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  • 2. MEDICAL ONCOLOGY 143 DIRECTOR OF DEPARTMENT HEADS OF DIVISION AND UNIT Paolo Corradini, MD Professor of Hematology, Università degli Studi, Milano Luca Gianni, MD phone number: +39 02 2390 2950 Medical Oncology 1 e-mail: paolo.corradini@istitutotumori.mi.it Emilio Bajetta, MD The Department consists of five clinical divisions (81 beds), one centralized day Medical Oncology 2 hospital (29 beds), 17 outpatient rooms, one operations office for clinical trials, and a Alessandro M. Gianni, MD laboratory area for cell manipulation, flow cytometry, clinical pharmacology, and Medical Oncology 3 molecular biology. The routine clinical activity is focused on the treatment of adult and pediatric patients Paolo G. Casali, MD Adult Sarcoma Medical Treatment with solid tumors and hematologic malignancies. Several Unit clinical programs are active, which range from conventional chemotherapy to phase I studies to the transplantation of Lisa Licitra, MD Head & Neck Cancer Unit hematopoietic cells. The Department is organized in Divisions which are in charge Paolo Corradini, MD of different aspects of cancer research and treatment. Hematology & Allogeneic Bone Marrow Transplantation • Medical Oncology 1 deals with breast cancer (BC) treatment and development of new drugs Franca Fossati Bellani, MD • Medical Oncology 2 deals with gastrointestinal, lung, renal Pediatric Oncology and prostate cancer, melanoma and neuroendocrine tumors Cristina Brambilla, MD • Medical Oncology 3 is engaged in preclinical and clinical Day Hospital Unit activities mainly in the field of malignant lymphomas, head and neck cancer and sarcomas • Pediatric Oncology is in charge of pediatric patients with cancer • The Hematology and Allogeneic Bone Marrow Transplantation Unit manages all types of hematologic malignancies and develops new treatment strategies, in particular in the allogeneic transplant setting • The Medical Day Hospital (DHM) deals with adult patients referred by the clinical divisions of the Department of Medical Oncology.
  • 3. 144 SCIENTIFIC REPORT 2008 MEDICAL ONCOLOGY 1 THE CLINICAL ACTIVITY OF MEDICAL ONCOLOGY 1 IS MAINLY IN THE FIELD OF BREAST CANCER AND NEW DRUG DEVELOPMENT. IN 2008 THE DIVISION ACTIVELY PARTICIPATED IN MORE THAN 20 PROJECTS. The staff of the Division of Medical Oncology 1 is organized in small groups of regular HEAD OF DIVISION staff members and fellows in training who are responsible for the coordinated Luca Gianni, MD management of clinical assistance and clinical research. Each group provides care to an STAFF MEMBERS assigned number of patients. The same group is in charge of the execution of specific Giulia Bianchi, MD; Giuseppe Capri, research programs with coordinated access to all the facilities available within the MD; Sara Cresta, MD; Gabriella Division: hospital beds, day-hospital activities, outpatient facilities, and a research Mariani, MD; Angela Moliterni, MD; Antonella Perotti, MD; Milvia laboratory for the pharmacokinetic and pharmacodynamic evaluation of new Zambetti, MD treatments. The Division is especially dedicated to the medical oncology treatment of women with CONSULTANT Cristiana Sessa, MD BC, and to the planning and performance of medical and/or multidisciplinary clinical trials related to BC. In addition, the Division is responsible for a strategic project of the RESEARCH MEMBERS Scientific Directorate for the programming, planning and execution of phase I and Giampaolo Bianchini, MD; Gianluca Del Conte, MD; Angelica Fasolo, MD; early phase II clinical trials in all solid tumor types. The project is endowed with an ad Silvia Govi, MD; Paola Mariani, MD hoc donation and is known as the “Montabone Project” (see Multidisciplinary Programs, page 27) by the name of the donor. The Division has gained the LABORATORY TECHNICIANS collaboration of Cristiana Sessa of the Oncology Institute of Southern Switzerland Alberta Locatelli, Biol Sci D; Lucia Viganò, Biol Sci D (IOSI) as the project leader and consultant for new drug development. The clinical research activities stem from a productive collaboration with different RESIDENTS institutes and cooperative groups. In particular, Medical