Abstract
Neuroendocrine tumors (NETs) show low but increasing incidence and originate in multiple organs, including the pancreas, midgut, caecum, rectum, appendix, colon, and lungs. Due to their stunning genetic, histological, and clinical variability, diagnosis and treatment of NETs are challenging. In addition, low incidence and high variability hamper the implementation of high evidence trials. Therefore, guidelines do not cover the complexity of NETs and, frequently, treatment decisions are taken by interdisciplinary tumor conferences at comprehensive cancer centers. Treatment aims are (i) control of tumor growth, (ii) symptom control, as well as (iii) the improvement of progression-free survival (PFS) and overall survival (OS). Here, we discuss high evidence trials facilitating the achievement of these treatment aims. The majority of the evidence exists for treatment with somatostatin analogue, everolimus, peptide receptor radionuclide therapy (PRRT) with 177Lu-DOTATATE, sunitinib, and telotristat. Among those, PRRT is the only treatment option that has the potential to control symptoms, stop tumor growth, and to improve PFS and OS. In contrast, only a low level of evidence exists for treatment with cytotoxic drugs such as streptozotocin and doxorubicine. Finally, we discuss novel treatment options by a combination of cytotoxic drugs, 177Lu-DOTATATE, and tyrosine kinase inhibitors to be tested in randomized prospective trials in the future. In addition, the application of innovative isotopes, such as 225Ac, for PRRT is discussed.
Highlights
Neuroendocrine neoplasms (NENs) have a low incidence, but are still the most common endocrine malignancies in the western hemisphere with an increasing number of newly diagnosed cases over the past years [1]
According to current World Health Organization (WHO) guidelines, NENs are split into well-differentiated NENs, defined as neuroendocrine tumors (NETs), and poorly differentiated NENs, defined as neuroendocrine carcinomas (NECs) [3]
Biotherapy with somatostatin analogues, the mammalian target of rapamycin (mTOR) inhibitor everolimus, the VEGF inhibitor sunitinib, and 177Lu-DOTATATE radionuclide therapy has emerged as evidence-based treatment of advanced G1/G2 neuroendocrine tumors prolonging progression-free survival (PFS) and/or overall survival (OS)
Summary
Neuroendocrine neoplasms (NENs) have a low incidence, but are still the most common endocrine malignancies in the western hemisphere with an increasing number of newly diagnosed cases over the past years [1]. Chromogranin A is the most important serum marker in NET patients to estimate tumor burden at the time of initial diagnosis and later on for monitoring of therapy response and detection of recurrence [10,11], its use is hampered by low specificity. Another useful serum tumor marker in NETs is neuron-specific enolase (NSE), which frequently correlates with dedifferentiation and increasing aggressiveness of tumors [12]. The main aims of these concepts, at least in G1 and G2 tumors, are (i) control of symptoms, (ii) control of tumor growth and reduction of tumor mass, or (iii) prolonging progression-free survival (PFS) and overall survival (OS)
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