The purpose of this study is to find out the maximum dose of SBRT that can be safely given after chemotherapy for treatment of pancreatic cancer that cannot be removed surgically.

Inclusion Criteria:

• Histologically or cytopathologically confirmed adenocarcinoma of the pancreas.

• Locally advanced, unresectable pancreatic cancer as confirmed by the multidisciplinary input from a hepatobiliary surgeon and as defined on CT as having tumor abutment of >180° (> 50%) of the circumference of the superior mesenteric artery (SMA) or celiac axis, unreconstructable superior mesenteric vein (SMV) or PV involvement.

• No evidence of distant metastasis either prior to or after induction chemotherapy.

• Completion of at least 3 months, but no more than 6 months of standard induction chemotherapy for LAPC, which may include FOLFIRINOX or gemcitabine and nab-paclitaxel, preferably within 2-4 weeks but no longer than 8 weeks.

• Pancreatic tumor size ≤ 5 cm.

• Age ≥18 years

• ECOG 0-1.

• Patients must have acceptable organ and marrow function as defined below:

  • Leukocytes >3,000/uL
  • Absolute neutrophil count >1,500/uL
  • Platelets >50,000/uL
  • Total bilirubin Within 2 x upper limit of normal
  • AST (SGOT)/ALT (SGPT) <2.5 x institutional upper limit of normal
  • Creatinine-Creatinine clearance Within 1.5 x upper limit of normal OR >60 mL/min for patients with creatinine levels above institutional normal

• Ability to understand and follow the breathing instructions involved in the respiratory gating procedure or to tolerate compression sufficient to reduce fiducial motion to ≤ 5mm

• Ability to understand and the willingness to sign a written informed consent document.

Exclusion Criteria:

• Patients who have had prior abdominal radiotherapy.
• Patients receiving any other investigational agents
• Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements.
• Contraindication to Magnetic Resonance Imaging
• Patients in which iodine contrast is contraindicated
• Pregnant and breastfeeding women are excluded. Women of child-bearing potential who are unwilling or unable to use an acceptable method of birth control to avoid pregnancy for the entire study period and for up to 4 weeks after the study are excluded. This applies to any woman who has experienced menarche and who has not undergone successful surgical sterilization or is not postmenopausal (defined as amenorrhea for at least 12 consecutive months, or women on hormone replacement therapy with serum FSH levels greater than 35 mIU/mL. A negative urine or serum pregnancy test must be obtained within 14 days prior to the start of study therapy in all women of child-bearing potential. Male subjects must also agree to use effective contraception for the same period as above.