Oncology 1 is leading the Claudio Adile, MD; Gianluca Cutolo, MD; Silvia Damian, MD; Chiara clinical and scientific coordination of the BC Working Group of the Michelangelo Dazzani, MD; Elena De Benedictis, Foundation, and has long been collaborating with the Southern Europe New Drugs MD; Debora Fumagalli, MD; Silvia Organization (SENDO). In addition, the Division coordinates one Italian and one Grecchi, MD; Maria Chiara Parati, MD European collaborative group aimed at the organization of phase III trials in operable BC. The Division has at its disposal 14 hospital beds dedicated to treatment planning and administration including pharmacokinetic and pharmacodynamic investigations. Overall, there were about 500 hospital admissions in 2008. More than 100 of these
  • 4. MEDICAL ONCOLOGY 145 were for patients enrolled in clinical trials of the Montabone Project or other sponsored studies. The growing number of such cases reflects the growing clinical research activity of the Division. The core of the clinical activity consists of outpatient care in six daily clinics. The number of visits is about 100 per day. In 2008 the Division provided more than 20,000 visits and 10,000 infusional treatment sessions. In addition, it offered around 1,200 consultations to patients at their first access to the Division, including second and further opinions. Treatment is delivered in the outpatient clinic or the Day Hospital according to the characteristics of the therapy to be administered. One of the six clinics is reserved for patients amenable to phase I treatment protocols. The Montabone Project has granted consultations for phase I studies to more than 350 patients who were referred from outside INT for enrollment into studies of early drug development. Together with the Divisions of Breast Surgery and Radiotherapy, Medical Oncology 1 runs a daily outpatient clinic where all newly referred patients to INT with a histologic or cytologic diagnosis of invasive BC are seen by a team of surgeons, medical oncologists and radiotherapists, if needed. The multidisciplinary team grants prompt staging and treatment planning for new cases of BC, allows uniform information and communication to patients, and speeds up the application of specific procedures, tailoring treatment to individual needs. In 2008 multidisciplinary consultations were provided to 1,300 patients surgically treated in the Institute for BC.
  • 5. 146 SCIENTIFIC REPORT 2008 MEDICAL ONCOLOGY 2 THE MISSION OF THE MEDICAL ONCOLOGY 2 IS TO TREAT CANCER AND RELATED DISEASES THROUGH INTEGRATED PROGRAMS IN PATIENT CARE, RESEARCH, AND CLINICAL TRIALS. Our Division is striving to realize this mission also through strong partnerships with HEAD OF DIVISION the other Divisions, as well as with other cancer centers nationally and internationally, Emilio Bajetta, MD in an effort to develop more effective therapies that are targeted to each patient’s STAFF MEMBERS unique disease profile. We evaluate different types of cancer, including gastrointestinal, Roberto Buzzoni, MD; Luigi Celio, lung, renal, prostate, melanoma and neuroendocrine tumors. We also manage MD; Michele Del Vecchio, MD; problems in cancer patients that may require specialized, multidisciplinary care in a Maria Di Bartolomeo, MD; Giuseppe Procopio, MD; Nicoletta comprehensive cancer center. Such problems include hematologic disorders due to Zilembo, MD chemotherapy treatments, pain, and infections. One of the main objectives of the Division is to provide state-of-the-art treatment of RESEARCH MEMBERS Laura Catena, MD; Marco primary malignant tumors. The clinical activity is mainly addressed to the diagnosis and Platania, MD treatment of gastrointestinal malignancies, thoracopulmonary, urogenital (prostate, bladder, kidney) and skin cancer (melanoma), with a special interest in RESIDENT Marianna Accolla, MD; Stefania neuroendocrine tumors. The goal is to maximize the response and quality of life of Canova, MD; Andrea Colombo, MD; each patient with advanced schedules of treatment. Particular attention is paid to Fiorella K. Dotti, MD; Angela Denaro, enrolling most patients into clinical research protocols. In the ward, which has 14 MD; Monika Ducceschi, MD; hospital