Toni Ibrahim BSc,MD, PhD
Head of Osteoncology and Rare Tumors Center Cancer Institute of Romagna,IRST-IRCCS Meldola, Italy
Che cosa è
l’Osteoncologia in Italia ?
Dichiarazione conflitto di interessi
Toni Ibrahim, 19/06/2019
Relationship Company/Organization
Honoraria Consultant EISAI
Grant to Institution Novartis
Partecipation expenses to congress Novartis, Pharmamar, Ipsen
Outline:
1- Hot topic in Oncology
2- Osteoncology = Evolution and Revolution 3- Conclusions
Microenvironment
Cancer Cells
Hot topic in Oncology
Cross
talk
TO DOMINATE CANCER….
Better understand CANCER BIOLOGY and
PATIENT NEEDS
Research Support
Figures Clinical
Researchers
Lab Researchers
We need to join forces and speak the same language…
NATIONAL PROJECT: MULTIDISCIPLINARY APPROACH TO PATIENTS WITH BONE METASTASES
Prof Dino Amadori
2000 2019
National training courses
2002 Bologna, Rome 2003 Naples, Bologna 2004 Naples, Florence
Course
in Osteoncology
2003 - 2005
II level University Masters in Osteoncology (Modena/Bologna/Forlì)
2009-2019
PhD in Osteoncology (Campus Roma)
Masters/PhD in Osteoncology Publications: 3 books
2003 - 2018
National training and practical courses in Osteoncology (Modena – Forlì- Meldola- Roma- Verona- others)
Establishment of Osteoncology Center
Establishment of Osteoncology field
National Bone
Metastases Data Base
Multidisciplinary Osteoncology School (MOS) 2008
2014 2016
This strategy could be one of the oncology experiences, the recent discipline:
THE OSTEONCOLOGY
Osteoncology = Evolution and Revolution in Oncology
Outline:
1- Hot topic in Oncology
2- Osteoncology = Evolution and Revolution 3- Conclusions
New Bone- Cancer relationship
EVOLUTION
Primitive tumors 1- Bone metastases
2- Cancer Treatment Induced Bone Loss (CTIBL)
REVOLUTION
- Foundation of a new field in Oncology:
OSTEONCOLOGY
- Care
: mono and multidisciplinary approach
- Research:
thanks to new Knowledge in the pathogenesis of bonemetastases, on 2018 the aim of treatments is not only to prevent SREs, but also to have an impact in the natural history of cancer.
Ibrahim T et al. Oncol Lett. 2013
Danno osseo indotto dai trattamenti antitumorali
0 2 4 6 8 Normal men
Late menop. women Early menop women Aromatase Inhibitor Bone Marrow transpl Androgen deprivation AI + GNrh agonist
Ovarian failure due chemiother
1%
2 % 2.6%
3.3%
4.6%
7.0%
7.6%
Lumbar spine BMD (% /year Bone Loss) 0.5%
Rate of BMD Loss
Impact of bone metastases
Skeletal Related Events
QoL Outcome Costs
Osteoporosis/
CTIBL
New Bone- Cancer relationship
EVOLUTION
Primitive tumors 1- Bone metastases
2- Cancer Treatment Induced Bone Loss (CTIBL)
REVOLUTION
- Foundation of a new field in Oncology:
OSTEONCOLOGY
- Care
: mono and multidisciplinary approach
- Research:
thanks to new Knowledge in the pathogenesis of bonemetastases, on 2019 the aim of treatments is not only to prevent SREs, but also to have an impact in the natural history of cancer.
