How to build a performing multidisciplinary team. Rome, Italy November 2012

Transcription

1 FINAL PROGRAM AND ABSTRACT BOOK 360 Degrees in liver metastases from colorectal cancer How to build a performing multidisciplinary team Rome, Italy November 2012

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3 Dear Colleague, On behalf of the Serono Symposia International Foundation I am delighted to welcome you to the continuing medical education (CME) accredited meeting "360 Degrees in liver metastases from colorectal cancer. How to build a performing multidisciplinary team". At this open discussion meeting leading international experts will come together to discuss current and future multidisciplinary approaches to the treatment of patients with liver metastases from colorectal cancer. You will also have the opportunity to earn CME credits. This interactive meeting is divided into five sessions, each addressing critical issues and supported by prominent invited lecturers. The most important component of the meeting is the discussion time. Time for questions from the audience, replies and debate will be indicated by a magic clock to enhance interaction between the audience and the panel of experts. I anticipate that this program will provide valuable insights into the multidisciplinary approach to liver metastases from colorectal cancer. It will also stimulate engaging and informative debate on many of the complex issues surrounding the management of patients with metastatic colorectal cancer. I look forward to your active participation. Sincerely, René Adam Centre Hépato-Biliaire Paul Brousse Hospital Université Paris Sud Villejuif, France 1

4 360 Degrees in liver metastases from colorectal cancer How to build a performing multidisciplinary team Serono Symposia International Foundation expert working group on: 360 Degrees in liver metastases from colorectal cancer How to build a performing multidisciplinary team Rome, Italy November 2012 Format Using an expert working group format there will be even more opportunities for discussion, debate, and dialogue on current issues in the management of metastatic colorectal cancer. Most important of all is the discussion time, allowing the audience to express their own views, ask questions and hear the opinions of recognized experts in the field. Opportunities for questions from the audience, replies and debate will be indicated by a magic clock to encourage greater interaction during the meeting. Aim of the conference Based on current evidence, the multidisciplinary approach is strongly recommended for improving the clinical outcome and survival of patients with liver metastases from colorectal cancer. This activity, supported by Serono Symposia International Foundation, will bring together a panel of experts in the field, led by Professor René Adam, with the aim of addressing critical issues related to managing liver metastases from colorectal cancer and building a high-performing multidisciplinary team. The meeting will focus on insights into how to achieve resectability, and will feature open discussion between experts over a number of the key issues. Learning objectives By the end of the meeting participants will be able to: Define the specific roles of different healthcare professionals in the context of a multidisciplinary team involved in the treatment of patients with liver metastases from colorectal cancer Combine surgical and medical treatments in order to improve the survival of patients with liver metastases from colorectal cancer Review daily clinical practice in light of the controversial topics discussed Target audience Multidisciplinary pairs comprising a medical and a surgical oncologist from hospital centers experienced in the treatment of liver metastases from colorectal cancer. Accreditation Serono Symposia International Foundation is accredited by the European Accreditation Council for Continuing Medical Education (EACCME ) to provide the following CME activity for medical specialists. The EACCME is an institution of the European Union of Medical Specialists (UEMS), The 360 Degrees in liver metastases from colorectal cancer. How to build a performing multidisciplinary team held in Rome, Italy on 9-10 November 2012, is designated for a maximum of 9 (nine) hours of European external CME credits. Each medical specialist should claim only those hours of credit that he/she actually spent in the educational activity. Through an agreement between the European Union of Medical Specialists and the American Medical Association, physicians may convert EACCME credits to an equivalent number of AMA PRA Category 1 Credits. Information on the process to convert EACCME credit to AMA credit can be found at 2

5 Live educational activities, occurring outside of Canada, recognized by the UEMS-EACCME for ECMEC credits are deemed to be Accredited Group Learning Activities (Section 1) as defined by the Maintenance of Certification Program of The Royal College of Physicians and Surgeons of Canada. The Expert Working Group 360 Degrees in liver metastases from colorectal cancer. How to build a performing multidisciplinary team (Rome, Italy November 2012), has been accredited with 9 (nine) Cat. 1 ESMO-MORA points. CME Accreditation for Italian participants SSIF SRL Società Scientifica di Formazione Internazionale Scientific Provider No has submitted this program 360 Degrees in liver metastases from colorectal cancer. How to build a performing multidisciplinary team held in Rome, Italy on 9-10 November 2012, for CME accreditation to the Italian National Commission for Continuing Medical Education in compliance with the procedures indicated by the Italian Ministry of Health. Background A former meeting to discuss the multidisciplinary approach to managing liver metastases from colorectal cancer (CRC) held at the Palazzo Farnese in Rome, October 2011 and organized by Serono Symposia International Foundation (SSIF) was the brainchild of Professor René Adam, Chairman of the Rome Meeting and President of the Medical Board of the Paul Brousse Hospital, Villejuif, France. The 2011 meeting involved 15 worldwide recognized experts from the following disciplines: radiology, surgery, oncology and pathology. From the discussions at the meeting, a position paper on managing liver metastases from CRC has been written and has been published on "The Oncologist" journal. The paper includes a new system to classify initial unresectability of liver metastases based on technical and oncological contraindications. It is hoped that this system may be widely adopted so that all patients presenting with CRC liver metastases are offered a similar standard of evaluation to guide treatment. To download the Highlights of the 2011 meeting held in Rome and a free PDF copy of the position paper please register for free to: All Serono Symposia International Foundation programs are organized solely to promote the exchange and dissemination of scientific and medical information. No forms of promotional activities are permitted. There may be presentations discussing investigational uses of various products. These views are the responsibility of the named speakers, and do not represent an endorsement or recommendation on the part of Serono Symposia International Foundation. This program is made possible thanks to educational grants received from: Arseus Medical, Besins Healthcare, Celgene, Centre d Esclerosi Multiple de Catalunya (Vall d'hebron University Hospital), ComtecMed, Congrex, Croissance Conseil, Cryo-Save, Datanalysis, Dos33, Esaote, European Society of Endocrinology, Ferring, Fondazione Humanitas, Fundación IVI, GE Healthcare, GlaxoSmithKline Pharmaceuticals, IPSEN, Johnson & Johnson Medical, ISFP International Society for Fertility Preservation, ISMH International Society of Men s Health, K.I.T.E., Karl Storz, Lumenis, Merck Serono Group, PregLem, Richard Wolf Endoscopie, Sanofi-Aventis, Stallergenes, Stopler, Teva Pharma, Toshiba Medical Systems, Université Catholique de Louvain (UCL), University of Catania. 3

6 Learning effectiveness project The world of CME is changing with many different live and online formats, and Serono Symposia International Foundation (SSIF) is continually trying to improve its CME activities. With your participation in a structured series of evaluations, SSIF can provide cutting-edge learning activities designed to give you the greatest value from the time you invest. SSIF is running the learning effectiveness project for this meeting. During the conference you will be asked to answer some questions to evaluate your knowledge and opinions on the specific topics that will be covered in these two days. We also kindly ask you to assess the program in various domains such as whether you were satisfied with the meeting, whether it met the stated learning objectives, whether the contents were neutral and will be applicable to your daily practice. After the event, you will be involved in two additional steps: Post-event: three weeks after the event we will you a short questionnaire which will give you the opportunity to tell us how much of what you learned has had an affect on your know-how and daily practice. Follow-up: three-months after the event, we will contact you with the final questionnaire. We will collate and analyse your responses and use the results to improve and develop our ongoing programs. Of course, we commit to maintaining the confidentiality of the information you provide and we will inform you about the results of the process regarding the activity that you attended. Thank you very much for participating in this project! follow us on SSIF_Oncology 4

7 General information Venue The conference takes place at the: NH Giustiniano Via Virgilio Roma, Italia Language The official language of this conference is English. Scientific secretariat Serono Symposia International Foundation Salita di San Nicola da Tolentino, 1/b Rome, Italy Associate Project Manager: Giovanna Rossi T +39-(0) F +39-(0) info@seronosymposia.org Medical Advisor: Cristina Raimondi Serono Symposia International Foundation is a Swiss Foundation with headquarters in 14, rue du Rhône, 1204 Geneva, Switzerland Organizing secretariat Meridiano Congress International Via Sapri, Rome, Italy Project coordinator: Titty Alvino T +39 (0) F +39 (0) c.alvino@meridiano.it To know more visit: 5

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9 Scientific program

10 Scientific Program 9-10 November 2012 Day 1 - Friday, 9 November Registration Welcome Session I L1: Liver metastases from colorectal cancer: the extent of the problem R. Adam (France) L2: What is an optimal multidisciplinary team (MDT). Impact of MDT management on patient outcome C. Teh (Philippines) Session II Introduction The multisciplinary team at work L3: How to appropriately evaluate the response to treatment? Are RECIST criteria still a valid tool? E. Loyer (USA) Discussion time - magic clock L4: How to define resectability? R. Adam (France) Session IV L9: Optimal systemic chemotherapy for patients with liver metastases from colorectal cancer: does it exist? A. Sobrero (Italy) L10: How to achieve a complete surgical resection? N. Kokudo (Japan) Discussion time - magic clock L11: Guidelines for high standard pathological examination. How to detect changes in molecular biology between primary cancer and metastases? L. Rubbia-Brandt (Switzerland) Discussion time - magic clock Coffee break Guidelines for optimal multidisciplinary team management of liver metastases from colorectal cancer Discussion time - magic clock Session V Pushing forward the frontiers Coffee break Session III L5: The opinion of the medical oncologist J. Tabernero (Spain) L6: The opinion of the surgeon J. Figueras (Spain) Discussion time - magic clock L7: Is it possible to cure patients with liver metastases? Opinion of the medical oncologist E. Van Cutsem (Belgium) L8: Is it possible to cure patients with liver metastases? Opinion of the surgeon N. Kokudo (Japan) Discussion time - magic clock Lunch Why achieving resection is so important? L12: Will predictive biomarkers help to improve treatment efficacy? A. Sobrero (Italy) L13: Clinical impact of changes in molecular biology between primary cancer and metastases or in the evolution of treatment J. Tabernero (Spain) Discussion time - magic clock How to optimize resectability L14: Opinion of the surgeon: Special techniques J.-N. Vauthey (USA) L15: Opinion of the oncologist: Intraarterial chemotherapy P. Rougier (France) Discussion time - magic clock Session VI When dreams become reality: the cured patients Case study presentation R. Adam (France) The voice of the patient End of the first day 8

