Background: Locally advanced pancreatic cancer (LAPC) remains one of the deadliest cancers. Radiation is listed as a first line therapy option in treatment guidelines and remains a common treatment for this patient population primarily for local disease control and symptoms. Herein, we performed an exploratory analysis to compare the toxicity and efficacy between patients receiving either stereotactic body radiation therapy (SBRT) or intensity-modulated radiation therapy (IMRT) during the induction phase (prior to randomization) of a Phase 3 trial for localized intra-arterial gemcitabine therapy. Methods: As part of the TIGeR-PaC Phase 3 trial, patients with LAPC and an ECOG of 0-1 underwent an induction phase and were treated with 2 cycles of gemcitabine and nab-paclitaxel prior to receiving SBRT (n=59; 33Gy in 5 Fractions) or IMRT (n=75; 50Gy in 25 fractions) with concurrent PO capecitabine BID Monday-Friday. We performed Mann-Whitney analyses to compare mean percent changes in tumor size (imaging performed prior and 1-month after radiation) and CA 19-9 tumor markers. Adverse event (AE) incidence data during and 2 weeks after completion of the last fraction of radiation was used to compare toxicity via a contingency table. Results: A total of 134 patients across 22 sites (63 male/71 female; median age: 68.5 years) underwent radiation with no significant difference in baseline demographics between SBRT and IMRT patients. The decision for SBRT vs. IMRT was site-driven and not pre-specified by the protocol. Of these, 104 had analyzable imaging data, 50 SBRT and 54 IMRT, with a mean baseline tumor size of 4.3 cm and 4.0 cm (p=0.17), respectively. Pancreatic tumor location included head (n=63), body (n=36), or other (n=5). There was no statistical significance between the mean percent change of tumor size between SBRT (-13.3%) and IMRT (-10.8%; p=0.834). Both arms had similar RECIST partial response (approximately 18% of patients) after treatment. Patients with analyzable CA 19-9 tumor marker data (14 SBRT, 17 IMRT) showed no significant difference in percent change (mean, 9.8%±111%, -40.7%±40%; p=0.262). The SBRT subgroup had significantly less patients drop-out due to clinical deterioration (1 SBRT, 9 IMRT; p=0.025) and experience any AE (26 SBRT, 49 IMRT; p=0.014), gastrointestinal AE (10 SBRT, 33 IMRT; p<0.001), grade 3 or higher AE (6 SBRT, 20 IMRT; p=0.017), and serious AE (2 SBRT, 10 IMRT; p=0.045) p=0.014, 0.017, 0.045, respectively). The main AEs and serious AEs were gastrointestinal events. Conclusions: When compared to IMRT, SBRT demonstrates improved tolerability for treatment of patients with LAPC with comparable clinical efficacy. Clinical trial information: NCT03257033.