New Developments in VHL-Associated Neuroendocrine Neoplasms.

Purpose Of Review: The purpose of this review is to outline the current knowledge on epidemiology, diagnosis and management of neuroendocrine neoplasms (NENs) that develop in the context of Von Hippel-Lindau (VHL) syndrome.

Recent Findings: Pancreatic NENs develop in 8-17% of VHL patients (vPNENs) and are mostly multi-focal, cystic and non-functioning. Surgical resection is recommended for vPNENS > 3 cm that exhibit higher metastatic potential or in tumors with short doubling time while in the 20% of cases with metastatic disease the HIF-2 A inhibitor belzutifan is considered a promising option.

Long-term persistence of glycemic dysregulation in patients with a history of pheochromocytoma/paraganglioma.

Context: Pheochromocytomas and paragangliomas (PPGLs) are rare endocrine tumors that frequently produce catecholamines. Catecholamine-induced cardiometabolic complications substantially contribute to increased morbidity and mortality in PPGL patients prior to surgical resection.

Objective: To determine whether markers of elevated cardiometabolic risk persist in patients following PPGL resection.

The diagnostic value of prolactin adjustment in bilateral inferior petrosal sinus sampling for differentiating Cushing's disease from the ectopic ACTH syndrome: a systematic review and meta-analysis.

Background: Adrenocorticotropin (ACTH)-dependent Cushing's syndrome can arise from a pituitary tumour (Cushing's disease) or an ectopic ACTH-secreting tumour, making precise differentiation essential for effective treatment. Bilateral inferior petrosal sinus sampling (BIPSS) is the gold standard for this differentiation, but false-negative results can limit its accuracy. Adding prolactin (PRL) measurement to BIPSS has been proposed to improve diagnostic precision.

High Prevalence of Sarcopenia in Patients with Newly Diagnosed Gastroenteropancreatic Neuroendocrine Tumours (GEP-NETs), but No Association with the Risk of Surgical Complications.

Sarcopenia is a muscle disease that occur across a lifetime. It is commonly described in the aging population but can occur earlier in life in patients with cancer. Previous studies demonstrated sarcopenia is highly prevalent in patients with gastroenteropancreatic neuroendocrine tumours (GEP-NETs).

Evolution of dosimetric parameters through PRRT and potential impact on clinical practice: data from the prospective phase II LUMEN study.

Background: Peptide receptor radionuclide therapy (PRRT) with [Lu]Lu-DOTA-TATE has emerged as a promising treatment for gastroenteropancreatic neuroendocrine tumours (GEP-NETs). Its treatment protocol is currently standardised for all patients, resulting in different patient outcomes. This study investigates the variability of tumours and organs-at-risk (kidneys and red marrow) dosimetric parameters across treatment cycles in patients with pancreatic and intestinal NETs.

Somatostatin receptor-linked α-particle therapy in neuroendocrine tumours.

The incidence and prevalence of neuroendocrine tumours (NETs) are on the rise, but to date, only complete surgical resection is curative. Among the various therapeutic options for metastatic disease, peptide receptor radionuclide therapy (PRRT), linking a radioactive moiety to an octreotide derivative, has been shown to be highly efficacious and a well-tolerated therapy, improving progression-free survival and prolonging overall survival. Nevertheless, complete responses are rare, and the current β-particle emitters have non-optimal radiobiological properties.

Neuroendocrine tumours and pregnancy: Real-world data from an European Neuroendocrine Tumour Centre of Excellence.

Neuroendocrine neoplasms (NENs) arise from the diffuse endocrine system and have been considered to be rare. However, the incidence and prevalence of these tumours have increased in recent years, and they are being seen in younger patients including women in the reproductive age group. Due to the paucity of data, diagnostic and therapeutic strategies in managing such tumours during pregnancy can be challenging to both treating physicians and patients.

Longitudinal Changes in Ki-67 Indices in Small-Intestinal Neuroendocrine Tumours and Their Impact on Survival.

Introduction: The purpose of this study was to evaluate longitudinal changes in Ki-67 indices of SI-NETs and assess the impact of these in overall survival (OS).

Methods: We screened 551 patients with SI-NETs diagnosed from 1993, through 2021, identified using the SI-NET databases from five European referral centres. Only patients with well-differentiated tumours and available baseline tumour samples and follow-up re-biopsies were included.

International consensus statement on the diagnosis and management of phaeochromocytoma and paraganglioma in children and adolescents.

Phaeochromocytomas and paragangliomas (PPGL) are rare neuroendocrine tumours that arise not only in adulthood but also in childhood and adolescence. Up to 70-80% of childhood PPGL are hereditary, accounting for a higher incidence of metastatic and/or multifocal PPGL in paediatric patients than in adult patients. Key differences in the tumour biology and management, together with rare disease incidence and therapeutic challenges in paediatric compared with adult patients, mandate close expert cross-disciplinary teamwork.

