Neuroendocrine Neoplasms of the Small Bowel and Pancreas

Abstract

The traditionally promulgated perspectives of neuroendocrine neoplasms (NEN) as rare, indolent tumours are blunt and have been outdated for the last 2 decades. Clear increments in their incidence over the past decades render them increasingly clinically relevant, and at initial diagnosis many present with nodal and/or distant metastases (notably hepatic). The molecular pathogenesis of these tumours is increasingly yet incompletely understood. Those arising from the small bowel (SB) or pancreas typically occur sporadically; the latter may occur within the context of hereditary tumour predisposition syndromes. NENs can also be associated with endocrinopathy of hormonal hypersecretion. Tangible advances in the development of novel biomarkers, functional imaging modalities and therapy are especially applicable to this sub-set of tumours. The management of SB and pancreatic neuroendocrine tumours (NET) may be challenging, and often comprises a multidisciplinary approach wherein surgical, medical, interventional radiological and radiotherapeu-tic modalities are implemented. This review provides a comprehensive overview of the epidemiology, pathophysiology, diagnosis and treatment of SB and pancreatic NETs. Moreover, we provide an outlook of the future in these tumour types which will include the development of precision oncology frameworks for individualised therapy, multi-analyte predictive biomarkers, artificial intelligence-derived clinical decision support tools and elucidation of the role of the microbiome in NEN development and clinical behaviour.According to SEER version 18, SBNEN and PanNEN incidences are currently estimated at 1.2 and 0.7 per 100,000, respectively [5]. The overall 20-year duration prevalence of all NEN is estimated at 171,321; SBNEN constituting 32,122 patients with 3-fold fewer PanNEN (10,707) [5]. Possible attributable factors for this increase evolving epidemiology include increased use of endoscopy and also improvements in the sensitivity of widely used imaging modalities, leading to increased detection of early-stage, asymptomatic disease [5].The median overall survival (OS) for NEN (irrespective of site and grade) is 9.3 years [5]. For SB (median OS: 14 years), this ranges from 70 months (advanced disease with distant metastases) to 170 months (localised disease) and from 30 months (Grade 3) to 160 months (Grade 1). For pancreas (median OS: 3.6 years): 21 months (advanced) to 235 months (localised disease) and from 15 months (Grade 3) to 140 months (Grade 1) [5].Multivariable analyses have identified that ethnicity, age, differentiation, stage and site all have statistically significant correlations with survival. In general, Caucasian ethnicity, age (< 50 years) and localised, well-differentiated NEN exhibit the best survival. SB tumour patients are approximately 1.5 times more likely to survive longer than those with PanNEN [19]. Many of these correlations are self-evident since they pertain to degree of malignancy, disease duration and patient performance status.OS (median 5-year) app...

Imaging and liquid biopsy in the prediction and evaluation of response to PRRT in neuroendocrine tumors: implications for patient management

“…A well-described advantage of early or late response assessment of SSTR-PET after PRRT is the early detection of new distant metastases resulting in predictive value for early diagnosis of therapy failure (unequivocal progression) [2,33,47].…”

“…Criteria for response assessment Molecular functional imaging of SSTR expression is not yet fully integrated into response criteria for NET-treatment [2] (Fig. 1).…”

“…The [ 18 F]F-FDG-PET response criteria in solid tumors (PERCIST) are not directly transferrable to NET disease [15]. Although recently standardized criteria for SSTR-PET imaging were presented [16], criteria for response assessment with molecular SSTR-PET still present an unmet need [2,5,17].…”

Frequency and Causes of False-Positive Elevated Plasma Concentrations of Fasting Gut Hormones in a Specialist Neuroendocrine Tumor Center

“…Neuroendocrine tumors (NETs) comprise a diverse set of neoplasms that can arise at various anatomical sites ( 1 ). NETs can present with diverse symptoms and many cases are also detected incidentally during investigations for unrelated medical conditions ( 2 ). Although many NETs are non-functional (i.e.…”

Peptide receptor radionuclide therapy controls inappropriate calcitriol secretion in a pancreatic neuro-endocrine tumor: a case report

“…Furthermore, up to 30-40% of the GEP-NETs are known to be functional (i.e. causing symptoms mediated by excessive hormone/peptide secretion) [16], and evidence is accumulating that PRRT is valuable in controlling these functional neuroendocrine tumor syndromes [17][18][19][20][21][22]. This case documents a rare finding of refractory hypercalcaemia of underlying malignancy due to a calcitriol-producing pancreatic neuroendocrine tumor, responding to peptide receptor radionuclide therapy (PRRT).…”