Stereotactic MRI-guided adaptive radiation therapy (SMART) for locally advanced pancreatic cancer: A prospective single-center cohort study

Purpose This prospective single-center cohort study evaluated outcomes and toxicity after ablative stereotactic magnetic resonance imaging (MRI)-guided adaptive radiation therapy (SMART) in patients with locally advanced pancreatic cancer (LAPC).Materials and methods Patients with LAPC treated within the MOMENTUM protocol (NCT04075305) received SMART (50 Gy/5 fractions) on a 1.5 T MRI-linear accelerator. Data were prospectively collected. Overall survival (OS), progression-free survival (PFS), risk of local progression, and toxicity were evaluated.Results Between February 2019 and September 2025, 118 patients with LAPC were treated. Median OS from the first SMART fraction was 13.2 months (95 % confidence interval [CI] 10.4-15.9), with a 2-year OS rate of 23.9 % (95 % CI 16.7-34.1). Median OS from diagnosis was 19.6 months (95 % CI 17.8-24.0). Median PFS from the first SMART fraction was 5.6 months (95 % CI 4.3-7.1), and 2-year PFS was 14.8 % (95 % CI 8.8-24.9 %). The cumulative incidence of local progression was 15.0 % at 1 year and 22.2 % at 2 years. Acute grade ≥ III gastrointestinal toxicity occurred in 6/112 assessed patients (5.4 %), including one grade IV ulcer perforation and one grade V duodenal perforation. Late grade ≥ III toxicity occurred in 3/93 assessed patients (3.2 %).Conclusion SMART provided encouraging local control with limited severe toxicity in patients with LAPC, while distant progression remained the dominant pattern of failure.