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Underdown MJ, Kappa S, Metts J, Cash T. Ewing Sarcoma, Desmoplastic Small Round Cell Tumor, and Other Round Cell Sarcomas. Hematol Oncol Clin North Am 2025:S0889-8588(25)00041-3. [PMID: 40374389 DOI: 10.1016/j.hoc.2025.04.003] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 05/17/2025]
Abstract
The classification of small round cell sarcomas encompasses a spectrum of diseases ranging from those that are more widely understood, such as Ewing sarcoma and desmoplastic small round cell tumor, to more newly characterized diseases such as capicua (CIC)-rearranged sarcomas, BCOR-altered sarcomas, and sarcomas with EWSR1-non-ETS fusions. This article provides background, unique molecular features, and current and emerging therapies for each round cell sarcoma subtype.
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Affiliation(s)
- M Jane Underdown
- Department of Pediatrics, Division of Pediatric Hematology/Oncology/BMT, University of Utah Health, Salt Lake City, UT, USA
| | - Sarah Kappa
- Department of Pediatrics, Texas Children's Cancer and Hematology Centers, Baylor College of Medicine, Houston, TX, USA
| | - Jonathan Metts
- Sarcoma Department, Moffitt Cancer Center, Tampa, FL, USA; Cancer and Blood Disorders Institute, Johns Hopkins All Children's Hospital, St Petersburg, FL, USA
| | - Thomas Cash
- Department of Pediatrics, Aflac Cancer and Blood Disorders Center, Children's Healthcare of Atlanta, Emory University School of Medicine, Atlanta, GA, USA.
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2
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Xiao F, Wang W. Development and verification of prognostic nomogram for extraskeletal Ewing's sarcoma based on the SEER database. Heliyon 2025; 11:e40854. [PMID: 39801991 PMCID: PMC11719304 DOI: 10.1016/j.heliyon.2024.e40854] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/14/2024] [Revised: 11/29/2024] [Accepted: 11/29/2024] [Indexed: 01/16/2025] Open
Abstract
Background Extraskeletal Ewing's sarcoma (EES) is a rare tumor, and there is currently no predictive model for overall survival of EES patients. This study sought to use data from the Surveillance, Epidemiology, and End Results (SEER) database to develop a clinical predictive model that could be used to assess the prognosis of EES patients. Methods We selected and downloaded prognostic data on 356 patients diagnosed with extraskeletal Ewing's sarcoma based on screening criteria, These patients were distributed between 2004 and 2015. 356 patients were randomly divided into a training cohort (70 %) and an internal validation cohort (30 %). After univariate or multifactor Cox regression analysis, the relevant variables were screened and a nomogram was constructed. The consistency index (C-index), calibration chart and receiver operating characteristic (ROC) curve were used to evaluate the established nomogram. The clinical utility of the model was verified by clinical decision curve.Study conducted and outcomes reported according to STROBE statement. Results After multifactor regression analysis, we identified five factors that were significantly associated with EES prognosis, and subsequently established a nomogram. Verification data showed that the C-index of this nomogram was 0.829 (95 % CI 0.774-0.884). the AUCs of the nomogram for predicting the 3- and 5-year OS were 0.91 and 0.863. the calibration curves and Decision curve analysis showed that nomogram could predict the prognosis of EES patients. Conclusion Stage, age, tumour size, chemotherapy, and surgery may be independent prognostic factors for EES. our study produced a survival nomogram that can be used to predict the prognosis of patients with EES and validated its performance, which may help clinicians evaluate the condition of patients with EES and choose personalised treatment.
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Affiliation(s)
- Feipeng Xiao
- Affiliated Hengyang Hospital, Hunan Normal University (Hengyang Central Hospital), Hengyang, 421001, China
| | - Weizhen Wang
- Hunan Cancer Hospital, Affiliated Cancer Hospital of Xiangya School of Medicine, Central South University, Changsha, 410000, China
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Koufopoulos NI, Samaras MG, Kotanidis C, Skarentzos K, Pouliakis A, Boutas I, Kontogeorgi A, Zanelli M, Palicelli A, Zizzo M, Broggi G, Caltabiano R, Kyriazoglou AI, Goutas D. Primary and Metastatic Pancreatic Ewing Sarcomas: A Case Report and Review of the Literature. Diagnostics (Basel) 2024; 14:2694. [PMID: 39682601 DOI: 10.3390/diagnostics14232694] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/15/2024] [Revised: 11/22/2024] [Accepted: 11/27/2024] [Indexed: 12/18/2024] Open
Abstract
Ewing sarcomas are rare tumors arising mainly in the bones and the surrounding soft tissues. Primary extraosseous Ewing sarcomas have also been described in several other organs and locations other than bones, including the pancreas. These tumors have well-defined histological, immunohistochemical, and molecular characteristics. In this manuscript, we present a case of primary Ewing sarcoma of the pancreas in a 29-year-old patient, and we systematically review the literature on both primary and metastatic Ewing sarcomas of the pancreas, describing their clinicopathological characteristics. We also discuss the differential diagnosis and the treatment of this rare entity.
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Affiliation(s)
- Nektarios I Koufopoulos
- Second Department of Pathology, Medical School, National and Kapodistrian University of Athens, Attikon University Hospital, 15772 Athens, Greece
| | - Menelaos G Samaras
- Second Department of Pathology, Medical School, National and Kapodistrian University of Athens, Attikon University Hospital, 15772 Athens, Greece
| | - Christakis Kotanidis
- Second Department of Pathology, Medical School, National and Kapodistrian University of Athens, Attikon University Hospital, 15772 Athens, Greece
| | - Konstantinos Skarentzos
- Second Department of Pathology, Medical School, National and Kapodistrian University of Athens, Attikon University Hospital, 15772 Athens, Greece
| | - Abraham Pouliakis
- Second Department of Pathology, Medical School, National and Kapodistrian University of Athens, Attikon University Hospital, 15772 Athens, Greece
| | - Ioannis Boutas
- Breast Unit, Rea Maternity Hospital, P. Faliro, 17564 Athens, Greece
| | - Adamantia Kontogeorgi
- Third Department of Obstetrics and Gynecology, Medical School, National and Kapodistrian University of Athens, Attikon University Hospital, 15772 Athens, Greece
| | - Magda Zanelli
- Pathology Unit, Azienda USL-IRCCS di Reggio Emilia, 42123 Reggio Emilia, Italy
| | - Andrea Palicelli
- Pathology Unit, Azienda USL-IRCCS di Reggio Emilia, 42123 Reggio Emilia, Italy
| | - Maurizio Zizzo
- Surgical Oncology Unit, Azienda USL-IRCCS di Reggio Emilia, 42122 Reggio Emilia, Italy
- Clinical and Experimental Medicine PhD Program, University of Modena and Reggio Emilia, 41121 Modena, Italy
| | - Giuseppe Broggi
- Department of Medical and Surgical Sciences and Advanced Technologies "G.F. Ingrassia", 95123 Catania, Italy
| | - Rosario Caltabiano
- Department of Medical and Surgical Sciences and Advanced Technologies "G.F. Ingrassia", 95123 Catania, Italy
| | - Anastasios I Kyriazoglou
- Second Propaedeutic Department of Medicine, Oncology Unit, National and Kapodistrian University of Athens, Attikon University Hospital, 15772 Athens, Greece
| | - Dimitrios Goutas
- Second Department of Pathology, Medical School, National and Kapodistrian University of Athens, Attikon University Hospital, 15772 Athens, Greece
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Ziomek M, Placzke J, Urbanek K, Skóra T, Rutkowski P, Spałek MJ. Case report: successful treatment of primary intradural extramedullary extraskeletal Ewing sarcoma in adult patient with intralesional surgery, chemotherapy, and proton beam therapy of the cerebrospinal axis. Ther Adv Med Oncol 2024; 16:17588359241297868. [PMID: 39552637 PMCID: PMC11569501 DOI: 10.1177/17588359241297868] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/23/2024] [Accepted: 10/19/2024] [Indexed: 11/19/2024] Open
Abstract
Ewing sarcoma is a rare malignant neoplasm that primarily affects bone in children. Extraskeletal location is less common, while intradural extramedullary Ewing sarcoma (IEES) in adults is a casuistic phenomenon. Due to its rarity, a standardized treatment strategy for IEES has not been established. The clinical use of proton beam therapy (PBT) for craniospinal irradiation (CSI) in the treatment of IEES has not been reported in the literature. A 41-year-old previously healthy man presented with disabling gluteal and lower extremity pain, decreased sensation, and progressive paraparesis without sphincter dysfunction. Imaging showed intradural extramedullary spinal lesions. The patient underwent urgent surgery. Histology and immunohistochemistry suggested a poorly differentiated neuroendocrine tumor. Negative chromogranin staining and a high Ki67 index prompted further investigation. Next-generation sequencing later confirmed an EWSR1/FLI1 translocation, leading to the diagnosis of extraskeletal Ewing sarcoma. The patient received standardized chemotherapy with marked clinical improvement. PBT CSI was initiated but was interrupted due to COVID-19 and other complications. At 20 months follow-up, no recurrence was observed, and the patient reported an active life. Despite intra-spinal spread and multiple complications, intensive chemotherapy combined with PBT CSI led to a favorable outcome. CSI rather than focal radiotherapy should be considered for patients with IEES limited to the cerebrospinal axis. PBT may be used as an alternative to photon radiotherapy to better spare organs at risk.
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Affiliation(s)
- Mateusz Ziomek
- Department of Soft Tissue/Bone Sarcoma and Melanoma, Maria Skłodowska-Curie National Research Institute of Oncology, Warsaw, Poland
| | - Joanna Placzke
- Department of Soft Tissue/Bone Sarcoma and Melanoma, Maria Skłodowska-Curie National Research Institute of Oncology, Warsaw, Poland
| | - Konrad Urbanek
- Department of Radiotherapy, Maria Skłodowska-Curie National Research Institute of Oncology, Kraków Branch, Kraków, Poland
| | - Tomasz Skóra
- Department of Radiotherapy, Maria Skłodowska-Curie National Research Institute of Oncology, Kraków Branch, Kraków, Poland
| | - Piotr Rutkowski
- Department of Soft Tissue/Bone Sarcoma and Melanoma, Maria Skłodowska-Curie National Research Institute of Oncology, Warsaw, Poland
| | - Mateusz Jacek Spałek
- Department of Soft Tissue/Bone Sarcoma and Melanoma, Maria Skłodowska-Curie National Research Institute of Oncology, Roentgena 5, Warsaw 02-781, Poland
- Department of Radiotherapy I, Maria Skłodowska-Curie National Research Institute of Oncology, Warsaw, Poland
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Imran M, Dar HA, Shahzad F, Farhan M, Jielani A, Daudi T, Dave T, Hina S, Mamoon N. Extra-skeletal Ewing sarcoma of the diaphragm in a young female: a case report. Ann Med Surg (Lond) 2024; 86:6731-6736. [PMID: 39525779 PMCID: PMC11543221 DOI: 10.1097/ms9.0000000000002528] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/13/2024] [Accepted: 08/02/2024] [Indexed: 11/16/2024] Open
Abstract
Introduction and importance Extra-skeletal Ewing sarcoma (EES) belongs to the family of primitive neuroectodermal tumors (PNET) and arises from soft tissue, with only 30 cases reported in the literature until now. Early diagnosis is crucial, and the management requires a multidisciplinary approach for better patient outcomes and survival. Case presentation A 20-year-old female presented to the surgical outpatient department with complaints of shortness of breath and right lower chest pain. Upon physical examination, a lipomatous lesion was observed. Ultrasound and CT scan showed a heterogeneously enhancing soft tissue mass in the right lower hemithorax causing erosion and osteolysis of the right 9th rib, involving intercostal muscles, and exerting mass effect on the underlying hemidiaphragm. Later USG-guided Tru-cut biopsy was performed to confirm the diagnosis, which reported Ewing sarcoma with CD 99, FL-1, and NKX 2.2 positive. En-bloc tumor resection along with a portion of the diaphragm was performed, and a tube thoracostomy was carried out. Chest wall reconstruction was done with mesh and a local muscle rotation flap cover. Adjuvant chemotherapy was initiated. Clinical discussion EES often presents with vague symptoms such as shortness of breath or abdominal or chest pain, thus making the diagnosis even more difficult. However, it has a relatively poor prognosis and thus is an important differential to rule out. Conclusion Extra-skeletal Ewing Sarcoma is a highly aggressive tumor that requires prompt diagnosis and treatment, with surgical resection being the first line of treatment. Adjuvant chemotherapy has also shown better outcomes.
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Affiliation(s)
- Muhammad Imran
- Department of General Surgery, Regional Headquarters Shaheed Saif Ur Rehman Hospital, Pakistan
| | - Habib Ahmad Dar
- Department of General Surgery, Scouts Medical Complex, Gilgit, Pakistan
| | | | | | - Asif Jielani
- Gilgit Institute of Nuclear Medicine, Oncology and Radiotherapy, Gilgit, Pakistan
| | - Tajammul Daudi
- Department of General Surgery, Regional Headquarters Shaheed Saif Ur Rehman Hospital, Pakistan
| | - Tirth Dave
- Bukovinian State Medical University, Chernivtsi, Ukraine
| | - Sadia Hina
- Department of General Surgery, Regional Headquarters Shaheed Saif Ur Rehman Hospital, Pakistan
| | - Nadira Mamoon
- Departement of Histopathology, Shifa International Hospital, Islamabad, Pakistan
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Yang G, Huang L, Wu J, Huang B, Zhang C, Li S, Wang F, Jiang X. Case report and literature review: A young man with giant intra-abdominal Ewing sarcoma. Medicine (Baltimore) 2024; 103:e39983. [PMID: 39465729 PMCID: PMC11460867 DOI: 10.1097/md.0000000000039983] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/19/2024] [Indexed: 10/29/2024] Open
Abstract
RATIONALE Extraosseous Ewing sarcoma (EES) is a rare manifestation within the Ewing sarcoma tumor family (ESFT). Its clinical manifestations lack specificity, intestinal obstruction is the main symptom but can also present with abdominal pain, gastrointestinal bleeding, and other discomforts, making it prone to misdiagnosis as intestinal mesenchymal tumor. PATIENT CONCERNS A 29-year-old male was admitted to the hospital with intestinal obstruction symptoms and abdominal CT suggesting "left abdominal occupation." DIAGNOSIS The patient was initially misdiagnosed as intestinal mesenchymal tumor, and was later definitively diagnosed as abdominal Ewing sarcoma by postoperative pathology and genetic testing. INTERVENTIONS Due to the patient's surgical indication, surgical resection with exploratory laparotomy was performed and then the patient underwent systemic chemotherapy. OUTCOMES Intraoperatively, we found a 15-cm tumor originating from the proximal jejunum, with invasion into the peritoneum, duodenum, jejunum, and colon. Finally, the pathological report revealed Ewing sarcoma. LESSONS Giant abdominal Ewing sarcoma with a diameter of 15 cm is rare. Considering postoperative pathology and genetic testing, abdominal Ewing sarcoma was suspected. The patient was successfully treated using surgery.
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Affiliation(s)
- Guang Yang
- Gusu School, Nanjing Medical University, Nanjing, China
| | - Lining Huang
- Department of Hepatobiliary Surgery, the Affiliated Suzhou Hospital of Nanjing Medical University, Suzhou, China
| | - Jianwu Wu
- Department of Hepatobiliary Surgery, the Affiliated Suzhou Hospital of Nanjing Medical University, Suzhou, China
| | - Bo Huang
- Department of Hepatobiliary Surgery, the Affiliated Suzhou Hospital of Nanjing Medical University, Suzhou, China
| | - Cong Zhang
- Gusu School, Nanjing Medical University, Nanjing, China
| | - Song Li
- Department of Hepatobiliary Surgery, the Affiliated Suzhou Hospital of Nanjing Medical University, Suzhou, China
| | - Feng Wang
- Department of Hepatobiliary Surgery, the Affiliated Suzhou Hospital of Nanjing Medical University, Suzhou, China
| | - Xinwei Jiang
- Department of Hepatobiliary Surgery, the Affiliated Suzhou Hospital of Nanjing Medical University, Suzhou, China
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Karabulut B, Yukruk FA, Yenidunya S, Kandemir O, Kosemehmetoglu K. Differential cyclin-E1 expression in CIC-rearranged sarcoma. Ann Diagn Pathol 2024; 72:152320. [PMID: 38703529 DOI: 10.1016/j.anndiagpath.2024.152320] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/08/2024] [Revised: 04/17/2024] [Accepted: 04/18/2024] [Indexed: 05/06/2024]
Abstract
CIC-rearranged sarcoma (CRS) is a group of high-grade undifferentiated small round cell sarcomas examined as a separate entity in the current WHO classification; since it shows more aggressive clinical behavior and distinct morphological and molecular features compared to Ewing sarcoma (ES). As CCNE1 expression is associated with tumor growth in CIC::DUX4 sarcomas, we aimed to demonstrate the value of cyclin E1 expression in CRS. Cyclin E1 immunohistochemistry and break-apart FISH for EWSR1 and CIC gene rearrangements were performed on 3-mm tissue microarrays composed of 40 small round cell tumors. Five cases were classified as CRS, whereas 22 were ES and 13 were unclassified (EWSR1-/CIC-). Among all three diagnostic groups, we found cyclin E1 expression level to be higher in CRS (80 %) and unclassified groups (61.5 %) compared to ES (4.5 %, p < 0.001). In addition, high cyclin E1 expression levels were associated with higher mean age at diagnosis, presence of atypical histology and myxoid stroma, low CD99 expression, and presence of metastasis at diagnosis. The sensitivity and specificity of high cyclin E1 expression in detecting non-ES cases were 95.5 % and 66.7 %, respectively. However, the correlation between cyclin E1 expression level and survival was not statistically significant. This is the first study that shows cyclin E1 immunohistochemical expression in EWSR1-negative undifferentiated small cell sarcomas, particularly CRS.
