A prospective study using a dose-intensified neoadjuvant intra-arterial chemotherapy regimen was designed to improve survival rates of young patients with primary, nonmetastatic osteosarcoma of the extremity. Arteriography was implemented to individualize duration of therapy by serially assessing change in tumor neovascularity. Intravenous doxorubicin and intra-arterial cisplatin were administered repetitively at 3-week intervals until > or = 90% reduction in tumor neovascularity was achieved. Surgery was delayed until this good arteriographic response was documented. After resection, prediction of tumor neovascularity was compared with tumor necrosis. Since 1987, 62 eligible patients younger than 22 years old were treated with an average of four neoadjuvant courses. Toxicities were manageable. Fifty-four (87%) patients had a good histologic response. The rate of limb preservation surgery was 93.5% (58/62). Accuracy and sensitivity of serial arteriography in predicting histologic response were 92% and 98% respectively, and greatly assisted surgical planning. With an average followup of 91 months, estimated Kaplan-Meier survival at 10 years was 93% and event-free survival was 86%. Osteosarcoma survival rates were significantly improved by the use of this regimen compared with previously reported results. Serial arteriography succeeded in individualizing duration of neoadjuvant therapy and led to a higher rate of good histologic response.
Level of evidence: Therapeutic study, level II-1 (prospective cohort study). See the Guidelines for Authors for a complete description of levels of evidence.