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Ashley K Clift Department of Surgery and Cancer, Imperial College London, London, UK

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Oskar Kornasiewicz Department of Surgery and Cancer, Imperial College London, London, UK
Department of Surgery, Warsaw Medical University, Warsaw, Poland

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Panagiotis Drymousis Department of Surgery and Cancer, Imperial College London, London, UK

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Omar Faiz Department of Surgery, St Mark’s Hospital, London, UK

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Harpreet S Wasan Department of Surgery and Cancer, Imperial College London, London, UK

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James M Kinross Department of Surgery and Cancer, Imperial College London, London, UK

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Thomas Cecil Peritoneal Malignancy Unit, Basingstoke and North Hampshire Hospital, Basingstoke, UK

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Andrea Frilling Department of Surgery and Cancer, Imperial College London, London, UK

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Goblet cell carcinomas (GCC) are a rare, aggressive sub-type of appendiceal tumours with neuroendocrine features, and controversy exists with regards to therapeutic strategy. We undertook a retrospective review of GCC patients surgically treated at two tertiary referral centres. Clinical and histopathological data were extracted from a prospectively maintained database. Survival analyses utilised Kaplan–Meier methodology. Twenty-one patients were identified (9 females). Median age at diagnosis was 55 years (range 32–77). There were 3, 6 and 9 grade 1, 2 and 3 tumours, respectively. One, 10, 5 and 5 patients had stage I, II, III and IV disease at diagnosis, respectively. There were 8, 10 and 3 Tang class A, B and C tumours, respectively. Index operation was appendectomy (n = 12), right hemicolectomy (n = 6) or resections including appendix/right colon, omentum and the gynaecological system (n = 3). Eight patients underwent completion right hemicolectomy. Surgery for recurrence included small bowel resection (n = 2), debulking with peritonectomy and heated intraperitoneal chemotherapy, and hysterectomy and bilateral salpingo-oophorectomy (all n = 1). Median follow-up was 30 months (range 2.5–123). One-, 3- and 5-year OS was 79.4, 60 and 60%, respectively. Mean OS (1-, 3-, and 5-year OS) for Tang class A, B and C tumours were 73.1 months (85.7, 85.7, 51.4%), 83.7 months (all 66.7%) and 28.5 months (66.7, 66.7%, not reached), respectively. Chromogranin A/B and 68Ga-DOTATATE PET/CT were not useful in follow-up, but CEA, CA 19-9, CA 125 and 18F-FDG PET/CT identified tumour recurrence. GCC must be clearly discriminated from relatively indolent appendiceal neuroendocrine neoplasms. 18F-FDG PET/CT and CEA/CA19-9/CA 125 are useful in detecting recurrence of GCC.

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Ashley K Clift Department of Surgery and Cancer, Imperial College London, London, UK

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Omar Faiz Department of Surgery, St Mark’s Hospital, London, UK

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Robert Goldin Centre for Pathology, Imperial College London, London, UK

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John Martin Department of Gastroenterology, Imperial College London, London, UK

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Harpreet Wasan Department of Surgery and Cancer, Imperial College London, London, UK

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Marc-Olaf Liedke Department of Surgery, Westkuesten Klinikum Heide, Heide, Germany

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Erik Schloericke Department of Surgery, Westkuesten Klinikum Heide, Heide, Germany

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Anna Malczewska Department of Surgery and Cancer, Imperial College London, London, UK
Department of Pathophysiology and Endocrinology, Medical University of Silesia, Katowice, Poland

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Guido Rindi Institute of Anatomic Pathology, Universita Cattolica del Sacro Cuore, Rome, Italy

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Mark Kidd Wren Laboratories, Branford, Connecticut, USA

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Irvin M Modlin Emeritus Professor Gastrointestinal Surgery, School of Medicine, Yale University, New Haven, Connecticut, USA

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Andrea Frilling Department of Surgery and Cancer, Imperial College London, London, UK

