Risk-Based Therapy for Localized Osteosarcoma

Rajkumar Venkatramani, Jeffrey Murray, Lee Helman, William Meyer, M. John Hicks, Robert Krance, Ching Lau, Eunji Jo, Murali Chintagumpala

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Abstract

Background: The outcome of localized osteosarcoma has remained constant over the past 30 years. Histological response to preoperative chemotherapy is the best predictor of outcome. Strategies to alter treatment based on histological response have not resulted in increased survival. Procedure: Patients with localized osteosarcoma received preoperative chemotherapy with cisplatin, doxorubicin, and methotrexate. Patients whose tumors had a good histological response (≥90% necrosis) continued with the same treatment postoperatively. Patients with poor histological response (<90% necrosis) received three courses of melphalan 100 mg/m2 on day -4, cyclophosphamide 2,000 mg/m2 on days -3, and -2 followed by stem cell infusion. Results: Fifty-two patients were enrolled. Median age was 14 years, and 56% of patients were male. The femur was the most common site. Forty patients underwent limb salvage surgery and amputation was performed in six patients. Forty-eight percent of tumors showed good histological response. Forty patients were evaluable for outcome; 18 patients with poor histologic response received high-dose chemotherapy. The 5-year event-free survival (EFS) and overall survival (OS) for patients treated on the high-dose chemotherapy arm were 28% (95% confidence interval [CI], 10-49) and 48% (95% CI, 23-69), respectively. The 5-year EFS and OS for patients treated on the standard chemotherapy arm were 62% (95% CI, 36-80) and 74% (95% CI, 44-90), respectively. All patients who received high-dose chemotherapy developed grade 3 or higher hematological toxicity. There were no treatment-related deaths. Conclusions: Postoperative alkylator intensification with high-dose cyclophosphamide and melphalan in patients with localized osteosarcoma with poor histological response failed to improve survival.

Original languageEnglish (US)
Pages (from-to)412-417
Number of pages6
JournalPediatric Blood and Cancer
Volume63
Issue number3
DOIs
StatePublished - Mar 1 2016

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Keywords

  • Clinical trials
  • High-dose chemotherapy
  • Necrosis
  • Osteosarcoma
  • Stem cell transplantation

ASJC Scopus subject areas

  • Pediatrics, Perinatology, and Child Health
  • Hematology
  • Oncology

Cite this

Venkatramani, R., Murray, J., Helman, L., Meyer, W., Hicks, M. J., Krance, R., Lau, C., Jo, E., & Chintagumpala, M. (2016). Risk-Based Therapy for Localized Osteosarcoma. Pediatric Blood and Cancer, 63(3), 412-417. https://doi.org/10.1002/pbc.25808