A Newsletter for Medical Professionals and ENETS Members

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1 A Newsletter for Medical Professionals and ENETS Members Summer/Fall 2013 The European Neuroendocrine Tumor Society (ENETS) Executive Committee: Chairman: Kjell Öberg, Uppsala, Sweden Vice-Chairman: Philippe Ruszniewski, Clichy, France Chairman-Elect: Martyn Caplin, London, United Kingdom Treasurer: Bertram Wiedenmann, Berlin, Germany Scientific Secretary: Aurel Perren, Bern, Switzerland Members: Dermot O Toole, Dublin, Ireland; Massimo Falconi, Ancona, Italy; Beata Kos-Kudła, Katowice, Poland; Ramon Salazar, Barcelona, Spain Editing: Language Editor/Coodination: Elizabeth Zach Layout and Publishing: Karger Publishing, Basel, Switzerland ENETS Coordinating Offi ce: Charité Universitätsmedizin Campus Virchow-Klinikum Department of Gastroenterology and Hepatology Augustenburger Platz 1 D Berlin, Germany Tel Fax enets.offi ce@charite.de In this issue: 10th Annual ENETS Conference ENETS Centers of Excellence Online NET Education GETNE Trial Letter from the Chairman In introducing this issue of the, I would like to extend a warm welcome to the many new Society members. Following the 10th Annual ENETS Conference, which was held 6 8 March 2013 in Barcelona, we received approximately 150 new membership applications, a record. On behalf of the ENETS Executive Committee, we appreciate your interest in ENETS and look forward to your participation in future events. Inside the Newsletter, you ll find an overview of the ENETS 2013 conference, which received very positive participant reviews. In the spring, the scientific organizing committee will already begin preliminary work on the 2014 meeting, using the topic suggestions, as well as suggestions for improvement, from comments received in Barcelona. Most noteworthy was the growing success of the conference postgraduate course, which will be a part of the 2014 meeting, along with a workbook. In addition, the Meet the Professor courses were extremely popular at Barcelona, with the waiting lists far exceeding the possible places. We look to expand that part of the program, as well as the nurses symposium. As of May 2013, the Society claims close to 1,200 Kjell Öberg members. ENETS offers several opportunities for our younger members to participate at the annual conference and thereby advance their knowledge of NET research. This year at Barcelona, ENETS awarded seven travel grants, six abstract awards and a research fellowship (funded together with Ipsen), and we plan to continue this giving in Plans are also underway to expand a summer school program for younger researchers. In other news, I d like to let all ENETS members know that we are in the process of improving our website so as to make it more dynamic and user-friendly. The 2012 ENETS Guidelines are available for download (not just for members) from the homepage, and information on the Centers of Excellence program is also there (members only). The latter has attracted increased interest, adding six new Centers this year to the already established 19. Inside the Newsletter, you ll also find more information on the e-learning project, which will soon be available via the ENETS website for members. Stay tuned for that and more. Meanwhile, ENETS is preparing to hold its 2013 Advisory Board Conference in the fall. The ENETS Advisory Board consists of 40 members, and the group reflects a balanced mix of disciplines and nationalities. As with previous years, case studies will be on the program, and these will then be presented at the 2014 Annual Conference. Board members will also likely review the GETNE trial, which you can read about in the Newsletter, too. Again, I thank you for your support and interest in ENETS, and in making it a viable and worthwhile medical society. I welcome all members to let us know how we can improve ENETS, and we look forward to your further engagement in the Society and in neuroendocrine tumor research. Kjell Öberg, Uppsala, Sweden

