Not surprisingly, patients who undergo amputation have lower local-recurrence rates than patients who undergo limb-salvage procedures. Patients with tumors of the femur have a higher local recurrence rate than patients with primary tumors of the tibia/fibula. Rotationplasty and other limb salvage procedures have been evaluated for both their functional outcome and their effect on survival. There is no difference in OS between patients initially treated by amputation and those treated with a limb sparing procedure. While limb-sparing resection is the current practice for local control at most pediatric institutions, there are few data to indicate that limb-salvage of the lower limb is substantially superior to amputation with regard to patient quality of life.
If complete surgical resection is not feasible or if surgical margins are inadequate, radiation therapy (RT) may improve the local control rate.[16,17] While it is accepted that the standard approach is primary surgical resection, a retrospective analysis of a small group of highly selective patients reported long-term event-free survival with external-beam RT for local control in some patients.[Level of evidence: 3iiiA] RT should be considered in patients with osteosarcoma of the head and neck who have positive or uncertain resection margins.[Level of evidence: 3iiA]
Almost all patients receive intravenous preoperative chemotherapy as initial treatment. Current chemotherapy protocols include combinations of the following agents: high-dose methotrexate, doxorubicin, cyclophosphamide, cisplatin, ifosfamide, etoposide, and carboplatin.[20,21,22,23,24,25,26,27,28,29] Although most patients with osteosarcoma receive high-dose methotrexate as part of initial therapy, patients treated with doxorubicin, cisplatin, cyclophosphamide, and vincristine (without high-dose methotrexate) have a similar outcome to that of patients receiving high-dose methotrexate.
In certain trials, extent of tumor necrosis is used to determine postoperative chemotherapy. In general, if tumor necrosis exceeds 90%, the preoperative chemotherapy regimen is continued. If tumor necrosis is less than 90%, some groups have incorporated drugs not previously utilized in the preoperative therapy. This approach is based on early reports from Memorial Sloan-Kettering Cancer Center (MSKCC) which suggested that adding cisplatin to postoperative chemotherapy improved the outcome for patients with less than 90% tumor necrosis. With longer followup, the outcome for patients with less than 90% tumor necrosis treated at MSKCC was the same whether they did or did not receive cisplatin in the postoperative phase of treatment. Subsequent trials performed by other groups have failed to demonstrate improved event-free survival (EFS) when drugs not included in the preoperative regimen were added to postoperative therapy.[22,31]
The Children's Oncology Group (COG) performed a prospective randomized trial in newly diagnosed children and young adults with localized osteosarcoma. All patients received cisplatin, doxorubicin, and high-dose methotrexate. One-half of the patients were randomly assigned to receive ifosfamide. In a second randomization, one-half of the patients were assigned to receive the biological compound muramyl tripeptide-phosphatidyl ethanolamine encapsulated in liposomes (L-MTP-PE) beginning after definitive surgical resection. The addition of ifosfamide did not improve outcome. The addition of MTP-PE produced improvement in EFS, which did not meet the conventional test for statistical significance (P = .08), and a significant improvement in OS (78% vs. 70%; P = .03).[Level of evidence: 1iiA] There has been speculation regarding the potential contribution of postrelapse treatment, although there were no differences in the postrelapse surgical approaches in the relapsed patients. The appropriate role of MTP in the treatment of osteosarcoma remains under discussion.