11 Day 2 - Saturday, 10 November Session VII Special issues How to manage complete clinical response (Missing metastases)? L16: The opinion of the radiologist A. Guthrie (UK) L17: The opinion of the medical oncologist P. Rougier (France) L18: The opinion of the surgeon C. Teh (Philippines) 9.30 Discussion time - magic clock 9.45 How to predict complete pathological response and should it be a new end point? L19: The opinion of the radiologist F. Kunstlinger (France) L20: The opinion of the surgeon J.-N. Vauthey (USA) L21: The opinion of the medical oncologist A. de Gramont (France) Discussion time - magic clock Coffee break L22: Surgery, exploring the limits: what patients are unlikely to benefit from surgery? R. Adam (France) Discussion time - magic clock L23: Adjuvant chemotherapy what treatment and how long? A. de Gramont (France) Discussion time - magic clock Elderly patients: which guidelines? L24: The opinion of the medical oncologist E. Van Cutsem (Belgium) L25: The opinion of the surgeon J. Figueras (Spain) Discussion time - magic clock End of the meeting and lunch 9

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13 René Adam Aimery de Gramont Joan Figueras Ashley Guthrie Norihiro Kokudo Francis Kunstlinger Evelyne Loyer Philippe Rougier Laura Rubbia-Brandt Alberto Sobrero Josep Tabernero Catherine Teh Eric Van Cutsem Jean-Nicolas Vauthey Faculty members

14 Biographies René Adam Scientific organizer / Speaker: Session I - Session II - Session VI - Session VII Centre Hépato-Biliaire Paul Brousse Hospital, Université Paris Sud Villejuif, France René Adam is President of the Medical Board of the Paul Brousse Hospital, Villejuif, France and Head of the Oncological Surgery Unit of the Hepato Biliary Center. Since 1994, he has held the position of Professor of Surgery at the Faculty of Medicine Kremlin Bicêtre at Paris South University, Paris. Professor Adam s main fields of activity and research are surgery of the liver, biliary tract and pancreas, and hepatic transplantation. He is particularly involved in the treatment of hepatocellular carcinoma and of liver metastases. Professor Adam chairs the European Liver Transplant Registry and LiverMetsurvey, the international Registry of Colorectal liver metastases. He is on the Editorial Board of The Oncologist and member of several international societies, including the American Society of Clinical Oncology (ASCO), the European Society of Surgical Oncology (ESSO), the European Society of Organ Transplantation (ESOT), the European Surgical Association (ESA) and the International Hepato-Pancreatic and Biliary Association (IHPBA). He is member of the board of the French Association of Surgery and, of the French Association of Hepato-Biliary Surgery and Liver Transplantation. He has delivered more than 600 lectures on his research interests around the world, and has more than 200 publications in peer-reviewed journals. Aimery de Gramont Speaker: Session VII Service d Oncologie Médicale Hôpital Saint-Antoine Paris, France Dr. Aimery de Gramont is Professor of Oncology since 1993 and Head of the Oncology Department since Dr. de Gramont earned his MD degree from the Faculty of Medicine in Paris, France and subsequently served an internship residency at Paris Hospitals and a residency at Laval University in Quebec, Canada. He serves as Chairman of the GERCOR multidisciplinary cancer research group and is a member of the French Cancer Society, French Internal Medicine Society, American Sociery of Clinical Oncology, and European Society for Medical Oncology. Dr. de Gramont is co-chairman of the scientific board of the International Society of Gasrrointestinal Oncology and was a member of the editorial board of the Journal of Clinical Oncology. He has authored or coauthored more than 250 journal articles and been an invited speaker in more than 30 countries. Dr. de Gramont's fundamental and preclinical research has focused primarily on the fields of cytogenetics, molecular biology, targeted therapies and adoptive immunotherapy, specifically in the areas of hematologic cytogenetics, cellular membranes in nocturnal paroxystic hemoglobinuria, activated macrophage adoptive immunotherapy, development and modulation of antimetabolites, and preclinical drug development. His clinical research has involved mainly haematology, gastro-intestinal and ovarian cancer therapy. He is team leader of the Group of Cancer Biology and Therapeutics, INSERM U938, Université Pierre et Marie Curie since As a member of GERCOD and GERCOR, Dr. de Gramont has played a pivotal role in a colon cancer program that has included 7 first-line phase II, 13 second-line phase II, 6 first-line phase III, and 4 adjuvant studies involving more than patients since He has served as chairman or cochairman on >20 different protocols. 12

15 Joan Figueras Speaker: Session III - Session VII Department Hepato-Biliary and Pancreatic Surgery Department of Surgery, "Dr Josep Trueta Hospital Girona, Spain Joan Figueras graduated in medicine in 1974 at the medical School, University of Barcelona. He has been chairman of the liver transplant unit of the Bellvitge Hospital from 1998 to In this hospital in 1984 the first liver transplant in Spain was performed by him and his unit and during 21 years more than 800 cadaveric liver transplants were performed by his unit. Joan Figueras has been chairman of the hepato-biliary and pancreatic unit of the Josep Trueta Hospital in Girona since In his unit, in the last year, they performed 80 liver liver resections and 26 duodenopancreatectomies in adults. He has participated to several studies about chemotherapy of liver metastases and surgical technique of hepatectomies and his main topics of interest in liver surgery are hepatocellular carcinoma, resection of liver metastases and hilar cholangiocarcinoma. Joan Figueras has been Professor of Surgery at University of Barcelona since 1990, teaching to more than one hundred medical visitors who are working today in many hospitals of Spain, in the field of hepatobiliary surgery. Ashley Guthrie Speaker: Session VII Department of Clinical Radiology St. James's University Hospital Leeds, UK Consultant Radiologist (Cross Sectional Imaging), St James s University Hospital Leeds, Honorary Senior Lecturer Leeds University. Main research interests gastrointestinal, liver and pancreatic radiology. Secretary of British Society of Gastrointestinal and Abdominal Radiologists, Fellow of the European Society of Gastrointestinal and Abdominal Radiologists organiser of Leeds Gastrointestinal Course for Radiologists. Member of Cancer Diagnostic Advisory Board, Department of Health, UK. 13

16 Biographies Norihiro Kokudo Speaker: Session III - Session IV University of Tokyo, Department HepatoBiliaryPancreatic Surgery Division, Artificial Organ and Transplantation Division Department of Surgery, Tokyo, Japan Dr. Norihiro Kokudo is the professor and chairman at Hepato-Biliary-Pancreatic Surgery Division and Artificial Organ and Transplantation Division, Department of Surgery, University of Tokyo Hospital. He earned his M.D. in 1981, and then Ph.D. in 1988 at University of Tokyo. From 1989 to 1991 he stayed at Department of Surgery, University of Michigan as a visiting research investigator. After 6 years at Cancer Institute Hospital, Tokyo, as a senior staff of GI surgery, he joined the current institution as an associate professor in He then rose to the current position in Dr. Kokudo has been conducting a number of research projects on surgical treatment of HCC, colorectal liver metastases, and living donor liver transplantation. As a vice-general administrator, he compiled 2 nd version of Japanese clinical practice guidelines for HCC in 2009 (Hepatol Res 2010; 40 suppl). He is currently compiling the 3 rd version as the chairman of the guideline committee. In April 2012, Dr. Kokudo was appointed as the President of Japan Surgical Society. He is an executive committee member of International Association of Surgeons, Gastroenterologists, and Oncologists (IASGO), and secretary elect for Asian-Pacific Hepato-Pancreato-Biliary Association (A-PHPBA). He is also a member of international Hepato-Pancreato-Biliary Association (IHPBA), International Society of Surgery, and The Society of Surgical Oncology. He is an associate editor of Hepatology Research and Surgery Today, and on the editorial board of World Journal of Surgery, Journal of HPB Science, HPB, Japanese Journal of Clinical Oncology, and Hepatogastroenterology. Francis Kunstlinger Speaker: Session VII Centre Hépato-Biliaire Paul Brousse Hospital Villejuif, France Dr. Francis Kunstlinger is a radiologist. After a training in surgery for 3 years he decided to specialize in radiology and abdominal interventional radiology. He worked at the surgical department of Prof. Bismuth at the P. Brousse Hospital in Villejuif with diagnostic abdominal imaging and he now continues his work there with Prof. Adam. Dr. Kunstlinger is particularly involved in activity of ultrasonography, contrast enhanced ultrasonography, CT and MRI in abdominal and hepatic imaging. He has more than 30 years of experience in abdominal imaging. 14