2 This year s ENETS Annual Conference, the 10th of its kind, was held in Barcelona, 6 8 March. While the number of participants close to 1,700 has levelled off in recent years, most noteworthy is the overwhelming growth in attendance at the conference s postgraduate course a record of nearly 500 participants and enthusiasm for the conference Meet the Professor sessions and nurses symposium. Following feedback from the conference, these events will be enhanced for next year s meeting. The postgraduate course gives participants an educational overview of the field of neuroendocrine neoplasia (NEN), whereas the nurses symposium this year focused on treatment challenges and side effects, as well as the quality of life for NEN patients. The two-day main program started on 7 March with a particularly well-attended session on the role of histopathology in NEN, discussing the role of different Ki-67 cut-off values in pancreatic NEN. Furthermore, the value of high Ki-67 index in predicting therapy response for cisplatin-based therapies and of low Ki-67 index for somatostatin analogue therapy was demonstrated. Another lecture featured a head-to-head discussion on the role of surgery in gastroenteropancreatic NEN. This session nicely showed the existing controversy about the treatment of pancreatic incidentaloma, which will become an increasing issue due to improvements in imaging techniques. During another lecture, the question was raised as to whether the current RECIST criteria for imaging modalities work well enough in predicting therapy response in NEN patients, especially if treated with new targeted therapies, where maybe features other than diameter of target lesions resemble treatment response. In the clinical abstracts session, the promising data of the phase II trials of Telotristat Etiprate in patients with refractory carcinoid syndrome were shown, which may in the future compromise another treatment option for carcinoid syndrome. Also discussed were controversies about well-differentiated NEN. First, the value of a wait-and-see approach was addressed. Secondly the question was raised as to whether FDG-PET may play a role in the diagnostic work-up of well-differentiated NEN. And following a tradition begun at ENETS 2012 in Copenhagen, a tumor board session was held, this time focusing on rare neuroendocrine neoplasia as ACTHoma, MTC and pulmonary NEN. After this a presentation on recently completed and future studies was given, including notable future phase III trials such as the NETTER-1 study comparing Lutetium-PRRT with Octreotide 60 mg in non-pancreatic NEN and the SEQTOR trial comparing the therapy sequence of Streptozotocin/5-FU followed by Everolimus and vice versa in pancreatic NEN. One session also presented the possible role of circulating neuroendocrine tumor cells in predicting response to chemotherapy, representing a promising future follow-up tool. And for the first time, a session was dedicated to lung NEN. This year s ENETS Life Achievement Awards was given to Larry Kvols from Tampa, Florida. In the dedication delivered by Jonathan Strosberg, a former student of Larry Kvols, Dr. Kvol s career was detailed along with anecdotes from his private life. Unfortunately, Dr. Kvols, because of illness, could not attend the Barcelona conference, but we expect to see him at the ENETS meeting in Sebastian Maasberg, MD, Berlin Registration numbers at this year s conference were comparable to recent previous meetings, however, attendance at the postgraduate course, expert sessions and the nurses symposium have increased substantially. Marco Volante gave two Meet the Professor lectures at Barcelona, and feedback for those talks was extremely positive. ENETS introduced a conference app for this year s annual conference and will expand on this for next year s event. ENETS chairman, Kjell Öberg, welcomed delegates to the 10th Annual ENETS Conference in Barcelona S. Karger AG, Basel Fax karger@karger.ch

3 Thomas Steinmüller presented on What should be done after removal of an appendiceal NET or goblet cell tumors? This year s recipient of the ENETS Translational Research Fellowship, sponsored in part by Ipsen, is Timon Vandamme. Here, he receives the award from ENETS chairman, Kjell Öberg. Guido Rindi, a former chairman of ENETS, gave a well-attended talk on Ki-67 cut-offs Annual Conference Coordination: Małgorzata Szott-Emus (project manager) Simon Hirschmann (technical management) Elizabeth Zach (development and communications) Uli Knell (project assistance, registration and logistics) Lenz Leberkern, Birgit Technik (graphic design, photography, logistics) Panelists at the session on histopathology session (l. to r.: Laura Tang, Jean-Yves Scoazec, Francesco Panzuto and Guido Rindi)

4 Ulrich Knigge accepts the award for his colleague, Ingrid Olsen, who placed third in the clinical research category for her abstract Goblet Cell Carcinoids: Characteristics of a Danish Cohort of 85 Patients Ulrich-Frank Pape, left, joins Kjell Öberg and Martyn Caplin (center, right) at the speakers table during the postgraduate course. Dr. Pape spoke on the role of TNM staging in NET management. Martyn Caplin, scientific secretary for ENETS, opened this year s popular postgraduate course. Plans are underway to enhance the course by developing an explanatory workbook next year. Dermot O Toole spoke at the postgraduate course on when EUS should be used. Ramon Salazar of Barcelona spoke on chemotherapy vs. molecular targeted therapy for pancreatic NET. Marianne Pavel discussed chemotherapy vs. molecular targeted therapy for intestinal NET. Jaroslaw Cwikła spoke on MIBG, Y-90 DOTATOC / TATE to Lutetium-177 DOTA Octreotate, evolution and survival of the fittest. Bertram Wiedenmann spoke at the postgraduate course on how to manage gastrointestinal complications in NETs.

