Transcript
DIAGNOSTIC IMAGING& RADIOTHERAPY
The Department of Diagnostic Imaging and Radiotherapy is made up of seven
Divisions and a number special units have been established within these Divisions: the
Magnetic Resonance Unit in Diagnostic Radiology 1, the Computed Tomography Unit
and the Intralesional Treatment Unit in Diagnostic Radiology 2, the Breast Imaging Unit
and the Diagnostic and Interventional Gastroenterology Unit in Diagnostic Radiology 3,
the Clinical PET Unit and the Radiometabolic Therapy and
Endocrinology Unit in Nuclear Medicine. The technologies in
the area of diagnostic imaging (diagnostic radiology and nuclear
medicine) provide not only morphologic information but also
functional parameters. The daily activity related to cancer
patients is structured in different steps: diagnosis of primary
cancer, characterization, staging and restaging, treatment
monitoring, and posttreatment follow-up. Besides diagnostic
procedures, a large part of the activity of the Department is
dedicated to cancer treatment. MRI research is carried out in
different fields: monitoring response to therapy, investigating
patients with a high genetic risk of cancer, and developing
software for imaging elaboration and quantitation.
Interventional radiology is an essential component of the
scientific culture of INT and several trials are dedicated to
central venous catheter placement, embolization and chemoembolization for regional
cancer treatment, and new approaches with radiofrequency ablation. A multi-
institutional lung cancer screening program with low-dose spiral CT has involved
Diagnostic Radiology Division. The Breast Imaging Unit is conducting studies on the
surveillance of young women who previously underwent radiation therapy and on the
early diagnosis of breast cancer in women with a genetic predisposition. New
diagnostic modalities such as elastosonography, a novel noninvasive technique, are
under evaluation. The Interventional Gastroenterology Unit performs procedures such
as percutaneous gastrojejunostomy, transluminal drainage of fluid collection, balloon
HEADS OF DIVISION AND UNIT
Daniele Vergnaghi, MDRadiology and Diagnostic Imaging 1 &Magnetic Resonance Unit
Alfonso Marchianò, MDRadiology and Diagnostic Imaging 2 &Computed Tomography Unit
Francesco Garbagnati, MDIntralesional Treatment Unit
Silvana Bergonzi, MDRadiology and Diagnostic Imaging 3 &Breast Imaging Unit
Guido Cozzi, MDDiagnostic and InterventionalGastroenterology Unit
Emilio Bombardieri, MDNuclear Medicine
Ettore Seregni, MDNuclear Medicine Therapy andEndocrinology Unit
Flavio Crippa, MDClinical PET Unit
Patrizia Olmi, MDRadiotherapy 1
Carlo Fallai, MDRadiotherapy 2
Renato Marchesini, Physics DMedical Physics
DIAGNOSTIC IMAGING & RADIOTHERAPY 169
DIRECTOR OF DEPARTMENT
Emilio Bombardieri, MDphone number: +39 02 2390 2220
e-mail: emilio.bombardieri@istitutotumori.mi.it
SCIENTIFIC REPORT 2008170
dilatation of stenoses, and palliative stenting. The Nuclear Medicine Division
contributes to research activity with high technology modalities like PET/CT to image
and better characterize cancer and develop new radiopharmaceuticals (positron-
emitting products and radiolabeled peptides and antibodies). These
radiopharmaceuticals are selective for tumor targeting and also for delivering “killer”
radiation energy to the tumor mass by the administration of high activities of specific
radioactive bullets. Dosimetric studies are of major interest in this area since the final
goal of these efforts is to provide physicians with quantitative data about the absorbed
dose to healthy organs (dose sparing) and tumor lesions (dose optimization to the
target). External beam radiation therapy is focused on organ and function preservation,
with the aim to deliver a higher total dose to the tumor and spare normal tissues as
much as possible. In the Radiation Therapy Division this is obtained by techniques like
3D-conformal stereotactic intensity-modulated radiation therapy (IMRT), image-guided
radiation therapy (IGRT), and brachytherapy with low and high dose rates. The newly
acquired linear accelerators permit both online and offline treatment verification,
which is especially needed for sophisticated techniques like IMRT and IGRT. High dose
rate brachytherapy is also used in uterine cancer, biliary tract cancer and breast cancer.
Several trials are addressing pediatric tumors. Research is ongoing on patients with
bone metastases and solid tumors (thyroid cancer, rectal cancer, prostate cancer, soft
tissue sarcomas, head and neck cancer). The Medical Physics group carries out studies
on natural fluorescence spectroscopy of human blood plasma for cancer detection, and
simulation of skin and melanocytic lesions with a melanoma-like phantom, mimicking
the clinical decision-making related to pigmented skin lesions and implementation of
the brachytherapy facility. This summary demonstrates that multidisciplinary interests
continue to stimulate clinical studies and basic research, and this is due to the
heterogeneity and interaction of the many components of the Department.
DIAGNOSTIC IMAGING & RADIOTHERAPY 171
In 2008 RD1 carried out 10,956 MRI scans and 36,529 conventional radiologicexaminations (chest, general bone, contrast radiology of kidney and urinary system).
MRI was used for the diagnosis of primary cancer, tumor staging, treatment
monitoring, and follow-up. The following new methodologies were improved:
- DCE-MRI (dynamic contrast-enhancement magnetic imaging)
- Diffusion technology
- Perfusion technology
- Spectroscopy of prostate cancer and of breast cancer
- Magnetic resonance urography and magnetic resonance cholangiopancreatography
and new technologies were established:
- Total body imaging
- MRI-guided breast biopsy.