Ibrahim T et al. Oncol Lett. 2013
Oncologist
Palliative Care Expert
Radiotherapist
Orthopedic Specialist
Radiologist
Physiatrist Clinical
Pathologist Pathologist
Lab Reasearchers Data Manager
Dedicated Nurse
Nuclear Medicine Physician
Patient with bone Cancer disease
Neurological surgeon
Otolaryngologist
General and
Endocrine surgeon Endocrinologist
Psicologist
NATIONAL PROJECT: MULTIDISCIPLINARY APPROACH TO PATIENTS WITH BONE METASTASES
Prof Dino Amadori
2000 2019
National training courses
2002 Bologna, Rome 2003 Naples, Bologna 2004 Naples, Florence
Course
in Osteoncology
2003 - 2005
II level University Masters in Osteoncology (Modena/Bologna/Forlì)
2009-2019
PhD in Osteoncology (Campus Roma)
Masters/PhD in Osteoncology Publications: 3 books
2003 - 2018
National training and practical courses in Osteoncology (Modena – Forlì- Meldola- Roma- Verona- others)
Establishment of Osteoncology Center
Establishment of Osteoncology field
National Bone
Metastases Data Base
Multidisciplinary Osteoncology School (MOS) 2008
2014 2016
Società Italiana di Osteoncologia Mission
ASSISTENZA
Promuovere la formazione di gruppi multidisciplinari per la cura dei pazienti con patologia oncologica ossea e favorire la nascita di nuovi centri specializzati
RICERCA
Promuovere e sostenere la ricerca di base, traslazionale e clinica, con particolare riferimento agli studi multidisciplinari
DIDATTICA
Favorire la formazione dei professionisti delle discipline connesse all’osteoncologia attraverso l’organizzazione di eventi formativi, convegni e la realizzazione di
pubblicazioni scientifiche dedicate
Società Italiana di Osteoncologia Governance
Consiglio Direttivo 2017/2020
Presidente: Gaetano Lanzetta Segretario: Stefano Severi Tesoriere: Vittorio Fusco Consiglieri :
- Asssistenza: Alfredo Berruti
- Ricerca preclinica: Francesco Pantano - Ricerca clinica: Toni Ibrahim
- Formazione: Roberto Casadei
Collegio dei Sindaci : Stefania Zoveto (Presidente), Tiziana Falbo, Laura Mercatali Sede legale: Via Pietro Marroncelli, 40 . 47014 Meldola (FC)
C.F. 92068610408 P.I. 04113560405
Rete Osteoncologia Nazionale
www.osteoncology.it
Centri accreditati di eccellenza:
- Centro di Osteoncologia presso l’istituto Scientifico Romagnolo per lo Studio e la Cura dei Tumori IRCCS di Meldola
- Centro di Osteoncologia presso l’istituto Oncologico Veneto IOV - Centro di Osteoncologia presso l’istituto Tumori Regina Elena, Roma - Centro di Osteoncologia presso l’Università Campus Biomedico, Roma Centri che rispettano i requisiti minimi:
- Centro di Osteoncologia presso l’istituto Neurotraumatologico Italiano, Grottaferrata (RM)
- Centro di Osteoncologia presso Ospedale Gradenigo (TO)
Multidisciplinary Osteoncology School (MOS) IRST,IRCCS, Meldola
Aims:
Promote training in Osteoncology (bone metastases/bone health):- Mono- and multidisciplinary care
- Basic, translational and clinical research
- Integration between assistance and research
Target :
All professionals interested in Osteoncology from lab to the clinic assistance Methodology: Theorical and practical coursesNational Bone Metastases Data Base
Materials and Methods
BM Data Base is a multicenter prospective observational study, which has as Coordinating Center (CC), IRCCS IRST of Meldola. The database will allow to gather information on the medical history of patients with BM using an online software tailored for these data.
•The platform of the database consists of 4 files containing information regarding patient demographics, characteristics of the primary tumors and BM, as well as their evolution, in particular the onset and the types of SRE.
The data are updated every 6 months by the participating centers and reviewed by CC.
For information about project, please contact:
Alberto Bongiovanni: alberto.bongiovanni@irst.emr.it Flavia Foca: flavia.foca@irst.emr.it
National Bone Metastases Data Base
• Italian Bone Metastases Database: Breast Cancer Prospective Data
- Abstract ASCO 2016 e AIOM 2016 - Abstract AIOM 2019 ( submitted)
- In corso Analisi dei dati e stesura Paper per pubblicazione nel 2019
• Italian Bone Metastases Database NSCLC: Cancer Prospective Data
• Bone Metastases NSCLC: ICI + DENOSUMAB vs ICI + Zoledronate
• Prospective Study on BM management in elderly patient’s
• Prospective Study Sarcoma Bone Metastases
National Bone Metastases data Base : Currently Projects …..
