Development of aModel System to Evaluate Local Recurrence in Osteosarcoma and Assessment of the Effects of Bone Morphogenetic Protein-2 DavidS.Geller,MichaelY. Singh,WendongZhang, JonathanGill,MichaelE.Roth,

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 mm resulted in local control following surgery alone. Margins greater than 36 mm resulted in local control following surgery and single-agent chemotherapy. Margins greater than 12 mm 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. Clin Cancer Res; 21(13); 3003–12. 2014 AACR. See related commentary by Weiss, p. 2889