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Gastroenteropancreatic neuroendocrine tumor

Ashwini Kalshetty, Anant Ramaswamy, Vikas Ostwal, Sandip Basu
BACKGROUND AND AIMS: Functioning and symptomatic disease resistant to conventional therapies constitutes a subset amongst neuroendocrine tumors (NETs) that are commonly considered for peptide receptor radionuclide therapy (PRRT). The aim of this study was to evaluate the efficacy of Lu-DOTATATE PRRT in this group with objective assessment criteria. MATERIALS AND METHODS: A total of 46 patients with refractory or progressive symptomatic GEP-NETs (previously treated at various stages with long-acting octreotide, chemotherapy, multikinase inhibitors, etc...
October 10, 2018: Nuclear Medicine Communications
Thomas Cuny, Wouter de Herder, Anne Barlier, Leo J Hofland
Gastroenteropancreatic neuroendocrine tumors (GEP-NETs) represent a group of heterogeneous tumors whose incidence increased over the past few years. Around half of patients already present with metastatic disease at the initial diagnosis. Despite extensive efforts, cytotoxic and targeted therapies have provided only limited efficacy for patients with metastatic GEP-NETs, mainly due to the development of a certain state of resistance. One factor contributing to both the failure of systemic therapies and the emergence of an aggressive tumor phenotype may be the tumor microenvironment (TME), comprising dynamic and adaptative assortment of extracellular matrix components and non-neoplastic cells, which surround the tumor niche...
November 1, 2018: Endocrine-related Cancer
Aura D Herrera-Martínez, Manuel D Gahete, Rafael Sánchez-Sánchez, Emilia Alors-Perez, Sergio Pedraza-Arevalo, Raquel Serrano-Blanch, Antonio J Martínez-Fuentes, Maria A Gálvez-Moreno, Justo P Castaño, Raúl M Luque
OBJECTIVES: The association between the presence and alterations of the components of the ghrelin system and the development and progression of neuroendocrine tumors (NETs) is still controversial and remains unclear. METHODS: Here, we systematically evaluated the expression levels (by quantitative-PCR) of key ghrelin system components of in gastroenteropancreatic (GEP)-NETs, as compared to non-tumor adjacent (NTA; n = 42) and normal tissues (NT; n = 14)...
October 8, 2018: Clinical and Translational Gastroenterology
Mauro Cives, Jonathan R Strosberg
Neuroendocrine tumors (NETs) are heterogeneous malignancies arising from the diffuse neuroendocrine system. They frequently originate in the gastroenteropancreatic (GEP) tract and the bronchopulmonary tree, and their incidence has steadily increased in the last 3 decades. Fundamental biologic and genomic differences underlie the clinical heterogeneity of NETs, and distinct molecular features characterize NETs of different grades and different primary sites. Although surgery remains the cornerstone of treatment for localized tumors, systemic treatment options for patients with metastatic NETs have expanded considerably...
October 8, 2018: CA: a Cancer Journal for Clinicians
Nelli Roininen, Sari Takala, Kirsi-Maria Haapasaari, Arja Jukkola-Vuorinen, Johanna Mattson, Päivi Heikkilä, Peeter Karihtala
OBJECTIVES: Due to the rarity of breast carcinomas with neuroendocrine features (NEBC), the knowledge on their biology is very limited but the identification of their biology and prognostic factors is essential to evaluate both pathogenesis and possible targeted treatment options. We assessed the expression of the well-characterized prognostic factors of gastroenteropancreatic neuroendocrine tumors (GEP-NET) in NEBC. METHODS: We assessed the immunohistochemical expression of neuron-specific enolase (NSE), thymidylate synthase (TS), p27, CD56, menin, and somatostatin receptor type 2A (SSTR-2A) in a series of 36 NEBC and 45 invasive ductal carcinomas (IDC)...
October 3, 2018: Oncology
Jean E Boucher, Robin Sommers
Neuroendocrine tumors (NETs), including gastroenteropancreatic NETs, or GEP-NETs, are heterogenous tumors that arise from diffuse neuroendocrine cells and other organs, such as the lung, ovary, and thyroid. Lutetium Lu 177 dotatate (Lutathera®) is a newly approved targeted therapy for patients with advanced GEP-NETs. Patients treated with octreotide long-acting release may be candidates for this second-line therapy. This article discusses lutetium Lu 177 dotatate therapy administration and patient care considerations...
October 1, 2018: Clinical Journal of Oncology Nursing
Hwajeong Lee, Zhiyan Fu, Brandon H Koo, Christine E Sheehan, Gloria Q Young, Jingmei Lin, Deepa T Patil, Zhaohai Yang
BACKGROUND: The expression profile of immunohistochemical markers of origin in poorly differentiated neuroendocrine carcinoma (PDNEC) is not well studied. MATERIALS AND METHODS: Seventy-four PDNECs from gastroenteropancreatic (GEP) organs and the lung, including 48 large cell NEC (LCNEC) and 26 small cell carcinomas (SmCC), were subject to immunohistochemical staining for CDX2, TTF1 and ISL1. The staining intensity (1 to 3) and percentage of positive tumor cells [0 (negative), 1 (<50%) and 2 (≥50%)] were assessed...