The research activity was focused on several institutional projects on:
• Multicenter surveillance of women with a high genetic or familial risk of breast
cancer (in collaboration with the Istituto Superiore Sanità, Rome);
• Prostate project on the study of patients by means of diffusion and DCE-MRI
evaluation and spectroscopy performed with endocoil;
• DCE-MRI applied to the evaluation of tumor response to specific treatments carried
out in some of the clinical Units.
RD1 continued its collaboration with the Department of Biomedical Engineering of the
Polytechnic of Milan aimed at developing software for image elaboration. In detail, a
project to evaluate the accuracy of both DCE-MRI and diffusion MRI for the diagnosis
of rectal cancer relapse was developed. The project on prostate DCE-MRI achieved a
high level of development.
RD1 collaborated with several clinical Units of the Institute in order to integrate
diagnostic imaging with clinical information and to monitor the response of primary
cancer to traditional and novel treatment strategies. The radiologists worked in close
RADIOLOGY AND DIAGNOSTIC IMAGING 1
THE DIVISION OF DIAGNOSTIC RADIOLOGY 1 (RD1) INCLUDES THE UNIT OF MAGNETIC RESONANCE IMAGING(MRI). THE DIRECTOR OF DIAGNOSTIC RADIOLOGY IS ALSO THE HEAD OF THE MRI UNIT.
HEAD OF DIVISIONDaniele Vergnaghi, MD
STAFF MEMBERSAlberto Laffranchi, MD; PaoloPotepan, MD; Giovanna Trecate, MD;Antonella Messina, MD; DavideScaramuzza, MD
RADIOLOGY TECHNICIANSValeria Tosi, RT; Carmelina Pannone,RT; Cinzia Fossaceca, RT; TinaMastrostefano; Antonella Laturra,RT; Nicola Pulerà, RT; MaurizioZattoni, RT; Annunziata Gaetano, RT;Luca Musumeci, RT
SCIENTIFIC REPORT 2008172
cooperation with the physicians of the Soft Tissue Sarcoma Unit, Pediatric Oncology
Unit, Colorectal Surgery Unit, and Head and Neck Unit.
The most relevant interest of the Division lies in the area of breast disease, with more
than 650 breast MRI examinations performed each year. An experience spanning nearly
20 years makes the Division a national reference center for breast cancer. Important
results were obtained in patients at high genetic risk for breast cancer and in patients
previously submitted to plastic and reconstructive surgery.
FIGURE 1Total Body Imaginga) T1 W imageb) T2 W fat satc) Fusion image between T1morfological e diffusion images.Arrows point pathologic tissuedue a myeloma disease.
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RD2 makes use of ultrasonography (US), computed tomography (CT), multifunctional
fluoroscopy and digital angiography. Diagnostic oncology and interventionally-oriented
radiology represent the daily activity. Inpatients and outpatients with cancer undergo a
diagnostic workup, including the different steps of patient management: primary
diagnosis, staging, follow-up and monitoring after surgical, chemotherapeutic and/or
radiotherapeutic treatment.
The interventional radiology activity includes long-term central venous catheter
placement, infusion chemotherapy, nutritional support, and infusional support. The
selection and follow-up of candidates for liver transplantation are on the way, including
perioperative standby for emergency diagnostic procedures related to transplant
salvage. All kinds of percutaneous biopsies are currently carried out.
During 2008, 1,133 diagnostic vascular procedures, 313 interventional vascular
procedures, about 500 long-term central venous catheter placements, 254 nonvascular
interventional procedures, and a total of 495 percutaneous biopsies in various body
districts were performed. A total of 7,500 US examinations were carried out.
Two CT scanners are available, both with fast multislice scanning capacity. About
22,000 diagnostic examinations per year and a substantial number of interventional
radiologic procedures are carried out. The Division has set up a study on
percutaneous cryoablation in selected patients with small renal masses. The initial
results in about 20 patients show a very good tolerability of the procedure and
excellent preliminary responses.
RD2 has developed several protocols dealing with embolization and
chemoembolization for regional cancer treatment. The main fields of interest are
primary liver cancer, liver metastases, and head and neck cancer. An international
RADIOLOGY AND DIAGNOSTIC IMAGING 2
WITHIN THE DIVISION OF DIAGNOSTIC RADIOLOGY 2 (RD2), TWO SPECIAL UNITS FOR SPECIFIC ACTIVITIESHAVE BEEN ESTABLISHED: THE UNIT OF COMPUTED TOMOGRAPHY AND THE UNIT OF INTRALESIONALTREATMENT WITH RADIOFREQUENCY. THE DIRECTOR OF THE RD2 DIVISION ALSO LEADS THE UNIT OFCOMPUTED TOMOGRAPHY.
HEAD OF DIVISIONAlfonso Marchianò, MD
STAFF MEMBERSFrancesco Garbagnati, MD; EnricoCivelli, MD; GiuseppeDi Tolla, MD; Laura F. Frigerio, MD;Rodolfo Lanocita, MD; Carlo Morosi,MD; Carlo Spreafico, MD
CONSULTANTSBruno Damascelli, MDGianluigi Patelli, MD
RADIOLOGY TECHNICIANSPietro Basile; Marilena Barbiero;Maria Ferrarello; Roberto Gallo;Giuseppina Gentile; EsterMazzarella; Roberto Nioi; GeremiaPorcelli (Radiogy Technicians'Coordinator); Salvatore Romaniello;Luciana Tanzini
SCIENTIFIC REPORT 2008174
multicenter study on the treatment of inoperable hepatocellular carcinoma with
intraarterial injection of radiolabeled microspheres is ongoing in collaboration with the
Divisions of Nuclear Medicine and Gastrointestinal and Hepatopancreatobiliary Surgery
& Liver Transplantation. Over 50 patients have been successfully treated with
microspheres. Alternative approaches with radiofrequency ablation and intraarterial
chemotherapy are proposed for primary and secondary liver cancer when other
conventional treatments are not possible. An innovative approach to control
recurrence of glioblastoma using intraarterial infusion of liposomal doxorubicin has
been approved and launched by INT and the Carlo Besta Neurologic Institute of Milan.