17 Evelyne Loyer Speaker: Session II Department of Diagnostic Radiology, Division of Diagnostic Imaging The University of Texas, MD Anderson Cancer Center Houston, Texas, USA Dr. Loyer is Professor of Diagnostic Radiology at The University of Texas MD Anderson Cancer Center in Houston, Texas. Dr. Loyer's clinical research focuses on the imaging of hepatobiliary malignancies particularly preoperative staging and assessment of the response to chemotherapy. Dr. Loyer developed non size based criteria of response to bevacizumab which correlate with the pathologic response in patients with metastatic colorectal carcinoma. Radiographic observations also lead to the development of a new pathologic indicator of response in the same patient's population. Philippe Rougier Speaker: Session V - Session VII Digestive Oncology Department HEGP (Hopital Européen Georges Pompidou) Paris, France Philippe Rougier is head of the Digestive Oncology Department at the Hopital Européen Georges Pompidou, Paris since He worked for the development of the digestive Oncology at the Institut Gustave Rossy for 17 years and at the Hopital Ambroise Paré for 13 years, in close collaboration with the surgical department (development of a medico-surgical federation) and favouring a multidisciplinary approach. Dr. Rougier main fields of activity are: clinical research on treatments and treatment strategy for all digestives tumors, colorectal, pancreatic, gastric, esophageal, biliary and liver tumors, rare tumors (Digestive Endocrine tumors and GIST); development of loco-regional treatments (intraarterial in animal model and in men); development of new products and new combinations, especially in the field of colo-rectal cancers, gastric, pancreatic and neuroendocrine tumors. Dr. Rougier is a consultant and expert in digestive oncology and he counts participation at numerous scientific boards and scientific associations. Dr. Rougier is Titular Member of the «Association Française d'etude des Cancers» since 1986 and has been member of the board from 1996 to He is Member of the European Society of Medical Oncology (ESMO) (since 1986), American Society of Clinical Oncology (ASCO) (since 1987), American Association for Cancer research (AACR) ( ), European Organization for Research and Treatment of Cancer, Gastrointestinal Clinical Cooperative Group (EORTC-GICCG) since 1985, (Member of the National Board ). Secretary of the l EORTC-GICCG (board): , Board of the ESDO (European Society of Digestive Oncology) since Dr Rougier has more than 350 publications in international journals with review. 15

18 Biographies Laura Rubbia-Brandt Speaker: Session IV Pathology Department Geneva University Hospital Geneva, Switzerland Laura Rubbia-Brandt is Director of the Division of Clinical Pathology, Geneva University Hospital Switzerland and full professor in pathology where she teaches GI and liver Pathology at Geneva Medical School. She received her medical education at the University of Geneva, and her specialty training at Division of Clinical Pathology, Geneva University Hospital Switzerland and Hôpital Beaujon, Paris, France. She is president of Swiss Hepato-Biliary pathology group, section of the Swiss society of pathology, vice-president of the swiss society of pathology, active member of the board of the Swiss association of study of liver, referent pathologist of the Swiss Hepatitis C Cohort Study Group, and member in GI pathology group of the Swiss Institute for Applied Cancer Research, member of the Unites state and Canadian academy of pathology (USCAP), Hans Pooper Liver pathology society, and the International Academy of Pathology (IAP). Laura Rubbia Brandt is the author of more than 140 scientific articles, 10 book chapters and reviews. Her research interests are pathogenesis of hepatic secondary effects neoadjuvant chemotherapy in colorectal metastasis and mechanisms and role of HCV infection in the development of hepatic steatosis. Alberto Sobrero Speaker: Session IV - Session V Medical Oncology Ospedale San Martino Genoa, Italy Alberto Sobrero has been the Head of the Medical Oncology Unit at Ospedale San Martino in Genova, Italy, since Before this, he was Associate Professor in Medical Oncology at the University of Florence and Udine. After receiving his medical degree from the University of Genova in 1978, Prof. Sobrero took up the position of postdoctoral Associate in Medical Oncology at Yale University, Connecticut, USA. In 1983, he became Associate Research Scientist in Medical Oncology at Yale. Before returning to Genova in 1985, he completed a residency in Internal Medicine at the Yale Affiliated Norwalk Hospital. In addition to being a member of several Italian scientific societies, Professor Sobrero is a member of the American Society of Clinical Oncology (ASCO), the American Association for Cancer Research (AACR), and the European Society for Medical Oncology (ESMO). From 2002 to 2006, Professor Sobrero has been the Chairman of the Protocol Review Committee of the European Organisation for Research and Treatment of Cancer (EORTC) and has been part of the faculty of the ASCO-FECS Clinical Research courses at Flims for 7 years. He has served on the editorial board of the Journal of Clinical Oncology , has been part of the Scientific Committee of ASCO ( ) and of the Educational Committee of ESMO ( ). His main research interests include fluoropyrimidines, gastrointestinal cancer treatment and clinical trial design and interpretation of targeted agents in oncology. 16

19 Josep Tabernero Speaker: Session III - Session V Vall d'hebron University Hospital Medical Oncology Service Barcelona, Spain Josep Tabernero is currently the Head of the Medical Oncology Department and the Head of the Gastrointestinal Tumors and Phase I Unit at the Vall d Hebron University Hospital in Barcelona, Spain. He is also the Director of the Vall d Hebron Institute of Oncology. He is actively involved in translational research and pharmacodynamic phase I studies with molecular targeted therapies and related translational research, with a special focus on EGFR-family inhibitors and IGFR-PI3K-Akt-mTOR pathway inhibitors, and phase 2 and 3 studies with new chemotherapy agents in gastrointestinal tumors. Dr. Tabernero received his medical degree from the Universitat Autònoma de Barcelona and completed his specialist training in medical oncology. He is a member of the European Society for Medical Oncology (ESMO) and the American Society of Clinical Oncology (ASCO), and a member of different Editorial Boards including the Journal of Clinical Oncology, Clinical Cancer Research, Cancer Discovery, Clinical Colorectal Cancer and Annals of Oncology. He has (co)authored approximately 180 peer-reviewed papers. He has also been member of the Educational and Scientific Committees of the ESMO, ECCO, ASCO Gastrointestinal, AACR and World Congress on Gastrointestinal Cancer (WCGIC) meetings. Catherine Teh Speaker: Session I - Session VII Liver Care Center, Department of Surgery Section of HPB Surgery, Makati Medical Center Makati City, Philippines Dr. Catherine Teh is the Chief of the Hepatobiliary Pancreatic Center of the Makati Medical Center and an active HPB & Liver Transplant consultant in the National Kidney & Transplant Institute. Likewise, she is an active consultant surgeon at the St Luke s Medical Center and a visiting surgeon at The Medical City. Dr. Teh is also a visiting faculty of the Institute de Recherche Contre les Cancer de Appereil Digestif, being an active faculty and having the passion for liver surgery, she has presented and delivered various talks of various topics on Liver Cancer, health, lifestyle and cancer. She has been active in workshops on liver surgery internationally and locally. She sits in the editorial board of the Hepatobiliary Pancreatic Diseases International Journal, peer reviewer in the Singapore Medical Journal and Hepatology Journal of the AASLD. She is a Board of Director of the Philippine College of Surgeons Metro Manila Chapter & is also a Board of Trustee of the Philippine Society of General Surgeons Metro Manila Chapter. She has authored a few manuscripts & has been extensively involved in conferences & talks on liver cancer globally. She is a member of the International Hepatobiliary Pancreatic Association, council member of the Asia-Pacific Hepatobiliary Pancreatic Association, SAGES, and many other international societies for HPB & Minimally Invasive Surgery. Dr. Teh is a graduate of the University of Santo Tomas. She furthered her training in GI surgery in England in 1998, in National Cancer Center in Singapore in specializing in Surgical Oncology & subspecializing in Hepatobiliary Pancreatic Surgery. She was simultaneously employed in Singapore Gen Hospital as a faculty until In 2006, Dr. Teh again furthered her training, this time in European Institute of Telesurgery in Strasbourg. She also earned another Diploma in Advanced Laparoscopic Surgery in the University of Louis Pasteur in France. Her passion in liver surgery brought her back to France and continues to spend some time at Centre Hepatobiliare at Hopital Paul Brousse in Paris with Rene Adam in the further studies & collaboration on Multidisciplinary Management of metastatic colon & rectal cancer. She recently earned her university diploma in HPB Cancers in the same centre from the Universite Paris Sud and furthered her skills & knowledge in Liver Transplantation both in Paul Brousse CHB and Hopital Henri Mondor under the mentorship of Prof Daniel Cherqui. 17

