Purpose: Treatment of hypovascular tumors, such as pancreatic adenocarcinoma, is challenging owing to inefficient drug delivery. This report examines the potential mechanism of localized drug delivery via transarterial microperfusion (TAMP) using a proprietary adjustable double-balloon occlusion catheter in a porcine model. Materials and Methods: Adult Yorkshire swine (N = 21) were used in the Institutional Animal Care & Use Committee- approved protocols. The RC-120 catheter (RenovoRx, Los Altos, California) was positioned into visceral, femoral, and pulmonary arteries with infusion of methylene blue dye, gemcitabine, or gold nanoparticles. Transmural delivery was compared under double-balloon occlusion with and without side-branch exclusion, single-balloon occlusion, and intravenous delivery. Intra-arterial pressure and vascular histologic changes were assessed. Results: Infusion with double-balloon occlusion and side-branch exclusion provided increased intra-arterial pressure in the isolated segment and enhanced perivascular infusate penetration with minimal vascular injury. Infusates were predominantly found in the vasa vasorum by electron microscopy. Conclusions: TAMP enhanced transmural passage mediated by localized increase in arterial pressure via vasa vasorum.

714 Background: Mesenteric venous thrombosis (MVT), defined as complete occlusion of the Superior Mesenteric Vein (SMV) or Main Portal Vein (MPV) is often incidentally identified on CT or MRI in patients with Locally Advanced Pancreatic Cancer (LAPC). There is very limited data describing the incidence and treatment of MVT in large studies in this patient population. Herein, we seek to establish the incidence of MVT and the treatment response in patients with LAPC. Methods: We conducted an analysis on 180 subjects with interpretable baseline imaging for MVT enrolled in the randomized Phase III TIGeR-PaC clinical trial (NCT03257033). Subjects who completed 4 Cycles of induction treatment (3 cycles of IV gemcitabine/nab-paclitaxel and 1 cycle of IMRT or SBRT) prior to randomization were analyzed. Baseline and end of induction CT scans were read by a board-certified radiologist to determine presence of MVT. Severe MVT was defined as complete occlusion of MPV and/or SMV. For patients who completed induction the end of induction CT was used to assess down staging of MVT. We analyzed the mean age between patients with and without MVT using a Mann-Whitney test and performed a contingency table with Pearson Chi-Square statistics to analyze tumor location. Results: Out of a total of 180 patients, 91 patients presented with severe MVT at baseline (50%). There was no difference in age (67 vs. 69) or sex (44% male vs. 39% male) for patients with and without MVT. The location of the tumor in the head of the pancreas was more prevalent in both groups (62% vs 53%, respectively). Out of 112 patients who completed induction, 60 presented with MVT at baseline (53%). Seventeen of these patients (28%) demonstrated partial or complete resolution of MVT during induction; most resolved MVT after the first 2 cycles of chemotherapy (15/17). Only a minority of these patients were on anticoagulation therapy (10/60, 17%). Conclusions: Severe MVT is much more prevalent in patients with LAPC than previously reported. Anticoagulation is underutilized in this cohort; however, chemotherapy may have a beneficial effect in downstaging MVT beyond anticoagulation. Clinical trial information: NCT03257033 .

TPS773 Background: Prognosis for locally advanced pancreatic cancer (LAPC) remains dismal even with advances in cancer therapy. Beyond systemic therapies, local disease control is important in these patients. Local double balloon mediated delivery of intra-arterial gemcitabine (IAG) was demonstrated to be safe in this patient population in a prior study1. TIGeR-PaC is an ongoing Phase-3 clinical trial comparing the efficacy of this approach compared to standard of care IV gemcitabine/nab-paclitaxel (GN) for patients with LAPC. Methods: The trial is designed with an induction phase of upfront systemic therapy prior to IAG. Patients with LAPC diagnosed within 6 weeks and ECOG 0-1, receive 3 cycles of GN and 1 cycle of radiation. The form of radiation was either IMRT, 50 Gy in 25 fractions, with concomitant capecitabine or SBRT, 33 Gy in 5 fractions (per site preference). Following induction, patients with non-progressive disease were randomized to receive IAG (8 treatments every two weeks for 16 weeks) or continuing therapy with 4 cycles of GN. After the 16 weeks of randomized therapy, the patients with non-progressive disease went on to continue systemic therapy (GN or capecitabine, per investigator’s preference) until disease progression and then followed for survival only. The primary endpoint is overall survival, and the study has an 80% power to detect a hazard ratio of 0.6 between the two arms. As of September 1st, 2022, 189 patients have been enrolled in the trial. In its initial design the trial expected a 35% drop out rate during the induction phase; however, two years into the trial the actual observed dropout rate was 53%. Beyond progression (22%), the key element of dropout rate was AE/SAE during radiation with IMRT/capecitabine (17%) vs. only 6% with SBRT. To increase accrual of randomized patients, the protocol and the statistical plan were modified to restrict the mode of radiation during induction to SBRT only starting December 2021. Since the modification of the protocol, the dropout rate during induction has decreased to 38%. As of this abstract, 43 patients have been randomized following induction with GN and SBRT. The rate of SAE during active treatment is not different between the 2 arms (20% in each arm), and the most common SAE is GI side effects in both arms. The protocol has a pre-planned interim analysis after 26 events, with 23 events at this writing we expect our first interim analysis later this year. 1. Rosemurgy AS, e al: J Pancreat Cancer. 2017;3(1):58-65. doi:10.1089/pancan.2017.0011. Clinical trial information: NCT03257033 .

713 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 .