2012 Sistema Sanitario

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3 Sistema Sanitario 2012

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5 scientific report 2012 Contents Introduction 4 Scientific Directorate 10 Independent Ethics Committee 16 Education and Training 18 Medical Directorate - Clinical Activity Management 26 CLINICAL-SCIENTIFIC DEPARTMENTS 30 Surgery Department 33 Gastrointestinal, Hepatopancreatobiliary Surgery, and Liver Transplantation 34 Colorectal Surgery 35 Breast Surgery 36 Melanoma and Sarcoma 37 Diagnostic Endoscopy and Endoscopic Surgery 38 Otolaryngology Surgery 39 Gynecologic Oncology 40 Thoracic Surgery 41 Plastic and Reconstructive Surgery 42 Urologic Surgery 43 Pediatric Surgery 45 Laser Therapy 46 Day Surgery 47 Medical Oncology Department 49 Medical Oncology 1 50 Medical Oncology 2 51 Adult Mesenchymal Tumor Medical Oncology 52 Head and Neck Cancer Medical Oncology 53 Medical Day Hospital 54 Hematology and Pediatric Onco-Hematology Department 57 Hematology and Allogeneic Bone Marrow Transplantation 58 Pediatric Oncology 59 SIMT, Immunohematology and Transfusion Medicine 60 Anesthesia, Intensive Care, Pain Therapy, and Palliative Care Department 63 Clinical Anesthesia 64 Intensive Care 65 Palliative Care, Pain Therapy, and Rehabilitation 66 Supportive Care in Cancer 67 Clinical Nutrition 68 Diagnostic Imaging and Radiotherapy Department 71 Radiology and Diagnostic Imaging 1 72 Radiology and Diagnostic Imaging 2 75 Nuclear Medicine 77 Radiation Oncology 1 79 Radiation Oncology 2 82 Medical Physics 83 Pathology and Laboratory Medicine Department 85 Anatomic Pathology Units 1, 2 and3 86 Laboratory Medicine 87 Experimental Oncology and Molecular Medicine Department 89 Immunobiology of Human Tumors 91 Molecular Therapies 92 Molecular Immunology 93 Biomarkers 95 Molecular Mechanisms of Cell Cycle Control 96 Molecular Mechanisms 97 Immunotherapy of Human Tumors 98 Tumor Genomics 99 Molecular Targeting 100 Molecular Pharmacology 101 AIRC Start Up Unit 102 Preventive and Predictive Medicine Department 105 Epidemiology and Prevention 106 Analytical Epidemiology and Health Impact 107 Evaluative Epidemiology 108 Cancer Registry and Environmental Epidemiology 109 Medical Genetics 110 Hereditary Digestive Tract Tumors 111 Molecular Basis of Genetic Risk and Genetic Testing 112 Genetic Epidemiology and Pharmacogenomics 113 SHARED RESEARCH RESOURCES 114 Cardiology 116 Respiratory Pathophysiology 117 Clinical Psychology 118 Medical Statistics, Biometry, and Bioinformatics 119 Tissue Bank 120 Functional Genomics, and Bioinformatics 121 Cancer Proteomics 122 RESEARcH ACTIVITY 124 Prostate Cancer Program 126 Breast Cancer: Outline of Clinical and Preclinical Research 131 Lung Cancer Program 134 Melanoma Program 140 Personalized Treatment of Sarcomas 145 Novel Approaches to Determine the Prognosis and Response to Treatment in Mature B-Cell Malignancies 148 Pediatric Brain Tumors 151 Development of Radiopharmaceuticals for Tumor Characterization, Molecular Imaging, and Therapy 157 PUBLICATIONS 161 Ongoing Projects Supported By external Organizations 201 Ongoing Clinical Studies 209

