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Pancreatic Neoplasms: HELP
Articles by Eric Baudin
Based on 30 articles published since 2009
(Why 30 articles?)
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Between 2009 and 2019, E. Baudin wrote the following 30 articles about Pancreatic Neoplasms.
 
+ Citations + Abstracts
Pages: 1 · 2
1 Guideline ENETS Consensus Guidelines for High-Grade Gastroenteropancreatic Neuroendocrine Tumors and Neuroendocrine Carcinomas. 2016

Garcia-Carbonero, R / Sorbye, H / Baudin, E / Raymond, E / Wiedenmann, B / Niederle, B / Sedlackova, E / Toumpanakis, C / Anlauf, M / Cwikla, J B / Caplin, M / O'Toole, D / Perren, A / Anonymous6950853. ·Medical Oncology Department, Hospital Universitario Doce de Octubre, Madrid, Spain. ·Neuroendocrinology · Pubmed #26731334.

ABSTRACT: -- No abstract --

2 Guideline Malignant insulinoma: recommendations for characterisation and treatment. 2013

Baudin, Eric / Caron, Philippe / Lombard-Bohas, Catherine / Tabarin, Antoine / Mitry, Emmanuel / Reznick, Yves / Taieb, David / Pattou, François / Goudet, Pierre / Vezzosi, Delphine / Scoazec, Jean-Yves / Cadiot, Guillaume / Borson-Chazot, Françoise / Do Cao, Christine / Anonymous2960768 / Anonymous2970768. ·Service de médecine nucléaire et d'oncologie endocrinienne, institut Gustave-Roussy, 94800 Villejuif, France. ·Ann Endocrinol (Paris) · Pubmed #23993836.

ABSTRACT: -- No abstract --

3 Review The Problem of High-Grade Gastroenteropancreatic Neuroendocrine Neoplasms: Well-Differentiated Neuroendocrine Tumors, Neuroendocrine Carcinomas, and Beyond. 2018

Sorbye, Halfdan / Baudin, Eric / Perren, Aurel. ·Department of Oncology, Haukeland University Hospital, Jonas Lies vei 65, Bergen 5021, Norway; Department of Clinical Science, Haukeland University Hospital, Jonas Lies vei 65, Bergen 5021, Norway. Electronic address: halfdan.sorbye@helse-bergen.no. · Endocrine Oncology, Gustave Roussy, rue Édouard-Vaillant 114, Villejuif 94800, France. · Department of Pathology, University of Bern, Murtenstrasse 31, Bern 3008, Switzerland. ·Endocrinol Metab Clin North Am · Pubmed #30098724.

ABSTRACT: 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. This article addresses how to diagnose and treat gastroenteropancreatic neuroendocrine neoplasms, focusing on well-differentiated neuroendocrine tumors versus neuroendocrine carcinomas.

4 Review Imaging of neuroendocrine tumors of the pancreas. 2016

Dromain, C / Déandréis, D / Scoazec, J-Y / Goere, D / Ducreux, M / Baudin, E / Tselikas, L. ·Service de radiodiagnostic et radiologie interventionnelle, bureau CIBM 09-084, rue Bugnon 46, 1011 Lausanne, Switzerland. Electronic address: Clarisse.Dromain@chuv.ch. · Imaging department, Gustave-Roussy Cancer Campus, 114, rue Édouard-Vaillant, 94805 Villejuif cedex, France. · Anapathology department, Gustave-Roussy Cancer Campus, 114, rue Édouard-Vaillant, 94805 Villejuif cedex, France. · Surgery department, Gustave-Roussy Cancer Campus, 114, rue Édouard-Vaillant, 94805 Villejuif cedex, France. · Oncology department, Gustave-Roussy Cancer Campus, 114, rue Édouard-Vaillant, 94805 Villejuif cedex, France. ·Diagn Interv Imaging · Pubmed #27876341.

ABSTRACT: Pancreatic neuroendocrine tumors (PNETs) are rare and represent a heterogeneous disease. PNET can be functioning or non-functioning with different clinical presentations and different prognosis based on WHO and pTNM classifications. The role of imaging includes the localization of small functioning tumor, differentiation of these tumors from adenocarcinoma, identification of signs of malignancy and evaluation of extent. PNETs have a broad spectrum of appearance. On CT and MRI, most of functioning PNETs are well defined small tumors with intense and homogeneous enhancement on arterial and portal phases. However, some PNETs with a more fibrous content may have a more delayed enhancement that is best depicted on the delayed phase. Other PNETs can present as purely cystic, complex cystic and solid tumors and calcified tumors. Non-functioning PNETs are larger with less intense and more heterogeneous enhancement. Functional imaging is useful for disease staging, to detect disease recurrence or the primary but also to select patient candidate for peptide receptor radiometabolic treatment. Somatostatin receptor scintigraphy (SRS) (Octreoscan

5 Review GEP-NETS update: Interventional radiology: role in the treatment of liver metastases from GEP-NETs. 2015

de Baere, Thierry / Deschamps, Frederic / Tselikas, Lambros / Ducreux, Michel / Planchard, David / Pearson, Ernesto / Berdelou, Amandine / Leboulleux, Sophie / Elias, Dominique / Baudin, Eric. ·Interventional RadiologyMedical OncologyNuclear Medicine and Endocrine OncologyOncology SurgeryEndocrinologyInstitut Gustave Roussy, 39 rue Camille Desmoulins, 94805 Villejuif, FranceUniversité Paris-SudLe Kremlin Bicêtre, France Interventional RadiologyMedical OncologyNuclear Medicine and Endocrine OncologyOncology SurgeryEndocrinologyInstitut Gustave Roussy, 39 rue Camille Desmoulins, 94805 Villejuif, FranceUniversité Paris-SudLe Kremlin Bicêtre, France debaere@igr.fr. · Interventional RadiologyMedical OncologyNuclear Medicine and Endocrine OncologyOncology SurgeryEndocrinologyInstitut Gustave Roussy, 39 rue Camille Desmoulins, 94805 Villejuif, FranceUniversité Paris-SudLe Kremlin Bicêtre, France. · Interventional RadiologyMedical OncologyNuclear Medicine and Endocrine OncologyOncology SurgeryEndocrinologyInstitut Gustave Roussy, 39 rue Camille Desmoulins, 94805 Villejuif, FranceUniversité Paris-SudLe Kremlin Bicêtre, France Interventional RadiologyMedical OncologyNuclear Medicine and Endocrine OncologyOncology SurgeryEndocrinologyInstitut Gustave Roussy, 39 rue Camille Desmoulins, 94805 Villejuif, FranceUniversité Paris-SudLe Kremlin Bicêtre, France. ·Eur J Endocrinol · Pubmed #25385817.

ABSTRACT: Neuroendocrine tumors from gastro-pancreatic origin (GEP-NET) can be responsible for liver metastases. Such metastases can be the dominant part of the disease as well due to the tumor burden itself or the symptoms related to such liver metastases. Intra-arterial therapies are commonly used in liver only or liver-dominant disease and encompass trans-arterial chemoembolization (TACE), trans-arterial embolization (TAE), and radioembolization (RE). TACE performed with drug emulsified in Lipiodol has been used for the past 20 years with reported overall survival in the range of 3-4 years, with objective response up to 75%. Response to TACE is higher when treatment is used as a first-line therapy and degree of liver involvement is lower. Benefit of TACE over TAE is unproven in randomized study, but reported in retrospective studies namely in pancreatic NETs. RE provides early interesting results that need to be further evaluated in terms of benefit and toxicity. Radiofrequency ablation allows control of small size and numbered liver metastases, with low invasiveness. Ideal metastases to target are one metastasis <5 cm, or three metastases <3 cm, or a sum of diameter of all metastases below 8 cm. Ablation therapies can be applied in the lung or in the bones when needed, and more invasive surgery should be probably saved for large-size metastases. Even if the indication of image-guided therapy in the treatment of GEP-NET liver metastases needs to be refined, such therapies allow for manageable invasive set of treatments able to address oligometastatic patients in liver, lung, and bones. These treatments applied locally will save the benefit and the toxicity of systemic therapy for more advanced stage of the disease.