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MESH Headings
- Humans
- Male
- Oncogene Proteins/metabolism
- Oncogene Proteins/genetics
- Female
- Adult
- Cyclin E/metabolism
- Cyclin E/genetics
- Middle Aged
- Gene Rearrangement
- Adolescent
- Biomarkers, Tumor/metabolism
- Biomarkers, Tumor/genetics
- Young Adult
- Child
- Repressor Proteins/metabolism
- Repressor Proteins/genetics
- Immunohistochemistry/methods
- Sarcoma, Ewing/metabolism
- Sarcoma, Ewing/pathology
- Sarcoma, Ewing/genetics
- Sarcoma/pathology
- Sarcoma/metabolism
- Sarcoma/genetics
- Sarcoma/diagnosis
- In Situ Hybridization, Fluorescence/methods
- Aged
- Child, Preschool
- RNA-Binding Protein EWS/genetics
- RNA-Binding Protein EWS/metabolism
- Sarcoma, Small Cell/metabolism
- Sarcoma, Small Cell/genetics
- Sarcoma, Small Cell/pathology
- Sarcoma, Small Cell/diagnosis
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Affiliation(s)
- Berna Karabulut
- Department of Pathology, Dr. Abdurrahman Yurtaslan Ankara Oncology Training and Research Hospital, Ankara 06200, Turkey.
| | - Fisun Ardic Yukruk
- Department of Pathology, Dr. Abdurrahman Yurtaslan Ankara Oncology Training and Research Hospital, Ankara 06200, Turkey
| | - Sibel Yenidunya
- Department of Pathology, Dr. Abdurrahman Yurtaslan Ankara Oncology Training and Research Hospital, Ankara 06200, Turkey
| | | | - Kemal Kosemehmetoglu
- Department of Pathology, Hacettepe University Faculty of Medicine, Ankara 06230, Turkey.
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Hajjaj OI, Corke L, Strahlendorf C, Hamilton SN, Feng X, Simmons CE. Treatment differences and long-term outcomes in adults and children with Ewing sarcoma. Cancer Epidemiol 2024; 92:102653. [PMID: 39179493 DOI: 10.1016/j.canep.2024.102653] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/30/2024] [Revised: 08/09/2024] [Accepted: 08/16/2024] [Indexed: 08/26/2024]
Abstract
INTRODUCTION Ewing sarcoma is an aggressive malignancy primarily affecting children and adolescents. Limited research is available on treatment practices, clinical course, and survival in adults. METHODS A multi-institution retrospective cohort study of all adults (>18 years) and children (≤18 years) with Ewing sarcoma treated in British Columbia, Canada between January 01, 2000 and December 31, 2018. RESULTS One-hundred seven individuals (66 adults, 41 children) were included in the analysis. 5-year OS was 58 % in adults and 75 % in children. For individuals with local disease, 5-year OS was 74 % in adults and 84 % in children. Adult status was associated with impaired PFS (HR, 1.8; 95 % CI, 1.0 - 3.1, p=0.04) and OS (HR, 1.8; 95 % CI, 0.9 - 3.5; p=0.088). A Charlson Comorbidity Index (CCI) ≥3 was associated with impaired survival in adults and children (HR, 3.9, 95 % CI, 2.0 - 7.5; p=<0.001); baseline CCIs were not significantly different between groups. Most adults (61/66; 92 %) and all children (41/41; 100 %) received systemic treatment with no significant difference in mean lines of therapy, treatment modalities or agents. Most children received interval-compressed chemotherapy (35/41; 85 %) compared to adults (19/61; 29 %; p=<0.001). Interval-compression was not significantly associated with improved survival in adults with local disease (HR, 0.51; 95 % CI 0.1 - 2.3; p=0.373). Children more often initiated treatment within 28 days of diagnosis (31/33; 94 %) compared to adults (41/64; 64 %, p=0.001). Treatment within 28 days was associated with improved survival in the entire cohort (HR, 2.04 95 % CI, 1.1 - 3.9; p = 0.03). This association was preserved in subanalysis of individuals with local disease (HR, 5.4; 95 % CI, 1.9 - 15; p = 0.001) and only adults (HR, 5.3, 95 % CI, 1.7 - 17; p = 0.005). DISCUSSION Survival for adults with Ewing sarcoma is inferior to children despite similarities in presentation, tumour characteristics and treatments. Further studies on the value of interval-compression in adults are required. Timely initation of treatment should be a priority for this disease.
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Affiliation(s)
- Omar I Hajjaj
- Department of Medicine, Queen's University, Kingston, ON, Canada; Department of Medical Oncology, BC Cancer, Vancouver, BC, Canada
| | - Lauren Corke
- Department of Medical Oncology, BC Cancer, Vancouver, BC, Canada
| | - Caron Strahlendorf
- Department of Pediatrics, BC Children's Hospital, Vancouver, BC, Canada; Department of Medicine, University of British Columbia, Vancouver, BC, Canada
| | - Sarah Nicole Hamilton
- Department of Medicine, University of British Columbia, Vancouver, BC, Canada; Department of Radiation Oncology, BC Cancer, Vancouver, BC, Canada
| | - Xiaolan Feng
- Department of Medical Oncology, Tom Baker Cancer Center, Calagary, AB, Canada; Department of Medicine, Cumming School of Medicine, Calagary, AB, Canada
| | - Christine E Simmons
- Department of Medical Oncology, BC Cancer, Vancouver, BC, Canada; Department of Medicine, University of British Columbia, Vancouver, BC, Canada.
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9
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Schulpen M, Haveman LM, van der Heijden L, Kaal SEJ, Bramer JAM, Fajardo RD, de Haan JJ, Hiemcke-Jiwa LS, Ter Horst SAJ, Jutte PC, Schreuder HWB, Tromp JM, van der Graaf WTA, van de Sande MAJ, Gelderblom H, Merks JHM, Karim-Kos HE. The survival disparity between children and adolescents and young adults (AYAs) with Ewing sarcoma in the Netherlands did not change since the 1990s despite improved survival: A population-based study. Eur J Cancer 2024; 208:114209. [PMID: 39018631 DOI: 10.1016/j.ejca.2024.114209] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/03/2024] [Revised: 06/28/2024] [Accepted: 07/03/2024] [Indexed: 07/19/2024]
Abstract
BACKGROUND Adolescents and young adults (AYAs) with Ewing sarcoma have a worse prognosis than children. Population-based survival evaluations stratifying findings by important clinical factors are, however, limited. This Dutch population study comprehensively compared survival of children and AYAs with Ewing sarcoma over three decades considering diagnostic period, tissue of origin, tumor site, and disease stage. METHODS Data on all children (0-17 years, N = 463) and AYAs (18-39 years, N = 379) diagnosed with Ewing sarcoma in the Netherlands between 1990-2018 were collected from the Netherlands Cancer Registry with follow-up until February 2023. Five-year relative survival was calculated using the cohort method. Multivariable analyses were conducted through Poisson regression. RESULTS Children with Ewing sarcoma had a significantly higher 5-year relative survival than AYAs (65 % vs. 44 %). An increasing trend in survival was noted reaching 70 % in children and 53 % in AYAs in 2010-2018. Results were similar for Ewing bone sarcoma and extraosseous Ewing sarcoma. AYAs had a poorer prognosis than children for most tumor sites and regardless of disease stage. Survival probabilities were 60 % vs. 78 % for localized disease and 20 % vs. 33 % for metastatic disease. Multivariable-regression analysis, adjusted for follow-up time, diagnostic period, sex, disease stage, and tumor site, confirmed increased excess mortality among AYAs compared with children (excess HR: 1.7, 95 % CI: 1.3-2.1). CONCLUSIONS Despite survival improvements since the 1990s, AYAs with Ewing sarcoma in the Netherlands continue to fare considerably worse than children. This survival disparity was present irrespective of tissue of origin, tumor site, and disease stage.
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Affiliation(s)
- Maya Schulpen
- Princess Máxima Center for pediatric oncology, Utrecht, the Netherlands
| | - Lianne M Haveman
- Princess Máxima Center for pediatric oncology, Utrecht, the Netherlands
| | | | - Suzanne E J Kaal
- Department of Medical Oncology, Radboud University Medical Center, Nijmegen, the Netherlands
| | - Jos A M Bramer
- Princess Máxima Center for pediatric oncology, Utrecht, the Netherlands; Department of Orthopedic Surgery and Sports Medicine, Amsterdam University Medical Centers, Amsterdam, the Netherlands
| | - Raquel Dávila Fajardo
- Princess Máxima Center for pediatric oncology, Utrecht, the Netherlands; Department of Radiation Oncology, University Medical Center Utrecht, Utrecht, the Netherlands
| | - Jacco J de Haan
- Department of Medical Oncology, University Medical Center Groningen, Groningen, the Netherlands
| | - Laura S Hiemcke-Jiwa
- Princess Máxima Center for pediatric oncology, Utrecht, the Netherlands; Department of Pathology, University Medical Center Utrecht, Utrecht, the Netherlands
| | - Simone A J Ter Horst
- Princess Máxima Center for pediatric oncology, Utrecht, the Netherlands; Division of Imaging and Oncology, University Medical Center Utrecht, Utrecht University, Utrecht, the Netherlands
| | - Paul C Jutte
- Department of Orthopedics, University Medical Center Groningen, Groningen, the Netherlands
| | - Hendrik W B Schreuder
- Princess Máxima Center for pediatric oncology, Utrecht, the Netherlands; Department of Orthopedics, Radboud University Medical Center, Nijmegen, the Netherlands
| | - Jacqueline M Tromp
- Department of Medical Oncology, Amsterdam University Medical Centers, Amsterdam, the Netherlands
| | - Winette T A van der Graaf
- Department of Medical Oncology, The Netherlands Cancer Institute, Amsterdam, the Netherlands; Department of Medical Oncology, Erasmus MC Cancer Institute, Erasmus University Medical Center, Rotterdam, the Netherlands
| | - Michiel A J van de Sande
- Princess Máxima Center for pediatric oncology, Utrecht, the Netherlands; Department of Orthopedics, Leiden University Medical Center, Leiden, the Netherlands
| | - Hans Gelderblom
- Department of Medical Oncology, Leiden University Medical Center, Leiden, the Netherlands
| | - Johannes H M Merks
- Princess Máxima Center for pediatric oncology, Utrecht, the Netherlands; Division of Imaging and Oncology, University Medical Center Utrecht, Utrecht University, Utrecht, the Netherlands
| | - Henrike E Karim-Kos
- Princess Máxima Center for pediatric oncology, Utrecht, the Netherlands; Department of Research and Development, Netherlands Comprehensive Cancer Organization (IKNL), Utrecht, the Netherlands.
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10
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Bianchi G, Laginestra MA, Simonetti E, Ibrahim T, Macrì F, Ostetto F, Tuzzato G, Paioli A, Gambarotti M, Cocchi S, Donati DM, Scotlandi K, Laranga R. Extraskeletal Ewing Sarcoma of the Extremities and Trunk: A Retrospective Analysis of a Mono-Institutional Series. Oncol Res Treat 2024; 47:496-508. [PMID: 39084202 DOI: 10.1159/000540613] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/30/2024] [Accepted: 07/23/2024] [Indexed: 08/02/2024]
Abstract
INTRODUCTION Extraskeletal Ewing sarcoma (EEwS) is a rare malignant tumor, and current international recommendations indicate systemic and local treatment like bone Ewing sarcoma (BEwS); to the best of our knowledge, very few studies tried to explore the clinical and genetic characteristics of this tumor, and the most appropriate treatment strategy remains uncertain. METHODS We reviewed 35 EEwS cases enrolled at Rizzoli Orthopedic Institute in Bologna, Italy, between 1988-2022. We performed RNA sequencing in 18 Ewing sarcoma cases, including 12 BEwSs and 6 EEwSs. We analyzed overall survival (OS), local relapse-free survival (LRFS), and metastasis-free survival (MFS) and the risk factors associated to survival. RESULTS Unsupervised hierarchical clustering showed no differences in the transcriptional profile between EEwS and BEwS. Five-year OS was 67% (95% confidence interval [CI]: 47-80), 5-year LRFS was 61% (95% CI: 43-75), and 5-year MFS was 55% (95% CI: 38-70). Recurrent tumors, larger than 8 cm, and elevated lactate dehydrogenase (LDH) serum value resulted to be negative prognostic factors. CONCLUSIONS The finding/detection of a genetic profile that is indistinguishable between EEwS and BEwS confirms the view that the two subgroups belong to the same tumor entity and supports the use of a single therapeutic approach for Ewing sarcoma, regardless of the site of origin. Statistical evaluation showed that size bigger than 8 cm, elevated LDH, and recurrent tumors had a worse prognosis, suggesting a risk-stratification method for identifying patients for specific therapy treatment. However, larger, multicenter, prospective trials are called for to validate our findings.
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Affiliation(s)
- Giuseppe Bianchi
- 3rd Orthopedic and Traumatologic Clinic prevalently Oncologic IRCCS Istituto Ortopedico Rizzoli, Bologna, Italy
| | | | - Elisa Simonetti
- Laboratory of Experimental Oncology, IRCCS Istituto Ortopedico Rizzoli, Bologna, Italy
| | - Toni Ibrahim
- Osteoncology, Bone and Soft Tissue Sarcomas and Innovative Therapies, IRCCS Istituto Ortopedico Rizzoli, Bologna, Italy
| | - Fabiana Macrì
- 3rd Orthopedic and Traumatologic Clinic prevalently Oncologic IRCCS Istituto Ortopedico Rizzoli, Bologna, Italy
| | - Federico Ostetto
- 3rd Orthopedic and Traumatologic Clinic prevalently Oncologic IRCCS Istituto Ortopedico Rizzoli, Bologna, Italy
| | - Gianmarco Tuzzato
- 3rd Orthopedic and Traumatologic Clinic prevalently Oncologic IRCCS Istituto Ortopedico Rizzoli, Bologna, Italy
| | - Anna Paioli
- Osteoncology, Bone and Soft Tissue Sarcomas and Innovative Therapies, IRCCS Istituto Ortopedico Rizzoli, Bologna, Italy
| | - Marco Gambarotti
- Pathology Department, IRCCS Istituto Ortopedico Rizzoli, Bologna, Italy
| | - Stefania Cocchi
- Pathology Department, IRCCS Istituto Ortopedico Rizzoli, Bologna, Italy
| | - Davide Maria Donati
- 3rd Orthopedic and Traumatologic Clinic prevalently Oncologic IRCCS Istituto Ortopedico Rizzoli, Bologna, Italy
- Department of Biomedical and Neuromotor Sciences (DIBINEM), University of Bologna, Bologna, Italy
| | - Katia Scotlandi
- Laboratory of Experimental Oncology, IRCCS Istituto Ortopedico Rizzoli, Bologna, Italy
| | - Roberta Laranga
- 3rd Orthopedic and Traumatologic Clinic prevalently Oncologic IRCCS Istituto Ortopedico Rizzoli, Bologna, Italy
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11
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Dehner CA, Lazar AJ, Chrisinger JSA. Updates on WHO classification for small round cell tumors: Ewing sarcoma vs. everything else. Hum Pathol 2024; 147:101-113. [PMID: 38280658 DOI: 10.1016/j.humpath.2024.01.007] [Citation(s) in RCA: 12] [Impact Index Per Article: 12.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/17/2023] [Revised: 01/16/2024] [Accepted: 01/22/2024] [Indexed: 01/29/2024]
Abstract
The WHO Classification of Soft Tissue and Bone Tumours currently recognizes four categories of undifferentiated small round cell sarcoma: Ewing sarcoma, round cell sarcoma with EWSR1-non-ETS fusions including NFATc2 and PATZ1, CIC-rearranged sarcoma, and sarcoma with BCOR genetic alterations. These neoplasms frequently pose significant diagnostic challenges due to rarity and overlapping morphologic and immunohistochemical findings. Further, molecular testing, with accompanying pitfalls, may be needed to establish a definitive diagnosis. This review summarizes the clinical, histologic, immunohistochemical, and molecular features of these neoplasms. In addition, differential diagnosis and areas of uncertainty and ongoing investigation are discussed.
