THE TREATMENT OF OSTEOSARCOMA OF THE EXTREMITIES WITH DETECTABLE LUNG METASTASES AT PRESENTATION: THE RIZZOLI EXPERIENCE ON 76 PATIENTS

Longhi A. Briccoli A,Bertoni F, Giacomini S, Mellano D, Monti C,Ferrari S and Bacci G. (Department of Muscoskeletal Oncology, Istituto Ortopedico Rizzoli, Bologna, Italy)

In the two past decades, it has been demonstrated that the combination of surgery + chemotherapy improves the prognosis for patients with osteosarcoma of the extremity without detectable metastases at presentation. By contrast, the efficacy of chemotherapy coupled with aggressive surgery has not been well established for metastatic disease at diagnosis. This study evaluates the efficacy of chemotherapy associated with simultaneous surgery of primary and metastatic lesions in patients with osteosarcoma of the extremity metastatic to the lung at presentation. Between March 86 and August 95, 76 patients with lung metastases originating from an osteosarcoma of the extremity were treated with chemotherapy, according to two different protocols successively activated, followed by simultaneous resection of primary and metastatic lesions (when feasible) and further chemotherapy. Both protocols (IOR/OS - 2 and IOR/OS - 5) provided MTX,CDP,ADM and IFO, but in the former protocol only the first three drugs were preoperatively employed. After primary chemotherapy, lung metastases disappeared in 12 patients, while in 18 cases they remained surgically unresectable.A11 these 30 patients had a surgical treatment of the primary tumor only. The other 46 patients underwent simultaneous resection of primary and metastatic lesions. The resection of metastases was complete in 42 cases and incomplete in 4. The 22 patients who never achieved a tumor-free status died in a few months. 54 patients reached remission: at a 84-month follow-up (34-144 mo.), 14 (26%) remained continuously free of disease, 39 relapsed with new metastases and 1 died of toxicity. For these 54 patients the 4-year disease-free survival and overall survival were 28% and 38% respectively. A strong correlation between the degree of necrosis of primary tumor and metastases was found in 30 of the 42 patients who had a complete simultaneous resection of primary and metastatic lesions. We conclude that the combination of aggressive chemotherapy with simultaneous resection of primary and metastatic lesions improves traditionally negative outcomes of patients with osteosarcoma of the extremity with lung metastases at presentation. In addition to this, the strong correlation found between the histologic response of primary and metastatic tumor supports the strategy, widely followed nowadays in the neoadjuvant treatment of osteosarcoma, of tailoring postoperative chemotherapy according to the histologic response of the primary tumor to preoperative chemotherapy.