Abstract

Introduction Extra-skeletal Ewing sarcoma is a rare malignant tumor, and current international recommendations indicate systemic and local treatment like bone Ewing sarcoma; to the best of our knowledge, very few studies tried to explore the clinical and genetic characteristics of this tumor and the most appropriate treatment strategy remains uncertain. Methods We reviewed 35 extra-skeletal Ewing sarcoma (EEwS) cases enrolled at Rizzoli Orthopedic Institute in Bologna, Italy between 1988-2022. We performed RNA sequencing in 18 Ewing sarcoma cases, including 12 bone Ewing sarcomas (BEwS) and 6 EEwS. We analyzed overall survival (OS), local relapse-free survival (LRFS), and metastasis-free survival (MFS) and the risk factors associated to survival. Results Unsupervised Hierarchical clustering showed no differences in the transcriptional profile between EEwS and BEwS. Five-year OS was 67% (95%CI 47-80), 5-year LRFS was 61% (95% CI 43-75), and 5-year MFS was 55% (95% CI 38-70). Recurrent tumors, larger than 8 cm, and elevated LDH serum value resulted to be a negative prognostic factor. Conclusions The founding of a genetic profile indistinguishable between EEwS and BEwS, confirms the view that includes the two subgroups in the same tumor entity and supports the use of a single therapeutic approach for Ewing sarcoma independently from the site of origin. Statistical evaluation showed that size bigger than 8cm, elevated LDH, and recurrent tumors had a worse prognosis, suggesting a risk-stratification method for identifying patients for specific therapy treatment. However, larger, multicentre, prospective trials are called for to validate our findings.