20 Biographies Eric Van Cutsem Speaker: Session III - Session VII Digestive Oncology Unit University Hospital Gasthuisberg Leuven, Belgium Eric Van Cutsem trained in internal medicine and gastroenterology in Leuven and specialised later in GI oncology in Leuven, Belgium. He is currently Professor of Internal Medicine at the University of Leuven and is head of the Digestive Oncology department at the University Hospital Gasthuisberg in Leuven, is board member of Leuven Cancer Institute and of the Department of Oncology at the University of Leuven. He obtained his degree of MD and PhD at the University of Leuven. He has a large clinical activity in Leuven and is involved and leads many national and international clinical and translational research projects on gastrointestinal cancer. Prof. Van Cutsem has published more than 320 peer-reviewed articles (on pubmed; H-factor: 66; >18000 citations) in prestigious journals including New England Journal Medicine, Journal of Clinical Oncology, Lancet, Lancet Oncology, JAMA, Annals of Oncology and European Journal of Cancer. He is co-editor of the reference textbook on gastrointestinal cancer: Principles and Practice of Gastrointestinal Oncology: Second edition, 2008, and is/has been an editorial board member of numerous prestigious journals, including Journal of Clinical Oncology, Annals of Oncology, and European Journal of Cancer and is associated editor of Targeted Oncology and editor of European Journal Cancer since January Eric Van Cutsem is a member of several scientific organizations. He is/was a member of the Scientific Program Committee and/or educational committee of ASCO, ASCO-GI cancers symposium, ESMO and ECCO. He is also a member of the ESMO faculty and joined the ESMO executive board on July 1, He served as secretary of the European Organisation for Research and Treatment of Cancer Gastrointestinal Cancer (EORTC-GI) group from January 2000 to 2003, and was chair of the EORTC-GI group from 2003 to 2007 and is chairman of PETACC (Pan-European Trials on Adjuvant Colon Cancer) since 2008, board member of the EORTC since 2009 and president of European Society of Digestive Oncology (ESDO) and is co-chairman of the European NeuroEndocrine Tumour Society (ENETS) registry. He is also chairman of the governmental colon cancer prevention task force in Flanders, Belgium and is president of BGDO (Belgian Group Digestive Oncology) and FAPA (Familial Adenomatous Polyposis Association). Eric Van Cutsem has been the founder of and is chair of the Scientific Committee of the World Congress on Gastrointestinal Cancer in Barcelona (in partnership with ESMO since 2005). Jean-Nicolas Vauthey Speaker: Session V - Session VII Department of Surgical Oncology, Division of Surgery The University of Texas, MD Anderson Cancer Center Houston, Texas, USA Dr. Vauthey is Professor of Surgery and Chief of the Liver Service in the Department of Surgical Oncology at The University of Texas MD Anderson Cancer Center in Houston, Texas. Dr. Vauthey s clinical research focuses on methods to measure and to improve outcome after hepatic resection for hepatobiliary malignancies. Dr. Vauthey proposed a standardized method for calculating the volume of the anticipated liver remnant prior to major liver resection. This method of measurement is used to compare patients prior to extended liver resection to determine the need for preoperative portal vein embolization. Dr. Vauthey created the International Cooperative Study Group for Hepatocellular Carcinoma. The group critically analyzed the staging system for hepatocellular carcinoma and questioned its complexity. Based on this work, the American Joint Committee on Cancer and the International Union Against Cancer adopted a new simplified staging system for hepatocellular carcinoma. Dr. Vauthey is the Chair of The American Joint Committee on Cancer Hepatobiliary Task Force for the 7 th Edition of the Manual for Staging Cancer. Dr. Vauthey has evaluated the use of preoperative chemotherapy in the multidisciplinary treatment of patients with hepatic colorectal metastases. He is the author of a treatment algorithm for hepatic colorectal liver metastases. Dr. Vauthey has been an invited speaker at many major national and international meetings, including the postgraduate courses of the Society for Surgery of the Alimentary Tract, the American College of Surgeons, and the Society of Surgical Oncology. Dr. Vauthey organized and chaired symposia at national and international meetings. Dr. Vauthey is the immediate past President of the Americas Hepato-Pancreato-Biliary Association. Dr Vauthey is in the Board of Trustees of the Society for Surgery of the Alimentary tract. Dr. Vauthey co-authored more than 300 publications in peer-reviewed journals and more than 85 reviews and book chapters in major textbooks. Dr. Vauthey is editor or co-editor of major textbooks devoted to hepatobiliary and pancreatic cancers. Dr. Vauthey organized and chaired Consensus Conferences on Colorectal Liver Metastases and Resectable and Borderline Resectable Pancreas Cancer, the Multidisciplinary Treatment of Hepatocellular Carcinoma. Dr. Vauthey is a reviewer for major surgical and medical journals. He is on the editorial board of major journals including the Journal of the American College of Surgeons, Surgery, Annals of Surgery, Annals of Surgical Oncology, Journal of Gastrointestinal Surgery, World Journal of Clinical Oncology, Liver Cancer, World Journal of Hepatology, and Updates in Surgery. Dr. Vauthey is the recipient of the prestigious 2011 Faculty Achievement Award in Patient Care for his commitment to the mission of The University of Texas MD Anderson Cancer. 18

21 Abstracts

22 L1 - Liver metastases from colorectal cancer: the extent of the problem René Adam Centre Hépato-Biliaire, Paul Brousse Hospital, Université Paris Sud Villejuif, France Patients with liver metastases from colorectal cancer (CRC) present a major public health challenge. Approximatelly, 1,2 million cases of CRC occur yearly worldwide, with 412,900 new cases diagnosed in western Europe alone and 150,000 in the United States. Resection of colorectal liver metastases (CRLM) is the only treatment offering the possibility of cure and has been shown to provide clear survival benefits. Unfortunately, only 10% to 20% of patients with CRLM are eligible for this procedure upfront. Systemic chemotherapy is currently the standard treatment approach for nonresectable CRLM. Incorporation of drugs such as oxaliplatin and irinotecan have led to a significant improvement of median survival as well as response rates compared with those achieved previously with 5-fluoracil (5-FU)/leucovorin-based regimens. More recently the introduction of targeted therapies have further amplified the efficacy of chemotherapy leading to increased response rates and median survival now approaching 24 months overall. The positive effect of this improved efficacy of newer regimens is downstaging tumors, rendering more patients resectable. Around % of unresectable patients responded in such extent to chemotherapy that they could benefit from rescue surgery with a 5-year survival of 35% at 5 years. To further increase the resectability rate of initially unresectable patients, specific techniques such as portal embolisation, radiofrequency ablation combined with resection, and two-stage hepatectomies are presently available. Overall the onco-surgical concept to combine chemotherapy and surgery is increasingly accepted as the best mean to improve the prognosis of advanced metastatic colorectal cancer. While merely palliative in the past, the treatment of colorectal cancer metastatic to the liver has currently switched to a strategy for long-term remission or even cure by combining the improved results of surgery and that of chemotherapy. Strategies are becoming more «agressive» and multidisciplinary, resulting yet in a significant gain in survival of many patients promised in the past, to a very poor outcome. The main challenge nowadays is to give access to this oncosurgical approach to all the patients likely to benefit from it, wherever the patient condition, the center and the country. The conditions to achieve this objective include: - Multidisciplinary management from the onset of the disease, a modality which is still not universally shared - An easy access to the new drugs when useful, in relation to the patient status - An accepted definition of non resectability and a consensus on the best chemotherapy regimen to optimize resectability and patient survival - A good collaboration between medical oncologists, surgeons, interventional radiologists and pathologists - The availability of specialized units involving experts in the different fields to provide patients with a real up-to- date evaluation and treatment 20

23 L2 - What is an optimal multidisciplinary team (MDT). Impact of MDT management on patient outcome Catherine Teh Liver Care Center, Department of Surgery, Section of HPB Surgery, Makati Medical Center Makati City, Philippines Traditional model of multidisciplinary health care system involves sequential or parallel referrals where patients are transferred from one clinic or service to another for diagnosis and treatment of cancer. This appears to be a disintegrated and confusing system that challenges optimal patient care. This brought forward a change in the landscape of cancer management in the recent past. The current concept of multidisciplinary team approach for cancer care has evolved from the complex and inefficient referral system. The optimal MDT model for colorectal cancer with liver metastasis is a patient-centered approach requiring a core team of specialists, including hepatobiliary and colorectal surgeons, medical oncologists, diagnostic and interventional radiologists, pathologists. Depending on institution size and availability of expertise, the multidisciplinary team are supported by nurses, nutritionists, palliative care, social service, and a cancer coordinator may ideally form part of the MDT. There appears to be a wide variation in the implementation and proceedings of an MDT from center to center. Although standard definition and universal guidelines are insufficient at the moment, various centers and institutions in practice are encouraged to practice and establish a more definitive approach to allow not only optimal patient care but also serve as a venue for education and training. Likewise, a strong backbone of data management is necessary to allow audit and reappraisal of the multidisciplinary team approach such that measurement of clinical outcomes as well as professional and institutional benefits may be assessed. Evidence for the performing multidisciplinary team approach in the management of colorectal cancer liver metastases is limited but growing. This paradigm shift has been an established approach in other disciplines and specialities such the management of morbid obesity, neurologic diseases, breast and lung cancer. Successful MDTs have shown to alter clinical decision and management options resulting to better clinical outcomes. Recommendations and guidelines maybe sought from experiences brought over from other disciplines in cancer care. 21

24 L3 - How to appropriately evaluate the response to treatment? Are RECIST criteria still a valid tool? Evelyne Loyer Department of Diagnostic Radiology, Division of Diagnostic Imaging, The University of Texas, MD Anderson Cancer Center, Houston, Texas, USA Radiographic response to treatment is currently the focus of new developments. Imaging response has historically relied solely on the quantification of change in tumor size as defined by such criteria as RECIST. Decrease in tumor size is a strong predictor of response, but is much less reliable when some, notably targeted therapies are utilized. One limitation of the RECIST criteria lay in the arbitrary choice of the cut off values defining the response categories. Two groups have recently suggested that a 10% decrease in tumor size, at an early time point, may be a better prognostic indicator than the 30% decrease mandated by RECIST for response. Furthermore, there is increasing evidence that the incorporation of non-size based morphologic criteria provide better correlation with pathologic response and survival than change in size alone. The role of FDG-PET in monitoring response is under evaluation. The aim of this presentation is to review the currently available imaging methods for assessing response to chemotherapy in hepatic metastases from colorectal cancer. 22

