Diagnostic characteristics, treatment outcomes, and prognostic factors in glucagonomas.

Objective: Glucagonomas are rare islet cell tumours, accounting for 2% of such tumours, with an annual incidence of 0.01-0.1 per million.

[F]FDG Metabolic Tumor Volume as a Prognostic Marker in Neuroendocrine Neoplasm: A Multicenter Study.

[F]FDG PET/CT avidity predicts higher-grade disease and worse prognosis in patients with metastatic neuroendocrine neoplasm. However, there is less evidence regarding the role of [F]FDG-avid tumor volume in predicting prognosis. We planned to determine whether metabolic tumor volume (MTV) on [F]FDG PET/CT predicts prognosis in patients with advanced gastroenteropancreatic neuroendocrine neoplasm (GEPNEN).

Octreotide infusion pump in patients with functional neuroendocrine tumors and refractory hormonal syndrome.

Objective: To evaluate clinical outcomes, safety and survival measures of octreotide infusion pump (OIP) therapy in patients with metastatic neuroendocrine tumors (NETs) and refractory hormonal syndrome.

Design: A retrospective analysis was conducted using data from patients treated with OIP therapy at a single center.

Methods: Data on demographics, disease characteristics, biochemical profiles and treatment outcomes were extracted from electronic patient records.

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.

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).

[F]FDG PET/CT-Avid Discordant Volume as a Biomarker in Patients with Gastroenteropancreatic Neuroendocrine Neoplasms: A Multicenter Study.

[F]FDG PET/CT and [Ga]Ga-DOTATATE PET/CT are both used to predict tumor biology in neuroendocrine neoplasms. Although the presence of discordant ([F]FDG-avid/non-[Ga]Ga-DOTATATE-avid) disease predicts poor prognosis, the significance of the volume of such discordant disease remains undetermined. The aim of this study is to investigate discordant tumor volume as a potential biomarker in patients with advanced gastroenteropancreatic neuroendocrine neoplasms (GEPNENs).

Plasma or serum 5-hydroxyindoleacetic acid can be used interchangeably in patients with neuroendocrine tumours.

5-hydroxyindole acetic acid, a metabolite of serotonin, is used in the diagnosis and monitoring of patients with neuroendocrine tumours, in particular patients with small intestinal neuroendocrine tumours associated with the carcinoid syndrome. Analysis of 5-hydroxyindole acetic acid was commonly performed in urine, but blood-based assays are now becoming available. The objective of this study was to assess how 5-hydroxyindole acetic acid compares in plasma and serum as a biochemical marker of neuroendocrine tumours.

Dual [Ga]DOTATATE and [F]FDG PET/CT in patients with metastatic gastroenteropancreatic neuroendocrine neoplasms: a multicentre validation of the NETPET score.

Background: Gastroenteropancreatic neuroendocrine neoplasms (GEPNENs) are heterogeneous in clinical course, biology, and outcomes. The NETPET score predicts survival by scoring uptake on dual [Ga]DOTATATE and [F]FDG PET/CT scans. We aimed to validate previous single-centre findings in a multicentre, international study.

Diffuse idiopathic pulmonary neuroendocrine cell hyperplasia (DIPNECH): Prevalence, clinicopathological characteristics and survival outcome in a cohort of 311 patients with well-differentiated lung neuroendocrine tumours.

Introduction: Diffuse idiopathic pulmonary neuroendocrine cell hyperplasia (DIPNECH) is considered to be a rare condition associated with lung neuroendocrine tumours (NET), and its natural history is poorly described. We aimed to assess the prevalence and clinicopathologic characteristics of DIPNECH in the lung NET population, and to investigate predictors of time-to-progression (TTP) and overall survival (OS).

Methods: We retrospectively identified patients diagnosed with DIPNECH between April 2005 and December 2020.

Distinguishing Cushing's disease from the ectopic ACTH syndrome: Needles in a haystack or hiding in plain sight?

