Ewing sarcoma: diagnosis, combination therapy. Literature review
https://doi.org/10.21294/1814-4861-2025-24-4-134-146
Abstract
Purpose of the study: to conduct a systemic literature review regarding current diagnosis and treatment strategies for ewing sarcoma (ES).
Material and Methods. The search for material for the review was conducted in the Medline, Web of science and Russian science Citation Index libraries. a total of 352 sources published during the period from 2004 to 2024 were selected for the analysis. The review was based on 67 publications.
Results. While surgery and radiation therapy have been crucial in treating ES, the introduction of chemotherapy has significantly improved patient outcomes. Many effective multidrug chemotherapy regimens developed in the 1960s and 1970s are still used as induction therapy for ES patients today. Much attention is paid to the problem of treating patients with relapses and refractory disease that are poorly responsive to chemotherapy. Currently, studies are underway to assess the feasibility of combining cytostatics with tyrosine kinase inhibitors, Dna repair inhibitors, inhibitors of other molecules, and autologous vaccines. available data regarding the effectiveness of high-dose chemotherapy with autologous transplantation and CaR-t cell therapy are contradictory. an obstacle to getting relatively rapid results from these studies is the small number of patients, which dictates the need for multi-center patient recruitment. In addition, the increased requirements of state regulatory bodies due to the childhood and adolescence of a large proportion of patients leave their mark.
Conclusion. Despite significant advances in the treatment of primary localized ewing sarcoma, the treatment results of metastatic disease and relapses are far from satisfactory. While the possibilities of cytostatic therapy appear to be exhausted, molecular targeting drugs have not yet received convincing evidence of clinical significance. However, future advances in treatment should still be expected from drugs that target the key points of the ES oncogenesis.
About the Authors
N. A. Falaleeva
A. Tsyb Medical Radiological Research Center – branch of the National Medical Research Radiological Centre, Ministry of Health of Russia
Russian Federation
Russian Federation
Natalia A. Falaleeva, MD, DSc, Head of the Department of Antitumor Drug Treatment of Malignant Neoplasms; Professor, Department of Internal Medicine, Obninsk Institute of Atomic Energy – branch of the National Research Nuclear University “MEPhI”
10, Marshal Zhukov st., Obninsk, 249031
A. A. Danilenko
A. Tsyb Medical Radiological Research Center – branch of the National Medical Research Radiological Centre, Ministry of Health of Russia
Russian Federation
Russian Federation
Anatoly A. Danilenko, MD, DSc, Senior Researcher, Department of Radiation and Drug Treatment of Hemoblastosis
10, Marshal Zhukov st., Obninsk, 249031
M. G. Syadrin
A. Tsyb Medical Radiological Research Center – branch of the National Medical Research Radiological Centre, Ministry of Health of Russia
Russian Federation
Russian Federation
Maxim G. Syadrin, MD, Oncologist, Department of Bone Marrow Transplantation
10, Marshal Zhukov st., Obninsk, 249031
References
1. Amadeo B., Penel N., Coindre J.-M., Ray-Coquard I., Ligier K., Delafosse P., Bouvier A.-M., Plouvier S., Gallet J., Lacourt A., Coureau G., Monnereau A., Mathoulin-Pélissier S., Desandes E. Incidence and time trends of sarcoma (2000–2013): results from the French network of cancer registries (FRANCIM). BMC Cancer. 2020; 20 (1): 190. doi: 10.1186/s12885-020-6683-0.
2. Kilpatrick S.E., Reith J.D., Rubin B. Ewing Sarcoma and the History of Similar and Possibly Related Small Round Cell Tumors: From Whence Have We Come and Where are We Going? Adv Anat Pathol. 2018; 25(5): 314–26. doi: 10.1097/PAP.0000000000000203.
3. Grünewald T.G.P., Bernard V., Gilardi-Hebenstreit P., Raynal V., Surdez D., Aynaud M.-M., Mirabeau O., Cidre-Aranaz F., Tirode F., Zaidi S., Perot G., Jonker A.H., Lucchesi C., Le Deley M.-C., Oberlin O., Marec-Bérard P., Véron A.S., Reynaud S., Lapouble E., Boeva V., Frio T.R., Alonso J., Bhatia S., Pierron G., Cancel-Tassin G., Cussenot O., Cox D.G., Morton L.M., Machiela M.J., Chanock S.J., Charnay P., Delattre O. Chimeric EWSR1-FLI1 regulates the Ewing sarcoma susceptibility gene EGR2 via a GGAA microsatellite. Nat Genet. 2015; 47(9): 1073–78. doi: 10.1038/ng.3363.
