Long-term results (>25 years) of a randomized, prospective clinical trial evaluating chemotherapy in patients with high-grade, operable osteosarcoma

Authors

  • Nicholas M. Bernthal MD,

    1. Department of Orthopedics, UCLA Orthopedic Hospital, David Geffen School of Medicine at UCLA, University of California-Los Angeles, Los Angeles, California
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  • Noah Federman MD,

    1. Department of Pediatrics, Hematology/Oncology, UCLA Jonsson Comprehensive Cancer Center, University of California-Los Angeles, Los Angeles, California
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    • The first 2 authors contributed equally to this article.

  • Frederick R. Eilber MD,

    Corresponding author
    1. Division of Surgical Oncology, University of California-Los Angeles, Los Angeles, California
    • Division of Surgical Oncology 10833 LeConte Avenue Rm 54-140 CHS, Los Angeles, CA 90095-1782
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  • Scott D. Nelson MD,

    1. Department of Pathology, University of California-Los Angeles, Los Angeles, California
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  • Jeffrey J. Eckardt MD,

    1. Department of Orthopedics, UCLA Orthopedic Hospital, David Geffen School of Medicine at UCLA, University of California-Los Angeles, Los Angeles, California
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  • Fritz C. Eilber MD,

    1. Division of Surgical Oncology, University of California-Los Angeles, Los Angeles, California
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  • William D. Tap MD

    Corresponding author
    1. Melanoma/Sarcoma Service, Division of Solid Tumors, Memorial Sloan-Kettering Cancer Center, New York, New York
    • Memorial Sloan-Kettering Cancer Center, Department of Medicine, Division of Solid Tumors, Melanoma and Sarcoma Service, 1275 York Avenue, New York, NY 10065
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    • Fax: (646) 422-2076


Abstract

BACKGROUND:

The authors present the long-term follow-up (>25 years) data from 1 of the original prospective, randomized trials that compared adjuvant chemotherapy with expectant management in patients with high-grade, localized osteosarcoma. In addition, the value of pathologic necrosis induced by a single cycle of neoadjuvant chemotherapy was analyzed as a predictive marker of disease-free and overall survival.

METHODS:

Fifty-nine patients with high-grade, localized osteosarcoma were enrolled in a prospective trial that was performed between 1981 and 1984 at the University of California-Los Angeles (UCLA). Patients were randomized to receive either adjuvant chemotherapy or observation after surgical resection. Long-term outcomes, follow-up, and pathologic review of all available histologic sections were performed.

RESULTS:

The 25-year disease-free survival rate was 28% for patients who received adjuvant chemotherapy compared with 15% for the untreated patients (P = .02). The overall survival rate at 25 years was also significantly higher for treated patients versus untreated patients (38% vs 15%; P = .02). Tumor necrosis >90% after a single round of chemotherapy was a statistically significant predictor of overall survival and disease-free survival for patients who received adjuvant therapy (164 months vs 65 months [P = .04] and 141 months vs 14 months [P < .01], respectively).

CONCLUSIONS:

Patients with high-grade, localized osteosarcoma who received adjuvant chemotherapy after undergoing definitive surgical resection had a statistically significant benefit in disease-free and overall survival that was maintained through 25 years. Tumor necrosis after just 1 cycle of neoadjuvant chemotherapy and radiation was predictive of overall survival and disease-free survival in patients who received adjuvant chemotherapy. Cancer 2012. © 2012 American Cancer Society.

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