Neuroendocrine tumors (NET) are rare
malignancies, with the most common site of origin being from the gastrointestinal tract, particularly the pancreas, small bowel and appendix. Pancreatic
neuroendocrine tumors can be functional, i.e.,
hormone secreting
tumors, e.g.,
insulinoma,
gastrinoma or
VIPoma, and can have distinctive symptoms leading to the diagnosis. In contrast nonfunctional
tumors, the majority of
PNET's, usually present later either incidentally or due to
tumor bulk symptoms. The recent WHO classification system in 2010 classified
PNET's into different stages and grades depending on the mitotic activity and Ki-67 labeling index.
PNET's have a broad range of prognoses depending on the histologic grade, differentiation and
biologic behavior. Computerized tomographic scanning (CT), magnetic resonance imaging (MRI) and
octreoscan are imaging tools used to diagnose
PNET, in addition to a confirmatory tissue diagnosis with immunohistochemical stains, typically obtained by either cytologic or histologic assessment. Symptomatic advanced
PNET's can be treated with a long-acting
somatostatin analogue for those
tumors with
somatostatin receptor positivity and which may also have antiproliferative activity. Another treatment modality is
peptide receptor radionucleotide
therapy (PRRT) in
somatostatin receptor-positive
tumors, albeit as yet with limited availability in the United States. Systemic
therapies with combination
cytotoxic agents e.g.,
streptozocin,
anthracyclines, and
capecitabine and
temozolomide, all have established activity in
PNET's.
Biologic agents targeting the
VEGF and mTOR signaling pathways, e.g.,
sunitinib,
bevacizumab or
everolimus are becoming integrated as treatments for
PNET's. Poorly differentiated, high grade
PNETs with a very high mitotic rate are treated with
platinum-based
chemotherapy regimens similar to treatment paradigms for
small cell carcinoma of the lung. For liver confined or predominant disease, strategies such as
cytoreductive surgery, hepatic artery embolization or radioembolization are treatment modalities to effect locoregional
tumor control. The next generation of studies in
PNET will help define optimal sequencing strategies of available
therapies and also will attempt to use
biomarker-guided approaches to select
therapies.