A multicenter observational clinical project with retrievable vena cava filters for
pulmonary embolism control in cancer patients is ongoing. RD2 staff offers teaching
courses and practical demonstrations to medical and nursing staff.
A study of central vein high-flow contrast injection through implanted infusional
devices in cancer patients has been activated. The aim of this clinical study is to exploit
the use of implanted central venous catheters or ports (currently used only for
chemotherapy and intravenous systemic support), thereby improving CT image quality
for cancer detection and staging, and treatment monitoring.
The lung cancer screening program (MILD) with low-dose spiral CT continued in 2008.
We performed over 5,000 low-dose spiral CT scans and are testing the prerelease of a
commercial system for computer-aided detection (CAD) of pulmonary nodules. We
have published a first report in Radiology on the assessment of in vivo precision
volumetric analysis and the estimation of the growth rate of small pulmonary nodules.
We are going to compare the performance of radiologists with or without the aid of the
CAD system for pulmonary nodule detection.
A new screening program is planned for the early detection of kidney cancer. Screening
will be done with noninvasive techniques such as ultrasonography. People in the 50- to
60-year age group living in the Lombardy region will be enrolled.
Intralesional Treatment (Head of Unit: F. Garbagnati)
In 1989 we started a research project to evaluate the possibility to treat inoperable liver
tumors with minimally invasive thermoablation procedures. To date we have treated
about 770 patients, most of whom suffering from inoperable liver tumors and some
having kidney, lung or bone neoplasms.
FIGURE 2Improving CT imaging in oncology.High flow contrast mediuminjection through implantableinfusional devices. Illustrativeexample. Right small-cell lungcancer. Superior vena cavainjection at 5 mL/sec throughPowerPort allows 3 dimensional(3D) volume rendering (VR)reconstruction.
DIAGNOSTIC IMAGING & RADIOTHERAPY 175
FIGURE 38 cm HCC treated in one session RFTAduring arterial stop flow withembolization. The pictures demonstrate TCevaluation of the HCC pre treatment (firstimage), the stop flow angiographicprocedures, TC evaluation during 3 yearsfollow with the complete necrosis of theHCC reduced in volume.After colecistectomy (calcoloticcolecistitis) it has been resected also thehepatic residual nodule (last picture)with the anatomopathological evidenceof a complete necrosis.
In 2008 we used intralesional radiofrequency therapy, simple or combined with arterial
stop flow, in one treatment session in 70 patients with hepatocellular carinomas with a
maximum diameter of 10 cm. We are collaborating with the Universities of Milan and
Pavia to evaluate new procedures and new technical possibilities. The combination of
intralesional radiofrequency therapy and arterial stop flow in large hepatocellular
carcinomas is very effective and in one session it is possible to treat tumors with a 10-
cm diameter during a one-day hospitalization (Figure 3).
Being part of RD2, the Intralesional Treatment Unit can benefit from the experience of
the interventional radiology staff and collaborate with all clinical and surgical Units to
treat unresectable tumors in the best way possible.
The Intralesional Treatment Unit also has the capacity to evaluate clinical results by
means of radiodiagnostic procedures with a highly precise intralesional approach
utilizing radiologic guidance. Ultrasound, CT and angiography procedures in
association with intralesional thermoablation techniques can significantly improve
treatment results.
With the Department of Biomedical Physics of the Milan Polytechnic we are evaluating
the quantitative assessment of radiofrequency ablation of liver lesions by means of
dedicated software using CT image processing.
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Diagnostic oncology and interventional radiology represent the daily activities of the
staff members. In 2008 about 39,000 diagnostic and interventional procedures were
performed. The two units share their technologists, while each unit has its own
radiologists with specific qualifications and expertise.
The activity of the Breast Imaging Unit consists mostly of clinical mammography and
breast ultrasound studies in symptomatic or treated patients; the same examinations
are carried out in asymptomatic women for screening and prevention. In all cases
patients are subjected to clinical examination by the radiologist. During 2008, 14,800
mammographic examinations and 8,360 breast ultrasound studies were performed and
460 second opinions released. Moreover, conventional radiodiagnostic procedures
were also performed on inpatients. In the same period, numerous interventional
procedures were carried out on patients with suspicious clinical or imaging findings
detected in INT or other diagnostic centers. These examinations included 658
instances of preoperative targeting of nonpalpable breast lesions and about 900
percutaneous breast biopsies.
In comparison with the previous year, there was a further increase in the number of
breast biopsies (+12.5%), especially vacuum-assisted procedures – both stereotactic
and ultrasound-guided (+34.7%). These methods show several advantages over
automated core biopsy, including sampling of numerous larger specimens. Moreover,
they reduce the rate of repeat biopsies and enable more accurate histologic
characterization. The goal of the diagnostic workup and breast biopsy is to find primary
or recurrent breast cancer (BC) at a preclinical stage, and distinguish benign from
malignant findings so that unnecessary surgery can be avoided. Biopsy of nonpalpable
breast lesions is a basic part of a multidisciplinary approach aimed at providing also the
biochemical parameters that are needed for surgical planning.