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MESH Headings
- Humans
- Sarcoma, Ewing/genetics
- Sarcoma, Ewing/pathology
- Sarcoma, Ewing/classification
- Sarcoma, Ewing/chemistry
- Bone Neoplasms/pathology
- Bone Neoplasms/genetics
- Bone Neoplasms/classification
- Sarcoma, Small Cell/genetics
- Sarcoma, Small Cell/pathology
- Sarcoma, Small Cell/classification
- Biomarkers, Tumor/genetics
- Biomarkers, Tumor/analysis
- World Health Organization
- Diagnosis, Differential
- Immunohistochemistry
- Soft Tissue Neoplasms/pathology
- Soft Tissue Neoplasms/genetics
- Soft Tissue Neoplasms/classification
- RNA-Binding Protein EWS/genetics
- Repressor Proteins/genetics
- Gene Rearrangement
- Proto-Oncogene Proteins/genetics
- Predictive Value of Tests
- Phenotype
- Genetic Predisposition to Disease
- Oncogene Proteins, Fusion/genetics
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Affiliation(s)
- Carina A Dehner
- Department of Anatomic Pathology and Laboratory Medicine, Indiana University, 635 Barnhill Drive, Indianapolis, IN, 46202, USA.
| | - Alexander J Lazar
- Department of Pathology, University of Texas MD Anderson Cancer Center, 1515 Holcombe Blvd, Houston, TX, 77030, USA; Department of Genomic Medicine, University of Texas MD Anderson Cancer Center, 1515 Holcombe Blvd, Houston, TX, 77030, USA.
| | - John S A Chrisinger
- Department of Pathology and Immunology, Division of Anatomic and Molecular Pathology, Washington University School of Medicine, 660 S. Euclid Ave, St. Louis, MO, 63110, USA.
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12
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Greenfield BM, Wilson MA, Schulte KJ, Silverstein S. Unveiling the Unlikely: Extraskeletal Ewing Sarcoma Masquerading as Gastrointestinal Bleeding. Cureus 2024; 16:e57109. [PMID: 38681455 PMCID: PMC11055616 DOI: 10.7759/cureus.57109] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/29/2024] [Accepted: 03/27/2024] [Indexed: 05/01/2024] Open
Abstract
While Ewing sarcoma is traditionally a malignant tumor of bone, it may uncommonly present extra-skeletally, leading to an array of puzzling presentations depending on the tissue involved. Here, we describe the case of a 66-year-old man who presented to the primary care office for evaluation of intermittent melena. He ultimately underwent capsule endoscopy and developed a secondary small bowel obstruction, unveiling his neoplasm. The tumor was then resected and managed with surveillance only, and the patient remains without evidence of disease after four years of follow-up.
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Affiliation(s)
- Bryan M Greenfield
- Primary Care Medicine, Nova Southeastern University Dr. Kiran C. Patel College of Allopathic Medicine, Fort Lauderdale, USA
| | - Madeleine A Wilson
- Primary Care Medicine, Nova Southeastern University Dr. Kiran C. Patel College of Allopathic Medicine, Fort Lauderdale, USA
| | - Kyle J Schulte
- Primary Care Medicine, Nova Southeastern University Dr. Kiran C. Patel College of Allopathic Medicine, Fort Lauderdale, USA
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13
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Aiba H, Kojima Y, Shimoi T, Sudo K, Yazaki S, Imai T, Yoshida A, Iwata S, Kobayashi E, Kawai A, Arakawa A, Ogawa C, Kimura H, Yonemori K. Incidence of skeletal-related events in patients with Ewing sarcoma: An observational retrospective study in Japan. Cancer Med 2024; 13:e7060. [PMID: 38466026 PMCID: PMC10926881 DOI: 10.1002/cam4.7060] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/08/2023] [Revised: 01/02/2024] [Accepted: 02/16/2024] [Indexed: 03/12/2024] Open
Abstract
BACKGROUND Skeletal-related events (SREs), including the pathological fracture, surgical treatment or radiation of bone lesions, malignant spinal cord compression, hypercalcemia, are important considerations when managing metastatic bone tumors; however, owing to their rarity, the incidence of SREs in patients with Ewing sarcoma remains unknown. METHODS We retrospectively reviewed the clinical data from 146 patients with Ewing sarcoma treated at a single institution from 2005 to 2019. The median age at diagnosis was 22.7 years. Fifty patients (34.2%) had metastatic disease at diagnosis. The primary outcome was the SRE-free rate among patients with Ewing sarcoma. Moreover, we identified the risk factors for SREs using univariate or multivariate analyses. RESULTS During the observational period (median, 2.6 years), SREs occurred in 23 patients. Radiation to the bone, malignant spinal cord compression, and hypercalcemia were documented as the initial SREs in 12 patients (52.2%), 10 patients (43.5%), and one patient (4.3%), respectively. The SRE-free rate was 94.2 ± 2.0, 87.3 ± 3.0, and 79.6 ± 3.8% at 1, 2, and 3 years after the initial visit, respectively. Multivariate analysis revealed bone metastasis at diagnosis (hazard ratio [HR] = 4.41, p = 0.007), bone marrow invasion (HR = 34.08, p < 0.001), and local progression or recurrence after definitive treatment (HR = 3.98, p = 0.012) as independent risk factors for SREs. CONCLUSIONS SREs are non-rare events that can occur during the treatment course for Ewing sarcoma, with an especially high incidence of malignant spinal cord compression. Patients with metastatic disease at diagnosis, especially in the bone or bone marrow, or with local progression or recurrence after definitive treatment, should be carefully monitored for the occurrence of SREs. The most effective methods to monitor the occurrence of SREs and new preventative therapies for SREs should be investigated in the future.
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Affiliation(s)
- Hisaki Aiba
- Department of Medical Oncology, National Cancer Center Hospital, National Cancer Center Hospital, Tokyo, Japan
- Department of Orthopaedic Surgery, Nagoya City University, Nagoya, Japan
| | - Yuki Kojima
- Department of Medical Oncology, National Cancer Center Hospital, National Cancer Center Hospital, Tokyo, Japan
| | - Tatsunori Shimoi
- Department of Medical Oncology, National Cancer Center Hospital, National Cancer Center Hospital, Tokyo, Japan
| | - Kazuki Sudo
- Department of Medical Oncology, National Cancer Center Hospital, National Cancer Center Hospital, Tokyo, Japan
| | - Shu Yazaki
- Department of Medical Oncology, National Cancer Center Hospital, National Cancer Center Hospital, Tokyo, Japan
| | - Toru Imai
- Department of Medical Oncology, National Cancer Center Hospital, National Cancer Center Hospital, Tokyo, Japan
| | - Akihiko Yoshida
- Department of Diagnostic Pathology, National Cancer Center Hospital, National Cancer Center Hospital, Tokyo, Japan
| | - Shintaro Iwata
- Department of Musculoskeletal Oncology and Rehabilitation, National Cancer Center Hospital, National Cancer Center Hospital, Tokyo, Japan
| | - Eisuke Kobayashi
- Department of Musculoskeletal Oncology and Rehabilitation, National Cancer Center Hospital, National Cancer Center Hospital, Tokyo, Japan
| | - Akira Kawai
- Department of Musculoskeletal Oncology and Rehabilitation, National Cancer Center Hospital, National Cancer Center Hospital, Tokyo, Japan
| | - Ayumu Arakawa
- Department of Pediatric Oncology, National Cancer Center Hospital, Tokyo, Japan
| | - Chitose Ogawa
- Department of Pediatric Oncology, National Cancer Center Hospital, Tokyo, Japan
| | - Hiroaki Kimura
- Department of Orthopaedic Surgery, Nagoya City University, Nagoya, Japan
| | - Kan Yonemori
- Department of Medical Oncology, National Cancer Center Hospital, National Cancer Center Hospital, Tokyo, Japan
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14
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Ghandour M, Semaan K, Saad E, Horsch A, Abdallah R, Semaan D. Clinicodemographic characteristics of extraosseous ewing sarcoma: A comparative meta-analysis of pediatric and adult patients. J Orthop 2023; 44:86-92. [PMID: 37731676 PMCID: PMC10507075 DOI: 10.1016/j.jor.2023.09.002] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/30/2023] [Accepted: 09/04/2023] [Indexed: 09/22/2023] Open
Abstract
Background Evidence suggests different presentation patterns and prognosis of extraosseous Ewing Sarcoma (EES) based on age. Thus, we carried out this study to test the difference between children and adult EES cases regarding clinicodemographic characteristics and prognosis. Methods A total of 4 databases were explored yielding 18 relevant studies for data synthesis. Outcomes included the comparison of demographic and clinical characteristics as well as prognosis between children and adults with EES. Log odds ratio (logOR) and its 95% confidence interval (CI) were pooled across studies. Statistical models/methods were selected based on heterogeneity. Results Our analysis included a total of 1261 children and 1256 adults. When we compared these two age categories, we did not observe a significant difference in the risk of developing EES [logOR = -0.13; 95% CI: -0.65: 0.39; I2 = 88.42%]. No significant differences regarding gender, tumor location, and size (≤5 vs. >5 cm), EWSR1 positivity, or management modality. We did not observe significant difference regarding clinical outcomes, such as 5-year overall survival and event-free survival, recurrence, mortality, no evidence of disease, and secondary metastasis. Conclusions Our findings highlight the absence of an association between the age category of patients and the incidence of EES, as well as its clinical outcomes.
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Affiliation(s)
- Maher Ghandour
- Orthopedics Department, Heidelberg University Hospital, Germany
- Orthopedics Department, Lebanese University, Lebanon
| | - Karl Semaan
- Medicine, Université Saint Joseph, Beirut, Lebanon
| | - Eddy Saad
- Medicine, Université Saint Joseph, Beirut, Lebanon
| | - Axel Horsch
- Orthopedics Department, Heidelberg University Hospital, Germany
| | | | - Doumit Semaan
- Orthopedics Department, Lebanese University, Lebanon
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15
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Al-Mohammad A, Dyson EW, Russo VM, Russo A. Drop metastasis from the extradural to the intradural space in spinal Ewing's sarcoma - a novel case report. Br J Neurosurg 2023:1-4. [PMID: 37723663 DOI: 10.1080/02688697.2023.2258205] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/03/2023] [Accepted: 09/06/2023] [Indexed: 09/20/2023]
Abstract
Spinal Ewing's Sarcoma is a rare tumour predominantly affecting children and adolescents. We describe the case of an 18-year-old male patient who first presented with a primary extradural cervical Ewing's sarcoma tumour, and 5 years later had a recurrence with thoracolumbar and lumbosacral intradural extramedullary Ewing's sarcoma tumours. Both presentations were successfully treated by surgical resection and adjuvant chemo- and radiotherapy, and he remains disease-free at 12 months follow-up. This is the first reported case of seeding of tumour from an extradural primary Ewing's sarcoma to intradural metastases. Total surgical resection of his initial cervical tumour, performed at another centre, was complicated by a dural tear and CSF leak. Thus, we propose that isolated drop metastasis via CSF fistula is the most likely mechanism for tumour spread in this case. Thus, clinicians may wish to counsel patients on the possibility of such spread if a CSF leak is encountered, and potentially increase the frequency of imaging surveillance of the whole spine in this context.
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Affiliation(s)
- Alaa Al-Mohammad
- The Victor Horsley Department of Neurosurgery, The Hospital for Neurology and Neurosurgery, London, UK
| | - Edward W Dyson
- The Victor Horsley Department of Neurosurgery, The Hospital for Neurology and Neurosurgery, London, UK
| | - Vittorio M Russo
- The Victor Horsley Department of Neurosurgery, The Hospital for Neurology and Neurosurgery, London, UK
| | - Antonino Russo
- The Victor Horsley Department of Neurosurgery, The Hospital for Neurology and Neurosurgery, London, UK
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16
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Wytiaz V, Schwartz E, Rice JD, Zhao L, Jasty R, Schuetze S, Chugh R. Disparate Outcomes, Biologic and Therapeutic Differences in Pediatric versus Adult Patients with Ewing Sarcoma. Oncology 2023; 102:1-8. [PMID: 37598679 DOI: 10.1159/000533412] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/07/2023] [Accepted: 07/31/2023] [Indexed: 08/22/2023]
Abstract
INTRODUCTION Ewing sarcoma (ES) is a small blue round cell sarcoma affecting a wide age spectrum. Clinical advances predominately stem from pediatric research consortia clinical trials. In most series, adults have poorer outcomes when compared to children. The aim of this study was to perform a detailed evaluation of factors potentially accounting for this difference. METHODS A single institution retrospective chart review was conducted on patients with ES diagnosed from 2005 to 2015, identified using a free-text search engine with the keywords "Ewing sarcoma" as well as a corresponding pathologic database. Data were analyzed based on age, pediatric (age <18) and adult (age >18 years), using a multivariate analysis model. RESULTS Eighty-eight ES patients (34 pediatric, 54 adult) were identified with a median age of 13 (range 3-18) and 31 (range 19-70) in their respective cohorts. Five-year overall survival (OS) was higher in pediatric patients (73.5% vs. 48.1%, p = 0.0213). By stage, 5-year OS in pediatric versus adult patients was 65% versus 20% (p = 0.0530) in metastatic (n = 32) and 68.1% versus 58.8% (p = 0.278) in localized (n = 56) patients. Lung-only metastases were present in 83% of metastatic pediatric patients versus 35% of adult metastatic patients. Pediatric patients received more cycles of first-line chemotherapy (13.8 vs. 11.4, p = 0.001), independent of stage. More cycles of chemotherapy correlated with improved OS (HR: 0.864, CI: 0.773-0.967) and progression-free survival (HR: 0.897, CI: 0.808-0.996). CONCLUSIONS Outcome differences were most notable in patients with metastatic disease, although not statistically significant. Our series found differences in presentation between pediatric and adult populations with adult patients receiving fewer cycles of chemotherapy. This may suggest that both variations in underlying disease biology and potentially differences in treatment may account for outcome disparities.
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Affiliation(s)
- Victoria Wytiaz
- Division of Hematology/Oncology, Department of Internal Medicine, University of Michigan, Ann Arbor, Michigan, USA,
| | - Eric Schwartz
- Oncology, Colorado Permanente Medical Group, Denver, Colorado, USA
| | - John D Rice
- Department of Biostatistics, University of Michigan, Ann Arbor, Michigan, USA
| | - Lili Zhao
- Department of Biostatistics, University of Michigan, Ann Arbor, Michigan, USA
| | - Rama Jasty
- Division of Hematology/Oncology, Department of Pediatrics, University of Michigan, Ann Arbor, Michigan, USA
| | - Scott Schuetze
- Division of Hematology/Oncology, Department of Internal Medicine, University of Michigan, Ann Arbor, Michigan, USA
| | - Rashmi Chugh
- Division of Hematology/Oncology, Department of Internal Medicine, University of Michigan, Ann Arbor, Michigan, USA
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17
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Worthy J, Ganguli MP, Kile MR, Satei AM, Mills ND. A Rare Case of Sinonasal Ewing Sarcoma With Radiologic-Pathologic Correlation. Cureus 2023; 15:e43708. [PMID: 37724222 PMCID: PMC10505484 DOI: 10.7759/cureus.43708] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 08/18/2023] [Indexed: 09/20/2023] Open
Abstract
An 89-year-old male presented with syncope and worsening difficulty in breathing through the left nostril. Computed tomography demonstrated a tumor in the anterior ethmoid air cells and maxillary sinus, which extended into the frontal lobe. Magnetic resonance imaging similarly demonstrated an aggressive lesion. This mass was difficult to differentiate from more commonly seen lesions at this location such as an esthesioneuroblastoma or nasopharyngeal carcinoma. Direct visualization, biopsy, and subsequent pathologic analysis eventually confirmed the diagnosis of malignant Ewing sarcoma (EWS). Our case explores the radiological findings of EWS originating from the ethmoid sinus, compares EWS with other common carcinomas in the same location, confirms the diagnosis through pathological correlation, and investigates the prognosis and treatment of these lesions. This case highlights the importance of a multidisciplinary approach to diagnose EWS when it occurs in an atypical location. The clinical team relied on input from the radiology, surgery, ENT, neurology, and pathology departments to make an accurate diagnosis and plan treatment for this aggressive tumor.
