• Circulating markers
• functioning neuroendocrine neoplasms
• gastro-entero-pancreatic neuroendocrine tumors
• neuroendocrine
• specific markers

• Humans
• Neuroendocrine Tumors/diagnosis
• Pancreatic Neoplasms

• Humans
• Middle Aged
• Neuroendocrine Tumors/surgery
• Neuroendocrine Tumors/pathology
• Insulinoma/pathology
• Gastrinoma
• Pancreatic Neoplasms/surgery
• Somatostatinoma

Peptide receptor radionuclide therapy (PRRT) using radionuclide-labeled somatostatin analogues is based on the overexpression of somatostatin receptors on neuroendocrine tumors and is shown to have a good safety profile and efficacy in different types of metastatic neuroendocrine tumors. As this therapy is usually not curative, most patients experience disease progression after initial PRRT. In these cases, retreatment with PRRT, also called salvage PRRT, can be a treatment option, but little is known about the efficacy and possible risk factors. In this retrospective study that included 32 patients, we found that the size of the largest lesion is a significant predictor of disease progression after salvage PRRT. This risk factor is easy to obtain and can help identify patients who may benefit from intensified follow-up strategies.

(1) Background: retreatment with radionuclide-labeled somatostatin analogues following disease progression after initial treatment cycles is often referred to as salvage peptide receptor radionuclide therapy (salvage PRRT). Salvage PRRT is shown to have a favorable safety profile in patients with metastatic neuroendocrine tumors (NETs), but numerous questions about the efficacy and prognostic or predictive factors remain to be answered. The purpose of this study was to evaluate two parameters that have shown prognostic significance in progression-free survival (PFS) in initial PRRT treatment, namely the size of the largest lesion (LLS) and the De Ritis ratio (aspartate aminotransferase (AST)/alanine aminotransferase (ALT)), as prognostic factors in the context of salvage PRRT. In addition, the PFS after initial PRRT was evaluated as a predictor of the PFS following salvage PRRT. (2) Methods: retrospective, monocentric analysis in 32 patients with NETs (gastroenteropancreatic, 23; unknown primary, 7; kidney, 1; lung, 1) and progression after initial PRRT undergoing retreatment with [¹⁷⁷Lu]Lu-DOTATOC. The prognostic values of LLS, the De Ritis ratio, and PFS after initial treatment cycles regarding PFS following salvage PRRT were evaluated with univariable and multivariable Cox regression. PFS was defined as the time from treatment start until tumor progression according to RECIST 1.1 criteria, death from any cause or start of a new treatment due to progression of cancer-related symptoms (namely carcinoid syndrome). (3) Results: progression after salvage PRRT was observed in 29 of 32 patients with median PFS of 10.8 months (95% confidence interval (CI), 8.0–15.9 months). A higher LLS (hazard ratio (HR): 1.03; p = 0.002) and a higher De Ritis ratio (HR: 2.64; p = 0.047) were associated with shorter PFS after salvage PRRT in univariable Cox regression. PFS after initial PRRT was not associated with PFS following salvage PRRT. In multivariable Cox regression, only LLS remained a significant predictor. (4) Conclusions: the size of the largest lesion is easy to obtain and might help identify patients at risk of early disease progression after salvage PRRT. Validation is required.

• Carcinoid syndrome
• Carcinoid tumor
• Gastroenteropancreatic tumor
• Neuroendocrine neoplasms

• Female
• Gastrointestinal Neoplasms/diagnosis
• Gastrointestinal Neoplasms/pathology
• Humans
• Male
• Neuroendocrine Tumors/diagnosis
• Neuroendocrine Tumors/pathology
• Pancreatic Neoplasms/diagnosis
• Pancreatic Neoplasms/pathology

• Neuroendocrine tumor
• PNET
• Pancreas
• Surgery

• Disease Management
• Humans
• Neuroendocrine Tumors/diagnosis
• Neuroendocrine Tumors/therapy
• Pancreas/diagnostic imaging
• Pancreatic Neoplasms/diagnosis
• Pancreatic Neoplasms/therapy
• Pancreaticoduodenectomy/methods
• Positron-Emission Tomography
• Tomography, X-Ray Computed

• P30 CA086862 NCI NIH HHS
• P50 CA174521 NCI NIH HHS
• T32 CA148062 NCI NIH HHS

Primary neuroendocrine tumors (NETs) in the presacral region are extremely rare, some of which are caused by other primary tumors or metastatic rectal carcinoids. Nevertheless, cases of NETs have been increasing in recent years. This report describes the first primary neuroendocrine tumor in the presacral region that was found at our hospital within the last five years.

The patient was identified as a 36-year-old woman with a presacral mass and pelvic floor pain. A digital rectal examination revealed a presacral mass with unclear margins and obvious tenderness. Magnetic resonance imaging (MRI) demonstrated a 57 mm × 29 mm presacral lump. An ultrasound-guided needle biopsy confirmed a well-differentiated neuroendocrine tumor. No other primary or metastatic tumors were found.