5 Conference delegates paid tribute to Hakan Ahlman, a founding member of ENETS who died in Dr. Ahlman contributed to the ENETS diagnosis and treatment guidelines and was a member of the ENETS Advisory Board. Jonathan Strosberg gave the dedication honouring Dr. Larry Kvols, this year s recipient of the ENETS Life Achievement Award. Unfortunately, Dr. Kvols, due to illness, could not attend the Barcelona conference. Dr. Larry Kvols in his younger years as an oncologist in training. The nurses symposium received great praise following the conference. Feedback indicates that many delegates would like to see the event extended to a one-day, as opposed to just a morning session. Bruno Niederle advocated for limited resection during a debate session on whether surgery improves outcome in GEP-NETs. Anja Rinke presented her abstract Risk of Recurrence in Patients with Neuroendocrine Tumors after R0-Resection. All photo credits go to Birgit Technik. Tao Cui, who works in the department of Kjell Öberg at Uppsala University, was awarded first prize in the basic science abstract category. David Gross gave the final conference lecture, a clinical case on lung NET, prepared by the ENETS Advisory Board.

6 Feedback: 10th Annual ENETS Conference The following graphic illustrates participant feedback from the 10th Annual ENETS Conference in Barcelona, 6 8 March Participants could also comment on the program and suggest topics for next year s conference in Barcelona. Work on the program has already begun and the 2014 conference program will be made public on the ENETS website in September.

7 In Memory of Håkan Ahlman Håkan Ahlman graduated from the University of Gothenburg in 1972 and earned his PhD in 1976 with a doctorial thesis on Fluorescence Histochemical Studies on Serotonin in the Small Intestine and the Influence of Vagal Nerve Stimulation. He was further a research fellow in surgery at the University of Illinois, Chicago between 1978 and 1979 and at Downstate Hospital, New York, He was Professor of Endocrine Surgery at Gothenburg University since He had a couple of hundred publications in the field of neuroendocrine tumors and was a founding member of ENET in 1995 and of ENETS in Professor Ahlman died from a malignant disease in October The Centers of Excellence The Centers of Excellence program has been very active over the past years. Since its inaugural test phase in 2008/2009, in which six test phase Centers were accredited, the program has expanded across Europe, attracting considerable interest. To date, 25 Centers of Excellence have been accredited via the rigorous auditing process and based on an ENETS-derived Catalogue of Requirements (the latter has also undergone slight amendments over the past two years) under supervision of the ENETS Advisory Board. Audits are managed by an independently validated ISO company (GSG Consulting), in conjunction with five expert auditors. (Due to the increased workload, an additional auditor was recruited in 2013). The ENETS Cert Commission would like to congratulate the six new Centers accredited this year: Neuroendocrine Tumour Centre Aarhus University Hospital, Aarhus; King s Health Partners NET Centre, London; NET Centre at University Hospital Zurich; Multidisciplinary Group for Neuroendocrine Tumors, Naples; Multidisciplinary NET Group Humanitas Cancer Center, Rozzano; Interdisziplinäres Endokrines und Neuroendokrines Tumorforum (IENET) am UCT Mainz, Mainz, Germany. As well as adding six new Centers to the program, the initial test phase Centers were re-audited, allowing for appraisal of qualitative and quantitative issues within individual Centers. Feedback was extremely positive, with all Centers reporting large increases in patient numbers; the scientific output has also increased considerably. The annual ENETS-Center of Excellence commission meeting was held in Barcelona in March We are encouraging applications from institutes in Eastern Europe. In addition, there has been much interest from Centers outside of Europe and ENETS is in the process of examining the possibility of opening the accreditation process beyond Europe. However, the logistical demands would be a major obstacle and no formal decision has yet been made on how best to proceed. The ENETS Centres of Excellence are: ENETS CoE Charité, Universitätsmedizin Berlin, Campus Virchow-Klinikum, Germany Contact: Bertram Wiedenmann Neuroendocrine Tumor (NET) Center, Uppsala University Hospital, Sweden Contact: Staffan Welin Neuroendocrine Tumor Center of Excellence, Rigshospitalet, University of Copenhagen, Denmark Contact: Ulrich Knigge Neuroendocrine Tumor (NET) Center Erasmus MC Rotterdam, The Netherlands Contact: Wouter de Herder Neuroendocrine Tumor (NET) Center Clichy, Hôpital Beaujon, Clichy, France Contact: Philippe Ruszniewski Neuroendocrine Tumor (NET) Center, Royal Free Hospital, London, United Kingdom Contact: Martyn Caplin Neuroendocrine Tumor (NET) Center, Fondazione IRCCS Istituto Nazionale dei Tumori, Milan, Italy Contact: Emilio Bajetta Liverpool NET Service, Merseyside Regional Neuroendocrine Service, Royal Liverpool University Hospital (RLUH), United Kingdom Contact: S.Vinjamuri National Center for Neuroendocrine Tumors, Oslo University Hospital, Rikshospitalet, Norway Contact: Deidi Bergestuen

