• Histologically confirmed pancreatic adenocarcinoma

• Borderline resectable pancreatic adenocarcinoma or locally advanced pancreatic adenocarcinoma

• No evidence of extrapancreatic disease on diagnostic imaging

• No evidence of invasion into the duodenum or stomach, as determined by EGD/EUS

• No prior treatment (chemotherapy, biological therapy, or radiotherapy) for pancreatic cancer

• No prior treatment with oxaliplatin, irinotecan, fluorouracil, or capecitabine

• ECOG Performance Status of 0-1

• No other malignancy within past five years (exceptions include basal cell carcinoma of the skin, cervical carcinoma in situ, and non-metastatic prostate cancer)

• No evidence of second malignancy at the time of study entry

• No interstitial pneumonia or extensive and symptomatic interstitial fibrosis of the lung

• No \> grade 2 sensory peripheral neuropathy

• No uncontrolled seizure disorder, active neurological disease, or known CNS disease

• No significant cardiac disease, including the following: unstable angina, New York Heart Association class II-IV congestive heart failure, myocardial infarction within six months prior to study enrollment

• Not pregnant and not nursing

• No other medical condition or reason that, in the opinion of the investigator, would preclude study participation

• Laboratory parameters as follows:

‣ Absolute neutrophil count ≥1,500/uL,

⁃ Platelet count ≥75,000/uL,

⁃ Hemoglobin ≥9 g,/dL,

⁃ Creatinine \<1.5 X ULN or estimated GFR \>30 ml/min,

⁃ Bilirubin \<1.5 X ULN,

⁃ AST and ALT \<3 X ULN,

⁃ Negative pregnancy test in women of childbearing potential

• Able to be treated with SBRT only at the Smilow New Haven campus

• Able to have fiducials placed in the pancreas