RADIOLOGY AND DIAGNOSTIC IMAGING 3
WITHIN THE DIVISION OF DIAGNOSTIC RADIOLOGY 3 (RD3) TWO UNITS FOR SPECIFIC ACTIVITIES HAVE BEENCREATED, THE BREAST IMAGING UNIT AND DIAGNOSTIC AND INTERVENTIONAL GASTROENTEROLOGY UNIT.THE DIRECTOR OF RD3 IS ALSO IN CHARGE OF THE BREAST IMAGING UNIT.
HEAD OF DIVISIONSilvana Bergonzi, MD
STAFF MEMBERSGuido Cozzi, MD; Claudio Ferranti,MD; Monica Marchesini, MD; MarcoMilella, MD; Monica Salvetti, MD;Gianfranco Scaperrotta, MD; LauraSuman, MD
RESEARCH MEMBERClaudia Costa, MD
POSTDOCTORAL FELLOWSSvetlanaTelyatnikova, MDAristeidis Livanos, MD
RADIOLOGY TECHNICIANSLuisa Colombo; Luciana Dedei;Enrico Depedri; Cristina Folini(Radiology TechnologistsCoordinator); Maria Pia Mannella;Stefania Sala; Anna Tavola
DIAGNOSTIC IMAGING & RADIOTHERAPY 177
With regard to research programs, the Unit is still engaged in the program of
surveillance and early diagnosis in women with a genetic predisposition (BRCA1 or
BRCA2) or a marked family history of BC, and a study is still ongoing in collaboration
with the Unit of Genetics and the Unit of Nuclear Magnetic Resonance. The Unit
actively participated in the ISS Italian Network for women at high BC risk.
The surveillance of young women submitted to radiation therapy of the thorax at
prepuberal or puberal age is ongoing in cooperation with the Pediatric Oncology
Division; this study is aimed at assessing the risk of such women developing BC.
Another collaborative study is being carried out with the Medical Oncology 1 Division
for the staging and follow-up of patients with BC accrued in different randomized trials
of neoadjuvant therapies. In this subset, ultrasound-guided breast biopsies are also
performed to provide a histologic diagnosis and prognostic parameters as required by
the trials, after failure of core-needle biopsy on palpable lesions.
US evaluation of lymphedema of the arm after mastectomy has been started with the
aim to provide detailed information about the characteristics of lymphedema and to
ascertain whether there is agreement between US imaging and clinical data.
SCIENTIFIC REPORT 2008178
Diagnostic and Interventional Gastroenterology(Head of Unit: G. Cozzi)
The clinical activity of the Unit is mostly oriented towards diagnostic and interventional
radiology of the digestive and biliary tracts and towards diagnostic and interventional
US applications. Moreover, at the beginning of the year a new field of diagnostic
application to the urinary tract was started. Interventional US procedures are mainly
performed in thyroid disease.
In 2008, 2,734 examinations were performed by the staff of the Unit. Double contrast
examinations were carried out when diagnostic problems occurred concerning the
upper and lower gastrointestinal tract. Water-soluble contrast examinations were
performed in early postsurgical checkups. Interventional procedures were performed
in patients with different biliopancreatic diseases; not only palliative definitive biliary
drains and stents were positioned, but curative procedures such as dilatation of
cicatricial stenoses, drainage of postsurgical fistulas, and stone removal were
successfully carried out.
A peculiarity of the Unit are gastrointestinal interventional procedures like
percutaneous gastrojejunostomy, transluminal drainage of fluid collection, balloon
dilatation of cicatricial stenoses, and palliative stenting of inoperable colonic lesions; all
these procedures can be used as alternatives to the endoscopic approach. Overall,
during 2008, 738 interventional procedures were performed in the Unit, with an
increase of 5.3% with respect to the previous year.
Among the large number (5,793) of US examinations, thyroid disease represents a
prominent field of interest. In the context of the INT “Progetto Tiroide”, in cooperation
with the multidisciplinary outpatient service of thyroid disease, 1,682 (+11.2%) neck
US examinations for the monitoring of thyroid nodules were performed. In 154 of
these patients, because of the clinical and/or radiologic suspicion of malignancy, US-
guided percutaneous biopsies were performed. In view of the high rate of
nondiagnostic results with fine-needle aspiration biopsy according to the literature,
Tru-Cut biopsies with 18-20-gauge needles have been used without any serious
complications.
Figure 4Right: on conventional B-mode image,the lesion was suspicious (BI-RADS 4)Left: totally blue Sonoelastographicimage coherent with malignancy.Histology: ductal infiltratingcarcinoma.
DIAGNOSTIC IMAGING & RADIOTHERAPY 179
The Division of Nuclear Medicine (NM) works is subdivided into different areas: 1) a
diagnostic unit for planar and tomographic scintigraphy (SPECT); 2) a PET unit for
clinical PET with a 17 MeV cyclotron and two PET scanners; 3) radiochemistry
laboratories for γ and β radiopharmaceuticals to be used for diagnosis and therapy; 4) a
biochemical laboratory for immunoradiometric assays; 5) a protected ward for
radiometabolic therapy; 6) a clinic for outpatients. The NM clinical activity in 2008
amounted to 5,706 tests of traditional diagnostic imaging, 3,517 PET examinations, 294
radiometabolic treatments, more than 80,000 in vitro tests, and 2,665 medical
examinations.
The research activities of the Division cover many issues: a) measurement of
biochemical marker changes associated with tumor response and evaluation of bone
metabolism parameters in patients with bone metastases; b) development of original
approaches for lymphoscintigraphy with intraoperative sentinel node detection in
cancer patients; c) radioreceptor scintigraphy of neuroendocrine tumors; d) studies on
clinical PET and validation of PET applications; e) development of new PET
radiopharmaceuticals; f) new radiometabolic therapy approaches to thyroid cancer,
neuroblastoma, ovarian cancer and lymphoma; g) dosimetric studies to optimize the
dose to the tumor for achieving the best efficacy.