beds for inpatients, the activity is managed by a permanent staff member with Valentina Guadalupi, MD; Filippo Pietrantonio, MD; Sara Pusceddu, the help of residents. The clinical hospitalization activity has been steadily increasing MD; Elena Verzoni, MD over the past year and there were about 720 admissions in 2008. Also the outpatient activity increased significantly, in 2008 the Division provided more than 29,000 visits and around 1,600 consultations to patients at their first access to INT, including second and further opinions. The medical outpatient clinic comprises four consulting rooms, one of which is dedicated to consultations and first-admittance visits. This service is provided 2-3 days after receipt of the patient’s request. The medical day-hospital of the Division has eight beds and a daily availability of 16 services where patients are monitored by a team of trained physicians and nurses; short-term chemotherapeutic treatments are performed in a dedicated room. The Medical Oncology 2 is actively engaged in research-driven patient care through our
  • 6. MEDICAL ONCOLOGY 147 multidisciplinary care centers in collaboration with colleagues from other disciplines to offer the most integrative approaches to cancer treatment. Our research programs are on the forefront of cancer research in the development of treatment schedules. We are an integral part of the Centro di Riferimento per lo Studio e la Cura dei Carcinoidi e dei Tumori Neuroendocrini (Ce.Ri.Ca.) which applies a multidisciplinary approach to the treatment of neuroendocrine tumors. This referral center operates through a multidisciplinary team, modern medical and surgical treatment, and basic and clinical research, to provide the best possible care to patients affected by neuroendocrine tumors. The research activity is focused on the development of new treatment strategies and the evaluation of drug efficacy and new drug combinations. Most of the ongoing programs utilize new drugs, primarily biologic agents (EGFR, VEGFR, Raf kinase inhibitors, and mTOR inhibitors). In particular, several studies have been opened to recruitment in 2008 and will be aimed at the assessment of RAD001 (everolimus), a novel oral derivative of rapamycin, which acts as a signal transduction inhibitor and whose target is mTOR. The research activity is partly related to the protocols managed by the Division itself and partly to the initiatives of a multicenter group for clinical research named I.T.M.O. (Italian Trials in Medical Oncology). In 2008, 20 new investigational protocols were initiated after ethical committee approval, and several proposed studies, both phase II and phase III, are under evaluation. In November 2008 Emilio Bajetta created the Fondazione Giacinto Facchetti per lo Studio e la Cura dei Tumori. The foundation’s objective is to promote and improve research and clinical activities in oncology, specifically related to the prevention, diagnosis and treatment of all types of cancer. Projects aimed directly at the patient and expected to yield rapid returns for clinical practice are favored by the new foundation.
  • 7. 148 SCIENTIFIC REPORT 2008 MEDICAL ONCOLOGY 3 THE DIVISION OF MEDICAL ONCOLOGY 3 CARRIES OUT BOTH PRECLINICAL AND CLINICAL TRANSLATIONAL RESEARCH MAINLY IN THE FIELD OF MALIGNANT LYMPHOMAS. The scientific activity of the Division covers several fields, including hematopoietic HEAD OF DIVISION stem cells, cell- and antibody-mediated immunotherapy, cell and gene therapy, and Alessandro M. Gianni, MD Professor of Medical Oncology, high-dose myeloablative chemotherapy with hematopoietic stem cell autografting. Università degli Studi, Milano The Division includes four areas: a) a 12-bed inpatient ward; b) a day hospital facility; c) an outpatient clinic with three consulting rooms; d) a cell processing laboratory. The STAFF MEMBERS Division provides care mainly for patients with non-Hodgkin’s lymphomas (NHL), Valeria Bonfante, MD; Carmelo Carlo-Stella, MD; Liliana Devizzi, MD; Hodgkin’s disease, multiple myelomas, and testicular tumors. Selected patients with Massimo Di Nicola, MD; Michele high-risk carcinomas (including breast, testicular and ovarian cancer) are treated - if