EJC Supplements RSS feed: Current Issue. The European Journal of Cancer (including EJC Supplements ), is an international comprehensive oncology journal that publishes original research, editorial comments, review articles and news on basic and preclinical research, clinical oncology (medical, paediatric, radiation, surgical), and on cancer epidemiology and prevention. EJC Supplements is available at no charge to subscribers of the European Journal of Cancer . Official Journal of the European Organisation for Research and Treatment of Cancer (EORTC), the European Association for Cancer Research (EACR), the European CanCer Organisation (ECCO) and the European Society of Mastology (EUSOMA). http://www.ejcancersupplements.info/?rss=yesElsevier Inc.en © 2012 Published by Elsevier Inc. All rights reserved. EJC Supplements1359-6349101March 2012 © 2012 Published by Elsevier Inc. All rights reserved. healthpermissions@elsevier.comhttp://www.ejcancersupplements.info/article/PIIS1359634912700010/abstract?rss=yesEditorial Board10.1016/S1359-6349(12)70001-0EJC Supplements 10, 1 (2012)2012-03-01EJC Supplements2012-03-01101S1359-6349(12)X0002-8iiiihttp://www.ejcancersupplements.info/article/PIIS1359634912700022/abstract?rss=yesAcknowledgements10.1016/S1359-6349(12)70002-2EJC Supplements 10, 1 (2012)2012-03-01EJC Supplements2012-03-01101S1359-6349(12)X0002-8ivvhttp://www.ejcancersupplements.info/article/PIIS1359634912700034/abstract?rss=yesThis issue commemorates the 50th anniversary of the European Organization for Research and Treatment of Cancer (EORTC); it includes a series of reports prepared by the EORTC groups and by the EORTC Headquarters staff that highlight the many achievements of this unique network of dedicated European investigators. It also stresses the EORTC's future strategies that will ensure the continuity of high quality cancer research needed to further improve treatments and thereby quality of life and survival for all patients with cancer.ForewordJean-Yves Blay10.1016/S1359-6349(12)70003-4EJC Supplements 10, 1 (2012)2012-03-01EJC Supplements2012-03-01101S1359-6349(12)X0002-812http://www.ejcancersupplements.info/article/PIIS1359634912700046/abstract?rss=yesAbstract: EORTC Headquarters plays a unique role in coordinating and supporting large-scale pan-European cancer clinical and translational research. Initially established to provide efficient methodological and coordinating services to the EORTC Research groups and to ensure professional involvement of the organization, it has grown over the years in step with an increasing number and complexity of cancer clinical trials. Recent advances in laboratories around the world have shed light on the biology of cancer, and EORTC Headquarters, armed with a competent and dedicated staff, continues to advance the state of cancer clinical research and implement the appropriate infrastructures to support the conduct of the next generation of cancer clinical trials. 50 years of the EORTC and the central role of the EORTC HeadquartersDenis Lacombe, John Bean, Jan Bogaerts, Andrew Bottomley, Laurence Collette, Caroline Gilotay, Ann Marinus, Sandrine Marréaud, Pascal Ruyskart, Richard Sylvester, Françoise Meunier10.1016/S1359-6349(12)70004-6EJC Supplements 10, 1 (2012)2012-03-01EJC Supplements2012-03-01101S1359-6349(12)X0002-8312http://www.ejcancersupplements.info/article/PIIS1359634912700058/abstract?rss=yesAbstract: Since the creation of the EORTC Headquarters in 1974, major advances have been made in the methodology used in the design and analysis of cancer clinical trials. However, the speed of these developments in the fields of biology, medicine, and statistics has greatly increased since the turn of the 21st century. These changes have all become possible because of the increased computer power now available. The landscape of therapeutic anti-cancer development changed completely with the advent of the so-called “targeted agents” that treat the underlying molecular basis of the disease rather than the symptoms of tumor proliferation. The new challenges posed by the clinical development of these numerous new agents that are expected to work in often yet-to-be-identified subgroups of patients induced a new wave of methodological developments. Some of these were readily embraced by the EORTC Headquarters statistics department, while others met with opposition. Our assessment is still in progress in many areas. Trials tend to become increasingly complex so that their planning relies on an increasing number of unknown parameters that need to be monitored during the trial itself, one development being “adaptive” design methodology. Because the knowledge required to design these new and more complex clinical trials and associated research program spans more disciplines (biology, genomics, radiology) and involves specialized knowledge within those disciplines, continued success requires further developing our partnerships with specialized departments (imaging, bio-informatics, biology, etc.) within EORTC Headquarters and in EORTC affiliated centers as well as collaborations with specialized statisticians from academia. Statistical methodology for personalized medicine: New developments at EORTC Headquarters since the turn of the 21st CenturyL. Collette, J. Bogaerts, S. Suciu, C. Fortpied, T. Gorlia, C. Coens, M. Mauer, B. Hasan, S. Collette, M. Ouali, S. Litière, J. Rapion, R. Sylvester10.1016/S1359-6349(12)70005-8EJC Supplements 10, 1 (2012)2012-03-01EJC Supplements2012-03-01101S1359-6349(12)X0002-81319http://www.ejcancersupplements.info/article/PIIS135963491270006X/abstract?rss=yesAbstract: Over the past decade a series of trials of the EORTC Brain Tumor Group (BTG) has substantially influenced and shaped the standard-of-care of primary brain tumors. All these trials were coupled with biological research that has allowed for better understanding of the biology of these tumors. In glioblastoma, EORTC trial 26981/22981 conducted jointly with the National Cancer Institute of Canada Clinical Trials Group showed superiority of concomitant radiochemotherapy with temozolomide over radiotherapy alone. It also identified the first predictive marker for benefit from alkylating agent chemotherapy in glioblastoma, the methylation of the O6-methyl-guanyl-methly-transferase (MGMT) gene promoter. In another large randomized trial, EORTC 26951, adjuvant chemotherapy in anaplastic oligodendroglial tumors was investigated. Despite an improvement in progression-free survival this did not translate into a survival benefit. The third example of a landmark trial is the EORTC 22845 trial. This trial led by the EORTC Radiation Oncology Group forms the basis for an expectative approach to patients with low-grade glioma, as early radiotherapy indeed prolongs time to tumor progression but with no benefit in overall survival. This trial is the key reference in deciding at what time in their disease adult patients with low-grade glioma should be irradiated. Future initiatives will continue to focus on the conduct of controlled trials, rational academic drug development as well as systematic evaluation of tumor tissue including biomarker development for personalized therapy. Important lessons learned in neurooncology are to dare to ask real questions rather than merely rapidly testing new compounds, and the value of well designed trials, including the presence of controls, central pathology review, strict radiology protocols and biobanking. Structurally, the EORTC BTG has evolved into a multidisciplinary group with strong transatlantic alliances. It has contributed to the maturation of neurooncology within the oncological sciences. EORTC topics in neurooncology: The long path from a focus on neurological complications of cancer towards molecularly defined trials and therapies in neurooncologyWolfgang Wick, Martin van den Bent, Charles Vecht, Alba Brandes, Denis Lacombe, Thierry Gorlia, Anouk Allgeier, Brigitta G. Baumert, Riccardo Soffietti, Marc Sanson, Abul B.M.F. Karim, Réne-Olivier Mirimanoff, Martin Taphoorn, Max Kros, Monika Hegi, Roger Stupp, on behalf of the EORTC Brain Tumor Group10.1016/S1359-6349(12)70006-XEJC Supplements 10, 1 (2012)2012-03-01EJC Supplements2012-03-01101S1359-6349(12)X0002-82026http://www.ejcancersupplements.info/article/PIIS1359634912700071/abstract?rss=yesAbstract: The EORTC Breast Cancer Group (BCG), created in 1962, is a multidisciplinary group involving surgeons, medical oncologists, radiation oncologists, pathologists, basic scientists, and clinical research fellows. Currently, more than 80 member's institutions across Europe are participating in the group studies. The main goal of the BCG is to conduct high-quality international clinical trials covering all areas of breast cancer care: from loco-regional to systemic disease control, and from in situ carcinoma to metastatic disease. Over 50 years, the BCG has performed dozens of clinical studies including several thousands of patients. Many practice-changing trials and major achievements were conducted optimizing local control, improving systemic therapy in early and metastatic breast cancer, pioneering work in clinical-translational trials and collaboration within intergroup trials. The strategic plan of the BCG for future research includes three distinct albeit overlapping areas: loco-regional therapy, (neo-)adjuvant systemic therapy, trials in the metastatic setting, and niche population studies. For each of these areas the group has considered the prevailing EORTC strategy of focusing on practice-changing studies and translational research, with an emphasis on niche trials. During five decades, the BCG has successfully performed a series of practice-changing trials enrolling several thousands of patients. These studies have contributed to the clinical knowledge on the treatment of breast cancer and have influenced clinical practice and breast cancer patients' outcome worldwide. The EORTC Breast Cancer Group: major achievements of 50 years of research and future directionsTanja Cufer, Fatima Cardoso, Gustavo Werutsky, Herve Bonnefoi, Etienne Brain, Luigi Cataliotti, Lissandra Dal Lago, Suzette Delaloge, Jacek Jassem, Geertjan van Tienhoven, Laura Van't Veer, Helen Westenberg, Sandrine Marreaud, Jan Bogaerts, Emiel Rutgers, David Cameron, on behalf of the EORTC Breast Cancer Group10.1016/S1359-6349(12)70007-1EJC Supplements 10, 1 (2012)2012-03-01EJC Supplements2012-03-01101S1359-6349(12)X0002-82733http://www.ejcancersupplements.info/article/PIIS1359634912700083/abstract?rss=yesAbstract: The EORTC Cancer in the ElderlyTask Force (ETF) aims to develop, conduct, coordinate and stimulate research on elderly patients with cancer. Towards this goal, the ETF has established close interactions with disease-oriented EORTC groups by having representatives from most of these groups attend the ETF meetings. In addition, the ETF reviews every new protocol for elderly-specific