Chemoradiation and Radiosurgery Boost in Treating Patients With Locally Advance Pancreatic Cancer That May or May Not be Removed by Surgery

Inclusion Criteria:

* Patients must have histologically or cytologically-confirmed pancreatic adenocarcinoma
* For the initial dose escalation study, patients must have locally advanced / unresectable pancreatic cancer; these are defined as follows:

  * No distant metastases
  * Hepatic artery encasement
  * Superior mesenteric artery (SMA) encasement \> 180 degrees
  * Any celiac axis abutment
  * Unreconstructable superior mesenteric vein (SMV)/portal occlusion
  * Aortic invasion or encasement
  * Metastases to lymph nodes beyond the field of resection
* For the expansion phase, patients must have borderline resectable or locally advanced / unresectable pancreatic cancer; these are defined as follows:

  * No distant metastases
  * At least 45 degree abutment of the hepatic artery or SMA
  * Any celiac axis abutment
  * Near complete occlusion of the SMV or portal vein
  * Unreconstructable or reconstructible SMV/portal occlusion
  * Aortic invasion or encasement
  * Metastases to lymph nodes beyond the field of resection
* Patients must have evaluable disease
* Women of childbearing potential must be non-pregnant (negative pregnancy test within 72 hours prior to radiation simulation, postmenopausal woman must have been amenorrheic for at least 12 months to be considered of non-childbearing potential) and nonlactating, and men and women must be willing to exercise an effective form of birth control (abstinence/contraception) while on study and for 3 months after therapy completed
* Eastern Cooperative Oncology Group (ECOG) performance status determined to be between 0 and 1
* Absolute neutrophil count (ANC) \>= 1,500/ul
* Platelets (PLT) \>= 100,000/ul
* Subjects must sign a written informed consent and Health Insurance Portability and Accountability Act (HIPAA) consent prior to performance of study-specific procedures or assessments and must be willing to comply with treatment and follow up
* Bilirubin less then 1.5 x upper limit of normal (ULN)
* Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) \< 3 x ULN
* Serum creatinine \< 1.5 x ULN

Exclusion Criteria:

* Patients who have had any prior therapy for pancreatic cancer
* Concurrent chemotherapy or biologic therapy
* A history of ataxia telangiectasia or other documented history of radiation hypersensitivity
* Scleroderma or active connective tissue disease
* Active inflammatory bowel disease
* Serious, active infections requiring treatment with IV antibiotics
* Uncontrolled intercurrent illness including, but not limited to, psychiatric illness/social situations that would limit compliance with study requirements