Magni, MD; Paola Matteucci, MD; eligible - in specific research programs offering high-dose myeloablative chemotherapy, Simonetta Viviani, MD vaccination, or new biologic agents. The majority of patients are enrolled in clinical RESEARCH MEMBER trials. During 2008, an average of 100 patients were treated as inpatients, resulting in a Anna Guidetti, MD total of 500 admissions. Forty patients were enrolled in clinical studies and underwent RESIDENTS high-dose sequential chemotherapy (HDS) and autologous stem cell transplantation. A Aurora Amabile, MD; Annalisa total of 1,300 treatments were administered in day hospital. An average of 300 new Bramati, MD; Cinzia Fasola, MD; outpatients requested examination. The activity of the cell processing laboratory Stefania Zambelli, MD consisted of 1,400 instances of CD34+ cell monitoring by FACS analysis and 270 stem cell cryopreservations. A pilot study using myeloablative yttrium-90 ibritumomab tiuxetan (Y-90 Zevalin) radioimmunotherapy with tandem stem cell autografting was performed in a prospective cohort of 46 refractory or relapsed NHL patients. These patients were not eligible for conventional chemotherapy-based myeloablative conditioning. The results obtained in these heavily pretreated patients showed that high-dose Zevalin is minimally toxic and fully applicable in an outpatient setting. Based on these data, a prospective randomized study comparing an R-CHOP with a Zevalin-based chemo- immunotherapy regimen was started in high-risk, newly diagnosed NHL patients and enrolled 20 patients in 2008. In addition, several randomized phase III clinical programs comparing optimal standard-dose chemotherapy with high-dose
  • 8. MEDICAL ONCOLOGY 149 chemotherapy regimens are ongoing in aggressive B-cell lymphomas, chronic lymphocytic leukemia, and testicular cancer. A retrospective analysis has evaluated the impact of adding rituximab to HDS for diffuse large B-cell lymphoma (DLBCL) and follicular lymphoma (FL). This multicenter analysis showed a significant improvement of disease-free and overall survival, demonstrating that rituximab should be included in HDS regimens for DLBCL and FL. Rituximab-containing HDS (R-HDS) as first-line treatment for high-risk FL has been evaluated in a prospective multicenter randomized trial comparing R-HDS versus CHOP- R. The study shows that R-HDS offers better disease control and molecular outcomes than CHOP-R. In addition, CHOP-R failures have a good outcome after R-HDS and relapsed/refractory FL could be the most appropriate target for R-HDS treatments. Analysis of a multicenter prospective trial randomizing patients with advanced Hodgkin’s disease to receive ABVD vs BEACOPP as first-line chemotherapy has been concluded. BEACOPP resulted in superior freedom from progression (FFP) in 16% of patients. Patients with selected subgroups of lymphomas and ovarian cancer are being entered into phase II pilot studies using autologous dendritic cells loaded with autologous tumor cells as anticancer vaccines. In particular, 18 relapsed patients with indolent NHL have been vaccinated with dendritic cells loaded with killed tumor cells. Six patients had clinical responses including three complete and three partial remissions. Immunologic monitoring of the enrolled patients documented significant changes in regulatory T cells, NK cells, anti-tumor T-cell frequencies, and humoral responses in responding patients. This indicates that the clinical responses may be the result of an active modulatory effect on different components of the immune system. Three phase II clinical trials investigating the efficacy and safety of epigenetic and targeted therapies in patients with relapsed/refractory lymphomas are being conducted. The role of epigenetic therapy is being investigated in a company- sponsored trial. This study evaluates the efficacy of the histone deacetylase inhibitor ITF2357 in combination with meclorethamine in Hodgkin’s lymphoma patients. The role of targeted therapies is being investigated in two investigator-sponsored trials which are evaluating the role of the multi-kinase inhibitor sorafenib as a single agent or in combination with the AKT inhibitor perifosine in relapsed/refractory lymphomas.