6 BACK TO CONTENTS FOREWORD Marco A. Pierotti Scientific Director Giuseppe De Leo President 4

7 scientific report 2012 Gerolamo Corno Managing Director In 2012, the Scientific Directorate supported the development of research resources by firstly promoting innovative initiatives in the organization of the Institute. Following the site visit in 2011, in April, we obtained the official renewal of our designation as a research and care center. While we are waiting for new guidelines from the Ministry of Health to update key institutional policies for research; debate on the role and mission of IRCCSs and the means to accomplish these has continued. From various quarters it was noted that the centers recognized as IRCCS require specific institutional regulations in order to function efficiently, but they have not been actually issued. This can create a de facto unclear situation where, on one hand, we need to keep our Institute up to the standards of a comprehensive cancer center while, on the other, in the absence of any dedicated regulation, we are still saddled to an organizational model that was prevalently tailored to the needs of hospitals. From a practical point of view, this means that the organization of INT is still structured in vertical departments that operate autonomously in the organization and management of projects and corresponding budgets. One of the main concerns for the Scientific Directorate is in finding ways to adapt this structure to the diverse needs of the various components of the Institute. The clinical sector requests an increasingly multidisciplinary approach to the disease, while the research area sees a discrepancy between unmet clinical needs and decisions concerning investment in research as a major obstacle to swift transfer of innovation to the bedside, which in the end is the objective of an IRCCS. To address these demands, we devised and implemented the idea of grafting new horizontal structures into traditional vertical departments (that could be seen as functional departments) thus generating a matrix model. The nature of the activities performed by the innovative horizontal structures can be grouped around the concepts of disease-oriented and problem-oriented projects: the first focuses on the major cancer types, such as breast, lung, prostate, and rare tumors, while the latter concentrates on cross specialty problems, such as early detection. In this regard, it is worth mentioning that in 2012 a project submitted by a large INT team was awarded substantial funding from the AIRC 5x1000 program, an achievement that enabled us to launch a problemoriented platform on early detection. Whether this new model will be successful depends on two conditions. First of all, each functional department must have the resources necessary to carry out its mission and manage them in autonomy, so as to compensate for the time physicians need to use for the project outside the organizational department to which they are assigned. Secondly, the PI, or the person responsible for a horizontal structure, must possess vision and leadership. Vision is indispensable to create strong projects that identify crucial unmet clinical needs and their priorities, while strong leadership is necessary to build trust among colleagues and to gather the professional 5

8 BACK TO CONTENTS scientific report 2012 Foreword expertise required. A crucial feature of this model is that it induces a physiologic renewal because the horizontal structures decay within a set timeframe when the project has either achieved its objective (and the structure is no longer needed) or has failed to do so (and rethinking or a change of direction is probably needed). Another objective that this Scientific Directorate has identified as crucial is the advancement and enhancement of our infrastructure for clinical trials. Through the ROL and Nerviano Medical Sciences (NMS) programs, we managed to promote new clinical trials in a period marked by the complete inactivity/ inertia of the Agenzia Italiana del Farmaco (AIFA) so that at INT, four clinical studies funded by the Regione Lombardia with the Nerviano CRO are currently active. The issue of clinical trials is both crucial and delicate, concerning not only our institute, but the wider European reality. It has been repeatedly noted that big pharma nowadays tend to move their clinical studies away from Europe to the so-called BRIC countries. We believe that this is an alarming trend and that it should be opposed, because sponsored clinical studies provide an exceptional opportunity of economic benefit that, among other beneficial consequences, enable us to launch and conduct independent, research-driven studies. To date, at INT there is an almost perfect balance between sponsored and unsponsored/independent clinical trials, so that an excessive decrease in the number of sponsored studies would probably put this delicate mechanism at risk. To face this challenge, we need to provide a more efficient offer. This was one of the main reasons why, in January 2012, the Scientific Directorate re-established the Clinical Trial Center with the mission of supporting clinical studies, especially investigator-driven phase I and II studies. The Clinical Trial Center works with validated SOP and electronic CRF and supports clinicians in managing various aspects of the clinical study, such as study design, statistical validation, file submission to the independent Ethic Committee and, if necessary, to regulatory authorities, budget and contract related issues, data management and data analysis with statistics, pharmacovigilance through an ad hoc trained pharmacist, and the management of enrolled patients by qualified research nurses. The Clinical Trial Center is also improving the organization of sponsored clinical studies by speeding up administrative processes, budget definition, patient recruitment, and data management. In 2012, the Clinical Trial Center managed 19 investigator driven and six sponsored clinical trials. The enhanced ability to manage and conduct clinical studies not only involves better exploitation of already available resources, but also compels us to start planning and implementing new infrastructures to complete an offer that, regarding clinical studies, in the future will provide not only data regarding patient response to a drug, but also the molecular profile of the treated tumor. To achieve this ambitious plan, a significant investment must be made. INT has already taken some steps in this direction: an institutional tissue bank is in place and fuunctioning, and a genomic platform has been designed; some of its structures have already been implemented in 2012 at the Pathology and Laboratory Medicine Department headed by Professor Pelosi and the Experimental Oncology and Molecular Medicine Department at the Amadeo Lab. We are also considering the special effort that, in the near future, we will have to make in the field of molecular imaging, a sector that is becoming increasingly important for the conduction of clinical trials with personalized drugs as it enables monitoring efficacy of the compounds at a very early stage. 6