Osteoncology Center
Osteoncology Center: Pathway Indicators
1- Effect on Quality of life and pain 2- Patient Satisfaction
3- Patient adherence
4- Attraction Index
5- Cost of service
Results: MDOT interventions
Results: BPI analysis
A significant improvement in the worst (p<0.0001) and current pain (p=0.03) was seen, together with a favorable impact on daily activities (p=0.02).
Results: Patient’s Satisfaction
Patient adherence
236 visits (1° semester 2018)
only one patient did not attend
the appointment at the Clinic
Attraction Index (2014-2018)
6961 patients
(percorso metastasi ossee e CTIBL)2509 (37 %) Area Vasta Romagna
4452 (63 %) Ext. Area Vasta Romagna
1016 (23 %) Ext. Emilia Romagna
Il percorso assistenziale in osteoncologia : l’esperienza del
gruppo integrato di cure dell’Azienda Ospedaliera S. Giovanni battista di Torino
The cost analysis of the GIC group confirms this change:
(120 patients GIC vs 35 patients pre-GIC):
• A mean cost reduction of 225 euro per patient;
• Diagnosis more expensive;
• Lower cost of hospital admission (surgery);
• Surgery definitive, not palliative kind (preventive fracture);
• Fifty percent reduction in waiting time from hospitalisation to surgery
Colangelo I, Mecosan 2006
New Bone- Cancer relationship
EVOLUTION
Primitive tumors 1- Bone metastases
2- Cancer Treatment Induced Bone Loss (CTIBL)
REVOLUTION
- Foundation of a new field in Oncology:
OSTEONCOLOGY
- Care
: mono and multidisciplinary approach
- Research:
thanks to new Knowledge in the pathogenesis of bonemetastases, on 2019 the aim of treatments is not only to prevent SREs, but also to have an impact in the natural history of cancer.
Ibrahim T et al. Oncol Lett. 2013
Bone Metastases Are a Mixture of Osteoblastic and Osteoclastic Lesions
Adapted from: Halvorson K et al. Clin J Pain. 2006;22:587.
At
http://www.meddean.luc.edu/lumen/MedEd/Radio/curriculum/Surgery/Met_bone_list1.htm
Osteoblastic Osteolytic
Myeloma Breast
Prostate
Mixed
OSTEOLYTIC MODEL: a vicious cycle
Buijs, The prostate,2009 RANK
OSTEOBLASTIC MODEL: a vicious cycle
Ibrahim T, Cancer 2010 (A) Prostate cancer cells secrete osteogenic growth factors, activating osteoblasts to deposit new bone matrix.
(B) Osteoblasts secrete a range of additional factors such as insulin-like growth factor (IGF), fibroblast growth factor (FGF), and transforming growth factor-b (TGFb).
(C) These factors attract prostate cancer cells, further enhancing their proliferation and growth.
Medical treatment of bone metastases has become
progressively complex and currently includes:
well known antitumor agents
bone targeted molecules
Treatment of Bone Metastases
Ibrahim T, Tumori 2013
The Metastatic Process: hypothesis
Bone (HSC, MSC) Peripheral
tissues
MSC, HSC
physiologica lHSC niche in
tissue
HSC patrolling
1
CTC, DTC
from primary tumor/bone
2
Peripheral tissues (bone, liver,
lung…)
Pre-metastatic niche
3
Metastatic niche
(bone, liver, lung…) Death
Dormancy
Metastatic growth
4
Primitive tumor Bone
(MSC, MF, Neut)
MSC, TAM, TAN STRESSING
FACTORS (cytokines, exosomes…)
HSC, Mac
Ibrahim T, not pubblished
CTIBL
The metastatic process/pre-metastatic Niche
Tumour cell
Osteoblast HSC
Tumour cell arriving in bone
Osteoblastic Niche
Hematopoietic stem cell niche
Perivascular Niche
Osteoblast cells regulate HSC cells and are closely linked with vascular remodeling and
osteoclast activity
Osteoclast
Shiozawa Y, Clinical Cancer Research, 2011
Bone Microenvironment
CTIBL
Summary
-The use of adjuvant BTT has now been demonstrated to reduce the development of bone metastasis, distant
recurrence, and breast cancer mortality among
postmenopausal women and in premenopausal women undergoing ovarian suppression.
