EUROpean Bone Over 40 Sarcoma Study (EURO-B.O.S.S.) is the first prospective multicenter international study for patients 41–65 year old with high-grade bone sarcoma

Patients with HG Osteosarcoma (OS), HG sarcoma NOS (S), Fibrosarcoma, MFH, Leiomyosarcoma, Dedifferentiated Chondrosarcoma (DCh) were included. Chemotherapy: Combinations of cisplatin/doxorubicin (CDP 100mg/m2/ADM 60mg/m2), ifosfamide/CDP(IFO 6g/m2/CDP 100mg/m2) and IFO/ADM (IFO 6g/m2/ADM 60mg/m2) were repeated three times (9 cycles). Surgery was planned after 3 cycles. Methotrexate (8g/m2) was postoperatively added in poor responders. Immediate surgery was allowed and 9 cycles with CDP, ADM, IFO were postoperatively given.

At December 2007, 140 patients were registered (median age 51 years). OS (51%), S (16%), and DCh (11%) were the more frequent histotypes. Synchronous metastases in 30 (21%) patients, central location of tumor in 45(32%).Surgical complete remission (SCR) was achieved in 84% of patients, (localized 91%, meta-static 37%) without difference among the histology groups. One surgical-related and one chemotherapy-related death were reported.

Grade4 WBC and PLT incidence was 55% and 17%.Renal toxicity and peripheral neurotoxicity were reported in 16% and 20% of patients. With a median follow-up of 25 months (4–68) 3 year OS was 58% (95%CI 48–68%) [7% (95%CI 0–19%) without SCR]. In patients with SCR, 3-year OS and EFS were 46% (95%CI 9–83%) and 0% in case of synchronous metastases and 69% (95%CI58–80%) and 45% (95%CI33–57%) for localized patients; 50% (95%CI 29–71%) and 40% (95%CI 20–59%) for patients with central tumor, 73% (95%CI61–85%) and 44% (95%CI31–57%) for those with extremity tumor; 68% (95%CI 52–83%) and 46% (95%CI 32–54%) for OS, 64% (95%CI 42–85%) and 48% (95%CI 25–71%) for S, 48% (95%CI 13–82%) and 27% (95%CI 1–54%) for DCh.

The protocol is feasible, but the chemotherapy-related toxicity is remarkable. Surgical complete remission is the main factor influencing survival. Central location and synchronous metastases are negative prognostic factors, but 50% 3-year OS can be achieved with aggressive local and systemic treatment. Osteosarcoma and high-grade sarcoma NOS benefit from chemotherapy more than patients with dedifferentiated chondrosarcoma.

Aims: Angiogenesis is a multistep phenomenon, critical for tumor growth and prognosis in many solid neoplasms. Microvessels density (MVD) is a method of assessing angiogenesis and adversely affects DFS and OS in breast, lung and colorectal cancer. Few data are available in STS in which stage and grading are until now fundamental.

Methods: Our perspective study determined the level of MVD in a series of STS and correlated these results with DFS and OS, comparing its prognostic value with grading and stage. MVD was determined with CD 31 immunostains in formalin fixed, paraffin embedded tissues. Intratumoral MVD was assessed by light microscopic analysis. Hot spots defined the positive areas. The study included 45 patients, 35 with localized and 10 with metastatic disease at diagnosis. All tumors were located in upper or lower extremities. Histology were: 13 liposarcoma,11 MFH, 5 leiomiosarcoma, 5 PNST, 3 rabdo, 3 synovialsarcoma, 3 undifferentiated and 2 fibrosarcoma. Following Coindre classification 23 pts had low grade and 22 high grade STS.

Results: median follow up is 23 months (2–84). At present 20 pts (44.4%) are alive and DF, 11 (24.4%) alive with disease, 14 (31.1%) dead. Median survival is 75 months. Median MVD of all specimens is 62 microvessels/mm² (7–161). 32 pts (71.1%) have low MVD (group A) and 13 pts (29.9%) high MVD (group B). Mean survival is 62.7 mo in group A (median 75) and 36 mo in group B (median not reached) (p 0.01); median DFS respectively 24 mo and 15 mo (p 0.01). There is also a significant association with histological grade and survival: 75 mo in low grade and 34 mo in high grade tumors (p 0.05) and presence of metastasis at diagnosis (median survival: M+23 mo, M−75 mo). Unfortunately no relationship between angiogenesis and grading is found.

Conclusions: Our study confirms the prognostic importance of grade and staging in pts with STS. Moreover the role of MVD in prognosis is well defined and should be used as a routine marker in STS histological diagnosis.