The treatment of osteosarcoma: present trends. The Scandinavian Sarcoma Group experience.

The study comprised 97 patients treated by the Scandinavian Sarcoma Group for high-grade, extremity-localized osteosarcoma. Chemotherapy was according to the T-10 protocol, with four courses of high-dose methotrexate (HDMTX) given preoperatively at weekly intervals. Seventeen percent of the patients obtained a good (grade III or IV) histologic response, 62% a moderate (grade II) response and 21% a poor (grade I) response. Grade II-IV responders had significantly higher serum MTX levels than grade I responders. Good responders had significantly better survival than moderate/poor responders, and had a trend towards both lower recurrence rate and longer time to recurrence. Five-year overall and relapse-free survival for all patients was 63% and 53%, respectively. Within a group of patients with similar primary tumour response, there was a trend for better survival with increasing serum MTX levels, indicating that individualization of MTX doses according to renal excretion rates may be indicated. The present results underline the importance of introducing effective chemotherapy from the start of osteosarcoma treatment, and that HDMTX alone seems to be insufficient preoperative therapy. The toxicity of HDMTX is generally mild, but we have by cerebral MRI found signal changes in white matter in 14/22 patients; changes that may represent subclinical MTX CNS toxicity. In the subsequent SSG osteosarcoma protocol, cisplatin and doxorubicin has been added to HDMTX from the start of treatment. Our data also suggest that an aggressive approach involving second-line chemotherapy and surgery is indicated for metastatic disease and that such an approach may lead to long-term survival in up to 30% of patients.