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Affiliation(s)
- Jennifer Worthy
- Medicine, Ross University School of Medicine, Bridgetown, BRB
| | | | - Mahlon R Kile
- Medicine, Ross University School of Medicine, Bridgetown, BRB
| | - Alexander M Satei
- Diagnostic Radiology, Trinity Health Oakland Hospital, Pontiac, USA
- Diagnostic Radiology, Wayne State University School of Medicine, Detroit, USA
| | - Nicholas D Mills
- Diagnostic Radiology, Trinity Health Oakland Hospital, Pontiac, USA
- Diagnostic Radiology, Wayne State University School of Medicine, Detroit, USA
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18
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Ioannidou M, Tsotridou E, Samoladas E, Tragiannidis A, Kouskouras K, Sfougaris D, Spyridakis I, Foroulis C, Galli-Tsinopoulou A, Hatzipantelis E. Unusual Manifestation of Extraosseous Ewing Sarcoma: Report of 3 Cases. Balkan J Med Genet 2023; 25:77-81. [PMID: 37265973 PMCID: PMC10230840 DOI: 10.2478/bjmg-2022-0022] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 06/03/2023] Open
Abstract
Ewing sarcoma (ES), described as a diffuse endothelioma of the bone, is divided into two categories: osseous and extraosseous, which mainly affects adolescents. Extraosseous Ewing Sarcomas (EES) are rare tumors originating from soft tissues. Their clinical presentation depends mainly on the primary location of the tumor and are highly chemosensitive and radiosensitive. The purpose of this study was to describe the clinical characteristics and outcomes of 3 children with EES and uncommon presentation treated in our Unit. The diagnosis of EES was confirmed by biopsy and cytogenetic analysis with fluorescence in situ hybridization (FISH). Surgical excision was planned as primary treatment, followed by adjuvant chemotherapy according to EURO-E.W.I.N.G protocol. To date, all patients are alive, 1, 3 and 4 years after completion of treatment, with no signs of recurrence or metastasis.
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Affiliation(s)
- M. Ioannidou
- Children’s and Adolescent’s Hematology-Oncology Unit of 2 Department of Pediatrics, Aristotle University of Thessaloniki, AHEPA University General Hospital, Thessaloniki, Greece
| | - E. Tsotridou
- Children’s and Adolescent’s Hematology-Oncology Unit of 2 Department of Pediatrics, Aristotle University of Thessaloniki, AHEPA University General Hospital, Thessaloniki, Greece
| | - E. Samoladas
- 2 Department of Orthopedic Surgery, Aristotle University of Thessaloniki, “Gennimatas” General Hospital, Thessaloniki, Greece
| | - A. Tragiannidis
- Children’s and Adolescent’s Hematology-Oncology Unit of 2 Department of Pediatrics, Aristotle University of Thessaloniki, AHEPA University General Hospital, Thessaloniki, Greece
| | - K. Kouskouras
- Department of Radiology, Aristotle University of Thessaloniki, AHEPA University General Hospital, Thessaloniki, Greece
| | - D. Sfougaris
- 1 Department of Pediatric Surgery, Aristotle University of Thessaloniki, “Gennimatas” General Hospital, Thessaloniki, Greece
| | - I. Spyridakis
- 2 Department of Pediatric Surgery, Aristotle University of Thessaloniki, “Papageorgiou” General Hospital, Thessaloniki, Greece
| | - C. Foroulis
- Department of Cardiothoracic Surgery, Aristotle University of Thessaloniki, AHEPA University General Hospital, Thessaloniki, Greece
| | - A. Galli-Tsinopoulou
- Children’s and Adolescent’s Hematology-Oncology Unit of 2 Department of Pediatrics, Aristotle University of Thessaloniki, AHEPA University General Hospital, Thessaloniki, Greece
| | - E. Hatzipantelis
- Children’s and Adolescent’s Hematology-Oncology Unit of 2 Department of Pediatrics, Aristotle University of Thessaloniki, AHEPA University General Hospital, Thessaloniki, Greece
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19
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Aiba H, Kojima Y, Shimoi T, Sudo K, Yazaki S, Imai T, Yoshida A, Iwata S, Kobayashi E, Kawai A, Arakawa A, Ogawa C, Kimura H, Yonemori K. Clinical characteristics of primary cutaneous and subcutaneous Ewing sarcoma. Jpn J Clin Oncol 2023:7136607. [PMID: 37093679 DOI: 10.1093/jjco/hyad031] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/02/2023] [Accepted: 03/24/2023] [Indexed: 04/25/2023] Open
Abstract
OBJECTIVE Given the rarity of cutaneous/subcutaneous Ewing sarcoma, their clinical characteristics remain poorly understood. In this study, we aimed to analyse the clinical characteristics of patients with cutaneous/subcutaneous Ewing sarcoma and review the treatment strategy. METHODS We reviewed the clinical data of 154 patients with Ewing sarcoma who were treated at our hospital between 2005 and 2019. Amongst these patients, 21 patients with cutaneous/subcutaneous Ewing sarcoma were analysed. As a basic strategy, patients with localized disease received intensive chemotherapy (vincristine-doxorubicin-cyclophosphamide/ifosfamide-etoposide), followed by definitive surgery with or without radiotherapy. In total, 15 patients underwent pre-diagnostic resection with macroscopic residue (seven patients) or non-macroscopic residue (eight patients) before intensive chemotherapy. RESULTS The median tumour length of the measurable lesions was 3.2 cm, and the ratio of metastasis was significantly lower than the Ewing sarcoma of other anatomical sites (10% vs. 37%, P = 0.013). Despite the pre-diagnostic resection, local recurrence after additional resection and/or adjuvant radiotherapy did not occur in any of the patients with localized disease. Overall survival was significantly higher in patients with cutaneous/subcutaneous Ewing sarcoma than in patients with Ewing sarcoma of other anatomical sites (hazard ratio = 0.33, P = 0.013). The event-free survival rate of cutaneous/subcutaneous Ewing sarcoma was also superior to that of Ewing sarcoma of other anatomical sites (hazard ratio = 0.35, P = 0.01). CONCLUSIONS Patients with cutaneous/subcutaneous Ewing sarcoma may have better prognosis than those with Ewing sarcoma at other anatomical sites. Although pre-diagnostic resection without appropriate investigations is not recommended, local control may be recovered by using a combination of additional resection, chemotherapy and radiotherapy.
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Affiliation(s)
- Hisaki Aiba
- Department of Medical Oncology, National Cancer Center Hospital, Tokyo, Japan
- Department of Orthopaedic Surgery, Nagoya City University, Nagoya, Japan
| | - Yuki Kojima
- Department of Medical Oncology, National Cancer Center Hospital, Tokyo, Japan
| | - Tatsunori Shimoi
- Department of Medical Oncology, National Cancer Center Hospital, Tokyo, Japan
| | - Kazuki Sudo
- Department of Medical Oncology, National Cancer Center Hospital, Tokyo, Japan
| | - Shu Yazaki
- Department of Medical Oncology, National Cancer Center Hospital, Tokyo, Japan
| | - Toru Imai
- Department of Medical Oncology, National Cancer Center Hospital, Tokyo, Japan
| | - Akihiko Yoshida
- Department of Diagnostic Pathology, National Cancer Center Hospital, Tokyo, Japan
| | - Shintaro Iwata
- Department of Musculoskeletal Oncology and Rehabilitation, National Cancer Center Hospital, Tokyo, Japan
| | - Eisuke Kobayashi
- Department of Musculoskeletal Oncology and Rehabilitation, National Cancer Center Hospital, Tokyo, Japan
| | - Akira Kawai
- Department of Musculoskeletal Oncology and Rehabilitation, National Cancer Center Hospital, Tokyo, Japan
| | - Ayumu Arakawa
- Department of Pediatric Oncology, National Cancer Center Hospital, Tokyo, Japan
| | - Chitose Ogawa
- Department of Pediatric Oncology, National Cancer Center Hospital, Tokyo, Japan
| | - Hiroaki Kimura
- Department of Orthopaedic Surgery, Nagoya City University, Nagoya, Japan
| | - Kan Yonemori
- Department of Medical Oncology, National Cancer Center Hospital, Tokyo, Japan
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Huang JH, Chen SH, Liao YM, Kao YC, Ho WL, Chang H, Tsai ML, Lee HL, Kuo CC, Tseng SH, Chang CY, Hsieh KLC, Lu LS, Chen YJ, Chiou JF, Hsieh TH, Liu YR, Hsu W, Li WT, Wu YC, Wu WC, Wang JL, Tsai JJ, Terashima K, Kiyotani C, Wong TT, Miser JS, Liu YL. Feasibility and Toxicity of Interval-Compressed Chemotherapy in Asian Children and Young Adults with Sarcoma. J Pers Med 2023; 13:jpm13040668. [PMID: 37109054 PMCID: PMC10146212 DOI: 10.3390/jpm13040668] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/08/2023] [Revised: 03/09/2023] [Accepted: 03/20/2023] [Indexed: 04/29/2023] Open
Abstract
Twelve Asian patients with sarcoma received interval-compressed (ic-) chemotherapy scheduled every 14 days with a regimen of vincristine (2 mg/m2), doxorubicin (75 mg/m2), and cyclophosphamide (1200-2200 mg/m2) (VDC) alternating with a regimen of ifosfamide (9000 mg/m2) and etoposide (500 mg/m2) (IE), with filgrastim (5-10 mcg/kg/day) between cycles. Carboplatin (800 mg/m2) was added for CIC-rearranged sarcoma. The patients were treated with 129 cycles of ic-VDC/IE with a median interval of 19 days (interquartile range [IQR], 15-24 days. Median nadirs (IQR) were neutrophil count, 134 (30-396) × 106/L at day 11 (10-12), recovery by day 15 (14-17) and platelet count, 35 (23-83) × 109/L at day 11 (10-13), recovery by day 17 (14-21). Fever and bacteremia were observed in 36% and 8% of cycles, respectively. The diagnoses were Ewing sarcoma (6), rhabdomyosarcoma (3), myoepithelial carcinoma (1), malignant peripheral nerve sheath tumor (1), and CIC-DUX4 Sarcoma (1). Seven of the nine patients with measurable tumors responded (one CR and six PR). Interval-compressed chemotherapy is feasible in the treatment of Asian children and young adults with sarcomas.
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Affiliation(s)
- Jia-Hui Huang
- Department of Pediatrics, Taipei Medical University Hospital, Taipei 110, Taiwan
| | - Shu-Huey Chen
- Department of Pediatrics, School of Medicine, College of Medicine, Taipei Medical University, Taipei 110, Taiwan
- Taipei Cancer Center, Taipei Medical University, Taipei 110, Taiwan
- Departments of Pediatrics, Shuang Ho Hospital, Ministry of Health and Welfare, Taipei Medical University, Zhonghe, New Taipei 235, Taiwan
| | - Yu-Mei Liao
- Division of Hematology and Oncology, Department of Pediatrics, Kaohsiung Medical University Hospital, Kaohsiung 807, Taiwan
| | - Yu-Chien Kao
- Taipei Cancer Center, Taipei Medical University, Taipei 110, Taiwan
- Department of Pathology, School of Medicine, College of Medicine, Taipei Medical University, Taipei 110, Taiwan
- Department of Pathology, Taipei Medical University Hospital, Taipei 110, Taiwan
| | - Wan-Ling Ho
- Department of Pediatrics, Taipei Medical University Hospital, Taipei 110, Taiwan
- Department of Pediatrics, School of Medicine, College of Medicine, Taipei Medical University, Taipei 110, Taiwan
- Taipei Cancer Center, Taipei Medical University, Taipei 110, Taiwan
| | - Hsi Chang
- Department of Pediatrics, Taipei Medical University Hospital, Taipei 110, Taiwan
- Department of Pediatrics, School of Medicine, College of Medicine, Taipei Medical University, Taipei 110, Taiwan
| | - Min-Lan Tsai
- Department of Pediatrics, Taipei Medical University Hospital, Taipei 110, Taiwan
- Department of Pediatrics, School of Medicine, College of Medicine, Taipei Medical University, Taipei 110, Taiwan
| | - Hsin-Lun Lee
- Taipei Cancer Center, Taipei Medical University, Taipei 110, Taiwan
- Department of Radiology, School of Medicine, College of Medicine, Taipei Medical University, Taipei 110, Taiwan
- Department of Radiation Oncology, Taipei Medical University Hospital, Taipei 110, Taiwan
| | - Chia-Chun Kuo
- Taipei Cancer Center, Taipei Medical University, Taipei 110, Taiwan
- Department of Radiation Oncology, Taipei Medical University Hospital, Taipei 110, Taiwan
- Department of Health Care Administration, College of Management, Taipei Medical University, Taipei 110, Taiwan
- Ph.D. Program for Cancer Molecular Biology and Drug Discovery, College of Medical Science and Technology, Taipei Medical University and Academia Sinica, Taipei 110, Taiwan
- Department of Radiation Oncology, Wan Fang Hospital, Taipei Medical University, Taipei 111, Taiwan
| | - Sung-Hui Tseng
- Taipei Cancer Center, Taipei Medical University, Taipei 110, Taiwan
- Department of Physical Medicine and Rehabilitation, School of Medicine, College of Medicine, Taipei Medical University, Taipei 110, Taiwan
- Department of Physical Medicine and Rehabilitation, Taipei Medical University Hospital, Taipei 110, Taiwan
- Neuroscience Research Center, Taipei Medical University Hospital, Taipei 110, Taiwan
| | - Chia-Yau Chang
- Department of Pediatrics, Taipei Medical University Hospital, Taipei 110, Taiwan
- Department of Pediatrics, School of Medicine, College of Medicine, Taipei Medical University, Taipei 110, Taiwan
- Taipei Cancer Center, Taipei Medical University, Taipei 110, Taiwan
| | - Kevin Li-Chun Hsieh
- Taipei Cancer Center, Taipei Medical University, Taipei 110, Taiwan
- Department of Radiology, School of Medicine, College of Medicine, Taipei Medical University, Taipei 110, Taiwan
- Department of Medical Imaging, Taipei Medical University Hospital, Taipei 110, Taiwan
- TMU Research Center of Cancer Translational Medicine, Taipei Medical University, Taipei 110, Taiwan
| | - Long-Sheng Lu
- Department of Radiology, School of Medicine, College of Medicine, Taipei Medical University, Taipei 110, Taiwan
- TMU Research Center of Cancer Translational Medicine, Taipei Medical University, Taipei 110, Taiwan
- Graduate Institute of Biomedical Materials and Tissue Engineering, College of Biomedical Engineering, Taipei Medical University, Taipei 110, Taiwan
- International PhD Program in Biomedical Engineering, Taipei Medical University, Taipei 110, Taiwan
- Department of Medical Research, Taipei Medical University Hospital, Taipei 110, Taiwan
- Center for Cell Therapy, Taipei Medical University Hospital, Taipei Medical University, Taipei 110, Taiwan
- International PhD Program for Cell Therapy and Regeneration, Taipei Medical University, Taipei 110, Taiwan
| | - Yin-Ju Chen
- Department of Radiology, School of Medicine, College of Medicine, Taipei Medical University, Taipei 110, Taiwan
- TMU Research Center of Cancer Translational Medicine, Taipei Medical University, Taipei 110, Taiwan
- Graduate Institute of Biomedical Materials and Tissue Engineering, College of Biomedical Engineering, Taipei Medical University, Taipei 110, Taiwan
- International PhD Program in Biomedical Engineering, Taipei Medical University, Taipei 110, Taiwan
- Department of Medical Research, Taipei Medical University Hospital, Taipei 110, Taiwan
| | - Jeng-Fong Chiou
- Department of Radiology, School of Medicine, College of Medicine, Taipei Medical University, Taipei 110, Taiwan
- Department of Radiation Oncology, Taipei Medical University Hospital, Taipei 110, Taiwan
- TMU Research Center of Cancer Translational Medicine, Taipei Medical University, Taipei 110, Taiwan
| | - Tsung-Han Hsieh
- Joint Biobank, Office of Human Research, Taipei Medical University, Taipei 110, Taiwan
| | - Yun-Ru Liu
- Taipei Cancer Center, Taipei Medical University, Taipei 110, Taiwan
- Joint Biobank, Office of Human Research, Taipei Medical University, Taipei 110, Taiwan
| | - Wayne Hsu
- Division of General Surgery, Department of Surgery, Taipei Medical University Hospital, Taipei 110, Taiwan
| | - Wei-Tang Li
- Division of Plastic Surgery, Department of Surgery, Taipei Medical University Hospital, Taipei 110, Taiwan
| | - Yu-Chung Wu
- Division of Thoracic Surgery, Department of Surgery, Taipei Medical University Hospital, Taipei 110, Taiwan
| | - Wei-Ciao Wu
- Division of Thoracic Surgery, Department of Surgery, Shuang Ho Hospital, Ministry of Health and Welfare, Taipei Medical University, Zhonghe, New Taipei 235, Taiwan
| | - Jinn-Li Wang
- Department of Pediatrics, School of Medicine, College of Medicine, Taipei Medical University, Taipei 110, Taiwan
- Taipei Cancer Center, Taipei Medical University, Taipei 110, Taiwan
- Department of Pediatrics, Wan Fang Hospital, Taipei Medical University, Taipei 111, Taiwan
| | - Jia-Jia Tsai
- Department of Pediatrics, Taipei Medical University Hospital, Taipei 110, Taiwan
| | - Keita Terashima
- Children's Cancer Center, National Center for Child Health and Development, Tokyo 157-8535, Japan
| | - Chikako Kiyotani
- Children's Cancer Center, National Center for Child Health and Development, Tokyo 157-8535, Japan
| | - Tai-Tong Wong
- Taipei Cancer Center, Taipei Medical University, Taipei 110, Taiwan
- TMU Research Center of Cancer Translational Medicine, Taipei Medical University, Taipei 110, Taiwan
- Graduate Institute of Clinical Medicine, College of Medicine, Taipei Medical University, Taipei 110, Taiwan
- Division of Pediatric Neurosurgery, Department of Neurosurgery, Taipei Medical University Hospital, Taipei 110, Taiwan
- Taipei Neuroscience Institute, Taipei Medical University, Taipei 110, Taiwan
| | - James S Miser
- Taipei Cancer Center, Taipei Medical University, Taipei 110, Taiwan
- Department of Pediatrics, City of Hope National Medical Center, Duarte, CA 91010, USA
| | - Yen-Lin Liu
- Department of Pediatrics, Taipei Medical University Hospital, Taipei 110, Taiwan
- Department of Pediatrics, School of Medicine, College of Medicine, Taipei Medical University, Taipei 110, Taiwan
- Taipei Cancer Center, Taipei Medical University, Taipei 110, Taiwan
- TMU Research Center of Cancer Translational Medicine, Taipei Medical University, Taipei 110, Taiwan
- Center for Cell Therapy, Taipei Medical University Hospital, Taipei Medical University, Taipei 110, Taiwan
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21
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Almohaisen GA, Alhuwairini SF, Aljrayed MA, Alenezi MM, Alsaab F. Extraskeletal Ewing's sarcoma of the head and neck region in pediatric patients: A case report and literature review. Int J Surg Case Rep 2023; 106:108142. [PMID: 37141776 PMCID: PMC10176168 DOI: 10.1016/j.ijscr.2023.108142] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/15/2022] [Revised: 03/23/2023] [Accepted: 03/23/2023] [Indexed: 05/06/2023] Open
Abstract
INTRODUCTION AND IMPORTANCE Extraskeletal Ewing's sarcoma (EES) is a collection of malignant cells that appear small and round and occur mostly in pediatrics and adolescence. Head and neck EES tumors are considered rare and require multidisciplinary care to achieve ideal results in management. CASE PRESENTATION A 14-year-old boy who complained of a mass protruding from the back of his neck which gradually increased in size in the last few months prior to the diagnosis. He was referred to a pediatric otolaryngology clinic with a one-year history of chronic painless nape swelling. Ultrasound prior to the referral was done and the findings revealed a well-defined rounded hypoechoic lesion with internal vascularity. MRI was done and the impression was a large subcutaneous, well defined enhancing soft tissue lesion which raised the suspicion of sarcoma. The multidisciplinary team decision was to go for complete resection with a free margin followed by chemoradiation postoperatively. No evidence of recurrence was detected throughout the follow-up. CLINICAL DISCUSSION The literature review included ages of the pediatric group from 4 months up to 18-year-old. Clinical features are highly dependable on the size and site of the lesion. Complete resection of the tumor plays an important role in the local control and prognosis. CONCLUSION We present a rare case of extraskeletal Ewing's sarcoma of the nape. Computed tomography and magnetic resonance imaging are frequently used as imaging modalities in evaluating and diagnosing EES. Management commonly includes surgery with adjuvant chemotherapy to decrease recurrence and prolong the survival rate.
