Respiratory-gated Stereotactic Body Radiation Therapy for Adenocarcinoma of the Pancreas or Periampullary Region

Inclusion Criteria

* Age \>18 years.
* Karnofsky Performance Status \>70%
* Histologically confirmed adenocarcinoma of the pancreas or ampulla of Vater; at least the majority of the histopathologic specimen must be identified as adenocarcinoma as opposed to another histologic subtype. In patients with a diagnosis of recurrent disease (based on radiographic progression and/or rising CA19-9 levels) and a history of a biopsy-proven adenocarcinoma of the pancreas or the ampulla of Vater, repeat biopsy of the recurrence site is not required for participation of the trial.
* Pancreatic or periampullary tumors must be less than 8.0 cm in greatest axial dimension at the time of treatment planning.
* Patients who have been treated with any combination of surgical resection and neoadjuvant/adjuvant conventional chemoradiation therapy for resectable disease or conventional chemoradiation as definitive treatment for unresectable or borderline resectable disease are eligible for the study, provided that at least 180 days have elapsed since completing any previous radiation treatment. Patients who have been receiving continued chemotherapy following their initial radiation treatment are eligible regardless of when the most recent chemotherapy was received. Those patients who have received prior radiation therapy will constitute Cohort A and will receive stereotactic body radiation (SBRT) as 5 gray (Gy) x 5.
* Patients who have not previously undergone radiation therapy can have a history of treatment with either chemotherapy (for unresectable/borderline resectable disease) or any combination of surgery and chemotherapy (for resectable disease). Patients with no history of prior radiation treatment will constitute Cohort B and will receive SBRT as 6.6 Gy x 5. Please note that patients must have received at least two cycles of chemotherapy (with selection of drugs at the discretion of the treating oncologist) before SBRT treatment on protocol.
* Acceptable organ and marrow function as defined below (within 2 weeks prior to radiotherapy):

  * Leukocytes \>3,000/μL
  * Absolute neutrophil count \>1,500μL
  * Platelets \>100,000/μL
  * Total Bilirubin ≤1.5x institutional upper limit of normal
  * Aspartate transaminase (AST(SGOT))/Alanine transaminase (ALT(SGPT)) \<2.5x institutional upper limit of normal
  * Creatinine ≤ institutional upper limit of normal OR creatinine clearance \>60 mL/min/1.73 m2 for patients with creatinine levels above institutional normal
* Ability to understand and the willingness to sign a written informed consent document.
* Life expectancy \> 3 months.
* Radio-opaque markers must be present within the tumor bed. In patients who have undergone surgical resection, radio-opaque surgical clips within the tumor bed can be used as fiducials. Patients without surgical clips in the tumor bed must be able to have fiducials placed endoscopically, laparoscopically, or through a CT- or ultrasound-guided technique. If not, the tumor must be posterior and adjacent to the aorta, and treatment will only be permitted at the discretion of the Principal Investigator.

Exclusion Criteria

* Age \< 18 years.
* Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection (or infections requiring systemic antibiotic treatment), active upper GI ulceration or hemorrhage, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements.
* Any concurrent malignancy other than non-melanoma skin cancer, non-invasive bladder cancer, early stage prostate cancer, or carcinoma in situ of the cervix. Patients with a previous non-pancreatic, non-periampullary malignancy without evidence of disease for \> 5 years will be allowed to enter the trial.
* Pregnant and breastfeeding women are excluded as are women of child-bearing potential who are unwilling or unable to use an acceptable method of birth control (hormonal or barrier method of birth control; abstinence) to avoid pregnancy for the duration of the study. Should a woman become pregnant or suspect she is pregnant while participating in this study, she should inform her treating physician immediately.
* Women who are not post-menopausal (as defined in Appendix III) and have a positive urine or serum pregnancy test or refuse to take a pregnancy test.
* Patients with a life expectancy of \< 3 months.
* Patients with metastatic disease.
* Patients with evidence of gross tumor invasion into the lumen of the stomach or small bowel are not eligible; if imaging suggests luminal invasion of tumor, this must be ruled out endoscopically before the patient can be enrolled on study.