Comprehensive consideration of our case report and literature reported by others suggests that a conclusive diagnosis of NETs should be based on computed tomography/MRI and pathological examinations. The treatment of primary NETs in the presacral region mainly relies on surgical procedures with follow-up.

• Neuroendocrine tumor
• Presacral
• Biopsy
• Case report

• breast surgery
• neuroimaging
• neurooncology
• neurosurgery
• surgical oncology

• VIPoma
• gastrinoma
• glucagonoma
• insulinoma
• recurrence
• symptomatic

• Chromogranin A
• endoscopy
• gastroenteropancreatic neuroendocrine tumor
• ki-67 antigen
• mitosis
• synaptophysin

• Carcinoid
• Ectopic ACTH
• Functional
• GEP NEN
• Gastrinoma
• Gastroenteropancreatic
• Hormonally active
• Insulinoma
• Neuroendocrine neoplasm
• Syndrome
• VIP
• Whipple´s triad
• Zollinger ellison

• Gastrointestinal Neoplasms/diagnosis
• Gastrointestinal Neoplasms/metabolism
• Humans
• Neuroendocrine Tumors/diagnosis
• Neuroendocrine Tumors/metabolism
• Pancreatic Neoplasms/diagnosis

Our understanding of the biology, genetics, and natural history of neuroendocrine tumors (NETs) of the gastrointestinal tract and pancreas has improved considerably in the last several decades and the spectrum of available therapeutic options is rapidly expanding. The management of patients with metastatic low or intermediate grade NETs has been revolutionized by the development of new treatment strategies such as molecular targeting therapies with everolimus and sunitinib, somatostatin analogs, tryptophan hydroxylase inhibitors, and peptide receptor radionuclide therapy that can be used alone or as a multimodal approach with or without surgery. To further define and clarify the utility, appropriateness, and the sequence of the growing list of available therapies for this patient population will require more high level evidence; however, data from well-designed randomized phase III clinical trials is rapidly accumulating that will further stimulate development of new management strategies. It is therefore important to thoroughly review emerging evidence and report major findings in frequent updates, which will expand our knowledge and contribute to a better understanding, characterization, and management of advanced NETs.

Background Lanreotide is a long-acting somatostatin analog with demonstrated efficacy against enteropancreatic neuroendocrine tumor (NET) in the phase III (CLARINET) study. Materials and Methods In this single-arm study, Japanese patients with grade (G) 1/G2 NET received lanreotide (120 mg/4 weeks) for 48 weeks. Those who completed the study were enrolled in a long-term extension study. The primary endpoint was the clinical benefit rate (CBR) defined as a complete response, partial response (PR), or stable disease (SD) over 24-weeks. Secondary endpoints included progression-free survival (PFS), objective response rate (ORR), safety, and pharmacokinetics. Results Thirty-two patients were recruited at 10 sites. The full analysis set (FAS) comprised 28 patients. Primary tumors were located in pancreas (12 patients), foregut (non-pancreas, lung; 1), midgut (2), hindgut (8), and unknown (5). Four patients had gastrinoma of the functional NET, and 3 had multiple endocrine neoplasia type 1. In the FAS, 39.3% had progressive disease at baseline. The CBR at 24 weeks was 64.3% (95% confidence interval; CI: 44.1–81.4), and median PFS was 36.3 weeks (95% CI: 24.1–53.1). PR was confirmed in 1 patient at 60 weeks during the extension study (ORR: 3.6%). Frequent adverse events related to lanreotide included injection site induration (28.1%), faeces pale (18.8%), flatulence (12.5%), and diabetes mellitus (12.5%). Conclusions The efficacy and safety of lanreotide in this study indicated its usefulness as a treatment option for Japanese NET patients. Trial registration: JapicCTI-132,375, JapicCTI-142,698.

• Japanese
• Lanreotide
• Neuroendocrine tumor
• Phase II
• Somatostatin analog

Peptide drugs for antineoplastic therapies usually have low oral bioavailability and short in vivo half-lives, requiring less preferred delivery methods. Lanreotide depot is a sustained-release somatostatin analog (SSA) formulation produced via an innovative peptide self-assembly method. Lanreotide is approved in the USA and Europe to improve progression-free survival (PFS) in patients with unresectable gastroenteropancreatic neuroendocrine tumors (GEP-NETs) and also approved in Europe for symptom control in carcinoid syndrome associated with GEP-NETs. This review discusses how the distinct molecule and formulation of lanreotide depot provide advantages to patients and health care providers, as well as the most recent clinical evidence demonstrating the safety and efficacy of lanreotide depot in inhibiting tumor growth and controlling hormonal symptoms in GEP-NETs.

The lanreotide depot formulation confers a remarkable pharmacokinetic profile with no excipients, comprised only of lanreotide acetate and water. Of note, lanreotide depot constitutes an example for peptide self-assembly based formulations, providing insights that could help future development of sustained-release formulations of other antineoplastic peptides. Most patients with GEP-NETs will present with inoperable or incurable disease; thus, medical management for symptoms and tumor control plays a crucial role. Recent long-term clinical studies have demonstrated that lanreotide depot is well tolerated, prolongs PFS in GEP-NET patients, and significantly reduces symptoms related to carcinoid syndrome.