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Affiliation(s)
- Ghadi A Almohaisen
- College of Medicine, King Saud bin Abdulaziz University for Health Sciences, Riyadh, Saudi Arabia.
| | - Sara F Alhuwairini
- College of Medicine, King Saud bin Abdulaziz University for Health Sciences, Riyadh, Saudi Arabia
| | - Maha A Aljrayed
- College of Medicine, King Saud bin Abdulaziz University for Health Sciences, Riyadh, Saudi Arabia
| | - Mazyad M Alenezi
- Department of Otolaryngology Head and Neck Surgery, College of Medicine, Qassim University, Qassim, Saudi Arabia
| | - Fahad Alsaab
- Department of Pediatric Surgery, Ministry of the National Guard-Health Affairs, Riyadh, Saudi Arabia; Department of Pediatric Surgery, King Abdullah International Medical Research Center, Riyadh, Saudi Arabia; Department of Pediatric Surgery, King Saud bin Abdulaziz University for Health Sciences, Riyadh, Saudi Arabia
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22
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Mendpara V, Sayed Mushir Ali A, Tango T, Bhadana R, Kanisetti V, Tiwari U, Sahu S, Pancholi M. A Case of Extraskeletal Ewing Sarcoma Treated With Wide Local Excision With Latissimus Dorsi Flap and Systemic Therapy. Cureus 2023; 15:e36175. [PMID: 37065414 PMCID: PMC10103811 DOI: 10.7759/cureus.36175] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 03/15/2023] [Indexed: 03/17/2023] Open
Abstract
Extraskeletal Ewing sarcoma (EES) is a rare tumor of the soft tissue that looks the same as skeletal Ewing sarcoma (ES). A male in his 50s was diagnosed with extraskeletal Ewing sarcoma (EES) of the right shoulder, which had infiltrated the muscles around the shoulder joints. Although uncommon, all members of the ES family of tumors, including EES, were treated following the same general protocol for sarcoma tumors. Due to the significant tumor size in this patient and local invasion, wide local excision and a latissimus dorsi flap were required. This case highlighted the management of EES, including the surgical removal of the mass on the right shoulder, followed by chemotherapy, which led to a successful outcome.
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23
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Chavan M, Dhakal S, Singh A, Rai V, Arora S, C Mallipeddi M, Das A. Ewing sarcoma genomics and recent therapeutic advancements. PEDIATRIC HEMATOLOGY ONCOLOGY JOURNAL 2023. [DOI: 10.1016/j.phoj.2023.02.001] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/10/2023] Open
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24
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Mathew J, Arjunan R, Dasappa A, Namachivayam A. Prognostic Factors and Clinical Outcomes in Extraskeletal Ewing Sarcoma: A Cohort Study. Ann Surg Oncol 2022; 30:3084-3094. [PMID: 36564656 DOI: 10.1245/s10434-022-12992-1] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/15/2022] [Accepted: 12/07/2022] [Indexed: 12/24/2022]
Abstract
BACKGROUND Extraskeletal Ewing sarcoma (ESE) is a lesser-known, rarer counterpart of Ewing sarcoma of bone. This single-center study sought to evaluate the prognosticators and outcomes following multimodality therapy in patients with ESE. METHODS Forty-seven patients with ESE, treated between 2013 and 2018 with a standardized protocol and multimodality therapy using established doxorubicin-based regimens, were followed-up to assess outcomes. RESULTS Median age at diagnosis was 20 (range 7-56) years, and 57.4% were male. Median tumor size was 7 (range 2-21) cm. The symptom-duration ranged from 1 to 8 (median 4) months. Tumor-site was trunkal in 61.7%, extremity in 23.4%, and head and neck 14.9%. Of the 35 patients with nonmetastatic disease at presentation, 13 underwent upfront surgery. The rest received chemotherapy followed by local treatment, which was surgical in 15 and radiotherapy in 5. At median follow-up of 24 (range 5-98) months, 55.3% patients had experienced events, and 29.8% had died of progressive disease. Three-year event-free survival was 41.1%, and overall survival was 53%. On univariate analysis, trunkal location, upfront surgery, and positive surgical margins were associated with inferior EFS. Trunkal tumors and upfront surgery were also associated with poorer OS. On multivariate analysis, trunkal location and margin-positive resections retained statistical significance for adverse EFS. CONCLUSIONS Unless clearly resectable upfront, ESE should be downstaged with chemotherapy before local treatment. A margin-negative resection should be the objective when performing surgery. Definitive radiotherapy is an alternative in tumors not amenable for complete excision or when anticipated postoperative morbidity precludes radical surgery.
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Affiliation(s)
- Joseph Mathew
- Department of Surgical Oncology, Kidwai Memorial Institute of Oncology, Bangalore, India.
| | - Ravi Arjunan
- Department of Surgical Oncology, Kidwai Memorial Institute of Oncology, Bangalore, India
| | - Ashwathappa Dasappa
- Department of Surgical Oncology, Kidwai Memorial Institute of Oncology, Bangalore, India
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25
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Ghandour M, Lehner B, Klotz M, Geisbüsch A, Bollmann J, Renkawitz T, Horsch A. Extraosseous Ewing Sarcoma in Children: A Systematic Review and Meta-Analysis of Clinicodemographic Characteristics. CHILDREN (BASEL, SWITZERLAND) 2022; 9:children9121859. [PMID: 36553303 PMCID: PMC9776445 DOI: 10.3390/children9121859] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Subscribe] [Scholar Register] [Received: 10/17/2022] [Revised: 11/22/2022] [Accepted: 11/26/2022] [Indexed: 12/04/2022]
Abstract
Background: We conducted this systematic review to provide comprehensive evidence on the prevalence, clinical features and outcomes of young extraosseous Ewing sarcoma (EES) cases. Methods: PubMed, Scopus, Web of Science, and Google Scholar were searched for articles reporting the occurrence of EES among children and adolescents (<21 years). The primary outcome included the rate of occurrence of EES among children and adolescents, while the secondary outcomes included the descriptive analyses of the demographic characteristics, tumor characteristics, and clinical outcomes of the affected cases. The data are reported as the effect size (ES) and its corresponding 95% confidence interval (CI). Results: A total of 29 studies were included. Twenty-four reported instances of childhood disease among all the EES cases [ES = 30%; 95%CI: 29−31%], while five studies reported extraosseous cases among the pediatric EES cases [ES = 22%; 95%CI: 13−31%]. The thorax is the most common location of childhood EES [33%; 95%CI: 20−46%] followed by the extremities [31%; 95%CI: 22−40%]. Concurrent chemotherapy and radiotherapy [57%; 95%CI: 25−84%] was the most commonly implemented management protocol in the pediatric EES cases. The rate of no evidence of disease and 5-year overall survival was 69% for both outcomes. Mortality occurred in 29% of cases, while recurrence and secondary metastasis occurred in 35% and 16% of cases, respectively. Conclusions: Our findings provide insight into the clinical features and outcomes of EES among children and adolescents.
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Affiliation(s)
- Maher Ghandour
- Department of Orthopedics, Heidelberg University Hospital, 69129 Heidelberg, Germany
| | - Burkhard Lehner
- Department of Orthopedics, Heidelberg University Hospital, 69129 Heidelberg, Germany
| | - Matthias Klotz
- Orthopedics and Trauma Surgery, Marienkrankenhaus Soest, 59494 Soest, Germany
| | - Andreas Geisbüsch
- Department of Orthopedics, Heidelberg University Hospital, 69129 Heidelberg, Germany
| | - Jakob Bollmann
- Department of Orthopedics, Heidelberg University Hospital, 69129 Heidelberg, Germany
| | - Tobias Renkawitz
- Department of Orthopedics, Heidelberg University Hospital, 69129 Heidelberg, Germany
| | - Axel Horsch
- Department of Orthopedics, Heidelberg University Hospital, 69129 Heidelberg, Germany
- Correspondence:
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26
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Nasri S, Aqamour R, Haddar L, Guerrouj I, Haddar K, Aichouni N, Kamaoui I, Skiker I. Extraskeletal Ewing sarcoma: A case report. Radiol Case Rep 2022; 17:4809-4813. [PMID: 36238207 PMCID: PMC9550844 DOI: 10.1016/j.radcr.2022.09.048] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/17/2022] [Revised: 09/07/2022] [Accepted: 09/13/2022] [Indexed: 11/18/2022] Open
Abstract
Extraskeletal Ewing sarcoma is a rare tumor mainly affecting young people, of poor prognosis with very high mortality rates especially in metastatic forms. It can affect different locations, without specific clinical signs, which delays the diagnosis. Imaging plays an important role for diagnosis, staging, preoperative assessment and surveillance. The diagnosis should be set early to a better management. We report a case of a 30-year-old man with a large extraskeletal Ewing sarcoma of the left thigh. The patient was initially treated with chemotherapy. Unfortunately, the tumor has increased in size making surgery impossible. The patient ultimately died of pulmonary metastases.
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27
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Matsuoka M, Onodera T, Yokota I, Iwasaki K, Hishimura R, Suzuki Y, Kondo E, Iwasaki N. Comparison of clinical features between patients with bone and soft tissue fibrosarcomas. J Surg Oncol 2022; 126:1299-1305. [PMID: 35938632 DOI: 10.1002/jso.27049] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/04/2022] [Revised: 07/15/2022] [Accepted: 07/26/2022] [Indexed: 11/05/2022]
Abstract
BACKGROUND AND OBJECTIVES Fibrosarcomas predominantly arise in soft tissues, but can also develop in bone. Because of their rarity, whether bone development has an impact on clinical features has not been addressed. METHODS We included fibrosarcoma patients diagnosed between 1983 and 2016 in the Surveillance, Epidemiology, and End Results database. Differences in clinical features between fibrosarcoma of bone (FS-B) and fibrosarcoma of soft tissue (FS-ST) were investigated. RESULTS After excluding patients without information regarding cause of death, site of origin, distant tumor or survival, 1443 patients were included. Of those, 98 patients had FS-B. Patients with FS-B were younger, more frequently male, with fibrosarcomas that more often developed in an extremity and were histologically high-grade. In contrast, no difference in potential to metastasize was observed. Survival was almost equal between FS-B and FS-ST (FS-B/FS-ST: cancer-specific survival, hazard ratio [HR]: 1.2, 95% confidence interval [CI]: 0.8-1.7; overall survival, HR: 1.3, 95% CI: 0.9-1.7). CONCLUSIONS Our results clearly indicated that patient backgrounds differed, such as younger age and greater tendencies to affect males, develop in an extremity and show high-grade tumor in patients with FS-B. In contrast, no differences were observed in distant metastatic potential or survival.
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Affiliation(s)
- Masatake Matsuoka
- Department of Orthopaedic Surgery, Faculty of Medicine and Graduate School of Medicine, Hokkaido University, Hokkaido, Japan
| | - Tomohiro Onodera
- Department of Orthopaedic Surgery, Faculty of Medicine and Graduate School of Medicine, Hokkaido University, Hokkaido, Japan
| | - Isao Yokota
- Department of Biostatistics, Graduate School of Medicine, Hokkaido University, Hokkaido, Japan
| | - Koji Iwasaki
- Department of Functional Reconstruction for the Knee Joint, Hokkaido University, Hokkaido, Japan
| | - Ryosuke Hishimura
- Department of Orthopaedic Surgery, Faculty of Medicine and Graduate School of Medicine, Hokkaido University, Hokkaido, Japan
| | - Yuki Suzuki
- Department of Orthopaedic Surgery, Faculty of Medicine and Graduate School of Medicine, Hokkaido University, Hokkaido, Japan
| | - Eiji Kondo
- Centre for Sports Medicine, Hokkaido University Hospital, Hokkaido, Japan
| | - Norimasa Iwasaki
- Department of Orthopaedic Surgery, Faculty of Medicine and Graduate School of Medicine, Hokkaido University, Hokkaido, Japan
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28
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Violon F, Burns R, Mihoubi F, Audard V, Biau D, Feydy A, Larousserie F. Intramedullary, periosteal, and extraskeletal Ewing sarcomas: retrospective study of a series of 126 cases in a reference center. Skeletal Radiol 2022; 51:1659-1670. [PMID: 35179621 DOI: 10.1007/s00256-021-03983-6] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/29/2021] [Revised: 12/16/2021] [Accepted: 12/25/2021] [Indexed: 02/02/2023]
Abstract
OBJECTIVE To evaluate the proportion of extraskeletal, periosteal, and intramedullary Ewing sarcomas among musculoskeletal Ewing sarcomas. MATERIAL AND METHOD Our single-center retrospective study included patients with musculoskeletal Ewing sarcoma diagnosed between 2005 and 2019 in our pathology center (cases from our adult bone tumor referral center and adult and pediatric cases referred for review). Recurrences, metastases, and visceral Ewing sarcomas were excluded. Intramedullary Ewing sarcomas were defined by involvement of the medullary cavity. Periosteal cases were defined by involvement of the subperiosteal area without extension to the medullary cavity. Extraskeletal cases were defined by the absence of involvement of the bone tissue and the subperiosteal area. RESULTS Our series included 126 patients with musculoskeletal Ewing sarcoma, including 118 skeletal Ewing sarcomas (93.7%) and 8 extraskeletal Ewing sarcomas (6.3%). Of the 118 skeletal Ewing sarcomas 112 were intramedullary (88.9%) and 6 were periosteal (4.8%). Extraskeletal Ewing sarcomas were more common in women and in patients older than 40 (p < 0.05). DISCUSSION The 6.3% proportion of extraskeletal Ewing sarcoma is lower than the median of 30% estimated from the literature. This difference could be explained by an overestimation of extraskeletal Ewing sarcomas of the chest wall (Askin tumors), an underestimation of periosteal cases confused with extraskeletal cases, and the presence of "Ewing-like" soft tissue sarcomas in previous series. Because of its prognostic and therapeutic impact, the distinction of morphologic subtypes requires the cooperation of experienced radiologists and pathologists.