All these studies have been carried out and developed in the two units belonging to
the NM: the Nuclear Medicine Therapy and Endocrinology Unit and the Clinical PET
Unit. They are described in the pertaining sections.
In addition, studies on sentinel node detection in endometrial cancer and gastric
cancer were carried out in a large series of patients. The first study was aimed at
evaluating the distribution of 99mTc-nanocolloid in the lymphatic network to detect
pelvic and lumbo-aortic metastases. In the majority of patients with early stage cancer,
this procedure may avoid unnecessary radical pelvic lymphadenectomy. This research,
NUCLEAR MEDICINE
HEAD OF DIVISIONEmilio Bombardieri, MD
STAFF MEMBERSFlavio Crippa, MD; Ettore Seregni, MD;Maria Rita Castellani, MD; MarcoMaccauro, MD; Gianluca Serafini, MD;Gianluca Aliberti, MD; Orunesu EvaMD; Alessandra Alessi, MD; ClaudioPascali, Chemist; Carlo Chiesa,Physigist; Vinicio De Sanctis,Engineer; Anna Bogni, Biol Sci
RESEARCH ASSOCIATESAngela Coliva, Chemist; FedericaPallotti, MD; Crispu Ornella, Chemist
RADIOLOGY TECHNICIANSMonica Testoni (RadiologyTechnologists Coordinator), GraziaAprigliano, Elena Fraigola, RossanaPavesi, Sergio Bavusi, Lidia Spano,Roberto Segreti, Stefano Vola, MatteoRagazzoni
LABORATORY TECHNICIANSGianenrico Cucchetti, Rita Filieri,Giovanni Nido, Biagio Perrone, Pietro DiNuzzi, Danilo Baratella
THE PHYSICIANS OF THIS DIVISION ARE NUCLEAR MEDICINE SPECIALISTS; SOME OF THEM ARE SPECIALIZEDALSO IN ENDOCRINOLOGY AND ONCOLOGY. OTHER PROFESSIONALS INCLUDE PHYSICISTS, RADIOLOGISTS,RADIOCHEMISTS, ENGINEERS, AND BIOLOGISTS, WORKING TOGETHER IN A MULTIDISCIPLINARY TEAM.
SCIENTIFIC REPORT 2008180
in collaboration with the Unit of Gynecologic Surgery, has become an Italian
multicenter trial. The second study aims to evaluate sentinel node lymphoscintigraphy
with 99mTc-nanocolloid for guiding lymphadenectomy in gastric cancer patients. This
technique proved feasible in T1-T2 cancer, with high sensitivity and a high negative
predictive value.
A multicenter Italian trial on the use of 111In-pentetreotide in nonfunctioning
neuroendocrine tumors is ongoing. The study assesses its diagnostic value in
comparison with other conventional radiologic modalities and, above all, aims to
demonstrate the potential prognostic value of somatostatin receptor positivity.
In the area of radiometabolic therapy other studies are ongoing on the use of high
doses of radiopharmaceuticals (131I and 131I-MIBG) for the treatment of advanced
thyroid and neuroendocrine tumors. This approach is possible only when adequate
pretreatment dosimetric evaluations are available.
In NM an important field of research and development concerns clinical dosimetry in
nuclear medicine treatments with a view to provide quantitative data on the absorbed
dose to cancer lesions and healthy organs.
In metastatic thyroid cancer a recent dosimetric study on patients treated with the
usual fixed activity confirmed that in all patients the injected activity could have been
significantly higher in subsequent treatments, if necessary. Our posttreatment
dosimetry drastically changed the ensuing therapeutic strategy in patients in whom the
tumor doses proved insufficient (even considering a factor of 2 or 3 of inaccuracy).
More than 40 patients with liver carcinomas were treated with intraarterial
radioembolization by means of glass microspheres loaded with 90Yttrium. Each
treatment was preceded by 99mTc-MAA dosimetry. Median injected activity was in the
range of 1-4.9 GBq, corresponding to an average absorbed dose in the treated lobe of
more than 100 Gy. In several cases it was possible to evaluate the tumor dose on planar
scans, which proved to be around 390 Gy (median). The extraordinarily high tumor
dose, never observed in other therapeutic applications, gave in some cases excellent
responses, i.e., complete disappearance of the lesion within 6 months.
Clinical PET (Head of Unit: F. Crippa)The PET Unit is involved in 1) the production of radioisotopes by cyclotron; 2) the
synthesis of PET radiopharmaceuticals, 3) PET imaging.
The activity of the cyclotron can be summarized as follows: a) production of 11C and
18F for research and routine procedures of the radiochemistry laboratory; b)
surveillance of cyclotron functioning to collect data about its reliability and
productivity; c) design and development of an improved loading system of 18F targets;
DIAGNOSTIC IMAGING & RADIOTHERAPY 181
d) development of 18F targets with higher productivity than the current ones. Some
results have been obtained in terms of yield and performance of production.
The radiochemistry laboratory activity is dedicated to the synthesis of molecules
labeled with positron-emitting nuclides such as 18F and 11C. The research activity can
be summarized as: 1) development of an innovative and simplified procedure for the
synthesis of [18F]FLT (fluorothymidine), for which a patent has been filed; 2)
implementation of this synthesis in one of the existing modules; 3) development of an
analytic method by HPLC for the evaluation of the chemical and radiochemical purity
of the produced [18F]FLT; 4) implementation of the synthesis of [11C]choline in the
same module employed for the routine production of [11C]methionine and testing of
the reaction conditions.