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Neuroendocrine tumours (NET) are clinically challenging due to their unpredictable behaviour. Nomograms, grading and staging systems are predictive tools with multiple roles in clinical practice, including patient prognostication. The NET nomogram allocates scores for various clinicopathological parameters, calculating percentage estimates for 5- and 10-year disease-specific survival of patients with small bowel (SB) NET. We evaluated the clinical utility of three prognostic systems in 70 SB NET patients: the NET nomogram, the World Health Organisation (WHO)/European Neuroendocrine Tumour Society (ENETS) grading system and the American Joint Commission on Cancer (AJCC)/Union Internationale Contre le Cancer (UICC) TNM staging method. Using Kaplan–Meier methodology, neither the WHO/ENETS grade (P = 0.6) nor the AJCC/UICC stage (P = 0.276) systems demonstrated significant differences in patient survival in the cohort. The NET nomogram was well calibrated to our data set, displaying favourable prediction accuracy. Harrel’s C-index for the nomogram (a measure of predictive power) was 0.65, suggesting good prediction ability. On Kaplan–Meier analyses, there were significant differences in patient survival when stratified into nomogram score-based risk groups: low-, medium- and high-risk tumours were associated with median estimated survivals of 156, 129 and 112 months, respectively (P = 0.031). Our data suggest that a multivariable analysis-based NET nomogram may be clinically useful for patient survival prediction. This study identifies the limitations of the NET nomogram and the imperfections of other currently used single or binary parameter methodologies for assessing neuroendocrine disease prognosis. The future addition of other variables to the NET nomogram will likely amplify the accuracy of this personalised tool.

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Logan Mills Institute of Liver Studies, King’s College Hospital, London, UK

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Panagiotis Drymousis Department of Surgery and Cancer, Imperial College, London, UK

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Yogesh Vashist Department of General, Visceral and Thoracic Surgery, University Medical Center, Hamburg-Eppendorf, Hamburg, Germany

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Christoph Burdelski Department of General, Visceral and Thoracic Surgery, University Medical Center, Hamburg-Eppendorf, Hamburg, Germany

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Andreas Prachalias Department of Surgery, King’s College Hospital, London, UK

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Parthi Srinivasan Department of Surgery, King’s College Hospital, London, UK

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Krishna Menon Department of Surgery, King’s College Hospital, London, UK

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Corina Cotoi Department of Histopathology, King’s College Hospital, London, UK

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Saboor Khan Department of Surgery, University Hospitals Coventry and Warwickshire, Coventry, UK

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Judith Cave Department of Oncology, University Hospital, Southampton, UK

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Thomas Armstrong Department of Surgery, University Hospital, Southampton, UK

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Martin O Weickert Department of Endocrinology, University Hospitals Coventry and Warwickshire, Coventry, UK

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Jakob Izbicki Department of General, Visceral and Thoracic Surgery, University Medical Center, Hamburg-Eppendorf, Hamburg, Germany

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Joerg Schrader Departments of Gastroenterology and Department of General, Visceral and Thoracic Surgery, University Medical Center Hamburg-Eppendorf, Hamburg, Germany

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Andreja Frilling Department of Surgery and Cancer, Imperial College, London, UK

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John K Ramage Institute of Liver Studies, King’s College Hospital, London, UK

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Raj Srirajaskanthan Institute of Liver Studies, King’s College Hospital, London, UK

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Small non-functioning pancreatic NETs (pNETs) ≤2 cm can pose a management dilemma in terms of surveillance or resection. There is evidence to suggest that a surveillance approach can be considered since there are no significant radiological changes observed in lesions during long-term follow-up. However, other studies have suggested loco-regional spread can be present in ≤2 cm pNETs. The aim of this study was to characterise the prevalence of malignant features and identify any useful predictive variables in a surgically resected cohort of pNETs. 418 patients with pNETs were identified from 5 NET centres. Of these 227 were included for main analysis of tumour characteristics. Mean age of patients was 57 years, 47% were female. The median follow-up was 48.2 months. Malignant features were identified in 38% of ≤2 cm pNETs. ROC analysis showed that the current cut-off of 20 mm had a sensitivity of 84% for malignancy. The rate of malignant features is in keeping with other surgical series and challenges the belief that small pNETs have a low malignant potential. This study does not support a 20 mm size cut-off as being a solitary safe parameter to exclude malignancy in pNETs.

