Ewing Sarcoma Family Tumors: Past, Present and Future Prospects

Author(s): Adil Abbas*, Mohammed N.S. Alaa

Journal Name: Current Cancer Therapy Reviews

Volume 17 , Issue 2 , 2021


Become EABM
Become Reviewer
Call for Editor

Graphical Abstract:


Abstract:

Ewing’s sarcoma (ES), also known as mesenchymal primitive neuroectodermal tumor (PNET), is a malignant round blue cell tumor (MRBCT) with a varying degree of neuronal differentiation. PNET arises from the primitive nerve cells of the central nervous system (CNS) but may also occur in the bones of the extremities, pelvis, vertebral column, and chest wall. Extraskeletal ES/PNET may affect the various soft tissues, including those of the pelvis, paraspinal region, and thoracopulmonary region.

Histopathological differentiation between ES, PNET, and other related sarcomas is often difficult. On light microscopy, the same histopathological appearance of ES has been termed PNET, Askin- Rosay (A-R) tumor, and malignant neuroepithelioma by various other authors. The immunohistochemical distinction is also difficult due to poor tissue differentiation and low intake of the various specific immunohistochemical markers. The most frequent translocation is t (11; 22) (q24; q12), resulting in the EWSR1-FLI1 fusion gene detected in nearly 90% of cases and is considered the hallmark of the diagnosis of ES, PNET, atypical ES, and A-R tumor. Therefore, ES, atypical ES, PNET, and A-R tumor are currently regarded as one entity grouped together under the Ewing Family Tumor (EFT) and are treated in an identical way. EFT represents only about 3% of all pediatric malignancies. The annual incidence is between 2 and 5 cases per million children per year. The peak prevalence of the tumor is between the ages of 10 and 15 years. The incidence is higher in males than in females, with a ratio of 1.3:1.

Newer groups of MRBCT that have great similarities to EFT are being recently described. These tumors, atypical EFT and Ewing’s like Sarcomas (ELS), bear similarities to EFT but have basic morphological and molecular differences. Optimal treatment requires the use of adjuvant and new-adjuvant chemotherapy (CTR), radical surgical resection and/or involves field radiotherapy (RT). The reported disease-free survival (DFS) and overall survival (OS) range between 45-80% and 36-71%, respectively. The overall prognosis for the metastatic and recurrent disease remains poor. The use of newer conventional and targeted medications, improved RT delivery, and surgical techniques may further improve the outcomes. The past few years have seen advances in genomics-based sarcoma diagnosis and targeted therapies. In this comprehensive review article, we provide a detailed report of EFT and discuss the various clinical aspects and the recent advances used in the diagnosis and treatment.

Keywords: Chemotherapy, Ewing's sarcoma, EWSR1-FLI1 gene fusion, primitive neuroectodermal tumor, radiotherapy, srurgery.