- The use of Denosumab has now been demonstrated in
prostate cancer patients at high risk of reccurence, to reduce the development of bone metastasis. No effect on mortality.
Bone Targeted Therapy Advanced setting
Adjuvant setting
Outline:
1- Hot topic in Oncology
2- Osteoncology = Evolution and Revolution 3- Conclusions
Osteoncology
Bone Health/Omeostasis
QoL
Outcome
Costs
NATURAL HISTORY OF CANCER
New Bone- Cancer relationship
EVOLUTION
Primitive tumors 1- Bone metastases
2- Cancer Treatment Induced Bone Loss (CTIBL)
REVOLUTION
- Foundation of a new field in Oncology:
OSTEONCOLOGY
- Care
: mono and multidisciplinary approach
- Research:
thanks to new Knowledge in the pathogenesis of bonemetastases, on 2018 the aim of treatments is not only to prevent SREs, but also to have an impact in the natural history of cancer.
Ibrahim T et al. Oncol Lett. 2013
Normal bone turnover: bone breackdown and bone formation are in equilibrium
T5
T5
L1 T11
T11 L1
- Progressivo calo del CA 15.3 (10/10: 50, 02/11: 29): Ca duttale inf mammario ER/PgR + in trattamento con Letrozolo - Stabilità pleurica: eupnoica;
- Dicembre 2010: si reca al PS per dolore acuto rachide con crolli e vertebroplastica T11 e L1;
- Persistenza del dolore che ha necessitato un ulteriore lungo ricovero e inserimento catetere epidurale;
- Gennaio 2011: consulenza CDO, inizia bisfosfonato ev con supplementazione di calcio e vitamina D3 - Aprile 2011: TC visceri e osso stabili, markers negativi e pz con analgesici orali (Oxycontin 30 x 2).
CDO-TR strategies for a new tarsversal discipline as Osteoncology and Rare Tumors
Method: Team (Lab/Clinic)
Specific expertise
National and International Network/Collaborations
Mono/multidisciplinary approach:
assistance and reasearch
Spontaneous Reasearch Pharmaceutical companies
2005
2011
2019
Princeton Univ. NY
(USA) Y. Kang
Campus Bio- medico Univ
Rome Prof Santini
TMHRI
Texas Univ.
Houston,USA M. Ferrari
Pathology Unit AVR
Leiden Univ Medical Centre (Olanda)
G. Van der Pluijm
Istituti Ortopedici Rizzoli, BO (Prof Donati)
Modena University Prof Catani Duke
University
(USA) X. Wang
National and International Collaborations
Regina Elena Institute
Rome Prof Biagini
Osteoncology National Network
Rare Tumors Network
CDO-TR
CCCN Romagna
L’Osteoncologia ……
Osteoncology and Rare Tumors Center CDO-TR
Director: Toni Ibrahim
Oncologists:
Alberto Bongiovanni Sebastiano Calpona Giandomenico Di Menna Lorena Gurrieri
Federica Recine Nada Riva
Valentina Fausti (Tr) Sivia De Bonis (Tr)
Lab Researchers:
Laura Mercatali Chiara Liverani Alessandro De Vita Chiara Spadazzi Giacomo Miserocchi Claudia Cocchi
Data Manager:
Benedetta Rossi Monia Dall’Agata
Alessandra Affatato Statistic:
Flavia Foca Pharmacyst:
Valentina Di Iorio Specialist Nurse:
Venetia Zavoiu
Centro di
Eccellenza
Member and Collaborations:
- CCCN of Romagna
- National Network of Osteoncology - National Network of Rare Tumors
- EURACAN (European Reference Network)
- University of Bologna, Modena, Milan and Ferrara - Alleanza Contro il Cancro
- Istituto Ortopedico Rizzoli - Princeton University, USA
- The Methodist Research Institute, Houston,USA - Leiden University, The Netherlends
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