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

PRIMARY OBJECTIVES: I. To determine the maximum tolerated dose (MTD) of a radiosurgery boost added to hypofractionated chemoradiation in patients with borderline resectable or unresectable pancreatic cancer. SECONDARY OBJECTIVES: I. To determine the effect of a radiosurgery boost added to hypofractionated chemoradiation on surgical morbidity (specifically, healing of the surgical anastomoses and abdominal wounds and late hemorrhage from blood vessels in the field) in patients with advanced borderline resectable (BLR) or unresectable pancreatic cancer. II. To evaluate the utility of diffusion-weighted magnetic resonance imaging (MRI) as an assessment of treatment response after chemoradiation followed by radiosurgery. III. To determine the feasibility of collecting tissue for immunohistochemistry (IHC) analysis via endoscopic ultrasound or computed tomography (CT)-guided fine needle aspiration. IV. To utilize pathologic response rates in dose escalated regions, hypofractionated regions, and the dose gradient region in between to better characterize the radiobiologic response of pancreatic cancer to radiation dose escalation. OUTLINE: This is a dose-escalation study of radiosurgery. Patients receive gemcitabine hydrochloride intravenously (IV) over 30 minutes once weekly and undergo hyperfractionated intensity-modulated radiation therapy (IMRT) 5 days a week in weeks 1-3. Patients then undergo a single fraction of radiosurgery boost in week 5 and then receive gemcitabine hydrochloride IV over 30 minutes once weekly in weeks 6-8. Treatment continues in the absence of disease progression or unacceptable toxicity. After completion of study treatment, patients are followed up every 3 months for 2 years, every 6 months for 2 years, and then annually thereafter.