Consensus recommendations for systemic therapies in the management of relapsed Ewing sarcoma: A report from the National Ewing Sarcoma Tumor Board.

Journal and index pages often block iframe embedding. This reader keeps the evidence details in Orthonotes and leaves the source page one click away.

Abstract

[Indexed for MEDLINE] 6. Nat Rev Dis Primers. 2022 Oct 6;8(1):66. doi: 10.1038/s41572-022-00393-3. Small round cell sarcomas. Cidre-Aranaz F(1)(2), Watson S(3)(4), Amatruda JF(5)(6), Nakamura T(7), Delattre O(4), de Alava E(8)(9), Dirksen U(10), Grünewald TGP(11)(12)(13). Author information: (1)Division of Translational Paediatric Sarcoma Research, German Cancer Research Center (DKFZ), German Cancer Consortium (DKTK), Heidelberg, Germany. florencia.cidrearanaz@kitz-heidelberg.de. (2)Hopp-Children's Cancer Center (KiTZ), Heidelberg, Germany. florencia.cidrearanaz@kitz-heidelberg.de. (3)Department of Medical Oncology, Institut Curie Hospital, Paris, France. (4)INSERM U830, Diversity and Plasticity of Childhood Tumors Lab, PSL Research University, SIREDO Oncology Center, Institut Curie Research Center, Paris, France. (5)Cancer and Blood Disease Institute, Children's Hospital Los Angeles, Los Angeles, CA, USA. (6)Departments of Paediatrics and Medicine, Keck School of Medicine, University of Southern California, Los Angeles, CA, USA. (7)Institute of Medical Science, Tokyo Medical University, Tokyo, Japan. (8)Institute of Biomedicine of Sevilla (IBiS), Virgen del Rocio University Hospital/CSIC/University of Sevilla/CIBERONC, Seville, Spain. (9)Department of Normal and Pathological Cytology and Histology, School of Medicine, University of Seville, Seville, Spain. (10)Department of Paediatrics, University Hospital Essen, Essen, Germany. (11)Division of Translational Paediatric Sarcoma Research, German Cancer Research Center (DKFZ), German Cancer Consortium (DKTK), Heidelberg, Germany. t.gruenewald@kitz-heidelberg.de. (12)Hopp-Children's Cancer Center (KiTZ), Heidelberg, Germany. t.gruenewald@kitz-heidelberg.de. (13)Institute of Pathology, Heidelberg University Hospital, Heidelberg, Germany. t.gruenewald@kitz-heidelberg.de. Undifferentiated small round cell sarcomas (SRCSs) of bone and soft tissue comprise a heterogeneous group of highly aggressive tumours associated with a poor prognosis, especially in metastatic disease. SRCS entities mainly occur in the third decade of life and can exhibit striking disparities regarding preferentially affected sex and tumour localization. SRCSs comprise new entities defined by specific genetic abnormalities, namely EWSR1-non-ETS fusions, CIC-rearrangements or BCOR genetic alterations, as well as EWSR1-ETS fusions in the prototypic SRCS Ewing sarcoma. These gene fusions mainly encode aberrant oncogenic transcription factors that massively rewire the transcriptome and epigenome of the as yet unknown cell or cells of origin. Additional mutations or copy number variants are rare at diagnosis and, depending on the tumour entity, may involve TP53, CDKN2A and others. Histologically, these lesions consist of small round cells expressing variable levels of CD99 and specific marker proteins, including cyclin B3, ETV4, WT1, NKX3-1 and aggrecan, depending on the entity. Besides locoregional treatment that should follow standard protocols for sarcoma management, (neo)adjuvant treatment is as yet ill-defined but generally follows that of Ewing sarcoma and is associated with adverse effects that might compromise quality of life. Emerging studies on the molecular mechanisms of SRCSs and the development of genetically engineered animal models hold promise for improvements in early detection, disease monitoring, treatment-related toxicity, overall survival and quality of life. © 2022. Springer Nature Limited. DOI: 10.1038/s41572-022-00393-3