emerged in patient-reported outcomes captured via PROMIS surveys during the preoperative window. SBRT patients demonstrated significantly better physical function and global physical health alongside less fatigue. Dr. Hall emphasized that this quality-of-life advantage was concentrated specifically during the active radiation phase, when one group completed treatments in five clinical visits while the other attended daily appointments over several weeks.
Common Questions About the SOFT Preop Trial Findings
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What was the primary endpoint of the SOFT Preop study?
The primary endpoint was pathologic lymph node positivity, evaluated as the presence of at least one positive node at surgical resection, which was observed in 41% of the SBRT group and 38% of the conventional chemoradiation group.
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How many patients completed treatment and underwent surgery in the trial?
Out of 102 total patients enrolled in the trial, 83 patients completed all planned therapy and successfully underwent surgical resection, with 41 in the SBRT arm and 42 in the conventional chemoradiation arm.
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What specific quality-of-life improvements were reported by SBRT patients?
Patients receiving SBRT reported significantly better-preserved physical function and global physical health, as well as reduced fatigue during the treatment period, compared with those undergoing daily conventionally fractionated chemoradiation.
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