[1]
Dancsok AR, Asleh-Aburaya K, Nielsen TO. Advances in sarcoma diagnostics and treatment. Oncotarget 2017; 8(4): 7068-93.
[http://dx.doi.org/10.18632/oncotarget.12548] [PMID: 27732970]
[2]
Forscher C, Mita M, Figlin R. Targeted therapy for sarcomas. Biologics 2014; 8: 91-105.
[http://dx.doi.org/10.2147/BTT.S26555] [PMID: 24669185]
[3]
Thanindratarn P, Dean DC, Nelson SD, Hornicek FJ, Duan Z. Advances in immune checkpoint inhibitors for bone sarcoma therapy. J Bone Oncol 2019; 15
[http://dx.doi.org/10.1016/j.jbo.2019.100221] [PMID: 30775238]
[4]
Gurney JG, Swensen AR, Bulterys M. Malignant bone tumors.Cancer incidence and survival among children and adolescents: United States SEER program 1975 – 1995. Bethesda, MD: National Cancer Institute, SEER Program NIH 1999; p. (99): 4649.
[5]
Ozaki T. Diagnosis and treatment of Ewing sarcoma of the bone: A review article. J Orthop Sci 2015; 20(2): 250-63.
[http://dx.doi.org/10.1007/s00776-014-0687-z] [PMID: 25691401]
[6]
Ewing J. Diffuse endothelioma of bone. Proceedings of the New York Pathology Society. 1921; 21: 17 – 24. CA Cancer J Clin 1972; 22(2): 95-8.
[http://dx.doi.org/10.3322/canjclin.22.2.95] [PMID: 4622125]
[7]
Lücke A. Beiträge zur Geschwulstlehre. Virchows. Arch Pathol Anat 1866; 35: 524-39.
[8]
Angervall L, Enzinger FM. Extraskeletal neoplasm resembling Ewing’s sarcoma Cancer 1975; 36(1): 240-51.
[9]
Nesbitt KA, Vidone RA. Primitive neuroectodermal tumor (neuroblastoma) arising in sciatic nerve of a child. Cancer 1976; 37(3): 1562-70.
[http://dx.doi.org/10.1002/1097-0142(197603)37:3<1562::AID-CNCR2820370346>3.0.CO;2-M] [PMID: 1260675]
[10]
Resnick D, Kyriakos M, Greenway G. Tumors and tumor-like lesions of bone: Imaging and pathology of specific lesions.Diagnosis of bone and joint disorders. Philadelphia, PA: Saunders 2002; pp. 4060-73.
[11]
Dorfman HD, Czerniak B. Ewing’s sarcoma and related entities.Bone tumors. St Louis, Mo: Mosby 1998; pp. 607-63.
[12]
Mohandas KM, Chinoy RF, Merchant NH, Lotliker RG, Desai PB. Malignant small cell tumour (Askin-Rosai) of the pericardium. Postgrad Med J 1992; 68(796): 140-2.
[http://dx.doi.org/10.1136/pgmj.68.796.140] [PMID: 1315028]
[13]
Xu Q, Xu K, Yang C, Zhang X, Meng Y, Quan Q. Askin tumor: Four case reports and a review of the literature. Cancer Imaging 2011; 11: 184-8.
[http://dx.doi.org/10.1102/1470-7330.2011.0025] [PMID: 22138531]
[14]
Seemayer TA, Thelmo WL, Bolande RP, Wiglesworth FW. Peripheral neuroectodermal tumors. Perspect Pediatr Pathol 1975; 2: 151-72.
[PMID: 1129029]
[15]
Lee WS, Kim YH, Chee HK, et al. Multimodal treatment of primary extraskeletal Ewing’s sarcoma of the chest wall: Report of 2 cases. Cancer Res Treat 2009; 41(2): 108-12.
[http://dx.doi.org/10.4143/crt.2009.41.2.108] [PMID: 19707510]
[16]
Fletcher CD, Hogendoorn P, Mertens F, Bridge J. WHO classification of tumours of soft tissue and bone. 4th ed. Lyon, France: IARC Press 2013.
[17]
Doyle LA. Sarcoma classification: An update based on the 2013 World Health Organization classification of tumors of soft tissue and bone. Cancer 2014; 120(12): 1763-74.
[http://dx.doi.org/10.1002/cncr.28657] [PMID: 24648013]
[18]
Tateishi U, Gladish GW, Kusumato M, et al. Chest wall tumors: Radiological findings and pathological correlation. Radiographics 2003; 23: 1491-508.
[http://dx.doi.org/10.1148/rg.236015527] [PMID: 14615560]
[19]
Shishikura A, Ushigome S, Shimoda T. Primitive neuroectodermal tumors of bone and soft tissue: Histological subclassification and clinicopathologic correlations. Acta Pathol Jpn 1993; 43(4): 176-86.
[http://dx.doi.org/10.1111/j.1440-1827.1993.tb01129.x] [PMID: 8388151]
[20]
Talleur AC, Navid F, Spunt SL, et al. Limited margin radiotherapy for children and young adults with Ewing’s sarcoma achieves high rate of local tumor control. Int J Radiat Oncol Biol Phys 2016; 96(1): 119-26.
[http://dx.doi.org/10.1016/j.ijrobp.2016.04.001] [PMID: 27319287]
[21]
Askin FB, Rosai J, Sibley RK, Dehner LP, McAlister WH. Malignant small cell tumor of the thoracopulmonary region in childhood: A distinctive clinicopathologic entity of uncertain histogenesis. Cancer 1979; 43(6): 2438-51.
[http://dx.doi.org/10.1002/1097-0142(197906)43:6<2438::AID-CNCR2820430640>3.0.CO;2-9] [PMID: 222426]
[22]
Li FP, Tu JT, Liu FS, Shiang EL. Rarity of Ewing’s sarcoma in China. Lancet 1980; 1(8180): 1255.
[http://dx.doi.org/10.1016/S0140-6736(80)91719-5] [PMID: 6104072]
[23]
Worch J, Matthay KK, Neuhaus J, Goldsby R, DuBois SG. Ethnic and racial differences in patients with Ewing sarcoma. Cancer 2010; 116(4): 983-8.
[http://dx.doi.org/10.1002/cncr.24865] [PMID: 20052725]
[24]
Fiorentino A, Chiumento C, Caivano R, Fusco V. Ewing sarcoma of the thoracic wall in a 54-year-old man. Tumori 2012; 98(1): e10-2.
[http://dx.doi.org/10.1177/030089161209800129] [PMID: 22495722]
[25]
Casaroto AR, DA Silva Sampieri MB, Soares CT, et al. Ewing’s sarcoma family tumors in the jaws: Case report, immunohistochemical analysis and literature review. In Vivo 2017; 31(3): 481-91.
[http://dx.doi.org/10.21873/invivo.11087] [PMID: 28438883]
[26]
