Ewing sarcoma – current diagnostic and therapeutic approaches

Czech version

Authors: A. Nohejlová Medková; P. Pacas; K. Kopečková
Authors‘ workplace: Onkologická klinika 2. LF UK a FN Motol a Homolka, Praha
Published in: Klin Onkol 2026; 39(2): 99-104
Category: Review
doi: https://doi.org/10.48095/ccko202699

Overview

Background: Ewing sarcoma belongs to the family of undifferentiated small round cell sarcomas of bone and soft tissue. It is characterized by a gene fusion involving EWSR1 and an ETS-family transcription factor gene. In 85–96% of cases, a specific chromosomal translocation results in the EWSR1-FLI1 fusion gene, whose product functions as an oncogene essential for tumorigenesis. Ewing sarcoma is most common in adolescents and young adults. It primarily affects the diaphyses of long bones, the pelvis, and the axial skeleton, although extraosseous involvement is not uncommon. This is a highly malignant neoplasm, and in most cases, micrometastases are already present at the time of diagnosis. The treatment is multimodal and includes local therapy (surgery and/or radiotherapy) and systemic chemotherapy. One of the greatest therapeutic challenges remains the long-term systemic control of the disease. To improve overall survival –⁠ especially in high-risk patients –⁠ innovative treatment strategies are essential, as the potential for intensifying chemotherapy has reached its limit due to treatment-related toxicity. Both diagnostic and therapeutic management should take place in specialized sarcoma centers. Aim: This article aims to provide an up-to-date overview of current diagnostic and therapeutic approaches in Ewing sarcoma.

Keywords:

Chemotherapy – Ewing sarcoma – targeted therapy

Sources

1. AACR. Founder James Ewing. [online]. Available from: https: //www.aacr.org/governance/james-ewing/.

2. Fernández CM, Sebio A, Rincon JO et al., Clinical practice guidelines for the treatment of Ewing sarcoma (Spanish Sarcoma Research Group-GEIS). Clin Transl Oncol 2025; 27 (3): 824–836. doi: 10.1007/s12094-024 -⁠ 03602-5.

3. Bílek O, Holánek M, Zvaríková M et al. Extraoseus Ewings sarcoma, primary affection of uterine cervix –⁠ case report. Klin Onkol 2015; 28 (4): 284–287. doi: 10.14735/amko2015284.

4. Král M, Kurfürstová D, Hartmann I et al. Ewing’s sarcoma of the urinary bladder –⁠ the urologic and pathologic differential diagnosis and current therapeutic options. Klin Onkol 2023; 36 (4): 314–319.

5. Zöllner SK, Amatruda JF, Bauer S et al. Ewing sarcoma –⁠ diagnosis, treatment, clinical challenges and future perspectives. J Clin Med 2021; 10 (8): 1685. doi: 10.3390/jcm10081685.

6. Procházka P, Vícha A, Kodet R et al. Nádory ze skupiny Ewingova sarkomu –⁠ molekulární biologie a genetika. Klin Onkol 2007; 20 (2): 205–208.

7. Dehner CA, Lazar AJ, Chrisinger JSA. Updates on WHO classification for small round cell tumors: Ewing sarcoma vs. everything else. Hum Pathol 2024; 147 : 101–113. doi: 10.1016/j.humpath.2024.01.007.

8. Gupta A, Riedel RF, Shah C et al. Consensus recommendations in the management of Ewing sarcoma from the National Ewing Sarcoma Tumor Board. Cancer 2023; 129 (21): 3363–3371. doi: 10.1002/cncr.34942.

9. Brennan B, Kirton L, Perrine MB et al. Comparison of two chemotherapy regimens in patients with newly diagnosed Ewing sarcoma (EE2012): an open-label, randomised, phase 3 trial. Lancet 2022; 400 (10362): 1513–1521. doi: 10.1016/S0140-6736 (22) 01 790-1.

10. Krákorová Adámková D, Tuček Š, Tomášek J et al. Léčba Ewingova sarkomu/periferního neuroektodermálního tumoru dospělých. Onkologie 2012; 6 (2): 91–95.

11. UCL. rEECur. [online]. Dostupné z: https: //www.ucl.ac.uk/medical-sciences/divisions/cancer/centres-and-networks/euro-ewing-consortium/clinical-trials/reecur.

12. Italiano A, Mir O, Mathoulin-Pelissier S et al. Cabozantinib in patients with advanced Ewing sarcoma or osteosarcoma (CABONE): a multicentre, single-arm, phase 2 trial. Lancet Oncol 2020; 21 (3): 446–455. doi: 10.1016/S1470-2045 (19) 30825-3.

13. Duffaud F, Blay JY, Le Cesne A et al. Regorafenib in patients with advanced Ewing sarcoma: results of a non-comparative, randomised, double-blind, placebo-controlled, multicentre Phase II study. Br J Cancer 2023; 129 (12): 1940–1948. doi: 10.1038/s41416-023-02 413-9.

14. Federico SM, Pappo AS, Sahr N et al. A phase I trial of talazoparib and irinotecan with and without temozolomide in children and young adults with recurrent or refractory solid malignancies. Eur J Cancer 2020; 137 : 204–213. doi: 10.1016/j.ejca.2020.06.014.

15. Guenther LM, Dharia NV, Ross L et al. A combination CDK4/6 and IGF1R inhibitor strategy for Ewing sarcoma. Clin Cancer Res 2019; 25 (4): 1343–1357. doi: 10.1158/1078-0432.CCR-18-0372.

16. Evdokimova V, Gassmann H, Radvanyi L et al. Current state of immunotherapy and mechanisms of immune evasion in Ewing sarcoma and osteosarcoma. Cancers 2022; 15 (1): 272. doi: 10.3390/cancers15010272.

17. Geen D, van Ewijk R, Tirtei E et al. Biological sample collection to advanced research and treatment: a fight osreosarcoma through European Research and Euro Ewing Consortium Statement. Clin Cancer Res 2024; 30 (16): 3395–3406. doi: 10.1158/1078-0432.CCR-24-0101.

18. Chicón-Bosch M, Sanchéz-Serra S, Rosàs-Lapeña M et al. Multi-omics profiling reveals key factors involved in Ewing sarcoma metastasis. Mol Oncol 2025; 19 (4): 1002–1028. doi: 10.1002/1878-0261.13788.

19. Anderton J, Moroz V, Marec-Bérard P et al. International randomised controlled trial for the treatment of newly diagnosed EWING sarcoma family of tumours –⁠ EURO EWING 2012 Protocol. Trials 2020; 21 (1): 96. doi: 10.1186/s13063-019-4026-8.