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      SEOM clinical guidelines for the diagnosis and treatment of gastroenteropancreatic neuroendocrine neoplasms (GEP-NENs) 2014

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          Abstract

          GEP-NENs are a challenging family of tumors of growing incidence and varied clinical management and behavior. Diagnostic techniques have substantially improved over the past decades and significant advances have been achieved in the understanding of the molecular pathways governing tumor initiation and progression. This has already translated into relevant advances in the clinic. This guideline aims to provide practical recommendations for the diagnosis and treatment of GEP-NENs. Diagnostic workup, histological and staging classifications, and the different available therapeutic approaches, including surgery, liver-directed ablative therapies, peptide receptor radionuclide therapy, and systemic hormonal, cytotoxic or targeted therapy, are briefly discussed in this manuscript. Clinical presentation (performance status, comorbidities, tumor-derived symptoms and hormone syndrome in functioning tumors), histological features [tumor differentiation, proliferation rate (Ki-67), and expression of somatostatin receptors], disease localization and extent, and resectability of primary and metastatic disease, are all key issues that shall be taken into consideration to appropriately tailor therapeutic strategies and surveillance of these patients.

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          Most cited references16

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          Sunitinib malate for the treatment of pancreatic neuroendocrine tumors.

          The multitargeted tyrosine kinase inhibitor sunitinib has shown activity against pancreatic neuroendocrine tumors in preclinical models and phase 1 and 2 trials. We conducted a multinational, randomized, double-blind, placebo-controlled phase 3 trial of sunitinib in patients with advanced, well-differentiated pancreatic neuroendocrine tumors. All patients had Response Evaluation Criteria in Solid Tumors-defined disease progression documented within 12 months before baseline. A total of 171 patients were randomly assigned (in a 1:1 ratio) to receive best supportive care with either sunitinib at a dose of 37.5 mg per day or placebo. The primary end point was progression-free survival; secondary end points included the objective response rate, overall survival, and safety. The study was discontinued early, after the independent data and safety monitoring committee observed more serious adverse events and deaths in the placebo group as well as a difference in progression-free survival favoring sunitinib. Median progression-free survival was 11.4 months in the sunitinib group as compared with 5.5 months in the placebo group (hazard ratio for progression or death, 0.42; 95% confidence interval [CI], 0.26 to 0.66; P<0.001). A Cox proportional-hazards analysis of progression-free survival according to baseline characteristics favored sunitinib in all subgroups studied. The objective response rate was 9.3% in the sunitinib group versus 0% in the placebo group. At the data cutoff point, 9 deaths were reported in the sunitinib group (10%) versus 21 deaths in the placebo group (25%) (hazard ratio for death, 0.41; 95% CI, 0.19 to 0.89; P=0.02). The most frequent adverse events in the sunitinib group were diarrhea, nausea, vomiting, asthenia, and fatigue. Continuous daily administration of sunitinib at a dose of 37.5 mg improved progression-free survival, overall survival, and the objective response rate as compared with placebo among patients with advanced pancreatic neuroendocrine tumors. (Funded by Pfizer; ClinicalTrials.gov number, NCT00428597.).
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            Treatment with the radiolabeled somatostatin analog [177 Lu-DOTA 0,Tyr3]octreotate: toxicity, efficacy, and survival.

            Despite the fact that most gastroenteropancreatic neuroendocrine tumors (GEPNETs) are slow-growing, median overall survival (OS) in patients with liver metastases is 2 to 4 years. In metastatic disease, cytoreductive therapeutic options are limited. A relatively new therapy is peptide receptor radionuclide therapy with the radiolabeled somatostatin analog [(177)Lu-DOTA(0),Tyr(3)]octreotate. Here we report on the toxicity and efficacy of this treatment, performed in over 500 patients. Patients were treated up to a cumulative dose of 750 to 800 mCi (27.8-29.6 GBq), usually in four treatment cycles, with treatment intervals of 6 to 10 weeks. Toxicity analysis was done in 504 patients, and efficacy analysis in 310 patients. Any hematologic toxicity grade 3 or 4 occurred after 3.6% of administrations. Serious adverse events that were likely attributable to the treatment were myelodysplastic syndrome in three patients, and temporary, nonfatal, liver toxicity in two patients. Complete and partial tumor remissions occurred in 2% and 28% of 310 GEPNET patients, respectively. Minor tumor response (decrease in size > 25% and < 50%) occurred in 16%. Median time to progression was 40 months. Median OS from start of treatment was 46 months, median OS from diagnosis was 128 months. Compared with historical controls, there was a survival benefit of 40 to 72 months from diagnosis. Treatment with [(177)Lu-DOTA(0),Tyr(3)]octreotate has few adverse effects. Tumor response rates and progression-free survival compare favorably to the limited number of alternative treatment modalities. Compared with historical controls, there is a benefit in OS from time of diagnosis of several years.
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              The epidemiology of gastroenteropancreatic neuroendocrine tumors.

              In this article, updated analyses of the National Cancer Institute Surveillance, Epidemiology and End Results (SEER) registry (1973-2007) are presented and compared with epidemiologic GEP-NET data from Europe and Asia. Several studies have demonstrated a steadily increasing incidence of GEP-NETs, and this escalation is still ongoing (SEER data 2004-2007). The common primary GEP-NET sites exhibit unique epidemiologic profiles with distinct patterns of incidence, age at diagnosis, stage, and survival. Overall, GEP-NET survival has improved over the past 3 decades, although the outcome for poorly differentiated tumors remains dismal. Copyright © 2011 Elsevier Inc. All rights reserved.
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                Author and article information

                Contributors
                rgcarbonero@gmail.com
                Journal
                Clin Transl Oncol
                Clin Transl Oncol
                Clinical & Translational Oncology
                Springer Milan (Milan )
                1699-048X
                1699-3055
                3 September 2014
                3 September 2014
                2014
                : 16
                : 12
                : 1025-1034
                Affiliations
                [ ]Medical Oncology Department, Hospital Universitario Virgen del Rocio, Instituto de Biomedicina de Sevilla (IBIS) (Universidad de Sevilla, CSIC, HUVR), Center affiliated to the Red Temática de Investigación Cooperativa en Cancer (RTICC), Instituto Carlos III, Spanish Ministry of Science and Innovation, Av. Manuel Siurot, s/n, 41013 Seville, Spain
                [ ]Medical Oncology Department, Hospital Universitario Central de Asturias, Asturias, Spain
                [ ]Medical Oncology Department, Instituto Catalán de Oncología (ICO), Barcelona, Spain, Center affiliated to the Red Temática de Investigación Cooperativa en Cancer (RTICC), Instituto Carlos III, Spanish Ministry of Science and Innovation, Seville, Spain
                [ ]Faculty of Life Sciences, University of Manchester, Manchester, UK
                [ ]Department of Medical Oncology, The Christie NHS Foundation Trust, Manchester, UK
                [ ]Medical Oncology Department, Hospital Universitario Virgen de la Victoria y Hospital Regional Universitario, Málaga, Spain
                Article
                1214
                10.1007/s12094-014-1214-6
                4239790
                25183048
                2b4dc455-b81b-400b-8b3b-79c8064b59ae
                © Federación de Sociedades Españolas de Oncología (FESEO) 2014
                History
                : 5 August 2014
                : 6 August 2014
                Categories
                Clinical Guides in Oncology
                Custom metadata
                © Federación de Sociedades Españolas de Oncología (FESEO) 2014

                Oncology & Radiotherapy
                guidelines,neuroendocrine tumors,neuroendocrine neoplasms,enteropancreatic,diagnosis,therapy

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