  • 9. 150 SCIENTIFIC REPORT 2008 Adult Sarcoma Medical Treatment The Adult Sarcoma Medical Treatment Unit takes care of patients aged over 18 years HEAD OF UNIT with adult-type soft tissue sarcomas (STS), gastrointestinal stromal tumors (GIST), and Paolo G. Casali, MD bone or childhood-type sarcomas (osteosarcoma, Ewing’s family of tumors, chordoma, STAFF MEMBERS etc.). The aim is to provide optimal care directly to patients treated within INT, and Rossella Bertulli, MD; Palma Dileo, remotely to those shared with other centers throughout Italy. Patient care is intimately MD; Federica Grosso, MD related to clinical research, also because of the rarity of these diseases, and has to be planned and provided as multidisciplinary care, in close cooperation with all the other Units focusing on sarcomas at INT. Distant “shared” patient care is carried out within the Italian Network for Rare Tumors. This project is funded by the Italian government, through the ACC network. The interest in distant clinical collaboration has led the Unit to be actively involved in the ongoing project for the development of the Regional Cancer Network of the Lombardia Region (ROL). The Unit serves as the coordinating center for rare solid tumors, including sarcomas, and is likewise involved in the overall running of the project. Patients referred to the Unit are being offered to participate in ongoing clinical studies, and a special effort is made to give Italian patients access to experimental agents with preliminary evidence of activity in sarcoma, thus contributing to their disease-specific development following the phase I/early phase II stage. This is accomplished within the framework of the Italian Sarcoma Group (ISG) and international collaborations. The Unit coordinates a work package of an EU-funded project, CONTICANET, for the advancement of a research network in Europe on STS. The Unit is actively involved in the consensus process to update the European Society for Medical Oncology (ESMO) Clinical Recommendations on STS and GIST and runs the sarcoma section of START (“State-of-the-Art Oncology in Europe”). Over the last years, an important subject of interest has been the development of molecular-targeted therapies for GISTs and sarcomas. The Unit has coordinated the intergroup European and Australasian trial on adjuvant imatinib in localized GIST, which was successfully closed to accrual in 2008. Clinical studies have been ongoing on further-line molecular-targeted therapies after failure of imatinib in advanced disease. The Unit first reported the antitumor activity of imatinib in chordoma, and is now developing its combination with mTOR inhibitors in this rare sarcoma subtype. In 2008, the Unit reported the antitumor activity of sunitinib in alveolar soft-part sarcomas. The Unit is also actively involved in the evaluation of the peculiar patterns of tumor response to molecular-targeted agents in sarcomas. The Unit has contributed to the development of the marine-derived compound trabectedin (ET-743), which was
  • 10. MEDICAL ONCOLOGY 151 approved in 2007 by the EU regulatory body, EMEA. The special activity of trabectedin in myxoid/round cell liposarcomas was first reported by the Unit and the biomolecular background for such outstanding antitumor activity in this chromosomal translocation-related subtype has been investigated. Sarcomas occurring in the young adult are the subject of a special effort by the Unit. Head And Neck Medical Oncology The Unit has at its disposal six hospital beds dedicated to diagnostic assessment, HEAD OF UNIT planning and administration of treatment, and supportive care for patients with head Lisa Licitra, MD and neck cancer. Three medical oncologists and 3 fellows in training are exclusively RESEARCH MEMBERS assigned to the Unit's activities. In 2008 there were 566 admissions for a total Laura Locati, MD; Paolo Bossi, MD; number of 187 patients; approximately two-thirds of these were new patients. The Cristiana Bergamini, MD; Rossella clinical activity consists of ambulatory care in one outpatient clinic that also offers Calderone, MD; Cecilia Liberatoscioli, MD two multidisciplinary outpatient sessions per week. The number of visits is about 260 per month, inclusive of first-access consultations. In 2008 the Unit offered 3,195 ambulatory visits and delivered over 250 infusional treatments. The research activity of the Unit is focused on head and neck cancer, including rare histologic types such as salivary gland tumors, sinonasal tumors, and thyroid cancer. The main research activity is related to combined medical and radiotherapy treatments including new drugs, organ function preservation, postoperative treatments, and studies on recurrent and metastatic disease. The research in 2008 comprised eight projects. The Unit is also involved in the development of the ROL and drafted multidisciplinary treatment guidelines for head and neck subsites already included in the project (nasopharyngeal cancer, salivary gland tumors, oropharyngeal cancer, and hypopharyngeal cancer). Moreover, the Unit is coordinating the START program, a project supported by the ACC (www.startoncology.net). START is intended as a state-of-the-art, web-based, constantly updated and freely accessible tool to support clinical oncologists and physicians in their everyday oncology practice, and focuses on effectiveness and available options in cancer diagnosis and treatment. START was initiated in an attempt to combine objective knowledge with clinical expertise, in addition to providing information for patients. The Unit coordinates clinical studies on head and neck cancer, including phase III randomized trials and phase II studies of innovative drugs in patients with advanced squamous cell carcinoma and thyroid cancer. The Unit is also involved in research activity into chemoradiation-induced toxicity and in supportive care projects, with specific reference to translational research, mainly focusing on tumor markers with prognostic or predictive value. The head of the Unit is chair of the translational subcommittee of the EORTC Head and Neck group.