The PET Unit is equipped to study patients with virtually all types of human
malignancies for staging and follow-up. In 2008 more than 3,500 PET scans were
performed in patients with lymphoma, breast cancer, colon cancer, melanoma, GIST
tumors, ovarian cancer, head and neck cancer, and brain tumors – both for tumor
detection and to evaluate the response to therapy. This routine activity provided
valuable information for patient management, changing therapeutic decisions in more
than 30% of cases.
As regards clinical research, the most important ongoing programs include:
• the use of FDG-PET and CT for the follow-up of asymptomatic melanoma patients
with a high risk of metastases. The goal of this research is the early detection of
metastases with potential for surgerical treatment;
• the use FDG-PET for early chemosensitivity evaluation in lymphoma patients. We
are participating in a multicenter study designed and coordinated by the GITIL
(Gruppo Italiano Terapie Innovative Linfomi);
• the use of FDG-PET to study sarcomas, with particular reference to GISTs and
chordomas. Our PET Unit provides imaging support to several clinical research
programs carried out by the Sarcoma Group of INT;
• the use of [11C]methionine to study brain tumors, in particular low-grade gliomas,
where FDG-PET lacks sensitivity as an imaging modality.
FIGURE 5PET provides metabolic images,since the uptake and thedistribution of theradipharmaceutical depends ontumour metabolism and thebackround activity. The same braintumour is differently visualizedaccording to fluorodeoxyglucose(FDG) and methionine (MET)pathways.
Nuclear Medicine Therapy and Endocrinology(Head of Unit: E. Seregni)
The Unit is part of the NM and its activity covers three main areas: nuclear medicine
therapy, a radioisotope laboratory, and an endocrinology outpatient clinic. Each area is
involved in routine and experimental procedures. More than 200 patients affected by
different diseases including thyroid cancer, neuroendocrine tumors and bone
metastasis were hospitalized in 2008 and treated with the appropriate
radiopharmaceuticals. Many other patients underwent experimental therapies with
new radiopharmaceuticals in clinical trials. At present three protocols are active:
• efficacy of myeloablative therapy with 90Y-Zevalin, an anti-CD20 murine monoclonal
antibody, in patients with non-Hodgkin’s lymphoma (11 patients treated in 2008);
• efficacy of tandem treatment with the somatostatin analogs 90Y-DOTA-TATE and
177Lu-DOTA-TATE of neuroendocrine tumors refractory to conventional therapies. The
protocol prescribes four treatment cycles in which the two radiopharmaceuticals are
alternated. In 2008 seven patients were treated with one or more cycles.
• efficacy of endoarterial treatment with 90Y-TheraSphere microspheres in
hepatocellular carcinoma. Up to now 47 patients with unresectable hepatocellular
carcinoma have been evaluated for 90Y radioembolization. Thirty-seven patients
entered the study and were treated with standard lobar activity of 90Y TheraSpheres.
The therapeutic activity was calculated so as to reach a fixed absorbed dose of 120 Gy
to the target lobe. Median follow-up was 10 months and, according to RECIST, WHO or
EASL criteria, complete or partial responses were obtained in 19-28% of patients, while
the overall response rate (SD, PR, CR) was 63-60%.
In the Radioisotopes Laboratory a wide panel of analytes consisting of tumor markers,
hormones and bone metabolism markers is routinely measured. During 2008 more
than 80,000 examinations were performed in hospitalized patients and outpatients.
The research activity of the laboratory is mainly performed in collaboration with the
Experimental Oncology Department and deals with different areas, including the study
of new bone metabolism parameters in patients with skeletal cancer. In this context the
biologic and clinical significance of two different isoforms (alpha and beta) of the C-
terminal peptide of type I collagen (CTX-1) is assessed in patients treated with
zoledronic acid. Other important ongoing studies are focused on the analysis of
calcitonin in transgenic mice bearing the RET C634R gene for the mapping of genetic
modulators of tumor progression in medullary thyroid cancer; and on the
characterization of primary thyrocyte cultures by measuring thyroglobulin and
calcitonin to clarify the molecular mechanisms of thyroid carcinogenesis. Also under
evaluation is the course of a panel of biomarkers including angiogenic factors,
adhesion molecules and growth factors in patients affected by advanced colorectal
cancer treated with antiangiogenic drugs.
In the endocrinology area, patients affected by thyroid and parathyroid disease,
neuroendocrine tumors, pituitary disease, osteoporosis and multiple endocrine
neoplasia (MEN2 and MEN1) are currently in active follow-up. We also evaluate and
correct endocrine sequelae in pediatric patients affected by neoplastic disease. The
research activity is mainly focused on pediatric patients and two studies are currently
ongoing: on the evaluation of the biologic and clinical effects of growth hormone
replacement in pediatric patients with brain tumors, and on the incidence of metabolic
syndrome and insulin resistance in pediatric patients as a consequence of
chemotherapy or other anticancer therapies. More than 70 patients have entered the
latter study.
182 SCIENTIFIC REPORT 2008
FIGURE 6Planar total body scintigraphy of apatient affected by ilealneuroendocrine carcinoma withhepatic and lymph-nodal metastasis.Images were acquired 72 hours postinjection of a) 90Y-DOTA-TATE (imageswere acquired exploitingbremsstrahlung of 90-yttrium) and b)177Lu-DOTA-TATE.