25 L4 - How to define resectability? René Adam Centre Hépato-Biliaire, Paul Brousse Hospital, Université Paris Sud Villejuif, France Resection of colorectal liver metastases (CRLM) is the only treatment offering the possibility of cure and has been shown to provide clear survival benefits. Unfortunately, only 10% to 20% of patients with CRLM are eligible for this procedure upfront. During the last 10 years, major advances in the management of CRLM have taken place involving principally three different fields: pre and postoperative chemotherapy (new and more effective chemotherapeutic agents), interventional radiology (portal embolisation and radiofrequency), and surgery (extension of indications and newer techniques). These advances as part of a multidisciplinary team approach have gradually but effectively increased the resectability rate to 20-30% of cases with a 5-year survival of 35-50%, marked improvement compared to previous figures. Past limits of resectability involved only metachronous unilobar metastases, 3 in number, 5 cm in maximum size, with > 1 cm of resection margin and CEA< 100 ng/ml, all factors leading to consider surgery in less than 10% of patients. Considering the inferior outcomes obtained for patients undergoing incomplete or no resection with 5-year survival in non operated patients extremely rare, we have moved currently to a more pragmatic policy to propose resection of CRLM whenever feasible and potentially curative, regardless of prognostic factors and presence of extrahepatic metastases. This extension in the indications of surgery underlines two conditions: 1. The volume of remnant safe liver after hepatic resection should be 30% of the total liver volume, 2. The overall surgical strategy should remove all the detectable tumoral deposits. However, universal definition of resectability is still lacking in relation to the important changes occurred in the past years and to the different expertise of surgical teams with regards to liver surgery. It is of paramount importance to come now to an international definition of resectability so that all patients could benefit from the sole treatment able to provide a clear survival benefit at long term if not a real chance of cure. The complexity of the problem comes from the fact that 2 types of limits for resectability should be considered: the technical limits (impossibility to leave at least 30% of safe remnant liver while removing the totality of tumors) and the oncological limits (excluding patients who will not benefit of resection although being technically resectable). We propose a new classification integrating these two type of factors, that should be validated on a prospective way and whose advantage would be obviously to offer the chance of resection to all patients likely to benefit from surgery but also to harmonize the inclusion of unresectable patients in all the trials involving conversion or palliative chemotherapy. This classification may help to define clearly the type of unresectable patients included in all clinical trials. 23

26 L5 - Why achieving resection is so important? The opinion of the medical oncologist Josep Tabernero Vall d'hebron University Hospital, Medical Oncology Service Barcelona, Spain Abstract not in hand at the time of printing. References: 1 - Chappel SC, Howles C 1991 Reevaluation of the roles of luteinizing hormone and follicle-stimulating hormone in the ovulatory process. Human Reproduction Filicori M, Cognigni GE, Pocognoli P et al Current concepts and novel applications of LH activity in ovarian stimulation. Trends in Endocrinology and Metabolism 14,

27 L6 - Why achieving resection is so important? The opinion of the surgeon Joan Figueras Department Hepato-Biliary and Pancreatic Surgery, Department of Surgery, "Dr Josep Trueta Hospital Girona, Spain Surgical resection remains the only treatment associated with long-term survival in patients with CRC liver metastases, with almost 25% of patients cured at 10 years. However, most patients with hepatic CRC metastases remain unresectable. A range of strategies have been developed to render a patient s disease surgically resectable (eg, portal vein embolization, neoadjuvant chemotherapy, and radiofrequency ablation. The current definition of resectability includes the potential for complete resection with tumor-free margins (R0 resection), with preservation of at least two disease-free liver segments with viable vascular inflow, outflow, and biliary drainage, and a future liver remnant volume of 30%. Approximately 30% of new cases of CRC have synchronous liver metastases. While synchronous CRC liver metastases are traditionally treated with a two-stage resection, recent improvements in perioperative care and post-surgical morbidity and mortality favor simultaneous resection in cases where the primary tumor is in the colon and the number of hepatic metastasis low. Resection of liver metastases first (reverse treatment) is considered the best option when hepatic disease is predominant and/or the primary tumor is asymptomatic or symptoms are easy to manage. Staged resections are generally favored in cases of multiple metastatic site. The number of liver metastases should not be a contraindication to resection and the resection of multiple bilobar hepatic metastases. An increasing number of patients with unresectable CRC liver metastases are being treated with a combination of systemic chemotherapy and radiofrequency ablation (RFA). References: 1 - Chappel SC, Howles C 1991 Reevaluation of the roles of luteinizing hormone and follicle-stimulating hormone in the ovulatory process. Human Reproduction Filicori M, Cognigni GE, Pocognoli P et al Current concepts and novel applications of LH activity in ovarian stimulation. Trends in Endocrinology and Metabolism 14,

28 L7 - Is it possible to cure patients with liver metastases? Opinion of the medical oncologist Eric Van Cutsem Digestive Oncology Unit, University Hospital Gasthuisberg Leuven, Belgium To optimize the chances of cure in patients with liver metastases, a multidisciplinary management in an expert team is required. A careful oncological and technical evaluation has to be done in each patient in order to determine technical, oncological respectability in patients medically fit enough to undergo a multimodal treatment including a resection of liver metastases. The combination of cytotoxics plus biological targeted agents increases the changes of a resection in patients with liver limited, but non-resectable metastases and contributes to higher conversion rates from non-resectable to resectable disease. This strategy has a clear impact on the outcome of patients with metastatic colorectal and offers chances for prolonged survival. References: 1 - Schmoll HJ, Van Cutsem E, Stein A, Valentini V, Glimelius B, Haustermans K, Nordlinger B, van de Velde CJ, Balmana J, Regula J, Nagtegaal ID, Beets-Tan RG, Arnold D, Ciardiello F, Hoff P, Kerr D, Köhne CH, Labianca R, Price T, Scheithauer W, Sobrero A, Tabernero J, Aderka D, Barroso S, Bodoky G, Douillard JY, El Ghazaly H, Gallardo J, Garin A, Glynne-Jones R, Jordan K, Meshcheryakov A, Papamichail D, Pfeiffer P, Souglakos I, Turhal S, Cervantes A. ESMO Consensus Guidelines for management of patients with colon and rectal cancer. A personalized approach to clinical decision making. Ann Oncol Oct;23(10): Adam R, De Gramont A, Figueras J, Guthrie A, Kokudo N, Kunstlinger F, Loyer E, Poston G, Rougier P, Rubbia-Brandt L, Sobrero A, Tabernero J, Teh C, Van Cutsem E, Jean-Nicolas V; of the EGOSLIM (Expert Group on OncoSurgery management of LIver Metastases) group. The Oncosurgery Approach to Managing Liver Metastases from Colorectal Cancer: A Multidisciplinary International Consensus. Oncologist Sep 7. [Epub ahead of print] 3 - Adam R, Haller DG, Poston G, Raoul JL, Spano JP, Tabernero J, Van Cutsem E. Toward optimized front-line therapeutic strategies in patients with metastatic colorectal cancer--an expert review from the International Congress on Anti-Cancer Treatment (ICACT) Ann Oncol Aug;21(8): Epub 2010 Mar 10. Review. 4 - Nordlinger B, Van Cutsem E, Gruenberger T, Glimelius B, Poston G, Rougier P, Sobrero A, Ychou M; European Colorectal Metastases Treatment Group; Sixth International Colorectal Liver Metastases Workshop. Combination of surgery and chemotherapy and the role of targeted agents in the treatment of patients with colorectal liver metastases: recommendations from an expert panel. Ann Oncol Jun;20(6): Epub 2009 Jan Poston GJ, Figueras J, Giuliante F, Nuzzo G, Sobrero AF, Gigot JF, Nordlinger B, Adam R, Gruenberger T, Choti MA, Bilchik AJ, Van Cutsem EJ, Chiang JM, D'Angelica MI. Urgent need for a new staging system in advanced colorectal cancer.j Clin Oncol Oct 10;26(29): Epub 2008 Aug Van Cutsem E, Nordlinger B, Adam R, Köhne CH, Pozzo C, Poston G, Ychou M, Rougier P; European Colorectal Metastases Treatment Group. Towards a pan- European consensus on the treatment of patients with colorectal liver metastases. Eur J Cancer Sep;42(14): Epub 2006 Aug 10. Review. 26

29 L8 - Is it possible to cure patients with liver metastases? Opinion of the surgeon Norihiro Kokudo University of Tokyo, Department HepatoBiliaryPancreatic, Surgery Division, Artificial Organ and Transplantation Division, Department of Surgery, Tokyo, Japan Although there has been a paradigm shift in the treatment of colorectal liver metastases (CRLM) after introduction of new chemotherapeutic agents, liver resection continues to be the only treatment option with a potential of cure. If we define 10-year survivors as cured cases, 20-40% of resectable CRLM can be cured by surgery alone. Liver remnant is the most common site of recurrence after liver resection, and repeated liver resection again provides a chance for cure. There have been a number of clinical trials to test the survival benefit of neoadjuvant, adjuvant, or perioperative chemotherapy for resectable CRLM. In this lecture, role of liver resection and chemotherapy will be discussed. Optimal primary endpoints for such clinical trials will also be discussed. 27

