BOSTON — What type of neoadjuvant therapy is best for patients with resectable, borderline, or locally advanced pancreatic ductal adenocarcinoma (PDAC)?

While neoadjuvant therapy has become more common, the optimal type and duration of treatment remain unclear, explained William Hall, MD, radiation oncologist at the Medical College of Wisconsin in Milwaukee.

To bridge this gap, Hall and colleagues compared two commonly used approaches — stereotactic body radiotherapy (SBRT) and conventionally fractionated chemoradiation — looking at a range of outcomes in the small, randomized phase 2 SOFT Preop trial.

The findings were nuanced.

There were no significant differences in pathologic lymph-node positivity or pathologic response between the approaches, “which was very reassuring,” said Hall, the principal investigator, who presented the findings at the American Society for Radiation Oncology (ASTRO) 2026 Annual Meeting. Patients reported better quality of life after five sessions of SBRT before surgery than after conventional chemoradiation, which involves 28 sessions over several weeks.

However, while the trial was not powered to detect survival differences, median overall survival was numerically shorter in the SBRT group by nearly 17 months. That gap closed to about 6 months when looking only at patients who completed treatment.

“The numerical difference in overall survival was quite surprising to us,” Hall said. But Hall says he still sees “a strong role” for SBRT, which is more convenient, well tolerated, and efficient.

In the study, 98 patients with resectable, borderline, or locally advanced type A PDAC were randomly assigned in a 1:1 ratio to SBRT (n = 50) and conventional chemoradiation (n = 48), with 83 patients completing all intended therapy (n = 41 and 42, respectively).

Before enrollment, most patients had received more than 2 months of neoadjuvant chemotherapy, most commonly FOLFIRINOX. SBRT included 33-40 Gy to the primary tumor with 25 Gy to elective nodes in five fractions with no chemotherapy. The chemoradiation arm received 50.4 Gy in 28 fractions, which included elective lymph nodes, and weekly gemcitabine or capecitabine.

Surgery was performed 4-6 weeks after radiation therapy. Patient-reported outcomes were captured using a PROMIS survey.

The rate of node positivity — the trial’s primary outcome — was 41% vs 38% in the SBRT group vs the chemoradiation group (P = .754). Local or regional recurrences were not common in either arm but occurred more frequently in the SBRT group — six patients vs two patients. Hall also reported no difference in surgical complications or pathologic response.

Median overall survival, tracked from the date of enrollment, was numerically shorter with SBRT — 26 months vs 43 months with chemoradiation (P = .639). Among the 83 patients who completed treatment, the gap was smaller — 39.6 months vs 45.5 months with SBRT vs chemoradiation.

Overall, 42.6% vs 57.5% of patients in the SBRT cohort vs the chemoradiation cohort were alive at 3 years (P = .198).

Median progression-free survival was also numerically shorter with SBRT — 14.28 months vs 21.6 months with chemoradiation (P = .96).

Patients reported significantly better physical function and global physical health as well as less fatigue with SBRT. Before surgery, patients receiving SBRT had a mean 0.57-point increase in their PROMIS Global Physical Health score compared with a 3.71-point decrease among those receiving chemoradiation. Their mean PROMIS Physical Function score increased by 3.64 points vs 0.82 points with SBRT vs chemoradiation.

“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,” said study discussant Daniel Chang, MD, radiation oncologist at the University of Michigan in Ann Arbor. “SBRT did not increase surgical complications, an often-cited concern, and in fact led to better preserved quality of life during treatment.”

Given the phase 2 findings, Hall believes “researchers should continue to explore the role of SBRT in the preoperative setting.”

No external funding was reported. Hall disclosed research and travel funding from Elekta and a leadership role at the company. He also reported payments from Aktis Oncology and Sonoptima and ownership interest in Sonoptima. Chang reported having no relevant disclosures. 

M. Alexander Otto is a physician assistant and award-winning journalist. He is also an MIT science journalism fellow. Email: aotto@medscape.net.