Durer Seren, Gasalberti David P., Shaikh Hira
SUNY Upstate Medical University
Inspira Health Network
Ewing sarcoma is an aggressive tumor of adolescents and young adults, constituting 10% to 15% of all bone sarcomas. James Ewing first described this condition in 1921. Ewing sarcoma represents 'classic' Ewing sarcoma of bone, extra-skeletal Ewing sarcoma, malignant small cell tumor of the chest wall (Askin tumor), and soft tissue-based primitive neuroectodermal tumors. Due to their similar histologic and immunohistochemical characteristics, these sarcomas originate from unique mesenchymal progenitor cells. Ewing sarcoma family tumors are characterized by non-random chromosomal translocations producing fusion genes that encode aberrant transcription factors. The t(11;22)(q24;q12) translocation is associated with 85% of tumors and leads to EWS-FLI-1 formation, whereas t(21;12)(22;12) and other less common translocations induced fusion comprises the remaining 10% to 15% of cases. The most commonly affected anatomical sites include the pelvis, axial skeleton, and femur; however, Ewing sarcoma may occur in almost any bone or soft tissue. Typically, patients present with pain and swelling over the site of involvement. Over the last 40 years, both local therapy and multiagent adjuvant chemotherapy have achieved considerable progress in the treatment of localized disease that improved the 5-year survival rate from less than 20% to greater than 70%, but the recurrence rate remains high. However, most present locally, and subclinical metastatic disease is present in almost all cases. Approximately 25% of patients with initially localized disease ultimately relapse. No standard therapy exists for relapsed and refractory Ewing sarcoma, with survival rates being less than 30% in those with isolated lung metastases and less than 20% in those with bone and bone marrow involvement. Given the considerations of toxicity and suboptimal survival from metastatic disease, there is an urgent unmet need to develop novel therapies for Ewing sarcoma.
尤因肉瘤是青少年和年轻成年人的一种侵袭性肿瘤，占所有骨肉瘤的10%至15%。詹姆斯·尤因于1921年首次描述了这种疾病。尤因肉瘤包括骨的“经典”尤因肉瘤、骨外尤因肉瘤、胸壁恶性小细胞瘤（阿斯金瘤）以及软组织型原始神经外胚层肿瘤。由于它们具有相似的组织学和免疫组化特征，这些肉瘤起源于独特的间充质祖细胞。尤因肉瘤家族性肿瘤的特征是产生编码异常转录因子的融合基因的非随机染色体易位。t(11;22)(q24;q12)易位与85%的肿瘤相关，导致EWS-FLI-1形成，而t(21;12)(22;12)和其他不太常见的易位诱导的融合占其余10%至15%的病例。最常受累的解剖部位包括骨盆、中轴骨骼和股骨；然而，尤因肉瘤几乎可发生于任何骨骼或软组织。通常，患者在受累部位出现疼痛和肿胀。在过去40年中，局部治疗和多药辅助化疗在局限性疾病的治疗方面都取得了显著进展，将5年生存率从不超过20%提高到了超过70%，但复发率仍然很高。然而，大多数肿瘤最初为局部性，几乎所有病例都存在亚临床转移性疾病。约25%最初为局限性疾病的患者最终会复发。复发性和难治性尤因肉瘤尚无标准治疗方法，孤立性肺转移患者的生存率低于30%，骨和骨髓受累患者的生存率低于20%。考虑到转移性疾病的毒性和生存效果欠佳，迫切需要开发针对尤因肉瘤的新疗法。
