Preoperative Folfirinox, Radiation Therapy for Resectable Adenocarcinoma of the Pancreas

Inclusion Criteria:

1. Cytologic or histologic proof of adenocarcinoma of the pancreas is required prior to treatment. Patients with Islet cell tumors are not eligible.
2. Only untreated patients with high risk pancreatic adenocarcinomas will be eligible for the study. For this study, such patients are defined as those who meet one or more of the following radiographic or serologic criteria: a)Primary tumor that involves the superior mesenteric vein causing a vein deformity or segmental venous occlusion with a patent vessel above and below suitable for reconstruction. b)Primary tumor that involves </= 180 degrees of the superior mesenteric artery (SMA), celiac axis or any of its branches on CT or MRI. c) Primary tumor that abuts or encases (>/= 50% of the vessel circumference) a short segment of the common hepatic artery (typically at the gastroduodenal artery origin)
3. (continuation of #2). d) Patients with a high CA19-9 (=/>500mg/dl) in the presence of a bilirubin =/< 2.0 mg/dL. e) Radiographic findings consistent with malignant peripancreatic lymphadenopathy outside the planned field on CT or MRI f) Radiographic findings of indeterminate liver or peritoneal lesions on CT or MRI concerning but not diagnostic of metastatic disease.
4. Patients cannot have known hepatic or peritoneal metastases detected by ultrasound (US), CT scan, MRI or laparotomy.
5. There will be no upper age restriction; patients with Eastern Cooperative Oncology Group (ECOG) 0-1 are eligible.
6. Adequate renal, and bone marrow function: a) Leukocytes >/= 3,000/uL. b) Absolute neutrophil count >/=1,500/uL.c) Platelets >/=100,000/Ul. d) Serum creatinine </= 2.0 mg/dL.
7. Hepatic function (endoscopic or percutaneous drainage as needed). a)Total bilirubin </= 2 X institutional upper limits of normal (ULN). b) AST (SGOT)/ALT (SGPT) </= 5 X institutional ULN.
8. Patients must have no fever or evidence of infection or other coexisting medical condition that would preclude protocol therapy.
9. Women of childbearing potential (defined as those who have not undergone a hysterectomy or who have not been postmenopausal for at least 24 consecutive months) must agree to practice adequate contraception and to refrain from breast feeding.
10. Patients must sign a study-specific consent form.

Exclusion Criteria:

1. Patients whose tumors are defined as locally advanced cancer or metastatic cancer are not eligible.
2. Unstable angina or New York Heart Association (NYHA) Grade II or greater congestive heart failure; multiple comorbidity that preclude a major abdominal surgery.
3. Known presence of metastases.
4. Inability to comply with study and/or follow-up procedures.
5. Patients < 18 years of age.
6. Pregnant women with a positive (blood B-HCG) pregnancy test are excluded from this study.
7. Patients with an active second malignancy with the exception of non-melanoma skin cancer.