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Cancer Health Center

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Ewing Sarcoma Treatment (PDQ®): Treatment - Health Professional Information [NCI] - General Information

Table 1. Characteristics of Children With Extraosseous Ewing Sarcoma and Skeletal Ewing Sarcoma

CharacteristicExtraosseous Ewing SarcomaSkeletal Ewing SarcomaP Value
Mean age (range), years20 (0-39)16 (0-39)<.001
Male gender53%63%<.001
White (nonwhite race)85% (15%)93% (8%)<.001
Axial primary sites (non-axial primary)73% (27%)54% (46%)<.001
Pelvic primary sites (nonpelvic primary)20% (80%)27% (73%).001

Prognostic Factors for Ewing Sarcoma

The two major types of prognostic factors for patients with Ewing sarcoma are as follows:

  • Pretreatment.
  • Treatment response.

Pretreatment factors

  • Site of tumor: Patients with Ewing sarcoma in the distal extremities have the best prognosis. Patients with Ewing sarcoma in the proximal extremities have an intermediate prognosis, followed by patients with central or pelvic sites.[18,19,20] Patients with tumors of the sacrum have a very poor prognosis.[21]
  • Tumor size or volume: Tumor size or volume has been shown to be an important prognostic factor in most studies. Cutoffs of a volume of 100 mL or 200 mL and/or single dimension greater than 8 cm are used to define larger tumors. Larger tumors tend to occur in unfavorable sites.[20,22]
  • Age: Infants and younger patients (aged <15 years) have a better prognosis than adolescents aged 15 years or older, young adults, or adults.[13,18,19,20,23] In North American studies, patients younger than 10 years have a better outcome than those aged 10 to 17 years at diagnosis (relative risk [RR], 1.4). Patients older than 18 years have an inferior outcome (RR, 2.5).[24] A retrospective review of two consecutive German trials for Ewing sarcoma identified 47 patients older than 40 years.[25] With adequate multimodal therapy, survival was comparable to the survival observed in adolescents treated on the same trials.
  • Gender: Girls with Ewing sarcoma have a better prognosis than boys.[11,19]
  • Serum lactate dehydrogenase (LDH): Increased serum LDH levels before treatment are associated with inferior prognosis. Increased LDH levels are also correlated with large primary tumors and metastatic disease.[19]
  • Metastases: Any metastatic disease defined by standard imaging techniques or bone marrow aspirate/biopsy by morphology is an adverse prognostic factor. The presence or absence of metastatic disease is the single most powerful predictor of outcome. Metastases at diagnosis are detected in about 25% of patients.[10] Patients with metastatic disease confined to lung have a better prognosis than patients with extrapulmonary metastatic sites.[18,20,26] The number of pulmonary lesions does not seem to correlate with outcome, but patients with unilateral lung involvement do better than patients with bilateral lung involvement.[27] Patients with metastasis to bone only seem to have a better outcome than patients with metastases to both bone and lung.[28] Based on an analysis from the SEER database, regional lymph node involvement in patients is associated with an inferior overall outcome when compared with patients without regional lymph node involvement.[29]
  • Prior treatment for cancer: Fifty-eight patients with Ewing sarcoma who were diagnosed after treatment for a prior malignancy (2.1% of patients with Ewing sarcoma in the SEER database) were compared with 2,756 patients in the SEER database with Ewing sarcoma as a first cancer over the same period. Patients with Ewing sarcoma as a second malignant neoplasm were older (secondary Ewing sarcoma, mean age of 47.8 years; primary Ewing sarcoma, mean age of 22.5 years), more likely to have a primary tumor in an axial or extraskeletal site, and had a worse prognosis (5-year overall survival for patients with secondary Ewing sarcoma, 43.5%; patients with primary Ewing sarcoma, 64.2%).[30]
  • Standard cytogenetics: Complex karyotype (defined as the presence of 5 or more independent chromosome abnormalities at diagnosis) and modal chromosome numbers lower than 50 appear to have adverse prognostic significance.[31]
  • Detectable fusion transcripts in morphologically normal marrow: Reverse transcriptase polymerase chain reaction 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.[32]
  • Other biological factors: Overexpression of the p53 protein, Ki67 expression, and loss of 16q may be adverse prognostic factors.[33,34,35] High expression of microsomal glutathione S-transferase, an enzyme associated with resistance to doxorubicin, is associated with inferior outcome for Ewing sarcoma.[36]
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