Inclusion Criteria (Both Arms):  Age 18 or older Able to provide informed consent Histologically confirmed primary pancreatic cancer, or willing to undergo endoscopic ultrasound (EUS) with synchronous fiducial marker placement and biopsy No evidence of distant metastases (M0) Medically fit to undergo surgical resection Life expectancy >6 months Adequate renal function to tolerate contrast dye for imaging ECOG Performance Status 0-2 Inclusion Criteria (Arm 1) Upfront resectable pancreatic cancer No evidence of nodal disease (N0) Appropriate to undergo a pancreaticoduodenectomy within 4-6 weeks of registration  Inclusion Criteria (Arm 2)  Borderline resectable or upfront resectable pancreatic cancer Plan for surgical resection independent of the biochemical or radiographic response to SABR  Exclusion Criteria (Both Arms):  Serious medical comorbidities or other contraindications to radiotherapy or surgery Gross disease involving duodenum or stomach Unable to have fiducials placed. Recurrent pancreatic cancer Prior abdominal radiation at any time Inability to attend full course of radiotherapy, surgery, or follow-up visits Contrast allergy Pregnant or lactating women  Exclusion Criteria (Arm 1):  Receipt of any neoadjuvant system therapy, standard cytotoxic therapy or experimental  Exclusion Criteria (Arm 2):  Elevated bilirubin or liver enzymes considered to be a contraindication to irinotecan chemotherapy, unless an intervention is planned to improve hepatic functioning