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Neuroendocrine Tumours pp 275–298Cite as

Nonfunctioning Pancreatic Neuroendocrine Tumors

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Abstract

Nonfunctioning pancreatic neuroendocrine tumors are quite rare, representing 2 % of all pancreatic malignancies and 85 % of all pancreatic neuroendocrine tumors. They are classified based on the Ki-67 labeling index as “tumors” when Ki-67 is <20 % and “carcinomas” when Ki-67 is >20 %. On a molecular basis, they are different from pancreatic adenocarcinoma, expressing menin-1, death domain-associated protein, alpha thalassemia/mental retardation syndrome X-linked, and mammalian target of rapamycin as the main mutated genes. As for treatment, surgery represents the only curative option, related to localized stage of disease, but regards a minority of patients. In the more frequent advanced stage, several nonsurgical options can be discussed and even cytoreductive surgery. Somatostatin analogs are recommended in progressing nonfunctioning pancreatic neuroendocrine tumors. Streptozotocin-based chemotherapy was approved in the 1970s. Over the last decade, several molecular-targeted agents and novel chemotherapeutics have been developed. In 2011, everolimus, a mammalian target of rapamycin inhibitor, and sunitinib, a multitargeted inhibitor, were approved for progressing well-/moderately differentiated pancreatic neuroendocrine tumors. Peptide radioreceptor therapy with 177Lutetium-DOTATATE is a promising systemic therapy for tumors highly expressing subtype-2 somatostatin receptors. Finally, a number of locoregional treatments, mainly liver directed and interventional radiology based, have been demonstrated to be useful within a global therapeutic strategy including cytoreduction. Patients with distant metastases have a median survival of 23 months compared with 124 and 70 months of those with localized and regional disease, respectively. Several clinical studies are ongoing to evaluate novel agents in tumors resistant to everolimus and sunitinib or as an alternative to them against different targets. Biological predictive markers of response are needed, and they should be included in the design of the new clinical trials.

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Authors and Affiliations

  1. Hematology-Oncology Unit, Fourth Department of Internal Medicine, Attikon University Hospital, Rimini 1, Athens, 12462, Greece

    Anna Koumarianou MD, PhD

  2. Gastrointestinal and Neuroendocrine Tumors Unit, European Institute of Oncology, Milan, 20141, Italy

    Nicola Fazio MD

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  1. Anna Koumarianou MD, PhD
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  2. Nicola Fazio MD
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Correspondence to Anna Koumarianou MD, PhD .

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Editors and Affiliations

  1. Department of Medical Oncology, Hacettepe University Cancer Institute, Ankara, Turkey

    Suayib Yalcin

  2. Department of Endocrine Oncology, Uppsala University Hospital, Uppsala, Sweden

    Kjell Öberg

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Koumarianou, A., Fazio, N. (2015). Nonfunctioning Pancreatic Neuroendocrine Tumors. In: Yalcin, S., Öberg, K. (eds) Neuroendocrine Tumours. Springer, Berlin, Heidelberg. https://doi.org/10.1007/978-3-662-45215-8_18

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