Predictive factors of disease-free survival for non-metastatic osteosarcoma of the extremity: An analysis of 300 patients treated at the Rizzoli Institute

Background: To identify predictive factors of disease-free survival (DFS) in patients with non-metastatic osteosarcoma of the extremity, treated with primary chemotherapy and delayed surgery. Patients and methods: The relationship between patient-related and treatment-related factors and prognosis was evaluated in 300 patients treated from 1986 to 1992 according to chemotherapy protocols based on high-dose methotrexate, cisplatin and doxorubicin, with the addition of ifosfamide in the post-operative phase. Univariate and multivariate analyses of prognostic factors for disease-free survival were performed. Results: With a median follow-up of 9.2 (4.4-12) years, eight-year DFS was 59% (95% confidence interval (95% CI): 54-64.9). Univariate analyses showed that tumor volume greater than or equal to 150 ml (P= 0.002), histologic subtype (P = 0.028), age > 12 years (P = 0.044), high serum lactate dehydrogenase (P = 0.044) and alkaline phosphatase (P = 0.064) levels adversely affected DFS. Gender of patients and site of tumor did not influence DFS. No differences in DFS were found among the three chemotherapy protocols, whereas the use of limb-sparing surgery vs. amputation or rotation plasty (P = 0.006) and a good histologic response to primary chemotherapy (P = 0.014) positively correlated with DFS. After multivariate analyses, tumor volume greater than or equal to 150 ml (P = 0.028), age > 12 years (P = 0.051), and histologic subtype (P = 0.052) retained prognostic significance. Conclusions: In patients with non-metastatic osteosarcoma of the extremity treated with neoadjuvant chemotherapy, the disease-free survival is significantly influenced by tumor volume, age, and histologic subtype.