The Management Strategies of Interventional Therapy and Drug Therapy of Complicated Pancreatic Neuroendocrine Neoplasms with Liver Metastases

Pancreatic neuroendocrine neoplasms (pNENs) are the most common type of gastro-entero-pancreatic neuroendocrine tumor. Over 60% of patients were detected with distant metastases after the initial diagnosis. Liver is the most common metastatic site, 65.5% of liver metastases are unresectable. The basic treatment strategy is system therapy, mainly including somatostatin analogues, target therapy, and chemotherapy with the effect of anti-hormone secretion and anti-proliferation. But the objective response ratio (ORR) of system therapy is mild. Hepatic artery direct therapies, including trans-arterial embolization (TAE), trans-arterial chemoembolization (TACE), and trans-arterial radioembolization (TARE) can reduce the hepatic tumor burden fast and safely. The ORR can be improved too. There is no significant difference in the efficacy of the three methods. TAE has the highest ORR among the three methods but no side effect of chemotherapy of TACE, so that it is widely used in clinical practice. The outcome of peptide receptor radionuclide therapy (PRRT) was proved to be satisfactory in the low-grade or intermediate grade pNENs that expressed high levels of somatostatin receptor or had a moderately metastatic hepatic tumor burden. The severe complications from PRRT are myelo-suppression and radiation nephrotoxicity. The combined therapy should be applied to the treatment of complicated pNENs with liver metastases. The general strategies are reducing the hepatic tumor burden as soon as possible by firstly applying system drugs and interventional therapy, and then the primary tumor should be resected in elective surgery.