  • 11. 152 SCIENTIFIC REPORT 2008 HEMATOLOGY AND ALLOGENEIC BONE MARROW TRANSPLANTATION (ETMO) THE RESEARCH ACTIVITY IS COMMITTED TO IMPROVING THE STANDARD THERAPEUTIC OPTIONS AND TO EVALUATE NEW OPPORTUNITIES IN THE FIELD OF HEMATOLOGIC MALIGNANCIES AND ALLOGENEIC TRANSPLANTATION OF HEMATOPOIETIC CELLS. Since 2001, the ETMO has been involved in clinical and preclinical research activities. The HEAD OF DIVISION Division is composed of a) an inpatient ward; b) a day hospital; c) an outpatient clinic; d) Paolo Corradini, MD a molecular hematology laboratory. The routine clinical activity focuses on the treatment STAFF MEMBERS of patients with hematologic malignancies. Several clinical studies are ongoing. Anna Dodero, MD; Raffaella Milani, Allogeneic transplantation represents not only a way to restore hematopoiesis after MD; Vittorio Montefusco, MD; Lucia high-dose chemoradiotherapy, but is also a form of adoptive immunotherapy. Its Farina, MD efficacy, however, is frequently hampered by its toxicity. This is particularly true when RESEARCH MEMBERS candidates are older than 40 years, heavily pretreated, or affected by other Cristiana Carniti, PhD; Niccolò comorbidities. In order to decrease the treatment-related morbidity and mortality and Frungillo, MD to enhance the graft-versus-tumor effect, we have developed a strategy in which RESIDENTS reduced-intensity chemotherapy is associated with a careful analysis of patient Sheila Piva, MD; Francesco Spina, comorbidities. We are now working on a new generation of transplant programs MD; Mara Morelli, MD; Silvia Mappa, MD including monoclonal antibodies in the conditioning regimen for refractory or relapsed B-cell malignancies or in the induction phase for T-cell malignancies. For patients who PhD STUDENT could benefit from allogeneic transplantation but lack an HLA-identical donor we have Anna Raganato, Biol Sci D new protocols to lower the toxicity and mortality of HLA-mismatched transplants. FELLOWS We are implementing a phase IA/II multicenter open label study of HCD-122, a Antonio Vendramin, Biol Sci D; monoclonal antibody administered to patients affected by Hodgkin’s and non- Simona Di Terlizzi, Biol Sci D Hodgkin’s lymphoma who relapsed after two lines of chemotherapy or after autografting. The primary endpoint is the assessment of the maximum tolerated dose and the recommended dose for phase II study. In addition, several clinical trials testing novel drugs for multiple myeloma are ongoing. Since 2008 a novel MRI method to prospectively evaluate bone lesions in multiple myeloma patients is under assessment. Research projects conducted in the ETMO laboratories are:
  • 12. MEDICAL ONCOLOGY 153 • Qualitative PCR analysis of minimal residual disease (MRD) and more recently quantitative real-time PCR have been found to be effective in predicting relapse after allogeneic stem cell transplantation in lymphoid malignancies for patients who have attained complete remission. We have conducted a study to assess whether molecular remissions could be achieved after a reduced-intensity conditioning regimen (RIC) followed by allogeneic stem cell transplantation (alloSCT) in relapsed chronic lymphocytic leukemia (CLL) patients and whether the assessment of MRD might be used to predict the clinical outcome. We have clearly demonstrated that relapsed patients can achieve a molecular remission after RIC alloSCT and suggested a MRD- driven intervention that might be useful to prevent overt hematologic relapse. • Another subject of research is the phenotypical, functional and molecular characterization of post-transplant T-cell and B-cell recovery to elucidate the kinetics of immune reconstitution. We are now assessing the role of rituximab included in the conditioning regimen for patients receiving autologous or allogeneic transplantation for CLL or CD20-positive NHL. To phenotypically and functionally characterize post-transplant T- and B-cell immune reconstitution, we experimentally use four-parameter flow cytometric analysis. We are also investigating whether improved regulatory T-cell (Treg) reconstitution correlates with the resolution of active graft-versus-host disease (GVHD) and a better clinical outcome. We are currently investigating whether TH17 cells contribute to the development of cGVHD in patients experiencing this pathologic condition. • Minimal residual disease will be studied in a national stem cell transplant protocol for peripheral T-cell lymphoma. • Proteomic profiling of plasma is a technique to identify new biomarkers. We have set up a protocol aimed at the identification of new plasma biomarkers in CLL patients using surface-enhanced laser desorption ionization time-of-flight (SELDI-TOF) mass spectrometry. Preliminary data show that the plasma profiles of patients with CLL are clearly distinguishable from those of healthy controls and seem to highlight a role for an acute-phase cytokine response in the pathophysiology of CLL.