30 L9 - Optimal systemic chemotherapy for patients with liver metastases from colorectal cancer: does it exist? Alberto Sobrero, Marta Di Benedetto Medical Oncology, Ospedale San Martino Genoa, Italy With the advent of more active combination chemotherapy (CT) than just single agent FU, resections of unresectable liver metastases have been reported. Since then disease downstaging has become a relevant endpoint of conversion therapy. Neoadjuvant CT of resectable metastases was also investigated, within the frame of a perioperative strategy i.e continuing CT after surgery. In addition to unresectable and resectable metastases, potentially resectable metastases are usually considered a third category, although CT used in this setting should be regarded as conversion therapy. Conversion therapy is most challenging, since it is directed against macroscopic metastases with the aim of shrinking them or altering their structure, whereas perioperative therapy is directed against micrometastases. A recent systematic review of 23 neoadjuvant CT trials on resectable colorectal liver metastases reported a median RR of 64%, with R0 resection rate of 93%, and median DFS of 21 months. In the only phase III study available, these figures dropped to 43%, 87% and 19 months, respectively. These studies do not allow to answer the question regarding the optimal neoadjuvant CT for resectable metastases, because the phase III investigated FOLFOX CT vs surgery alone, and the other studies are single arm phase II. However if the patient has not received adjuvant FOLFOX this doublet seems most advisable, whereas in case of prior exposure to FOLFOX, either no preoperative CT or FOLFIRI can be considered. In nonresectable metastases the Tournigand study provide a randomized comparison between FOLFOX and FOLFIRI reporting a higher RR for FOLFOX with corresponding liver metastases R0 resection rate of 22% compared to 9% with FOLFIRI. This conversion rate of FOLFOX was confirmed (33% on 44 patients) in a phase II study. In a randomized phase III trial, Falcone et al. demonstrated an increased RR (66% vs 41%) and R0 resection rate (36% vs 12% in patients with liver only metastases) for the triplet regimen FOLFOXIRI compared with FOLFIRI, but these data were not confirmed in a similar randomized study. Further increased RR is reported with the addition of monoclonal antibodies to standard CT. At least 3 studies showed consistent improvements in RR (ranging from 59% to 79%) with addition of Cetuximab to CT in K-RAS wild type tumors. In the phase III CRYSTAL trial the rate of R0 liver resection increased from 1.5% with CT only to 4.3% with the addition of Cetuximab. The NO16966 trial, which compared XELOX/FOLFOX with or without Bevacizumab, demonstrated a non-statistically significant increase in the resection rate with the antibody (17.1% vs 12.6% for patient with liver metastases only). On a separate track, the old-fashioned locoregional treatment via hepatic arterial CT infusion (combined with systemic doublets) has recently been reported as extremely efficacious from a conversion viewpoint, although the limitation of this approach continues to be the lack of widespread experience that condition a high complication rate of catheters, limiting this approach to the experimental setting. The whole literature indicate therefore that either a CT triplet or a doublet plus cetuximab in K-RAS wt tumors are the most efficacious converting regimens. 28

31 L10 - How to achieve a complete surgical resection? Norihiro Kokudo University of Tokyo, Department HepatoBiliaryPancreatic, Surgery Division, Artificial Organ and Transplantation Division, Department of Surgery, Tokyo, Japan Liver resection for colorectal liver metastases (CRLM) has been accepted as the only available treatment that leads to a possible cure with long-term survival. Indications for liver resection have gradually been expanded thanks to advances in preoperative assessments and surgical techniques. Moreover, recent vast strides in chemotherapy including molecular targeted drugs have provided surgeons with the possibility to convert unresectable cases to resectable ones. Nonetheless, multiplicity of the tumors and adjacency or direct invasion to the major vessels are lingering obstacles to achieve a complete resection, even when marked tumor shrinkage is obtained by systemic chemotherapy. To achieve R0 resection, every recent advance in liver surgery including 3-D simulation, portal vein embolization, intraoperative ultrasonography, and vascular reconstruction, should be applied to preserve maximal liver remnant. In this lecture, strategies to achieve a complete resection for CRLM with zero mortality will be presented by showing representative cases and surgical outcomes in the author s institution. References: 1 - Chappel SC, Howles C 1991 Reevaluation of the roles of luteinizing hormone and follicle-stimulating hormone in the ovulatory process. Human Reproduction Filicori M, Cognigni GE, Pocognoli P et al Current concepts and novel applications of LH activity in ovarian stimulation. Trends in Endocrinology and Metabolism 14,

32 L11 - Guidelines for high standard pathological examination. How to detect changes in molecular biology between primary cancer and metastases? Laura Rubbia-Brandt Pathology Department, Geneva University Hospital Geneva, Switzerland By diagnosing and classifying tumors and assessing biomarkers predictive for treatment response and disease prognosis, pathological examination is of major importance for patients with cancer. Molecular pathology that encompasses molecular and genetic approaches is more and more used in on a daily day practice. The pathologist is thus an established member of the multidisciplinary team. Standardization for pathological examination and knowledge of element of molecular pathology are today important to provide high standard of care for patients with colorectal cancer. 30

33 L12 - Will predictive biomarkers help to improve treatment efficacy? Alberto Sobrero Medical Oncology, Ospedale San Martino Genoa, Italy There is no doubt that the future of any cancer treatment will transit through a better knowledge of the molecular factors that constitute the pathogenetic drivers of the disease. This will mean a new, molecularly based classification of each neoplasm. So far this has had an impact in GIST, hematologic malignancies, breast cancer, non small cell lung cancer. The impact of the new molecular classification on colorectal cancer has been marginal sofar. K ras is a predictor of resistance more than sensitivity, B RAF is prognostic, but with no predictive relevance, MSI importance is again very limited mostly because of the prevalent prognostic value over the predictive value and genomic signatures are not mature for clinical practice decision making. Two conditions need to be satisfied for a change in this direction to occur: that a true driver of the disease is identified and that inhibitors of this function with substantial clinical efficacy are developed. 31

34 L13 - Clinical impact of changes in molecular biology between primary cancer and metastases or in the evolution of treatment Josep Tabernero Vall d'hebron University Hospital, Medical Oncology Service Barcelona, Spain Abstract not in hand at the time of printing. References: 1 - Chappel SC, Howles C 1991 Reevaluation of the roles of luteinizing hormone and follicle-stimulating hormone in the ovulatory process. Human Reproduction Filicori M, Cognigni GE, Pocognoli P et al Current concepts and novel applications of LH activity in ovarian stimulation. Trends in Endocrinology and Metabolism 14,

35 L14 - How to optimize resectability Opinion of the surgeon: Special techniques Jean-Nicolas Vauthey Department of Surgical Oncology, Division of Surgery, The University of Texas, MD Anderson Cancer Center Houston, Texas, USA Several surgical strategies are available to optimize resectability. The first combines tumor downsizing with appropriate chemotherapy and liver remnant upsizing with portal vein embolization. The technique of portal vein embolization can be optimized in a small liver remnant with the addition of segment IV embolization to right portal vein embolization and with the use of spherical particles in addition to coils. When chemotherapy with an antiangiogenic agent is used prior to resection of advanced bilateral liver metastases, selection of candidates for resection based on the morphologic radiologic criteria of response can contribute to the long term oncologic success of the resection. Recent data indicate that R1 resection in the context of an optimal morphologic radiologic response is associated with a survival similar to resection with negative margins. Several oncologic surgical strategies are available for patients with synchronous or advanced disease: 1. two stage hepatectomy; 2. ALPPS (associated liver partition and portal vein ligation for stage hepatectomy); 3. the reverse approach. References: 1 - Chappel SC, Howles C 1991 Reevaluation of the roles of luteinizing hormone and follicle-stimulating hormone in the ovulatory process. Human Reproduction Filicori M, Cognigni GE, Pocognoli P et al Current concepts and novel applications of LH activity in ovarian stimulation. Trends in Endocrinology and Metabolism 14,

36 L15 - How to optimize resectability Opinion of the oncologist: Intraarterial chemotherapy Philippe Rougier Digestive Oncology Department, HEGP (Hopital Européen Georges Pompidou) Paris, France Resectability has become a major goal in the treatment of patients with liver metastases (LM) from colorectal cancer (CRC) without extra-hepatic lesions, because it results in longer survival rates and in 10 to 20% of the cases in survival without recurrence over 10 years. There is a close relation between the response rate to chemotherapy and the rate of secondary resections in patients with initially non resectable LM, so that all the treatments which potentially increase the response rate might be useful. This is the case for intraarterial hepatic chemotherapy (IAHC) which allows a higher concentration of drugs to reach the LM and by favoring the catabolism of drugs in the liver (first passage effect) to decrease the systemic exposure. It has been used in expert centers for more than 40 years and it is now demonstrated or suggested that IAHC: Results in in a very high RR (over 60%) and more complete responses using active drugs like oxaliplatin. Combined with active IV chemotherapy (LV5FU2, irinotecan, FOLFIRI, targeted therapies ) it allows to decrease the risk of extrahepatic progression and acts in synergy with IAHC on the LM. Is feasible without using the implantable pumps and the cathether placement may be done by radiological route. Is active in naïve patients as well as in LM resistant to systemic chemotherapy. Seems to decrease the risk of hepatic recurrence after resection of LM when IAHC is used as adjuvant treatment. IAHC is therefore one of the weapons to be used against LM which may be associated with all the other local and/or systemic treatments. Its development will be influenced by the discovery of new active drugs tailored to be administered by IAH route and, by the development of new intra-arterial vectors and spheres which may simplify the IAHC and the development of chemo-embolization combined with systemic treatments. 34