6 Review Gastroenteropancreatic high-grade neuroendocrine carcinoma. 2014

Sorbye, Halfdan / Strosberg, Jonathan / Baudin, Eric / Klimstra, David S / Yao, James C. ·Department of Oncology, Haukeland University Hospital, Bergen, Norway. ·Cancer · Pubmed #24771552.

ABSTRACT: Gastroenteropancreatic (GEP) neuroendocrine neoplasms are classified as low-grade, intermediate-grade, and high-grade tumors based on morphologic criteria and the proliferation rate. Most studies have been conducted in patients with well differentiated (low-grade to intermediate-grade) neuroendocrine tumors. Data are substantially scarcer on poorly differentiated, high-grade neuroendocrine carcinoma (NEC), which includes the entities of small cell carcinoma and large cell NEC. A literature search of GEP-NEC was performed. Long-term survival was poor even among patients who presented with localized disease. Several studies highlighted heterogeneity within the high-grade NEC category and a need for the further identification of discreet prognostic and predictive groups. Tumors with a Ki-67 proliferation index <55% were less responsive to platinum-based chemotherapy, and patients with such tumors or with well differentiated morphology had better survival than patients who had tumors with poorly differentiated morphology or a higher Ki-67 index. Treatment options beyond platinum-based chemotherapy are emerging. A revision of the World Health Organization high-grade NEC classification seems to be necessary based on recent data. Platinum-based chemotherapy may not be the optimal treatment for patients who have GEP-NEC with a moderately high proliferation rate. Adequate diagnostic and prognostic stratifications constitute the basis for future progress.

7 Review [Targeted therapies, prognostic and predictive factors in endocrine oncology]. 2013

Hescot, S / Baudin, E / Borson-Chazot, F / Lombès, M. ·Inserm U693, Faculté de médecine Paris-Sud, Université Paris-Sud, Le Kremlin-Bicêtre, France; Médecine nucléaire et Oncologie endocrinienne, Institut Gustave-Roussy, Université Paris-Sud, Villejuif, France. Electronic address: segolene.hescot@u-psud.fr. · Inserm U693, Faculté de médecine Paris-Sud, Université Paris-Sud, Le Kremlin-Bicêtre, France; Médecine nucléaire et Oncologie endocrinienne, Institut Gustave-Roussy, Université Paris-Sud, Villejuif, France. · Groupement hospitalier Lyon-Est, Fédération d'endocrinologie et Centre de médecine nucléaire, Bron, France. · Inserm U693, Faculté de médecine Paris-Sud, Université Paris-Sud, Le Kremlin-Bicêtre, France; Service d'endocrinologie et maladies de la reproduction, Assistance publique-Hôpitaux de Paris, Hôpital de Bicêtre, Le Kremlin-Bicêtre, F-94275, France. ·Ann Endocrinol (Paris) · Pubmed #24356287.

ABSTRACT: A better understanding of molecular mechanisms responsible for tumorigenesis has allowed the development of targeted drugs designed to improve the outcome of cancer. In endocrine tumors, several molecules have demonstrated efficacy in terms of progression free survival during phase III trials such as vandetanib and cabozantinib in medullary thyroid carcinoma, sorafenib in differentiated thyroid carcinoma and everolimus or sunitinib for pancreatic neuroendocrine tumors. Rare cancer network has allowed ongoing phase III trials in malignant pheochromocytoma and adrenocortical carcinoma. However, to date no specific predictive biomarker has yet been identified for a personalized cancer medicine. We review recent advances in endocrine oncology concerning molecular targets identification, targeted therapies and predictive or prognostic markers.

8 Review Intervention in gastro-enteropancreatic neuroendocrine tumours. 2012

Baudin, Eric / Planchard, David / Scoazec, Jean-Yves / Guigay, Joël / Dromain, Clarisse / Hadoux, Julien / Debaere, Thierry / Elias, Dominique / Ducreux, Michel. ·Department of Nuclear Medicine and Endocrine Oncology, Institut Gustave Roussy, 39 rue Camille Desmoulins, 94805 Villejuif Cedex, France. baudin@igr.fr ·Best Pract Res Clin Gastroenterol · Pubmed #23582924.

ABSTRACT: Neuroendocrine tumours require dedicated interventions to control their capacity to secrete hormones but also, antitumour growth strategies. Recommendations for early interventions in NET include the management of hormone-related symptoms and poorly differentiated neuroendocrine carcinomas. In contrast, prognostic heterogeneity is a key feature of well differentiated NET that complexified the antitumour strategy whatever the stage in this subgroup of tumour. In this review, timely therapeutic interventions to control hormone-related symptoms and tumour growth in GEP NET patients are discussed. The necessity of controlling hormone-related symptoms as the first step of any strategy affects also the tumour growth control strategy. In the absence of cure at the metastatic stage, progresses are expected in the recognition of well differentiated NET subgroups that display either excellent or poor prognosis.

9 Review Chromogranin A assay in clinical practice. 2010

d'Herbomez, M / Do Cao, C / Vezzosi, D / Borzon-Chasot, F / Baudin, E / Anonymous6310662. ·Département de médecine nucléaire, centre de biologie pathologie, CHRU, 59037 Lille cedex, France. m-dherbomez@chru-lille.fr ·Ann Endocrinol (Paris) · Pubmed #20538257.

ABSTRACT: Chromogranins belong to the family of secretory chromogranin and secretogranin proteins. They are found in secretory vesicles throughout the neuroendocrine system. Chromogranin A (CgA) is the main component. CgA acts as a prohormone submitted to processes of degradation through which active peptides are generated. CgA has auto, para and endocrine functions. It is widely used as an immunohistochemical marker. Despite the lack of international standardization, and the lack of an accurate definition of the diagnostic cut-off levels, some CgA assays are reliable. Numerous studies have suggested that CgA determination may be of interest for the diagnosis and the follow-up of various endocrine tumors. Plasma levels of this general marker are proportional to tumor mass. The localization of the primitive tumor, the presence of associated hormonal secretions and possible renal failure and/or hypergastrinemia must be taken into consideration for proper interpretation of CgA levels. New clinical indications are emerging for the evaluation of stress in intensive care units and the assessment of cardiovascular risk. New assays estimating the concentration of active peptides are under development.

10 Clinical Trial Everolimus Effect on Gastrin and Glucagon in Pancreatic Neuroendocrine Tumors. 2017

Pavel, Marianne E / Chen, David / He, Wei / Cushman, Stephanie / Voi, Maurizio / de Vries, Elisabeth G E / Baudin, Eric / Yao, James C. ·From the *Department of Hepatology and Gastroenterology, Charité Universitätsmedizin Berlin/Campus Virchow Klinikum, Berlin, Germany; †Novartis Pharmaceuticals Corporation, East Hanover, NJ; ‡Department of Medical Oncology, University Medical Center, University of Groningen, Groningen, The Netherlands; §Oncologie Endocrinienne et Médecine Nucléaire, Institut Gustave-Roussy, Villejuif, France; and ∥Department of Gastrointestinal Medical Oncology, University of Texas MD Anderson Cancer Center, Houston, TX. ·Pancreas · Pubmed #28609362.

ABSTRACT: OBJECTIVES: The pharmacodynamic effects of everolimus on gastrointestinal hormone levels have not been described in patients with pancreatic neuroendocrine tumors (pNETs). We report the effects of everolimus on gastrin and glucagon levels in patients with progressive pNET in RADIANT-1 (a single-arm phase II trial) and RADIANT-3 (a placebo-controlled, randomized, phase III trial). METHODS: Serum gastrin and glucagon levels were determined by immunoassay at baseline and at predose in subsequent treatment cycles in patients with elevated baseline hormone levels. The analyses included 158 patients from RADIANT-1 and 404 patients from RADIANT-3. RESULTS: In RADIANT-1, everolimus induced a rapid, sustained decrease in median gastrin and glucagon levels to approximately 60% and 70% of baseline levels, respectively. In RADIANT-3, everolimus consistently reduced median gastrin and glucagon levels by greater than 50% and approximately 40%, respectively (everolimus vs placebo, P < 0.0001), whereas with placebo, both hormones at each time point were essentially the same as their baseline levels. In patients with concomitant octreotide long-acting repeatable treatment, the moderate pharmacodynamic effect on lowering gastrin was greater than that seen with everolimus alone. CONCLUSIONS: In addition to prolonging progression-free survival in patients with pNET, everolimus down-regulates excess production of 2 gastrointestinal hormones, which may help control their associated clinical syndromes.

