Inclusion Criteria:
1. One or more of the following:
A) Participants who have histologically confirmed new diagnosis of unresectable, non-metastatic, LAPAC as assessed by the multidisciplinary tumor board based on pre-RT imaging and clinical assessment, and are amenable to SBRT.
B) Patients who received prior systemic therapy for unresectable LAPAC may be consented and enrolled if they still have localized unresectable LAPAC amenable to SBRT.
C) Participants with newly diagnosed LAPAC who received systemic therapy for borderline resectable pancreatic adenocarcinoma and have become unresectable following preoperative multidisciplinary assessment, are eligible for the study if the patient meets the eligibility criteria based on staging following systemic therapy.
D) Participants with newly diagnosed borderline resectable pancreatic adenocarcinoma.
2. Age ≥18 years.
3. ECOG performance status ≤2 (see Appendix A).
4. Life expectancy of greater than 6 months.
5. A negative serum pregnancy test prior to PET-MR imaging, for women of child-bearing age.
6. Ability to understand and the willingness to sign a written informed consent document.
7. Eligible for treatment on the integrated magnet resonance linear accelerator (MRL).
Exclusion Criteria:
1. Patients who have had prior RT to upper abdomen.
2. Patients who are receiving any other concomitant investigational agents. Participants who have entered the follow-up phase of an investigational study may participate as long as it has been 4 weeks after the last dose of the previous investigational agent.
3. Patients with early stage resectable (I-II) pancreatic cancer, or known distant metastases.
4. Contraindication to MRI scan as per current institutional guidelines.
5. 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.
6. Pregnant women are excluded from this study because of the potential teratogenic or abortifacient effects. Because there is an unknown but potential risk for adverse events in nursing infants, breastfeeding should be discontinued.
7. Patients who have a known additional malignancy that is progressing or has required active treatment within the past 3 years. Participants with basal cell carcinoma of the skin, squamous cell carcinoma of the skin (other than head and neck region), or carcinoma in situ (e.g., in situ cervical cancer or breast carcinoma) that have undergone potentially curative therapy are not excluded.
8. History or current evidence of any condition, therapy, or laboratory abnormality, known psychiatric or substance abuse disorders that might confound the results of the study, interfere with the participant's participation for the full duration of the study, or is not in the best interest of the participant to participate, in the opinion of the treating investigator.
