Origin and Incidence of Ewing Family of Tumors
Prognostic Factors for Ewing Tumor of Bone
        Pretreatment factors
        Treatment response factors to preoperative therapy

The National Cancer Institute provides the PDQ pediatric cancer treatment information summaries as a public service to increase the availability of evidence-based cancer information to health professionals, patients, and the public.

Cancer in children and adolescents is rare. Children and adolescents with cancer should be referred to medical centers that have a multidisciplinary team of cancer specialists with experience treating the cancers that occur during childhood and adolescence. This multidisciplinary team approach incorporates the skills of the primary care physician, pediatric surgical subspecialists, radiation oncologists, pediatric oncologists/hematologists, rehabilitation specialists, pediatric nurse specialists, social workers, and others to ensure that children receive treatment, supportive care, and rehabilitation that will achieve optimal survival and quality of life. Refer to the PDQ Supportive Care summaries for specific information about supportive care for children and adolescents with cancer.

Guidelines for pediatric cancer centers and their role in the treatment of pediatric patients with cancer have been outlined by the American Academy of Pediatrics.[1] At these pediatric cancer centers, clinical trials are available for most types of cancer that occur in children and adolescents, and the opportunity to participate in these trials is offered to most patients/families. Clinical trials for children and adolescents with cancer are generally designed to compare potentially better therapy with therapy that is currently accepted as standard. Most of the progress made in identifying curative therapies for childhood cancers has been achieved through clinical trials. Information about ongoing clinical trials is available from the NCI Web site.

In recent decades, dramatic improvements in survival have been achieved for children and adolescents with cancer. Childhood and adolescent cancer survivors require close follow-up because cancer therapy side effects may persist or develop months or years after treatment. Refer to the PDQ summary on Late Effects of Treatment for Childhood Cancer for specific information about the incidence, type, and monitoring of late effects in childhood and adolescent cancer survivors.

Note: Some citations in the text of this section are followed by a level of evidence. The PDQ Pediatric and Adult Treatment Editorial Boards use a formal ranking system to help the reader judge the strength of evidence linked to the reported results of a therapeutic strategy. (Refer to the PDQ summary on Levels of Evidence for more information.)

Studies using immunohistochemical markers,[2] cytogenetics,[3,4] molecular genetics, and tissue culture [5] indicate that classic Ewing sarcoma, primitive neuroectodermal tumor, and Askin tumor (chest wall), as well as extraosseous Ewing sarcoma (EOE) are all derived from the same primordial bone marrow-derived mesenchymal stem cell.

The median age of patients with Ewing family of tumors (EFT) is 15 years, and more than 50% of patients are adolescents. Well-characterized cases of EFT in neonates and infants have been described.[6] Based on data from 1,426 patients entered on European Intergroup Cooperative Ewing Sarcoma Studies (EI-CESS), 59% of patients are male and 41% are female. Primary sites include lower extremity (41%), upper extremity (9%), chest wall (16%), pelvis (26%), spine (6%), and skull (2%). For EOE, the most common sites are trunk (32%), extremity (26%), head and neck (18%), retroperitoneum (16%), and other sites (9%).[7]

There are two major types of prognostic factors for patients with Ewing tumor of bone (ETB): pretreatment factors and treatment response factors.

• Site: Patients with ETB in the distal extremities have the best prognosis. Patients with ETB in the proximal extremities have an intermediate prognosis, followed by patients with central or pelvic sites.[8-10]



• Size: Tumor volume has been shown to be an important prognostic factor in most studies. Cutoffs of either 100 mL or 200 mL are used to define larger tumors. Larger tumors tend to occur in unfavorable sites.[10,11]



• Pathologic fracture: Pathologic fractures do not appear to be a prognostic factor for ETB.[12]



• Age: Younger patients (<10 years) have a better prognosis than adolescents, young adults, or adults.[8-10]



• Gender: Girls with ETB have a better prognosis than boys.[9]



• Serum lactate dehydrogenase: Increased serum lactate dehydrogenase (LDH) levels prior to treatment are associated with inferior prognosis. Increased LDH levels are also correlated with large primary tumors and metastatic disease.[9]



• Metastases: Any metastatic disease defined by standard imaging techniques or bone marrow aspirate/biopsy by morphology is an adverse prognostic factor. Patients with metastatic disease confined to lung have a better prognosis than patients with extrapulmonary metastatic sites.[8,10,13] Positron emission tomography (PET) scans using fluorine-18-fluorodeoxyglucose (FDG) have been shown to provide additional information and have a relevant impact on therapy planning.[14]