4. Eaton B.R., Claude L., Indelicato D.J., Vatner R., Yeh B., Schwarz R., Laack N. Ewing sarcoma. Pediatr Blood Cancer. 2021; 68 Suppl 2: e28355. doi: 10.1002/pbc.28355.
5. Shashaa M.N., Alkarrash M.S., Kitaz M.N., Hawash S., Otaqy M.B., Tarabishi J., Rhayim R., Alloush H. Ewing’s sarcoma in scapula, epidemiology, clinical manifestation, diagnosis and treatment: A literature review. Ann Med Surg (Lond). 2022; 77: 103617. doi: 10.1016/j.amsu.2022.103617.
6. Spector L.G., Hubbard A.K., Diessner B.J., Machiela M.J., Webber B.R., Schiffman J.D. Comparative international incidence of Ewing sarcoma 1988 to 2012. Int J Cancer. 2021; 149(5): 1054–66. doi: 10.1002/ijc.33674.
7. Soft Tissue and Bone Tumours: WHO Classification of Tumours. 2020. 5th ed., vol. 3. ISBN: 978-92-832-4502-5.
8. Yoshida A. Ewing and Ewing-like sarcomas: A morphological guide through genetically-defined entities. Pathol Int. 2023; 73(1): 12–26. doi: 10.1111/pin.13293.
9. McCuiston A., Bishop J.A. Usefulness of NKX2.2 Immunohistochemistry for Distinguishing Ewing Sarcoma from Other Sinonasal Small Round Blue Cell Tumors. Head Neck Pathol. 2018; 12(1): 89–94. doi: 10.1007/s12105-017-0830-1.
10. Toki S., Wakai S., Sekimizu M., Mori T., Ichikawa H., Kawai A., Yoshida A. PAX7 immunohistochemical evaluation of Ewing sarcoma and other small round cell tumours. Histopathology. 2018; 73(4): 645–52. doi: 10.1111/his.13689.
11. Wang G.Y., Thomas D.G., Davis J.L., Ng T., Patel R.M., Harms P.W., Betz B.L., Schuetze P.M., McHugh J.B., Horvai A.E., Cho S-J., Lucas D.R. EWSR1-NFATC2 Translocation-associated Sarcoma Clinicopathologic Findings in a Rare Aggressive Primary Bone or Soft Tissue Tumor. Am J Surg Pathol. 2019; 43(8): 1112–22. doi: 10.1097/PAS.0000000000001260.
12. Dehner C.A., Lazar A.J., Chrisinger J.S.A. Updates on WHO classification for small round cell tumors: Ewing sarcoma vs. everything else. Hum Pathol. 2024; 147:101–13. doi: 10.1016/j.humpath.2024.01.007.
13. Tsuda Y., Dickson B.C., Swanson D., Sung Y.-S., Zhang L., Meyers P., Healey J.H., Antonescu C.R. Ewing sarcoma with FEV gene rearrangements is a rare subset with predilection for extraskeletal locations and aggressive behavior. Genes Chromosomes Cancer. 2020; 59(5): 286–94. doi: 10.1002/gcc.22828.
14. Fernández C.M., Sebio A., Rincón J.O., Broto J.M., Benlloch A.M., Plaza D.M., Pousa A.L., Alegría I.G., Giuppi M., Ballesteros E.C., Bernabeu D., de Alava E., Morales C.V. Clinical practice guidelines for the treatment of Ewing sarcoma (Spanish Sarcoma Research Group-GEIS). Clin Transl Oncol. 2025; 27(3): 824–36. doi: 10.1007/s12094-024-03602-5.
15. Ferguson J.L., Turner S.P. Bone Cancer: Diagnosis and Treatment Principles. Am Fam Physician. 2018; 98 (4): 205–13.
16. Pizzo P., Poplack D., Adamson P., Blaney S., Helman L. Principles and practice of pediatric Oncology. Philadelphia. Wolters Kluwer, 2015. 7th ed. Faculty Bookshelf. ISBN: 9781451194234.