37 L16 - How to manage complete clinical response (Missing metastases)? - The opinion of the radiologist Ashley Guthrie Department of Clinical Radiology, St. James's University Hospital Leeds, UK Colorectal liver metastases may disappear either because there has been a complete pathological response and there is no residual disease or because the lesion: liver contrast is affected and the lesion ceases to be detectable. A complete radiological (usually with CT) is encountered in approximately 4% cases. Lesions become undetectable on imaging because of effects on the lesion ie changes in size and/or character, and /or on the liver parenchyma. The most important effect is reduction in size below the detection threshold of the imaging technique. This may be partially offset if the lesion responds to chemotherapy by becoming cystic this occurs in the minority of cases. Steatosis, steatohepatitis and sinusoidal obstructive syndrome may occur as a consequence of chemotherapy and may reduce lesion: liver contrast. A long lasting complete response to disappearing metastases is reported to occur in 17 73% of lesions. In general surgical decision should be based on the pre-chemotherapy imaging and there should be caution if liver has to be left in situ that has previously been shown to contain metastases. 35

38 L17 - How to manage complete clinical response (Missing metastases)? - The opinion of the medical oncologist Philippe Rougier Digestive Oncology Department, HEGP (Hopital Européen Georges Pompidou) Paris, France Complete response (CR) has not been considered as a major goal in the treatment of liver metastases (LM) of colorectal cancer (CRC) even if there are some evidences that CR are usually associated with a longer survival in patients with unresectable LM. In case of potentially resectable LM CR may be a good or a bad thing! It is a good thing when CR allows secondary resection but in this cases it always results in missing metastases which do not correspond to pathological CR and are not resected and still present or at risk of recurrence in over 80% of the cases. Nevertheless in patients with a high numbers of LM a R0 resection is only feasible if some of them disappear and are in CR! It is a bad thing if the disappearance of some LM impose to remove secondarily a large amount of normal liver to be able to resect a central metastasis which has disappeared. To avoid unnecessary CR there are different ways: To stop chemotherapy before the disappearance of the lesions potentially resectables by doing a careful follow-up of the patients. To mark by a coil LM which are at risk of CR (small lesion of less than 2 cm?) to be able to remove them at surgery. To administer in post operative an IAHC when missing metastases are let in place because in the IGR (Villejuif) experience it has resulted in an important decrease in the rates of hepatic recurrence and this strategy is presently tested in a prospective trial. 36

39 L18 - How to manage complete clinical response (Missing metastases)? - The opinion of the surgeon Catherine Teh Liver Care Center, Department of Surgery, Section of HPB Surgery, Makati Medical Center Makati City, Philippines The aim of preoperative chemotherapy in unresectable or berderline resectable liver metastases in colorectal cancer is to achieve resectability and or R0 resection for local control especially those with good clinical response. However, in some cases, CCR after chemotherapy happens although this is not very common. CCR is a surgical dilemma. The three fundamental questions that poses major challenges to the HPB surgeon are: 1. whether to resect or not and what to resect, 2. is complete clinical response synonymous with cure? 3. what prognosis do we expect in these patients in terms of recurrence rate and survival. Although there is a paucity of additional data as well as conflicting results regarding the outcome and management of CCR. It remains to be certain that patients who appear to have complete clinical response have a better survival compared to those with none or partial response after chemotherapy. In the era of improved chemotherapeutic agents and the advent of biological / targeted therapies, complete clinical response maybe truly achieved. A study by the MMSKC group have described a few factors that may determine the probability of complete clinical response, such as normalization of CEA levels, use of MRI as imaging and use of HAI chemotherapy. Despite a more favorable outcome in these small subset of patients, many groups still advocate to resect the initial sites of metastases whenever possible. References: 1 - Chappel SC, Howles C 1991 Reevaluation of the roles of luteinizing hormone and follicle-stimulating hormone in the ovulatory process. Human Reproduction Filicori M, Cognigni GE, Pocognoli P et al Current concepts and novel applications of LH activity in ovarian stimulation. Trends in Endocrinology and Metabolism 14,

40 L19 - How to predict complete pathological response and should it be a new end point? - The opinion of the radiologist Francis Kunstlinger Centre Hépato-Biliaire, Paul Brousse Hospital Villejuif, France Complete pathological response does not necessarily mean complete morphological response and, conversely, complete morphological response does not always correspond to complete pathological response. For this reason, even in case of disappearing lesions after primary chemotherapy, the site of metastases has to be resected and a complete pathological response needs to be confirmed by histological examination. More difficult for the radiologist is to evaluate if the persistence of an image correspond to a necrotic and fibrous scar with no viable tumor. Prospective studies exploring both vascularisation with CT MRI - contrast Ultrasoud and metabolic study with PET/CT and MRI with diffusion are needed to demonstrate if complete pathological response might be predicted by imaging. 38

41 L20 - How to predict complete pathological response and should it be a new end point? - The opinion of the surgeon Jean-Nicolas Vauthey Department of Surgical Oncology, Division of Surgery, The University of Texas, MD Anderson Cancer Center Houston, Texas, USA Pathologic tumor response to chemotherapy has recently been recognized as an important prognostic factor in patients treated with preoperative chemotherapy for breast, esophageal, gastric and colorectal cancer. In metastatic colorectal cancer to the liver, the degree of pathologic response has been graded 1/ using a scale of 1-5, 2/ using the percentage of residual cell, (0% residual tumor, major response) (1%-49% residual tumor) and (minor response > or = 50% residual tumor); or 3/ more recently based on tumor thickness as measured in millimeters at the periphery of the metastases (< 5 mm vs. > 5mm). All these semiquantative measurements have been shown to correlate with disease free survival and/or overall survival. We have previously published an excellent correlation between pathologic response measured as percentage of residual tumor cell and morphologic radiologic criteria in patients receiving preoperative chemotherapy with bevacizumab. Optimal morphologic radiologic response is associated with major or complete pathologic response. In a recent study reporting 209 hepatectomies with analysis of morphologic response criteria, an optimal morphologic radiologic response was independently associated with disease-free and overall survival after hepatectomy. Optimal morphologic response was not a unique feature of treatment with bevacizumab but was also observed in 12% of patients receiving oxaliplatin without bevacizumab. 39

42 L21 - How to predict complete pathological response and should it be a new end point? - The opinion of the medical oncologist Aimery de Gramont Service d Oncologie Médicale, Hôpital Saint-Antoine Paris, France Abstract not in hand at the time of printing. References: 1 - Chappel SC, Howles C 1991 Reevaluation of the roles of luteinizing hormone and follicle-stimulating hormone in the ovulatory process. Human Reproduction Filicori M, Cognigni GE, Pocognoli P et al Current concepts and novel applications of LH activity in ovarian stimulation. Trends in Endocrinology and Metabolism 14,

43 L22 - Surgery, exploring the limits: what patients are unlikely to benefit from surgery? René Adam Centre Hépato-Biliaire, Paul Brousse Hospital, Université Paris Sud Villejuif, France Resection of colorectal liver metastases (CRLM) is the only treatment offering the possibility of cure and has been shown to provide clear survival benefits. Therefore the main end point of the treatment strategy of CRLM is to increase their resectability. On the other hand, the extension of indications could lead to propose resection of CRLM to patients that do not really benefit from surgery. Methods We have defined as failure of surgery any patient death occurring within 1 year after liver surgery. In a retrospective analysis of LiverMetSurvey (LMS), patients characteristics, data from the primary and from the metastases, type and response to pre and postoperative chemotherapy as well as data from the operative procedure were evaluated with regards to death within 1 year. Uni and multivariate analysis were performed to identify the predictive factors independently associated to survival at 1 year. Results From January 2005 to June 2011, among 7653 pts resected from CRLM with a follow-up more than 1 year, 6816 pts (89%) survived at 1 year while 837 (11%) died within 1 year. At univariate analysis, age of the patient localization of the primary and presence of metastatic lymph nodes, serum CEA levels at diagnosis, time interval between the primary and CRLM, number and size of CRLM, uni or bilateral distribution, the presence of concomittent extrahepatic tumor, the extent and completeness of hepatectomy as well as the length and response to preoperative chemotherapy and the performance and delay (from liver resection) of postoperative chemotherapy, were all significantly associated to patient survival at 1 year (all p<0.0001). At multivariate analysis, 9 factors remained independently associated to patient death at 1 year: Risk Factor OR CI95% p R2 resection 2.43 [1.82;3.23] <.0001 Right localization 1.92 [1.55;2.38] <.0001 Recipient Age 70yrs 1.74 [1.42;2.14] <.0001 Concomitant Extrahepatic disease 1.72 [1.33;2.22] <.0001 Progression after preop. chemoth [1.05;2.48] Major hepatectomy 1.60 [1.29;1.99] <.0001 Metastases 30 mm 1.52 [1.24;1.86] <.0001 Node N2 or N3 Primary 1.34 [1.08;1.65] metastases 1.31 [1.06;1.63] Conclusions Around 10% of patients resected from CRLM do not really benefit from surgery. Risk factors of surgical treatment failure are clearly established allowing multidisciplinary teams to identify the patients highly risky not to benefit from surgery. 41

