Italian

Sarcoma

Group

IItaliantalian

SSarcomaarcoma

GGrouproup

StartedJune 1997

StartedJune 1997

FormalizedOctober 2002Formalized

October 2002

www.italiansarcomagroup.org

68 Centers

• 14 National Institutes

• 14 Universities

• 34 Pubblic Hospitals

• 6 Private Hospitals

68 Centers

• 14 National Institutes

• 14 Universities

• 34 Pubblic Hospitals

• 6 Private Hospitals

Italian Sarcoma GroupItalian Sarcoma Group

210 members210 members

11

1 31

11

18

10 2

1

1 111

1 3

1

1

2 at november 2005at november 2005

11

1 1

1

2

5

1

1BELGIUM

1

1

2

11

11

1

6

1

• ISG/SSG I (localized disease): 3/1997 - 3/2001, 182 pts JCO 2005

• ISG/SSG II (metastatic disease): 3/1998 - 12/2002, 57 pts ASCO 2005

• ISG/OS I (localized disease) activated 4/2001, 212 pts

• EUROBOSS (ISG/SSG/COSS) (> 40 yrs) activated 12/2002, 79 pts

• High risk (relapsed patients) activated 12/2002, 28 pts

• ISG/SSG I (localized disease): 3/1997 - 3/2001, 182 pts JCO 2005

• ISG/SSG II (metastatic disease): 3/1998 - 12/2002, 57 pts ASCO 2005

• ISG/OS I (localized disease) activated 4/2001, 212 pts

• EUROBOSS (ISG/SSG/COSS) (> 40 yrs) activated 12/2002, 79 pts

• High risk (relapsed patients) activated 12/2002, 28 pts

Osteosarcoma ProtocolsOsteosarcoma ProtocolsItalian Sarcoma GroupItalian Sarcoma Group

• ISG/SSG III (standard risk)activated 6/99, 240 pts

• ISG/SSG IV (high risk)activated 6/99, 74 pts ASCO 2005

• ISG/AIEOP (very high risk)activated 12/2002, 19 pts

• Relapsed Patientsactivated 12/2002, 22 pts

• ISG/SSG III (standard risk)activated 6/99, 240 pts

• ISG/SSG IV (high risk)activated 6/99, 74 pts ASCO 2005

• ISG/AIEOP (very high risk)activated 12/2002, 19 pts

• Relapsed Patientsactivated 12/2002, 22 pts

Ewing’s Sarcoma ProtocolsEwing’s Sarcoma ProtocolsItalian Sarcoma GroupItalian Sarcoma Group

• ISG/STS0101 (neoadjuvant EpiDOX+IFX, in high risk

localized disease) with Spanish Group (222 pts)

• ISG/STS 03/02 (neodjuvant IFO+RT in

retroperitoneal) (15 pts)

• HD-IFX in continuous infusion (2nd-4th line)

• Gemcytabine in leiomyosarcomas (2nd-3rd line)

• Paclitaxel in angiosarcomas (2a line)

• Miniallogenic Transplant (advanced disease,

responsive patients)

• Imatinib in advanced chordoma (35 pts)

• ISG/STS0101 (neoadjuvant EpiDOX+IFX, in high risk

localized disease) with Spanish Group (222 pts)

• ISG/STS 03/02 (neodjuvant IFO+RT in

retroperitoneal) (15 pts)

• HD-IFX in continuous infusion (2nd-4th line)

• Gemcytabine in leiomyosarcomas (2nd-3rd line)

• Paclitaxel in angiosarcomas (2a line)

• Miniallogenic Transplant (advanced disease,

responsive patients)

• Imatinib in advanced chordoma (35 pts)

Adult soft tissue sarcomas - ProtocolsAdult soft tissue sarcomas - ProtocolsItalian Sarcoma GroupItalian Sarcoma Group

• GIOTTO (observational, 2004-2005, in collaboration with

Novartis) (>700 pts)

• REGISTER (retrospective, histhological)

• 62024 (adjuvant Imatinib), intergroup with EORTC

• Institutions from the ISG participated in the following

studies on new agents in GIST:• SU11248 (international) CLOSED

• PTK787 (international)

• AMG706 (international)

• GIOTTO (observational, 2004-2005, in collaboration with

Novartis) (>700 pts)

• REGISTER (retrospective, histhological)

• 62024 (adjuvant Imatinib), intergroup with EORTC

• Institutions from the ISG participated in the following

studies on new agents in GIST:• SU11248 (international) CLOSED

• PTK787 (international)

• AMG706 (international)

GIST ProtocolsGIST Protocols

Possible accrualPossible accrual

Italian Population : 57 MillionsItalian Population : 57 Millions

Osteosarcoma: 90/120 (75%!)