17. Kubo T., Furuta T., Johan M.P., Sakuda T., Ochi M., Adachi N. A meta-analysis supports core needle biopsy by radiologists for better histological diagnosis in soft tissue and bone sarcomas. Medicine (Baltimore, United States). 2018; 97(29): e11567. doi: 10.1097/MD.0000000000011567.
18. Aryal A., Kumar V.S., Shamim S.A., Gamanagatti S., Khan S.A. What Is the Comparative Ability of 18F-FDG PET/CT, 99mTc-MDP Skeletal Scintigraphy, and Whole-body MRI as a Staging Investigation to Detect Skeletal Metastases in Patients with Osteosarcoma and Ewing Sarcoma? Clin Orthop Relat Res. 2021; 479(8): 1768–79. doi: 10.1097/CORR.0000000000001681.
19. Fendler W.P., Chalkidis R.P., Ilhan H., Knösel T., Herrmann K., Issels R.D., Bartenstein P., Cyran C.C., Lindner L.H., Hacker M. Evaluation of several FDG PET parameters for prediction of soft tissue tumour grade at primary diagnosis and recurrence. Eur Radiol. 2015; 25(8): 2214–21. doi: 10.1007/s00330-0153654-y.
20. Hwang J.P., Lim I., Kong C.B., Jeon D.G., Byun B.H., Kim B.I., Choi C.W., Lim S.M. Prognostic value of SUVmax measured by pretreatment Fluorine-18 fluor odeoxyglucose positron emission Tomography/ Computed tomography in patients with Ewing sarcoma. PLoS One. 2016; 11(4): e0153281. doi: 10.1371/journal.pone.0153281.
21. Raciborska A., Bilska K., Drabko K., Michalak E., Chaber R., Pogorzała M., Połczyńska K., Sobol G., Wieczorek M., Muszyńska-Rosłan K., Rychlowska-Pruszyńska M., Rodriguez-Galindo C., Dziuk M. Response to chemotherapy estimates by FDG PET is an important prognostic factor in patients with Ewing sarcoma. Clin Transl Oncol. 2016; 18(2): 189–95. doi: 10.1007/s12094-015-1351-6.
22. Andreani L., Ipponi E., Ruinato A.D., Lupi T., Di Sacco F., Volterrani D., Coccoli L., Capanna R. Can FDG-PET assess the response to chemotherapy and predict tissue necrosis in osteosarcoma and Ewing sarcoma? Folia Med (Plovdiv). 2024; 66(2): 196–202. doi: 10.3897/folmed.66.e117148.
23. Ning M.S., Perkins S.M., Borinstein S.C., Holt G.E., Stavas M.J., Shinohara E.T. Role of radiation in the treatment of non-metastatic osseous Ewing sarcoma. J Med Imaging Radiat Oncol. 2016; 60(1): 119–28. doi: 10.1111/1754-9485.12389.
24. Kubo T., Furuta T., Johan M.P., Adachi N., Ochi M. Percent slope analysis of dynamic magnetic resonance imaging for assessment of chemotherapy response of osteosarcoma or Ewing sarcoma: systematic review and meta-analysis. Skeletal Radiol. 2016; 45(9):1235–42. doi: 10.1007/s00256-016-2410-y.
25. Yadgarov M., Berikashvili L., Rakova E., Likar Y. 18 F-FDG PET Metabolic Parameters for the Prediction of Histological Response to Induction Chemotherapy in Osteosarcoma and Ewing Sarcoma: A Systematic Review and Network Meta-analysis. Clin Nucl Med. 2024; 49(12): 640–49. doi: 10.1097/RLU.0000000000005412.
26. Annovazzi A., Ferraresi V., Anelli V., Covello R., Vari S., Zoccali C., Biagini R., Sciuto R. [18F] FDG PET/CT quantitative parameters for the prediction of histological response to induction chemotherapy and clinical outcome in patients with localised bone and soft-tissue Ewing sarcoma. Eur Radiol. 2021; 31(9): 7012–21. doi: 10.1007/s00330-021-0741-w.
27. Jehanno N., Corradini N., Gaspar N., Brahmi M., Valentin T., Revon Rivière G., Lervat C., Probert J., Entz-Werle N., Mansuy L., Plantaz D., Rios M., Saumet L., Verité C., Castex M.P., Thebaud E., Cassou-Mounat T., Plissonnier A.S., Mosseri V., Cordero C., Laurence V. Role of (18)FFDG-PET/CT in the initial staging of very high-risk Ewing Sarcoma in a prospective multicentric Phase II Study: Is there still a place for bone marrow sampling? Br J Cancer. 2024; 131(10): 1605–12. doi: 10.1038/s41416-024-02864-8.
