Purpose. Extraskeletal chondrosarcoma is a rare tumor with an indolent course and high propensity for local recurrence and metastasis. This tumor most commonly presents in the proximal extremities of middle-aged males, and is commonly asymptomatic. Although slow growing, these tumors have a significant risk of eventual relapse and metastases, especially to the lung. There are no clinical trials that investigated the best treatment options for this tumor given its very low incidence. The aim of this study is to present the surgical and clinical results of extraskeletal chondrosarcoma, which is a rare tumor. Methods. In our clinic, the information of 13 patients who were diagnosed with extra-skeletal chondrosarcoma between 2006 and 2018 were retrospectively reviewed. Demographic information, tumor size, surgical treatments, chemotherapy and radiotherapy status, follow-up times, recurrence and metastases of the patients were recorded. Results. This study included 13 patients with an average age of 53.6 ± 15 (range, 28 to 73) years diagnosed with extraskelatal chondrosarcoma. In 8 of the patients, the tumor was located in the lower limbs and it was observed that the thigh was located mostly (46.2%). The mean follow-up period of the patients was 52.8 ± 19.9 (range, 24 to 96) months. All patients underwent extensive resection and only one patient had a positive surgical margin. In the follow-up, 5 (38.5%) of the patients developed recurrence, while 6 patients had lung metastasis (46.2%) and 53.8% (7 patients) of the patients exitus. The mean tumor size was 10.4 ± 3.2 (range, 5 to 17) cm. The median survival time of the patients in the study was 61 (50.5–71.4) months. The 5-year survival rate is 51.8%. There was no significant difference between survival times according to age, gender, side, limb location, postoperative RT, recurrence and presence of lung metastasis (log rank tests p > 0.05). The cut off value for exitus obtained by ROC analysis of tumor size was determined as 11 cm (fig 1). Accordingly, the survival time of patients with 11 cm and above tumor size was observed to be statistically significantly shorter. Conclusion. Consequently, ECM is a rare soft tissue sarcoma with high local recurrence and metastasis capacity. Therefore, close follow-up is recommended. The first option should be extensive resection. Studies with large patient series on the prognostic factors of the future ECM are needed. For any figures or tables, please contact the authors directly

Summary Statement. Combination of sorafenib with irradiation achieved synergistic effect with dose reduction in both 143B and HOS cell lines. This demonstrated the potential application of sorafenib in the treatment of osteosarcoma metastasis and radiation resistance. Introduction. More than 20% of patients with osteosarcoma die of the disease within 5 years due to tumour relapse and metastasis. Identifying new treatment that works singly or in combination with conventional therapies is urgently required. We previously found that the Ras/Raf/MAPK pathway was associated with lung metastasis in a 143B inoculated osteosarcoma orthotopic mouse model. 1. Sorafenib, a multi-kinase inhibitor, has shown potent anticancer effect including in osteosarcoma. 2. through the inhibition of Raf-1 and other targets. 3. The aims of this study were to investigate effect of sorafenib on osteosarcoma cell lines with or without activated Ras/Raf/MAPK signalling and to decide whether sorafenib could enhance irradiation on these cells. Materials and Methods. Osteosarcoma cell lines 143B (HOS with Ras gene transfection), HOS and U2OS were used. Clonogenic assay was applied for assessing tumour growth and colony formation with or without treatment. Sorefenib was provided by Bayer gratis. Irradiation was performed using the Therapax DXT300 Orthovoltage Radiation System (Pantak, Connecticut, USA). Three doses of sorafenib (1, 2, 4 ug/ml) and three doses of radiation (50, 100, 200 cGy) were used with vehicle controls. In the combination therapy sorafenib was given at pre-, concurrent and post-irradiation. Each treatment was duplicated with the experiment being repeated once. Results. Sorafenib monotherapy achieved 50% inhibition (EC50) effects in all three tested cell lines with 7.05 ug/ml for 143B, 1.59 for HOS and 2.41 for U2OS. The 143B cell line was seriously resistant to irradiation with EC50 of 167 Gy, whilst other cell lines were relatively sensitive (HOS, 1.5 Gy and U2OS, 1.0 Gy). Combination of sorafenib with irradiation achieved synergistic effect with dose reduction in both 143B and HOS cell lines, but no obvious effect in U2OS cells. Discussion. Sorafenib demonstrated inhibitory effects on cell growth and colony formation even in a Ras/Raf/MAPK signalling activated osteosarcoma cell line, suggesting its potential application in the treatment of some metastatic osteosarcoma. Activated Ras/Raf/MAPK signalling is one of the mechanisms of radiation resistance and the synergistic effect of soratenib with irradiation combination therapy in this cell population indicated it's potential application in the treatment of irradiation resistant osteosarcoma. The dose reduction achieved by this combination could benefit patients with less specific side effects