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.

Selective Internal Radiotherapy in Liver Tumors: Early Promise Yet to be Fulfilled.

Selective intra-arterial radiotherapy (SIRT) is a technique which has evolved over the past 30 years. In present this is primarily used to treat primary and secondary tumors in the liver. The technique normally depends on the delivery of a therapeutic radiopharmaceutical or radiolabeled particulate via a radiologically placed intra-arterial catheter in the hepatic artery.

Dosimetry and pharmacokinetics of [Lu]Lu-satoreotide tetraxetan in patients with progressive neuroendocrine tumours.

Purpose: To evaluate the dosimetry and pharmacokinetics of the novel radiolabelled somatostatin receptor antagonist [Lu]Lu-satoreotide tetraxetan in patients with advanced neuroendocrine tumours (NETs).

Methods: This study was part of a phase I/II trial of [Lu]Lu-satoreotide tetraxetan, administered at a median cumulative activity of 13.0 GBq over three planned cycles (median activity/cycle: 4.

[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).

A phase I/II study of the safety and efficacy of [Lu]Lu-satoreotide tetraxetan in advanced somatostatin receptor-positive neuroendocrine tumours.

Purpose: We present the results of an open-label, phase I/II study evaluating the safety and efficacy of the novel somatostatin receptor (SSTR) antagonist [Lu]Lu-satoreotide tetraxetan in 40 patients with previously treated, progressive neuroendocrine tumours (NETs), in which dosimetry was used to guide maximum administered activity.

Methods: This study was conducted in two parts. Part A consisted of 15 patients who completed three cycles of [Lu]Lu-satoreotide tetraxetan at a fixed administered activity and peptide amount per cycle (4.

Safety and Efficacy of 177 Lu-DOTATATE in Neuroendocrine Tumor Patients With Extensive Bone Disease.

Aim: The aim of this study was to assess the efficacy and safety of 177 Lu-DOTATATE in patients with neuroendocrine tumors (NETs) and extensive bone metastases, that is, more than 50% of the skeleton involved.

Method: A single-center retrospective analysis was performed in 30 patients (13 women and 17 men, mean age, 60 years; range, 35-77 years) undergoing 177 Lu-DOTATATE therapy. Patients had progressive metastatic NETs with extensive skeletal metastases (>50% skeletal involvement seen on baseline 68 Ga-DOTATATE PET/CT).

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.

Single centre retrospective review of outcome of Lu-DOTATATE peptide receptor radionuclide therapy in the treatment of progressive metastatic neuroendocrine tumours: Survival, toxicity, and prognostic factors.

The aim of this study was to evaluate the efficacy and safety of Lu-DOTATATE therapy in advanced metastatic disease. A retrospective analysis of 395 patients (180 female, 215 males, mean age 62) with progressive metastatic neuroendocrine tumours (NETs) who were treated with Lu-DOTATATE was performed. Overall, 115 patients had less than four cycles and 280 completed four cycles of treatment.

Optimisation of radioligand therapy in neuroendocrine tumours: Current and evolving evidence.

Treatment of neuroendocrine tumours (NETs) with radioligand therapy (RLT) for example, Lu-DOTATATE is generally well-tolerated and prolongs time to progression in most patients. However, approximately 20% of patients are nonresponders. In addition, complete responses are rare (<5% of patients), and durable responses beyond 3-4 years are uncommon.

Insulinoma: a quarter century of dietary control.

Summary: Insulinomas are rare pancreatic neuroendocrine neoplasms (NENs) that are typically sporadic and solitary, with the majority being <2 cm in diameter at diagnosis. The median duration of symptoms before diagnosis is variable; however, this is usually in the region of 12-18 months. We report on an insulinoma diagnosed some 25 years following initial symptoms, having by that stage attained a diameter of 4 cm.

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.

Efficacy and safety of Lu‑DOTATATE in patients with advanced pancreatic neuroendocrine tumours: data from the NETTER-R international, retrospective study.

Purpose: NETTER-R aimed to determine the efficacy, safety and tolerability of Lu-DOTATATE in patients with progressive, advanced pancreatic neuroendocrine tumours (panNETs) using retrospective real-world data from multiple sites.

Methods: This international study retrospectively included patients with panNETs treated with Lu-DOTATATE. The primary endpoint was progression-free survival (PFS) by Response Evaluation Criteria in Solid Tumors version 1.

Safety of Peptide Receptor Radionuclide Therapy with Lu-DOTATATE in Neuroendocrine Tumor Patients with Chronic Kidney Disease.