September 13, 2018: Annals of Diagnostic Pathology
Nitya Raj, Nicola Fazio, Jonathan Strosberg
In recent years, there have been important scientific advances in the biologic characterization of neuroendocrine neoplasms and in their treatment. This review will describe these scientific advances, the evolving systemic treatment approaches, and important topics to be addressed in future research.
May 23, 2018: American Society of Clinical Oncology Educational Book
Eric Liu, Scott Paulson, Anthony Gulati, Jon Freudman, William Grosh, Sheldon Kafer, Prasana C Wickremesinghe, Ronald R Salem, Lisa Bodei
BACKGROUND: The clinical relevance of molecular biomarkers in oncology management has been recognized in breast and lung cancers. We evaluated a blood-based multigene assay for management of neuroendocrine tumors (NETs) in a real-world study (U.S. registry NCT02270567). Diagnostic accuracy and relationship to clinical disease status in two cohorts (treated and watch-and-wait) were evaluated. MATERIALS AND METHODS: Patients with NETs ( n = 100) were followed for 6-12 months...
August 29, 2018: Oncologist
Ana P Santos, Ana C Santos, Clara Castro, Luís Raposo, Sofia S Pereira, Isabel Torres, Rui Henrique, Helena Cardoso, Mariana P Monteiro
The determinants for gastroenteropancreatic neuroendocrine tumors (GEP-NET) recent burden are matters of debate. Obesity and metabolic syndrome (MetS) are well established risks for several cancers even though no link with GEP-NETs was yet established. Our aim in this study was to investigate whether well-differentiated GEP-NETs were associated with obesity and MetS. Patients with well-differentiated GEP-NETs ( n = 96) were cross-matched for age, gender, and district of residence with a control group ( n = 96) derived from the general population in a case-control study...
August 27, 2018: Cancers
Levent Dizdar, Thomas A Werner, Jasmin C Drusenheimer, Birte Möhlendick, Katharina Raba, Inga Boeck, Martin Anlauf, Matthias Schott, Wolfgang Göring, Irene Esposito, Nikolas H Stoecklein, Wolfram T Knoefel, Andreas Krieg
To determine the role of BRAFV600E mutation and MAPK signaling as well as the effects of BRAF and MEK directed therapy in gastroenteropancreatic neuroendocrine neoplasia (GEP-NEN), with a focus on highly aggressive gastroenteropancreatic neuroendocrine carcinoma (GEP-NEC). Using Sanger sequencing of BRAF exon 15 we determined the frequency of BRAFV600E mutations in 71 primary GEP-NENs. MEK phosphorylation was examined by immunohistochemistry in corresponding tissue samples. To evaluate the biological relevance of BRAFV600E mutation and MAPK signaling in GEP-NECs, effects of a pharmacological BRAF and MEK inhibition were analyzed in NEC cell lines both in vitro and in vivo...
August 24, 2018: International Journal of Cancer. Journal International du Cancer
Andrew E Hendifar, Deepti Dhall, Jonathan R Strosberg
Neuroendocrine neoplasms (NEN) most commonly arise in the gastroenteropancreatic system and lungs. The incidence of NEN is increasing globally, with improved diagnostic techniques identifying patients with early-stage disease. The number of approved therapies for the treatment of advanced disease has grown substantially in the past decade. The treatment algorithm for advanced NEN is evolving from one that is directed by primary site-specific classification to one that is directed by biologic classification, as evidenced by overlapping systemic treatments across the primary tumor sites...
August 13, 2018: Oncologist
Halfdan Sorbye, Eric Baudin, Aurel Perren
High-grade gastroenteropancreatic neuroendocrine neoplasms are well-differentiated neuroendocrine tumors or poorly differentiated small/large cell neuroendocrine carcinoma. Distinguishing these entities relies on different genetic backgrounds and resulting different biology. The new classification creates several problems. Almost all clinical treatment data on neuroendocrine neoplasms do not stratify between well and poorly differentiated, providing insufficient help in treatment selection. Treatment of gastroenteropancreatic neuroendocrine neoplasms should separate between well-differentiated neuroendocrine tumors and neuroendocrine carcinoma, and depends on primary tumor site, stage, proliferation rate, and clinical course...
September 2018: Endocrinology and Metabolism Clinics of North America
Changyin Feng, Qiaoling Zheng, Yinghong Yang, Meifang Xu, Yuane Lian, Jianping Huang, Yiting Jiang
PURPOSE: Apolipoprotein B mRNA editing enzyme catalytic polypeptide-like 3B (APOBEC3B) is known as a source of mutations in multiple cancers. Gastroenteropancreatic neuroendocrine neoplasms (GEP-NENs) are a group of heterogeneous tumors. However, the expression and significance of APOBEC3B in GEP-NENs remains unclear. MATERIALS AND METHODS: A total of 158 cases of GEP-NENs, including 78 cases of biopsy or endoscopic submucosal dissection resection specimens and 83 cases of surgical resection specimens were collected in this study...