28. Campbell K.M., Shulman D.S., Grier H.E., DuBois S.G. Role of bone marrow biopsy for staging new patients with Ewing sarcoma: A systematic review. Pediatr Blood Cancer. 2021; 68(2): e28807. doi: 10.1002/pbc.28807.
29. Guinot A., Tabone-Eglinger S., Isnardi V., Bahri H., Surdez D., Delattre O., Pierron G., Villemeur M., Lapouble E., Brahmi M., Bouhamama A., Corradin M., Marec-Bérard P. Staging of newly diagnosed Ewing sarcoma: Results of bone marrow aspiration and biopsy versus (18) FDG-PET/CT imaging for bone marrow involvement. Eur J Cancer. 2023; 179: 56–64. doi: 10.1016/j.ejca.2022.11.002.
30. Hajjaj O.I., Corke L., Strahlendorf C., Hamilton S.N., Feng X., Simmons C.E. Treatment differences and long-term outcomes in adults and children with Ewing sarcoma. Cancer Epidemiol. 2024: 92: 102653. doi: 10.1016/j.canep.2024.102653.
31. Chan R.C., Sutow W.W., Lindberg R.D., Samuels M.L., Murray J.A., Johnston D.A. Management and results of localized Ewing’s sarcoma. Cancer. 1979; 43(3): 1001–6. doi: 10.1002/1097-0142(197903)43:3<1001::aidcncr2820430332>3.0.co;2-p.
32. Grier H.E., Krailo M.D., Tarbell N.J., Link M.P., Fryer C.J., Pritchard D.J., Gebhardt M.C., Dickman P.S., Perlman E.J., Meyers P.A., Donaldson S.S., Moore S., Rausen A.R., Vietti T.J., Miser J.S. Addition of ifosfamide and etoposide to standard chemotherapy for Ewing’s sarcoma and primitive neuroectodermal tumor of bone. N Engl J Med. 2003; 348(8): 694–701. doi: 10.1056/NEJMoa020890.
33. Granowetter L., Womer R., Devidas M., Krailo M., Wang C., Bernstein M., Marina N., Leavey P., Gebhardt M., Healey J., Shamberger R.C., Goorin A., Miser J., Meyer J., Arndt C.A., Sailer S., Marcus K., Perlman E., Dickman P., Grier H.E. Dose-intensified compared with standard chemotherapy for nonmetastatic Ewing sarcoma family of tumors: a Children’s Oncology Group Study. J Clin Oncol. 2009; 27(15): 2536–41. doi: 10.1200/JCO.2008.19.1478.
34. Womer R.B., West D.C., Krailo M.D., Dickman P.S., Pawel B.R., Grier H.E., Marcus K., Sailer S., Healey J.H., Dormans J.P., Weiss A.R. Randomized controlled trial of interval-compressed chemotherapy for the treatment of localized Ewing sarcoma: a report from the Children’s Oncology Group. J Clin Oncol. 2012; 30(33): 4148–54. doi: 10.1200/JCO.2011.41.5703.
35. CashT., KrailoM.D., BuxtonA.B., PawelB.R., HealeyJ.H., Binitie O., Marcus K.J., Grier H.E., Grohar P.J., Reed D.R., Weiss A.R., Gorlick R., Janeway K.A., DuBois S.G., Womer R.B. Long-Term Outcomes in Patients With Localized Ewing Sarcoma Treated With Interval-Compressed Chemotherapy on Children’s Oncology Group Study AEWS0031. J Clin Oncol. 2023; 41(30): 4724–28. doi: 10.1200/JCO.23.00053.
36. Leavey P.J., Laack N.N., Krailo M.D., Buxton A., Randall R.L., DuBois S.G., Reed D.R., Grier H.E., Hawkins D.S., Pawel B., Nadel H., Womer R.B., Letson G.D., Bernstein M., Brown K., Maciej A., Chuba P., Ahmed A.A., Indelicato D.J., Wang D., Marina N., Gorlick R., Janeway K.A., Mascarenhas L. Phase III Trial Adding Vincristine-Topotecan-Cyclophosphamide to the Initial Treatment of Patients With Nonmetastatic Ewing Sarcoma: A Children’s Oncology Group Report. J Clin Oncol. 2021; 39(36): 4029–38. doi: 10.1200/JCO.21.00358.