Ewing’s Sarcoma: 50/60 (80%!)

Adult soft tissue sarcomas: 700/1400 (50%?)

Osteosarcoma: 90/120 (75%!)

Ewing’s Sarcoma: 50/60 (80%!)

Adult soft tissue sarcomas: 700/1400 (50%?)

Italian Sarcoma GroupItalian Sarcoma Group

Started January 1st, 2005 - 3 year projectStarted January 1st, 2005 - 3 year project

Total grant: 2.530.500,00 EuroTotal grant: 2.530.500,00 Euro

Website: WWW.PROTHETS.ORG

Dr. Piero Picci (Co-ordinator)

*Partner 1 Istituti Ortopedici Rizzoli (IOR, Italy)

Dr.ssa Katia Scotlandi

*Partner 2 Institut National de la Santé et de la Recherche Médicale (INSERM, France)

Pr. Alain Bernard

*Partner 3 Laboratory for Experimental Orthopaedic Research (UKM, Germany)

Dr. Frans van Valen

*Partner 4 University of Helsinki (UH.DMG, Finland)

Prof. Sakari Knuutila

*Partner 5 Department of Pathology, University of Valencia (UVEG, Spain)Prof. Antonio Lombart-Bosch

*Partner 6 Children´s Cancer Research Institute (CCRI, Austria)

Prof. Dr. Heinrich Kovar

*Partner 7 Université Paris 7 Denis-Diderot (UP7 DD, France)

Dr. Bernard Perbal

*Partner 8 Centre National de la Recherche Scientifique (CNRS, France)

Dr. Claude Malvy

*Partner 9 Belozersky Inst. of Physico-Chemical Biology of the Moscow State Univ. (BI.MSU)

Dr.ssa Marina Gottikh

*Partner 10 GenX Laboratories srl (GENX, Italy)

Dr. Alessandro Borsatti

*Partner 11 MABGENE S.A. (MABG, France)Agnès Leconte

Dr. Piero Picci (Co-ordinator)

*Partner 1 Istituti Ortopedici Rizzoli (IOR, Italy)

Dr.ssa Katia Scotlandi

*Partner 2 Institut National de la Santé et de la Recherche Médicale (INSERM, France)

Pr. Alain Bernard

*Partner 3 Laboratory for Experimental Orthopaedic Research (UKM, Germany)

Dr. Frans van Valen

*Partner 4 University of Helsinki (UH.DMG, Finland)

Prof. Sakari Knuutila

*Partner 5 Department of Pathology, University of Valencia (UVEG, Spain)Prof. Antonio Lombart-Bosch

*Partner 6 Children´s Cancer Research Institute (CCRI, Austria)

Prof. Dr. Heinrich Kovar

*Partner 7 Université Paris 7 Denis-Diderot (UP7 DD, France)

Dr. Bernard Perbal

*Partner 8 Centre National de la Recherche Scientifique (CNRS, France)

Dr. Claude Malvy

*Partner 9 Belozersky Inst. of Physico-Chemical Biology of the Moscow State Univ. (BI.MSU)

Dr.ssa Marina Gottikh

*Partner 10 GenX Laboratories srl (GENX, Italy)

Dr. Alessandro Borsatti

*Partner 11 MABGENE S.A. (MABG, France)Agnès Leconte

PROTHETS - OBJECTIVESPROTHETS - OBJECTIVES1. Prognostic factors: fusion transcripts, secondary

cytogenetic and molecular alterations, CD99, IGF-IR, NOVH, erbB-2, TTF1

2. Targeted therapeutic approaches: EWS/FLI1, CD99, erbB-2, IGF-IR, TRAIL

3. Genomic profiles for evaluation of tumor progression and response to chemotherapy

1. Prognostic factors: fusion transcripts, secondary cytogenetic and molecular alterations, CD99, IGF-IR, NOVH, erbB-2, TTF1

2. Targeted therapeutic approaches: EWS/FLI1, CD99, erbB-2, IGF-IR, TRAIL

3. Genomic profiles for evaluation of tumor progression and response to chemotherapy

WP3: Prognostic relevance of selected promising predictive markers

87 primary or established cell lines445 paraffin block material145 frozen material80 serum collected from ESFT pts3 tissue arraysMore than 200 inclusions for EM

87 primary or established cell lines445 paraffin block material145 frozen material80 serum collected from ESFT pts3 tissue arraysMore than 200 inclusions for EM

Evaluation of prognostic value of new genes

GALS3BP

HINT1

STOML2

CANX

FVT1

RPS4Y1

Prognostic value in a very small clinical series:

36 primary untreated biopsies, homogenous for histology, checked for RNA quality

Confirmatory studies: Protein analysis Tissue Array

Functional studies: in vitro siRNA silencing or forced expression