Advances in diagnosis and treatment of pancreatic neuroendocrine tumors.

OBJECTIVE: To review the current state of pancreatic neuroendocrine tumors (PNETS)
Methods: The literature published between 2005 and 2014 in PUBMED, Medline, Google Scholar, Cochrane reports, and ClinicalTrials.gov was examined for relevance to the topic.
RESULTS: PNETS have an incidence <1 per 100,000 individuals and may functionally secrete biologically active substances or be nonfunctional (NF-PNETs). PNETs occur both sporadically and in patients with various inherited disorders. Pathology and staging range from benign, well-differentiated to metastatic and dedifferentiated and are dependent on the mitotic and Ki67 indices of cell proliferation. Bone alkaline phosphatase and N-terminal telopeptide (N-telopeptide) are markers of osteoblasts and osteoclast activation, and pancreastatin, neurokinin A (NKA), chromogranin A (CgA) and neuron-specific enolase are used to determine response to therapy and prognosis. Surgical resection of the primary tumor is recommended, even when there are metastases. New techniques are being developed for tumor localization (68Ga-tetra-azacyclododecane tetra-acetic acid-octreotate [DOTATATE] positron emission tomography [PET] scans). Somatostatin (SST) that binds to SST receptors (SSTRs) 2 and 5 partially controls symptoms and tumor growth. Two new agents have been approved for treating PNETs: a tyrosine kinase inhibitor and a mammalian target of rapamycin (mTOR) inhibitor that increases progression-free survival (PFS). An exciting addition is the use of peptide receptor radiotherapy (PRRT) using SST as the peptide with a carrier such as 68Gallium (68Ga) for localization or 177Lutetium (177Lu) or 99Yttrium (99Y) for therapy.
CONCLUSION: There have been advances in PNET diagnosis, tumor localization, and therapies in the last decade, and increased understanding of their pathophysiology is likely to be rewarded with new and emerging treatments for PNETs in the not too distant future.