11 Clinical Trial A Phase II Study of BEZ235 in Patients with Everolimus-resistant, Advanced Pancreatic Neuroendocrine Tumours. 2016

Fazio, Nicola / Buzzoni, Roberto / Baudin, Eric / Antonuzzo, Lorenzo / Hubner, Richard A / Lahner, Harald / DE Herder, Wouter W / Raderer, Markus / Teulé, Alexandre / Capdevila, Jaume / Libutti, Steven K / Kulke, Matthew H / Shah, Manisha / Dey, Debarshi / Turri, Sabine / Aimone, Paola / Massacesi, Cristian / Verslype, Chris. ·European Institute of Oncology, Milan, Italy nicola.fazio@ieo.it. · IRCCS National Tumor Institute, Milan, Italy. · Institut Gustave Roussy, Villejuif, France. · Careggi University Hospital, Florence, Italy. · The Christie NHS Foundation Trust, Manchester, U.K. · University of Duisburg-Essen, Essen, Germany. · Erasmus MC, Rotterdam, the Netherlands. · University Hospital of Vienna, Vienna, Austria. · Vall d'Hebron University Hospital, Vall d'Hebron Institute of Oncology, Barcelona, Spain. · Montefiore Medical Center and Albert Einstein College of Medicine, New York, NY, U.S.A. · Dana-Farber Cancer Institute, Boston, MA, U.S.A. · The James Cancer Hospital and Solove Research Institute, The Ohio State University, Columbus, OH, U.S.A. · Novartis Healthcare Private Limited, Hyderabad, India. · Novartis Pharma AG, Basel, Switzerland. · Novartis Oncology, Paris, France. · University Hospitals Leuven, Leuven, Belgium. ·Anticancer Res · Pubmed #26851029.

ABSTRACT: BACKGROUND: This was a two-stage, phase II trial of the dual phosphatidylinositol 3-kinase/mammalian target of rapamycin inhibitor BEZ235 in patients with everolimus-resistant pancreatic neuroendocrine tumours (pNETs) (NCT01658436). PATIENTS AND METHODS: In stage 1, 11 patients received 400 mg BEZ235 orally twice daily (bid). Due to tolerability concerns, a further 20 patients received BEZ235 300 mg bid. Stage 2 would be triggered by a 16-week progression-free survival (PFS) rate of ≥60% in stage 1. RESULTS: As of 30 June, 2014, 29/31 patients had discontinued treatment. Treatment-related grade 3/4 adverse events were reported in eight (72.7%) patients at 400 mg and eight (40.0%) patients at 300 mg, including hyperglycaemia, diarrhoea, nausea, and vomiting. The estimated 16-week PFS rate was 51.6% (90% confidence interval=35.7-67.3%). CONCLUSION: BEZ235 was poorly tolerated by patients with everolimus-resistant pNETs at 400 and 300 mg bid doses. Although evidence of disease stability was observed, the study did not proceed to stage 2.

12 Clinical Trial Bevacizumab combined with 5-FU/streptozocin in patients with progressive metastatic well-differentiated pancreatic endocrine tumours (BETTER trial)--a phase II non-randomised trial. 2014

Ducreux, Michel / Dahan, Laetitia / Smith, Denis / O'Toole, Dermot / Lepère, Céline / Dromain, Clarisse / Vilgrain, Valérie / Baudin, Eric / Lombard-Bohas, Catherine / Scoazec, Jean-Yves / Seitz, Jean-François / Bitoun, Laurence / Koné, Sébastien / Mitry, Emmanuel. ·Gastrointestinal Oncology Department, Gustave Roussy Institute, Villejuif, France; Faculté de Médecine, Paris Sud Uiversty Le Kremlin Bicêtre, France. Electronic address: Michel.DUCREUX@igr.fr. · Gastrointestinal Oncology Department, La Timone Hospital, Aix-Marseille Université, Marseille, France. Electronic address: laetitia.dahan@mail.hp-hm.fr. · Medical Oncology Department, Saint-André Hospital, Bordeaux, France. Electronic address: denis.smith@chu-bordeaux.fr. · Clinical Medicine and Gastroenterology Department, St James's Hospital and Trinity College, Dublin, Ireland. Electronic address: OTOOLED1@tcd.ie. · Medical Oncology Department, Georges Pompidou European Hospital, Paris, France. Electronic address: celine.lepere@egp.aphp.fr. · Radio Diagnostic Department, Gustave Roussy Institute, Villejuif, France. Electronic address: dromain@igr.fr. · Radiology Department, Beaujon Hospital, Clichy, France. Electronic address: valerie.vilgrain@bjn.aphp.fr. · Nuclear Medicine and Endocrine Oncology Department, Gustave Roussy Institute, Villejuif, France. Electronic address: Eric.BAUDIN@igr.fr. · Medical Oncology Department, Edouard Herriot Hospital, Lyon, France. Electronic address: catherine.lombard-bohas@chu-lyon.fr. · Pathology Department, Edouard Herriot Hospital, Lyon, France. Electronic address: jy.scoazec@gmail.com. · Gastrointestinal Oncology Department, La Timone Hospital, Aix-Marseille Université, Marseille, France. Electronic address: Jean-francois.SEITZ@ap-hm.fr. · Clinial Operating Department, Roche Laboratories, Boulogne-Billancourt, France. Electronic address: laurence.bitoun@roche.com. · Oncology Department, Roche Laboratories, Boulogne-Billancourt, France. Electronic address: sebastien.kone@roche.com. · Medical Oncology Department, Curie Institute, Paris, France. Electronic address: emmanuel.mitry@curie.net. ·Eur J Cancer · Pubmed #25454412.

ABSTRACT: AIM OF THE STUDY: Neuroendocrine tumours are highly vascular neoplasms known to overexpress vascular endothelial growth factor (VEGF) and its receptor. Bevacizumab, an inhibitor of VEGF, was assessed in combination with chemotherapy in pancreatic neuroendocrine tumour (P-NET). PATIENTS AND METHODS: BETTER was a multicentre, open-label, non-randomised, two-group phase II trial. Patients with progressive metastatic, well-differentiated P-NET received a minimum of 6 month treatment of bevacizumab at 7.5 mg/kg IV on d1 q3w with 5-FU at 400 mg/m2/day and streptozocin at 500 mg/m2/day IV from d1 to d5 every 42 days. The primary end-point was progression-free survival (PFS); secondary end-points were overall survival (OS), overall response rate, safety and quality of life. RESULTS: A total of 34 patients were included. Median age was 55 years, 65% of patients were men, 97% had an Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1 and 97% had a Ki-67 proliferative index of <15%. After a maximum of 24 month follow-up per patient, the median PFS assessed by investigators was 23.7 months [95% confidence interval (CI): 13.1; not reached], 19 (56%) patients had a partial response and 15 (44%) had stable disease as best response. OS rate at 24 months was 88%. The most frequently reported grade 3-4 adverse events were hypertension (21% patients), abdominal pain (12%) and thromboembolic events (9%). CONCLUSION: Bevacizumab with 5-FU/streptozocin in the treatment of pancreatic NETs seems to be feasible with a PFS of 23.7 months, which deserves further attention. No unexpected toxicity was observed.

13 Clinical Trial Daily oral everolimus activity in patients with metastatic pancreatic neuroendocrine tumors after failure of cytotoxic chemotherapy: a phase II trial. 2010

Yao, James C / Lombard-Bohas, Catherine / Baudin, Eric / Kvols, Larry K / Rougier, Philippe / Ruszniewski, Philippe / Hoosen, Sakina / St Peter, Jessica / Haas, Tomas / Lebwohl, David / Van Cutsem, Eric / Kulke, Matthew H / Hobday, Timothy J / O'Dorisio, Thomas M / Shah, Manisha H / Cadiot, Guillaume / Luppi, Gabriele / Posey, James A / Wiedenmann, Bertram. ·Department of Gastrointestinal Medical Oncology, The University of Texas M. D. Anderson Cancer Center, 1515 Holcombe Blvd, Unit 426, Houston, TX 77030, USA. jyao@mdanderson.org ·J Clin Oncol · Pubmed #19933912.

