Ewing’s Sarcoma of Bone

Moore, Drew D.; Haydon, Rex C.

doi:10.1007/978-3-319-07323-1_5

Cited by 38 publications

(43 citation statements)

References 68 publications

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“…The incidence of Ewing sarcoma peaks in adolescents and young adults and most patients in this age group present with localized bone tumors and no overt evidence of metastatic disease [1], [2]. Treatment for localized Ewing sarcoma has been intensified over the past two decades and upfront, compressed cycles of alternating vincristine/doxorubicin/cyclophosphamide and ifosfamide/etoposide is the current standard of cared and has led to a significant improvement in survival in this patient population [3]. However, for patients who present with overt metastatic disease or who relapse following initial therapy, survival estimates remain dismal.…”

Section: Introductionmentioning

confidence: 99%

Micro-Environmental Stress Induces Src-Dependent Activation of Invadopodia and Cell Migration in Ewing Sarcoma

et al. 2016

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Metastatic Ewing sarcoma has a very poor prognosis and therefore new investigations into the biologic drivers of metastatic progression are key to finding new therapeutic approaches. The tumor microenvironment is highly dynamic, leading to exposure of different regions of a growing solid tumor to changes in oxygen and nutrient availability. Tumor cells must adapt to such stress in order to survive and propagate. In the current study, we investigate how Ewing sarcoma cells respond to the stress of growth factor deprivation and hypoxia. Our findings reveal that serum deprivation leads to a reversible change in Ewing cell cytoskeletal phenotypes. Using an array of migration and invasion techniques, including gelatin matrix degradation invadopodia assays, we show that exposure of Ewing sarcoma cells to serum deprivation and hypoxia triggers enhanced migration, invadopodia formation, matrix degradation and invasion. Further, these functional changes are accompanied by and dependent on activation of Src kinase. Activation of Src, and the associated invasive cell phenotype, were blocked by exposing hypoxia and serum-deprived cells to the Src inhibitor dasatinib. These results indicate that Ewing sarcoma cells demonstrate significant plasticity in response to rapidly changing micro-environmental stresses that can result from rapid tumor growth and from necrosis-causing therapies. In response to these stresses, Ewing cells transition to a more migratory and invasive state and our data show that Src is an important mediator of this stress response. Our data support exploration of clinically available Src inhibitors as adjuvant agents for metastasis prevention in Ewing sarcoma.

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Section: Introductionmentioning

confidence: 99%

Micro-Environmental Stress Induces Src-Dependent Activation of Invadopodia and Cell Migration in Ewing Sarcoma

et al. 2016

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“…[4][5][6] Multimodal therapy includes systemic therapy as well as surgery and radiotherapy (RT). 7 Until now, clinical trials on ES have principally focused on a comprehensive investigation of systemic treatment. [8][9][10] Although multi-agent chemotherapy is well defined as the standard of care for ES patients, the best approach for local control of ES of the chest wall remains a matter of discussion.…”

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confidence: 99%

Local Control in Ewing Sarcoma of the Chest Wall: Results of the EURO-EWING 99 Trial

et al. 2015

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Background. Primary Ewing sarcoma (ES) can sometimes present as a chest-wall tumor. Multidisciplinary management, including chemotherapy and local treatment consisting of surgery, radiotherapy (RT), or both, has improved the survival of patients with localized ES; however, the best approach to achieving local control remains controversial.Methods. We retrospectively analyzed data from 198 patients with non-metastatic ES of the chest wall, who were registered in the database of the German Society of Pediatric Hematology and Oncology between July 1998 and April 2009. The majority of patients (n = 130) presented with rib tumors; 7 patients received RT only, 85 patients underwent surgery alone, and 106 patients were treated with a combination of surgery and RT. Results. Overall survival in all patients was 78 and 71 % at 3 and 5 years, respectively. Event-free survival at 5 years (5-year EFS) was 57 % in the RT group, 73 % in the surgery group and 63 % in the surgery ? RT group. In patients with complete resections, 5-year EFS did not improve with the addition of RT compared with surgery alone. There was no difference in the 5-year EFS in patients with partial (63 %) or total (64 %) resection of the affected ribs, and median follow-up was 4.71 years (range 0.40-13.48). Conclusions. Complete tumor resection is the best way to achieve local control of ES of the chest wall; additional RT is only useful in patients with incomplete resection. The main limitation of this study was its retrospective nature, and the benefit of total resection of the affected ribs could not be proved.Ewing sarcoma (ES) is a rare, highly malignant disease found in children, adolescents, and young adults, with a reported incidence of three persons per million people per year within a Caucasian population. Median age at diagnosis is 15 years, 1 and the chest wall is the primary site of presentation in 14 % of patients. The tumor most commonly originates from osseous structures (ribs 9 %, scapula 4 %, clavicle 1 %, or sternum \1 %), and even less frequently from the soft tissue of the chest wall (\1 %). 2 ESs of the chest wall have also been referred to as Askin's tumors, 3 until an identical molecular signature revealed a common origin.Multidisciplinary management has improved the 5-year survival of patients with localized disease to rates of 60-70 % and higher. 4-6 Multimodal therapy includes systemic therapy as well as surgery and radiotherapy (RT). 7 Until now, clinical trials on ES have principally focused on a comprehensive investigation of systemic treatment. 8-10 Although multi-agent chemotherapy is well defined as the standard of care for ES patients, the best approach for local control of ES of the chest wall remains a matter of discussion. 11 Local treatment of chest-wall tumors is often challenging, especially in young patients, as both local treatment modalities (surgery and RT) may be associated with significant long-term sequelae. 12 Due to the rarity of ES of the chest wall, only a limited number of patient series have been publis...

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“…Notably, we found numerous copy number changes, including homozygous segmental chromosomal deletions involving RB1, PTCH1 , and ATRX , genes that are characteristically disrupted in osteosarcomas instead of Ewing sarcomas [13–15]. Additionally, the analysis demonstrated absence of genomic rearrangements affecting specific regions of the EWSR1 gene known to be involved in Ewing-like chromosomal translocations [12,16]. The high number of chromosomal alterations seen in this patients tumor is consistent with chromoplexy classically seen in osteosarcoma [13,15].…”

Section: Case Descriptionmentioning

confidence: 99%

Osteosarcoma With Apparent Ewing Sarcoma Gene Rearrangement

Mathias

Chou²,

Meyers

et al. 2016

Journal of Pediatric Hematology/Oncology

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Poorly differentiated round cell sarcomas present diagnostic challenges due to their variable morphology and lack of specific immunophenotypic markers. We present a case of a 15-year-old female with a tibial tumor that exhibited features of Ewing-like sarcoma, including apparent rearrangement of the EWSR1 gene. Hybridization capture-based next-generation DNA sequencing showed evidence of complex genomic rearrangements, absence of known pathogenic Ewing-like chromosome translocations, and deletions RB1, PTCH1, and ATRX, supporting the diagnosis of osteosarcoma. This illustrates the potential of clinical genomic profiling to improve diagnosis and enable specifically targeted therapies for cancers with complex pathologies.

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Ewing’s Sarcoma of Bone

Cited by 38 publications

References 68 publications

Micro-Environmental Stress Induces Src-Dependent Activation of Invadopodia and Cell Migration in Ewing Sarcoma

Micro-Environmental Stress Induces Src-Dependent Activation of Invadopodia and Cell Migration in Ewing Sarcoma

Local Control in Ewing Sarcoma of the Chest Wall: Results of the EURO-EWING 99 Trial

Osteosarcoma With Apparent Ewing Sarcoma Gene Rearrangement

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