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Kjell Oberg Uppsala University, Uppsala, Sweden

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Eric Krenning Erasmus Medical Center, Rotterdam, Netherlands

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Anders Sundin Uppsala University, Uppsala, Sweden

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Lisa Bodei Memorial Sloan Kettering Cancer Center, New York, New York, USA

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Mark Kidd Wren Laboratories, Branford, Connecticut, USA

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Margot Tesselaar Netherlands Cancer Institute, Amsterdam, Netherlands

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Valentina Ambrosini University of Bologna, Bologna, Italy

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Richard P Baum Zentralklinik Bad Berka, Bad Berka, Germany

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Matthew Kulke Dana Farber Cancer Institute, Boston, Massachusetts, USA

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Marianne Pavel Charite Hospital, Berlin, Germany

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Jaroslaw Cwikla University of Warmia and Mazury, Olsztyn, Poland

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Ignat Drozdov Wren Laboratories, Branford, Connecticut, USA

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Massimo Falconi Ospedale San Raffaele, Milan, Italy

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Nicola Fazio IEO (European Institute of Oncology), Milan, Italy

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Andrea Frilling Imperial College London, London, UK

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Robert Jensen National Institutes of Health, Bethesda, Maryland, USA

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Klaus Koopmans Martini Ziekenhuis, Groningen, Netherlands

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Tiny Korse Netherlands Cancer Institute, Amsterdam, Netherlands

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Dik Kwekkeboom Erasmus Medical Center, Rotterdam, Netherlands

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Helmut Maecke University Hospital Freiburg, Freiburg, Germany

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Giovanni Paganelli Instituto Scientifico Romagnolo per lo Studio e la Cura dei Tumori, Meldola, Italy

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Ramon Salazar Instituto Catala d’Oncologia, Barcelona, Spain

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Stefano Severi Instituto Scientifico Romagnolo per lo Studio e la Cura dei Tumori, Meldola, Italy

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Jonathan Strosberg H. Lee Moffitt Cancer Center, Tampa, Florida, USA

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Vikas Prasad Charite Hospital, Berlin, Germany

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Aldo Scarpa University of Verona, Verona, Italy

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Ashley Grossman Univeristy of Oxford, Oxford, UK

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Annemeik Walenkamp University of Groningen, Groningen, Netherlands

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Mauro Cives H. Lee Moffitt Cancer Center, Tampa, Florida, USA

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Irene Virgolini Medical University Innsbruck, Innsbruck, Austria

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Andreas Kjaer Copenhagen University, Copenhagen, Denmark

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Irvin M Modlin Yale University, New Haven, Connecticut, USA

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The complexity of the clinical management of neuroendocrine neoplasia (NEN) is exacerbated by limitations in imaging modalities and a paucity of clinically useful biomarkers. Limitations in currently available imaging modalities reflect difficulties in measuring an intrinsically indolent disease, resolution inadequacies and inter-/intra-facility device variability and that RECIST (Response Evaluation Criteria in Solid Tumors) criteria are not optimal for NEN. Limitations of currently used biomarkers are that they are secretory biomarkers (chromogranin A, serotonin, neuron-specific enolase and pancreastatin); monoanalyte measurements; and lack sensitivity, specificity and predictive capacity. None of them meet the NIH metrics for clinical usage. A multinational, multidisciplinary Delphi consensus meeting of NEN experts (n = 33) assessed current imaging strategies and biomarkers in NEN management. Consensus (>75%) was achieved for 78% of the 142 questions. The panel concluded that morphological imaging has a diagnostic value. However, both imaging and current single-analyte biomarkers exhibit substantial limitations in measuring the disease status and predicting the therapeutic efficacy. RECIST remains suboptimal as a metric. A critical unmet need is the development of a clinico-biological tool to provide enhanced information regarding precise disease status and treatment response. The group considered that circulating RNA was better than current general NEN biomarkers and preliminary clinical data were considered promising. It was resolved that circulating multianalyte mRNA (NETest) had clinical utility in both diagnosis and monitoring disease status and therapeutic efficacy. Overall, it was concluded that a combination of tumor spatial and functional imaging with circulating transcripts (mRNA) would represent the future strategy for real-time monitoring of disease progress and therapeutic efficacy.

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