questions within the protocol review process of the EORTC aiming to reduce ageism within study protocols. Since 2006, the ETF decided to focus on three aspects: open a discussion on specific methodology for clinical trials in the older population; create a common language for describing heterogeneity between older individuals, the EORTC minimal dataset for geriatric assessment in older cancer patients; and develop specific clinical trials in the older population. This article reports the achievements of the ETF in these three domains and discusses its future strategies. The EORTC Cancer in the Elderly Task Force, a Protostar for EORTC's futureHans Wildiers, Etienne Brain, Bjorn Penninckx, Alistair Ring, Lazzaro Repetto, Pierre Soubeyran, Silvio Monfardini, Matti Aapro, Ulrich Wedding10.1016/S1359-6349(12)70008-3EJC Supplements 10, 1 (2012)2012-03-01EJC Supplements2012-03-01101S1359-6349(12)X0002-83438http://www.ejcancersupplements.info/article/PIIS1359634912700095/abstract?rss=yesAbstract: The EORTC Children's Leukemia Group (CLG) is a spin-off from the EORTC Hemopathies Working Party (adults and children). After a decade of collaboration in the adult-pediatric group it became clear that there was not only a large difference in cure rates between children and adults, but many chemotherapeutic-toxic borders were substantially different. During the following decade the CLG was not only a witness of a very exciting battle against childhood leukemia, but it also contributed substantially to better cure rates for these diseases. The main activity of the CLG was concentrated on the field of acute lymphoblastic leukemia (ALL). Fine tuning of treatment elements using the BFM design as a backbone has been done very successfully over the past decades. The CLG has many achievements, and the major ones include: the 58831 trial showing the superfluity of the prophylactic Central Nervous System (CNS) radiotherapy in ALL patients when a adequate systemic and CNS directed chemotherapy is ascertained. The 58881 trial demonstrated that the assessment of minimal residual disease (MRD) at completion of induction in ALL is a key step in the process to categorizing and allocating patients into different risk groups, and that MRD is a powerful and independent prognostic factor. This same 58881 trial showed the clear difference in efficacy of different asparaginases resulting in an optimization of the use these drugs and a revival of interest for the asparaginases in the treatment of ALL. In the near future the CLG will focus mainly on translational research projects and innovative biologically targeted treatment approaches, on collaborations with other children's leukemia groups in intergroup studies, and on the evaluation of the long-term outcome of childhood cancer survivors. The EORTC Children's Leukemia Group: Preclinical and clinical research and resulting achievementsYves Benoit, Stefan Suciu, Hélène Cavé, Alice Ferster, Nicole Dastugue, Patrick Lutz, Françoise Mazingue, Alain Robert, Anne Uyttebroeck, Lucilia Norton, Nicolas Sirvent, Pierre Rohrlich, Matthias Karrasch, Yves Bertrand, on behalf of the EORTC Children's Leukemia Group10.1016/S1359-6349(12)70009-5EJC Supplements 10, 1 (2012)2012-03-01EJC Supplements2012-03-01101S1359-6349(12)X0002-83945http://www.ejcancersupplements.info/article/PIIS1359634912700101/abstract?rss=yesAbstract: This article describes the achievements of the Cutaneous LymphomaTask Force (CLTF) over the recent decade in their goal to optimize classification and response criteria and establish new treatment options for patients suffering from cutaneous T-cell lymphomas (CTCL). Collaborative work with the International Society of Cutaneous Lymphoma (ISCL) and the United States Cutaneous Lymphoma Consortium (USCLC) has led to publication of pivotal manuscripts proposing revised staging proposals for Mycosis fungoides (MF)/Sézary syndrome (SS) and also non MF/SS primary cutaneous lymphomas as well as the recent publication of a proposal for defining endpoints in MF/SS. Major achievements of the EORTC Cutaneous Lymphoma Task Force (CLTF)Sean Whittaker, Robert Knobler, Pablo Ortiz, Maarten Vermeer, Matthias Karrasch, Baktiar Hasan, Denis Lacombe, Werner Kempf, Reinhard Dummer, Martine Bagot, on behalf of the EORTC Cutaneous Lymphoma Task Force (CLTF)10.1016/S1359-6349(12)70010-1EJC Supplements 10, 1 (2012)2012-03-01EJC Supplements2012-03-01101S1359-6349(12)X0002-84650http://www.ejcancersupplements.info/article/PIIS1359634912700113/abstract?rss=yesAbstract: During the last decades, the evolution of treatment - including radiotherapy, chemotherapy and targeted agents - has improved the cure and survival of patients with gastrointestinal (GI) cancer. Within the past 50 years of the EORTC's existence, significant progress has been made in the fight against cancer. During this time several cancer clinical trials were completed, and through these we are able to identify the most notable advances in GI cancer research done by the EORTC Gastrointestinal Tract Cancer Group (GI Group). Several EORTC clinical trials results have changed practice (e.g. standard of care of liver metastases of colorectal cancer has been changed by the EPOC trial) or have helped to support new treatment strategies in either early- or advanced-stage GI cancers. In addition to its clinical activities the group has started an extensive program of translational research. This changed strategy towards a