44 L23 - Adjuvant chemotherapy what treatment and how long? Aimery de Gramont Service d Oncologie Médicale, Hôpital Saint-Antoine Paris, France Adjuvant therapy, with the goal of reducing the risk of relapse after resection of liver metastasis from colorectal cancer, is an important topic as approximately 70% of these patients will experience recurrence of the metastases either in the liver or in other sites. Adjuvant therapy is standard in stage III and in selected stage II colon cancer. In stage III, fluoropyrimidine-based chemotherapy has reduced the risk of relapse of approximately 40% and with the addition of oxaliplatin, an additional 20%. The absolute disease-free benefit ranges between 10 to 25% for fluoropyrimidines to 15-40% for fluoropyrimidines plus oxaliplatin. Of note all other drugs, including irinotecan and targeted therapies such as the anti-vegf monoclonal antibody bevacizumab and the anti-egfr antibody cetuximab failed to reduce the recurrence rate in the adjuvant setting. However, there is limited data on adjuvant therapy for resected colorectal metastases. Fluoropyrimidines trials have been undersized and accrual was difficult when a potential active treatment was compared to no therapy. Oxaliplatin-based chemotherapy has been used pre- and post-operatively and results were lower than expected, based on the stage III experience. Furthermore, patients with metachroneous resected colorectal metastases may have previously received adjuvant therapy for their primary tumor and if they have failed, there is no reason that a second course of the same adjuvant therapy may be active. Based on these data we believe that preoperative and/or adjuvant therapy should still be administered in case of resected synchroneous colorectal metastases. Adjuvant post-operative chemotherapy is not needed in case of exposure to the same adjuvant therapy for the primary cancer. The regimen should be oxaliplatin plus fluoropyrimidines, FOLFOX or XELOX, for a duration of 6 months (bi-monthly FOLFOX 12 cycles, every-three weeks XELOX 8 cycles). In case of neuropathy, fluoropyrimidines alone should be considered. Well designed trials are needed to compare pre-operative and adjuvant therapy. 42

45 L24 - Elderly patients: which guidelines? The opinion of the medical oncologist Eric Van Cutsem Digestive Oncology Unit, University Hospital Gasthuisberg Leuven, Belgium There are very few specific evidence based guidelines or recommendations available on the management in elderly patients. However, elderly patients can and should also be treated relatively aggressively if life expectancy is good, if the general condition and organ function is adequate and if there is no important comorbidity. The strategy is also influenced by the expectations of the patient and his environment. References: 1 - Schmoll HJ, Van Cutsem E, Stein A, Valentini V, Glimelius B, Haustermans K, Nordlinger B, van de Velde CJ, Balmana J, Regula J, Nagtegaal ID, Beets-Tan RG, Arnold D, Ciardiello F, Hoff P, Kerr D, Köhne CH, Labianca R, Price T, Scheithauer W, Sobrero A, Tabernero J, Aderka D, Barroso S, Bodoky G, Douillard JY, El Ghazaly H, Gallardo J, Garin A, Glynne-Jones R, Jordan K, Meshcheryakov A, Papamichail D, Pfeiffer P, Souglakos I, Turhal S, Cervantes A. ESMO Consensus Guidelines for management of patients with colon and rectal cancer. A personalized approach to clinical decision making. Ann Oncol Oct;23(10): Audisio RA, Papamichael D. Treatment of colorectal cancer in older patients. Nat Rev Gastroenterol Hepatol Oct 9. doi: /nrgastro [Epub ahead of print] 3 - Pallis AG, Papamichael D, Audisio R, Peeters M, Folprecht G, Lacombe D, Van Cutsem E. EORTC Elderly Task Force experts' opinion for the treatment of colon cancer in older patients. Cancer Treat Rev Feb;36(1): Epub 2009 Nov 26. Review. 4 References: - Kyriakou F, Kountourakis P, Papamichael D. Targeted agents: review of toxicity in the elderly metastatic colorectal cancer patients. Target Oncol Dec;6(4): Chappel SC, Howles doi: C /s Reevaluation of the roles Epub of 2011 luteinizing Nov 9. hormone Review. and follicle-stimulating hormone in the ovulatory process. Human Reproduction 5 - Papamichael D, Audisio R, Horiot JC, Glimelius B, Sastre J, Mitry E, Van Cutsem E, Gosney M, Köhne CH, Aapro M; SIOG. Treatment of the elderly colorectal 2 - cancer Filicori patient: M, Cognigni SIOG GE, expert Pocognoli recommendations. P et al Ann Current Oncol. concepts 2009 Jan;20(1):5-16. and novel applications Epub 2008 of Oct LH 15. activity Review. in ovarian stimulation. Trends in Endocrinology and Metabolism 14,

46 L25 - Elderly patients: which guidelines? The opinion of the surgeon Joan Figueras Department Hepato-Biliary and Pancreatic Surgery, Department of Surgery, "Dr Josep Trueta Hospital Girona, Spain Liver resection has been accepted as the standard treatment of colorectal liver metastases (LM). It has been also demonstrated that hepatectomy can be performed safely in elderly patients. From 1990 to 2006, 648 patients underwent hepatectomy for colorectal LM in our Centre. Patients were classified in two groups according to age. Group <70y included 488 patients younger than 70 years and group >70y included 160 patients aged 70 years or older. There were no statistical differences regarding epidemiological data and primary tumour characteristics. The surgical technique, transfusion, and the type of hepatectomy performed and the duration of the operation were also similar. Regarding the LM, older patients had a higher proportion of metachronic diagnosis and the interval between surgery of the primary and hepatectomy was longer. Older patients had a great proportion of solitary LM. However, LM were bigger. Postoperative morbidity was superior in older patients, mainly because of more pulmonary infection. Oncological results after resection of colorectal LM in elderly patients are excellent, because disease free survival and specific hepatic recurrence rate are similar to younger patient. Actuarial survival was lower in elderly patients. However, when excluding 30 days mortality 5- years survival is 39% and similar to the other series. Patients older than 70 years with colorectal carcinoma, needs a closer follow-up in order to detect LM earlier, with a smaller size. Probably surgical indications and postoperative care in older patients must be improved. 44

47 Disclosure of faculty relationships Serono Symposia International Foundation adheres to guidelines of the European Accreditation Council for Continuing Medical Education (EACCME) and all other professional organizations, as applicable, which state that programs awarding continuing education credits must be balanced, independent, objective, and scientifically rigorous. Investigative and other uses for pharmaceutical agents, medical devices, and other products (other than those uses indicated in approved product labeling/package insert for the product) may be presented in the program (which may reflect clinical experience, the professional literature or other clinical sources known to the presenter). We ask all presenters to provide participants with information about relationships with pharmaceutical or medical equipment companies that may have relevance to their lectures. This policy is not intended to exclude faculty who have relationships with such companies; it is only intended to inform participants of any potential conflicts so that participants may form their own judgements, based on full disclosure of the facts. Further, all opinions and recommendations presented during the program and all program-related materials neither imply an endorsement nor a recommendation on the part of Serono Symposia International Foundation. All presentations represent solely the independent views of the presenters/authors. The following faculty provided information regarding significant commercial relationships and/or discussions of investigational or non-emea/fda approved (off-label) uses of drugs: René Adam Declared receipt of grants and contracts from Sanofi, receipt of honoraria or consultation fee from Merck, Pfizer, Roche, Sanofi. Declared he is member of a company advisory board, board of directors or other similar group for Merck, Roche, Sanofi. Aimery de Gramont Declared receipt of honoraria or consultation fee from Roche, Sanofi. Joan Figueras Declared receipt of grants and contracts from Roche, he declared receipt of honoraria or consultation fees from Roche, Merck Serono, Sanofi-Aventis. Ashley Guthrie Declared receipt of honoraria or consultation fee from Bayer. Norihiro Kokudo Declared receipt of grants and contracts from Birstol-Myers Squibb and Merck Serono. Declared he is member of a company advisory board, board of directors or other similar group for Bayer. Francis Kunstlinger Declared no potential conflict of interest. Evelyne Loyer Declared no potential conflict of interest. Philippe Rougier Declared receipt of honoraria or consultation fee from: Sanofi, Merck-Serono, Ipsen, Pfizer, Lilly, Bayer. Declared he is member of a company advisory board, board of directors or other similar group for Sanofi, Merck-Serono. He declared that his presentation will discuss off-labeled or otherwise non-approved uses of products: use of oxaliplatin intra arterially and other drugs like mitomycin C and irinotecan without any commercial aims and support from the industry, concerning product which are no more covered by a licence of exclusivity. Laura Rubbia-Brandt Declared no potential conflict of interest. Alberto Sobrero Declared receipt of honoraria or consultation fee, declared he is member of a company advisory board, board of directors or other similar group, declared participation in a company sponsored speaker s bureau. Josep Tabernero Declared receipt of honoraria or consultation fees from Amgen, BMS, Genentech, Merck KGaA, Millennium, Novartis, Onyx, Pfizer, Roche, Sanofi. He declared participation in a company sponsored speaker s bureau for Amgen, Merck-Serono, Novartis, Roche, Sanofi. Catherine Teh Declared no potential conflict of interest. Eric Van Cutsem Declared receipt of grants, contracts, research grant from Merck-Serono, Roche, Amgen Jean-Nicolas Vauthey Declared no potential conflict of interest. 45

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