ABSTRACT: PURPOSE No established treatment exists for pancreatic neuroendocrine tumor (NET) progression after failure of chemotherapy. Everolimus (RAD001), an oral inhibitor of mammalian target of rapamycin, in combination with octreotide has demonstrated encouraging antitumor activity in patients with NETs. PATIENTS AND METHODS This open-label, phase II study assessed the clinical activity of everolimus in patients with metastatic pancreatic NETs who experienced progression on or after chemotherapy. Patients were stratified by prior octreotide therapy (stratum 1: everolimus 10 mg/d, n = 115; stratum 2: everolimus 10 mg/d plus octreotide long-acting release [LAR], n = 45). Tumor assessments (using Response Evaluation Criteria in Solid Tumors) were performed every 3 months. Chromogranin A (CgA) and neuron-specific enolase (NSE) were assessed monthly if elevated at baseline. Trough concentrations of everolimus and octreotide were assessed. Results By central radiology review, in stratum 1, there were 11 partial responses (9.6%), 78 patients (67.8%) with stable disease (SD), and 16 patients (13.9%) with progressive disease; median progression-free survival (PFS) was 9.7 months. In stratum 2, there were two partial responses (4.4%), 36 patients (80%) with SD, and no patients with progressive disease; median PFS was 16.7 months. Patients with an early CgA or NSE response had a longer PFS compared with patients without an early response. Coadministration of octreotide LAR and everolimus did not impact exposure to either drug. Most adverse events were mild to moderate and were consistent with those previously seen with everolimus. CONCLUSION Daily everolimus, with or without concomitant octreotide LAR, demonstrates antitumor activity as measured by objective response rate and PFS and is well tolerated in patients with advanced pancreatic NETs after failure of prior systemic chemotherapy.

14 Clinical Trial Prognostic factors influencing survival from metastatic (stage IV) gastroenteropancreatic well-differentiated endocrine carcinoma. 2009

Durante, Cosimo / Boukheris, Houda / Dromain, Clarisse / Duvillard, Pierre / Leboulleux, Sophie / Elias, Dominique / de Baere, Thierry / Malka, David / Lumbroso, Jean / Guigay, Joël / Schlumberger, Martin / Ducreux, Michel / Baudin, Eric. ·Service de Médecine Nucléaire et de Cancérologie Endocrinienne, Institut Gustave-Roussy, Université Paris XI, 94805 Villejuif Cedex, France. ·Endocr Relat Cancer · Pubmed #19240182.

ABSTRACT: Survival of metastatic gastroenteropancreatic well-differentiated endocrine carcinoma (GEP WDEC) is not well characterized. We evaluated the long-term outcome and prognostic factors for survival in 118 patients with distant metastases from GEP WDEC. Inclusion criteria were 1) pathological review by a single pathologist according to the present WHO criteria, 2) absence of previous therapy apart from surgery, 3) complete morphological evaluation within 3 months including somatostatin receptor scintigraphy, and 4) follow-up at Gustave-Roussy Institute until death or study's end. Clinical, biological marker, and pathological parameters were analyzed in univariate and multivariate statistical models. Survival after the first complete imaging work-up of the metastatic disease was determined using Kaplan-Meier method. Overall, survival for 5 years after the diagnosis of metastatic disease was 54%. In multivariate analysis, age (hazard ratio (HR): 1.05, 95% confidence interval (CI): 1.01-1.08, P = 0.01), the number of liver metastases (HR: 3.4, 95% CI: 1.4-8.3, P = 0.01), tumor slope (HR: 1.1, 95% CI: 1.0-1.1, P = 0.001), and initial surgery (HR: 0.3, 95% CI: 0.1-0.8, P = 0.01) were predictive of survival. Five-year survival was 100%, 91% (95% CI, 51-98%), 62% (95% CI, 37-83%), and 9% (95% CI, 6-32%) when patients had 0, 1, 2, 3 or more poor prognostic features respectively. This study enables the stratification of metastatic GEP WDEC patients into distinct risk groups. These risk categories can be used to tailor therapeutic approaches and also to design and interpret clinical trials.

15 Article Tumor growth rate as a metric of progression, response, and prognosis in pancreatic and intestinal neuroendocrine tumors. 2019

Dromain, Clarisse / Pavel, Marianne E / Ruszniewski, Philippe / Langley, Alison / Massien, Christine / Baudin, Eric / Caplin, Martyn E / Anonymous2211132. ·Department of Diagnostic and Interventional Radiology, CHUV University Hospital, Lausanne, Switzerland. Clarisse.Dromain@chuv.ch. · Department of Medicine 1, Division of Endocrinology and Diabetology, Friedrich-Alexander Universität Erlangen-Nürnberg, Universitätsklinikum Erlangen, Erlangen, Germany. · Division of Gastroenterology and Pancreatology, Beaujon Hospital, Clichy, France. · Faculty of Medicine, Paris Diderot University, Paris, France. · Ipsen, Boulogne-Billancourt, France. · APHP, Hypertension unit, Georges Pompidou European Hospital, F-75015, Paris, France. · Endocrine Tumour and Nuclear Medicine Unit, Gustave-Roussy Cancer Campus, Villejuif, France. · Neuroendocrine Tumour Unit, Department of Gastroenterology, Royal Free Hospital, London, UK. ·BMC Cancer · Pubmed #30642293.

ABSTRACT: BACKGROUND: Lanreotide depot/autogel antitumor activity in intestinal/pancreatic neuroendocrine tumors (NETs) was demonstrated in the phase-3 CLARINET study (NCT00353496), based on significantly prolonged progression-free survival (PFS) versus placebo. METHODS: During CLARINET, patients with metastatic intestinal/pancreatic NETs received lanreotide depot/autogel 120 mg or placebo every 4 weeks for 96 weeks. Imaging data (response evaluation criteria in solid tumors [RECIST] v1.0, centrally reviewed) were re-evaluated in this post hoc analysis of tumor growth rate (TGR) in NETs. TGR (%/month) was calculated from two imaging scans during relevant periods: pre-treatment (TGR RESULTS: TGR CONCLUSIONS: TGR provides valuable information on tumor activity and prognosis in patients with metastatic intestinal/pancreatic NETs, and identifies early lanreotide depot/autogel antitumor activity. TRIAL REGISTRATION: Retrospective registration, 18 July 2006; EudraCT: 2005-004904-35; ClinicalTrials.gov: NCT00353496 .

16 Article Chemotherapy for Well-Differentiated Pancreatic Neuroendocrine Tumours with a Ki-67 Index ≥10%: Is There a More Effective Antitumour Regimen? A Retrospective Multicentre Study of the French Group of Endocrine Tumours (GTE). 2018

Roquin, Guillaume / Baudin, Eric / Lombard-Bohas, Catherine / Cadiot, Guillaume / Dominguez, Sophie / Guimbaud, Rosine / Niccoli, Patricia / Legoux, Jean-Louis / Mitry, Emmanuel / Rohmer, Vincent / Ruszniewski, Philippe / Walter, Thomas / Ducreux, Michel / Couvelard, Anne / Scoazec, Jean-Yves / Ramond-Roquin, Aline / Caroli-Bosc, François-Xavier / Hentic, Olivia. ·Department of Hepatogastroenterology and Digestive Oncology, CHU Angers, Angers University, LUNAM University, Angers, France. ·Neuroendocrinology · Pubmed #28152531.