37. Brunetto A.L., Castillo L.A., Petrilli A.S., Macedo C.D., Boldrini E., Costa C., Almeida M.T., Kirst D., Rodriguez-Galindo C., Pereira W.V., Watanabe F.M., Pizza M., Benites E., Morais V., Gadelha A., Nakasato A., Abujamra A.L., Gregianin L.J. Carboplatin in the treatment of Ewing sarcoma: Results of the first Brazilian collaborative study group for Ewing sarcoma family tumors-EWING1. Pediatr Blood Cancer. 2015; 62 (10): 1747–53. doi: 10.1002/pbc.25562.
38. Anderton J., Moroz V., Marec-Bérard P., Gaspar N., Laurence V., Martín-Broto J., Sastre A., Gelderblom H., Owens C., Kaiser S., FernándezPinto M., Fenwick N., Evans A., Strauss S., Whelan J., Wheatley K., Brennan B. 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.
39. Brennan B., Kirton L., Marec-Bérard P., Gaspar N., Laurence V., Martín-Broto J., Sastre A., Gelderblom H., Owens C., Fenwick N., Strauss S., Moroz V., Whelan J., Wheatley K. Comparison of two chemotherapy regimens in patients with newly diagnosed Ewing sarcoma (EE2012): an open-label, randomised, phase 3 trial. Lancet. 2022; 400(10362): 1513–21. doi: 10.1016/S0140-6736(22)01790-1.
40. Whelan J., Le Deley M.-C., Dirksen U., Teuff G.L., Brennan B., Gaspar N., Hawkins D.S., Amler S., Bauer S., Bielack S., Blay J.-Y., Burdach S., Castex M.-P., Dilloo D., Eggert A., Gelderblom H., Gentet J-C., Hartmann W., Hassenpflug W.-A., Hjorth L., Jimenez M., Klingebiel T., Kontny U., Kruseova J., Ladenstein R., Laurence V., Lervat C., MarecBerard P., Marreaud S., Michon J., Morland B., Paulussen M., Ranft A., Reichardt P., van den Berg H., Wheatley K., Judson I., Lewis I., Craft A., Juergens H., Oberlin O.; Euro-E.W.I.N.G.99 and EWING-2008 Investigators. High-Dose Chemotherapy and Blood Autologous Stem-Cell Rescue Compared With Standard Chemotherapy in Localized High-Risk Ewing Sarcoma: Results of Euro-E.W.I.N.G.99 and Ewing-2008. J Clin Oncol. 2018; 36(31): JCO2018782516. doi: 10.1200/JCO.2018.78.2516.
41. Koch R., Gelderblom H., Haveman L., Brichard B., Jürgens H., Cyprova S., van den Berg H., Hassenpflug W., Raciborska A., Ek T., Baumhoer D., Egerer G., Eich H.T., Renard M., Hauser P., Burdach S., Bovee J., Bonar F., Reichardt P., Kruseova J., Hardes J., Kühne T., Kessler T., Collaud S., Bernkopf M., Butterfaß-Bahloul T., Dhooge C., Bauer S., Kiss J., Paulussen M., Hong A., Ranft A., Timmermann B., Rascon J., Vieth V., Kanerva J., Faldum F., Metzler M., Hartmann W., Hjorth L., Bhadri V., Dirksen U. High-Dose Treosulfan and Melphalan as Consolidation Therapy Versus Standard Therapy for High-Risk (Metastatic) Ewing Sarcoma. J Clin Oncol. 2022; 40(21): 2307–20. doi: 10.1200/JCO.21.01942.
42. Dirksen U., Brennan B., Le Deley M.C., Cozic N., van den Berg H., Bhadri V., Brichard B., Claude L., Craft A., Amler S., Gaspar N., Gelderblom H., Goldsby R., Gorlick R., Grier H.E., Guinbretiere J.M., Hauser P., Hjorth L., Janeway K., Juergens H., Judson I., Krailo M., Kruseova J., Kuehne T., Ladenstein R., Lervat C., Lessnick S.L., Lewis I., Linassier C., Marec-Berard P., Marina N., Morland B., Pacquement H., Paulussen M., Randall R.L., Ranft A., Le Teuff G., Wheatley K., Whelan J., Womer R., Oberlin O., Hawkins D.S.; Euro-E.W.I.N.G. 99 and Ewing 2008 Investigators. High-Dose Chemotherapy Compared With Standard Chemotherapy and Lung Radiation in Ewing Sarcoma With Pulmonary Metastases: Results of the European Ewing Tumour Working Initiative of National Groups, 99 Trial and EWING 2008. J Clin Oncol. 2019; 37(34): 3192–202. doi: 10.1200/JCO.19.00915.
