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Gastroenteropancreatic neuroendocrine tumor

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
[Lutetium-177-DOTA(0),Tyr(3)]octreotate (177 Lu-DOTATATE) is a radiolabeled somatostatin analog that has been approved by the U.S. Food and Drug Administration 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 (PRRT) involves more planning, coordination, concomitant medication administration (anti-emetic medications and amino acids) and direct patient care...
August 3, 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
We evaluated health-related quality of life (HRQoL) in patients with metastatic gastroenteropancreatic neuroendocrine tumors (GEPNET) over the course of first peptide receptor radionuclide therapy (PRRT) to first restaging, and compared scores with general population (GP) norms. Methods: We used data from routine HRQoL monitoring with the European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire-Core 30. Patients received 4-6 cycles of 177 Lu-DOTATATE or 90 Y-DOTATOC. To be eligible for analysis, patients had to have at least one HRQoL assessment before PRRT and one after treatment completion...
July 24, 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
Nicole Panarelli, Kathrin Tyryshkin, Justin Wong, Adrianna Majewski, Xiaojing Yang, Theresa Scognamiglio, Michelle Kang Kim, Kimberley Bogardus, Thomas Tuschl, Yao-Tseng Chen, Neil Renwick
Gastroenteropancreatic neuroendocrine tumors (GEP-NETs) can be challenging to evaluate histologically. microRNAs (miRNAs) are small RNA molecules that often are excellent biomarkers due to their abundance, cell-type- and disease-stage specificity, and stability. To evaluate miRNAs as adjunct tissue markers for classifying and grading well-differentiated GEP-NETs, we generated and compared miRNA expression profiles from four pathological types of GEP-NETs. Using quantitative barcoded small RNA sequencing and state-of-the-art sequence annotation, we generated comprehensive miRNA expression profiles from archived pancreatic, ileal, appendiceal, and rectal NETs...
July 18, 2018: Endocrine-related Cancer
Inbal Uri, Simona Grozinsky-Glasberg
Background: Neuroendocrine tumors (NETs) are rare neoplasms, with an estimated annual incidence of ~ 6.9/100,000. NETs arise throughout the body from cells of the diffuse endocrine system. More than half originate from endocrine cells of the gastrointestinal tract and the pancreas, thus being referred to as gastroenteropancreatic NETs (GEP NETs). The only treatment that offers a cure is surgery, however most patients are diagnosed with metastatic disease, and curative surgery is usually not an option...
2018: Clinical Diabetes and Endocrinology
Monika Wagner, Dima Samaha, Jesus Cuervo, Harshila Patel, Marta Martinez, William M O'Neil, Paula Jimenez-Fonseca
INTRODUCTION: Unresectable, well-differentiated nonfunctioning gastroenteropancreatic neuroendocrine tumors (GEP-NETs) can be monitored (watchful waiting, WW) or treated with systemic therapy such as somatostatin analogues (SSAs) to delay progression. We applied a reflective multicriteria decision analysis (MCDA) shared-decision framework (previously developed for the USA) to explore what matters to Spanish patients and clinicians considering GEP-NET treatment options. METHODS: The EVIDEM-derived framework was updated and adapted to the Spanish context...
July 9, 2018: Advances in Therapy
Nadine Zimmermann, Juliana Knief, Tim Kacprowski, Pamela Lazar-Karsten, Tobias Keck, Franck Billmann, Sebastian Schmid, Kim Luley, Hendrik Lehnert, Georg Brabant, Christoph Thorns
The incidence of neuroendocrine neoplasias (NEN) continues to increase. Since the primary tumor cannot be diagnosed in some cases of metastatic disease, new biomarkers are clearly needed to find the most probable site of origin. Tissue samples from 79 patients were analyzed and microRNA profiles were generated from a total of 76 primary tumors, 31 lymph node and 14 solid organ metastases. NEN metastases were associated with elevated levels of miR-30a-5p, miR-210, miR-339-3p, miR-345 and miR-660. Three microRNAs showed a strong correlation between proliferation index and metastatic disease in general (miR-150, miR-21 and miR-660)...
June 19, 2018: Oncotarget
Franziska Briest, Yawen Wang, Ruza Arsenic, Sefer Elezkurtaj, Erika Berg, Sonja Greshake, Adrian C Lock, Dieter Hörsch, Christian N Arnold, Michael Hummel, Britta Siegmund, Patricia Grabowski
BACKGROUND/AIM: Gastroenteropancreatic neuroendocrine neoplasms (GEP-NENs) are rare and heterogeneous tumors. Therapeutic targets remain to be identified and apart from the proliferation marker Ki-67, useful prognostic markers are rare. Mitotic proteins, such as forkheadbox protein M1 (FOXM1), survivin and aurora kinases, play a role in GEP-NEN progression. In this study, immunohistochemistry was used to analyze how this protein network is expressed in different subgroups of GEP-NENs and determine potential expression patterns that could be useful as tumor markers...
