French Sarcoma Group CTOS meeting, Nov 2004 Thank you for inviting the French Sarcoma to participate to this session of CTOS; As it is the first time, I should have to say a few wordsto introduce ourself. CTOS meeting, Nov 2004

FNCLCC Sarcoma Group Started from a multicentric work of pathologists since 1980’s (JM Coindre)  FNCLCC grading Established in 1980’s by the FNCLCC to coordinate clinical research on sarcomas among the 20 french cancer centers (BN Bui). Open to other public and private structures treating cancer patients since 2000 : French Sarcoma Group 2004 : n=37 institutions (comprehensive cancer ctrs, Univ. Hospitals, private clinics... + CHUV Lausanne) The FNCLCC sarcoma group was established in the early 80 ’s. 400 to 500 patients with sarcomas are treated in our centers each year, half of them for their first tretament . This represent approximatively half of the sarcomas expected in France. The group is now opening to other hospitalls mainly university h ospitals.

FNCLCC Lille Rouen Paris Nancy Caen Strasbourg Angers Nantes Dijon (Curie, IGR, St-Cloud) Nancy Caen Reims Strasbourg Rennes Angers Nantes Dijon Clermont- Ferrand The French Federation of Cancer Center is the coordinating structure for the 20 public cancer centers in France. Are settled in Paris and the others are spread in the country Lyon Bordeaux Nice Toulouse Marseille Montpellier

French Sarcoma Group Objectives Education and improvement of the quality of patient care Basic, translational and clinical research Intergroup collaborations (EORTC…) The FNCLCC sarcoma group was established in the early 80 ’s. 400 to 500 patients with sarcomas are treated in our centers each year, half of them for their first tretament . This represent approximatively half of the sarcomas expected in France. The group is now opening to other hospitalls mainly university h ospitals.

Pathology (coord. : J.M .Coindre) FNCLCC soft tissue sarcoma database (2500 patients 1985  2004) all pathologies collegially reviewed monthly Patient recorded from initial diagnosis all cases documented with patients and tumors characteristics, treatment data and evolution FNCLCC Grading Frozen tissue bank (1000 sarcomas, 300 benign tumors) to allow diagnostic and prognostic studies on homogenous groups by tumor types or localizations The activity of the pathologists is very important in our group, since the elaboration of the so-called French grading system. They are very active in the field of diagnosis and prognostication improvement . They have constituted 2 important tools. First, a database including only patients with a pathology collegially reviewed on a 15 heads microscope, and patient initially treated at least for a part in our institutions , and this provide complete data on tumors, treatment and evolution. Second, we are federating the frozen tissue banks All the cases will be centrally registered and attached to the patients data.

Molecular biology (coord. : A. Aurias) Chromosomal and genomic abnormalities of sarcomas Diagnostic and prognosis of sarcomas (eg : MFH and undifferentiated sarc) (A. Aurias) Arraying of STS to define new entities and molecular pathways (A. Aurias) Gene expression and response to chemotherapy (J. Robert) A first part of the group activity is on biology. . This activity is coordonaated by A. Aurias, from the Institut Curie. And is centered mainly, at tthe present time on the genetics of sarcomas with hopefully a better kwowledge of those tumors in the next future. the micro-arrays techniques have been made available. Beside this, we are interested in the use of these techniques to look at behavior of the tumor while treated with chemotherapy

Clinical trials (JY Blay, A. Le Cesne, BN Bui) Soft tissue sarcomas PAC 02 : phase III study of intensification after remission induction in advanced STS (Palsar II) (BN Bui); n=127 Randomized phase II study of dose reduction (0.5 vs 1 vs 2 vs 4 mg) of TNF in isolated limb perfusion (S.Bonvalot); n=102 A phase II trial of imatinib in locally advanced non resectable aggressive fibromatosis (JY Blay); n=9 A phase II trial of weekly paclitaxel in advanced angiosarcomas (N Penel) The third part of our activity concern clinica l trials . Foe soft tissue sarcomas, we have 3 open trials on advanced tumors. The first is a phase III trial of chemotherapy intensification with PBSC, on patients responding to MAID chemotherapy. The pilot study as been published by JY BLAY a few weeks ago in the JCO. Because the new drugs studies are not available to many centers of our group, we have engaged phase II studies with association of minimally active drugs but with putative synergis. We have also opened a study