translational, multidisciplinary program regarded as the basis for future developments. This review of the major achievements of the GI Group shows that it has played an important role in the scientific development of the understanding and treatment of GI cancer over the last 50 years. The EORTC Gastrointestinal Tract Cancer Group: 50 years of research contributing to improved gastrointestinal cancer managementGustavo Werutsky, Michel Ducreux, Manfred Lutz, Murielle Mauer, Eric Van Cutsem, Theo Ruers, Gunnar Folprecht, Markus Moehler, Daniela Aust, Jean-Luc Van Laethem, Florian Lordick, Bernard Nordlinger, Arnaud Roth, on behalf of the EORTC Gastrointestional Tract Cancer Group10.1016/S1359-6349(12)70011-3EJC Supplements 10, 1 (2012)2012-03-01EJC Supplements2012-03-01101S1359-6349(12)X0002-85157http://www.ejcancersupplements.info/article/PIIS1359634912700125/abstract?rss=yesAbstract: Founded 35 years ago, the European Organisation for Research and Treatment of Cancer Genito-Urinary Cancers Group (GU Group) has carried out a total of 99 phase I, II and III clinical trials in the fields of bladder, prostate, kidney, testicular and penile cancer. Meta-analyses have answered clinically important questions that the individual studies could not answer by themselves. From its very beginning, the GU Group has adopted a multidisciplinary approach, with collaboration among urologists, medical oncologists, radiation oncologists, pathologists and biostatisticians. It has also had a very successful collaboration with the EORTC Radiation Oncology Group and with national organizations such as the UK Medical Research Council. The results of their work, which remain standards in the field today, have directly led to major worldwide improvements in day to day clinical practice and have been incorporated into treatment guidelines such as those of the European Association of Urology. The group's intention is to build on this important legacy and to continue to develop and recruit to the multicenter, international randomized studies that have been their hallmark. Their primary aim will be to focus on clinical trials that investigate strategic therapeutic questions and which have the potential to change medical practice and improve our understanding of urologic malignancies. This includes studies with strong translational research components, prospective clinico-genomic and cancer biology/biomarker data and clinical trials addressing rare tumor types. To carry this strategy into the future, the contribution of individual clinicians, collaborative cancer trial groups and pharmaceutical companies is of fundamental importance. The EORTC Genito-Urinary Cancers Group: 35 years of achievements and future strategyR. Sylvester, L. Collette, A. Bex, N. Clarke, C.N. Sternberg, B. Tombal, on behalf of the EORTC Genito-Urinary Cancers Group10.1016/S1359-6349(12)70012-5EJC Supplements 10, 1 (2012)2012-03-01EJC Supplements2012-03-01101S1359-6349(12)X0002-85865http://www.ejcancersupplements.info/article/PIIS1359634912700137/abstract?rss=yesAbstract: After more than 30 years of clinical and translational research, and having contributed to large randomized international clinical trials in gynecologic cancer, the multidisciplinary EORTC Gynecologic Cancer Group (GCG) currently is dealing with one of the greatest challenges in cancer research, which is to discover and establish clinically useful predictive and prognostic factors, to identify subgroups of patients based on genomic patterns and activated pathways and to design clinical trials appropriate for such subgroups. EORTC GCG current and future research has to include the validation of prognostic and predictive markers, the identification of novel therapies that target specific pathways, and a better understanding of the molecular basis for resistance. These studies will require the collection of large numbers of biologic specimens, both at time of diagnosis and at time of recurrence and, whenever possible, during treatment. These objectives can only be reached with transversal cooperation within the EORTC framework (Pathobiology group, Imaging group, etc.), as well as international cooperation. Support from private industry will also be important in the context of a high-standard cooperation among industry and academia. The EORTC with its unique multidisciplinary infrastructure and long experience in cancer research is taking part through the EORTC GCG in international networks focused on gynecological cancer research on a large scale. Intergroup collaboration and international contribution to establish the current and future world-wide standards of care is also a priority for the GCG. The GCG also has a good track record in rare tumors and will continue working on rare diseases along with international partners. EORTC Gynecological Cancer Group on the frontline of practice-changing clinical trialsAntonio Casado, Bjorn Penninckx, Nick Reed, Maria E.L. van der Burg, Els M.J.J. Berns, Dionyssios Katsaros, Annamaria Ferrero, Fernando Mota, Antonio Jimeno, Jan Vermorken, Sergio Pecorelli, Corneel Coens, Ignace Vergote, on behalf of the EORTC Gynecological Cancer Group10.1016/S1359-6349(12)70013-7EJC Supplements 10, 1 (2012)2012-03-01EJC Supplements2012-03-01101S1359-6349(12)X0002-86675http://www.ejcancersupplements.info/article/PIIS1359634912700149/abstract?rss=yesHead and neck cancer, mostly of squamous cell origin, ranks sixth among the most common cancers, accounting for