DIAGNOSTIC IMAGING & RADIOTHERAPY 183
HEAD OF DIVISIONPatrizia Olmi, MD
STAFF MEMBERSNice Bedini, MD; Anna Di Russo, MD;Vittorio Fossati, MD; Lorenza Gandola,MD; Laura Lozza, MD; Ester Orlandi, MD;Mauro Palazzi, MD; Fulvia Soncini, MD;Silvia Tana, MD; Francesca Valvo, MD;Sergio Villa, MD
RESIDENTSBarbara Avuzzi, MD; Serena Berretta,MD; Marzia Franceschini, MD; SaraMorlino, MD; Patrizia Pittoni, MD
POSTDOCTORAL FELLOWSSimona Fantini; Emilia Pecori, MD
RADIOLOGIC TECHNOLOGISTSPintaudi Ciro (Radiology TechniciansCoordinator), Cosimo Attolino, AriannaBianchini, Giuseppina Bonanno,Alberto Buzzetti, Carmelo Campolo,Pasquale Contessa, Paolo D'Agnese,Daniele D'Alessio, Carmelo Di Marco,Lucio Donatone, Rosa Fortunato, SaraFrasca, Piera Fusar Poli, FrancaGaetano, Manuela Gatti, ManuelaGuerra, Daniela Pierograndi, CarlaValenti
Three linacs have internal multileaf collimators and are suited to deliver IMRT. The new
machines permit both online and offline treatment verification, which is especially
needed for currently used sophisticated techniques such as IMRT and IGRT. The fourth
linac is equipped with a dynamic multileaf collimator accessory that makes it possible
to deliver stereotactic treatment. The Xio planning system has been upgraded and has
led to a more frequent use of image fusion. This technique was applied in 118 patients
during the planning phase. A high dose rate brachytherapy facility is available; it is
equipped with a Selectron machine for all types of brachytherapy and allows to treat
patients on an outpatient basis. A Plato treatment planning system specifically devised
for brachytherapy is available.
In 2008, 357 brachytherapy treatments were performed in 73 patients with
gynecologic, biliary duct and breast cancer. Overall, the RT1 Division has provided care
for 1,699 patients, one third of whom (506) were aged 70 years or over. CT simulation
was performed in 1810 cases (>1/patient). 3D treatment planning was performed in
2134 cases and IMRT planning in 162 patients. Patient setup was customized by
preparing 556 positioning/immobilization devices. IGRT was given in 288 cases, mainly
using the fiducial marker system in prostate cancer.
The research activity was mainly focused on clinical trials (see section “Ongoing
Clinical Studies”, page 221) on: pediatric tumors (medulloblastoma, ependymomas,
high-grade gliomas, high-risk neuroblastoma, Wilms’tumor, soft-tissue sarcomas, bone
tumors, Ewing's family tumors and late effects such as thyroid neoplasms after
irradiation for childhood cancer) and tumors in adult patients (soft tissue sarcomas,
head and neck cancer). A ISS cooperative study: a position paper on 3D-CRT was
issued in 2008. A new study on the welfare-related issues of the elderly oncologic
patient: 40 patients were enrolled in 2008.
RADIOTHERAPY 1
THE RADIOTHERAPY 1 (RT1) DIVISION IS EQUIPPED WITH FIVE LINEAR ACCELERATORS AND ONE COBALT UNIT.
SCIENTIFIC REPORT 2008184
Its facilities include eight beds in four shielded rooms, one operating room and one
office, for inpatient preparatory procedures and outpatient follow-up, respectively.
In addition to external beam radiotherapy, the RT2 administers high dose ratebrachytherapy. Brachytherapy is given as endocavitary treatment in uterine cancers, as
endoluminal brachytherapy in biliary tract cancers, and as interstitial brachytherapy in
breast cancer with high dose rate equipment (Selectron®). High dose rate treatment is
generally delivered in the outpatient setting. During 2008, 73 patients were treated
with 357 fractions and 216 treatment plans.
Combination chemoradiotherapy treatment is also provided, mainly in gynecologic,
anorectal and head and neck cancers. Two hundred and fifty cycles of chemotherapy
were given during 2008. Supportive care for acute and, less frequently, late
radiotherapy-related complications is given as well.
RT2 cooperates with the Diagnostic Radiology Divisions in the care of patients
undergoing chemoembolization, intraarterial chemotherapy, and other oncologically
targeted interventional procedures requiring hospitalization.
Overall, 376 patients were referred to RT2 during 2008; their mean hospital stay was
6.1 days.
RT2 cooperates with RT1 in the planning and delivery of external beam radiation
treatments to outpatients, mainly for breast cancer, gynecologic malignancies, head
and neck cancer and soft tissue sarcomas, and in patients with metastatic tumors or
patients needing palliative care.
The staff members participate actively in the head and neck, breast, and gynecologic
cancer groups; they collaborate with the multidisciplinary outpatient clinic for head
and neck cancer together with RT1, the Otolaryngology Division, Maxillofacial Division,
and Medical Oncology (Head & Neck Unit). RT2 is involved in special techniques of
treatment delivery such as cranial and extracranial (body) stereotactic radiotherapy.
RADIOTHERAPY 2
RADIATION THERAPY 2 (RT2) IS THE INPATIENT SECTION OF THE DEPARTMENT OF DIAGNOSTIC IMAGING ANDRADIOTHERAPY.
HEAD OF DIVISIONCarlo Fallai, MD
STAFF MEMBERSAnnamaria Cerrotta, MD
POSTDOCTORAL FELLOWMonica Alicia Garcia, MD
DIAGNOSTIC IMAGING & RADIOTHERAPY 185
RT2 has taken part in the general accreditation process, and has contributed to theupdating of several guidelines for radiation treatment (IMRT in head and neck cancer,
multidisciplinary clinic’s guidelines for head and neck cancer; thyroid cancer).