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Affiliation(s)
- F Violon
- Service de Pathologie, Hôpital Cochin, AP‑HP, Paris, France.,Faculté de Médecine de Nancy, Université de Lorraine, Nancy, France
| | - R Burns
- Service de Radiologie, Hôpital Cochin, AP-HP, Paris, France.,Université de Paris, Paris, France
| | - F Mihoubi
- Service de Radiologie, Hôpital Cochin, AP-HP, Paris, France
| | - V Audard
- Service de Pathologie, Hôpital Cochin, AP‑HP, Paris, France
| | - D Biau
- Université de Paris, Paris, France.,Service de Chirurgie Orthopédique, Hôpital Cochin, AP-HP, Paris, France
| | - A Feydy
- Service de Radiologie, Hôpital Cochin, AP-HP, Paris, France.,Université de Paris, Paris, France
| | - F Larousserie
- Service de Pathologie, Hôpital Cochin, AP‑HP, Paris, France. .,Université de Paris, Paris, France.
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29
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Giannikopoulos P, Parham DM. Pediatric Sarcomas: The Next Generation of Molecular Studies. Cancers (Basel) 2022; 14:2515. [PMID: 35626119 PMCID: PMC9139929 DOI: 10.3390/cancers14102515] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/08/2022] [Revised: 05/13/2022] [Accepted: 05/13/2022] [Indexed: 02/04/2023] Open
Abstract
Pediatric sarcomas constitute one of the largest groups of childhood cancers, following hematopoietic, neural, and renal lesions. Partly because of their diversity, they continue to offer challenges in diagnosis and treatment. In spite of the diagnostic, nosologic, and therapeutic gains made with genetic technology, newer means for investigation are needed. This article reviews emerging technology being used to study human neoplasia and how these methods might be applicable to pediatric sarcomas. Methods reviewed include single cell RNA sequencing (scRNAseq), spatial multi-omics, high-throughput functional genomics, and clustered regularly interspersed short palindromic sequence-Cas9 (CRISPR-Cas9) technology. In spite of these advances, the field continues to be challenged by a dearth of properly annotated materials, particularly from recurrences and metastases and pre- and post-treatment samples.
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Affiliation(s)
| | - David M. Parham
- Department of Anatomic Pathology, Children’s Hospital Los Angeles, Los Angeles, CA 90027, USA
- Department of Pathology, University of Southern California Keck School of Medicine, Los Angeles, CA 90033, USA
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30
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Livellara V, Bergamaschi L, Puma N, Chiaravalli S, Podda M, Casanova M, Gasparini P, Pecori E, Alessandro O, Nigro O, Sironi G, Gattuso G, Terenziani M, Spreafico F, Meazza C, Biassoni V, Schiavello E, Massimino M, Luksch R, Ferrari A. Extraosseous Ewing sarcoma in children and adolescents: A retrospective series from a referral pediatric oncology center. Pediatr Blood Cancer 2022; 69:e29512. [PMID: 34962687 DOI: 10.1002/pbc.29512] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/23/2021] [Revised: 11/01/2021] [Accepted: 11/20/2021] [Indexed: 11/06/2022]
Abstract
BACKGROUND Extraosseous Ewing sarcoma is a rare entity and less is known about its clinical behavior and optimal treatment than for its counterpart in bone. This study is a retrospective analysis on a cohort of patients <21 years treated according to a "soft tissue sarcoma approach." METHODS The "extraosseous" origin of the tumor was established on radiological findings, based on the lack of any bone involvement. Patients were treated using a multimodality approach including surgery, radiotherapy, and chemotherapy. All patients received chemotherapy with alkylating agents and anthracyclines for 25 weeks (nine courses). Radiotherapy (45-54.8 Gy) was required for all cases except those who had an initial R0 resection of tumors smaller than 5 cm. RESULTS Fifty-seven patients (age 2-20 years, median 14) were treated from 1990 to 2020. Ten-year event-free survival (EFS) and overall survival (OS) were 77.5% and 85.5% in patients with localized disease, and 11.1% and 29.6% in those with metastatic disease (p < .001) (follow-up 5-349 months, median 107 months). In patients with localized disease, the most recent IVADo-IVE regimen achieved excellent survivals, that is, 10-year EFS 95.5%. CONCLUSIONS Our study showed that satisfactory results were achieved in patients with localized extraosseous Ewing sarcoma treated with a tailored approach derived from soft tissue sarcoma protocols, which was less intensive and shorter as compared to the standards utilized for the management of bone Ewing sarcoma. Our study suggests that the extraskeletal site might be considered as a variable to stratify patients and modulate treatment intensity accordingly in Ewing sarcoma protocol.
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Affiliation(s)
- Virginia Livellara
- Pediatric Oncology Unit, Medical Oncology and Hematology Department, Fondazione IRCCS Istituto Nazionale dei Tumori, Milan, Italy
| | - Luca Bergamaschi
- Pediatric Oncology Unit, Medical Oncology and Hematology Department, Fondazione IRCCS Istituto Nazionale dei Tumori, Milan, Italy
| | - Nadia Puma
- Pediatric Oncology Unit, Medical Oncology and Hematology Department, Fondazione IRCCS Istituto Nazionale dei Tumori, Milan, Italy
| | - Stefano Chiaravalli
- Pediatric Oncology Unit, Medical Oncology and Hematology Department, Fondazione IRCCS Istituto Nazionale dei Tumori, Milan, Italy
| | - Marta Podda
- Pediatric Oncology Unit, Medical Oncology and Hematology Department, Fondazione IRCCS Istituto Nazionale dei Tumori, Milan, Italy
| | - Michela Casanova
- Pediatric Oncology Unit, Medical Oncology and Hematology Department, Fondazione IRCCS Istituto Nazionale dei Tumori, Milan, Italy
| | - Patrizia Gasparini
- Tumor Genomics Unit, Fondazione IRCCS Istituto Nazionale dei Tumori, Milan, Italy
| | - Emilia Pecori
- Pediatric Radiotherapy Unit, Radiation Oncology Unit, Fondazione IRCCS Istituto Nazionale dei Tumori, Milan, Italy
| | - Ombretta Alessandro
- Pediatric Radiotherapy Unit, Radiation Oncology Unit, Fondazione IRCCS Istituto Nazionale dei Tumori, Milan, Italy
| | - Olga Nigro
- Pediatric Oncology Unit, Medical Oncology and Hematology Department, Fondazione IRCCS Istituto Nazionale dei Tumori, Milan, Italy
| | - Giovanna Sironi
- Pediatric Oncology Unit, Medical Oncology and Hematology Department, Fondazione IRCCS Istituto Nazionale dei Tumori, Milan, Italy
| | - Giovanna Gattuso
- Pediatric Oncology Unit, Medical Oncology and Hematology Department, Fondazione IRCCS Istituto Nazionale dei Tumori, Milan, Italy
| | - Monica Terenziani
- Pediatric Oncology Unit, Medical Oncology and Hematology Department, Fondazione IRCCS Istituto Nazionale dei Tumori, Milan, Italy
| | - Filippo Spreafico
- Pediatric Oncology Unit, Medical Oncology and Hematology Department, Fondazione IRCCS Istituto Nazionale dei Tumori, Milan, Italy
| | - Cristina Meazza
- Pediatric Oncology Unit, Medical Oncology and Hematology Department, Fondazione IRCCS Istituto Nazionale dei Tumori, Milan, Italy
| | - Veronica Biassoni
- Pediatric Oncology Unit, Medical Oncology and Hematology Department, Fondazione IRCCS Istituto Nazionale dei Tumori, Milan, Italy
| | - Elisabetta Schiavello
- Pediatric Oncology Unit, Medical Oncology and Hematology Department, Fondazione IRCCS Istituto Nazionale dei Tumori, Milan, Italy
| | - Maura Massimino
- Pediatric Oncology Unit, Medical Oncology and Hematology Department, Fondazione IRCCS Istituto Nazionale dei Tumori, Milan, Italy
| | - Roberto Luksch
- Pediatric Oncology Unit, Medical Oncology and Hematology Department, Fondazione IRCCS Istituto Nazionale dei Tumori, Milan, Italy
| | - Andrea Ferrari
- Pediatric Oncology Unit, Medical Oncology and Hematology Department, Fondazione IRCCS Istituto Nazionale dei Tumori, Milan, Italy
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Hypoxia-activated neuropeptide Y/Y5 receptor/RhoA pathway triggers chromosomal instability and bone metastasis in Ewing sarcoma. Nat Commun 2022; 13:2323. [PMID: 35484119 PMCID: PMC9051212 DOI: 10.1038/s41467-022-29898-x] [Citation(s) in RCA: 16] [Impact Index Per Article: 5.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/18/2021] [Accepted: 04/05/2022] [Indexed: 11/08/2022] Open
Abstract
Adverse prognosis in Ewing sarcoma (ES) is associated with the presence of metastases, particularly in bone, tumor hypoxia and chromosomal instability (CIN). Yet, a mechanistic link between these factors remains unknown. We demonstrate that in ES, tumor hypoxia selectively exacerbates bone metastasis. This process is triggered by hypoxia-induced stimulation of the neuropeptide Y (NPY)/Y5 receptor (Y5R) pathway, which leads to RhoA over-activation and cytokinesis failure. These mitotic defects result in the formation of polyploid ES cells, the progeny of which exhibit high CIN, an ability to invade and colonize bone, and a resistance to chemotherapy. Blocking Y5R in hypoxic ES tumors prevents polyploidization and bone metastasis. Our findings provide evidence for the role of the hypoxia-inducible NPY/Y5R/RhoA axis in promoting genomic changes and subsequent osseous dissemination in ES, and suggest that targeting this pathway may prevent CIN and disease progression in ES and other cancers rich in NPY and Y5R. Ewing sarcoma tumour cells frequently metastasize to the bone but the molecular mechanisms governing this process are not well understood. Here, the authors show that neuropeptide Y/Y5 receptor pathway is activated in the hypoxic tumour microenvironment, which results in cytokinesis defects and chromosomal instability, leading to bone invasion.
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A case report of retroperitoneal Ewing sarcoma requiring adrenalectomy. Int J Surg Case Rep 2022; 95:106966. [PMID: 35597126 PMCID: PMC9127152 DOI: 10.1016/j.ijscr.2022.106966] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/06/2021] [Revised: 03/24/2022] [Accepted: 03/25/2022] [Indexed: 12/02/2022] Open
Abstract
Introduction and importance Ewing's sarcoma is a rare entity of malignant in both skeletal and extra-skeletal sites. There are few patients reported as Extra-Skeletal Sarcoma, and fewer reported cases for Extraskeletal Ewing sarcoma involving the retroperitoneal region. Reporting such a rare entity will add to literature in helping the diagnosis and management of such cases. Case presentation We present a case of 26 year old previously healthy female complaining of a vague abdominal pain and discovered to have retroperitoneal Ewing sarcoma adherent to left adrenal gland. Clinical discussion She was managed with a combination of neoadjuvant chemotherapy and resection through exploratory laparotomy. Conclusion In short, Ewing sarcoma should be considered in the differential diagnosis for young patient who is presenting with a retroperitoneal mass.
Ewing's sarcoma is a rare entity of malignant in both skeletal and extra-skeletal sites. There are few patients reported as Extra-Skeletal Sarcoma (ESS). EES involving retroperitoneal region, from previous studies. We present a case of EES involving the retroperitoneal region and its subsequent management.
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Wang JG, Wei QF, Tang QM. Regarding the Children's Oncology Group AEWS1031 Trial for Ewing Sarcoma. J Clin Oncol 2022; 40:1506. [PMID: 35235371 DOI: 10.1200/jco.21.02546] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/20/2022] Open
Affiliation(s)
- Ji-Gan Wang
- Ji-Gan Wang, MD, Qiu-Fen Wei, MD, and Qu-Mei Tang, MD, Pediatrics Department, Maternal and Child Health Hospital of Guangxi Zhuang Autonomous Region, Nanning, Guangxi, China; Guangxi Clinical Research Center for Pediatric Diseases, Guangxi, China
| | - Qiu-Fen Wei
- Ji-Gan Wang, MD, Qiu-Fen Wei, MD, and Qu-Mei Tang, MD, Pediatrics Department, Maternal and Child Health Hospital of Guangxi Zhuang Autonomous Region, Nanning, Guangxi, China; Guangxi Clinical Research Center for Pediatric Diseases, Guangxi, China
| | - Qu-Mei Tang
- Ji-Gan Wang, MD, Qiu-Fen Wei, MD, and Qu-Mei Tang, MD, Pediatrics Department, Maternal and Child Health Hospital of Guangxi Zhuang Autonomous Region, Nanning, Guangxi, China; Guangxi Clinical Research Center for Pediatric Diseases, Guangxi, China
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Panda G, Chandrasekharan A, Das S, Bhargava P, Srinivas S, Laskar S, Mokal S, Rekhi B, Khanna N, Menon N, Patil V, Noronha V, Joshi A, Prabhash K, Banavali SD, Gupta S, Bajpai J. Outcomes of Ewing sarcoma in adults over 40 years of age from a low-middle income country. Ecancermedicalscience 2022; 16:1361. [PMID: 35685954 PMCID: PMC9085161 DOI: 10.3332/ecancer.2022.1361] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/05/2021] [Indexed: 11/30/2022] Open
Abstract
Introduction The data on outcomes and toxicity in adult Ewing sarcoma (ES) patients, particularly those aged ≥40 years, is exceedingly scarce around the world, particularly in low- and middle-income countries (LMICs) and mandates research. Methods The study involved histologically ascertained ES patients aged ≥40 years who registered at our institute from 2013 to 2018. Prospectively collected data were analysed for overall survival (OS), event-free survival (EFS) and chemotherapy-related toxicities. Results There were 66 patients, of which 34 were non-metastatic, and 32 were denovo metastatic, recurrent or had doubtful metastasis. At presentation, median age was 46 years, and 42 (63.6%) had extra-skeletal primary and 24 (36.3%) had extremity tumours. Curative treatment was offered to 40 (60.6%) patients. Significant grade 3/4 toxicities in non-metastatic and metastatic cohort, respectively, were febrile neutropenia (61.3%, 37.5%), anaemia (58.1%, 37.5%), thrombocytopenia (45.2%, 25.0%), peripheral neuropathy (25.8%, 12.5%) and dyselectrolytemia (25.8%, 6.25%). Chemotherapy-related toxicity led to death in three patients in the metastatic cohort, versus none in the non-metastatic patients. The 5 year EFS and OS for non-metastatic cohort were 53.8% and 67.8%, while the same for metastatic cohort were 20.7% and 27.5%, respectively. On multivariate analysis, Eastern Cooperative Oncology Group-performance status >2 and metastasis at presentation predicted poorer EFS and OS. Additionally, raised lactate dehydrogenase, larger tumours (>8 cm) and palliative intent treatment predicted worse EFS, while extra-skeletal primary and female gender were indicators of worse OS. Conclusions Older adult ES patients benefit from aggressive multimodality treatment even in LMIC infrastructure. However, careful patient selection, close monitoring and pertinent dose modifications is imperative due to higher propensity for potential toxicities.
