Abstract 5034: Quantification of required surgical margins in a xenograft osteosarcoma model with and without single-agent chemotherapy.
Authors: Geller David S. , Singh Michael , Zhang Wendong , Vilanueva-Siles Esperanza , Park Amy , Piperdi Sajida , Gorlick Richard 
Published: August 2014

Abstract
In addition to systemic therapy, complete surgical excision is essential for successful treatment of osteosarcoma. Currently, the gold standard is to perform a "wide excision," however the definition of a wide excision is descriptive only. There is no current clear consensus on what constitutes an adequate "wide excision." The purpose of this project is to quantify an adequate "wide excision," defined by lack of local and/or distant recurrence using a xenograft murine model both with and without single agent chemotherapy. Patient-derived osteosarcoma tumor cells (OS17 and 187) were cultured and surgically implanted into the proximal metaphyseal tibia of female SCID mice. Once tumors were papable, amputations were performed under general anesthesia in either an intralesional, marginal, or wide manner. Histological sectioning was conducted in a standardized fashion to obtain measurements of bone and soft tissue margins. Mice were followed for six weeks, after which amputation stumps were evaluated for local recurrence while both the lungs and livers were assessed for metastatic dissemination. Thereafter, a second group of mice underwent implantation and amputation as previously described. They were thereafter treated with either cisplatin or doxorubicin over a course 4 weeks and followed for an additional 6 weeks to identify local and distant recurrence. In mice implanted with either OS17 or 187 and treated without chemotherapy, surgical bone margins lower than 100μm reliably resulted in local recurrence while margins greater than 700μm showed no recurrence. A variable recurrence rate was found between margins of 100μm and 700 μm. Similarly, soft-tissue margins below 50μm reliably resulted in local recurrence while margins greater then 600μm showed no recurrence. In mice implanted with OS17 and thereafter treated with chemotherapy, no recurrence was seen above bone or soft-tissue margins of 14μm while mice implanted with 187 showed no recurrence above bone margins of 25μm or soft tissue margins above 10μm. Metastatic disease did not overtly develop and may require a longer period of observation. In conclusion, single agent chemotherapy appears to reliably decrease the surgical margin required to obtain adequate local control in this xenograft model. Combination chemotherapy may prove to further decrease necessary margins, which ultimately may have ramifications on surgical morbidity and long-term reconstructive and functional outcome for patients with localized high-grade osteosarcoma.
Citation Format: David S. Geller, Michael Singh, Wendong Zhang, Esperanza Vilanueva-Siles, Amy Park, Sajida Piperdi, Richard Gorlick. Quantification of required surgical margins in a xenograft osteosarcoma model with and without single-agent chemotherapy. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 5034. doi:10.1158/1538-7445.AM2013-5034