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Noncolorectal gastrointestinal cancers include pancreatic, hepatobiliary, gastric, small bowel, and esophageal cancer. Pancreatic cancer has the worst prognosis of these cancers with a 5-year survival rate of less than 5%. Treatment of noncolorectal gastrointestinal cancers often includes a multimodal approach combining surgery, radiotherapy, and chemotherapy. Targeted therapies and biologic therapies are currently being investigated in many of these tumor types, and healthcare practitioners are challenged to remain up to date on the emerging clinical data for noncolorectal gastrointestinal cancers.