Aim of this study is to evaluate if low-dose radiotherapy (LDR) can intensify local effect of a chemotherapy regimen with Gem-based doublets administered sequentially with stereotactic body radiotherapy (SBRT) and to assess the safety and efficacy of this combined treatment on patients affected by locally advanced pancreatic adenocarcinoma (LAPC).

Inclusion Criteria:

• Pathologically confirmed adenocarcinoma of the pancreas
• Patients with unresectable disease based on institutional standardized criteria of unresectability or patients whose disease appeared potentially resectable on axial CT imaging but were found unresectable at surgery
• Eastern Cooperative Oncology Group (ECOG) performance status ≤ 2. Age ≥ 18
• Patients with biliary or gastroduodenal obstruction must have drainage or surgical bypass prior to starting treatment
• Patients with radiographically assessable disease
• Adequate bone marrow, hepatic and renal function: -Hemoglobin >10.0 g/dL, absolute neutrophil count > 1.5 x 10^9/L, platelet count > 100 x 10^9/L. -Aspartate transaminase (AST or SGOT) and alanine transaminase (ALT or SGPT) should be ≤ 3 x upper limit of normal (ULN). -Total bilirubin < 2 mg/dL. Patients with elevated bilirubin due to obstruction should be stented and their bilirubin should decrease to < 2 mg/dL prior to study entry. - Creatinine < 3 mg/dL or Creatinine clearance > 40 mL/min (calculated according to Cockroft and Gault)

Exclusion Criteria:

• Evidence of metastatic disease in the major viscera or peritoneal seeding or ascites
• Gastric or duodenal obstruction
• Previous peripheral neuropathy
• Previous irradiation to the planned field; previous chemotherapy for pancreatic cancer
• Malignancy (within the past two years) except non-melanomatous skin cancer or carcinoma in situ of the cervix, uterus, or bladder