Observational Study on GEP-and Pulm-NET Treated at FPG

Neuroendocrine tumors (NETs) are a heterogeneous group of rare epithelial neoplasms arising from cells of the diffuse neuroendocrine system. In recent years their incidence has been constantly increasing and up to 80% of cases already begin in an advanced stage. The most frequent site of primary localization is the gastroenteropancreatic tract (GEP-NET) in 60% of cases, followed, in 25%, by the lung (L-NET). Clinically, NETs are classified as functioning (F) or non-functioning (NF) based on the presence of symptoms caused by hormonal secretion produced by tumor cells. NETs are characterized by great clinical and biological, inter- and intra-tumoral heterogeneity. The WHO classification identifies four categories: well-differentiated NETs, G1, G2 and G3, and poorly differentiated neuroendocrine carcinomas (NECs), which represent 10%-20% of all neuroendocrine neoplasms. This classification, together with the TNM stage according to the American Joint Committee on Cancer (AJCC 8th edition) takes on an important prognostic value. However, these two criteria are not exhaustive in predicting the aggressiveness of the pathology nor the response to oncological therapies. There is therefore a clear clinical need, to date unsatisfied, for new prognostic and predictive biomarkers, which can better define the heterogeneity of NETs by implementing classification and staging, to guide prognosis and support therapeutic decisions.

The main feature of all well-differentiated NETs is the overexpression of the somatostatin receptor, measured by PCR-based or immunohistochemistry (IHC)-based methods or by imaging. Among these receptors, the SSTR2A subtype is the most commonly expressed. Diagnostic and therapeutic approaches aimed at SSTR have shown advantages but it is not clear how much the degree of expression of SSTR in positive patients influences the response to treatment and whether it has a correlation with survival, regardless of the oncological treatments used. Furthermore, since the expression of this receptor appears inversely proportional to the degree of differentiation and can be different within the same disease between primary tumor and metastatic disease, this receptor could have a further role as a measure of tumor heterogeneity and disease progression.