Phase II Study of First-line SBRT in Patients With Non-Metastatic Unresectable Pancreatic Cancer

Inclusion Criteria - All Patients: * Biopsy proven, non-metastatic, pancreatic cancer * Unresectable disease based on institutional standardized criteria for unresectability * Eastern Cooperative Oncology Group (ECOG) Performance Status 0-2 * CT scan of chest and abdomen (3-phase pancreas protocol), and PET-CT within 4 weeks of study entry * Patients with biliary or gastroduodenal obstruction must have drainage, duodenal stenting, or gastric bypass prior to initiating radiation * All disease must be encompassed in a single radiation field * No evidence or history of an autoimmune dysfunction * Negative pregnancy test within 7 days of study entry * No prior or concurrent chemotherapy * No previous or concurrent immunotherapy for pancreatic cancer * Liver enzymes ≤ 3 times upper limit of normal (ULN): total bilirubin (Tbili) ≤ 3.9 (biliary stents are allowed); aspartic transaminase (AST) ≤ 177; alanine transaminase (ALT) ≤ 198; Alkaline phosphatase (ALK-P) ≤ 378 * Adequate pretreatment organ function: Creatinine no greater than 1.5mg/dL; Total calcium no greater than 11.0mg/dL; prothrombin time (PT) no greater then 14 seconds; partial thromboplastin time (PTT) no greater then 40 seconds * Ability to give informed consent * Adequate baseline hematopoietic function: total white blood cell count equal to or greater than 3,000/mm³; absolute granulocyte count greater than 1,500/mm³; absolute lymphocyte count greater than 500/mm³; platelet count equal to or greater than 100,000/mm³ Inclusion Criteria - TBRI Group: * All Participant inclusion criteria * Amenable to leukapheresis as determined by a leukapheresis nurse * Primary tumor that is accessible to direct intratumoral injection by CT-guidance confirmed by interventional radiologist * No history of autoimmune disease * No history of human immunodeficiency virus (HIV) or acquired immune deficiency syndrome (AIDS) or other immunosuppressive diseases * No active viral or bacterial infection * No use of steroids or any other immunosuppressive drug at least 4 weeks prior to enrollment on study Exclusion Criteria - All Patients: * Prior history of radiotherapy that overlaps with the planned ports to the primary pancreatic tumor * Patients with tumors that are not accessible to direct access cannot be included in the study. * Prior or concurrent chemotherapy * Prior history of antineoplastic therapy or irradiation * Prior treatment with anti-tumor vaccines not allowed * Patients with a history of autoimmune diseases * A history of HIV infection, AIDS or other immunosuppressive disease state. The need to exclude patients with HIV/AIDS is because one of the endpoints of the study is immune response. People with HIV have a compromised immune system and enrollment in this study could confound the results (TBRI only) * Patients requiring corticosteroids are ineligible because one of the endpoints of the study is immune response. Since steroids modulate the immune system, enrollment of patients on steroids could confound the results. There must be no use of corticosteroids in the fours weeks preceding entry into the study (TBRI only). * Active bacterial, fungal or viral infection * Active bleeding (hemoptysis, melena, etc.) * Women who are currently pregnant or actively breast feeding. Women of childbearing potential must have a negative serum pregnancy test and must use effective contraception during trial participation * Any medical or psychiatric illness which in the opinion of the principal investigator might compromise a patient's ability to tolerate or complete treatment * Any patient requiring blood thinners (due to risk of gastrointestinal \[GI\] bleed)