The study, known as the SOFT Preop trial, compared two very different ways of delivering preoperative radiation. One group of patients received stereotactic body radiation therapy, or SBRT, a technique that delivers highly focused, precisely targeted doses of radiation in just five treatment sessions. The other group underwent conventionally fractionated radiation therapy given with concurrent chemotherapy, a regimen that requires patients to come in for 28 separate treatments spread over several weeks. The central question was whether the longer, more traditional approach would produce better tumor response before surgery, or whether the compressed five-session schedule could achieve comparable results with far less disruption to patients’ lives.

The trial enrolled 102 patients with resectable, borderline resectable, or selected locally advanced pancreatic adenocarcinoma. Every participant had already tolerated at least one month of chemotherapy before joining the study, and most had received more than two months of systemic therapy. Importantly, there was no conclusive evidence that any patient had developed distant metastatic progression at the time of enrollment, meaning the trial captured a population whose disease was still potentially curable with surgery. Participants were then randomly assigned to one of the two radiation schedules, with both approaches treating the primary tumor and the regional lymph nodes at high risk for cancer involvement, allowing a direct comparison across similar treatment areas. Surgery was planned four to six weeks after radiation therapy in both arms.

The primary endpoint of the trial was deliberately chosen to be an objective measure of treatment response: the proportion of patients in whom cancer remained detectable in their lymph nodes at the time of surgery. Residual lymph node involvement after preoperative treatment is associated with worse outcomes and provides a concrete, pathologic yardstick for comparing radiation schedules. Among the 83 patients who completed all planned treatment and underwent surgery, lymph nodes remained positive for cancer in 41 percent of the SBRT group and 38 percent of the chemoradiation group, a difference that was not statistically significant. Researchers also found no significant differences in pathologic tumor response, complication rates, or the achievement of clear surgical margins.

William A. Hall, MD, principal investigator of the trial and professor and chair of radiation oncology at the Medical College of Wisconsin in Milwaukee, acknowledged that the results ran counter to one of the study’s underlying expectations. The trial was designed with the hypothesis that the longer course of chemoradiation might produce more tumor downstaging before surgery, but the pathologic outcomes proved essentially equivalent between the two schedules. According to Dr. Hall, that equivalence makes the team more confident that a carefully planned five-treatment approach can serve as a platform for future studies in this disease.

Survival data from the trial, while not statistically conclusive, offered a nuanced picture. During a median follow-up of approximately 3.4 years, local or regional recurrence was uncommon, occurring in six patients who received SBRT and two who received chemoradiation. Median progression-free survival was approximately 14 months in the SBRT arm and 22 months in the chemoradiation arm. Median overall survival measured from study enrollment was 26 months with SBRT and 43 months with chemoradiation. However, because patients entered the trial only after completing an initial course of chemotherapy, these estimates do not include the first months of treatment following diagnosis. Among the patients who completed all planned therapy, including surgery, a group comprising more than 80 percent of participants, median survival was 39.6 months with SBRT and 45.5 months with chemoradiation. At three years, 43 percent of patients in the SBRT group and 58 percent in the chemoradiation group were alive. None of these differences reached statistical significance, and the trial was explicitly not powered to detect survival differences. Dr. Hall noted that 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 and most clinically meaningful separation between the two approaches emerged in patient-reported outcomes during the preoperative treatment period. Patients who received SBRT reported significantly better physical function and overall physical health, along with less fatigue, compared with those receiving weeks of daily chemoradiation. The quality-of-life benefit was concentrated precisely during the radiation phase, when one group was finishing treatment in five visits while the other was commuting to the clinic every day for several weeks. After surgery, those differences were no longer statistically significant, suggesting that the advantage of the shorter schedule lies in easing the treatment experience itself rather than in altering the recovery trajectory afterward.

For a disease as aggressive as pancreatic cancer, this finding carries real weight. Pancreatic cancer is difficult to control because it carries a high risk of recurring near the original tumor and of spreading elsewhere in the body. For selected patients whose disease has not spread to distant organs and may be surgically removed, treatment typically begins with chemotherapy, and radiation may be added before surgery to treat the tumor and nearby areas at risk for microscopic disease. Questions have long persisted about which patients benefit most from preoperative radiation and which schedule is preferable, and until this study, SBRT had never been tested against a longer course of preoperative chemoradiation in a randomized trial. As systemic therapies improve and patients live longer, durable control around the pancreas may become increasingly important, and Dr. Hall argued that if five total visits to radiation oncology can prevent local recurrence while preserving a high quality of life, that option belongs routinely in treatment discussions with this patient population.

The findings come with important caveats that the investigators themselves emphasized. This was a single-institution phase 2 trial conducted by an experienced multidisciplinary pancreatic cancer team, and it was not designed to establish that SBRT and chemoradiation provide equivalent cancer control. Larger multicenter studies will be needed to determine whether the results can be reproduced in other settings. The SBRT regimen also included lower-dose treatment to the regional lymph nodes, which differs significantly from some other pancreatic SBRT approaches that treat only the primary tumor. Dr. Hall suggested that an approach including radiotherapy to regional nodes during a course of SBRT may provide a valuable platform for future investigation, and he stressed that many questions about preoperative radiation in pancreatic cancer remain unanswered.

Expert commentary from within the radiation oncology community reinforced the trial’s significance. Daniel Chang, MD, FASTRO, ASTRO Pancreatic Cancer Guideline Chair and a radiation oncologist at the University of Michigan in Ann Arbor, said the randomized trial demonstrates that SBRT may be a safe and effective alternative to conventionally fractionated chemoradiation for patients receiving preoperative radiation. He noted that 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. In his view, the results make a clear case that researchers should continue to explore the role of SBRT in the preoperative setting. For patients who have already spent months in cancer care before facing a major operation, the message from this trial is straightforward: a five-treatment radiation option, delivered by an experienced team, may preserve both their physical function and their time, while the next generation of larger studies determines how broadly this approach should be adopted.

Subject of Research: Preoperative stereotactic body radiation therapy versus conventional chemoradiation for pancreatic cancer

Article Title: Short-course radiation therapy better preserves physical function before pancreatic cancer surgery

Article References: Short-course radiation therapy better preserves physical function before pancreatic cancer surgery. (n.d.). Original publication

Image Credits: AI Generated

DOI: Not provided

Keywords: pancreatic cancer, SBRT, radiation therapy, chemoradiation, preoperative treatment, randomized phase 2 trial, ASTRO, quality of life, surgical outcomes, lymph node involvement, patient-reported outcomes, Medical College of Wisconsin