ABSTRACT: BACKGROUND: The best chemotherapy regimen for well- differentiated pancreatic neuroendocrine tumours (pNETs) with a Ki-67 index ≥10% is still debated. We evaluated the antitumour efficacy of various first-line chemotherapy regimens (streptozocin based, platinum based, or dacarbazine/temozolomide based) in this situation. METHODS: In this retrospective multicentre study of the French Group of Endocrine Tumours (GTE), we recruited consecutive patients with advanced well-differentiated pNETs and a Ki-67 index ≥10% receiving chemotherapy between 2000 and 2012. The primary endpoint was progression-free survival (PFS) according to RECIST. RESULTS: Seventy-four patients (42 men, median age 55.5 years) were enrolled from 10 centres. Fifty-one patients (69%) had grade 2 NET and 61 (82%) were stage IV. Median overall survival was 36.3 months. Forty-four patients (59%) received streptozocin-based, 18 (24%) platinum-based, and 12 (16%) dacarbazine/temozolomide-based chemotherapy regimens. These 3 groups were similar regarding age, functioning tumours, grade, the number of metastatic sites, and surgery for primary tumours, but not regarding surgery for metastases and time since diagnosis. Grade 3 NET (HR 2.15, 95% CI: 1.18-3.92, p = 0.012) and age above 55 years (HR 1.84, 95% CI: 1.06-3.18, p = 0.030) were associated with shorter median PFS in the multivariate analyses. Compared to streptozocin-based chemotherapy, no difference was found in terms of PFS for the platinum-based or for the dacarbazine/temozolomide-based chemotherapy regimen: median PFS was 7.2, 7.5, and 7.2 months, respectively (p = 0.51). CONCLUSIONS: Patients with intermediate or highly proliferative well-differentiated pNETs may benefit from 1 of the 3 chemotherapy regimens. Increased age and grade 3 were associated with shorter median PFS. Randomised studies searching for response predictors and the best efficacy-tolerance ratio are required to personalise the strategy.

17 Article Management of gastric neuro-endocrine tumours in a large French national cohort (GTE). 2017

Manfredi, Sylvain / Walter, Thomas / Baudin, Eric / Coriat, Romain / Ruszniewski, Philippe / Lecomte, Thierry / Laurenty, Anne-Pascale / Goichot, Bernard / Rohmer, Vincent / Roquin, Guillaume / Cojocarasu, Oana-Zvetlana / Lombard-Bohas, Catherine / Lepage, Côme / Morcet, Jeff / Cadiot, Guillaume. ·CHU Dijon, hepato-gastroenterology unit, University of Bourgogne Franche-Comté, INSERM, LNC UMR1231, F-21000, Dijon, France. sylvain.manfredi@chu-dijon.fr. · Département d'Oncologie Médicale, Hospices Civils de Lyon, Hôpital Edouard Herriot, 69437, Lyon, cedex 03, France. · Gustave Roussy, Département d'Oncologie Endocrinienne, 94805, Villejuif cedex, France. · Department of Gastroenterology and Digestive Oncology, Cochin Teaching Hospital, Paris Descartes University, Paris, France. · Beaujon Hospital and Paris Diderot University, Clichy, France. · CHRU de Tours, service d'Hépato-Gastroenterologie, CNRS, UMR 7292, GICC & Université Francois-Rabelais, Tours, France. · Department of Medical Oncology, Institut Claudius Regaud, Toulouse, France. · Department of Internal Medicine, Endocrinology and Nutrition, Hôpitaux Universitaires de Strasbourg, Faculté de Médecine, Université de Strasbourg, Strasbourg, France. · Service d'endocrinologie et maladies métaboliques, CHU d'Angers, 4 rue Larrey, 49100, Angers, France. · Service d'Hépato-Gastro-Entérologie, CHU Angers, Angers, France. · CH Le Mans, Le Mans, France. · CHU Dijon, hepato-gastroenterology unit, University of Bourgogne Franche-Comté, INSERM, LNC UMR1231, F-21000, Dijon, France. · CIC, Université de Rennes 1, Rennes, France. · Department of Hepato-Gastroenterology and Digestive Oncology, Robert-Debré University Hospital, Reims, France. ·Endocrine · Pubmed #28664309.

ABSTRACT: INTRODUCTION: Gastric neuro-endocrine tumours are rare. European guidelines for the management of neuro-endocrine tumours have been published in 2012. The aim of our survey was to study the management of gastric neuro-endocrine tumours registered in the national cohort. A prospective national cohort registers the Neuro-endocrine tumours in France since January 2003 (GTE network). We reviewed all the individual medical reports of gastric neuro-endocrine tumours in order to collect data on treatment. RESULTS: One hundred and ninety seven gastric neuro-endocrine tumours diagnosed between 1964 and 2013 in 20 centres were registered. For 181 cases data were considered complete for our survey. Eighty four tumours were type 1 (46.4%); five types 2 (2.8%); 52 types 3 (28.7%) and 40 types 4 (22.1%). Types 1 and 2 were first endoscopically managed in 93 and 60% of cases, respectively, whereas surgery was first done in 45 and 42%, respectively, of types 3 and 4. Systemic treatment, chemotherapy and/or somatostatin analogue, was first administered exclusively for types 3 and 4. Near 3% of types 1 and 40% of types 2 received at a time somatostatin analogue treatment. Five-year survival rates were 98.3, 100, 63.2 and 31.8% for types 1, 2, 3 and 4, respectively. CONCLUSION: The great majority of gastric neuro-endocrine tumours registered in this national cohort are treated in accordance with the current guidelines. The survival rates we reported must be interpreted with caution, because this cohort registered preferentially selected patients eligible for treatment. The registration of all the gastric neuro-endocrine tumours, in particular type 1 considered as benign and type 4 not eligible for specific anti-cancer treatment must be encouraged.

18 Article Poorly differentiated gastro-entero-pancreatic neuroendocrine carcinomas: Are they really heterogeneous? Insights from the FFCD-GTE national cohort. 2017

Walter, T / Tougeron, D / Baudin, E / Le Malicot, K / Lecomte, T / Malka, D / Hentic, O / Manfredi, S / Bonnet, I / Guimbaud, R / Coriat, R / Lepère, C / Desauw, C / Thirot-Bidault, A / Dahan, L / Roquin, G / Aparicio, T / Legoux, J-L / Lombard-Bohas, C / Scoazec, J-Y / Lepage, C / Cadiot, G / Anonymous3550906. ·University Hospital, Lyon, France. Electronic address: thomas.walter@chu-lyon.fr. · University Hospital, Poitiers, France. · Gustave Roussy Institute, Villejuif, France. · FFCD, Dijon, France. · Trousseau Hospital, Tours, France. · Beaujon Hospital, Clichy, France. · University Hospital, Rennes, France. · Valenciennes Hospital, Valenciennes, France. · University Hospital, Toulouse, France. · Cochin Hospital, University Paris Descartes, Paris, France. · Georges Pompidou European Hospital, University Paris-V, Paris, France. · University Hospital, Lille, France. · Hôpitalde Bicêtre, Le Kremlin Bicêtre, France. · La Timone Hospital, Marseille, France. · University Hospital, Angers, France. · Avicenne Hospital, Bobigny, France. · Hôpital de la Source, Orléans, France. · University Hospital, Lyon, France. · FFCD, Dijon, France; University Hospital, Dijon, France. · University Hospital, Reims, France. ·Eur J Cancer · Pubmed #28501762.

ABSTRACT: BACKGROUND: Diagnosis and management of poorly differentiated gastro-entero-pancreatic (GEP) neuroendocrine carcinomas (NECs) remain challenging. Recent studies suggest prognostic heterogeneity. We designed within the French Group of Endocrine Tumours a prospective cohort to gain insight in the prognostic stratification and treatment of GEP-NEC. PATIENTS AND METHODS: All patients with a diagnosis of GEP-NEC between 1st January 2010 and 31st December 2013 could be included in this national cohort. Adenoneuroendocrine tumours were excluded. RESULTS: 253 patients from 49 centres were included. Median age was 66 years. Main primary locations were pancreas (21%), colorectal (27%), oesophagus-stomach (18%); primary location was unknown in 20%. Tumours were metastatic at diagnosis in 78% of cases. Performance status (PS) at diagnosis was 0-1 in 79% of patients. Among the 147 (58%) cases reviewed by an expert pathological network, 39% were classified as small cell NEC and 61% as large cell NEC. Median Ki67 index was 75% (range, 20-100). Median overall survival was 15.6 (13.6-17.0) months. Significant adverse prognostic factors in univariate analysis were PS > 1 (hazard ratio [HR] = 2.5), metastatic disease (HR = 1.6), NSE>2 upper limit of normal [ULN]; HR = 3.2), CgA>2 ULN (HR = 1.7) and lactate dehydrogenase >2 ULN (HR = 2.1). After first-line palliative chemotherapy (CT1) with platinum-etoposide (n = 152), objective response, progression-free survival and overall survival were 50%, 6.2 and 11.6 months; they were 24%, 2.9 and 5.9, respectively, after post-CT1 FOLFIRI regimen (n = 72). CONCLUSIONS: We report a large prospective series of GEP-NEC which show the predominance of large cell type and advanced stage at diagnosis. Prognosis was found more homogeneous than previously reported, mainly impacted by PS and tumour burden.

