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Xavier M Keutgen, Erik Schadde, Rodney F Pommier, Thorvardur R Halfdanarson, James R Howe, Electron Kebebew
Over 50% of patients with gastroenteropancreatic neuroendocrine tumors (GEP-NETs) have stage IV disease at presentation and the most likely organ to be affected by metastases is the liver. Hepatic involvement and hepatic tumor burden is a key prognostic factor affecting survival of these patients and 80% eventually die of liver failure due to tumor dissemination within the liver. This commentary explores the efficacy and limitations of systemic treatments in patients with GEP-NETs and liver metastases. Landmark randomized trials using systemic therapies including sandostatin (PROMID), lanreotide (CLARINET), everolimus (RADIANT 3 and 4), sunitinib and Peptide Receptor Radionuclide Therapy (NETTER-1) have not shown efficacy in reducing liver tumor burden in patients with stage IV GEP-NETs with liver metastases as outlined in this review...
October 11, 2018: Seminars in Oncology
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
W A van der Zwan, T Brabander, B L R Kam, J J M Teunissen, R A Feelders, J Hofland, E P Krenning, W W de Herder
PURPOSE: Therapy with [177 Lu-DOTA,Tyr3 ]octreotate is effective in patients with grade I/II metastasized and/or inoperable bronchial neuroendocrine tumour (NET) or gastroenteropancreatic NET (GEP-NET). In this study, we investigated the efficacy and safety of salvage treatment with [177 Lu-DOTA,Tyr3 ]octreotate. METHODS: Patients with progressive bronchial NET or GEP-NET were selected for re-(re)treatment if they had benefited from initial peptide receptor radionuclide therapy (I-PRRT) with a minimal progression-free survival (PFS) of 18 months...
September 28, 2018: European Journal of Nuclear Medicine and Molecular Imaging
Aura D Herrera-Martínez, Sergio Pedraza-Arevalo, Fernando L-López, Manuel D Gahete, María A Gálvez-Moreno, Justo P Castaño, Raúl M Luque
Background: Biguanides and statins have been reported to exert beneficial effects on various cancer types. However, their precise effects and underlying molecular mechanisms are still poorly understood. Materials and Methods: We analyzed the relation between metabolic-syndrome, i.e., presence of type-2 diabetes (T2DM), hyperlipidemia and their treatment, with histological, epidemiological, and prognosis variables in two patient cohorts with neuroendocrine-tumors [NETs: lung-carcinoids (LCs; n=81) and gastro-entero-pancreatic (GEP-NET; n=100)]...
September 27, 2018: Journal of Clinical Endocrinology and Metabolism
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
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
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
Andrea Palermo, Ettore Capoluongo, Rossella Del Toro, Silvia Manfrini, Paolo Pozzilli, Daria Maggi, Giuseppe Defeudis, Francesco Pantano, Roberto Coppola, Francesco Maria Di Matteo, Marco Raffaelli, Paola Concolino, Alberto Falchetti
CONTEXT: Clinical phenotype variability in MEN1 syndrome exists and evidence for an established genotype-phenotype is lacking. However, a higher aggressiveness of MEN1-associated gastro-entero-pancreatic (GEP) (neuro)endocrine tumours (NETs) tumours has been reported when MEN1 gene truncating mutations are detected. We found a novel germline truncating mutation of MEN1 gene at exon 10 in a subject with an aggressive clinical behavior of GEP-NETs. Successively, other two mutant-affected familial members have been identified...
September 2018: Hormones: International Journal of Endocrinology and Metabolism
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
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
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-NET), it remains unclear whether SSA combined with PRRT or as maintenance therapy can provide prolonged survival compared with 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...
October 1, 2018: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
Nader Hirmas, Raya Jadaan, Akram Al-Ibraheem
Purpose and Methods: Patients with inoperable and metastasized neuroendocrine tumors (NETs), particularly those with grades 1 and 2, usually receive treatment with somatostatin analogues (SSAs). Peptide receptor radionuclide therapy (PRRT) has gained momentum over the past two decades in patients who progress on SSAs. 177Lu-DOTATATE is currently the most widely used radiopeptide for PRRT. We reviewed the recent evidence on PRRT and the treatment of gastroentero-pancreatic neuroendocrine tumors (GEP-NETs)...
June 2018: Nuclear Medicine and Molecular Imaging
(no author information available yet)
OncoTreat identified master regulators in gastroenteropancreatic neuroendocrine tumors (GEP-NET).
August 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...
July 2018: Nature Genetics
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