Clinical research projects are on: head and neck cancer (activities in this field have
been carried out in collaboration with the Division of Medical Oncology and RT1);
gynecologic cancer (in October 2008 PORTEC-3 was started in collaboration with the
Gynecology Department. This is a randomized prospective multicenter phase III trial
comparing concurrent chemoradiation and adjuvant chemotherapy with pelvic
radiation alone in high-risk and advanced-stage endometrial carcinoma. The study is
led by the Dutch Cooperative Gynecologic Oncology Group and aims to establish the
overall survival, failure-free survival, pelvic and distant recurrence rates and to compare
treatment-related toxicity and quality of life in the different treatment arms).
SCIENTIFIC REPORT 2008186
In cooperation with the Radiotherapy Divisions, the Physics Department of the
University of Milan, and the Nuclear Engineering Department of the Milan Polytechnic,
gel-layer dosimeters are currently under study as a reliable alternative to films,
semiconductor arrays or thermoluminescent dosimeters (TLD). Among various
experiments, we evaluated the reliability of Fricke gel-layer dosimeters (FGLD) for the
measurement of the in-phantom dose distribution produced by a 192Ir brachytherapy
source. To this aim, a series of measurements of the same irradiation setup composed
of a tissue-equivalent phantom were performed with FGLD and TLD and compared
with the dose distributions obtained by means of the treatment planning system.
The use of Fricke gel-layer dosimetry shows promise for high dose rate brachytherapy
applications, offering three-dimensional dose information with good spatial resolution.
In vivo characterization of melanin in melanocytic lesions by means of reflectance
spectroscopy. The aim of our research, performed in collaboration with the Day
Surgery Unit, was to assess the role of both eumelanin and pheomelanin in the various
steps of tumor progression from melanocytic lesion to dysplastic nevus to horizontal
and vertical growth phase melanoma. A retrospective analysis was performed on 1,671
multispectral images of in vivo pigmented skin lesions, including 288 melanomas. An
innovative model was developed to assess the content of eumelanin and pheomelanin
in the lesions starting from their absorbance spectra. Analysis of the absorbance
spectra in the different groups showed that the levels of eumelanin and pheomelanin
increased and decreased, respectively, from dysplastic nevi to invasive melanomas. In
both cases, the trend of melanin levels was associated with the progression from
dysplastic nevi to vertical growth phase melanomas, reflecting a possible hierarchy in
the natural history of the early phases of the disease. Our results suggest that diffuse
reflectance spectroscopy to differentiate eumelanin and pheomelanin in in vivo lesions
is a promising technique and is useful to develop better strategies for the
characterization of the various melanocytic lesions.
MEDICAL PHYSICS
HEAD OF DIVISIONRenato Marchesini, Physics D
STAFF MEMBERSMarta Borroni, Physics D; UgoCerchiari, Physics D; Valeria Mongioj,Physics D; Emanuele Pignoli, PhysicsD; Stefano Tomatis, Physics D;Giancarlo Zonca, Physics D
RESEARCH MEMBERManuela Lualdi, Physics D
POSTDOCTORAL FELLOWMauro Carrara, Physics D
RADIOLOGY TECHNICIANSVito Cosentino, Salvatore Manciero(Coordinator), Luca Marrone, DarioPosté, Claudio Stucchi
THE MAIN AREAS OF SCIENTIFIC INTEREST OF THE MEDICAL PHYSICS DIVISION ARE:DOSIMETRY IN HIGH DOSE RATE BRACHYTHERAPY.
DIAGNOSTIC IMAGING & RADIOTHERAPY 187
FIGURE 7Experimental set-up of the 192Ir brachytherapy source and thetissue-equivalent phantom with (a) thermoluminescent dosimetersand (b) Fricke gel-layer dosimeters; (c) superficial dose distributionproduced by the source (activity: 285GBq) at 1cm distance,obtained by means of a circular gel dosimeter and a suitablydeveloped software.
Hereditary nonpolyposis colorectal cancer (HNPCC) carriers and abnormal oral
mucosa light reflectance. Oral light reflectance has been suggested as a new clinical
marker in HNPCC carriers, which could be used in first level colorectal cancer (CRC)
population screening programs. With the aim to validate this new marker in identifying
susceptibility to CRC, additional studies were carried out in cooperation with the
Colorectal Cancer Unit. Fifty-six surviving members of various genetically unrelated
HNPCC kindreds were enrolled in the study. They were all subjected to HNPCC genetic
molecular studies and 42 of them showed HNPCC mutation. In addition, 10 healthy
controls were enrolled. For each study subject, spectrophotometric images in 20
different regions of the vestibular oral mucosa were acquired. The mean reflectance
spectra in HNPCC carriers and control subjects were evaluated for the entire region
and the vessel-free region. In both cases, no evidence of a significant difference
between the curves was obtained at any wavelength, in contrast to the findings
previously reported.
Magnetic resonance in vivo spectroscopy H1. Three-dimensional magnetic resonance
spectroscopy is an emerging sensitive tool for the metabolic evaluation of prostate
cancer. Choline, creatine, and citrate peaks provide relevant metabolic information for
the discrimination of prostate cancer. Resonance for choline, creatine, and citrate
occurs at distinct frequencies (approximately 3.2, 3 and 2.6 ppm, respectively) in the
spectrum. The spectral trace of prostate cancer is characterized by raised choline (a
normal cell membrane constituent, which is elevated in many tumors) and/or reduced
citrate (a constituent of normal prostate tissue). In 2008 we were asked to collaborate
with magnetic resonance radiologists to tune up the spectra acquisition methodology
and the data analysis of spectroscopic imaging of prostate cancer. The ratio of choline
and creatine to citrate in regions with normal prostate tissue has been established.
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