19 Article Not All Patients with a Pancreatic Neuroendocrine Tumour Will Benefit from All Approved or Recommended Therapeutic Options: A Real-Life Retrospective Study. 2017

Berdelou, Amandine / Boige, Valérie / Arfi-Rouche, Julia / Malka, David / Ederhy, Stéphane / Izzedine, Hassan / Leboulleux, Sophie / Chougnet, Cécile N / Burtin, Pascal / De Baere, Thierry / Laplanche, Agnès / Elias, Dominique / Schlumberger, Martin / Scoazec, Jean-Yves / Ducreux, Michel / Baudin, Eric. ·Department of Nuclear Medicine and Endocrine Tumours, Gustave Roussy, Université Paris XI, Villejuif, France. ·Neuroendocrinology · Pubmed #27225439.

ABSTRACT: BACKGROUND: At least nine therapeutic options are recommended or approved for pancreatic neuroendocrine tumour (pNET). The primary endpoint of this study was to determine the number of therapeutic lines given before death. Secondary endpoints were to determine toxic events as a function of number of therapeutic lines and of time. METHODS: Patients with pNET treated between 1998 and 2010 at our centre were characterised. All therapeutic lines were recorded as well as tumour- or toxic-related deaths. Persistent treatment-related toxicity (PTRT) was defined as: chronic kidney disease, anaemia, thrombocytopenia, neutropenia, severe liver failure, cardiac failure and recurrent sepsis, precluding at least one other therapeutic option or second cancers. RESULTS: Ninety-two patients were analysed. The median follow-up was 7 years. The 1-, 2- and 5-year overall survival rates were 90, 81 and 51%, respectively. After 3 and 5 therapeutic lines, 23 and 50% of patients had died, respectively. After 3 and 5 lines, the frequency of toxic events was 8 and 24%, respectively. Overall, 17 toxic events were observed including 6 treatment-related deaths and 11 PTRT. After 1, 2 and 5 years of treatment, the frequency of toxic events was 6, 9 and 16%, respectively. CONCLUSION: Tumour- and toxic-related deaths as well as PTRT may preclude access to all therapeutic options in patients with pNET. Optimised risk benefit sequence should be investigated.

20 Article Unraveling the intrafamilial correlations and heritability of tumor types in MEN1: a Groupe d'étude des Tumeurs Endocrines study. 2015

Thevenon, J / Bourredjem, A / Faivre, L / Cardot-Bauters, C / Calender, A / Le Bras, M / Giraud, S / Niccoli, P / Odou, M F / Borson-Chazot, F / Barlier, A / Lombard-Bohas, C / Clauser, E / Tabarin, A / Pasmant, E / Chabre, O / Castermans, E / Ruszniewski, P / Bertherat, J / Delemer, B / Christin-Maitre, S / Beckers, A / Guilhem, I / Rohmer, V / Goichot, B / Caron, P / Baudin, E / Chanson, P / Groussin, L / Du Boullay, H / Weryha, G / Lecomte, P / Schillo, F / Bihan, H / Archambeaud, F / Kerlan, V / Bourcigaux, N / Kuhn, J M / Vergès, B / Rodier, M / Renard, M / Sadoul, J L / Binquet, C / Goudet, P. ·CHU de DijonCentre de Génétique et Centre de Référence Anomalies du Développement et Syndromes Malformatifs, University of Burgundy, EA4271 GAD, Dijon, FranceINSERMCIC1432, Dijon, FranceCentre Hospitalier Universitaire de DijonCentre d'Investigation Clinique, éssais cliniques/épidémiologie clinique, Dijon FranceCentre Hospitalier Régional et Universitaire de LilleService de Médecine interne et Endocrinologie, Clinique Marc Linquette, Lille, FranceHospices Civils de LyonHôpital E. Herriot, Génétique moléculaire et clinique, Lyon, FranceCentre Hospitalier Universitaire de NantesClinique d'Endocrinologie, Nantes, FranceAPHMservice d'Oncologie Médicale, Institut Paoli-Calmettes, Université Aix-Marseille, Marseille, FranceCHRU de LilleService d'Hormonologie, Métabolisme-Nutrition, Oncologie, Pôle de Biologie Pathologie Génétique, Université de Lille2, Lille, FranceHospices Civils de Lyon et Université LYON1Groupement hospitalier Est, Fédération d'Endocrinologie, Lyon, FranceAP-HMHôpital la Conception, Laboratoire de Biologie Moléculaire, Marseille, FranceAix-Marseille UniversityCRN2M UMR 7286-CNRS, Marseille, FranceHospices Civils de LyonHôpital E. Herriot, Service d'Oncologie, Lyon, FranceUniversité Paris-DescartesFaculté de Médecine Paris-Descartes-Paris-V, UMR-S970, Paris, FranceAPHPHôpital Cochin, Laboratoire d'Oncogénétique, Paris, FranceCentre Hospitalier Universitaire et Université de Bordeaux 2Service d'Endocrinologie,Hôpital du Haut Levêque, Pessac,FranceAPHPHôpital Cochin, Service de Biochimie et de Génétique Moléculaire,Paris, FranceCentre Hospitalier Universitaire de GrenobleService d'Endocrinologie, Diabète et Maladies métaboliques, Hôpital Michalon, Grenoble,FranceCentre Hospitalier Universitaire de LiègeDomaine Universitaire du Sart-Tilman, University of Liège, Laboratoire de génétique moléculaire, Liège, BelgiumAPHPHôpital Beaujon et Université Paris 7 Denis Diderot, Service de Gastroentérologie-pancréa ·Eur J Endocrinol · Pubmed #26392472.

ABSTRACT: BACKGROUND: MEN1, which is secondary to the mutation of the MEN1 gene, is a rare autosomal-dominant disease that predisposes mutation carriers to endocrine tumors. Most studies demonstrated the absence of direct genotype-phenotype correlations. The existence of a higher risk of death in the Groupe d'étude des Tumeurs Endocrines-cohort associated with a mutation in the JunD interacting domain suggests heterogeneity across families in disease expressivity. This study aims to assess the existence of modifying genetic factors by estimating the intrafamilial correlations and heritability of the six main tumor types in MEN1. METHODS: The study included 797 patients from 265 kindred and studied seven phenotypic criteria: parathyroid and pancreatic neuroendocrine tumors (NETs) and pituitary, adrenal, bronchial, and thymic (thNET) tumors and the presence of metastasis. Intrafamilial correlations and heritability estimates were calculated from family tree data using specific validated statistical analysis software. RESULTS: Intrafamilial correlations were significant and decreased along parental degrees distance for pituitary, adrenal and thNETs. The heritability of these three tumor types was consistently strong and significant with 64% (s.e.m.=0.13; P<0.001) for pituitary tumor, 65% (s.e.m.=0.21; P<0.001) for adrenal tumors, and 97% (s.e.m.=0.41; P=0.006) for thNETs. CONCLUSION: The present study shows the existence of modifying genetic factors for thymus, adrenal, and pituitary MEN1 tumor types. The identification of at-risk subgroups of individuals within cohorts is the first step toward personalization of care. Next generation sequencing on this subset of tumors will help identify the molecular basis of MEN1 variable genetic expressivity.