43. Luksch R., Tienghi A., Hall K.S., Fagioli F., Picci P., Barbieri E., Gandola L., Eriksson M., Ruggieri P., Daolio P., Lindholm P., Prete A., Bisogno G., Tamburini A., Grignani G., Abate M.E., Podda M., Smeland S., Ferrari S. Primary metastatic Ewing’s family tumors: results of the Italian Sarcoma Group and Scandinavian Sarcoma Group ISG/SSG IV Study including myeloablative chemotherapy and total-lung irradiation. Ann Oncol. 2012; 23(11): 2970–76. doi: 10.1093/annonc/mds117.
44. Dang A., Feng X., Hamm J., Holloway C.L., Truong P.T. Survival Outcomes in Metastatic Ewing Sarcoma Treated With Whole-Lung Radiation. Cureus. 2022; 14(7): e26750. doi: 10.7759/cureus.26750.
45. DuBois S.G., Krailo M.D., Glade-Bender J., Buxton A., Laack N., Randall R.L., Chen H.X., Seibel N.L., Boron M., Terezakis S., Hill-Kayser C., Hayes A., Reid J.M., Teot L., Rakheja D., Womer R., Arndt C., Lessnick S.L., Crompton B.D., Kolb E.A., Daldrup-Link H., Eutsler E., Reed D.R., Janeway K.A., Gorlick R.G. Randomized Phase III Trial of Ganitumab With Interval-Compressed Chemotherapy for Patients With Newly Diagnosed Metastatic Ewing Sarcoma: A Report From the Children’s Oncology Group. J Clin Oncol. 2023; 41(11): 2098–107. doi: 10.1200/JCO.22.01815.
46. Koscielniak E., Sparber-Sauer M., Scheer M., Vokuhl C., Kazanowska B., Ladenstein R., Niggli F., Ljungman G., Paulussen M., Bielack S.S., Seitz G., Fuchs J., Hallmen E., Klingebiel T. Extraskeletal Ewing sarcoma in children, adolescents, and young adults. An analysis of three prospective studies of the Cooperative Weichteilsarkomstudiengruppe (CWS). Pediatr Blood Cancer. 2021; 68(10): e29145. doi: 10.1002/pbc.29145.
47. Bisogno G., De Salvo G.L., Bergeron C., Melcón S.G., Merks J.H., Kelsey A., Martelli H., Minard-Colin V., Orbach D., Glosli H., Chisholm J., Casanova M., Zanetti I., Devalck C., Ben-Arush M., Mudry P., Ferman S., Jenney M., Ferrari A.; European paediatric Soft tissue sarcoma Study Group. Vinorelbine and continuous low-dose cyclophosphamide as maintenance chemotherapy in patients with high-risk rhabdomyosarcoma (RMS 2005): a multicentre, open-label, randomised, phase 3 trial. Lancet Oncol. 2019; 20(11): 1566–75. doi: 10.1016/S1470-2045(19)30617-5.
48. Duffaud F., Blay J.Y., Le Cesne A., Chevreau C., Boudou-Rouquette P., Kalbacher E., Penel N., Perrin C., Laurence V., Bompas E., Saada-Bouzid E., Delcambre C., Bertucci F., Cancel M., Schiffler C., Monard L., Bouvier C., Vidal V., Gaspar N., Chabaud S. 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): 1940–48. doi: 10.1038/s41416-023-02413-9.
49. DuBois S.G., Krailo M.D., Gebhardt M.C., Donaldson S.S., Marcus K.J., Dormans J., Shamberger R.C., Sailer S., Nicholas R.W., Healey J.H., Tarbell N.J., Randall R.L., Devidas M., Meyer J.S., Granowetter L., Womer R.B., Bernstein M., Marina N., Grier H.E. Comparative evaluation of local control strategies in localized Ewing sarcoma of bone: a report from the Children’s Oncology Group. Cancer. 2015; 121(3): 467–75. doi: 10.1002/cncr.29065.
