Long-term outcome for patients with nonmetastatic osteosarcoma of the extremity treated at the Istituto Ortopedico Rizzoli according to the Istituto Ortopedico Rizzoli Osteosarcoma-2 protocol: An updated report

Purpose: To provide an estimate of long-term prognosis for patients with os teosarcoma of the extremity treated in a single institution with neoadjuvan t chemotherapy and observed for at least 10 years. Patients and Methods: Patients with nonmetastatic osteosarcoma of the extre mity were preoperatively treated with high-dose methotrexate, cisplatin, an d doxorubicin (ADM). Postoperatively, good responders (90% Or more tumor ne crosis) received the same three drugs-used before surgery, whereas poor res ponders (less than 90% tumor necrosis) received ifosfamide and etoposide in addition to those three drugs. Results: For the 164 patients who entered the study between September 1986 and December 1989, surgery was a limb salvage in 136 cases (82%) and a good histologic response was observed in 117 patients (71%). At a follow-up ran ging from 10 to 13 years (median, 11.5 years), 101 patients (61%) remained continuously free of disease, 61 relapsed, and two died of ADM-induced card iotoxicity. There were no differences in prognosis between good and poor re sponding patients. ADM-induced cardiotoxicity (six patients), male infertil ity (10 of the 12 assessable patients), and second malignancies (seven pati ents) were the major complications of chemotherapy. Despite the large numbe r of limb salvages performed, only four local recurrences (2.4%) were regis tered. Conclusion: With an aggressive neoadjuvant chemotherapy, it is possible to cure more than 60% of patients with nonmetastatic osteosarcoma of the extre mity and amputation may be avoided in more than 80% of them, Because local or systemic relapses, myocardiopathies, and second malignancies are possibl e even 5 years or more after the beginning of treatment, a long-term follow -up is recommended for these patients. J Clin Oncol 18:4016-4027. (C) 2000 by American Society of Clinical Oncology.