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Superior Survival in Treatment of Primary Nonmetastatic Pediatric Osteosarcoma of the Extremity

From the Institute for Limb Preservation at Presbyterian/St. Luke’s Medical Center (RMW, JWC, BAJ, PMC, KF, SDP, SLS, CMK, ABC) and The Children’s Hospital (LO), Denver, Colorado.

Correspondence: Address correspondence and reprint requests to: Anne B. Camozzi, BA, The Institute for Limb Preservation at Presbyterian/St. Luke’s Medical Center, 1601 E. 19th Avenue, Suite 3250, Denver, CO 80210; Fax: 303-839-6399; E-mail: anne.camozzi{at}healthonecares.com

ABSTRACT

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 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 (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.

Key Words: Osteosarcoma • Doxorubicin • Cisplatin • Tumor vascularity • Infusions • Intra-arterial

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