• Histopathology: The degree of neural differentiation is not a prognostic factor in ETB.[15,16]



• Molecular pathology: The EWS-FL1 translocation associated with EFT can occur at several potential breakpoints in each of the genes which join to form the novel segment of DNA. Some variants of the novel gene created by the translocation have been associated with a more favorable prognosis.[17]



• Detectable fusion transcripts in morphologically normal marrow: Reverse transcription polymerase chain reaction (RT-PCR) can be used to detect fusion transcripts in bone marrow. In a single retrospective study utilizing patients with normal marrow morphology and no other metastatic site, fusion transcript detection in marrow was associated with an increased risk of relapse.[18]



• Other biological factors: Overexpression of the p53 protein [19] and loss of 16q [20] may be adverse prognostic factors.

Multiple studies have shown that patients with minimal or no residual viable tumor after presurgical chemotherapy have a significantly better event-free survival compared with patients with larger amounts of viable tumor.[21-24] Female gender and younger age predict a good histologic response to preoperative therapy.[25] Patients with poor response to presurgical chemotherapy have an increased risk for local recurrence.[26] For patients who receive preinduction and postinduction chemotherapy positron emission tomography (PET) scans, decreased PET uptake following chemotherapy correlated with good histologic response.[27]

References

1. Guidelines for the pediatric cancer center and role of such centers in diagnosis and treatment. American Academy of Pediatrics Section Statement Section on Hematology/Oncology. Pediatrics 99 (1): 139-41, 1997.  [PUBMED Abstract]
   
   
2. Olsen SH, Thomas DG, Lucas DR: Cluster analysis of immunohistochemical profiles in synovial sarcoma, malignant peripheral nerve sheath tumor, and Ewing sarcoma. Mod Pathol 19 (5): 659-68, 2006.  [PUBMED Abstract]
   
   
3. Delattre O, Zucman J, Melot T, et al.: The Ewing family of tumors--a subgroup of small-round-cell tumors defined by specific chimeric transcripts. N Engl J Med 331 (5): 294-9, 1994.  [PUBMED Abstract]
   
   
4. Dagher R, Pham TA, Sorbara L, et al.: Molecular confirmation of Ewing sarcoma. J Pediatr Hematol Oncol 23 (4): 221-4, 2001.  [PUBMED Abstract]
   
   
5. Llombart-Bosch A, Carda C, Peydro-Olaya A, et al.: Soft tissue Ewing's sarcoma. Characterization in established cultures and xenografts with evidence of a neuroectodermic phenotype. Cancer 66 (12): 2589-601, 1990.  [PUBMED Abstract]
   
   
6. Kim SY, Tsokos M, Helman LJ: Dilemmas associated with congenital ewing sarcoma family tumors. J Pediatr Hematol Oncol 30 (1): 4-7, 2008.  [PUBMED Abstract]
   
   
7. Raney RB, Asmar L, Newton WA Jr, et al.: Ewing's sarcoma of soft tissues in childhood: a report from the Intergroup Rhabdomyosarcoma Study, 1972 to 1991. J Clin Oncol 15 (2): 574-82, 1997.  [PUBMED Abstract]
   
   
8. Cotterill SJ, Ahrens S, Paulussen M, et al.: Prognostic factors in Ewing's tumor of bone: analysis of 975 patients from the European Intergroup Cooperative Ewing's Sarcoma Study Group. J Clin Oncol 18 (17): 3108-14, 2000.  [PUBMED Abstract]
   
   
9. Bacci G, Longhi A, Ferrari S, et al.: Prognostic factors in non-metastatic Ewing's sarcoma tumor of bone: an analysis of 579 patients treated at a single institution with adjuvant or neoadjuvant chemotherapy between 1972 and 1998. Acta Oncol 45 (4): 469-75, 2006.  [PUBMED Abstract]
   
   
10. Rodríguez-Galindo C, Liu T, Krasin MJ, et al.: Analysis of prognostic factors in ewing sarcoma family of tumors: review of St. Jude Children's Research Hospital studies. Cancer 110 (2): 375-84, 2007.  [PUBMED Abstract]
    
    
11. Ahrens S, Hoffmann C, Jabar S, et al.: Evaluation of prognostic factors in a tumor volume-adapted treatment strategy for localized Ewing sarcoma of bone: the CESS 86 experience. Cooperative Ewing Sarcoma Study. Med Pediatr Oncol 32 (3): 186-95, 1999.  [PUBMED Abstract]
    