Tazi I, Zafad S, Madani A, Harif M, Quessar A, Benchekroun S. Askin tumor: A case report with literature review Cancer Radiother 2009; 13(8): 771-4.
[http://dx.doi.org/10.1016/j.canrad.2009.05.016] [PMID: 19692278]
[27]
Takagi-Takahashi Y, Shijubo N, Yamada G, et al. Peripheral primitive neuroectodermal tumor of the chest wall of a 69-year-old man. Intern Med 2004; 43(7): 578-81.
[http://dx.doi.org/10.2169/internalmedicine.43.578] [PMID: 15335184]
[28]
Tanveer N, Kaur N, Mishra K, Wadhwa N, Singh N. Is it Askin tumour? A question you must ask even in elderly. J Clin Diagn Res 2014; 8(10): FD21-3.
[http://dx.doi.org/10.7860/JCDR/2014/9522.5030] [PMID: 25478359]
[29]
Wolpert F, Grotzer MA, Niggli F, Zimmermann D, Rushing E. Ewing’s sarcoma as a second malignancy in long-term survivors of childhood hematologic malignancies Sarcoma 2016; 11.
[30]
Parikh PM, Charak BS, Banavali SD, et al. Treatment of Askin Rosai tumor--need for a more aggressive approach. J Surg Oncol 1988; 39(2): 126-8.
[http://dx.doi.org/10.1002/jso.2930390212] [PMID: 2845198]
[31]
Dickinson J, Watts AC, Robb JE. Extra-osseous Ewing’s sarcoma. J Bone Joint Surg 2009; 91-B(Suppl. 11): 215.
[32]
Gogna S, Parshad S, Karwasra RK, Goyal P, Gogna S. Bilateral synchronus Askin’s tumor-case report & review of literature. Indian J Surg Oncol 2016; 7(1): 124-6.
[http://dx.doi.org/10.1007/s13193-016-0489-1] [PMID: 27065698]
[33]
Cotterill SJ, Ahrens S, PAULussen M, et al. Prognostic factors in Ewing’s tumors of bone: Analysis of 975 patients from the European intergroup cooperative sarcoma study group. J Clin Oncol 2000; 18: 3108-14.
[http://dx.doi.org/10.1200/JCO.2000.18.17.3108] [PMID: 10963639]
[34]
Bacci G, Toni A, Avella M, et al. Long-term results in 144 localized Ewing’s sarcoma patients treated with combined therapy. Cancer 1989; 63(8): 1477-86.
[http://dx.doi.org/10.1002/1097-0142(19890415)63:8<1477::AID-CNCR2820630805>3.0.CO;2-8] [PMID: 2924256]
[35]
Bacci G, Ferrari S, Bertoni F, et al. Prognostic factors in nonmetastatic Ewing’s sarcoma of bone treated with adjuvant chemotherapy: Analysis of 359 patients at the Istituto Ortopedico Rizzoli. J Clin Oncol 2000; 18(1): 4-11.
[http://dx.doi.org/10.1200/JCO.2000.18.1.4] [PMID: 10623687]
[36]
Laskar S, Nair C, Mallik S, et al. Prognostic factors and outcome in Askin-Rosai tumor: A review of 104 patients. Int J Radiat Oncol Biol Phys 2011; 79(1): 202-7.
[http://dx.doi.org/10.1016/j.ijrobp.2009.10.039] [PMID: 20399028]
[37]
Patterson FR, Basra SK. Ewing’s sarcoma.Orthopaedic knowledge update: Musculoskeletal tumors 2. Rosemont: American Academy of Orthopaedic Surgeons 2007; pp. 175-83.
[38]
Györke T, Zajic T, Lange A, et al. Impact of FDG PET for staging of Ewing sarcomas and primitive neuroectodermal tumours. Nucl Med Commun 2006; 27(1): 17-24.
[http://dx.doi.org/10.1097/01.mnm.0000186608.12895.69] [PMID: 16340719]
[39]
Gulati D, Bahal A, Dhar AK, Chakravorty N, Muttagikar MP, Lakhtakia R. Askin Rosai tumour. Med J Armed Forces India 2007; 63(3): 284-5.
[http://dx.doi.org/10.1016/S0377-1237(07)80158-4] [PMID: 27408020]
[40]
Carter BW, Benveniste MF, Betancourt SL, et al. Imaging evaluation of malignant chest wall neoplasms. Radiographics 2016; 36(5): 1285-306.
[http://dx.doi.org/10.1148/rg.2016150208] [PMID: 27494286]
[41]
Galyfos G, Karantzikos GA, Kavouras N, Sianou A, Palogos K, Filis K. Extraosseous Ewing sarcoma: Diagnosis, prognosis and optimal management. Indian J Surg 2016; 78(1): 49-53.
[http://dx.doi.org/10.1007/s12262-015-1399-0] [PMID: 27186040]
[42]
Folpe AL, Goldblum JR, Rubin BP, et al. Morphologic and immunophenotypic diversity in Ewing family tumors: A study of 66 genetically confirmed cases. Am J Surg Pathol 2005; 29(8): 1025-33.
[PMID: 16006796]
[43]
Noguera R, Triche TJ, Navarro S, Tsokos M, Llombart-Bosch A. Dynamic model of differentiation in Ewing’s sarcoma cells. Comparative analysis of morphologic, immunocytochemical, and oncogene expression parameters. Lab Invest 1992; 66(2): 143-51.
[PMID: 1310513]
[44]
Llombart-Bosch A, Machado I, Navarro S, et al. Histological heterogeneity of Ewing’s sarcoma/PNET: An immunohistochemical analysis of 415 genetically confirmed cases with clinical support. Virchows Arch 2009; 455(5): 397-411.
[http://dx.doi.org/10.1007/s00428-009-0842-7] [PMID: 19841938]
[45]
Hameed M. Small round cell tumors of bone Arch Pathol Lab Med 2007; 131(2): 192-204.
[46]
Parham DM, Hijazi Y, Steinberg SM, et al. Neuroectodermal differentiation in Ewing’s sarcoma family of tumors does not predict tumor behavior. Hum Pathol 1999; 30(8): 911-8.
[http://dx.doi.org/10.1016/S0046-8177(99)90244-7] [PMID: 10452503]
[47]
Sawin RS, Conrad EU III, Park JR, Waldhausen JH. Preresection chemotherapy improves survival for children with Askin tumors. Arch Surg 1996; 131(8): 877-80.
[http://dx.doi.org/10.1001/archsurg.1996.01430200087015] [PMID: 8712913]
[48]
Suh CH, Ordóñez NG, Hicks J, Mackay B. Ultrastructure of the Ewing’s sarcoma family of tumors. Ultrastruct Pathol 2002; 26(2): 67-76.
[http://dx.doi.org/10.1080/01913120252959236] [PMID: 12036094]
[49]