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Affiliation(s)
- Goutam Panda
- Department of Medical Oncology, Tata Memorial Hospital, Homi Bhabha National Institute, Mumbai, 400012, India
| | - Arun Chandrasekharan
- Department of Medical Oncology, Tata Memorial Hospital, Homi Bhabha National Institute, Mumbai, 400012, India
| | - Shasanka Das
- Department of Medical Oncology, Tata Memorial Hospital, Homi Bhabha National Institute, Mumbai, 400012, India
| | - Prabhat Bhargava
- Department of Medical Oncology, Tata Memorial Hospital, Homi Bhabha National Institute, Mumbai, 400012, India
| | - Sujay Srinivas
- Department of Medical Oncology, Tata Memorial Hospital, Homi Bhabha National Institute, Mumbai, 400012, India
| | - Siddhartha Laskar
- Department of Radiation Oncology, Tata Memorial Hospital, Homi Bhabha National Institute, Mumbai, 400012, India
| | - Smruti Mokal
- Department of Biostatistics, Tata Memorial Hospital, Homi Bhabha National Institute, Mumbai, 400012, India
| | - Bharat Rekhi
- Department of Pathology, Tata Memorial Hospital, Homi Bhabha National Institute, Mumbai, 400012, India
| | - Nehal Khanna
- Department of Radiation Oncology, Tata Memorial Hospital, Homi Bhabha National Institute, Mumbai, 400012, India
| | - Nandini Menon
- Department of Medical Oncology, Tata Memorial Hospital, Homi Bhabha National Institute, Mumbai, 400012, India
| | - Vijay Patil
- Department of Medical Oncology, Tata Memorial Hospital, Homi Bhabha National Institute, Mumbai, 400012, India
| | - Vanita Noronha
- Department of Medical Oncology, Tata Memorial Hospital, Homi Bhabha National Institute, Mumbai, 400012, India
| | - Amit Joshi
- Department of Medical Oncology, Tata Memorial Hospital, Homi Bhabha National Institute, Mumbai, 400012, India
| | - Kumar Prabhash
- Department of Medical Oncology, Tata Memorial Hospital, Homi Bhabha National Institute, Mumbai, 400012, India
| | - Shripad D Banavali
- Department of Medical Oncology, Tata Memorial Hospital, Homi Bhabha National Institute, Mumbai, 400012, India
| | - Sudeep Gupta
- Department of Medical Oncology, Tata Memorial Hospital, Homi Bhabha National Institute, Mumbai, 400012, India
| | - Jyoti Bajpai
- Department of Medical Oncology, Tata Memorial Hospital, Homi Bhabha National Institute, Mumbai, 400012, India
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Kobayashi H, Zhang L, Hirai T, Tsuda Y, Ikegami M, Tanaka S. Comparison of clinical features and outcomes of patients with leiomyosarcoma of bone and soft tissue: a population-based cohort study. Jpn J Clin Oncol 2021; 52:143-150. [PMID: 34791360 DOI: 10.1093/jjco/hyab176] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/21/2021] [Accepted: 11/01/2021] [Indexed: 11/14/2022] Open
Abstract
BACKGROUND Leiomyosarcoma commonly occurs in soft tissue but rarely in the bone. Whether leiomyosarcoma of bone and soft tissue have similar clinical characteristics and outcomes remains unknown. METHODS This retrospective analysis was based on data from the Bone and Soft Tissue Tumor Registry in Japan. Patients with leiomyosarcoma of bone and soft tissue were enrolled. Overall survival and distant metastasis-free survival were estimated using the Kaplan-Meier method, and the Cox regression model was used to identify the prognostic factors. RESULTS A total of 888 patients (60 leiomyosarcoma of bone and 828 leiomyosarcoma of soft tissue) were included in the study. Clinical characteristics were similar between the two groups, except for younger age in leiomyosarcoma of bone than in leiomyosarcoma of soft tissue (median 56 years vs. 66 years, P < 0.0001). To evaluate the prognostic factors and efficacy of adjuvant chemotherapy, data of localized and locally curative cases were extracted (total 572: 33 leiomyosarcoma of bone and 539 leiomyosarcoma of soft tissue). The 5-year overall survival rates of leiomyosarcoma of bone and soft tissue patients were similar (63.8% vs. 75.2%, P = 0.43); the 5-year distant metastasis-free survival tended to be worse in leiomyosarcoma of bone than in leiomyosarcoma of soft tissue (37.4% vs. 57.9%, P = 0.28). Larger tumor size (≥5 cm) and older age (≥65 years) correlated with poor overall survival in leiomyosarcoma of soft tissue patients. Adjuvant chemotherapy tended to prolong the overall survival of both leiomyosarcoma of bone (P = 0.11) and leiomyosarcoma of soft tissue patients with tumor size >10 cm (P = 0.06). CONCLUSIONS The clinical characteristics and outcomes of leiomyosarcoma of bone and soft tissue patients were similar. In localized cases, adjuvant chemotherapy may improve the survival of leiomyosarcoma of bone and soft tissue patients with large-size tumor.
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Affiliation(s)
- Hiroshi Kobayashi
- Department of Orthopedic Surgery, The University of Tokyo, Tokyo, Japan
| | - Liuzhe Zhang
- Department of Orthopedic Surgery, The University of Tokyo, Tokyo, Japan
| | - Toshihide Hirai
- Department of Orthopedic Surgery, The University of Tokyo, Tokyo, Japan
| | - Yusuke Tsuda
- Department of Orthopedic Surgery, The University of Tokyo, Tokyo, Japan
| | - Masachika Ikegami
- Department of Musculoskeletal Oncology, Tokyo Metropolitan Cancer and Infectious Diseases Center Komagome Hospital, Tokyo, Japan
| | - Sakae Tanaka
- Department of Orthopedic Surgery, The University of Tokyo, Tokyo, Japan
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Mori M, Honda K, Tsubouchi H, Sakata J, Kato S, Suzuki S. Neoadjuvant chemotherapy for Ewing’s sarcoma family tumors of the uterine cervix: A case report. Gynecol Oncol Rep 2021; 38:100895. [PMID: 34926774 PMCID: PMC8651897 DOI: 10.1016/j.gore.2021.100895] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/05/2021] [Revised: 11/16/2021] [Accepted: 11/18/2021] [Indexed: 11/24/2022] Open
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Koscielniak E, Sparber-Sauer M, Scheer M, Vokuhl C, Kazanowska B, Ladenstein R, Niggli F, Ljungman G, Paulussen M, Bielack SS, Seitz G, Fuchs J, Hallmen E, Klingebiel T, On Behalf Of The Cws Study Group. 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:e29145. [PMID: 34089219 DOI: 10.1002/pbc.29145] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/02/2020] [Revised: 04/22/2021] [Accepted: 05/09/2021] [Indexed: 11/11/2022]
Abstract
BACKGROUND We have analyzed the outcome of patients with localized extraskeletal Ewing sarcoma (EES) treated in three consecutive Cooperative Weichteilsarkomstudiengruppe (CWS) soft tissue sarcoma (STS) studies: CWS-91, CWS-96, and CWS-2002P. METHODS Patients were treated in CWS-91 with four- (vincristine, dactinomycin, doxorubicin, and ifosfamide [VAIA] or cyclophosphamide [VACA II]) or five-drug (+etoposide [EVAIA]) cycles, in CWS-96 they were randomly assigned to receive VAIA or CEVAIE (+carboplatin and etoposide), and in CWS-2002P with VAIA III plus optional maintenance therapy (MT) with cyclophosphamide and vinblastine. Local therapy consisted of resection and/or radiotherapy (RT). RESULTS Two hundred forty-three patients fulfilled the eligibility criteria. The 5-year event-free survival (EFS) and overall survival (OS) were 63% (95% confidence interval [CI] 57-69) and 73% (95% CI 67-79), respectively. The 5-year EFS by study was 64% (95% CI 54-74) in CWS-91, 57% (95% CI 48-66) in CWS-96, and 79% (95% CI 67-91) in CWS-2002P (n.s.). The 5-year OS was 72% (95% CI 62-82) in CWS-91, 70% (95% CI 61-79) in CWS-96, and 86% (95% CI 76-96) in CWS-2002P (n.s.). In CWS-96, 5-year EFS and OS in the VAIA arm versus the CEVAIE were 65% (95% CI 52-81) versus 55% (95% CI 39-76) log-rank p = .13, and 85% (95% CI 75-96) versus 61% (95% CI 45-82), log-rank p = .09. CONCLUSION Our analysis provides interesting information on the treatment and specificities of EES, which can be useful for a better understanding of this rare entity and should be considered in the development of future clinical trials for Ewing sarcoma defined as FET-ETS fusion positive tumors.
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Affiliation(s)
- Ewa Koscielniak
- Klinikum Stuttgart-Olgahospital, Pediatrics 5 (Oncology, Hematology, Immunology), Stuttgart, Germany.,University of Tuebingen, Tuebingen, Germany
| | - Monika Sparber-Sauer
- Klinikum Stuttgart-Olgahospital, Pediatrics 5 (Oncology, Hematology, Immunology), Stuttgart, Germany
| | - Monika Scheer
- Department of Pediatric Oncology/Hematology, Charité-Universitätsmedizin, Berlin, Germany
| | - Christian Vokuhl
- Institute of Children's Pathology, University of Bonn, Bonn, Germany
| | - Bernarda Kazanowska
- Department of Pediatric Hematology/Oncology and BMT, University of Wroclaw, Wroclaw, Poland
| | | | - Felix Niggli
- Department of Pediatric Oncology, University of Zürich, Zurich, Switzerland
| | - Gustaf Ljungman
- Department of Women's and Children's Health, Uppsala University, Uppsala, Sweden
| | | | - Stefan S Bielack
- Klinikum Stuttgart-Olgahospital, Pediatrics 5 (Oncology, Hematology, Immunology), Stuttgart, Germany
| | - Guido Seitz
- Department of Pediatric Surgery, University Children's Hospital Marburg, Marburg, Germany
| | - Joerg Fuchs
- Department of Pediatric Hematology and Oncology, Hospital for Children and Adolescents, University of Tuebingen, Tuebingen, Germany
| | - Erika Hallmen
- Klinikum Stuttgart-Olgahospital, Pediatrics 5 (Oncology, Hematology, Immunology), Stuttgart, Germany
| | - Thomas Klingebiel
- Department for Children and Adolescents, University Hospital, Goethe University, Frankfurt, Germany
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Abrahao-Machado LF, Pinto F, Antunes B, Volc S, Boldrini E, Camargo OPD, Reis RM. Clinical impact of brachyury expression in Ewing sarcoma patients. Adv Med Sci 2021; 66:321-325. [PMID: 34273746 DOI: 10.1016/j.advms.2021.06.002] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/23/2020] [Revised: 05/21/2021] [Accepted: 06/25/2021] [Indexed: 10/20/2022]
Abstract
PURPOSE The T-box transcription factor brachyury has been demonstrated as a prognostic factor in a variety of cancer types and considered a novel oncotarget in solid tumors. Brachyury acts as a regulator of the epithelial-mesenchymal transition (EMT) process, leading to more aggressive behavior and poorer prognosis. However, recent literature evidence suggests a tumor suppressor role in other neoplasms. In the present study, we aimed to study brachyury expression and its prognostic impact in Ewing sarcoma, an aggressive neoplasm of young individuals. METHODS We analyzed the expression of brachyury by immunohistochemistry in a series of 96 Ewing sarcomas in a tissue microarray and investigated the association of the protein expression with the clinical parameters and overall survival. RESULTS More than half of the cases (51%, n = 49) depicted positive nuclear brachyury expression, while a lack of expression was observed in 49% (n = 47) of cases. Nuclear brachyury staining was significantly associated with non-white ethnicity (p = 0.04) and axial localization (p = 0.025). Importantly, lack of brachyury expression was significantly associated with lower overall survival in multivariate analyses (hazard ratio - HR: 2.227, p = 0.008). CONCLUSIONS Our findings indicate, that brachyury is an independent prognostic biomarker in Ewing sarcoma, which might suggest a tumor suppressor role and which yet to be fully elucidated.
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Jagodzińska-Mucha P, Raciborska A, Koseła-Paterczyk H, Kozak K, Bilska K, Świtaj T, Falkowski S, Dawidowska A, Rutkowski P, Ługowska I. Age as a Prognostic Factor in Patients with Ewing Sarcoma-The Polish Sarcoma Group Experience. J Clin Med 2021; 10:jcm10163627. [PMID: 34441922 PMCID: PMC8397138 DOI: 10.3390/jcm10163627] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/07/2021] [Revised: 08/14/2021] [Accepted: 08/15/2021] [Indexed: 12/03/2022] Open
Abstract
Ewing sarcoma (ES) is a rare and aggressive disease that requires multidisciplinary treatment with the use of chemotherapy, radiotherapy, and surgery. Our retrospective study aimed to analyze the prognostic factors and treatment results in different age groups of patients. Between 1998 and 2018, 569 patients with ES were treated in two referral centers. The patients were divided into four age groups (≤10 years; 11–18 years; 19–25, and >25). The treatment results and prognostic factors were assessed for each group. For statistical analyses, we used the Chi2 test, the Kaplan–Meier estimator with a log-rank test, and the multivariate Cox model. Five-year overall survival (OS) rate was 56%. In the age subgroups: ≤10 years, 11–18 years, 19–25 years, and >25 years, the 5-year OS rates were 75%, 58%, 41%, and 52%, respectively. Favorable prognostic factors: female gender (p = 0.024), non-axial localization (p = 0.005), VIDE regimen (p < 0.001), and surgery as a local treatment (p < 0.001) dominated in the group ≤10 years. In multivariate analysis, male (HR = 1.53), axial localization (HR = 1.46), M1 status at presentation (HR = 2.64), and age > 10 years (HR = 2.29) were associated with shorter OS. The treatment results in ES are significantly better in children aged ≤10 years; the challenge is to provide therapy for adolescents and young adults. The diagnostics and treatment of ES patients must be provided in referral centers.
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Affiliation(s)
- Paulina Jagodzińska-Mucha
- Department of Soft Tissue/Bone Sarcoma and Melanoma, Maria Sklodowska-Curie National Research Institute of Oncology, 02-781 Warsaw, Poland; (H.K.-P.); (K.K.); (T.Ś.); (S.F.); (P.R.); (I.Ł.)
- Correspondence: ; Tel.: +48-225-462-031
| | - Anna Raciborska
- Department of Oncology and Surgical Oncology for Children and Youth, Mother and Child Institute, 01-211 Warsaw, Poland; (A.R.); (K.B.)
| | - Hanna Koseła-Paterczyk
- Department of Soft Tissue/Bone Sarcoma and Melanoma, Maria Sklodowska-Curie National Research Institute of Oncology, 02-781 Warsaw, Poland; (H.K.-P.); (K.K.); (T.Ś.); (S.F.); (P.R.); (I.Ł.)
| | - Katarzyna Kozak
- Department of Soft Tissue/Bone Sarcoma and Melanoma, Maria Sklodowska-Curie National Research Institute of Oncology, 02-781 Warsaw, Poland; (H.K.-P.); (K.K.); (T.Ś.); (S.F.); (P.R.); (I.Ł.)
| | - Katarzyna Bilska
- Department of Oncology and Surgical Oncology for Children and Youth, Mother and Child Institute, 01-211 Warsaw, Poland; (A.R.); (K.B.)
| | - Tomasz Świtaj
- Department of Soft Tissue/Bone Sarcoma and Melanoma, Maria Sklodowska-Curie National Research Institute of Oncology, 02-781 Warsaw, Poland; (H.K.-P.); (K.K.); (T.Ś.); (S.F.); (P.R.); (I.Ł.)
| | - Sławomir Falkowski
- Department of Soft Tissue/Bone Sarcoma and Melanoma, Maria Sklodowska-Curie National Research Institute of Oncology, 02-781 Warsaw, Poland; (H.K.-P.); (K.K.); (T.Ś.); (S.F.); (P.R.); (I.Ł.)
| | - Anna Dawidowska
- Early Phase Clinical Trials Unit, Maria Sklodowska-Curie National Research Institute of Oncology, 02-781 Warsaw, Poland;
| | - Piotr Rutkowski
- Department of Soft Tissue/Bone Sarcoma and Melanoma, Maria Sklodowska-Curie National Research Institute of Oncology, 02-781 Warsaw, Poland; (H.K.-P.); (K.K.); (T.Ś.); (S.F.); (P.R.); (I.Ł.)
| | - Iwona Ługowska
- Department of Soft Tissue/Bone Sarcoma and Melanoma, Maria Sklodowska-Curie National Research Institute of Oncology, 02-781 Warsaw, Poland; (H.K.-P.); (K.K.); (T.Ś.); (S.F.); (P.R.); (I.Ł.)
- Department of Oncology and Surgical Oncology for Children and Youth, Mother and Child Institute, 01-211 Warsaw, Poland; (A.R.); (K.B.)
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Qumsiyeh Y, Fernández KS, Fata C, Barthel ER. Retroperitoneal Ewing sarcoma requiring nephrectomy for local control. JOURNAL OF PEDIATRIC SURGERY CASE REPORTS 2021. [DOI: 10.1016/j.epsc.2021.101902] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/16/2022] Open
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Seipel AH, Mechahougui H, Mach N, Triponez F, Faquin WC, De Vito C. Primary Extra-Osseous Ewing Sarcoma of the Thyroid: A Case Report and Review of the Literature. Head Neck Pathol 2021; 16:581-586. [PMID: 34312795 PMCID: PMC9187785 DOI: 10.1007/s12105-021-01365-x] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/02/2021] [Accepted: 07/14/2021] [Indexed: 11/15/2022]
Abstract
Extra-osseous Ewing sarcoma (ES) is a rare and aggressive malignant tumor found in a variety of organs. Primary ES of the thyroid is exceedingly rare and few cases have been documented to date. We describe the case of a 54-year old woman with a history of breast carcinoma in whom a unique hypermetabolic left thyroid nodule was identified during a follow-up PET-CT scan. An ultrasound examination showed a hypoechogenic nodule of 3.7 cm. A cytological diagnosis of poorly differentiated thyroid carcinoma was made, and a total thyroidectomy was performed. The surgical specimen revealed a poorly differentiated neoplasm composed of medium-sized cells with scant cytoplasm, expressing pancytokeratin, CD99 and NKX2.2 but lacking p63 and p40 expression. Molecular analysis revealed a EWSR1-FLI1 fusion transcript supporting the diagnosis of a primary extra-osseous ES of the thyroid. The patient received adjuvant chemotherapy and has no evidence of recurrent disease.
