A 65-year-old with an unresectable 32 mm × 29 mm pancreatic adenocarcinoma invading into the portal vein confluence underwent investigational therapy with EUS guided fine needle injection of a modified adenovirus with a TNF gene inserted upstream of a radiation sensitive promoter. A 22 gauge needle was inserted under EUS guidance into the mass, followed by injection of the liquid chemotherapy drug directly into the tumor. The entire area of tumor became hyperechoic with the fluid injection. The patient then underwent radiation therapy a few hours later, which resulted in local release of TNF. The process was repeated weekly for a total of 5 weeks.