Utilizing Standard of Care Induction Chemotherapy Followed by MR-LINAC Radiotherapy and Surgical Exploration to Improve Resectability Rates in Potentially Resectable Locally Advanced Pancreatic Cancer

Prior treatment

• Disease meeting non-operative/unresectable ABC criteria, including any of the following:
  • Anatomic: SMA encasement ≥ 270°; CHA involvement to the celiac origin/trifurcation; aortic invasion; no reconstructable SMV-PV segment; IVC invasion.
  • Biologic: CA19-9 ≥ 600 U/mL (after biliary drainage if obstructed) or clear radiographic/biochemical progression prior to starting protocol therapy.
  • Conditional: ECOG ≥ 2, ASA ≥ IV, or comorbidities that preclude major abdominal surgery despite optimization.
• Prior radiotherapy to the pancreas or overlapping abdominal fields that would preclude protocol RT.
• Prior pancreatic resection or local ablative therapy (e.g., IRE/RFA) to the primary tumor.
• Prior systemic therapy for current LAPC (neoadjuvant/induction) before consent/enrollment.
• Contraindications to MRI/MR-guided therapy (e.g., non-MRI-compatible implants) or severe claustrophobia not manageable with standard measures.
• Concurrent malignancy requiring active systemic treatment (except adequately treated non-melanoma skin cancer or in-situ cervical cancer).
• Concurrent enrollment in another interventional clinical trial that, in the opinion of the investigator, could interfere with outcomes of this study.

Other illness

• Metastatic disease on staging (distant organ or peritoneal metastases).
• Active, uncontrolled infection or clinically significant cardiac, pulmonary, or hepatic disease that, in the investigator's judgment, poses unacceptable risk.
• Known hypersensitivity to intended study medications or essential components of supportive care that cannot be mitigated.

Age

• Patients age \< 18 or ≥ 90 years.

Other

• Uncontrolled biliary obstruction not amenable to adequate drainage.
• Pregnant or breastfeeding individuals.
• Inability to provide informed consent or to comply with study procedures/assessments; absence of a legally authorized representative when needed.

• Male or female patients age 18 or older.
• Histologically or cytologically confirmed pancreatic ductal adenocarcinoma.
• Locally advanced, potentially resectable disease per ABC criteria after multidisciplinary review:
  • Anatomic: Tumor-artery contact \>180° but \<270° with the SMA or celiac, or ≤180° with mild contour irregularity but no frank stenosis; common hepatic artery (CHA) contact not reaching the celiac axis; venous involvement with a reconstructable SMV-PV segment.
  • Biologic: CA19-9 \< 600 U/mL (after biliary drainage if obstructed) and no evidence of radiographic/biochemical progression at baseline.
  • Conditional: ECOG 0-1, comorbidities optimized, albumin ≥ 3.0 g/dL.
  • No evidence of metastatic disease on staging imaging and laparoscopy.
• Measurable or evaluable disease on pancreas-protocol CT or MRI (RECIST v1.1).
• Adequate organ function, including all of the following (local lab ULN applied):
  • ANC ≥ 1.5 × 10⁹/L; platelets ≥ 100 × 10⁹/L; hemoglobin ≥ 9 g/dL.
  • Total bilirubin ≤ 1.5 × ULN (≤ 3 × ULN if adequately stented); AST/ALT ≤ 2.5 × ULN.
  • Creatinine clearance ≥ 50 mL/min (Cockcroft-Gault or equivalent).
• ASA physical status I-III.
• Life expectancy ≥ 12 weeks.
• Able and willing to comply with study visits/procedures
• Informed consent obtained; HIPAA authorization per institutional policy.
• For participants of childbearing potential: negative pregnancy test at screening and agreement to use effective contraception during protocol therapy and the specified post-therapy interval.