How I treat neuroendocrine tumours

Abstract

Neuroendocrine tumours (NETs) constitute a heterogeneous group of neoplasms characterised by variable endocrine activity and somatostatin receptor expression, with the latter allowing the use of targeted therapeutic concepts. Currently accepted treatment strategies for advanced well-differentiated NET include somatostatin analogues octreotide and lanreotide, peptide receptor radionuclide therapy using radiolabelled somatostatin analogues, mammalian target of Rapamycin inhibitor everolimus, tyrosine kinase inhibitor sunitinib, interferon alpha and classical cytostatic, such as streptozotocin-based and temozolomide-based treatment. Indication, use and approval of these treatments differ based on primary tumour origin, grading and symptomatic burden and require an optimised multidisciplinary cooperation of medical oncologists, endocrinologists and nuclear medicine specialists. Interestingly, hot topics in oncology including immunotherapy and use of next-generation-sequencing techniques currently play a minor role for the treatment of NETs. The recent revision of the WHO classification including the recognition of the novel NET G3 category allows for potentially more tailored treatment strategies in the near future. However, this new entity also poses a therapeutic challenge as only limited data are currently available. The present article aims to provide an overview on our personal treatment concepts for advanced NETs with a focus on tumours of gastroenteropancreatic origin.

Treatment of Advanced Gastro-Entero-Pancreatic Neuro-Endocrine Tumors: A Systematic Review and Network Meta-Analysis of Phase III Randomized Controlled Trials

“…Several new therapies have been approved to treat well-differentiated advanced gastro-entero-pancreatic neuroendocrine neoplasms (GEP–NENs) in the last twenty years [ 1 ]. European Neuro-Endocrine Tumor Society (ENETS) and North American Neuro-Endocrine Tumor Society (NANETS) guidelines [ 2 , 3 , 4 ] recommend somatostatin analogs (SSAs) alone as first-line therapy.…”

Myeloid and T-Cell Microenvironment Immune Features Identify Two Prognostic Sub-Groups in High-Grade Gastroenteropancreatic Neuroendocrine Neoplasms

“…Overall, cases in cluster 1 showed more myeloid infiltrates, lymphoid T cell, HLA antigens and inhibitory receptors and ligands in the stroma compared to cluster 2 (Figure 3, Supplementary Table S2). Specifically, a significant increase in score estimated for myeloid Arginase S (mean 5.95 (3)(4)(5)(6)(7)(8)(9)(10)(11)(12) vs. 3.87 (0-9), p = 0.002), CD33 S (mean 3.90 (1-9) vs. 1.57 (0-4), p < 0.0001) and CD163 S (mean 5.64 (3-12) vs. 3.87 (2-6), p = 0.008) were observed in cluster 1. Moreover, CD66 S showed an increase (mean 1.77 (0-6) vs. 0.96 (0-3) p = 0.11), but without statistical differences.…”

“…Accurate diagnosis of these diseases is critical for correct prognosis and clinical management. High-grade G3 NET and NEC need a complex therapeutic approach due to a lack of clinical data and low response to treatments; to date, there are no consensus guidelines for the management of these rare and aggressive neoplasms [3][4][5]. Moreover, NECs are often diagnosed at a later stage and treated with platinum-etoposide chemotherapy with fractional efficacy [6][7][8].…”

Role of FGF System in Neuroendocrine Neoplasms: Potential Therapeutic Applications

“…Receptor tyrosine kinases are a subclass of tyrosine kinases with a relevant role in several cellular processes including proliferation, differentiation, motility and metabolism. Dysregulation of these receptors plays a relevant role in neoplastic development and progression for several tumors, including NENs ( 6 , 7 ).…”