A Study of Photon and Proton Chemoradiotherapy as Definitive or Neoadjuvant Therapy in Non-Metastatic Pancreatic Cancer

Inclusion Criteria: -Age ≥ 18 years

* Histological confirmation of adenocarcinoma of the pancreas (head, body, or tail of pancreas)
* Imaging consistent with T1-4, N0-2, M0 pancreas cancer, including potentially resectable, borderline resectable, or unresectable disease as per National Comprehensive Cancer Network (NCCN) classification. When CT of the chest, abdomen, and pelvis are performed, this must be with contras per pancreas protocol. Imagining with positron emission tomography (PET)/magnetic resonance imaging (MRI) alone is acceptable on study. If PET/CT is performed, a separate pancreas protocol CT is required for inclusion.
* Must have received neoadjuvant chemotherapy at the discretion of medical oncology
* Medical oncology consultation to confirm that patient is an appropriate candidate for concurrent chemotherapy and surgical oncology consultation for confirmation of resection status.

  * Note: Patients who have received previous chemotherapy for pancreatic cancer are allowed to participate in this study, unless they experienced a previous allergic reaction to the drugs used in this study.
* Planned to receive CRT, consisting of proton beam therapy (PBT) or intensity-modulated radiation therapy (IMRT) (45 Gy/15 fractions) with concurrent chemotherapy with 5FU or Capecitabine.
* Eastern Cooperative Oncology Group (ECOG) Performance Status 0-1 or Karnofsky Performance Status 70-100 (Appendix III).
* Willing to sign consent onto the Mayo Clinic Radiotherapy Patient Outcomes Registry and Biobanking study, Institutional Review Board (IRB) 15-000136

  * Patients do not need to agree to Biobank blood draw.
  * Patients at Mayo Clinic Arizona are not required to consent to the Registry.
* Willing to sign consent for blood collection onto the Pancreas SPORE, IRB 354-06.
* Able to complete standard of care clinical questionnaire(s) by themselves or with assistance.

Exclusion Criteria:

* Presence of non-regional nodal involvement or distant metastatic disease (M1)
* Prior RT to the thorax, abdomen, or pelvis
* History of prior malignancy \< 2 years of enrollment, except non-melanotic skin cancer or carcinoma-in-situ of the cervix
* Immunocompromised patients and patients known to be HIV positive and not currently receiving antiretroviral therapy.

  * Note: Patients known to be HIV positive, but without clinical evidence of an immunocompromised state, are eligible for this trial.
* Receiving any investigational agent concurrent with CRT which would be considered as a treatment for the primary neoplasm.
* Any of the following because this study involves an agent that has known genotoxic, mutagenic and teratogenic effects:

  * Pregnant women
  * Nursing women
  * Men or women of childbearing potential who are unwilling to employ adequate contraception
* Co-morbid systemic or psychiatric illnesses or other severe concurrent disease which, in the judgment of the investigator, would make the patient inappropriate for entry into this study or interfere significantly with the proper assessment of safety and toxicity of the prescribed regimens.
* 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.