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

2. Italian Sarcoma Group 172 Members 53 Centers • 10 I.R.C.C.S.
BELGIO
53 Centers
• 10 I.R.C.C.S.
• 12 Universities
• 25 Public Hospitals
• 6 Private Hospitals 1 1 1 1 9 1 8 1 1 2 2 1 1 1 1 1 1 2 1 1 1 1 3 1 1 2 1 3 1
172 Members
at 24 March 2004 1

3. Osteosarcoma ISG/SSG I - Localized disease
PRE-OP MTX-CDP1/ADM1-IFO X 2
POST-OP ADM2-IFO-MTX-CDP2 X 3 (4 IN POOR)
MTX: Methotrexate 12 g/m2 as 4 hours i.v. infusion, increase by
2 g/m2 if 4 hours serum MTX in previous course was < 1000 µmol/l
CDP1: Cisplatin 60 mg/m2/24 hour as 48 hours continuous i.v. infusion
CDP2: Cisplatin 75 mg/m2/24 hour as 48 hours continuous i.v. infusion
ADM1: Adriamycin (Doxorubicin) 75 mg/m2 as 24 hours continuous i.v. Infusion
ADM2: Adriamycin (Doxorubicin) 90 mg/m2 as 24 hours continuous i.v. infusion
Ifo: Ifosfamide 3 g/m2/24 hour as 120 hours (5 day) continuous i.v. infusion

4. ISG/SSG I (localized osteosarcoma)
March 1997 – May 2000
Total cases: 182 OS
EFS
Manuscript ready for submission

5. Postoperative treatment
Osteosarcoma ISG/SSG II - Metastases at diagnosis
Postoperative treatment
week
ADM2: Adriamycin (Doxorubicin) 90 mg/m2 as 24 hours continuous i.v. infusion
Cy: Cyclofosfamide 4000 mg/m2 as 3 hour continuous i.v. infusion
E1: Etoposide 200 mg/m2/day as 72 hour (3 day ) continuous i.v. infusion
HDEC+PBSC rescue:
Etoposide 450 mg/m2/day as 4 day continuous i.v. infusion Carboplatin 375 mg/m2/day for 4 days (2 hour infusion)
Peripheral blood stem cell (PBSC) rescue at 72 hours after and of chemotherapy

6. (metastatic osteosarcoma) Abstract to be presented ASCO 2005
ISG/SSG II
(metastatic osteosarcoma)
March 1998 – December 2003
Total cases: 47
Abstract to be presented ASCO 2005

7. LOCALIZED OSTEOSARCOMA
ISG/OS-1
April 2001 – Ongoing
At october 2004: 166 pts.
Necrosis ≥ 90% A-M-P
Necrosis < 90% A-I-M-P
Arm A
(M-P/A) x 2
RANDOM
Arm B
M-P/A- M-I/P- M-I/A
P/A-M-M-I/P-I/A
Pts. expected: 264 in 5 yrs.

8. EURO-B.O.S.S. EUROpean Bone Over 40 Sarcoma Study
Italian Sarcoma Group
Cooperative OSteosarcoma Study
Scandinavian Sarcoma Group
CDP-ADM-IFO as adjuvant or neoadjuvant treatment (MTX only in selected patients)
December 2002-ongoing
At october 2004: 30 patients ISG

9. ISG/SSG III and IV (Ewing family tumors)
Standard L O C A T H E R P Y
R 1
VACA-IE
Necrosis
VAC+IE
HDT
R 2
HiperVAI+CE
VAC+IE
HDT
Mini-allo
R 3
HiperCE
VAC+IE
HDT

10. ISG/SSG III (Standard risk) 70 pts. completed HD treatment
June 1999 – ongoing
At October 2004: 223 patients
GOOD RESPONDERS 53%
RESPONSE 183 pts.
POOR RESPONDERS 47%
70 pts. completed HD treatment
No major organ toxicity
No toxic death

11. June 1999 – ongoing At October 2004: 72 patients
ISG/SSG IV (High risk)
June 1999 – ongoing
At October 2004: 72 patients
- 10 progression disease
- 1 toxic death
41 PTS completed
HD treatment
3 year OS 54% (38-69)
Median FU 19 months (1-62)
Abstract to be presented at ASCO 2005

12. Localized High Risk STS Protocol (ISG/STS1)
Italian Sarcoma Group
Localized High Risk STS Protocol (ISG/STS1) R A N D O M
IFO + EPI x 2
IFO + EPI x 3
CONTROL
• IFO 9 g/m2 in 3 days
• EPI 120 mg/m2 2 days
• MESNA mg/m2 3 days
• G-CSF 300 mcg days

13. Milano INT 38 Bologna IOR 36 Milano ICH 11 Torino Gradenigo 9
Aviano/Gorizia 8
Brescia 6
Milano IEO 2
Napoli INT 2
Torino IRCC 2
Ravenna 1
------
115 l

14. Jan 2002
ISG 115
GEIS Jan
137

15. Adult soft tissue sarcoma…
ISG/STS1 (neoadjuvant EpiDOX+IFX, in localized high-risk disease)
HD-IFX cont inf (2nd-4th line)
Gemcytabine in leiomyosarcoma (2nd-3rd line)
Paclitaxel in angiosarcoma (2nd line)
Miniallogenic transplant (advanced disease, responsive patients)

16. GIST…
GIOTTO (observational study, 2004, in collaboration with Novartis)
REGISTER (pathology retrospective study)
62024 (adjuvant Imatinib), intergroup EORTC-led trial
SU11248 (company’s sponsored international study)
PTK787 (international study)

17. Italian Population: 57 Million
ITALIAN SARCOMA GROUP
POTENTIAL OF ACCRUAL
Italian Population: 57 Million
OSTEOSARCOMA: /120 = 75%
EWING’S FAMILY: 50/60 > 80%
SOFT TISSUE SARCOMAS: 700/1400 = 50%

18. A European Project within the VI framework

19. 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)
Assoc. 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

20. 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

21. Graphical presentation
of work packages

22. Starting January 1st, 2005 - 3 year project Website: WWW.PROTHETS.ORG
Total grant: ,00 Euro
Website:

23. May 24-25 ISG Annual Meeting May 27 Meeting of European Sarcoma Groups
SSG
GEIS
EORTC
France
Poland
Germany
etc.