Development of a model system to evaluate local recurrence in osteosarcoma and assessment of the effects of bone morphogenetic protein-2

David S. Geller, Michael Y. Singh, Wendong Zhang, Jonathan Gill, Michael E. Roth, Mimi Y. Kim, Xianhong Xie, Christopher K. Singh, Howard D. Dorfman, Esperanza Villanueva-Siles, Amy Park, Sajida Piperdi, Richard Gorlick

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10 Scopus citations

Abstract

Purpose: It is increasingly relevant to better define what constitutes an adequate surgical margin in an effort to improve reconstructive longevity and functional outcomes following osteosarcoma surgery. In addition, nonunion remains a challenging problem in some patients following allograft reconstruction. Bone morphogenetic protein-2 (BMP-2) could enhance osseous union, but has been historically avoided due to concerns that it may promote tumor recurrence. Experimental Design: An orthotopic xenograft murine model was utilized to describe the natural temporal course of osteosarcoma growth. Tumors were treated either with surgery alone, surgery and single-agent chemotherapy, or surgery and dual-agent chemotherapy to assess the relationship between surgical margin and local recurrence. The effect of BMP-2 on local recurrence was similarly assessed. Results: Osteosarcoma tumor growth was categorized into reproducible phases. Margins greater than 997 um resulted in local control following surgery alone. Margins greater than 36 um resulted in local control following surgery and single-agent chemotherapy. Margins greater than 12 (xm resulted in local control following surgery and dual-agent chemotherapy. The application of exogenous BMP-2 does not confer an increased risk of local recurrence. Conclusions: This model reliably reproduces the clinical, radiographic, and surgical conditions encountered in human osteosarcoma. It successfully incorporates relevant chemotherapy, further paralleling the human experience. Surgical margins required to achieve local control in osteosarcoma can be reduced using single-agent chemotherapy and further decreased using dual-agent chemotherapy. The application of BMP-2 does not increase local recurrence in this model.

Original languageEnglish (US)
Pages (from-to)3003-3012
Number of pages10
JournalClinical Cancer Research
Volume21
Issue number13
DOIs
StatePublished - Jul 1 2015

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ASJC Scopus subject areas

  • Oncology
  • Cancer Research

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