July 2018: Anticancer Research
Anna Yordanova, Marcel M Wicharz, Karin Mayer, Peter Brossart, Maria A Gonzalez-Carmona, Christian P Strassburg, Rolf Fimmers, Markus Essler, Hojjat Ahmadzadehfar
PURPOSE: Although somatostatin analogues (SSA) and peptide receptor radionuclide therapy (PRRT) are validated therapies in patients with advanced gastroenteropancreatic neuroendocrine tumors (GEP-NETs), it remains unclear whether SSA combined with PRRT or as maintenance therapy can provide prolonged survival compared to patients treated with PRRT alone. In this retrospective study, we aimed to investigate whether there is a survival benefit to adding SSA to PRRT as a combination therapy and/or maintenance therapy...
June 27, 2018: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
Erik S Mittra
OBJECTIVE: The purposes of this article are to increase understanding of the concepts of theranostics and peptide receptor radionuclide therapy (PRRT) as they apply to neuroendocrine tumors (NETs); review the key 1, 2, and 3 clinical trial data leading to the approval of 177 Lu-tetraazacyclododecanetetraacetic acid-octreotide (177 Lu-DOTATATE); and foster understanding of the practical aspects and future directions of PRRT for NETs. CONCLUSION: In January 2018, 177 Lu-DOTATATE therapy was approved in the United States (previously approved in Europe in September 2017) for adult patients with somatostatin receptor-positive gastroenteropancreatic neuroendocrine tumors, including those of the foregut, midgut, and hindgut...
August 2018: AJR. American Journal of Roentgenology
Yuhong Wang, Yuanjia Chen, Xiaoxing Li, Wanming Hu, Yu Zhang, Luohai Chen, Minhu Chen, Jie Chen
BACKGROUND: The neuronal intermediate filament alpha-internexin (α-internexin) is a cytoskeleton protein which is involved in the tumor initiation and progression. In this study, we examined the expression and prognosis value of α-internexin in gastroenteropancreatic neuroendocrine neoplasms (GEP-NENs). METHODS: α-internexin was detected with immunohistochemical staining in 286 tumor specimens from patients with GEP-NENs. Methylation status of α-internexin was evaluated by bisulfite genomic sequencing...
June 26, 2018: BMC Cancer
(no author information available yet)
OncoTreat identified master regulators in gastroenteropancreatic neuroendocrine tumors (GEP-NET).
June 22, 2018: Cancer Discovery
Mariano J Alvarez, Prem S Subramaniam, Laura H Tang, Adina Grunn, Mahalaxmi Aburi, Gabrielle Rieckhof, Elena V Komissarova, Elizabeth A Hagan, Lisa Bodei, Paul A Clemons, Filemon S Dela Cruz, Deepti Dhall, Daniel Diolaiti, Douglas A Fraker, Afshin Ghavami, Daniel Kaemmerer, Charles Karan, Mark Kidd, Kyoung M Kim, Hee C Kim, Lakshmi P Kunju, Ülo Langel, Zhong Li, Jeeyun Lee, Hai Li, Virginia LiVolsi, Roswitha Pfragner, Allison R Rainey, Ronald B Realubit, Helen Remotti, Jakob Regberg, Robert Roses, Anil Rustgi, Antonia R Sepulveda, Stefano Serra, Chanjuan Shi, Xiaopu Yuan, Massimo Barberis, Roberto Bergamaschi, Arul M Chinnaiyan, Tony Detre, Shereen Ezzat, Andrea Frilling, Merten Hommann, Dirk Jaeger, Michelle K Kim, Beatrice S Knudsen, Andrew L Kung, Emer Leahy, David C Metz, Jeffrey W Milsom, Young S Park, Diane Reidy-Lagunes, Stuart Schreiber, Kay Washington, Bertram Wiedenmann, Irvin Modlin, Andrea Califano
We introduce and validate a new precision oncology framework for the systematic prioritization of drugs targeting mechanistic tumor dependencies in individual patients. Compounds are prioritized on the basis of their ability to invert the concerted activity of master regulator proteins that mechanistically regulate tumor cell state, as assessed from systematic drug perturbation assays. We validated the approach on a cohort of 212 gastroenteropancreatic neuroendocrine tumors (GEP-NETs), a rare malignancy originating in the pancreas and gastrointestinal tract...
June 18, 2018: Nature Genetics
Yanji Luo, Jie Chen, Bingqi Shen, Meng Wang, Huasong Cai, Ling Xu, Luohai Chen, Minhu Chen, Zi-Ping Li, Shi-Ting Feng
OBJECTIVE: To identify a reliable early indicator of deriving progression-free survival (PFS) benefit in patients with advanced gastroenteropancreatic neuroendocrine tumors (GEP-NETs) treated with octreotide long-acting repeatable (LAR). METHODS: We investigated the images of 50 patients with well-differentiated advanced GEP-NETs treated with LAR octreotide and underwent baseline and follow-up thoracic, abdominal, and pelvic computed tomography. Receiver-operating characteristic (ROC) analysis and the Kaplan-Meier method were used to identify the optimal threshold to distinguish between those with and without significant improvement of PFS...
June 6, 2018: European Radiology
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