Visceral sarcomas Uterine sarcomas A prospective randomized phase II trial of Surgery+RT vs Surgery +APIx3+ RT in high grade uterine sarcomas (P. Pautier); n=34 A prospective randomized phase II trial of Gemcitabin vs Gemcitabine + docetaxel in relapsed uterine sarcomas (F. Duffaud & P. Pautier) The third part of our activity concern clinica l trials . Foe soft tissue sarcomas, we have 3 open trials on advanced tumors. The first is a phase III trial of chemotherapy intensification with PBSC, on patients responding to MAID chemotherapy. The pilot study as been published by JY BLAY a few weeks ago in the JCO. Because the new drugs studies are not available to many centers of our group, we have engaged phase II studies with association of minimally active drugs but with putative synergis. We have also opened a study

Visceral sarcomas GIST: BFR14 prospective phase III trial testing Glivec maintenance vs interuption after 3 years (Blay & Le Cesne) Participation to the EORTC 62024 adjuvant imatinib trial in GIST (P. Casali) Phase II trials of a new KIT inhibitor AB1010 in front line and in imatinib refractory patients (Le Cesne & Blay) The third part of our activity concern clinica l trials . Foe soft tissue sarcomas, we have 3 open trials on advanced tumors. The first is a phase III trial of chemotherapy intensification with PBSC, on patients responding to MAID chemotherapy. The pilot study as been published by JY BLAY a few weeks ago in the JCO. Because the new drugs studies are not available to many centers of our group, we have engaged phase II studies with association of minimally active drugs but with putative synergis. We have also opened a study

Soft tissue sarcomas : future studies Clinical trials Soft tissue sarcomas : future studies A prospective randomized phase III trial of Surgery+EBRT vs Surgery alone in retroperitoneal sarcomas (C.Le Péchoux) A prospective randomized phase III trial of Surgery+EBRT vs Surgery alone in limb sarcomas R0 margins>1 cm The third part of our activity concern clinica l trials . Foe soft tissue sarcomas, we have 3 open trials on advanced tumors. The first is a phase III trial of chemotherapy intensification with PBSC, on patients responding to MAID chemotherapy. The pilot study as been published by JY BLAY a few weeks ago in the JCO. Because the new drugs studies are not available to many centers of our group, we have engaged phase II studies with association of minimally active drugs but with putative synergis. We have also opened a study

Bone sarcomas: clinical trials Ewing sarcoma PAC 01 : protocol Euro-E.W.I.N.G 99 (with SFOP, UKCCSG, SIAK, GPOH) (O. Oberlin) Phase II trial of CDDP + VP16 in relapsed ES/PNET (O. Oberlin) For Ewing sarcomas, we are part of an intergroup study called… This is a complex study with different questions according to the prognostic classification of the patients and according to the response to an initial chemotherapy using a 4 drugs regimen As for osteosarcoma, we are opening a trial in adults, to confirm on a xti institutional basis the results obtained in Villejuif with

Bone sarcomas: clinical trials Osteosarcoma OSAD 1993. Phase II of IP as induction chemotherapy in localized osteosarcomas (JY Blay) OSAD 2000 (PAC 04). Phase II of API-AI as induction chemotherapy (A. Le Cesne) Followed by: A prospective randomized phase III trial testing HDCT in poor histological responders to preoperative regimen in first line treatment of osteosarcomas (with SFOP) For Ewing sarcomas, we are part of an intergroup study called… This is a complex study with different questions according to the prognostic classification of the patients and according to the response to an initial chemotherapy using a 4 drugs regimen As for osteosarcoma, we are opening a trial in adults, to confirm on a xti institutional basis the results obtained in Villejuif with

Education and improvement of primary care CME for the management of the pathology of STS since 1980’s Pathology review since 1989 Internet presentation of clinical cases CME in different french regions through cancer networks Clinical practice guidelines (SOR project) (Br J Cancer, Bull Cancer, www.fnclcc.fr...) A first part of the group activity is on biology. . This activity is coordonaated by A. Aurias, from the Institut Curie. And is centered mainly, at tthe present time on the genetics of sarcomas with hopefully a better kwowledge of those tumors in the next future. the micro-arrays techniques have been made available. Beside this, we are interested in the use of these techniques to look at behavior of the tumor while treated with chemotherapy

FNCLCC S.O.R. Project Guidelines for the management of patients with cancer at the first treatment. SOR for osteosarcomas and adult soft tissue sarcomas - First issue in 1995 (Bull Cancer 1995) - Updates: osteosarcoma (1999, Br J Cancer), adult STS (2004) Retrospective and prospective evaluation of the adhesion to CPGs in regional cancer Network (Ann Oncol 2004)

Conclusions: FSG Clinical and Public Health research Education Intergroup studies