Our purpose was to assess the efficacy and safety of Lu-DOTATATE in neuroendocrine tumor patients with reduced renal function. A single-center retrospective analysis was performed on 33 patients with an estimated glomerular filtration rate (eGFR) of less than 60 mL/min/1.73 m Of these, 26 had chronic kidney disease (CKD) stage 3a (eGFR, 45-60 mL/min/1.

Treatment of neuroendocrine tumours with Lu-peptide receptor radionuclide therapy: Challenging clinical scenarios and their management.

Peptide receptor radionuclide therapy (PRRT) for the treatment of patients with neuroendocrine tumours is usually well tolerated, with selection based on existing guidelines. However, there are various scenarios where the risk-benefit analysis of PRRT needs to be evaluated to limit any complications associated with PRRT. This review looks at 11 key scenarios where the risk-benefit of PRRT needs to be closely evaluated.

Prognostic stratification for patients with neuroendocrine tumours receiving 177Lu-Dotatate.

177Lu-Dotatate is increasingly used in patients with advanced neuroendocrine tumour (NET). However, few prognostic markers are available to stratify progression-free survival (PFS) of patients who received 177Lu-Dotatate. Clinicopathological data including baseline circulating biomarkers of patients with advanced NET who received 177Lu-Dotatate were routinely collected and were retrospectively analysed.

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.

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.

Efficacy and tolerability of peptide receptor radionuclide therapy (PRRT) in advanced metastatic bronchial neuroendocrine tumours (NETs).

Introduction: Peptide receptor radionuclide therapy (PRRT) has been proven to be effective in gastro-entero-pancreatic neuroendocrine tumours (NETs) using Yttrium (Y)- or Lutetium (Lu)-based somatostatin peptides, with Lu-DOTATATE recently licensed. There is less published evidence of PRRT in metastatic bronchial NETs.

Objective: The aim of this study was to evaluate the efficacy, safety and toxicity of PRRT in patients with bronchial NETs, to expand the evidence base in this rare type of tumour.

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.

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.

Antiproliferative Effect of Above-Label Doses of Somatostatin Analogs for the Management of Gastroenteropancreatic Neuroendocrine Tumors.

Background: Above-label doses of somatostatin analogs (SSAs) are increasingly utilized in the management of inoperable/metastatic gastroenteropancreatic neuroendocrine tumors (GEP-NETs), progressing on standard 4-weekly regimens.

Objective: To evaluate the antiproliferative effect of 3-weekly SSA administration in a retrospective GEP-NET cohort.

Methods: Patients with advanced GEP-NET, treated with long-acting release (LAR) octreotide 30 mg or lanreotide Autogel 120 mg at a 3-weekly interval, after disease progression on standard 4-weekly doses, were retrospectively identified.

Safety, tolerability and clinical implementation of 'ready-to-use' gallium-DOTA0-Tyr3-octreotide (Ga-DOTATOC) (SomaKIT TOC) for injection in patients diagnosed with gastroenteropancreatic neuroendocrine tumours (GEP-NETs).

Background: Ga-DOTA0-Tyr3-octreotide (Ga-DOTATOC) positron emission tomography-CT (PET-CT) has superior diagnostic performance compared to the licensed tracer OctreoScan single photon emission CT-CT in patients with gastroenteropancreatic neuroendocrine tumours (GEP-NETs). A new preparation of Ga-DOTATOC using a new 'ready-to-use' Ga-DOTATOC formulation for injection has been developed (Ga-DOTATOC (SomaKIT TOC)).

Objectives: This study aimed to assess the safety and tolerability of Ga-DOTATOC (SomaKIT TOC) and evaluate the feasibility and robustness of implementing it in a NET clinical imaging service.

The impact of Ga-68 DOTATATE PET/CT imaging on management of patients with paragangliomas.

Objective: Paragangliomas are rare tumours of neural crest origin that express high levels of somatostatin receptor. Ga-68 DOTATATE PET/CT is a widely accepted method for imaging of neuroendocrine tumours. This study was performed to review a Ga-68 DOTATATE PET/CT patient database and to establish the impact of the modality on patient treatment.

Orbital metastases from neuroendocrine neoplasms: clinical implications and outcomes.

Purpose: Neuroendocrine neoplasms (NENs) may rarely metastasise to the orbit. Published data on epidemiology, incidence and preferred treatment is limited. We present the largest cohort of symptomatic and asymptomatic NEN patients with orbital metastases and data on epidemiological parameters, symptoms as well as diagnostic/treatment modalities used.

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).