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Affiliation(s)
- Amanda H. Seipel
- grid.150338.c0000 0001 0721 9812Department of Clinical Pathology, Geneva University Hospital, Geneva, Switzerland
| | - Hiba Mechahougui
- grid.150338.c0000 0001 0721 9812Department of Clinical Oncology, Geneva University Hospital, Geneva, Switzerland
| | - Nicolas Mach
- grid.150338.c0000 0001 0721 9812Department of Clinical Oncology, Geneva University Hospital, Geneva, Switzerland
| | - Frédéric Triponez
- grid.8591.50000 0001 2322 4988Department of Thoracic and Endocrine Surgery, Geneva University Hospitals and Faculty of Medicine, University of Geneva, Geneva, Switzerland
| | - William C. Faquin
- grid.32224.350000 0004 0386 9924Department of Pathology, Massachusetts General Hospital and Harvard Medical School, Boston, MA 02114 USA
| | - Claudio De Vito
- grid.150338.c0000 0001 0721 9812Department of Clinical Pathology, Geneva University Hospital, Geneva, Switzerland
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Abbas A, Alaa MN. Ewing Sarcoma Family Tumors: Past, Present and Future Prospects. CURRENT CANCER THERAPY REVIEWS 2021. [DOI: 10.2174/1573394716999201125204643] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/07/2023]
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.
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Affiliation(s)
- Adil Abbas
- College of Medicine, King Saud Bin Abdulaziz University for Health Sciences, The Pediatric Hematology/Oncology Setion, Princess Nourah Oncology Centre, King Abdulaziz Medical City, Jeddah, Saudi Arabia
| | - Mohammed N.S. Alaa
- Department of Laboratory Medicine, King Saud Bin Abdulaziz University for Health Sciences, King Abdulaziz Medical City, Jeddah, Saudi Arabia
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Multi-modality management of extraosseous Ewing sarcoma: 10-year experience from a tertiary care centre. JOURNAL OF RADIOTHERAPY IN PRACTICE 2021. [DOI: 10.1017/s1460396920000126] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/06/2022]
Abstract
AbstractAim:To analyse the presentation, diagnosis and patterns of care of extraosseous Ewing sarcoma treated at our institution between 2008 and 2018.Methods:Electronic medical records of extraosseous Ewing sarcoma patients treated at our institution between January 2008 and April 2018 were reviewed. Kaplan–Meier curves were plotted to assess the overall and disease-free survival with 95% confidence intervals. A univariate analysis was carried out to assess the impact of variables such as surgical excision, completeness of surgery, completeness of chemotherapy and addition of radiation therapy on the survivorship.Results:The records of 65 patients treated at our institution were available for review. The mean age was 26·4 years. The most frequent sites of extraosseous Ewing tumour were kidney—9/65 (13·8%) and brain—10/65 (15·4%). Sixteen (24·6%) patients presented with inoperable/metastatic disease at diagnosis. The other 49 (75·4%) had localised disease at presentation. The median overall survival of the 49 non-metastatic patients was 46 months, and the disease-free survival was 45 months.Conclusion:Extraosseous Ewing sarcoma is a rare and aggressive tumour diagnosed by molecular techniques. Multi-modality treatment including surgical resection with wide margins, adjuvant radiation when indicated and completion of systemic chemotherapy results in optimum outcomes.
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Shadhu K, Ramlagun-Mungur D, Ping XC. Ewing sarcoma of the jejunum: A case report and literature review. World J Gastrointest Surg 2021; 13:507-515. [PMID: 34122739 PMCID: PMC8167841 DOI: 10.4240/wjgs.v13.i5.507] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/04/2020] [Revised: 04/22/2021] [Accepted: 04/29/2021] [Indexed: 02/06/2023] Open
Abstract
BACKGROUND Ewing sarcomas (ESs) are highly aggressive malignancy and are predominant in the long bones of extremities of children and young adults with a slight male predilection and rarely presents at extra skeletal locations.
CASE SUMMARY A 55-year-old woman came to our hospital after finding elevated tumor biomarkers during her physical examination. Her enhanced computed tomography scan showed a jejunal mass. The patient underwent laparoscopic enterectomy. The mass was later diagnosed as ES, evidenced by fluorescence in situ hybridization whereby the GLP ES breakpoint region 1 probe was used, showing that more than 10% of the cells showed a red-green-yellow signal proving the breakpoint rearrangement of the ES breakpoint region 1 gene in chromosome 22.
CONCLUSION We describe a case of localized ES at the jejunum in China based on the literature.
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Affiliation(s)
- Kamleshsingh Shadhu
- Department of General Surgery, Gastrointestinal Surgery, The First Affiliated Hospital of Nanjing Medical University, Nanjing 210029, Jiangsu Province, China
- Pre-registration House Officer, Medical Council of Mauritius, Floreal 0000, Plaine Whilhems, Mauritius
| | - Dadhija Ramlagun-Mungur
- Department of General Surgery, Gastrointestinal Surgery, The First Affiliated Hospital of Nanjing Medical University, Nanjing 210029, Jiangsu Province, China
- Pre-registration House Officer, Medical Council of Mauritius, Floreal 0000, Plaine Whilhems, Mauritius
| | - Xiao-Chun Ping
- Department of General Surgery, Gastrointestinal Surgery, The First Affiliated Hospital of Nanjing Medical University, Nanjing 210029, Jiangsu Province, China
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Pediatric Extraskeletal Ewing Sarcoma Originating in the Heart: A Case Report and Review of the Literature. J Pediatr Hematol Oncol 2021; 43:147-151. [PMID: 31688622 DOI: 10.1097/mph.0000000000001622] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/14/2019] [Accepted: 08/09/2019] [Indexed: 12/27/2022]
Abstract
Extraosseous Ewing sarcoma of primary cardiac origin is an extremely rare variety among pediatric cardiac neoplasms. We report a case of extraosseous Ewing sarcoma of primary cardiac origin in a 9-year-old girl, treated with debulking surgery, adjuvant chemotherapy, and radiotherapy.
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Asselin E, Bowditch S, Kaye S, Awasthi S, Malogolowkin M. Recurrent hyperkeratotic lesion on the plantar foot in a 13-year-old girl. Pediatr Dermatol 2021; 38:680-682. [PMID: 34224617 DOI: 10.1111/pde.14534] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 11/28/2022]
Affiliation(s)
- Ellen Asselin
- Davis, School of Medicine, University of California, Sacramento, CA, USA
| | - Sylvia Bowditch
- Davis, School of Medicine, University of California, Sacramento, CA, USA.,Davis, Medical Center, University of California, Sacramento, CA, USA
| | - Shaina Kaye
- Davis, School of Medicine, University of California, Sacramento, CA, USA.,Davis, Medical Center, University of California, Sacramento, CA, USA
| | - Smita Awasthi
- Davis, School of Medicine, University of California, Sacramento, CA, USA.,Davis, Medical Center, University of California, Sacramento, CA, USA
| | - Marcio Malogolowkin
- Davis, School of Medicine, University of California, Sacramento, CA, USA.,Davis, Medical Center, University of California, Sacramento, CA, USA
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A Case of Ewing Sarcoma of the Bladder Presenting in Early Infancy. J Pediatr Hematol Oncol 2021; 43:e478-e480. [PMID: 33625095 DOI: 10.1097/mph.0000000000002107] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/03/2020] [Accepted: 12/28/2020] [Indexed: 10/22/2022]
Abstract
A 6-week-old female presented with gross hematuria and was diagnosed with Ewing sarcoma of the bladder through ultrasound and cystoscopic biopsies, along with a negative metastatic workup. She was treated with transurethral resection, chemotherapy consisting of with vincristine, cycolphosphamide, doxorubicin, ifosfamide and etoposide, and partial cystectomy. After completing chemotherapy, the patient has been doing well with no evidence of disease. There have been 14 other cases, 4 pediatric, of Ewing sarcoma of the bladder reported. To our knowledge, our case is the youngest patient reported with this disease.
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Abboud A, Masrouha K, Saliba M, Haidar R, Saab R, Khoury N, Tawil A, Saghieh S. Extraskeletal Ewing sarcoma: Diagnosis, management and prognosis. Oncol Lett 2021; 21:354. [PMID: 33747211 DOI: 10.3892/ol.2021.12615] [Citation(s) in RCA: 52] [Impact Index Per Article: 13.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/21/2020] [Accepted: 02/02/2021] [Indexed: 12/26/2022] Open
Abstract
Extraskeletal Ewing sarcoma (EES) is a relatively uncommon primary tumor of the soft tissues, which accounts for 20-30% of all reported cases of ES. Being uncommon, all members of the ES family tumors are treated following the same general protocol of sarcoma tumors. The present review summarizes the diagnosis, management and prognosis of EES, focusing on the differences between the subtypes of ESS. The clinical features and imaging of EES are also discussed. Magnetic resonance imaging is the modality of choice for diagnostic imaging and local staging, while core-needle biopsy with pathological testing is used to obtain a definitive diagnosis. Although several oncology groups endorse that ES family of tumors should be treated with similar algorithm and protocols, some studies have demonstrated that surgery and radiotherapy may be used as a form of local control. However, further studies are required to conclude the optimum treatment option for EES.
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Affiliation(s)
- Abdallah Abboud
- Division of Orthopedic Surgery, Department of Surgery, American University of Beirut Medical Center, Beirut 1013, Lebanon
| | - Karim Masrouha
- Division of Orthopedic Oncology, Department of Orthopedic Surgery, NYU Langone Health, New York, NY 10016, USA
| | - Maelle Saliba
- Department of Pathology and Laboratory Medicine, American University of Beirut Medical Center, Beirut 1013, Lebanon
| | - Rachid Haidar
- Division of Orthopedic Surgery, Department of Surgery, American University of Beirut Medical Center, Beirut 1013, Lebanon
| | - Raya Saab
- Department of Pediatrics and Adolescent Medicine, American University of Beirut Medical Center, Beirut 1013, Lebanon
| | - Nabil Khoury
- Department of Diagnostic Radiology, American University of Beirut Medical Center, Beirut 1013, Lebanon
| | - Ayman Tawil
- Department of Pathology and Laboratory Medicine, American University of Beirut Medical Center, Beirut 1013, Lebanon
| | - Said Saghieh
- Division of Orthopedic Surgery, Department of Surgery, American University of Beirut Medical Center, Beirut 1013, Lebanon
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Murray DB, Horan J, Beausang A, Husien MB. Primary intradural/extradural Ewing's sarcoma of the sacral spine: A case report and literature review. Surg Neurol Int 2021; 12:17. [PMID: 33500832 PMCID: PMC7827301 DOI: 10.25259/sni_766_2020] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/26/2020] [Accepted: 12/19/2020] [Indexed: 11/21/2022] Open
Abstract
Background: Ewing’s sarcoma (ES) is a malignant mesenchymal tumor, most often found in the long bones, and usually affecting children and adolescents in the second decade of life. ES of the spine is a clinical rarity. Case Description: A 45-year-old male presented with a 3-month history of lower back pain which acutely worsened in conjunction with urinary retention. The magnetic resonance imaging revealed a mass extending from L5 to S2 with additional extension through the left S2-3 neural foramen. The metastatic workup was negative. At surgery, the lesion was both intradural and extradural. Following complete surgical resection, the patient was later treated with radiation and chemotherapy. Conclusion: Here, we report an adult male who acutely presented with low back pain attributable to primary intradural/extradural sacral ES.
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Affiliation(s)
- Daniel B Murray
- National Centre for Neurosurgery, Beaumont Hospital/RCSI, Dublin, Ireland
| | - Jack Horan
- National Centre for Neurosurgery, Beaumont Hospital/RCSI, Dublin, Ireland
| | - Alan Beausang
- Department of Neuropathology, Beaumont Hospital, Dublin, Ireland
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Liu Y, Yuan Y, Zhang F, Hu K, Qiu J, Hou X, Yan J, Lian X, Sun S, Liu Z, Shen J. Outcome of multidisciplinary treatment of peripheral primitive neuroectodermal tumor. Sci Rep 2020; 10:15656. [PMID: 32973274 PMCID: PMC7519088 DOI: 10.1038/s41598-020-72680-6] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/27/2019] [Accepted: 09/01/2020] [Indexed: 11/26/2022] Open
Abstract
Peripheral primitive neuroectodermal tumors (PNETs) constitute very rare and aggressive malignancies. To date, there are no standard guidelines for management of peripheral PNETs due to the paucity of cases arising in various body sites. Therapeutic approach is derived from Ewing sarcoma family, which currently remains multimodal. Our study retrospectively analyzed 86 PNET patients from February 1, 1998 to February 1, 2018 at Peking Union Medical College Hospital with an additional 75 patients from review of literature. The clinicopathologic and treatment plans associated with survival was investigated. Surgery, chemotherapy, female sex, small tumor size, no lymph node metastasis, R0 surgical resection, (vincristine + doxorubicin + cyclophosphamide)/(isophosphamide + etoposide) regimen, and more than 10 cycles of chemotherapy were associated with improved overall survival in univariate analysis. Surgery, more than 10 cycles of chemotherapy, and small tumor size were independent prognostic factors for higher overall survival. Our data indicates that multimodal therapy is the mainstay therapeutic approach for peripheral PNET.
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Affiliation(s)
- Yidi Liu
- Department of Radiation Oncology, Peking Union Medical College Hospital. Chinese Academy of Medical Sciences & Peking Union Medical College, No.1 Shuaifuyuan Wangfujing, Dongcheng District, Beijing, 100730, People's Republic of China
| | - Yan Yuan
- Department of Radiation Oncology, Peking Union Medical College Hospital. Chinese Academy of Medical Sciences & Peking Union Medical College, No.1 Shuaifuyuan Wangfujing, Dongcheng District, Beijing, 100730, People's Republic of China
| | - Fuquan Zhang
- Department of Radiation Oncology, Peking Union Medical College Hospital. Chinese Academy of Medical Sciences & Peking Union Medical College, No.1 Shuaifuyuan Wangfujing, Dongcheng District, Beijing, 100730, People's Republic of China
| | - Ke Hu
- Department of Radiation Oncology, Peking Union Medical College Hospital. Chinese Academy of Medical Sciences & Peking Union Medical College, No.1 Shuaifuyuan Wangfujing, Dongcheng District, Beijing, 100730, People's Republic of China
| | - Jie Qiu
- Department of Radiation Oncology, Peking Union Medical College Hospital. Chinese Academy of Medical Sciences & Peking Union Medical College, No.1 Shuaifuyuan Wangfujing, Dongcheng District, Beijing, 100730, People's Republic of China
| | - Xiaorong Hou
- Department of Radiation Oncology, Peking Union Medical College Hospital. Chinese Academy of Medical Sciences & Peking Union Medical College, No.1 Shuaifuyuan Wangfujing, Dongcheng District, Beijing, 100730, People's Republic of China
| | - Junfang Yan
- Department of Radiation Oncology, Peking Union Medical College Hospital. Chinese Academy of Medical Sciences & Peking Union Medical College, No.1 Shuaifuyuan Wangfujing, Dongcheng District, Beijing, 100730, People's Republic of China
| | - Xin Lian
- Department of Radiation Oncology, Peking Union Medical College Hospital. Chinese Academy of Medical Sciences & Peking Union Medical College, No.1 Shuaifuyuan Wangfujing, Dongcheng District, Beijing, 100730, People's Republic of China
| | - Shuai Sun
- Department of Radiation Oncology, Peking Union Medical College Hospital. Chinese Academy of Medical Sciences & Peking Union Medical College, No.1 Shuaifuyuan Wangfujing, Dongcheng District, Beijing, 100730, People's Republic of China
| | - Zhikai Liu
- Department of Radiation Oncology, Peking Union Medical College Hospital. Chinese Academy of Medical Sciences & Peking Union Medical College, No.1 Shuaifuyuan Wangfujing, Dongcheng District, Beijing, 100730, People's Republic of China
| | - Jie Shen
- Department of Radiation Oncology, Peking Union Medical College Hospital. Chinese Academy of Medical Sciences & Peking Union Medical College, No.1 Shuaifuyuan Wangfujing, Dongcheng District, Beijing, 100730, People's Republic of China.
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