approximately 6% of all cases of cancer. Each year, more than 500,000 new cases are diagnosed worldwide. Approximately 60% of patients present with advanced disease (stages III and IV), for which the prognosis is poor. The multimodal curative standard treatment of squamous cell carcinoma of the head and neck (SCCHN) includes surgery followed by adjuvant treatment (radiotherapy ± chemotherapy) or primary radiotherapy in combination with chemotherapy (concurrent chemoradiation or induction chemotherapy) and/or targeted therapy. Despite this multimodality intensified approach, more than 50% of patients with locally advanced SCCHN will relapse.From chemoprevention and organ preservation programs to post-operative management: major achievements and strategies of the EORTC Head and Neck Cancer GroupJ.A. Langendijk, L. Licitra, A. Psyrri, R. Knecht, G. Andry, C. Fortpied, R. Karra Gurunath10.1016/S1359-6349(12)70014-9EJC Supplements 10, 1 (2012)2012-03-01EJC Supplements2012-03-01101S1359-6349(12)X0002-87681http://www.ejcancersupplements.info/article/PIIS1359634912700150/abstract?rss=yesAbstract: Imaging data have the potential to provide information on disease profiling pertaining to diagnosis, prognosis, selection of therapy, monitoring of response to therapy and pharmacokinetic information of drugs. Selection of the most appropriate imaging modality for a specific task will be vital for diagnosis, stratification, treatment response or treatment efficacy, toxicity assessment, and treatment outcome measures (progression-free survival). The EORTC Imaging Group was formed to establish and maintain the scientific and clinical value of advanced imaging in EORTC clinical trials. The group focuses on the development of specific analytical and review procedures as well as quality control procedures, in the context of clinical trials conducted by the EORTC groups. EORTC Imaging GroupNandita DeSouza, Otto S. Hoekstra, Ursula Nestle, Sigrid Stroobants, Ronald Boellaard, Cornelia Schaefer-Prokop, Lalitha Shankar, Liisa Pylkkanen, Ivalina Hristova, John Bean, on behalf of the EORTC Imaging Group10.1016/S1359-6349(12)70015-0EJC Supplements 10, 1 (2012)2012-03-01EJC Supplements2012-03-01101S1359-6349(12)X0002-88287http://www.ejcancersupplements.info/article/PIIS1359634912700162/abstract?rss=yesAbstract: The EORTC Infectious Disease Group (IDG) and its forerunners, the International Antimicrobial Therapy Cooperative Group (IATCG) and the Invasive Fungal Infection Group (IFIG), have helped drive and develop clinical practice in the management of bacterial and fungal infectious diseases. Besides undertaking seminal studies, the group in its various forms has played a key role in understanding the nature and management of the infectious complications that arise during the treatment of cancer, particularly hematological malignancies. The IATCG was also instrumental in setting the stage for large randomized controlled trials to address therapies for dealing with infections that developed during neutropenia. The three most important achievements of the group were in finding a rational basis for managing bacterial and fungal infections, the establishment of disease definitions, and the development of the guidelines. Three major achievements of the Infections Disease GroupMatteo Bassetti, Catherine Cordonnier, Johan Maertens, Oscar Marchetti, Marianne Paesmans, Liisa Pylkkanen, Paul E. Verweij, J. Peter Donnelly10.1016/S1359-6349(12)70016-2EJC Supplements 10, 1 (2012)2012-03-01EJC Supplements2012-03-01101S1359-6349(12)X0002-88893http://www.ejcancersupplements.info/article/PIIS1359634912700174/abstract?rss=yesAbstract: The EORTC Leukemia Group (LG) has a long history of promoting the study of leukemias and related malignancies and reports here on three of their most significant achievements. In acute myelogenous leukemia (AML), the LG and Italian group GIMEMA started their fruitful collaboration in 1986 with the AML-8 trial with 1519 inclusions. In the AML-8A trial, in patients who reached complete remission, without a HLA identical sibling, autograft provided longer disease-free survival than a second course of consolidation, whereas the best outcome was observed in patients with a donor, who had to be allografted. The AML-10 trial set a new standard of treatment for induction/consolidation with replacement of daunorubicin by either idarubicin or mitoxantrone. The AML-12 trial tested the effect of high-dose cytosine-arabinoside during induction (2109 inclusions, data base locked in August 2011 for final analysis). Development of intergroup trials focusing on subgroups of AML bearing specific genetic abnormalities is now mandatory to validate the “targeted approach” of driving molecular events. In high-risk myelodysplastic syndrome (MDS), the phase III trial conducted by the LG in collaboration with the German MDS Study Group showed that the response rate of decitabine versus best supportive care was higher (complete or partial remissions, 19% versus 0%, and hematologic improvement, 15% versus 2%), progression-free survival was significantly prolonged (median 6.6 versus 3 months), cumulative incidence of AML was significantly decreased (22% versus 33% at one year), but the impact on OS was less evident (median 10.1 versus 8.5 months; hazard ratio 0.88). Quality of life had improved significantly in patients in the decitabine arm. The assessment of HDAC inhibitors, such as vorinostat, will probably be tested in