50. Shamberger R.C., LaQuaglia M.P., Gebhardt M.C., Neff J.R., Tarbell N.J., Marcus K.C., Sailer S.L., Womer R.B., Miser J.S., Dickman P.S., Perlman E.J., Devidas M., Linda S.B., Krailo M.D., Grier H.E., Granowetter L. Ewing sarcoma/primitive neuroectodermal tumor of the chest wall: impact of initial versus delayed resection on tumor margins, survival, and use of radiation therapy. Ann Surg. 2003; 238(4): 563–67; discussion 567–68. doi: 10.1097/01.sla.0000089857.45191.52.
51. Ahmed S.K., Randall R.L., DuBois S.G., Harmsen W.S., Krailo M., Marcus K.J., Janeway K.A., Geller D.S., Sorger J.I., Womer R.B., Granowetter L., Grier H.E., Gorlick R.G., Laack N.N.I. Identification of Patients With Localized Ewing Sarcoma at Higher Risk for Local Failure: A Report From the Children’s Oncology Group. Int J Radiat Oncol Biol Phys. 2017; 99(5): 1286–94. doi: 10.1016/j.ijrobp.2017.08.020.
52. Wardelmann E., Haas R.L., Bovée J.V., Terrier P., Lazar A., Messiou C., LePechoux C., Hartmann W., Collin F., Fisher C., Mechtersheimer G., DeiTos A.P., Stacchiotti S., Jones R.L., Gronchi A., Bonvalot S. Evaluation of response after neoadjuvant treatment in soft tissue sarcomas; the European Organization for Research and Treatment of Cancer-Soft Tissue and Bone Sarcoma Group (EORTC-STBSG) recommendations for pathological examination and reporting. Eur J Cancer. 2016; 53: 84–95. doi: 10.1016/j.ejca.2015.09.021.
53. Callan A.K., Alexander J.H., Montgomery N.I., Lindberg A.W., Scharschmidt T.J., Binitie O. Contemporary surgical management of osteosarcoma and Ewing sarcoma. Pediatr Blood Cancer. 2025; 72 Suppl 2: e31374. doi: 10.1002/pbc.31374.
54. Alvarez-SanNicolas J., Gracia-Alegria I., Trullols-Tarrago L., Peiro-Ibañez A., Lamas-Gomez C. Prognostic factors and survival in Ewing’s sarcoma treated by limb salvage surgery. Clin Transl Oncol. 2019; 21(10): 1374–82. doi: 10.1007/s12094-019-02067-1.
55. HaeuslerJ., RanftA., BoellingT., GoshegerG., Braun-Munzinger G., Vieth V., Burdach S., van den Berg H., Juergens H., Dirksen U. The value of local treatment in patients with primary, disseminated, multifocal Ewing sarcoma (PDMES). Cancer. 2010; 116(2): 443–50. doi: 10.1002/cncr.24740.
56. Gerrand G., Bate J., Seddon B., Dirksen U., Randall R.L., van de Sande M., O’Donnell P., Tuckett J., Peake D., Jeys L., Saifuddin A., Grainger M., Whelan J. Seeking international consensus on approaches to primary tumour treatment in Ewing sarcoma. Clin Sarcoma Res. 2020; 10(1): 21. doi: 10.1186/s13569-020-00144-6.
57. Foulon S., Brennan B., Gaspar N., Dirksen U., Jeys L., Cassoni A., Claude L., Seddon B., Marec-Berard P., Whelan J., Paulussen M., Streitbuerger A., Oberlin O., Juergens H., Grimer R., Le Deley M.C. Can postoperative radiotherapy be omitted in localised standard-risk Ewing sarcoma? An observational study of the Euro-E.W.I.N.G. group. Eur J Cancer. 2016; 61: 128–36. doi: 10.1016/j.ejca.2016.03.075.
58. Kacar M., Nagel M.B., Liang J., Li Y., Neel M.D., Lucas M.T. Jr, McCarville M.B., Santiago T., Pappo A.S., Krasin M.J. Radiation therapy dose escalation achieves high rates of local control with tolerable toxicity profile in pediatric and young adult patients with Ewing sarcoma. Cancer. 2024; 130(10): 1836–43. doi: 10.1002/cncr.35196.