In the context of ACTH-dependent Cushing's syndrome, ectopic ACTH secretion from a neuroendocrine tumour is not uncommon, and needs to be carefully differentiated from pituitary-dependent Cushing's syndrome, Cushing's disease, in order to optimise therapy. Some cases may be quite obvious, while in others the diagnosis may be difficult to confirm and the source of ACTH problematic, as many clinical and biochemical tests may overlap with Cushing's disease. Imaging is essential, but needs to be interpreted in the light of both anatomical as well as functional imaging modalities.

Metastatic medullary thyroid carcinoma: a new way forward.

Medullary thyroid carcinoma (MTC) is a rare malignancy comprising 1-2% of all thyroid cancers in the United States. Approximately 20% of cases are familial, secondary to a germline RET mutation, while the remaining 80% are sporadic and also harbour a somatic RET mutation in more than half of all cases. Up to 15-20% of patients will present with distant metastatic disease, and retrospective series report a 10-year survival of 10-40% from time of first metastasis.

The Combined Interpretation of 68Ga-DOTATATE PET/CT and 18F-FDG PET/CT in Metastatic Gastroenteropancreatic Neuroendocrine Tumors: A Classification System With Prognostic Impact.

Purpose: Gastroenteropancreatic neuroendocrine neoplasms (GEP NEN) are widely heterogeneous in their biological behavior, and predicting prognosis and optimal treatment strategies can be challenging. 68Ga-DOTATATE PET/CT is a sensitive imaging modality for well-differentiated NEN and indicates a favorable prognosis, whereas 18F-FDG PET/CT avidity indicates disease that is potentially more aggressive. There has been emerging interest in the combined interpretation of 68Ga-DOTATATE and 18F-FDG PET and its prognostic significance.

The quality of clinical trials in neuroendocrine tumours; have we learnt from our mistakes? An evaluation of phase II and phase III clinical trials.

The quality and reporting of neuroendocrine tumour (NET) clinical trials has previously been found to be heterogeneous impairing trial interpretability. We aimed to perform an updated review of the quality of phase II/III clinical trials in NET to assess if trial design and reporting have improved since 2011. We performed a PubMed search for phase II/III trials evaluating systemic anticancer therapies or liver-directed therapies published between 2011 and 2018.

Metastatic Medullary Thyroid Cancer: The Role of 68Gallium-DOTA-Somatostatin Analogue PET/CT and Peptide Receptor Radionuclide Therapy.

Context: Metastatic medullary thyroid cancer (MTC) is a rare malignancy with minimal treatment options. Many, but not all, MTCs express somatostatin receptors.

Objective: Our aim was to explore the role of 68Ga-DOTA-somatostatin analogue (SSA) positron emission tomography (PET)/computed tomography (CT) in patients with metastatic MTC and to determine their eligibility for peptide receptor radionuclide therapy (PRRT).

High-Grade Gastroenteropancreatic Neuroendocrine Neoplasms and Improved Prognostic Stratification With the New World Health Organization 2019 Classification: A Validation Study From a Single-Institution Retrospective Analysis.

Objectives: There is a pressing need to develop clinical management pathways for grade 3 (G3) gastroenteropancreatic neuroendocrine neoplasms (GEP NEN).

Methods: We performed a retrospective study on patients with metastatic G3 GEP NEN. The relationship between baseline characteristics and progression-free survival and overall survival was analyzed using the Kaplan-Meier method.

Lu-DOTATATE in older patients with metastatic neuroendocrine tumours: safety, efficacy and health-related quality of life.

Purpose: The safety and efficacy of Lu-DOTATATE in older patients with advanced neuroendocrine tumours (NET) are not well understood.

Methods: Patients ≥70 years of age and treated with Lu-DOTATATE were included. Toxicity, health-related quality of life (HRQoL), objective response, progression-free survival (PFS) and overall survival (OS) were assessed.

High-dose Somatostatin Analogues for Progressive Neuroendocrine Tumours.

Neuroendocrine tumours are a heterogeneous group of neoplasms with a variety of treatment options, but studies suggest they should in most cases, if they are not curable surgically, be treated initially with monthly long-acting somatostatin analogues. New data recently published suggest that if patients show progression on the current analogues at the recommended doses, increasing the dose or frequency of these analogues may provide a further therapeutic effect, although proper randomised trials will be necessary to confirm this effect.