the next trial. Also in MDS, relevant genetic lesions involved in the pathogenesis of this disease were identified using single nucleotide polymorphisms array-based genomic profiling and genomic sequencing in 102 patients with MDS. Acquired abnormalities of the TET2 gene were identified in 26% of the cases and in the EZH2 gene in 5-10% of the patients. TET2 mutations were detected in 96% of the bone marrow cells, including CD34+ progenitor cells, suggesting that TET2 mutations could be an early event during disease evolution. In normal bone marrow, TET2 expression was elevated in granulocytes, suggesting a role in myelopoiesis. Conclusion: during the last 25 years the EORTC LG in cooperation with GIMEMA made a considerable contribution to the improvement of treatment results of patients with acute leukemia or MDS. EORTC Leukemia Group achievementsRoel Willemze, Stefan Suciu, Jean-Pierre Marie, Matthias Karrasch, Joop Jansen, Sergio Amadori, Petra Muus, Boris Labar, Frédéric Baron, Dominik Selleslag, Pierre Wijermans, Dominique Bron, Ann Hagemeijer, Giovanna Meloni, Michael Lübbert, Theo de Witte, on behalf of the EORTC Leukemia Group10.1016/S1359-6349(12)70017-4EJC Supplements 10, 1 (2012)2012-03-01EJC Supplements2012-03-01101S1359-6349(12)X0002-89498http://www.ejcancersupplements.info/article/PIIS1359634912700186/abstract?rss=yesAbstract: The EORTC Lung Cancer Group (LCG) maintains a multidisciplinary clinical trial portfolio. Over the years research has moved from investigators' ideas, to pharmacological company driven studies of new drugs, to the more recent biological marker driven studies. Non-small cell lung cancer (NSCLC) is the most common malignancy and has been the area of greatest activity. Malignant pleural mesothelioma (MPM) is a rare, aggressive tumor with a poor prognosis which has been a surprising area of collaborative research in the LCG for many years. Small cell lung cancer (SCLC) is well named, as it has become ‘small’ in every way, and has changed from being the most hopeful of tumors to what has now become a trialist's despair. This review will provide a review of major clinical trials and the contribution of the LCG. Challenges and priorities in the way forward will be presented and discussed. Treatment for non small cell lung cancer, small cell lung cancer and pleural mesothelioma within the EORTC Lung Cancer Group: past, present and futureMary E.R. O'Brien, Jan P. van Meerbeeck, Veerle F. Surmont, Corinne Faivre Finn10.1016/S1359-6349(12)70018-6EJC Supplements 10, 1 (2012)2012-03-01EJC Supplements2012-03-01101S1359-6349(12)X0002-899104http://www.ejcancersupplements.info/article/PIIS1359634912700198/abstract?rss=yesAbstract: Since 1964, the EORTC Lymphoma Group has conducted nine consecutive randomized phase III trials on early-stage Hodgkin lymphoma aimed at increasing efficacy while decreasing short- and long-term toxicities. Event-free and overall survival significantly improved from about 50% and 70%, respectively, in the early years to over 80% and 90%, respectively, more recently. Identification of prognostic subgroups appeared to be a successful method to tailor treatment strategies. Radiotherapy fields have become more restricted whereas chemotherapy has become standard. Early PET-CT has been introduced to investigate the possibility of treatment adaptation. Longitudinal quality-of-life assessment has become an integral part of our studies. An ongoing study focuses on the rehabilitation and quality of long-term survival in all 6658 Hodgkin lymphoma patients treated in EORTC trials since the earliest beginning. In advanced stages overall outcome has improved as well with 10-year survival rates of over 75%. Clinical achievements of the EORTC Lymphoma Group and aspects of future group strategyP. Meijnders, P. Carde, T. Girinsky, J.C. Kluin-Nelemans, M. Henry-Amar, J.M.M. Raemaekers, M. Karrasch, R. van der Maazen, for the EORTC Lymphoma Group10.1016/S1359-6349(12)70019-8EJC Supplements 10, 1 (2012)2012-03-01EJC Supplements2012-03-01101S1359-6349(12)X0002-8105111http://www.ejcancersupplements.info/article/PIIS1359634912700204/abstract?rss=yesAbstract: Since its inception in 1969, the EORTC Melanoma Group has employed a multidisciplinary approach in the fight against melanoma and has registered significant achievements in many areas of melanoma treatment and research. The group showed that sentinel node (SN) tumor burden according to the Rotterdam Criteria and the microanatomic location were the most important prognostic factors for melanoma-specific survival and non-SN positivity in the completion lymph node dissection specimen. They demonstrated that extended schedule escalated dose temozolomide is feasible and has an acceptable safety profile. They also showed that the interferon-a targeted therapy should occur in a targeted patient population, and should probably not be offered to 70% of the patients that are currently being given this treatment. Through EORTC trial 18991, Sylatron™, pegylated interferon a-2b, for the treatment of melanoma patients with microscopic or gross nodal involvement within 84 days of definitive surgical resection including complete lymphadenectomy, was approved by the US FDA. The present article describes the achievements and future strategies of the Melanoma Group. EORTC Melanoma Group achievementsAlessandro Testori, Stefan Suciu, Alexander C.J. van Akkooi, Martin Cook, Ghanem Ghanem, R. Karra Gurunath, Ulrich Keilholz, Leon