59. Laskar S., Sinha S., Chatterjee A., Khanna N., Manjali J.J., Puri A., Gulia A., Nayak P., Vora T., Chinnaswamy G., Prasad M., Bajpai J., Juvekar S., Desai S., Janu A., Rangarajan V., Purandare N., Shah S., Rekhi B., Jambhekar N., Muckaden M.A., Kurkure P. Radiation Therapy Dose Escalation in Unresectable Ewing Sarcoma: Final Results of a Phase 3 Randomized Controlled Trial. Int J Radiat Oncol Biol Phys. 2022; 113(5): 996–1002. doi: 10.1016/j.ijrobp.2022.04.024.
60. Paulussen M., Ahrens S., Craft A.W., Dunst J., Fröhlich B., Jabar S., Rübe C., Winkelmann W., Wissing S., Zoubek A., Jürgens H.J. Ewing’s tumors with primary lung metastases: survival analysis of 114 (European Intergroup) Cooperative Ewing’s Sarcoma Studies patients. Clin Oncol. 1998; 16(9): 3044–52. doi: 10.1200/JCO.1998.16.9.3044.
61. Scobioala S., Eich H.T. Risk stratification of pulmonary toxicities in the combination of whole lung irradiation and high-dose chemotherapy for Ewing sarcoma patients with lung metastases: a review. Strahlenther Onkol. 2020; 196(6): 495–504. doi: 10.1007/s00066-020-01599-8.
62. Granowetter L., Womer R., Devidas M., Krailo M., Wang C., Bernstein M., Marina N., Leavey P., Gebhardt M., Healey J., Shamberger R.C., Goorin A., Miser J., Meyer J., Arndt C.A., Sailer S., Marcus K., Perlman E., Dickman P., Grier H.E. Dose-intensified compared with standard chemotherapy for nonmetastatic Ewing sarcoma family of tumors: a Children’s Oncology Group Study. J Clin Oncol. 2009; 27(15): 2536–41. doi: 10.1200/JCO.2008.19.1478.
63. Collier A.B. 3rd, KrailoM.D., DangH.M., DuBoisS.G., Hawkins D.S., Bernstein M.L., Bomgaars L.R., Reed D.R., Gorlick R.D., Janeway K.A. Outcome of patients with relapsed or progressive Ewing sarcoma enrolled on cooperative group phase 2 clinical trials: A report from the Children’s Oncology Group. Pediatr Blood Cancer. 2021; 68(12): e29333. doi: 10.1002/pbc.29333.
64. Leavey P.J., Mascarenhas L., Marina N., Chen Z., Krailo M., Miser J., Brown K., Tarbell N., Bernstein M.L., Granowetter L., Gebhardt M., Grier H.E.; Children’s Oncology Group. Prognostic factors for patients with Ewing sarcoma (EWS) at first recurrence following multimodality therapy: A report from the Children’s Oncology Group. Pediatr Blood Cancer. 2008; 51(3): 334–8. doi: 10.1002/pbc.21618.
65. Xu J., Xie L., Sun X., Liu K., Liang X., Cai Z., Tang X., Guo W. Longer versus Shorter Schedules of Vincristine, Irinotecan, and Temozolomide (VIT) for Relapsed or Refractory Ewing Sarcoma: A Randomized Controlled Phase 2 Trial. Clin Cancer Res. 2023; 29(6): 1040–46. doi: 10.1158/1078-0432.CCR-22-3546.
66. Strauss S.J., Berlanga P., McCabe M.G. Emerging therapies in Ewing sarcoma. Curr Opin Oncol. 2024; 36(4): 297–304. doi: 10.1097/CCO.0000000000001048.
67. Lam P.Y., Omer N., Wong J.K.M., Tu C., Alim L., Rossi G.R., Victorova M., Tompkins H., Lin C.Y., Mehdi A.M., Choo A., Elliott M.R., Coleborn E., Sun J., Mercer T., Vittorio O., Dobson L.J., McLellan A.D., Brooks A., Tuong Z.K., Cheetham S.W., Nicholls W., Souza-Fonseca-Guimaraes F. Enhancement of anti-sarcoma immunity by NK cells engineered with mRNA for expression of a EphA2-targeted CAR. Clin Transl Med. 2025; 15(1): e70140. doi: 10.1002/ctm2.70140.
Review
For citations:
Falaleeva N.A., Danilenko A.A., Syadrin M.G. Ewing sarcoma: diagnosis, combination therapy. Literature review. Siberian journal of oncology. 2025;24(4):134-146. (In Russ.) https://doi.org/10.21294/1814-4861-2025-24-4-134-146
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