Franchi A, Pasquinelli G, Cenacchi G, et al. Immunohistochemical and ultrastructural investigation of neural differentiation in Ewing sarcoma/PNET of bone and soft tissues. Ultrastruct Pathol 2001; 25(3): 219-25.
[http://dx.doi.org/10.1080/01913120120194] [PMID: 11465478]
[50]
Gu M, Antonescu CR, Guiter G, Huvos AG, Ladanyi M, Zakowski MF. Cytokeratin immunoreactivity in Ewing’s sarcoma: Prevalence in 50 cases confirmed by molecular diagnostic studies. Am J Surg Pathol 2000; 24(3): 410-6.
[http://dx.doi.org/10.1097/00000478-200003000-00010] [PMID: 10716155]
[51]
Mansoori H, Moiz B. Extensive marrow infiltration in epidural Ewing sarcoma. Blood Res 2016; 51(3): 156.
[http://dx.doi.org/10.5045/br.2016.51.3.156] [PMID: 27722124]
[52]
Chauhan K, Jain M, Grover S, Shukla P, Rusia U, Grover RK. Bone marrow metastasis in nonhematologic malignancies: Data from a cancer hospital. Clin Cancer Investig J 2016; 5(2): 103-9.
[http://dx.doi.org/10.4103/2278-0513.177131]
[53]
Özpolat HT, Yilmaz E, Goksoy HS, et al. Detection of bone marrow involvement with FDG PET/CT in patients with newly diagnosed lymphoma. Blood Res 2018; 53(4): 281-7.
[http://dx.doi.org/10.5045/br.2018.53.4.281] [PMID: 30588464]
[54]
Bailey K, Cost C, Davis I, et al. Emerging novel agents for patients with advanced Ewing sarcoma: A report from the Children’s Oncology Group (COG) new agents for Ewing sarcoma task force. F1000Res 2019.
[55]
Neilsen PM, Pishas KI, Callen DF, Thomas DM. Targeting the p53 Pathway in Ewing Sarcoma. Sarcoma 2011; 2011
[http://dx.doi.org/10.1155/2011/746939] [PMID: 21197471]
[56]
Delattre O, Zucman J, Plougastel B, et al. Gene fusion with an ETS DNA-binding domain caused by chromosome translocation in human tumours. Nature 1992; 359(6391): 162-5.
[http://dx.doi.org/10.1038/359162a0] [PMID: 1522903]
[57]
Turc-Carel C, Philip I, Berger MP, Philip T, Lenoir G. Chromosomal translocation (11; 22) in cell lines of Ewing’s sarcoma Cancer Genet Cytogenet 1984; 12(1): 1-19.
[58]
Ladanyi M. EWS-FLI1 and Ewing’s sarcoma: Recent molecular data and new insights. Cancer Biol Ther 2002; 1(4): 330-6.
[http://dx.doi.org/10.4161/cbt.1.4.2900] [PMID: 12432241]
[59]
de Alava E, Pardo J. Ewing tumor: Tumor biology and clinical applications. Int J Surg Pathol 2001; 9(1): 7-17.
[http://dx.doi.org/10.1177/106689690100900104] [PMID: 11469351]
[60]
Bridge RS, Rajaram V, Dehner LP, Pfeifer JD, Perry A. Molecular diagnosis of Ewing sarcoma/primitive neuroectodermal tumor in routinely processed tissue: A comparison of two FISH strategies and RT-PCR in malignant round cell tumors. Mod Pathol 2006; 19(1): 1-8.
[http://dx.doi.org/10.1038/modpathol.3800486] [PMID: 16258512]
[61]
Gaspar N, Di Giannatale A, Geoerger B, et al. Bone Sarcomas: From biology to targeted therapies. Sarcoma Volume 2012; pp. 1-17.
[62]
Liang C, Mao H, Tan J, et al. Synovial sarcoma: Magnetic resonance and computed tomography imaging features and differential diagnostic considerations. Oncol Lett 2015; 9(2): 661-6.
[http://dx.doi.org/10.3892/ol.2014.2774] [PMID: 25621034]
[63]
Lamplot JD, Denduluri S. The current and future therapies for human osteosarcoma. Curr Cancer Ther Rev 2013; 9(1): 55-77.
[64]
Kasalak Ö, Overbosch J, Adams HJA, et al. Diagnostic value of MRI signs in differentiating Ewing sarcoma from osteomyelitis. Acta Radiol 2019; 60(2): 204-12.
[http://dx.doi.org/10.1177/0284185118774953] [PMID: 29742917]
[65]
Ferrari A, De Salvo GL, Brennan B, et al. Synovial sarcoma in children and adolescents: The European Pediatric Soft Tissue Sarcoma Study Group prospective trial (EpSSG NRSTS 2005). Ann Oncol 2015; 26(3): 567-72.
[http://dx.doi.org/10.1093/annonc/mdu562] [PMID: 25488687]
[66]
Wang H, Pei Nie P, Dong C, et al. CT and MRI findings of soft tissue adult fibrosarcoma in extremities. BioMed Res Int 2018; 1-7.
[67]
Hashemi J, Gharahdaghi M, Ansaripour E, Jedi F, Hashemi S. Radiological features of osteoid osteoma: Pictorial review. Iran J Radiol 2011; 8(3): 182-9.
[http://dx.doi.org/10.5812/kmp.iranjradiol.17351065.3392] [PMID: 23329939]
[68]
Saeed M, Plett S, Kim GE, Daldrup-Link H, Courtier J. Radiological-pathological correlation of pleomorphic liposarcoma of the anterior mediastinum in a 17-year-old girl. Pediatr Radiol 2010; 40(Suppl. 1): S68-70.
[http://dx.doi.org/10.1007/s00247-010-1797-1] [PMID: 20827472]
[69]
Boehme KA, Schleicher SB, Traub F, Rolauffs B. Chondrosarcoma: A rare misfortune in aging human cartilage? the role of stem and progenitor cells in proliferation, malignant degeneration and therapeutic resistance. Int J Mol Sci 2018; 19(1): 311.
[http://dx.doi.org/10.3390/ijms19010311] [PMID: 29361725]
[70]
El Ochi MR, El Hammoumi MM, Biyi A, et al. Pulmonary tumor diagnosed as an undifferentiated sarcoma with epithelioid features: A case report. J Med Case Reports 2016; 10(1): 274.
[http://dx.doi.org/10.1186/s13256-016-1056-7] [PMID: 27716413]
[71]
Liu C, Yan Xi1, Li M, et al. Dedifferentiated chondrosarcoma: Radiological features, prognostic factors and survival statistics in 23 patients. PLoS One 12(3): e0173665.
[http://dx.doi.org/10.1186/s13256-016-1056-7] [PMID: 27716413]