  • 13. 154 SCIENTIFIC REPORT 2008 PEDIATRIC ONCOLOGY FOR MORE THAN 30 YEARS THE DIVISION HAS TAKEN CARE OF PEDIATRIC PATIENTS WITH SOLID TUMORS AND AROUND 200 NEWLY DIAGNOSED PATIENTS WERE ADMITTED EACH YEAR. The Division is involved in a number of ongoing trials, the most important of which are HEAD OF DIVISION reported below. Franca Fossati-Bellani, MD Central nervous system (CNS) (M. Massimino). The Division takes part in the SIOP STAFF MEMBERS (International Society of Pediatric Oncology) network for medulloblastoma/PNET. INT Michela Casanova, MD; Graziella has been elected as the national coordinator for future trials. Coordination continues for Cefalo, MD; Andrea Ferrari, MD; the second national AIEOP (Associazione Italiana Ematologia e Oncologia Pediatrica) Roberto Luksch, MD; Maura Massimino, MD; Daniela Polastri, cooperative study on ependymoma. A total of 80 patients have been accrued. MD; Filippo Spreafico, MD; Monica High-grade gliomas: a SIOP randomized protocol including bevacizumab as part of Terenziani, MD multimodality therapy is under way. RESEARCH MEMBERS Low-grade gliomas: a reduced-dose chemotherapy regimen is maintaining response Cristina Meazza, MD; Marta Podda, rates at the level reported in a previously published INT patient series. MD; Lorena Passoni, DVM PhD; Brain stem gliomas: an international phase III study on the effectiveness of an Serena Catania, MD; Elisabetta Schiavello, MD antibody against EGFR (nimotuzumab) has been concluded, the results of which are pending. Future trials will be focused on maintaining the same quality of life while RESIDENTS improving the results obtained with nimotuzumab. Veronica Biassoni, MD; Francesca Neuroblastoma (R. Luksch). SIOP pan-European specific investigative programs are Favini, MD; Patrizia Giannatempo, MD; Cristiana Caprio, MD; Tiziana applied for the treatment of infants, localized resectable disease, locally advanced Coliva, MD; Alma Domi, MD disease, and metastatic disease. A phase II study of Glivec in recurrent disease and a phase I study of vaccination with neuroblastoma-specific antigens for relapsed or LABORATORY TECHNICIAN Elena Barzanò resistant disease have been started. Nephroblastoma (Wilms’ tumor) (F. Spreafico). The Division coordinates the AIEOP CONSULTANT PSYCHOLOGISTS Nephroblastoma Scientific Committee and the treatment of renal tumors. Within the Carlo Alfredo Clerici, MD Barbara Giacon, Psychologist European Renal Tumor Study Group, the Division has taken the responsibility to promote trials for recurrent tumors. CONSULTANT NEUROLOGIST Malignant lymphomas (F. Spreafico). The Division participates in international trials Fabio Simonetti, MD on anaplastic large cell lymphoma and lymphoblastic lymphoma.