van Kempen, Serge Leyvraz, Martin Mihm, Julia Newton-Bishop, Poulam Patel, Caroline Robert, Dirk Schadendorf, Gaetan de Schaetzen, Alan Spatz, Esther de Vries, Alexander M.M. Eggermont10.1016/S1359-6349(12)70020-4EJC Supplements 10, 1 (2012)2012-03-01EJC Supplements2012-03-01101S1359-6349(12)X0002-8112119http://www.ejcancersupplements.info/article/PIIS1359634912700216/abstract?rss=yesAbstract: The increasing demand for personalized cancer therapy requires a strong, intense, and continuous collaboration between pre-clinical and clinical investigators. As a part of the EORTC Translational Research Divison, the EORTC PathoBiology Group (EORTC PBG), focuses on discovery and validation of cancer biomarkers, providing both scientific evidence as well as quality assurance. The clinically relevant target-identification and validation studies carried out in the last decades within the EORTC PBG represent a paradigm for EORTC studies in which laboratory investigations on human biologic material are used to support the development of drugs directed to defined target molecules. The experience acquired within the EORTC PBG with respect to standardization of cancer biomarker test kits and reagents, quality assessment/assurance of cancer biomarker determinations, development of standard operating procedures for assessment of these markers as well as instruction of methodologies and teaching of ethical issues represent a valuable contribution of the EORTC PBG to the onco-translational strategies of the EORTC. Identification, validation and clinical implementation of cancer biomarkers: Translational strategies of the EORTC PathoBiology GroupMaria Grazia Daidone, John A. Foekens, Nadia Harbeck, John Martens, Nils Brunner, Christoph Thomssen, Jacqueline A. Hall, Roberto Salgado, Juergen Dittmer, Anneke Geurts-Moespot, M. Joe Duffy, Fred C.G.J. Sweep, Manfred Schmitt, on behalf of the European Organisation for Research and Treatment of Cancer (EORTC) PathoBiology Group10.1016/S1359-6349(12)70021-6EJC Supplements 10, 1 (2012)2012-03-01EJC Supplements2012-03-01101S1359-6349(12)X0002-8120127http://www.ejcancersupplements.info/article/PIIS1359634912700228/abstract?rss=yesAbstract: The EORTC Pharmacology and Molecular Mechanism Group (PAMM) focuses on applied research to translate basic/fundamental research discoveries in cancer biology into new drug discovery and development. PAMM provides a unique platform on the pharmacology, pharmacokinetics, pharmacodynamics of drug effects, molecular mechanisms of anticancer agents, and drug-related molecular pathology. For these purposes the group stimulates the interaction between basic scientists and clinicians in order to perform translational research on the pharmacology and molecular mechanisms of anticancer agents in Europe. The group has extensive expertise in various disciplines of pharmacology and has developed standards for studies performed in conjunction with clinical trials equivalent to those of good laboratory practice (GLP). The group serves as master organization for other EORTC (sub-)committees in the maximal interest of these groups and of the EORTC as a whole. PAMM merged with Preclinical Therapeutics Models Group (PTMG) in 2000 and with the Screening and Pharmacology Group (SPG) in 2003. The latter group continued as the Drug Discovery Committee within PAMM. The groups have always been involved in the development of anticancer agents, evolving from platinum analogs, anthracyclines, nitrosoureas, antifolates in the 1980's, to drugs derived from natural sources (trabectedin, taxanes) in the 1990's, and anti-signaling drugs, DNA alkylators, in the last decade. Several of these drugs have been registered. Mechanistic studies focused on drug activation/inactivation, target (DNA, receptors) in relation to efficacy and toxicity such as with several antimetabolites (5-fluorouracil, methotrexate), topoisomerase inhibitors (irinotecan), tyrosine kinase inhibitors (imatinib), acridones (C-1311), etc. The group recently included pharmacogenetics in the identification of genetic polymorphisms in order to use this information for personalized therapy. EORTC-related new drug discovery and development activities: role of the Pharmacology and Molecular Mechanisms GroupG.J. Peters, E. Chatelut, A.K. Larsen, N. Zaffaroni, on behalf of PAMM10.1016/S1359-6349(12)70022-8EJC Supplements 10, 1 (2012)2012-03-01EJC Supplements2012-03-01101S1359-6349(12)X0002-8128140http://www.ejcancersupplements.info/article/PIIS135963491270023X/abstract?rss=yesAbstract: The impact of cancer on patients' lives can be measured using self-reported questionnaires, known as Health-Related Quality of Life (HRQOL) measures. HRQOL is defined as a multi-dimensional construct covering disease and treatment-related symptoms, physical, psychological, and social functioning. The EORTC Quality of Life Group (QLG) was created in 1984 with the mission to develop measures of HRQOL and to promote and coordinate clinical studies concerning the quality of life of cancer patients. The EORTC Quality of Life Department (QL Department) was founded in 1993 with the support of an EU grant to provide administrative, practical and scientific support to co-operative groups conducting clinical trials with HRQOL outcomes. We are proud to report significant scientific achievements that have made us international leaders in HRQOL research and have led to real changes to cancer patient treatments. We developed a modular