[72]
Chbani L, Guillou L, Terrier P, et al. Epithelioid sarcoma: A clinicopathologic and immunohistochemical analysis of 106 cases from the French sarcoma group. Am J Clin Pathol 2009; 131(2): 222-7.
[http://dx.doi.org/10.1309/AJCPU98ABIPVJAIV] [PMID: 19141382]
[73]
Mohan RPS, Verma S, Siddhu VK, Agarwal N. Malignant fibrous histiocytoma. BMJ Case Rep 2013; 2013: bcr2013008875.
[http://dx.doi.org/10.1136/bcr-2013-008875] [PMID: 23729703]
[74]
Machado I, Noguera R, Mateos EA, et al. The many faces of atypical Ewing’s sarcoma. A true entity mimicking sarcomas, carcinomas and lymphomas. Virchows Arch 2010.
[http://dx.doi.org/10.1007/s00428-010-1023-4] [PMID: 21181413]
[75]
Renzi S, Anderson ND, Light N, Gupta A. Ewing-like sarcoma: An emerging family of round cell sarcomas. J Cell Physiol 2019; 234(6): 7999-8007.
[http://dx.doi.org/10.1002/jcp.27558] [PMID: 30257034]
[76]
Specht K, Hartmann W. Ewing sarcomas and Ewing-like sarcomas: New aspects Pathologe 2018; 39(2): 154-63.
[http://dx.doi.org/10.1007/s00292-018-0421-2] [PMID: 29480450]
[77]
Sbaraglia M, Righi A, Gambarotti M, Dei Tos AP. Ewing sarcoma and Ewing-like tumors. Virchows Arch 2020; 476(1): 109-19.
[http://dx.doi.org/10.1007/s00428-019-02720-8] [PMID: 31802230]
[78]
Raney RB, Asmar L, Newton WA Jr, et al. Ewing’s sarcoma of soft tissues in childhood: A report from the Intergroup Rhabdomyosarcoma Study, 1972 to 1991. J Clin Oncol 1997; 15(2): 574-82.
[http://dx.doi.org/10.1200/JCO.1997.15.2.574] [PMID: 9053479]
[79]
Chow E, Merchant TE, Pappo A, Jenkins JJ, Shah AB, Kun LE. Cutaneous and subcutaneous Ewing’s sarcoma: An indolent disease. Int J Radiat Oncol Biol Phys 2000; 46(2): 433-8.
[http://dx.doi.org/10.1016/S0360-3016(99)00391-0] [PMID: 10661351]
[80]
Shek TWH, Chan GCF, Khong PL, Chung LP, Cheung ANY. Ewing sarcoma of the small intestine. J Pediatr Hematol Oncol 2001; 23(8): 530-2.
[http://dx.doi.org/10.1097/00043426-200111000-00013] [PMID: 11878783]
[81]
Schuck A, Ahrens S, Paulussen M, et al. Local therapy in localized Ewing tumors: Results of 1058 patients treated in the CESS 81, CESS 86, and EICESS 92 trials. Int J Radiat Oncol Biol Phys 2003; 55(1): 168-77.
[http://dx.doi.org/10.1016/S0360-3016(02)03797-5] [PMID: 12504050]
[82]
Venkitaraman R, George MK, Ramanan SG, Sagar TG. A single institution experience of combined modality management of extra skeletal Ewings sarcoma World J Surg Oncol 2007; 5: 3.
[83]
Ozaki T, Hillmann A, Hoffmann C, et al. Significance of surgical margin on the prognosis of patients with Ewing’s sarcoma. A report from the Cooperative Ewing’s Sarcoma Study. Cancer 1996; 78(4): 892-900.
[http://dx.doi.org/10.1002/(SICI)1097-0142(19960815)78:4892::AID-CNCR29>3.0.CO;2-P] [PMID: 8756387]
[84]
Shamberger RC, LaQuaglia MP, Gebhardt MC, et al. 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): 563-7.
[http://dx.doi.org/10.1097/01.sla.0000089857.45191.52] [PMID: 14530727]
[85]
Saenz NC, Hass DJ, Meyers P, et al. Pediatric chest wall Ewing’s sarcoma. J Pediatr Surg 2000; 35(4): 550-5.
[http://dx.doi.org/10.1053/jpsu.2000.0350550] [PMID: 10770379]
[86]
Tanaka K, Ozaki T. New TNM classification (AJCC eighth edition) of bone and soft tissue sarcomas: JCOG Bone and Soft Tissue Tumor Study Group. Jpn J Clin Oncol 2019; 49(2): 103-7.
[http://dx.doi.org/10.1093/jjco/hyy157] [PMID: 30423153]
[87]
Cates JMM. The AJCC 8th Edition staging system for soft tissue sarcoma of the extremities or trunk: A cohort study of the SEER Database. J Natl Compr Canc Netw 2018; 16(2): 144-52.
[http://dx.doi.org/10.6004/jnccn.2017.7042] [PMID: 29439175]
[88]
Coindre JM. Grading of soft tissue sarcomas, review and update. Arch Pathol Lab Med 2006; 130: 1448-53.
[89]
Khouri J, Coffin CM, Spunt SL, et al. Grading of non-rhabdomyosarcoma soft tissue sarcoma in children and adolescents: A comparison of parameters used for the FNCLCC and POG systems. Cancer 2010; 116(9): 2266-74.
[http://dx.doi.org/10.1002/cncr.24929] [PMID: 20166208]
[90]
Schöffski P, Cornillie J, Wozniak A, Li H, Hompes D. Soft tissue sarcoma: An update on systemic treatment options for patients with advanced disease Oncol Res Treat 2014; 37: 355-62.
[91]
Burgert EO Jr, Nesbit ME, Garnsey LA, et al. Multimodal therapy for the management of nonpelvic, localized Ewing’s sarcoma of bone: Intergroup study IESS-II. J Clin Oncol 1990; 8(9): 1514-24.
[http://dx.doi.org/10.1200/JCO.1990.8.9.1514] [PMID: 2099751]
[92]
Grier HE, Krailo MD, Tarbell NJ, et al. 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.
[http://dx.doi.org/10.1056/NEJMoa020890] [PMID: 12594313]
[93]
Womer RB, West DC, Krailo MD, et al. Randomized comparison of every-two-week vs. every three-week chemotherapy in Ewing sarcoma family tumors (ESFT) J Clini Oncol 2008; 26(15): 10504.
[94]
Le Deley MC, Paulussen M, Lewis I, et al. Cyclophosphamide compared with ifosfamide in consolidation treatment of standard-risk Ewing sarcoma: Results of the randomized noninferiority Euro-EWING99-R1 trial. J Clin Oncol 2014; 32(23): 2440-8.
[http://dx.doi.org/10.1200/JCO.2013.54.4833] [PMID: 24982464]
[95]