21 Article Therapeutic Strategies for Advanced Pancreatic Neuroendocrine Tumors with Segmental Portal Hypertension. 2015

Dumont, F / Goudard, Y / Caramella, C / Goéré, D / Baudin, E / Elias, D. ·Department of Surgical Oncology, Gustave Roussy Cancer Campus, 114 rue Edouard Vaillant, 94805, Villejuif Cedex, France, fredericdumont3108@yahoo.fr. ·World J Surg · Pubmed #25804547.

ABSTRACT: BACKGROUND: Pancreatic neuroendocrine tumors (PNET) locally advanced may lead to significant local symptoms especially segmental portal hypertension (SPH) with risk of bleeding. The aim of our study was to evaluate the role of SPH on the PNET management in an expert center. METHODS: Forty-two patients treated for locally advanced PNET with SPH between January 1984 and December 2012 were retrospectively analyzed. RESULTS: The median age was 55 years (25-75). The median tumor size was 7.5 cm (3-20). Thirty four (80.9%) patients were metastatic mainly in the liver (n=33, 79%) with a frequent (n=16, 38.1%) involvement>20%. The surgery was impossible because of SPH in 7 (16.6%) cases. Pancreatic resection was performed in 28 (66.7%) cases by distal pancreatectomy. Neoadjuvant chemotherapy (n=24, 57%) had no impact on SPH with no modification of collateral circulation. Among operated on patients, complete macroscopic resection was obtained in 19 (67.8%) patients. The mortality and severe morbidity rate was respectively 3.6 and 18%. Five year overall survival (OS) was similar in operated and no operated patients. (61%; p=0.64). The 5-year OS was 77.9 or 55.4% in patients who underwent a complete or incomplete macroscopic resection of primary and metastases, respectively. CONCLUSION: PNET resection associated with SPH is feasible with a low morbimortality. SPH was not improved by chemotherapy. Prolonged survival was observed after complete macroscopic resection.

22 Article Long-term results of the surgical management of insulinoma patients with MEN1: a Groupe d'étude des Tumeurs Endocrines (GTE) retrospective study. 2015

Vezzosi, Delphine / Cardot-Bauters, Catherine / Bouscaren, Nicolas / Lebras, Maëlle / Bertholon-Grégoire, Mireille / Niccoli, Patricia / Levy-Bohbot, Nathalie / Groussin, Lionel / Bouchard, Philippe / Tabarin, Antoine / Chanson, Philippe / Lecomte, Pierre / Guilhem, Isabelle / Carrere, Nicolas / Mirallié, Eric / Pattou, François / Peix, Jean Louis / Goere, Diane / Borson-Chazot, Françoise / Caron, Philippe / Bongard, Vanina / Carnaille, Bruno / Goudet, Pierre / Baudin, Eric. ·Service d'EndocrinologieMaladies Métaboliques et Nutrition, Centre Hospitalier Universitaire Rangueil-Larrey, Université Paul Sabatier et INSERM U1037, Toulouse, FranceCHRU de LilleClinique Marc-Linquette, Service d'Endocrinologie-Métabolisme, Lille, FranceService d'EpidémiologieCentre Hospitalier Universitaire, Toulouse, FranceClinique d'EndocrinologieCentre Hospitalier Universitaire, Nantes, FranceService d'EndocrinologieCentre Hospitalier Est, Hospices Civils de Lyon, Université Lyon 1 et INSERM U1052, Lyon, FranceService d'EndocrinologieDiabète et Maladies Métaboliques, Centre Hospitalier Universitaire La Timone, Marseille, FranceService d'EndocrinologieCentre Hospitalier Universitaire de Reims, Hôpital Robert Debré, Reims, FranceService d'EndocrinologieCentre Hospitalier Universitaire de Cochin, Paris, FranceService d'EndocrinologieGroupement Hospitalier Universitaire Est, Hôpital Saint Antoine, Paris, FranceService d'EndocrinologieCentre Hospitalier Universitaire, Hôpital du Haut Levêque, Pessac, FranceService d'Endocrinologie et des Maladies de la ReproductionHôpitaux Universitaires Paris-Sud, Hôpital de Bicêtre, Le Kremlin-Bicêtre, FranceUnité ENDCHRU Bretonneau, Tours, FranceService d'EndocrinologieDiabète et Maladies Métaboliques, CHU de Rennes, Hôpital Sud, Rennes, FranceService de Chirurgie digestiveCHU Purpan, Toulouse, FranceClinique de Chirurgie Digestive et EndocrinienneCHU Nantes, Nantes, FranceService de Chirurgie Générale et EndocrinienneCHU Lille, Lille Cedex, FranceService de Chirurgie EndocrinienneHospices Civils de Lyon, Centre Hospitalier Lyon Sud, Pierre Bénite, FranceService de Chirurgie OncologiqueInstitut Gustave Roussy, Villejuif, FranceService de Chirurgie EndocrinienneCentre Hospitalier Universitaire de Dijon, Dijon, FranceService de Médecine Nucléaire et de Cancérologie EndocrineInstitut Gustave Roussy, Villejuif, France. · Service d'EndocrinologieMaladies Métaboliques et Nutrition, Centre Hospitalier Universitaire Rangueil-Larrey, Université Paul Sabatier et INSERM U1037, Toulouse, FranceCHRU de LilleClinique Marc-Linquette, Service d'Endocrinologie-Métabolisme, Lille, FranceService d'EpidémiologieCentre Hospitalier Universitaire, Toulouse, FranceClinique d'EndocrinologieCentre Hospitalier Universitaire, Nantes, FranceService d'EndocrinologieCentre Hospitalier Est, Hospices Civils de Lyon, Université Lyon 1 et INSERM U1052, Lyon, FranceService d'EndocrinologieDiabète et Maladies Métaboliques, Centre Hospitalier Universitaire La Timone, Marseille, FranceService d'EndocrinologieCentre Hospitalier Universitaire de Reims, Hôpital Robert Debré, Reims, FranceService d'EndocrinologieCentre Hospitalier Universitaire de Cochin, Paris, FranceService d'EndocrinologieGroupement Hospitalier Universitaire Est, Hôpital Saint Antoine, Paris, FranceService d'EndocrinologieCentre Hospitalier Universitaire, Hôpital du Haut Levêque, Pessac, FranceService d'Endocrinologie et des Maladies de la ReproductionHôpitaux Universitaires Paris-Sud, Hôpital de Bicêtre, Le Kremlin-Bicêtre, FranceUnité ENDCHRU Bretonneau, Tours, FranceService d'EndocrinologieDiabète et Maladies Métaboliques, CHU de Rennes, Hôpital Sud, Rennes, FranceService de Chirurgie digestiveCHU Purpan, Toulouse, FranceClinique de Chirurgie Digestive et EndocrinienneCHU Nantes, Nantes, FranceService de Chirurgie Générale et EndocrinienneCHU Lille, Lille Cedex, FranceService de Chirurgie EndocrinienneHospices Civils de Lyon, Centre Hospitalier Lyon Sud, Pierre Bénite, FranceService de Chirurgie OncologiqueInstitut Gustave Roussy, Villejuif, FranceService de Chirurgie EndocrinienneCentre Hospitalier Universitaire de Dijon, Dijon, FranceService de Médecine Nucléaire et de Cancérologie EndocrineInstitut Gustave Roussy, Villejuif, France eric.baudin@gustaveroussy.fr. ·Eur J Endocrinol · Pubmed #25538206.

ABSTRACT: OBJECTIVE: Management of insulinomas in the context of MEN1 remains poorly studied. The aim of this study was to evaluate long-term results of various surgical approaches in a large cohort of insulinoma-MEN1 patients. DESIGN AND METHODS: Consecutive insulinoma-MEN1 patients operated on for a nonmetastatic insulinoma between 1957 and 2010 were retrospectively selected from the MEN1 database of the French Endocrine Tumor Group. The type of surgery was categorized as distal pancreatectomy (DP), total pancreatectomy/cephalic duodenopancreatectomy (TP/CDP), or enucleation (E). Primary endpoint was time until recurrence of hypoglycemia after initial surgery. Secondary endpoints were post-operative complications. RESULTS: The study included 73 patients (median age=28 years). Surgical procedures were DP (n=46), TP/CDP (n=9), or E (n=18). After a median post-operative follow-up of 9.0 years (inter-quartile range (IQR): 2.5-16.5 years), 60/73 patients (82.2%) remained hypoglycemia free. E and TP/CDP were associated with a higher risk of recurrent hypoglycemia episodes (unadjusted hazard ratio: 6.18 ((95% CI: 1.54-24.8); P=0.010) for E vs DP and 9.51 ((95% CI: 1.85-48.8); P=0.007) for TP/CDP vs DP. After adjustment for International Union against Cancer pTNM classification, enucleation remained significantly associated with a higher probability of recurrence. Long-term complications had occurred in 20 (43.5%) patients with DP, five (55.6%) with TP/CDP, but in none of the patients who have undergone E (P=0.002). CONCLUSION: In the French Endocrine database, DP is associated with a lower risk for recurrent hypoglycemia episodes. Due to lower morbidity, E alone might be considered as an alternative.