8 Gruppo Multidisciplinare Regionale Tumori Neuroendocrini, Dept. of Internal Medicine and Endocrine Sciences, Perugia, Italy Contact: Piero Ferolla Zentrum für Neuroendokrine Tumore, Zentralklinik Bad Berka GmbH, Bad Berka, Germany Contact: Dieter Hoersch Neuroendocrine Tumor (NET) Center, Hôpital Edouard HERRIOT, Lyon, France Contact: Catherine Lombard-Bohas Marburger NET-Zentrum, Universitätsklinikum Giessen and Marburg GmbH, Standort Marburg, Germany Contact: Anja Rinke Oxford NET Centre at Oxford Radcliffe Hospitals (ORH), Oxford, United Kingdom Contact: Denis Talbot Christie Neuroendocrine Tumour, Service (ChristieNETS), The Christie NHS Foundation Trust, Manchester, United Kingdom Contact: Juan Valle Neuroendocrine Tumor (NET) Center, University Hospital Gasthuisberg-KU Leuven, Belgium Contact: Eric Van Cutsem Neuroendocrine Tumor (NET) Center Imperial College Healthcare NHS Trust Hammersmith Hospital, London, United Kingdom Contact: Andrea Frilling GEPNET_KUM Interdisciplinary Center of Neuroendocrine Tumors of the GastroEnteroPancreatic System Klinikum der LMU München, Campus Grosshadern, Munich, Germany Contact: Christoph Auernhammer Neuroendocrine Tumor (NET) Center AvL-NKI, Amsterdam, The Netherlands Contact: Margot Tesselaar Kings Health Partners NET centre affiliated to Kent Oncology and Hampshire Hospitals c/o Institute of Liver Studies, King s College Hospital NHS Foundation Trust, London, United Kingdom Contact: John Ramage Neuroendocrine Tumour Centre Aarhus University Hospital, AUH-NET Centre, Aarhus, Denmark Contact: Henning Groenbaek Neuroendocrine Tumor (NET) Center UniversitätsSpital Zürich, Switzerland Contact: Peter Bauerfeind Multidisciplinary Group for Neuroendocrine Tumors, Federico II University Hospital, National Cancer Institute G. Pascale Foundation Antonio Cardarelli Hospital, Naples, Italy Contact: Francesca Marciello Multidisciplinary NET Group Humanitas Cancer Center Istituto Clinico Humanitas, Rozzano (Milan), Italy Contact: Alessandro Zerbi Interdisziplinäres endokrines und neuroendokrines Tumorboard (IENET) Universitätsmedizin der Johannes Gutenberg-Universität Mainz, Germany Contacts: Matthias Weber, Christian Fottner GETNE1206 CLINICAL TRIAL: THE SEQTOR STUDY Randomized phase III open label cross-over study to compare the efficacy and safety of everolimus followed by chemotherapy with STZ-5FU upon progression or the reverse sequence, chemotherapy with STZ-5FU followed by everolimus upon progression, in advanced progressive pnets (SEQTOR study), is on its final. Present: During the last three months, the trial has advanced in parallel as follows: Agreement between GETNE and ENETS: An agreement has been signed to reflect the relationship between both organizations concerning SEQTOR: GETNE will be the sponsor of the study and ENETS shall give scientific auspice and support. Drs Ramon Salazar and Kjell Öberg are the PI and the translational studies coordinators, respectively. Agreement on Study costs: A budget has been generated considering CRO tasks, followed by an estimation of subsidizer distribution of study budget. Protocol finalization (a new secondary end point has been added to the protocol): A retrospective radiological assessment of images from the patients included in the study will be used for the validation of ENETS Composite Score as a secondary study objective. Sites identification: Thirty-nine interested sites have been identified by now, allowing the CRO, Quintiles Limited, to go straight ahead with Site Interest Forms and contact the sites in order to prepare a preselecting visit for final definition of sites. The study initiation has been delayed in order to finalize all legal and logistical details, which have been challenging. This being an academic 5 M Euro trial, it was crucial to assure financing all along the study period. The first patient in is expected for August Future: There are some pending issues to consider in the next few months: Contracts with subsidizer (under signature) and CRO (to be agreed) should be closed. There is a need for funds for the collection of images from sites and its sending to Paris for a centralized evaluation. There is a site in Denmark interested in sponsoring a translational substudy. Two Italian sites and one site from the Netherlands have shown last minute interest in the study, which will be considered depending on the study budget.

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