Granowetter L, Womer R, Devidas M, et al. 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.
[http://dx.doi.org/10.1200/JCO.2008.19.1478] [PMID: 19349548]
[96]
Chawla SP, Papai Z, Mukhametshina G, et al. First-Line Aldoxorubicin vs Doxorubicin in metastatic or locally advanced unresectable soft-tissue sarcoma: A phase 2b randomized clinical trial. JAMA Oncol 2015; 1(9): 1272-80.
[http://dx.doi.org/10.1001/jamaoncol.2015.3101] [PMID: 26378637]
[97]
Meyers PA, Krailo MD, Ladanyi M, et al. High-dose melphalan, etoposide, total-body irradiation, and autologous stem-cell reconstitution as consolidation therapy for high-risk Ewing’s sarcoma does not improve prognosis. J Clin Oncol 2001; 19(11): 2812-20.
[http://dx.doi.org/10.1200/JCO.2001.19.11.2812] [PMID: 11387352]
[98]
Miser JS, Krailo MD, Tarbell NJ, et al. Treatment of metastatic Ewing’s sarcoma or primitive neuroectodermal tumor of bone: Evaluation of combination ifosfamide and etoposide--a Children’s Cancer Group and Pediatric Oncology Group study. J Clin Oncol 2004; 22(14): 2873-6.
[http://dx.doi.org/10.1200/JCO.2004.01.041] [PMID: 15254055]
[99]
Ladenstein R, Hartmann O, Pincerton R, et al. A multivariate and matched pair analysis on high – risk Ewing tumors patients treated by megatherapy and stem cell reinfusion in Europe. Proc Annu Meet Am Soc Clin Oncol. 18: 555.
[100]
Tenneti P, Zahid U, Iftikhar A, et al. Role of high-dose chemotherapy and autologous hematopoietic cell transplantation for children and young adults with relapsed Ewing’s sarcoma: A systematic review. Sarcoma 2018; 2018: 2640674.
[101]
Nesbit ME Jr, Gehan EA, Burgert EO Jr, et al. Multimodal therapy for the management of primary, nonmetastatic Ewing’s sarcoma of bone: A long-term follow-up of the First Intergroup study. J Clin Oncol 1990; 8(10): 1664-74.
[http://dx.doi.org/10.1200/JCO.1990.8.10.1664] [PMID: 2213103]
[102]
Houdek MT, Griffin AM, Ferguson PC, Wunder JS. Morbid obesity increases the risk of postoperative wound complications, infection, and repeat surgical procedures following upper extremity limb salvage surgery for soft tissue sarcoma. Hand (N Y) 2019; 14(1): 114-20.
[http://dx.doi.org/10.1177/1558944718797336] [PMID: 30145914]
[103]
Karkhur Y, Maini L, Tiwari A, Verma T. Ewings sarcoma of ilium: Resection and reconstruction with femoral head allograft. J Clin Orthop Trauma 2017; 8(Suppl. 1): S53-7.
[http://dx.doi.org/10.1016/j.jcot.2017.07.002] [PMID: 28878542]
[104]
Murakami H, Demura S, Kato S, et al. Increase of IL-12 following reconstruction for total en bloc spondylectomy using frozen autografts treated with liquid nitrogen. PLoS One 2013; 8(5): e64818.
[http://dx.doi.org/10.1371/journal.pone.0064818] [PMID: 23734222]
[105]
Tsuchiya H, Wan SL, Sakayama K, Yamamoto N, Nishida H, Tomita K. Reconstruction using an autograft containing tumour treated by liquid nitrogen. J Bone Joint Surg Br 2005; 87(2): 218-25.
[http://dx.doi.org/10.1302/0301-620X.87B2.15325] [PMID: 15736747]
[106]
Krasin MJ, Rodriguez-Galindo C, Davidoff AM, et al. Efficacy of combined surgery and irradiation for localized Ewings sarcoma family of tumors. Pediatr Blood Cancer 2004; 43(3): 229-36.
[http://dx.doi.org/10.1002/pbc.20095] [PMID: 15266406]
[107]
Ren Y, Zhang Z, Shang L, You X. Surgical resection of primary Ewing’s Sarcoma of bone improves overall survival in patients presenting with metastasis. Med Sci Monit 2019; 25: 1254-62.
[http://dx.doi.org/10.12659/MSM.913338] [PMID: 30770526]
[108]
Raz DJ, Clancy SL, Erhunmwunsee LJ. Surgical management of the radiated chest wall and its complications. Thorac Surg Clin 2017; 27(2): 171-9.
[http://dx.doi.org/10.1016/j.thorsurg.2017.01.011] [PMID: 28363372]
[109]
Tukiainen E. Chest wall reconstruction after oncological resections. Scand J Surg 2013; 102(1): 9-13.
[http://dx.doi.org/10.1177/145749691310200103] [PMID: 23628630]
[110]
Basharkhah A, Pansy J, Urban C, Höllwarth ME. Outcomes after interdisciplinary management of 7 patients with Askin tumor Pediatr Surg Int 29(5): 431-6.
[111]
Baliski CR, Schachar NS, McKinnon JG, Stuart GC, Temple WJ. Hemipelvectomy: A changing perspective for a rare procedure. Can J Surg 2004; 47(2): 99-103.
[PMID: 15132462]
[112]
Dunst J, Sauer R, Burgers JM, et al. Radiation therapy as local treatment in Ewing’s sarcoma. Results of the Cooperative Ewing’s Sarcoma Studies CESS 81 and CESS 86. Cancer 1991; 67(11): 2818-25.
[http://dx.doi.org/10.1002/1097-0142(19910601)67:11<2818::AID-CNCR2820671118>3.0.CO;2-Y] [PMID: 2025847]
[113]
Wilkins RM, Pritchard DJ, Burgert EO Jr, Unni KK. Ewing’s sarcoma of bone. Experience with 140 patients. Cancer 1986; 58(11): 2551-5.
[http://dx.doi.org/10.1002/1097-0142(19861201)58:11<2551::AID-CNCR2820581132>3.0.CO;2-Y] [PMID: 3768846]
[114]
Cidre-Aranaz F, Alonso J. EWS/FLI1 target genes and therapeutic opportunities in Ewing Sarcoma. Front Oncol 2015; 5: 162.
[http://dx.doi.org/10.3389/fonc.2015.00162] [PMID: 26258070]
[115]
Nathenson MJ, Conley AP, Sausville E. Immunotherapy: A new (and old) approach to treatment of soft tissue and bone Sarcomas. Oncologist 2018; 23(1): 71-83.
