Study of Proton Therapy in Adjuvant Pancreatic Cancer

Inclusion Criteria: * Undergone pancreaticoduodenectomy with curative intent * Pathologically-confirmed pancreatic adenocarcinoma of the pancreatic head (adenocarcinoma must be the predominant component of the histology) * Completed 2 cycles of adjuvant chemotherapy composed of 5-fluorouracil, leucovorin, oxaliplatin, and irinotecan * Complete resection (R0) or resection with microscopic positive magins (R1) * Adequate healing post-operatively * Bone marrow function: absolute neutrophil count (ANC) ≥ 1,500/mm3; Platelets ≥ 100 × 109/L; hemoglobin ≥ 9.0 g/dL. Patients may have a transfusion of red blood cells to meet the hemoglobin requirement. * Renal function: serum creatinine ≤ 1.5 × upper normal limit of institution's normal range or creatinine clearance ≥ 30 mL/min for subjects with creatinine levels above institutional normal * Hepatic function: AST and ALT ≤ 3.0 × the upper normal limit of institution's normal range. Total bilirubin ≤ 1.5 × the upper normal limit of institution's normal range. * Partial Thromboplastin Time (PTT) must be ≤ 1.5 × upper normal limit of institution's normal range and INR (International Normalized Ratio) \< 1.5. Subjects on anticoagulant (such as warfarin) will be permitted to enroll as long as the INR is in the acceptable therapeutic range as determined by the investigator. * Eastern Cooperative Oncology Group (ECOG) Performance Status (PS) of 0-1 * Prior neoadjuvant chemotherapy is alllowed * Patients must have fully recovered from all effects of surgery. Patients must have had at least two weeks after minor surgery and four weeks after major surgery before starting therapy. Minor procedures requiring "Twilight" sedation such as endoscopies or mediport placement may only require a 24-hour waiting period, but this must be discussed with an investigator. * Women of childbearing potential must have a negative serum pregnancy test within 14 days prior to initiation of treatment and/or postmenopausal women must be amenorrheic for at least 12 months to be considered of non-childbearing potential * Patient is capable of understanding and complying with parameters as outlined in the protocol and able to sign and date the informed consent, approved by the Institutional Review Board (IRB), prior to the initiation of any screening or study-specific procedures Exclusion Criteria: * Ampullary adenocarcinoma * Women who are pregnant or breastfeeding * Macroscopic positive margins (R2) or evidence of residual local or metastatic disease * Resection not including pancreaticoduodenectomy * Known allergy or intolerance to leucovorin, 5-fluorouracil, oxaliplatin, or irinotecan * Prior radiation to the upper abdomen * Inability to swallow pills or bowel obstruction * Any invasive cancer in the previous 3 years requiring chemotherapy, radiation, or anticancer therapy following surgery * Insurance unwilling to pre-authorize PRT, FFX, and (if necessary) pegfilgrastim * Clinically significant liver disease (Patients with resolved hepatitis B infection are eligible if HBsAg testing is negative; Patients with resolved hepatitis C infection are eligible if viral RNA PCR is negative) * Uncontrolled HIV infection (CD4 count must be at least 200 and viral load undectable on a stable antiretroviral regimen to be eligible for enrollment) * Major surgery within 4 weeks prior to enrollment