9 scientific report 2012 Foreword Concerning our ability to find resources, 2012 confirms a positive trend in the funding obtained from private and public agencies. We need, however, to look at new ways to improve the financial performance of our research. In this context, in 2012 an INT-NMS project on clinical development of the molecule danusertib (taken from the NMS pipeline) was launched. Danusertib is an aurora-kinase inhibitor that has already completed Phase I and II trials, and can therefore be compared with similar drugs. The agreement for the joint development of the molecule includes commercial terms regulating on one hand the commitment of the INT to the clinical development of danusertib and, on the other, the transfer to INT of the revenue arising from commercial exploitation of the molecule. Notwithstanding the difficulties related to the still unresolved issue of research staff (lack of tenure track, halt on the creation of new permanent positions), we note with great satisfaction once again an increase in INT Impact Factor for 2012 (2,519.29) and number of publications (518). The excellence of our scientific production is also reflected in the Scimago Institutions Ranking, where we were included in the list of the Top Ten Impact Factor and published papers Impact Factor Published Papers

10 BACK TO CONTENTS scientific report 2012 Foreword European Cancer Institutes. Research at the INT comprises a variety of innovative research fields in oncology: an overview of the work and accomplishments of the various Departments and Units can be found, as always, in the pages of this Report. The ROL continued its commitment to consolidating and expanding the results achieved so far according to the instructions by the Regional Cancer Committee that were included in the Operational Plan approved by the Lombardy Region. On 15 May 2012, the first year of activity was completed and ROL presented a poster summarizing its vision, mission, and initiatives to ASCO 2012 in Chicago. Continuing on a very positive note, we are delighted to announce that Dr Andrea Necchi obtained the Conquer Cancer Foundation of ASCO Merit Award for his exceptional clinical study on the treatment of urothelial cancer using a molecular targeted drug, the results of which were published in Lancet. INT submitted the Me.Me.Me project on breast cancer prevention and metformin to the ERC funding scheme, one of the most selective for investigator-driven research projects, and succeeded in obtaining substantial funding ( 2.5 million over five years). 85 anni di storia di lotta ai tumori During the preparation of this Scientific Report, INT celebrated its 85th anniversary. The occasion was marked by the inauguration of a wall panel in the Institute entrance hall, featuring photographs of the Scientific Directors who led INT over the years. 8

11 scientific report 2012 Foreword At an international level, the Scientific Directorate is involved in the EurocanPlatform project as the co-coordinator of a Working Group, and is present in the Network Steering Committee of TRANSCAN and in the Board of Directors of the WIN Consortium. At the General Assembly of the Organisation of European Cancer Institutes (OECI), the Scientific Director gave a presentation illustrating the reasons behind the success of the START-OECI project ( The European Options and Recommendations of Diagnosis and Therapy ). The European vision of the Scientific Directorate was disseminated at ECCO Oncopolicy Forum with a presentation on the The Future of Personalized Cancer Medicine in Europe. In Paris, during a meeting of the WP8 of the European Partnership for Action Against Cancer (EPAAC), the Scientific Director also participated in a round table on Public- Private Partnerships in early phase clinical research. 9