[http://dx.doi.org/10.1634/theoncologist.2016-0025] [PMID: 28935774]
[116]
Olmos D, Martins AS, Jones RL, et al. Targeting the insulin-like growth factor 1 receptor in Ewing’s Sarcoma: Reality and expectations. Sarcoma 2011; 2011: 402508.
[http://dx.doi.org/10.1155/2011/402508] [PMID: 21647361]
[117]
Subbiah V, Kurzrock R. Ewing’s sarcoma: Overcoming the therapeutic plateau. Discov Med 2012; 13(73): 405-15.
[PMID: 22742646]
[118]
Huang HY, Illei PB, Zhao Z, et al. Ewing sarcomas with p53 mutation or p16/p14ARF homozygous deletion: A highly lethal subset associated with poor chemoresponse. J Clin Oncol 2005; 23(3): 548-58.
[http://dx.doi.org/10.1200/JCO.2005.02.081] [PMID: 15659501]
[119]
Hensel T, Giorgi C, Schmidt O, et al. Targeting the EWS-ETS transcriptional program by BET bromodomain inhibition in Ewing sarcoma. Oncotarget 2016; 7(2): 1451-63.
[http://dx.doi.org/10.18632/oncotarget.6385] [PMID: 26623725]
[120]
Thomas S, Aggarwal R, Jahan T, et al. A phase I trial of panobinostat and epirubicin in solid tumors with a dose expansion in patients with sarcoma. Ann Oncol 2016; 27(5): 947-52.
[http://dx.doi.org/10.1093/annonc/mdw044] [PMID: 26903311]
[121]
Kolb EA, Kushner BH, Gorlick R, et al. Long-term event-free survival after intensive chemotherapy for Ewing’s family of tumors in children and young adults. J Clin Oncol 2003; 21(18): 3423-30.
[http://dx.doi.org/10.1200/JCO.2003.10.033] [PMID: 12972518]
[122]
Paulussen M, Ahrens S, Burdach S, et al. European Intergroup Cooperative Ewing Sarcoma Studies. Primary metastatic (stage IV) Ewing tumor: Survival analysis of 171 patients from the EICESS studies. Ann Oncol 1998; 9(3): 275-81.
[http://dx.doi.org/10.1023/A:1008208511815] [PMID: 9602261]
[123]
Bölling T, Schuck A, Paulussen M, et al. Whole lung irradiation in patients with exclusively pulmonary metastases of Ewing tumors. Toxicity analysis and treatment results of the EICESS-92 trial. Strahlenther Onkol 2008; 184(4): 193-7.
[http://dx.doi.org/10.1007/s00066-008-1810-x] [PMID: 18398583]
[124]
Staege MS, Hutter C, Neumann I, et al. DNA microarrays reveal relationship of Ewing family tumors to both endothelial and fetal neural crest-derived cells and define novel targets. Cancer Res 2004; 64(22): 8213-21.
[http://dx.doi.org/10.1158/0008-5472.CAN-03-4059] [PMID: 15548687]
[125]
Wiles ET, Bell R, Thomas D, Beckerle M, Lessnick SL. ZEB2 represses the epithelial phenotype and facilitates metastasis in ewing sarcoma. Genes Cancer 2013; 4(11-12): 486-500.
[http://dx.doi.org/10.1177/1947601913506115] [PMID: 24386509]
[126]
Choo S, Wang P, Newbury R, Roberts W. Reactivation of TWIST1 contributes to Ewing sarcoma metastasis Pediatr Blood Cancer 2018; 65(1): 10.1002/pbc.26721.
[127]
Van Mater D, Wagner L. Management of recurrent Ewing sarcoma: Challenges and approaches. OncoTargets Ther 2019; 12: 2279-88.
[http://dx.doi.org/10.2147/OTT.S170585] [PMID: 30988632]
[128]
Shankar AG, Ashley S, Craft AW, Pinkerton CR. Outcome after relapse in an unselected cohort of children and adolescents with Ewing sarcoma. Med Pediatr Oncol 2003; 40(3): 141-7.
[http://dx.doi.org/10.1002/mpo.10248] [PMID: 12518341]
[129]
Hanna SA, David LA, Gikas PD, Tindall AJ, Cannon SR, Briggs TWR. Very late local recurrence of Ewing’s sarcoma--can you ever say ‘cured’? A report of two cases and literature review. Ann R Coll Surg Engl 2008; 90(7): W12-5.
[http://dx.doi.org/10.1308/147870808X303146] [PMID: 18831863]
[130]
Scobioala S, Ranft A, Wolters H, et al. Impact of whole lung irradiation on survival outcome in patients with lung relapsed Ewing sarcoma. Int J Radiat Oncol Biol Phys 2018; 102(3): 584-92.
[131]
Bacci G, Longhi A, Ferrari S, et al. Pattern of relapse in 290 patients with nonmetastatic Ewing’s sarcoma family tumors treated at a single institution with adjuvant and neoadjuvant chemotherapy between 1972 and 1999. Eur J Surg Oncol 2006; 32(9): 974-9.
[http://dx.doi.org/10.1016/j.ejso.2006.01.023] [PMID: 16621429]
[132]
Singh A, Abhinay A, Kumar A, Prasad R, Ghosh A, Mishra OP. Askin tumor: A rare neoplasm of thoracopulmonary region. Lung India 2016; 33(2): 196-8.
[http://dx.doi.org/10.4103/0970-2113.177458] [PMID: 27051109]
[133]
Ladenstein R, Pötschger U, Le Deley MC, et al. Primary disseminated multifocal Ewing sarcoma: Results of the Euro-EWING 99 trial. J Clin Oncol 2010; 28(20): 3284-91.
[http://dx.doi.org/10.1200/JCO.2009.22.9864] [PMID: 20547982]
[134]
Pinto A, Dickman P, Parham D. Pathobiologic markers of the Ewing sarcoma family of tumors: State of the art and prediction of behaviour Sarcoma 2011; 15.
[135]
Cash T, McIlvaine E, Krailo MD, et al. Comparison of clinical features and outcomes in patients with extraskeletal versus skeletal localized Ewing sarcoma: A report from the Children’s Oncology Group. Pediatr Blood Cancer 2016; 63(10): 1771-9.
[http://dx.doi.org/10.1002/pbc.26096] [PMID: 27297500]
[136]
Barker LM, Pendergrass TW, Sanders JE, Hawkins DS. Survival after recurrence of Ewing’s sarcoma family of tumors. J Clin Oncol 2005; 23(19): 4354-62.
[http://dx.doi.org/10.1200/JCO.2005.05.105] [PMID: 15781881]
