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      Guidelines for the management of gastroenteropancreatic neuroendocrine (including carcinoid) tumours (NETs)

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          Abstract

          These guidelines update previous guidance published in 2005. They have been revised by a group who are members of the UK and Ireland Neuroendocrine Tumour Society with endorsement from the clinical committees of the British Society of Gastroenterology, the Society for Endocrinology, the Association of Surgeons of Great Britain and Ireland (and its Surgical Specialty Associations), the British Society of Gastrointestinal and Abdominal Radiology and others. The authorship represents leaders of the various groups in the UK and Ireland Neuroendocrine Tumour Society, but a large amount of work has been carried out by other specialists, many of whom attended a guidelines conference in May 2009. We have attempted to represent this work in the acknowledgements section. Over the past few years, there have been advances in the management of neuroendocrine tumours, which have included clearer characterisation, more specific and therapeutically relevant diagnosis, and improved treatments. However, there remain few randomised trials in the field and the disease is uncommon, hence all evidence must be considered weak in comparison with other more common cancers.

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          The European Organization for Research and Treatment of Cancer QLQ-C30: a quality-of-life instrument for use in international clinical trials in oncology.

          In 1986, the European Organization for Research and Treatment of Cancer (EORTC) initiated a research program to develop an integrated, modular approach for evaluating the quality of life of patients participating in international clinical trials. We report here the results of an international field study of the practicality, reliability, and validity of the EORTC QLQ-C30, the current core questionnaire. The QLQ-C30 incorporates nine multi-item scales: five functional scales (physical, role, cognitive, emotional, and social); three symptom scales (fatigue, pain, and nausea and vomiting); and a global health and quality-of-life scale. Several single-item symptom measures are also included. The questionnaire was administered before treatment and once during treatment to 305 patients with nonresectable lung cancer from centers in 13 countries. Clinical variables assessed included disease stage, weight loss, performance status, and treatment toxicity. The average time required to complete the questionnaire was approximately 11 minutes, and most patients required no assistance. The data supported the hypothesized scale structure of the questionnaire with the exception of role functioning (work and household activities), which was also the only multi-item scale that failed to meet the minimal standards for reliability (Cronbach's alpha coefficient > or = .70) either before or during treatment. Validity was shown by three findings. First, while all interscale correlations were statistically significant, the correlation was moderate, indicating that the scales were assessing distinct components of the quality-of-life construct. Second, most of the functional and symptom measures discriminated clearly between patients differing in clinical status as defined by the Eastern Cooperative Oncology Group performance status scale, weight loss, and treatment toxicity. Third, there were statistically significant changes, in the expected direction, in physical and role functioning, global quality of life, fatigue, and nausea and vomiting, for patients whose performance status had improved or worsened during treatment. The reliability and validity of the questionnaire were highly consistent across the three language-cultural groups studied: patients from English-speaking countries, Northern Europe, and Southern Europe. These results support the EORTC QLQ-C30 as a reliable and valid measure of the quality of life of cancer patients in multicultural clinical research settings. Work is ongoing to examine the performance of the questionnaire among more heterogenous patient samples and in phase II and phase III clinical trials.
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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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              One hundred years after "carcinoid": epidemiology of and prognostic factors for neuroendocrine tumors in 35,825 cases in the United States.

              PURPOSE Neuroendocrine tumors (NETs) are considered rare tumors and can produce a variety of hormones. In this study, we examined the epidemiology of and prognostic factors for NETs, because a thorough examination of neither had previously been performed. METHODS The Surveillance, Epidemiology, and End Results (SEER) Program registries were searched to identify NET cases from 1973 to 2004. Associated population data were used for incidence and prevalence analyses. Results We identified 35,618 patients with NETs. We observed a significant increase in the reported annual age-adjusted incidence of NETs from 1973 (1.09/100,000) to 2004 (5.25/100,000). Using the SEER 9 registry data, we estimated the 29-year limited-duration prevalence of NETs on January 1, 2004, to be 9,263. Also, the estimated 29-year limited-duration prevalence in the United States on that date was 103,312 cases (35/100,000). The most common primary tumor site varied by race, with the lung being the most common in white patients, and the rectum being the most common in Asian/Pacific Islander, American Indian/Alaskan Native, and African American patients. Additionally, survival duration varied by histologic grade. In multivariate analysis of patients with well-differentiated to moderately differentiated NETs, disease stage, primary tumor site, histologic grade, sex, race, age, and year of diagnosis were predictors of outcome (P < .001). CONCLUSION We observed increased reported incidence of NETs and increased survival durations over time, suggesting that NETs are more prevalent than previously reported. Clinicians need to be become familiar with the natural history and patterns of disease progression, which are characteristic of these tumors.
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                Author and article information

