The value of serial arteriography in osteosarcoma: delivery of chemotherapy, determination of therapy duration, and prediction of necrosis.

PURPOSE: To investigate the value of serial arteriography to assess tumor response, predict necrosis, and individualize the duration of a combined intravenous (IV) and intraarterial (IA) neoadjuvant chemotherapy protocol in patients with biopsy-proven high-grade osteosarcoma or malignant fibrohistiocytoma of bone. MATERIALS AND METHODS: Between July 1987 and March 2003, 109 patients completed a chemotherapy protocol of neoadjuvant IV doxorubicin and IA cisplatin. Patients were eligible regardless of age, disease stage, or disease site. A minimum of three IA cycles followed by definitive surgery was required for inclusion in the final analysis. IA dose and duration were increased for tumors larger than 10 cm. Initial arteriograms were scored as indicating mild, moderate, or marked tumor neovascularity (TNV). Subsequent arteriograms were prospectively compared with the baseline image for percent change in TNV. Treatment continued until a maximum of five cycles were administered or one of three criteria were met: (i) at least 90% decrease in TNV, (ii) plateau of effect, or (iii) no response. RESULTS: Of 408 IA procedures, 42 patients underwent three cycles, 53 underwent four, and 14 required five cycles of neoadjuvant therapy. There was a 2.5% minor complication rate. Eighty-six percent of patients exhibited at least 90% decrease in TNV and 82% exhibited good histologic response (> or =90% tumor necrosis). Serial arteriography predicted a good histologic response with an accuracy of 90% and a sensitivity of 97%. CONCLUSIONS: Serial arteriography was highly sensitive and accurately predicted good responses. This individually modified, dose-intensified neoadjuvant protocol yielded an excellent histologic response rate with minimal complications. Future endeavors should involve a multiinstitutional study of this unique approach.

Superior survival in treatment of primary nonmetastatic pediatric osteosarcoma of the extremity.

BACKGROUND: A protocol to treat osteosarcoma of the extremity was developed at two local institutions. METHODS: The study involved a dose-intensified neoadjuvant protocol of intravenous doxorubicin and intra-arterial cisplatin administered repetitively until maximum angiographic response was noted. Definitive surgery was delayed until > or =90% reduction in tumor neovascularity was documented. Prospective assessment of serial arteriograms was highly accurate (94%) in predicting histological response and assisted in surgical planning. After resection, if patients were determined to be good responders (> or =90% tumor necrosis), they underwent a 4-month postoperative course with the same agents. Poor responders (<90% necrosis) were treated with alternative agents for 12 months from diagnosis. Forty-seven assessable patients with primary, high-grade, nonmetastatic osteosarcoma of the extremity were included in this analysis. The median age was 15 years (range, 7-21 years). RESULTS: Patients underwent an average of four preoperative intra-arterial courses. Forty-three patients underwent limb-preservation procedures, and 41 had >90% tumor necrosis. With an average follow-up of 92 months (range, 20-178 months), 39 patients were continuously disease free, 3 died of disease, 1 died of other causes, and 4 have no evidence of disease 11 to 51 months after relapse (all pulmonary metastases). There were no local recurrences. Kaplan-Meier analysis demonstrated a 10-year overall survival of 92% and an event-free survival of 84%. CONCLUSIONS: This study demonstrates excellent survival with a dose-intensified neoadjuvant protocol. Future endeavors should involve a multi-institutional randomized study comparing this approach with another multiagent intravenous neoadjuvant protocol.