    
12. Bramer JA, Abudu AA, Grimer RJ, et al.: Do pathological fractures influence survival and local recurrence rate in bony sarcomas? Eur J Cancer 43 (13): 1944-51, 2007.  [PUBMED Abstract]
    
    
13. Miser JS, Krailo MD, Tarbell NJ, et al.: Treatment of metastatic Ewing's sarcoma or primitive neuroectodermal tumor of bone: evaluation of combination ifosfamide and etoposide--a Children's Cancer Group and Pediatric Oncology Group study. J Clin Oncol 22 (14): 2873-6, 2004.  [PUBMED Abstract]
    
    
14. Völker T, Denecke T, Steffen I, et al.: Positron emission tomography for staging of pediatric sarcoma patients: results of a prospective multicenter trial. J Clin Oncol 25 (34): 5435-41, 2007.  [PUBMED Abstract]
    
    
15. Parham DM, Hijazi Y, Steinberg SM, et al.: Neuroectodermal differentiation in Ewing's sarcoma family of tumors does not predict tumor behavior. Hum Pathol 30 (8): 911-8, 1999.  [PUBMED Abstract]
    
    
16. Luksch R, Sampietro G, Collini P, et al.: Prognostic value of clinicopathologic characteristics including neuroectodermal differentiation in osseous Ewing's sarcoma family of tumors in children. Tumori 85 (2): 101-7, 1999 Mar-Apr.  [PUBMED Abstract]
    
    
17. de Alava E, Kawai A, Healey JH, et al.: EWS-FLI1 fusion transcript structure is an independent determinant of prognosis in Ewing's sarcoma. J Clin Oncol 16 (4): 1248-55, 1998.  [PUBMED Abstract]
    
    
18. Schleiermacher G, Peter M, Oberlin O, et al.: Increased risk of systemic relapses associated with bone marrow micrometastasis and circulating tumor cells in localized ewing tumor. J Clin Oncol 21 (1): 85-91, 2003.  [PUBMED Abstract]
    
    
19. Abudu A, Mangham DC, Reynolds GM, et al.: Overexpression of p53 protein in primary Ewing's sarcoma of bone: relationship to tumour stage, response and prognosis. Br J Cancer 79 (7-8): 1185-9, 1999.  [PUBMED Abstract]
    
    
20. Ozaki T, Paulussen M, Poremba C, et al.: Genetic imbalances revealed by comparative genomic hybridization in Ewing tumors. Genes Chromosomes Cancer 32 (2): 164-71, 2001.  [PUBMED Abstract]
    
    
21. Paulussen M, Ahrens S, Dunst J, et al.: Localized Ewing tumor of bone: final results of the cooperative Ewing's Sarcoma Study CESS 86. J Clin Oncol 19 (6): 1818-29, 2001.  [PUBMED Abstract]
    
    
22. Rosito P, Mancini AF, Rondelli R, et al.: Italian Cooperative Study for the treatment of children and young adults with localized Ewing sarcoma of bone: a preliminary report of 6 years of experience. Cancer 86 (3): 421-8, 1999.  [PUBMED Abstract]
    
    
23. Wunder JS, Paulian G, Huvos AG, et al.: The histological response to chemotherapy as a predictor of the oncological outcome of operative treatment of Ewing sarcoma. J Bone Joint Surg Am 80 (7): 1020-33, 1998.  [PUBMED Abstract]
    
    
24. Oberlin O, Deley MC, Bui BN, et al.: Prognostic factors in localized Ewing's tumours and peripheral neuroectodermal tumours: the third study of the French Society of Paediatric Oncology (EW88 study). Br J Cancer 85 (11): 1646-54, 2001.  [PUBMED Abstract]
    
    
25. Ferrari S, Bertoni F, Palmerini E, et al.: Predictive factors of histologic response to primary chemotherapy in patients with Ewing sarcoma. J Pediatr Hematol Oncol 29 (6): 364-8, 2007.  [PUBMED Abstract]
    
    
26. Lin PP, Jaffe N, Herzog CE, et al.: Chemotherapy response is an important predictor of local recurrence in Ewing sarcoma. Cancer 109 (3): 603-11, 2007.  [PUBMED Abstract]
    
    
27. Hawkins DS, Schuetze SM, Butrynski JE, et al.: [18F]Fluorodeoxyglucose positron emission tomography predicts outcome for Ewing sarcoma family of tumors. J Clin Oncol 23 (34): 8828-34, 2005.  [PUBMED Abstract]
    
    

Back to Top

< Previous Section  |  Next Section >