Understanding the Treatment Algorithm of Patients with Metastatic Pancreatic Neuroendocrine Neoplasms: A Single-Institution Retrospective Analysis Comparing Outcomes of Chemotherapy, Molecular Targeted Therapy, and Peptide Receptor Radionuclide Therapy in 255 Patients.

Background: The number of therapeutic options for patients with pancreatic neuroendocrine neoplasms (PNEN) has increased, but the optimal therapeutic algorithm has not been defined due to lack of randomised trials comparing different modalities.

Methods: We performed a retrospective study in patients with metastatic PNEN treated with ≥1 line of systemic therapy. The relationship between baseline characteristics, treatment type, and time to treatment failure (TTF), time to progression (TTP), and overall survival (OS) was analysed using the Kaplan-Meier method.

Should immunohistochemical expression of mismatch repair (MMR) proteins and microsatellite instability (MSI) analysis be routinely performed for poorly differentiated colorectal neuroendocrine carcinomas?

Summary: Colorectal poorly differentiated neuroendocrine carcinomas (NECs) are typically associated with poor outcomes. The mechanisms of their aggressiveness are still being investigated. Microsatellite instability (MSI) has recently been found in colorectal NECs showing aberrant methylation of the MLH1 gene and is associated with improved prognosis.

Cardiac Metastases in Patients with Neuroendocrine Tumours: Clinical Features, Therapy Outcomes, and Prognostic Implications.

Background: Cardiac metastases (CM) from neuroendocrine tumours (NET) are rare; however, with the introduction of new molecular imaging modalities, such as 68Ga-DOTATATE PET-CT for NET diagnosis and re-staging, they are now identified more frequently. This study presents a single-institution experience on the NET CM characteristics, management, and prognostic implications.

Methods: Between January 1998 and January 2020, 25 NET patients with CM were treated in our unit.

Predictors of antiproliferative effect of lanreotide autogel in advanced gastroenteropancreatic neuroendocrine neoplasms.

Purpose: The antiproliferative properties of lanreotide autogel (LAN) in gastroenteropancreatic neuroendocrine neoplasms (GEP NENs) were demonstrated in the CLARINET study. However, there is limited literature regarding factors that affect progression-free survival (PFS) in patients with GEP NENs treated with LAN.

Methods: We identified a total of 191 treatment-naive patients with advanced GEP NENs and positive SSTR uptake on imaging (Octreoscan or Gallium DOTATATE Positron Emission Tomography [GaPET]) who received first-line LAN monotherapy, albeit at various starting doses (60, 90 or 120 mg/month).

Peptide Receptor Radionuclide Therapy as a Novel Treatment for Metastatic and Invasive Phaeochromocytoma and Paraganglioma.

At present there is no clinical guideline or standardised protocol for the treatment of metastatic or invasive phaeochromocytoma and paraganglioma (collectively known as PPGL) due to the rarity of the disease and the lack of prospective studies or extended national databases. Prognosis is mainly determined by genetic predisposition, tumour burden, rate of disease progression, and location of metastases. For patients with progressive or symptomatic disease that is not amenable to surgery, there are various palliative treatment options available.

Unmet Medical Needs in Pulmonary Neuroendocrine (Carcinoid) Neoplasms.

Pulmonary carcinoids (PCs) display the common features of all well-differentiated neuroendocrine neoplasms (NEN) and are classified as low- and intermediate-grade malignant tumours (i.e., typical and atypical carcinoid, respectively).

FET PET in the evaluation of indeterminate brain lesions on MRI: Differentiating glioma from other non-neoplastic causes - A pilot study.

We aimed to determine the utility of FET PET in the management of indeterminate CNS lesions found on MRI. We performed a retrospective analysis of patients with FET PET at a single tertiary institution from 2011 to 2015. FET PET images were processed using usual methods and measurements taken including SUVmax, TBRmax, and analysis of dynamic series where available (Kipeak, Vdpeak, as well as tumor:background ratio for these variables).