August 8, 2018: Applied Immunohistochemistry & Molecular Morphology: AIMM
Sally C Lau, Omar Abdel-Rahman, Winson Y Cheung
Gastroenteropancreatic (GEP) neuroendocrine tumors (NETs) represent a heterogeneous group of tumors that is associated with an indolent course. Octreotide has a positive effect on disease stabilization in well-differentiated midgut NETs, but a meaningful survival analysis was not possible due to insufficient events. Higher doses of octreotide long-acting release (LAR) are often used in clinical practice for control of carcinoid symptoms and our objective was to determine if dose of octreotide correlates with survival...
August 4, 2018: Medical Oncology
Amanda Abbott, Christopher G Sakellis, Eric Andersen, Yuji Kuzuhara, Lauren Gilbert, Kelly Boyle, Matthew H Kulke, Jennifer A Chan, Heather A Jacene, Annick D Van den Abbeele
177 Lu-DOTATATE is a radiolabeled somatostatin analog that has been approved by the U.S. Food and Drug Administration (FDA) for the treatment of somatostatin receptor-positive gastroenteropancreatic neuroendocrine tumors in adults. Radionuclide therapies have been administered for many years within nuclear medicine departments in North America. However, in comparison to other radiotherapies, 177 Lu-DOTATATE peptide receptor radionuclide therapy involves more planning, coordination, concomitant medication administration (antiemetic medications and amino acids), and direct patient care...
September 2018: Journal of Nuclear Medicine Technology
Simron Singh, Lesley Moody, David L Chan, David C Metz, Jonathan Strosberg, Timothy Asmis, Dale L Bailey, Emily Bergsland, Kari Brendtro, Richard Carroll, Sean Cleary, Michelle Kim, Grace Kong, Calvin Law, Ben Lawrence, Alexander McEwan, Caitlin McGregor, Michael Michael, Janice Pasieka, Nick Pavlakis, Rodney Pommier, Michael Soulen, David Wyld, Eva Segelov
There is no consensus on optimal follow-up for completely resected gastroenteropancreatic neuroendocrine tumors. Published guidelines for follow-up are complex and emphasize closer surveillance in the first 3 years after resection. Neuroendocrine tumors have a different pattern and timescale of recurrence, and thus require more practical and tailored follow-up. The Commonwealth Neuroendocrine Tumour Collaboration convened an international multidisciplinary expert panel, in collaboration with the North American Neuroendocrine Tumor Society, to create patient-centered follow-up recommendations for completely resected gastroenteropancreatic neuroendocrine tumors...
July 26, 2018: JAMA Oncology
Caroline Martini, Sabine Buxbaum, Margarida Rodrigues, Bernhard Nilica, Lorenza Scarpa, Bernhard Holzner, Irene Virgolini, Eva-Maria Gamper
In patients with metastatic gastroenteropancreatic neuroendocrine tumors (NETs), we evaluated health-related quality of life (HRQoL) from the first peptide receptor radionuclide therapy (PRRT) to the first restaging and compared the scores with general-population (GP) norms. Methods: The data were from routine HRQoL monitoring using the core quality-of-life questionnaire of the European Organization for Research and Treatment of Cancer (EORTC QLQ-C30). Patients received 4-6 cycles of 177 Lu-DOTATATE or 90 Y-DOTATOC...
October 2018: Journal of Nuclear Medicine: Official Publication, Society of Nuclear Medicine
Miklós Tóth
Gastroenteropancreatic neuroendocrine tumors have been increasing in frequency over the past decades. The goal of this paper is to provide a concise overview of various treatment options based mainly on consensus guidelines. The only curative therapy for these tumors is timely surgical intervention including endoscopic removal of early stage neuroendocrine tumors. Since at initial diagnosis about half of these patients present with advanced disease, systemic drug and non-drug treatments are discussed in details...
July 20, 2018: Magyar Onkologia
Levent Dizdar, Jasmin Drusenheimer, Thomas Artur Werner, Birte Möhlendick, Sina Christin Schütte, Irene Esposito, Timm Filler, Wolfram Trudo Knoefel, Andreas Krieg
<br>Background: Gastroenteropancreatic neuroendocrine carcinomas (GEP-NECs) are biologically aggressive tumors, associated with a very poor survival. Due to their rarity, our knowledge on GEP-NEC biology is very limited. The aim of this study was to establish a GEP-NEC cell line model that might contribute to a better understanding of this rare malignant disease to further develop novel therapeutic approaches in preclinical studies. METHODS: Small cell neuroendocrine cancer cell line NEC-DUE3 was derived from a lymph node metastasis of a neuroendocrine carcinoma (NEC) located at the anal canal...
July 19, 2018: Neuroendocrinology
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