Evaluation of outcome and prognostic factors in extraosseous Ewing sarcoma

Biswas, Bivas; Shukla, Nootan Kumar; Deo, S. V. S.; Agarwala, Sandeep; Sharma, Daya Nand; Vishnubhatla, Sreenivas; Bakhshi, Sameer

doi:10.1002/pbc.25095

Cited by 50 publications

(59 citation statements)

References 31 publications

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“…Previous reports have suggested that there may be clinical differences between patients with EES and skeletal ES . For example, patients with extraskeletal disease have been reported to be older and have a propensity for axial tumor origin.…”

Section: Introductionmentioning

confidence: 99%

Comparison of clinical features and outcomes in patients with extraskeletal versus skeletal localized Ewing sarcoma: A report from the Children's Oncology Group

Cash

McIlvaine

Krailo

et al. 2016

Pediatric Blood & Cancer

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BACKGROUND The prognostic significance of having extraskeletal vs. skeletal Ewing sarcoma in the setting of modern chemotherapy protocols is unknown. The purpose of this study was to compare the clinical characteristics, biologic features, and outcomes for patients with extraskeletal and skeletal Ewing sarcoma. METHODS Patients had localized Ewing sarcoma (ES) and were treated on two consecutive protocols using 5-drug chemotherapy (INT-0154 and AEWS0031). Patients were analyzed based on having an extraskeletal (n=213) or skeletal (n=826) site of tumor origin. Event-free survival (EFS) was estimated using the Kaplan-Meier method, compared using the log-rank test, and modeled using Cox multivariate regression. RESULTS Patients with extraskeletal Ewing Sarcoma (EES) were more likely to have axial tumors (72% vs. 55%; P < 0.001), less likely to have tumors > 8 cm (9% vs. 17%; P < 0.01), and less likely to be white (81% vs. 87%; P < 0.001) compared to patients with skeletal ES. There was no difference in key genomic features (type of EWSR1 translocation, TP53 mutation, CDKN2A mutation/loss) between groups. After controlling for age, race, and primary site, EES was associated with superior EFS [hazard ratio = 0.69; 95% CI: 0.50–0.95; P = 0.02]. Among patients with EES, age ≥ 18 years, non-white race, and elevated baseline erythrocyte sedimentation rate (ESR) were independently associated with inferior EFS. CONCLUSION Clinical characteristics, but not key tumor genomic features, differ between EES and skeletal ES. Extraskeletal origin is a favorable prognostic factor, independent of age, race, and primary site.

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Section: Introductionmentioning

confidence: 99%

Comparison of clinical features and outcomes in patients with extraskeletal versus skeletal localized Ewing sarcoma: A report from the Children's Oncology Group

Cash

McIlvaine

Krailo

et al. 2016

Pediatric Blood & Cancer

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“…However, for patients who present with overt metastatic disease or who relapse following initial therapy, survival estimates remain dismal. Common sites of Ewing sarcoma metastasis are the lungs, bones and bone marrow and metatastic spread can be detected at any time, including many years after initial presentation [4], [5]. Despite attempts to identify biomarkers of aggressive disease, it is still not clear why some patients never develop metastasis and others go on to relapse at distant sites despite experiencing initial clinical remissions [6].…”

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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“…As synovial sarcoma is a rare malignancy, a specific tumor marker has never been established. However, LDH is known to reflect the progression of sarcomas and is suggested to be a prognostic factor of sarcoma (15). In the present case, the LDH value reflected both the tumor size and progression.…”

Section: Discussionmentioning

confidence: 58%

Primary Pleural Synovial Sarcoma Treated with Pazopanib

et al. 2015

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A 42-year-old woman presented with chest pain and breathlessness with a nodule measuring 2×2 cm in size at the base of the right lung. A bronchoscopic examination did not reveal any malignancy. However, the patient developed difficulty in breathing, enlargement of the nodule, and right pleural effusion 14 days later. A video-assisted thoracic surgical biopsy specimen revealed the presence of pleural synovial sarcoma. The patient was treated with doxorubicin-ifosfamide combination chemotherapy because of metastasis to the pelvis. However, after a transient partial clinical response, there was a relapse of refractory disease. Although treated with pazopanib as second-line chemotherapy, the patient died eight months after the initial presentation.

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Evaluation of outcome and prognostic factors in extraosseous Ewing sarcoma

Abstract: These data of EES suggests that low hemoglobin and high WBC count adversely affect EFS. Overall outcome was significantly better for EES than skeletal primary tumors.

Cited by 50 publications

References 31 publications

Comparison of clinical features and outcomes in patients with extraskeletal versus skeletal localized Ewing sarcoma: A report from the Children's Oncology Group

Comparison of clinical features and outcomes in patients with extraskeletal versus skeletal localized Ewing sarcoma: A report from the Children's Oncology Group

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

Primary Pleural Synovial Sarcoma Treated with Pazopanib

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