  • 14. MEDICAL ONCOLOGY 155 Hodgkin’s lymphoma (G. Cefalo). A single-center clinical study is evaluating response- based treatment to minimize side effects (no radiotherapy in case of complete response to chemotherapy). Soft-tissue sarcomas (STS) (A. Ferrari). Member of the European Pediatric STS Study Group (EpSSG): a protocol for localized rhabdomyosarcoma (which includes a randomized trial on the induction and efficacy of maintenance metronomic therapy), and a protocol dedicated to non-rhabdomyosarcoma STS, coordinated by the Division. A new protocol for metastatic patients is investigating the addition of bevacizumab to cytotoxic chemotherapy. Bone tumors (F. Fossati-Bellani, G. Cefalo, R. Luksch). Nonmetastatic osteogenic sarcoma and Ewing family tumors are treated according to Italian Sarcoma Group (ISG) protocols. Germ-cell malignancies (M. Terenziani). The Division is the national coordinator for this trial. Ninety-four malignant cases were registered and enrolled in the protocol; 106 teratomas were registered. Rare childhood tumors (A. Ferrari). The Division co-coordinates a national-scale cooperative project for the most uncommon pediatric cancers. Since the project started, 457 patients <18 years have been enrolled, one third from the Division. New drugs (M. Casanova). Thanks to accreditation as ITCC, the number of sponsored studies has increased. The phase II study of gemcitabine/oxaliplatin in refractory/relapsed pediatric solid tumors was completed. Recruitment to the international randomized study to evaluate docetaxel in the induction treatment of nasopharyngeal carcinoma was higher than expected. The pediatric phase I trial on a monoclonal antibody antagonist of the IGF-receptor (CP751,871) was closed. Late effects - Secondary breast cancer (M. Terenziani). Collaboration with IARC to investigate the risk of secondary breast cancer in women treated during infancy/young age for childhood tumors. Sixty-six patients and 162 control women are candidates for the study. An institutional screening program is in progress for girls who underwent radiation therapy to the chest; preliminary data were presented at the 2008 ASCO meeting. Late effects - Endocrine sequelae (M. Massimino). More than 300 patients with primary brain tumors were screened for endocrine complications: growth hormone deficits were detected and treated in 67 patients. Amelioration of neuropsychologic performance due to growth hormone therapy was also observed. Long-term follow-up of adults cured of a childhood cancer (D. Polastri). Data of 1,060 INT survivors are collected in a national register: the results about functional impairment or social disabilities are pending.
  • 15. 156 SCIENTIFIC REPORT 2008 MEDICAL DAY HOSPITAL DHM DEALS WITH ADULT PATIENTS REFERRED FOR TREATMENT BY THE CLINICAL DIVISIONS OF THE DEPARTMENT OF MEDICAL ONCOLOGY. It takes care of the administration of treatments requiring close observation, including HEAD OF UNIT supportive therapies and blood transfusions. New drugs and innovative regimens Maria Cristina Brambilla, MD belonging to scientific research protocols are developed, administered and monitored in STAFF MEMBER this Unit. Diagnostic procedures are also performed, consisting mainly of bone marrow Laura A.M. Ferrari, MD biopsy and aspiration, thoracentesis, paracentesis, lumbar puncture, and liver biopsy. Therapies prescribed in the outpatient clinic of our Department are supervised by two physicians and prepared in DHM, where, in a protected area equipped with two air flow cabinets, specialized nurses dilute the chemotherapeutic compounds. This activity is supported by the Pharmacy Unit. A separate section of the Unit is dedicated to standard regimens of short duration, biologic therapies, infusional pump systems, and management of central venous catheters, which are administered by the nursing staff. Special care is given to the management and prevention of acute side effects of therapies, in particular allergic reactions, emesis, diarrhea, and extravasation of cytotoxic drugs. In 2008 the therapeutic activity and medical procedures comprised 12,692 short therapies (treatment carried out in Iniettorato), 7,952 long therapies (treatment administered in DHM but prescribed as “File F”), and 1,123 DHM therapies (treatment requiring admission), amouting to a total of 21,763 procedures. The monthly average of long therapies and DHM activity was about 750. Referrals to DHM by the different Divisions of the Medical Oncology Department were distributed as follows: Medical Oncology 1, 33%; Medical Oncology 2, 38%; Medical Oncology 3, 13%; ETMO, 13%; Head and Neck Unit, 2%; Sarcoma Unit, 1%. The cancers types were breast cancer 34%, gastrointestinal tumors 25%, lymphoma and hematologic malignancies 25.5%, melanoma 4%, lung cancer 6%, head and neck cancer 2%, sarcomas 1%, and other tumors 3%.
  • 16. MEDICAL ONCOLOGY 157 An observational study on complementary and alternative medicines (CAM) developed in collaboration with the Unit of Pharmacy, Medical Office, Regione Lombardia and WHO started in June 2007, ended in June 2008 and enrolled 353 patients. Two hundred and fifty-three women (72% with breast cancer) and 76 men were interviewed at the start of chemotherapy. Two hundred and seven (59%) were over 50 years of age. The results of these interviews showed that 99 of 353 patients (28%) were using some kind of alternative medication such as homeopathy or herbal remedies. Follow-up is ongoing to verify if the concomitant use of CAM with conventional chemotherapy could increase the risk of undesired interactions, unexpected toxicities, and clinical problems. It is therefore important that both oncologists and patients are aware of the possible clinical implications of CAM use.