[137]
Miller BJ, Lynch CF, Buckwalter JA. Conditional survival is greater than overall survival at diagnosis in patients with osteosarcoma and Ewing’s sarcoma. Clin Orthop Relat Res 2013; 471(11): 3398-404.
[http://dx.doi.org/10.1007/s11999-013-3147-8] [PMID: 23821136]
[138]
Gupta AA, Pappo A, Saunders N, et al. Clinical outcome of children and adults with localized Ewing sarcoma: Impact of chemotherapy dose and timing of local therapy. Cancer 2010; 116(13): 3189-94.
[http://dx.doi.org/10.1002/cncr.25144] [PMID: 20564643]
[139]
Terrier P, Llombart-Bosch A, Contesso G. Small round blue cell tumors in bone: Prognostic factors correlated to Ewing’s sarcoma and neuroectodermal tumors. Semin Diagn Pathol 1996; 13(3): 250-7.
[PMID: 8875713]
[140]
Saeter G, Elomaa I, Wahlqvist Y, et al. Prognostic factors in bone sarcomas. Acta Orthop Scand Suppl 1997; 273: 156-60.
[http://dx.doi.org/10.1080/17453674.1997.11744723] [PMID: 9057608]
[141]
Mendenhall CM, Marcus RB Jr, Enneking WF, Springfield DS, Thar TL, Million RR. The prognostic significance of soft tissue extension in Ewing’s sarcoma. Cancer 1983; 51(5): 913-7.
[http://dx.doi.org/10.1002/1097-0142(19830301)51:5<913::AID-CNCR2820510525>3.0.CO;2-0] [PMID: 6821856]
[142]
Pan HY, Morani A, Wang WL, et al. Prognostic factors and patterns of relapse in ewing sarcoma patients treated with chemotherapy and r0 resection. Int J Radiat Oncol Biol Phys 2015; 92(2): 349-57.
[http://dx.doi.org/10.1016/j.ijrobp.2015.01.022] [PMID: 25772182]
[143]
Van Maldegem AM, Hogendoorn PCW, Hassan AB. The clinical use of biomarkers as prognostic factors in Ewing sarcoma. Clinical Sarcoma Research 2012, 2: 7. Clin Sarcoma Res 2012; 2(1): 7.
[http://dx.doi.org/10.1186/2045-3329-2-7] [PMID: 22587879]
[144]
Landier W, Armenian S, Bhatia S. Late effects of childhood cancer and its treatment. Pediatr Clin North Am 2015; 62(1): 275-300.
[http://dx.doi.org/10.1016/j.pcl.2014.09.017] [PMID: 25435123]
[145]
Wood J, Ver Halen J, Samant S, Florendo N. Radiation-induced sarcoma masquerading as osteoradionecrosis: Case report and literature review. J Laryngol Otol 2015; 129(3): 279-82.
[http://dx.doi.org/10.1017/S0022215114003326] [PMID: 25650528]
[146]
Mitchell MJ, Logan PM. Radiation-induced changes in bone. Radiographics 1998; 18(5): 1125-36.
[http://dx.doi.org/10.1148/radiographics.18.5.9747611] [PMID: 9747611]
[147]
Cooley L, Dendle C, Wolf J, et al. Consensus guidelines for diagnosis, prophylaxis and management of Pneumocystis jirovecii pneumonia in patients with haematological and solid malignancies, 2014. Intern Med J 2014; 44(12b): 1350-63.
[http://dx.doi.org/10.1111/imj.12599] [PMID: 25482745]
[148]
Proudfoot R, Phillips B, Wilne S. Guidelines for the prophylaxis of Pneumocystis Jirovecii Pneumonia (PJP) in children with solid tumors. J Pediatr Hematol Oncol 2017; 39(3): 194-202.
[http://dx.doi.org/10.1097/MPH.0000000000000771] [PMID: 28267082]
[149]
Ward EJ, Henry LM, Friend AJ, Wilkins S, Phillips RS. Nutritional support in children and young people with cancer undergoing chemotherapy. Cochrane Database Syst Rev 2015; (8): CD003298.
[http://dx.doi.org/10.1002/14651858.CD003298.pub3] [PMID: 26301790]
[150]
Ülger Ö, Yıldırım Şahan T, Çelik SE. A systematic literature review of physiotherapy and rehabilitation approaches to lower-limb amputation. Physiother Theory Pract 2018; 34(11): 821-34.
[http://dx.doi.org/10.1080/09593985.2018.1425938] [PMID: 29351504]
[151]
Srivastava K, Chaudhury S. Rehabilitation after amputation: Psychotherapeutic intervention module in Indian scenario. Sci World J 2014; 2014: 469385.
[http://dx.doi.org/10.1155/2014/469385] [PMID: 24526895]
[152]
Spunt S, Harper J, Krasin M, et al. Ewing sarcoma as second malignant neoplasm following treatment of a primary malignant neoplasm during childhood. Cancer 2006; 107(1): 201-6.
[http://dx.doi.org/10.1002/cncr.21962] [PMID: 16721801]
[153]
Applebaum MA, Goldsby R, Neuhaus J, DuBois SG. Clinical features and outcomes in patients with secondary Ewing sarcoma. Pediatr Blood Cancer 2013; 60(4): 611-5.
[http://dx.doi.org/10.1002/pbc.24251] [PMID: 22847990]
[154]
Borinstein SC, Beeler N, Block JJ, et al. COG Ewing Sarcoma Biology Committee. A decade in banking Ewing Sarcoma: A Report from the Children’s oncology group. Front Oncol 2013; 3: 57.
[http://dx.doi.org/10.3389/fonc.2013.00057] [PMID: 23519678]
[155]
Lamhamedi-Cherradi S-E, Menegaz BA, Ramamoorthy V, et al. An oral formulation of YK-4-279: Preclinical efficacy and acquired resistance patterns in Ewing Sarcoma. Mol Cancer Ther 2015; 14(7): 1591-604.
[http://dx.doi.org/10.1158/1535-7163.MCT-14-0334] [PMID: 25964201]
[156]
Wilky BA, Kim C, McCarty G, et al. RNA helicase DDX3: A novel therapeutic target in Ewing sarcoma. Oncogene 2016; 35(20): 2574-83.
[http://dx.doi.org/10.1038/onc.2015.336] [PMID: 26364611]


Rights & PermissionsPrintExport Cite as

Article Details

VOLUME: 17
ISSUE: 2
Year: 2021
Published on: 25 November, 2020
Page: [107 - 136]
Pages: 30
DOI: 10.2174/1573394716999201125204643
Price: $65

Article Metrics

PDF: 127
HTML: 2