system for HRQOL measurement consisting of the EORTC QLQ-C30, a core cancer quality of life questionnaire and supplementary questionnaire modules. The EORTC-QLQ-C30 has been one of the most widely used cancer questionnaires in randomized trials in oncology as demonstrated by systematic reviews. To date, the EORTC QLQ-C30 has been translated and linguistically validated into more than 60 languages. HRQOL outcome measures have been an integral part of EORTC clinical trials for the last 30 years. We present examples of significant, practice-changing clinical trials evaluating HRQOL in several cancer sites, such as brain tumors, breast and ovarian cancers, and malignant melanoma. In a series of systematic reviews, we examined the quality of reporting HRQOL in international cancer clinical trials, and the impact of the results on oncology practice that led to a recommendation to improve CONSORT (Consolidated Standards of Reporting Trials) with regard to reporting of HRQOL. The QLG is an international leader in methodological research in the measurement of HRQOL in oncology and pursues research in several key areas, such as cross-cultural differences between populations in HRQOL assessment, Computer-Adaptive Testing, electronic administration of EORTC QLQ-C30, and summary scores for EORTC QLQ-C30. In summary, the QLG and QL Department have been international leaders in the field. Our questionnaires have brought HRQOL assessment to the fore in many international trials that have changed oncology practice and brought the patient's perspective into cancer research. Health-Related Quality of Life in EORTC clinical trials — 30 years of progress from methodological developments to making a real impact on oncology practiceG. Velikova, C. Coens, F. Efficace, E. Greimel, M. Groenvold, C. Johnson, S. Singer, L van de Poll-Franse, T. Young, A. Bottomley, on behalf of EORTC Quality of Life Group and EORTC Quality of Life Department10.1016/S1359-6349(12)70023-XEJC Supplements 10, 1 (2012)2012-03-01EJC Supplements2012-03-01101S1359-6349(12)X0002-8141149http://www.ejcancersupplements.info/article/PIIS1359634912700241/abstract?rss=yesAbstract: After the foundation of the EORTC in 1962, the Radio-Chemotherapy Group within this organization split in 1973 into two groups. One of these groups, concentrating on Hodgkin's and Non-Hodgkin's Lymphoma, later became the Lymphoma Group while the other became the Radiotherapy Group. During the 1990's the latter changed its name to the Radiation Oncology Group (ROG), underscoring its position within the field of multidisciplinary oncology research. By 2011 the ROG had initiated or participated in 83 clinical studies, of which more than 73% were randomized phase III trials. It has concentrated on almost every disease site from brain to gynecological tumors with emphasis on brain, head and neck, breast, prostate, and lower gastro-intestinal tumours. The ROG has published several hundreds peer-reviewed articles, including publications in prestigious journals such as the New England Journal of Medicine or Lancet Oncology. Since its foundation, the ROG has understood the importance of conducting a proper Radiotherapy Quality Assurance (RT-QA) program for every clinical trial aiming at guaranteeing the quality of radiotherapy, i.e. minimizing any uncertainties in the conduction of trials. As radiotherapy evolved from two-dimensional to Intensity Modulated Radio Therapy, this program has progressively matured with time to be part of a worldwide RT-QA consortium in 2012. EORTC Radiation Oncology Group: 50 years of continuous accomplishmentsVincent Grégoire, Harry Bartelink, Jacques Bernier, Michel Bolla, Jean-François Bosset, Laurence Collette, Karin Haustermans, Jean-Claude Horiot, Coen W. Hurkmans, René Mirimanoff, Philip Poortmans, Damien C. Weber, Philippe Maingon10.1016/S1359-6349(12)70024-1EJC Supplements 10, 1 (2012)2012-03-01EJC Supplements2012-03-01101S1359-6349(12)X0002-8150159http://www.ejcancersupplements.info/article/PIIS1359634912700253/abstract?rss=yesAbstract: The EORTC Soft Tissue and Bone Sarcoma Group (STBSG) develops, stimulates, and coordinates studies on all aspects of sarcomas, and over the years they have made significant achievements in the research and treatment of sarcomas. Through EORTC trials 62001, 62005, 62024, and 62063, they established imatinib in the treatment of gastrointestinal stromal tumors (GIST). Because the STBSG has conducted a large number of clinical trials in advanced disease and collected and stored all trial data in a consistent format, they were able to use these data in retrospective studies and develop progression-free survival as the primary endpoint for phase II studies in advanced soft-tissue sarcoma. This database also served as a basis for research projects analyzing subgroups of tumors like malignant peripheral nerve sheath tumors, and for exploring prognostic and predictive factors for first-line chemotherapy including ifosfamide, and proved to be of value when analyzing the results of adjuvant chemotherapy in adolescents and young adults as compared to the adult patient population. This article describes these achievements and looks into the future strategy of the STBSG. Achievements of the EORTC Soft Tissue and Bone Sarcoma GroupPeter Hohenberger, Martine van Glabbeke, Monia Ouali, Ian Judson10.1016/S1359-6349(12)70025-3EJC Supplements 10, 1 (2012)2012-03-01EJC Supplements2012-03-01101S1359-6349(12)X0002-8160166