The unique depot formulation and delivery method of lanreotide confer advantages in the treatment of metastatic GEP-NETs, contributing to improvements in NET-related symptoms and PFS without reducing quality of life in this patient population.

• Depot preparations
• Drug formulation
• Lanreotide
• Neuroendocrine tumors

• Carcinoid
• Diagnostics
• Multimodal
• Neuroendocrine
• Therapy
• Tumor

Despite the considerable impact of neuroendocrine tumors (NETs) on patients’ daily lives, the journey of the patient with a NET has rarely been documented, with published data to date being limited to small qualitative studies. NETs are heterogeneous malignancies with nonspecific symptomology, leading to extensive health care use and diagnostic delays that affect survival. A large, international patient survey was conducted to increase understanding of the experience of the patient with a NET and identify unmet needs, with the aim of improving disease awareness and care worldwide.

An anonymous, self-reported survey was conducted (online or on paper) from February to May 2014, recruiting patients with NETs from > 12 countries as a collaboration between the International Neuroendocrine Cancer Alliance and Novartis Pharmaceuticals. Survey questions captured information on sociodemographics, clinical characteristics, NET diagnostic experience, disease impact/management, interaction with medical teams, NET knowledge/awareness, and sources of information. This article reports the most relevant findings on patient experience with NETs and the impact of NETs on health care system resources.

A total of 1,928 patients with NETs participated. A NET diagnosis had a substantially negative impact on patients’ personal and work lives. Patients reported delayed diagnosis and extensive NET-related health care resource use. Patients desired improvement in many aspects of NET care, including availability of a wider range of NET-specific treatment options, better access to NET experts or specialist centers, and a more knowledgeable, better-coordinated/-aligned NET medical team.

This global patient-reported survey demonstrates the considerable burden of NETs with regard to symptoms, work and daily life, and health care resource use, and highlights considerable unmet needs. Further intervention is required to improve the patient experience among those with NETs.

• Neuroendocrine neoplasm
• computed tomography (CT)
• detection
• magnetic resonance imaging (MRI)
• staging
• treatment response

• Cystic pancreatic neoplasms
• Cystic pancreatic neuroendocrine tumors
• Endoscopic ultrasound
• Fine-needle aspiration biopsy

• Pancreas
• neuroendocrine
• neuroendocrine tumor (NET)
• treatment

• 177Lu-DOTATATE
• Affinitor
• Everolimus
• Metastasis
• RAD001

• Biomarkers, Tumor/metabolism
• Chromogranin A/genetics
• Chromogranin A/metabolism
• Epigenomics
• Female
• Gastrointestinal Neoplasms/genetics
• Gastrointestinal Neoplasms/pathology
• Gene Expression Regulation, Neoplastic/genetics
• Germ-Line Mutation
• Humans
• Immunohistochemistry
• Male
• Neuroendocrine Tumors/genetics
• Neuroendocrine Tumors/pathology
• Phosphopyruvate Hydratase/genetics
• Phosphopyruvate Hydratase/metabolism
• Polymerase Chain Reaction
• Polymorphism, Single Nucleotide

• Adult
• Aged
• Aged, 80 and over
• Female
• Humans
• Incidence
• Intestinal Neoplasms/epidemiology
• Intestinal Neoplasms/pathology
• Male
• Middle Aged
• Neoplasm Metastasis
• Neuroendocrine Tumors/epidemiology
• Neuroendocrine Tumors/pathology
• Pancreatic Neoplasms/epidemiology
• Pancreatic Neoplasms/pathology
• Retrospective Studies
• Stomach Neoplasms/epidemiology
• Stomach Neoplasms/pathology

• Animals
• Carcinoma, Neuroendocrine/metabolism
• Connective Tissue Growth Factor/metabolism
• ErbB Receptors/metabolism
• Humans
• Signal Transduction/physiology
• Transforming Growth Factor alpha/metabolism
• Transforming Growth Factor beta/metabolism

• R01 DK080871 NIDDK NIH HHS
• DK080871 NIDDK NIH HHS

Pancreatic neuroendocrine tumors (PNETs) are rare neoplasms. They are clinically diverse and divided into functioning and nonfunctioning disease, depending on their ability to produce symptoms due to hormone production. Surgical resection is the only curative treatment and remains the cornerstone therapy for this patient group, even in patients with advanced disease. Over the last decade there has been a noticeable trend towards more aggressive surgery as well as more minimally invasive surgery in patients with PNETs. This has resulted in improved long-term survival in patients with locally advanced and metastatic disease treated aggressively, as well as shorter hospital stays and comparable long-term outcomes in patients with limited disease treated minimally invasively. There are still controversies related to issues of surgical treatment of PNETs, such as to what extent enucleation, lymph node sampling, and vascular reconstruction are beneficial for the oncologic outcome. Histopathologic tumor classification is of high clinical importance for treatment planning and prognostic evaluation of patients with PNETs. A constant challenge, which relates to the treatment of PNETs, is the lack of an internationally accepted histopathological classification system. This paper reviews current issues on the surgical treatment of sporadic PNETs with specific focus on surgical approaches and tumor classification.