The Department consists of five clinical divisions (81 beds), one centralized day
hospital (29 beds), 17 outpatient rooms, one operations office for clinical trials, and a
laboratory area for cell manipulation, flow cytometry, clinical pharmacology, and
The routine clinical activity is focused on the treatment of adult and pediatric patients
with solid tumors and hematologic malignancies. Several
clinical programs are active, which range from conventional
chemotherapy to phase I studies to the transplantation of
The Department is organized in Divisions which are in charge
of different aspects of cancer research and treatment.
• Medical Oncology 1 deals with breast cancer (BC) treatment
and development of new drugs
• Medical Oncology 2 deals with gastrointestinal, lung, renal
and prostate cancer, melanoma and neuroendocrine tumors
• Medical Oncology 3 is engaged in preclinical and clinical
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.
HEADS OF DIVISION AND UNIT
Luca Gianni, MD
Medical Oncology 1
Emilio Bajetta, MD
Medical Oncology 2
Alessandro M. Gianni, MD
Medical Oncology 3
Paolo G. Casali, MD
Adult Sarcoma Medical Treatment
Lisa Licitra, MD
Head & Neck Cancer Unit
Paolo Corradini, MD
Hematology & Allogeneic Bone
Franca Fossati Bellani, MD
Cristina Brambilla, MD
Day Hospital Unit
MEDICAL ONCOLOGY 143
DIRECTOR OF DEPARTMENT
Paolo Corradini, MD
Professor of Hematology, Università degli Studi, Milano
phone number: +39 02 2390 2950
SCIENTIFIC REPORT 2008144
The staff of the Division of Medical Oncology 1 is organized in small groups of regular
staff members and fellows in training who are responsible for the coordinated
management of clinical assistance and clinical research. Each group provides care to an
assigned number of patients. The same group is in charge of the execution of specific
research programs with coordinated access to all the facilities available within the
Division: hospital beds, day-hospital activities, outpatient facilities, and a research
laboratory for the pharmacokinetic and pharmacodynamic evaluation of new
The Division is especially dedicated to the medical oncology treatment of women with
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
Scientific Directorate for the programming, planning and execution of phase I and
early phase II clinical trials in all solid tumor types. The project is endowed with an ad
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
collaboration of Cristiana Sessa of the Oncology Institute of Southern Switzerland
(IOSI) as the project leader and consultant for new drug development.
The clinical research activities stem from a productive collaboration with different
institutes and cooperative groups. In particular, Medical Oncology 1 is leading the
clinical and scientific coordination of the BC Working Group of the Michelangelo
Foundation, and has long been collaborating with the Southern Europe New Drugs
Organization (SENDO). In addition, the Division coordinates one Italian and one
European collaborative group aimed at the organization of phase III trials in
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
MEDICAL ONCOLOGY 1
HEAD OF DIVISION
Luca Gianni, MD
Giulia Bianchi, MD; Giuseppe Capri,
MD; Sara Cresta, MD; Gabriella
Mariani, MD; Angela Moliterni, MD;
Antonella Perotti, MD; Milvia
Cristiana Sessa, MD
Giampaolo Bianchini, MD; Gianluca
Del Conte, MD; Angelica Fasolo, MD;
Silvia Govi, MD; Paola Mariani, MD
Alberta Locatelli, Biol Sci D; Lucia
Viganò, Biol Sci D
Claudio Adile, MD; Gianluca Cutolo,
MD; Silvia Damian, MD; Chiara
Dazzani, MD; Elena De Benedictis,
MD; Debora Fumagalli, MD; Silvia
Grecchi, MD; Maria Chiara
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.
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
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.
SCIENTIFIC REPORT 2008146
Our Division is striving to realize this mission also through strong partnerships with
the other Divisions, as well as with other cancer centers nationally and internationally,
in an effort to develop more effective therapies that are targeted to each patient’s
unique disease profile. We evaluate different types of cancer, including gastrointestinal,
lung, renal, prostate, melanoma and neuroendocrine tumors. We also manage
problems in cancer patients that may require specialized, multidisciplinary care in a
comprehensive cancer center. Such problems include hematologic disorders due to
chemotherapy treatments, pain, and infections.
