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.
Wilkins
Ross M
RM
Institute for Limb Preservation at Presbyterian/St. Luke's Medical Center, Denver, Colorado 80210, USA.
Cullen
John W
JW
Odom
Lorrie
L
Jamroz
Brandt A
BA
Cullen
Patsy McGuire
PM
Fink
Kyle
K
Peck
Sanford D
SD
Stevens
Sydney L
SL
Kelly
Cynthia M
CM
Camozzi
Anne B
AB
D000293:Adolescent; D000328:Adult; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000008:administration & dosage* / Q000627:therapeutic use*; D001859:Bone Neoplasms / Q000098:blood supply / Q000188:drug therapy* / Q000601:surgery; D002648:Child; D002945:Cisplatin / Q000008:administration & dosage; D004317:Doxorubicin / Q000008:administration & dosage; D005260:Female; D006801:Humans; D007261:Infusions, Intra-Arterial; D007262:Infusions, Intravenous; D008297:Male; D009364:Neoplasm Recurrence, Local; D009367:Neoplasm Staging; D009389:Neovascularization, Pathologic; D012516:Osteosarcoma / Q000098:blood supply / Q000188:drug therapy* / Q000601:surgery; D011379:Prognosis; D012039:Regional Blood Flow; D016019:Survival Analysis
D004317:Doxorubicin; D002945:Cisplatin