Ewing sarcoma family of tumors

As the second most common bone malignancy in children and adolescents, Ewing sarcoma family tumors (ESFT) represent a clinically heterogeneous group of tumors that harbor a near-universal chromosomal translocation of the EWSR1 gene, which partners with one of several ETS genes to produce an oncogenic fusion protein (classically EWS-FLI1) that functions as an aberrant transcription factor. Though the 5-year survival rate for those diagnosed with metastatic disease at the time of diagnosis has remained stubbornly low for more than four decades at approximately 20-25%, an aggressive multidisciplinary approach that integrates surgery, radiation therapy, chemotherapy, and supportive care has markedly improved the likelihood of survival for patients with localized disease to almost 75%. Herein, we focus initially on the clinical features and biology of ESFT, with subsections that relate to epidemiology, clinical presentation, pathogenesis, diagnosis, staging, and prognostic features, before concluding with a summary of the latest treatment guidelines and nascent therapeutic targets that have recently emerged. Given the relative rarity of ESFT and recent trend towards precision-guided therapies capable of inducing sometimes-dramatic tumor regression among a subset of patients, referral to a tertiary care center that specializes in the treatment of ESFT is recommended; this is particularly important when tumors have recurred or metastasized - scenarios where experimental therapies may help prolong survival.