Extraosseous Ewing Sarcoma

From 1987 to 2004, 111 patients with nonmetastatic extraosseous Ewing sarcoma were enrolled on the RMS-88 and RMS-96 protocols.[71] Patients with initial complete tumor resection received ifosfamide, vincristine, and actinomycin (IVA) while patients with residual tumor received IVA plus doxorubicin (VAIA) or IVA plus carboplatin, epirubicin, and etoposide (CEVAIE). Seventy-six percent of patients received radiation.

From 1987 to 2004, 111 patients with nonmetastatic extraosseous Ewing sarcoma were enrolled on the RMS-88 and RMS-96 protocols.[71] Patients with initial complete tumor resection received ifosfamide, vincristine, and actinomycin (IVA) while patients with residual tumor received IVA plus doxorubicin (VAIA) or IVA plus carboplatin, epirubicin, and etoposide (CEVAIE). Seventy-six percent of patients received radiation.

The 5-year EFS rate was 59%, and the OS rate was 69%.

From 1987 to 2004, 111 patients with nonmetastatic extraosseous Ewing sarcoma were enrolled on the RMS-88 and RMS-96 protocols.[71] Patients with initial complete tumor resection received ifosfamide, vincristine, and actinomycin (IVA) while patients with residual tumor received IVA plus doxorubicin (VAIA) or IVA plus carboplatin, epirubicin, and etoposide (CEVAIE). Seventy-six percent of patients received radiation.

In a multivariate analysis, independent adverse prognostic factors included axial primary, tumor size greater than 10 cm, Intergroup Rhabdomyosarcoma Studies Group III, and lack of radiation therapy.

In a retrospective French study, patients with extraosseous Ewing sarcoma were treated using a rhabdomyosarcoma regimen (no anthracyclines) or a Ewing sarcoma regimen (includes anthracyclines).[72,73]

In a retrospective French study, patients with extraosseous Ewing sarcoma were treated using a rhabdomyosarcoma regimen (no anthracyclines) or a Ewing sarcoma regimen (includes anthracyclines).[72,73]

Patients who received the anthracycline-containing regimen had a significantly better EFS and OS than patients who did not receive anthracyclines.

Two North American Ewing sarcoma trials included patients with extraosseous Ewing sarcoma.[24,74] In a review of data from the POG-9354 (INT-0154) and EWS0031 (NCT00006734) studies, 213 patients with extraosseous Ewing sarcoma and 826 patients with Ewing sarcoma of bone were identified.[75][Level of evidence C2]

Two North American Ewing sarcoma trials included patients with extraosseous Ewing sarcoma.[24,74] In a review of data from the POG-9354 (INT-0154) and EWS0031 (NCT00006734) studies, 213 patients with extraosseous Ewing sarcoma and 826 patients with Ewing sarcoma of bone were identified.[75][Level of evidence C2]

The HR for EFS of extraosseous Ewing sarcoma was superior (0.62), and extraosseous Ewing sarcoma was a favorable risk factor, independent of age, race, and primary site.

In addition to the above review, the COG AEWS1031 (NCT01231906) trial subsequently treated patients using a compressed chemotherapy schedule (every 2 weeks). Patients were randomly assigned to receive standard cycles of vincristine, doxorubicin, and cyclophosphamide, alternating with either ifosfamide and etoposide or vincristine, topotecan and cyclophosphamide every third cycle. There were 116 patients with extraosseous tumors, 114 patients with pelvic bone tumors, and 399 patients with nonpelvic bone tumors.[26]

In addition to the above review, the COG AEWS1031 (NCT01231906) trial subsequently treated patients using a compressed chemotherapy schedule (every 2 weeks). Patients were randomly assigned to receive standard cycles of vincristine, doxorubicin, and cyclophosphamide, alternating with either ifosfamide and etoposide or vincristine, topotecan and cyclophosphamide every third cycle. There were 116 patients with extraosseous tumors, 114 patients with pelvic bone tumors, and 399 patients with nonpelvic bone tumors.[26]

There were no differences in patient outcomes between the treatment regimens.

In addition to the above review, the COG AEWS1031 (NCT01231906) trial subsequently treated patients using a compressed chemotherapy schedule (every 2 weeks). Patients were randomly assigned to receive standard cycles of vincristine, doxorubicin, and cyclophosphamide, alternating with either ifosfamide and etoposide or vincristine, topotecan and cyclophosphamide every third cycle. There were 116 patients with extraosseous tumors, 114 patients with pelvic bone tumors, and 399 patients with nonpelvic bone tumors.[26]

The 5-year EFS rates were 75% (95% CI, 65%–82%) for patients with pelvic bone tumors, 78% (95% CI, 73%–81%) for patients with nonpelvic bone tumors, and 85% (95% CI, 76%–90%) for patients with extraosseous primary sites (global P value = .124).

The Cooperative Weichteilsarkomstudiengruppe (CWS) performed a retrospective analysis of 243 patients with nonmetastatic extraosseous Ewing sarcoma treated on three consecutive soft tissue sarcoma studies between 1991 and 2008. Several different drug regimens were used, all containing vincristine, doxorubicin, and alkylating agents.[76]

The Cooperative Weichteilsarkomstudiengruppe (CWS) performed a retrospective analysis of 243 patients with nonmetastatic extraosseous Ewing sarcoma treated on three consecutive soft tissue sarcoma studies between 1991 and 2008. Several different drug regimens were used, all containing vincristine, doxorubicin, and alkylating agents.[76]

The outcome improved over time, but it was difficult to assign causality to any specific therapy with these historical comparisons.

The Cooperative Weichteilsarkomstudiengruppe (CWS) performed a retrospective analysis of 243 patients with nonmetastatic extraosseous Ewing sarcoma treated on three consecutive soft tissue sarcoma studies between 1991 and 2008. Several different drug regimens were used, all containing vincristine, doxorubicin, and alkylating agents.[76]

Patients with extremity primary tumors (compared with other locations) and patients with smaller tumors had better outcomes.

The Cooperative Weichteilsarkomstudiengruppe (CWS) performed a retrospective analysis of 243 patients with nonmetastatic extraosseous Ewing sarcoma treated on three consecutive soft tissue sarcoma studies between 1991 and 2008. Several different drug regimens were used, all containing vincristine, doxorubicin, and alkylating agents.[76]

The 5-year EFS rate varied, from 57% to 79%, with the better outcome seen in the most recent protocol.

In a review of 78 reported cases (some lacking molecular confirmation), the OS rate was 91%. Adequate local control, defined as a complete resection with negative margins, radiation therapy, or a combination, significantly reduced the incidence of relapse. Standard chemotherapy for Ewing sarcoma is often used for these patients because there are no data to suggest which patients could be treated less aggressively.[77,78]

A series of 56 patients with cutaneous or subcutaneous Ewing sarcoma confirmed the excellent outcome with the use of standard systemic therapy and local control. Attempted primary definitive surgery often resulted in the need for either radiation therapy or more function-compromising surgery, supporting the recommendation of biopsy only as initial surgery, rather than up-front unplanned resection.[79][Level of evidence C2]