One of the main objectives of the Division is to provide state-of-the-art treatment of
primary malignant tumors. The clinical activity is mainly addressed to the diagnosis and
treatment of gastrointestinal malignancies, thoracopulmonary, urogenital (prostate,
bladder, kidney) and skin cancer (melanoma), with a special interest in
neuroendocrine tumors. The goal is to maximize the response and quality of life of
each patient with advanced schedules of treatment. Particular attention is paid to
enrolling most patients into clinical research protocols. In the ward, which has 14
hospital beds for inpatients, the activity is managed by a permanent staff member with
the help of residents. The clinical hospitalization activity has been steadily increasing
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
MEDICAL ONCOLOGY 2
HEAD OF DIVISION
Emilio Bajetta, MD
Roberto Buzzoni, MD; Luigi Celio,
MD; Michele Del Vecchio, MD;
Maria Di Bartolomeo, MD;
Giuseppe Procopio, MD; Nicoletta
Laura Catena, MD; Marco
Marianna Accolla, MD; Stefania
Canova, MD; Andrea Colombo, MD;
Fiorella K. Dotti, MD; Angela Denaro,
MD; Monika Ducceschi, MD;
Valentina Guadalupi, MD; Filippo
Pietrantonio, MD; Sara Pusceddu,
MD; Elena Verzoni, MD
THE MISSION OF THE MEDICAL ONCOLOGY 2 IS TO TREAT CANCER AND RELATED DISEASES THROUGH
INTEGRATED PROGRAMS IN PATIENT CARE, RESEARCH, AND CLINICAL TRIALS.
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
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
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.
SCIENTIFIC REPORT 2008148
The scientific activity of the Division covers several fields, including hematopoietic
stem cells, cell- and antibody-mediated immunotherapy, cell and gene therapy, and
high-dose myeloablative chemotherapy with hematopoietic stem cell autografting.
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
Division provides care mainly for patients with non-Hodgkin’s lymphomas (NHL),
Hodgkin’s disease, multiple myelomas, and testicular tumors. Selected patients with
high-risk carcinomas (including breast, testicular and ovarian cancer) are treated - if
eligible - in specific research programs offering high-dose myeloablative chemotherapy,
vaccination, or new biologic agents. The majority of patients are enrolled in clinical
trials. During 2008, an average of 100 patients were treated as inpatients, resulting in a
total of 500 admissions. Forty patients were enrolled in clinical studies and underwent
high-dose sequential chemotherapy (HDS) and autologous stem cell transplantation. A
total of 1,300 treatments were administered in day hospital. An average of 300 new
outpatients requested examination. The activity of the cell processing laboratory
consisted of 1,400 instances of CD34+ cell monitoring by FACS analysis and 270 stem
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
MEDICAL ONCOLOGY 3
HEAD OF DIVISION
Alessandro M. Gianni, MD
Professor of Medical Oncology,
Università degli Studi, Milano
Valeria Bonfante, MD; Carmelo
Carlo-Stella, MD; Liliana Devizzi, MD;
Massimo Di Nicola, MD; Michele
Magni, MD; Paola Matteucci, MD;
Simonetta Viviani, MD
Anna Guidetti, MD
Aurora Amabile, MD; Annalisa
Bramati, MD; Cinzia Fasola, MD;
Stefania Zambelli, MD
THE DIVISION OF MEDICAL ONCOLOGY 3 CARRIES OUT BOTH PRECLINICAL AND CLINICAL TRANSLATIONAL
RESEARCH MAINLY IN THE FIELD OF MALIGNANT LYMPHOMAS.
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.
SCIENTIFIC REPORT 2008150
Adult Sarcoma Medical Treatment
The Adult Sarcoma Medical Treatment Unit takes care of patients aged over 18 years
with adult-type soft tissue sarcomas (STS), gastrointestinal stromal tumors (GIST), and
bone or childhood-type sarcomas (osteosarcoma, Ewing’s family of tumors, chordoma,
etc.). The aim is to provide optimal care directly to patients treated within INT, and
remotely to those shared with other centers throughout Italy. Patient care is intimately
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
HEAD OF UNIT
Paolo G. Casali, MD
Rossella Bertulli, MD; Palma Dileo,
MD; Federica Grosso, MD
MEDICAL ONCOLOGY 151
HEAD OF UNIT
Lisa Licitra, MD
Laura Locati, MD; Paolo Bossi, MD;
Cristiana Bergamini, MD; Rossella
Calderone, MD; Cecilia
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,
planning and administration of treatment, and supportive care for patients with head
and neck cancer. Three medical oncologists and 3 fellows in training are exclusively
assigned to the Unit's activities. In 2008 there were 566 admissions for a total
number of 187 patients; approximately two-thirds of these were new patients. The
clinical activity consists of ambulatory care in one outpatient clinic that also offers
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.