The Clinical Utility of the NETest in Patients with Small Intestinal Neuroendocrine Neoplasms (Si-NENs): A "Real-Life" Study.

Current biomarkers do not adequately predict the behaviour of neuroendocrine neoplasms (NENs). This study assessed the NETest, a multianalyte blood biomarker, in patients with small intestinal NENs (Si-NENs). We studied two patient groups: Group 1: metastatic Si-NENs ( = 102) and Group 2: post-operatively disease-free according to 68Ga-DOTATATE PET ( = 16).

Pre-clinical phaeochromocytoma and paraganglioma models: Cell lines, animal models, and a human primary culture model.

While the establishment of human phaeochromocytoma and paraganglioma (PPGL) cell lines has proven to be particularly difficult over several decades of research, there are other reliable pre-clinical PPGL models currently available. This review provides a summary of these models, together with our recently established personalised drug screening platform using patient-derived PPGL primary cultures. Such currently available PPGL models include murine and rat PPGL cell lines, of which only one cell line (PC12) is publicly accessible through a cell repository, and PPGL animal models, of which the patient-derived xenograft models are promising but complex to establish.

177 Lu-DOTATATE PRRT Safety and Organ-at-Risk Dosimetry in Patients With Gastroenteropancreatic Neuroendocrine Tumors : Data From the Prospective Phase 2 LUMEN Study.

Purpose: The aim of this study was to assess the association among toxicity, dosimetry of organs-at-risk, and disease progression in patients with gastroenteropancreatic neuroendocrine tumors (GEP-NETs) treated with 177 Lu-DOTATATE.

Patients And Methods: Thirty-seven patients with GEP-NETs underwent 177 Lu-DOTATATE peptide receptor radionuclide therapy (PRRT) in a single-arm, prospective, phase 2 study, where patients were followed up with blood tests, isotopic glomerular filtration rate (iGFR), and imaging examinations (CT/MRI and PET) every 6 months until disease progression. Adverse events (AEs) graded per CTCAEv4.

Synchronous neuroendocine liver metastases in comparison to primary pancreatic neuroendocrine tumors on MRI and SSR-PET/CT.

Background: The study aimed to compare and correlate morphological and functional parameters in pancreatic neuroendocrine tumors (pNET) and their synchronous liver metastases (NELM), while also assessing prognostic imaging parameters.

Methods: Patients with G1/G2 pNET and synchronous NELM underwent pretherapeutic abdominal MRI with DWI and 68Ga-DOTATATE/TOC PET/CT were included. ADC (mean, min), SNR_art and SNT_T2 (SNR on arterial phase and on T2) and SUV (max, mean) for three target NELM and pNET, as well as tumor-free liver and spleen (only in PET/CT) were measured.

Clinical impact of using [F]AlF-NOTA-octreotide PET/CT instead of [Ga]Ga-DOTA-SSA PET/CT: Secondary endpoint analysis of a multicenter, prospective trial.

[F]AlF-NOTA-octreotide ([F]AlF-OC) is a promising alternative for [Ga]Ga-DOTA-somatostatin analogs (SSAs) in positron emission tomography (PET) imaging of the somatostatin receptor (SSTR). Our aim is to assess changes in TNM staging and differences in patient management between [F]AlF-OC PET/CT and [Ga]Ga-DOTA-SSA PET/CT in the work-up of neuroendocrine tumor (NET) patients. Patients who underwent both [F]AlF-OC and [Ga]Ga-DOTA-TATE or [Ga]Ga-DOTA-NOC PET/CT in our multicenter study (Pauwels et al.

Endoscopic submucosal dissection for rectal neuroendocrine tumours: A multicentric retrospective study.

Introduction: Endoscopic Submucosal Dissection (ESD) has been reported as a feasible and effective treatment for Rectal Neuroendocrine Tumours (R-NETs). However, most of the experience on the topic comes from retrospective tertiary centre from Eastern Asia. Data on ESD for R-NETs in Western centres are lacking.

Clinical management of typical and atypical carcinoids/neuroendocrine tumors in ENETS centres of excellence (CoE): Survey from the ENETS lung NET task force.

Lung carcinoid tumours are neuroendocrine neoplasms originating from the bronchopulmonary tract's neuroendocrine cells, accounting for only 1%-3% of all lung cancers but 30% of all neuroendocrine tumours. The incidence of lung carcinoids, both typical and atypical, has been increasing over the years due to improved diagnostic methods and increased awareness among clinicians and pathologists. The most recent WHO classification includes a subgroup of lung carcinoids with atypical morphology and higher mitotic count and/or Ki67 labelling index.