                Journal
                Gut
                gut
                gutjnl
                Gut
                BMJ Group (BMA House, Tavistock Square, London, WC1H 9JR )
                0017-5749
                1468-3288
                3 November 2011
                January 2012
                3 November 2011
                : 61
                : 1
                : 6-32
                Affiliations
                [1 ]Basingstoke and North Hampshire Hospital, Basingstoke, UK
                [2 ]Department of Gastroenterology, County Durham and Darlington Foundation Trust, Darlington, UK
                [3 ]Peptide Laboratory, Royal Victoria Hospital, Belfast, UK
                [4 ]Department of Clinical Pharmacology, University of Sheffield, Sheffield, UK
                [5 ]Department of Radiology, Southampton General Hospital, Southampton, UK
                [6 ]Department of Gastroenterology, University College London, London, UK
                [7 ]Department of Oncology, Addenbrookes Hospital, Cambridge University Hospitals NHS Foundation Trust, Cambridge, UK
                [8 ]Department of Cardiology, Royal Free Hospital, London, UK
                [9 ]Department of Gastroenterology, University Hospitals of Morecambe Bay Foundation Trust, Barrow-in-Furness, UK
                [10 ]Nuclear Medicine, Kings College London, London, UK
                [11 ]Department of Oncology, University College London, London, UK
                [12 ]Department of Endocrinology, University of Sheffield, Sheffield, UK
                [13 ]Department of Surgery, University of Liverpool, Liverpool, UK
                [14 ]Department of Oncology, Beatson Centre, Glasgow, UK
                [15 ]Department of Radiology, Queen Mary's University, London, UK
                [16 ]Department of Oncology, University of Leicester, Leicester, UK
                [17 ]Academic Department of Endocrinology, Diabetes and Metabolism, Oxford University, Oxford, UK
                [18 ]Department of Gastroenterology, Royal Free Hospital, London, UK
                [19 ]Department of Medical Oncology, The Christie Hospital NHS Foundation Trust, Manchester, UK
                [20 ]Department of Histopathology, St James's University Hospital, Leeds, UK
                Author notes
                Correspondence to Dr John K Ramage, Basingstoke and North Hampshire Hospital, Aldermaston Road, Basingstoke RG24 9NA, UK; john.ramage@ 123456bnhft.nhs.uk
                Article
                gutjnl-2011-300831
                10.1136/gutjnl-2011-300831
                3280861
                22052063
                0f2665b4-d0fe-43d2-b52e-d46256c7435c
                © 2011, Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions.

                This is an open-access article distributed under the terms of the Creative Commons Attribution Non-commercial License, which permits use, distribution, and reproduction in any medium, provided the original work is properly cited, the use is non commercial and is otherwise in compliance with the license. See: http://creativecommons.org/licenses/by-nc/2.0/ and http://creativecommons.org/licenses/by-nc/2.0/legalcode.

                History
                : 12 August 2011
                : 19 September 2011
                Categories
                Guidelines
                1506

                Gastroenterology & Hepatology
                diarrhoea,decision analysis,gallbladder cancer,salmonella,clinical decision-making,bilary duct carcinoma,endocrine tumours,sepsis,pancreatic tumours,pancreatic endocrine tumour,pancreatic pathology,neuroendocrine tumours,neuroendocrine cells,pancreatitis,histopathology,intestinal obstruction,infective colitis,cancer,peptide receptors,pancreatic cancer

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