SCIENTIFIC REPORT 2008152
Since 2001, the ETMO has been involved in clinical and preclinical research activities. The
Division is composed of a) an inpatient ward; b) a day hospital; c) an outpatient clinic; d)
a molecular hematology laboratory. The routine clinical activity focuses on the treatment
of patients with hematologic malignancies. Several clinical studies are ongoing.
Allogeneic transplantation represents not only a way to restore hematopoiesis after
high-dose chemoradiotherapy, but is also a form of adoptive immunotherapy. Its
efficacy, however, is frequently hampered by its toxicity. This is particularly true when
candidates are older than 40 years, heavily pretreated, or affected by other
comorbidities. In order to decrease the treatment-related morbidity and mortality and
to enhance the graft-versus-tumor effect, we have developed a strategy in which
reduced-intensity chemotherapy is associated with a careful analysis of patient
comorbidities. We are now working on a new generation of transplant programs
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
could benefit from allogeneic transplantation but lack an HLA-identical donor we have
new protocols to lower the toxicity and mortality of HLA-mismatched transplants.
We are implementing a phase IA/II multicenter open label study of HCD-122, a
monoclonal antibody administered to patients affected by Hodgkin’s and non-
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:
HEMATOLOGY AND ALLOGENEIC BONE MARROW
HEAD OF DIVISION
Paolo Corradini, MD
Anna Dodero, MD; Raffaella Milani,
MD; Vittorio Montefusco, MD; Lucia
Cristiana Carniti, PhD; Niccolò
Sheila Piva, MD; Francesco Spina,
MD; Mara Morelli, MD; Silvia
Anna Raganato, Biol Sci D
Antonio Vendramin, Biol Sci D;
Simona Di Terlizzi, Biol Sci D
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.
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.
SCIENTIFIC REPORT 2008154
The Division is involved in a number of ongoing trials, the most important of which are
Central nervous system (CNS) (M. Massimino). The Division takes part in the SIOP
(International Society of Pediatric Oncology) network for medulloblastoma/PNET. INT
has been elected as the national coordinator for future trials. Coordination continues for
the second national AIEOP (Associazione Italiana Ematologia e Oncologia Pediatrica)
cooperative study on ependymoma. A total of 80 patients have been accrued.
High-grade gliomas: a SIOP randomized protocol including bevacizumab as part of
multimodality therapy is under way.
Low-grade gliomas: a reduced-dose chemotherapy regimen is maintaining response
rates at the level reported in a previously published INT patient series.
Brain stem gliomas: an international phase III study on the effectiveness of an
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
improving the results obtained with nimotuzumab.
Neuroblastoma (R. Luksch). SIOP pan-European specific investigative programs are
applied for the treatment of infants, localized resectable disease, locally advanced
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
resistant disease have been started.
Nephroblastoma (Wilms’ tumor) (F. Spreafico). The Division coordinates the AIEOP
Nephroblastoma Scientific Committee and the treatment of renal tumors. Within the
European Renal Tumor Study Group, the Division has taken the responsibility to
promote trials for recurrent tumors.
Malignant lymphomas (F. Spreafico). The Division participates in international trials
on anaplastic large cell lymphoma and lymphoblastic lymphoma.
HEAD OF DIVISION
Franca Fossati-Bellani, MD
Michela Casanova, MD; Graziella
Cefalo, MD; Andrea Ferrari, MD;
Roberto Luksch, MD; Maura
Massimino, MD; Daniela Polastri,
MD; Filippo Spreafico, MD; Monica
Cristina Meazza, MD; Marta Podda,
MD; Lorena Passoni, DVM PhD;
Serena Catania, MD; Elisabetta
Veronica Biassoni, MD; Francesca
Favini, MD; Patrizia Giannatempo,
MD; Cristiana Caprio, MD; Tiziana
Coliva, MD; Alma Domi, MD
Carlo Alfredo Clerici, MD
Barbara Giacon, Psychologist
Fabio Simonetti, MD
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.
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
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.
SCIENTIFIC REPORT 2008156
It takes care of the administration of treatments requiring close observation, including
supportive therapies and blood transfusions. New drugs and innovative regimens
belonging to scientific research protocols are developed, administered and monitored in
this Unit. Diagnostic procedures are also performed, consisting mainly of bone marrow
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
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%.
MEDICAL DAY HOSPITAL
HEAD OF UNIT
Maria Cristina Brambilla, MD
Laura A.M. Ferrari, MD
DHM DEALS WITH ADULT PATIENTS REFERRED FOR TREATMENT BY THE CLINICAL DIVISIONS OF THE
DEPARTMENT OF MEDICAL ONCOLOGY.
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.