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.

Rationale: Osteosarcoma predominantly affects adolescents and young adults. Reduced fertility in men is well documented following treatment for osteosarcoma and related to chemotoxicity.

We have however not found data about the health of children of patients formerly treated for osteosarcoma.

Among our few patients we have had one offspring with an infantile fibrosarcoma successfully treated with high dose chemotherapy and surgery. One mother has secondary gastric malignancy after successful pregnancy.

With this contribution we want to draw the attention to include data of children in the long-term implications of osteosarcoma and its treatment.

Materials and Methods: Patients: Of 75 patients with osteosarcoma 11 patients (5 women, 6 men) have 16 children‚ produced’ after completed oncologic treatment

All women became pregnant as planned. There are no female patients evidently infertile. One man among our patients shows azoospermia and is infertile. One man with oliogespermia has a healthy daughter after successful vitro fertilisation.

All patients have had treatment for osteosarcoma after puberty.

Offsprings: Pregnancy and delivery were uneventful for all children. The one girl mentioned above at birth showed a tumor of the Plexus brachialis which was a biopsy proven infantile fibrosarcoma. She received high dose chemotherapy. Resection of the tumor retaining the brachial at 9 months of age showed only scarce tumor residuals; she is disease free at 4 years of age. Her two siblings are healthy

Conclusion: We want to stress that in follow up studies events during pregnancy and health of offsprings should be included.