I I talian talian S S arcoma arcoma G G roup roup Started June 1997 www.italiansarcomagroup.org I I talian talian Started June 1997 S S arcoma arcoma G G roup roup Formalized October 2002

Italian Sarcoma Group 210 members 68 Centers • 14 National Institutes BELGIUM 68 Centers • 14 National Institutes • 14 Universities • 34 Pubblic Hospitals • 6 Private Hospitals 1 1 1 8 1 1 1 1 1 1 1 10 1 1 3 1 2 1 1 1 1 1 6 2 1 1 1 1 1 3 1 1 1 1 2 1 5 1 210 members at november 2005 2

Osteosarcoma Protocols Italian Sarcoma Group Osteosarcoma Protocols • 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

Ewing’s Sarcoma Protocols Italian Sarcoma Group Ewing’s Sarcoma Protocols • 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 Patients activated 12/2002, 22 pts

Adult soft tissue sarcomas - Protocols Italian Sarcoma Group Adult soft tissue sarcomas - Protocols • 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)

GIST Protocols • 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)

Italian Population : 57 Millions Italian Sarcoma Group Possible accrual Italian Population : 57 Millions Osteosarcoma: 90/120 (75%!) Ewing’s Sarcoma: 50/60 (80%!) Adult soft tissue sarcomas: 700/1400 (50%?)

Started January 1st, 2005 - 3 year project Website: WWW.PROTHETS.ORG Total 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

PROTHETS - OBJECTIVES Prognostic factors: fusion transcripts, secondary cytogenetic and molecular alterations, CD99, IGF-IR, NOVH, erbB-2, TTF1 Targeted therapeutic approaches: EWS/FLI1, CD99, erbB-2, IGF-IR, TRAIL Genomic profiles for evaluation of tumor progression and response to chemotherapy

WP3: Prognostic relevance of selected promising predictive markers 87 primary or established cell lines 445 paraffin block material 145 frozen material 80 serum collected from ESFT pts 3 tissue arrays More 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