Stereotactic MRI-guided On-table Adaptive Radiation Therapy (SMART) for Locally Advanced Pancreatic Cancer

Inclusion Criteria:

1. Histologically or cytologically confirmed locally advanced adenocarcinoma of the pancreas that is considered unresectable or borderline resectable on institutional standardized criteria of unresectability or medical inoperability. Patients with and without regional adenopathy are eligible as long as lymph nodes are adjacent to primary tumor.
2. Greater than or equal to 3 months of systemic chemotherapy
3. At least 18 years of age.
4. Eastern Cooperative Oncology Group (ECOG) performance status ≤ 1
5. Normal bone marrow and organ function as defined below:

   1. Absolute neutrophil count ≥ 500/mcL (microliters)
   2. Platelets ≥ 50,000/mcL
   3. Hemoglobin ≥ 8.0 g/dL (deciliters)
   4. Total bilirubin ≤ 1.5 x IULN
   5. Aspartate Aminotransferase AST(SGOT) / Alanine Aminotransferase ALT(SGPT) ≤ 3.0 x Institutional Upper Limit of Normal (IULN)
6. Women of childbearing potential and men must agree to use adequate contraception (hormonal or barrier method of birth control, abstinence) prior to study entry and for the duration of study participation. Should a woman become pregnant or suspect she is pregnant while participating in this study, she must inform her treating physician immediately.
7. Ability to understand and willingness to sign an Institutional Review Board (IRB) approved written informed consent document (or that of legally authorized representative, if applicable).

Exclusion Criteria:

1. Distant metastatic disease as assessed by staging positron emission tomography / computed tomography (PET/CT) or CT of the chest and abdomen within 6 weeks of starting radiation therapy
2. Carbohydrate antigen (CA19.9) \> 500 U/ml.
3. Prior radiotherapy to the region of the study cancer that would result in overlap of radiation therapy fields.
4. Currently receiving any other investigational agents.
5. Major surgery within 4 weeks prior to first day of treatment.
6. Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, or cardiac arrhythmia.
7. Pregnant and/or breastfeeding. Women of childbearing potential must have a negative pregnancy test within 14 days of study entry.
8. Medical/psychological contraindication to magnetic resonance imaging (MRI).