23 Article [Malignant insulinoma: recommendations for workup and treatment]. 2014

Baudin, Eric / Caron, Philippe / Lombard-Bohas, Catherine / Tabarin, Antoine / Mitry, Emmanuel / Reznick, Yves / Taieb, David / Pattou, François / Goudet, Pierre / Vezzosi, Delphine / Scoazec, Jean-Yves / Cadiot, Guillaume / Borson-Chazot, Françoise / Do Cao, Christine / Anonymous1650795. ·Institut Gustave-Roussy, service de médecine nucléaire et d'oncologie endocrinienne, 94805 Villejuif cedex, France. Electronic address: eric.baudin@igr.fr. · CHU Rangueil-Larrey, pôle cardiovasculaire et métabolique, service d'endocrinologie et maladies métaboliques, 31059 Toulouse cedex 9, France. · Hôpital Édouard-Herriot, Fédération des spécialités digestives, 69003 Lyon, France. · Hôpital Haut-Lévêque, service d'endocrinologie, 33600 Pessac, France. · Institut Curie, hôpital René-Huguenin, service d'onco-gastroentérologie, 92210 Saint-Cloud, France. · CHU Côte-de-Nacre, unité fonctionnelle d'endocrinologie et maladies métaboliques, 14033 Caen cedex, France. · CHU de la Timone, service central de biophysique et de médecine nucléaire, 13005 Marseille, France. · Hôpital Claude-Huriez, service de chirurgie endocrinienne, 59000 Lille, France. · CHU de Dijon, service de chirurgie générale et endocrinienne, 21000 Dijon, France. · Institut Gustave-Roussy, service de biologie et de pathologie médicales, 94805 Villejuif cedex, France. · Hôpital Robert-Debré, service d'hépato-gastro-entérologie et de cancérologie digestive, 51100 Reims, France. · Hospices Civils de Lyon, Fédération d'endocrinologie du pole Est, Fédération d'endocrinologie et centre de médecine nucléaire, 69500 Lyon, France. · Hôpital Claude-Huriez, service d'endocrinologie et de maladies métaboliques, 59000 Lille, France. ·Presse Med · Pubmed #24857257.

ABSTRACT: Insulinoma are malignant in 4 to 14 % of cases. Their rarity and the sparse data available in the literature have limited publication of specific guidelines for their management. The following review aim to provide up-to-date recommendations on initial evaluation including pathologic grading, measures to control hypoglycemia, antitumor strategies and long term follow-up. Will be discussed in detail respective indications of surgery, diazoxide, somatostatin analogs, everolimus, sunitinib, liver directed treatments including arterial embolization, chemotherapy and radiometabolic therapy. A Medline search using terms "insulinoma", "neuroendocrine pancreatic tumors", "islet cell carcinoma", "malignant insulinoma" was performed limiting the selection to English language articles and adult age cases, along with cross referencing.

24 Article Are G3 ENETS neuroendocrine neoplasms heterogeneous? 2013

Vélayoudom-Céphise, Fritz-Line / Duvillard, Pierre / Foucan, Lydia / Hadoux, Julien / Chougnet, Cecile N / Leboulleux, Sophie / Malka, David / Guigay, Joël / Goere, Diane / Debaere, Thierry / Caramella, Caroline / Schlumberger, Martin / Planchard, David / Elias, Dominique / Ducreux, Michel / Scoazec, Jean-Yves / Baudin, Eric. ·Department of Nuclear Medicine and Endocrine Oncology, Villejuif, France. ·Endocr Relat Cancer · Pubmed #23845449.

ABSTRACT: The new WHO classification of gastroenteropancreatic (GEP) neuroendocrine tumors (NET) implies that G3 neoplasms with mitotic index >20 and/or Ki67 index >20% are neuroendocrine carcinomas (NEC), described as poorly differentiated, small or large cell types, by analogy with lung NEC. To characterize the subgroup of non-small-cell-type GEP and thoracic NET with mitotic index >20 and/or Ki67 >20% according to their pathological features, response to cisplatin and overall survival (OS). We reviewed pathological and clinical presentation of G3 non-small-cell-type NET referred to our institution for 5 years. Data from 166 patients with metastatic thoracic and GEP-NET were collected. Twenty-eight patients (17%) fulfill the inclusion criteria. Tumors were classified as well-differentiated NET (G3-WDNET) in 42.8% of cases and poorly differentiated, large-cell NEC (G3-LCNEC) in 57.2% of cases. Plasma chromogranin A or neuron-specific enolase were elevated in 42 and 25% respectively of G3-WDNET and 31 and 50% of G3-LCNEC. Somatostatin receptor scintigraphy was positive in 88 and 50% of G3-WDNET or G3-LCNEC respectively. Complete or partial response to cisplatin was observed in 31% of cases, all classified as G3-LCNEC. The median OS was 41 months for G3-WDNET but 17 months for G3-LCNEC (P=0.34). Short survival was observed in 25% of G3-WDNET but 62.5% of G3-LCNEC patients (P=0.049). G3 ENETS GEP and thoracic neuroendocrine neoplasms (NEN) could constitute a heterogeneous subgroup of NEN as regards diagnosis, prognosis, and treatment. If confirmed, future classifications may consider splitting them into two groups according to their morphological differentiation.

25 Article Frequency and characterization of gastro-entero-pancreatic neuroendocrine tumor patients with high-grade of uptake at somatostatin receptor scintigraphy. 2013

Chougnet, Cecile N / Leboulleux, Sophie / Caramella, Caroline / Lumbroso, Jean / Borget, Isabelle / Déandreis, Désirée / Duvillard, Pierre / Elias, Dominique / de Baere, Thierry / Vélayoudom-Céphise, Fritz-Line / Guigay, Joël / Ducreux, Michel / Schlumberger, Martin / Baudin, Eric. ·Departments of Nuclear Medicine and Endocrine Tumors, Institut Gustave Roussy, University Paris-Sud, 114 Rue Edouard Vaillant, 94805 Villejuif Cedex, France. ·Endocr Relat Cancer · Pubmed #23404855.

ABSTRACT: Recent studies suggest that the somatostatin receptor scintigraphy (SRS) grade of uptake is a predictor of response to peptide receptor radionuclide therapy (PRRT). To identify and characterize patients with well-differentiated (WD) neuroendocrine neoplasm (NEN) displaying a high-grade uptake at SRS. Patients with WD-NEN, whose SRS films were available for review, were retrospectively included. SRS was reviewed by three independent readers and classified into four subgroups based on a modified Krenning's scale (mKS): no uptake (group-0), homogeneous grade 1-2 uptake (group-1), homogeneous grade 3-4 (group-2), and heterogeneous grade 1-4 (group-3). A simplified scale (sS) of SRS was also used to look for characteristics of patients with high-grade uptake. One hundred and six WD-NEN patients were enrolled. Group-0, group-1, group-2, and group-3 were found in 17, 8, 33, and 42% of cases respectively. High-grade uptake at sS (75% of cases) was correlated with older age, functioning NEN, high chromogranin-A level, and grade 1 (G1) NEN based on mitotic count. Based on the mKS or sS scales, no difference on survival was found. Thirty-three to seventy-five percent of metastatic NEN patients can be considered candidates for PRRT based on homogeneous or heterogeneous high-grade uptake. Functioning G1 NEN patients could be the best candidates for PRRT. Randomized trials are expected to confirm this result.

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