Objective  After establishing standard multi-modal therapy, prognosis of refractory and metastatic high-grade osteosarcoma remains dismal and unchanged over the last decades. Early clinical intervention to newly detected metastatic lesions is crucial and effective for better prognosis. Arsenic trioxide (ATO) is one of the oldest remedies used in traditional oriental medicine and is recently rediscovered as an immunomodulator due to its activity against other solid tumors. This study aims to evaluate the efficiency of ATO combined with first-line chemotherapy in treating pulmonary metastatic osteosarcoma patients with long-term follow-up in our institution.

  Methods  Osteosarcoma patients with pulmonary metastasis were intravenously administered with ATO (5-10 mg) daily combined with first-line chemotherapy for their treatment. A total of 119 patients were finally enrolled; 65 presented metastasis, and 54 relapsed with lung metastasis.

  Results   Two-year and five-year overall survival (OS) rates for these patients reached 52.6% and 30.9%, respectively. Only 20 cases underwent thoracotomies (16.8%). Our five-year OS was nearly similar to that of other institutions (37% in Rizzoli, Italy). We observed that combined with bone metastasis, bilateral metastasis, and > 3 pulmonary nodules, incomplete resection of pulmonary lesions deteriorated the disease and significantly influenced survival as compared with all other parameters.

  Conclusion  Combined with conventional chemotherapy, ATO may be effective and well-tolerated as new therapeutic option for patients with nonresectable pulmonary metastatic osteosarcoma. Lung metastasectomy should be strictly selected only for populations who benefit from this treatment.