Localized Ewing Sarcoma: Interval-Compressed vs Standard-Timing Chemotherapy

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As reported in the Journal of Clinical Oncology by Cash et al, 10-year follow-up of the Children’s Oncology Group Study AEWS0031 has shown a maintained event-free survival benefit with interval-compressed chemotherapy vs standard-timing chemotherapy in patients with localized Ewing sarcoma. Interval-compressed chemotherapy was associated with an overall survival advantage over standard chemotherapy.

Study Details

In the trial, 568 patients were randomly assigned to receive vincristine/doxorubicin/cyclophosphamide and ifosfamide/etoposide alternating once every 3 weeks (standard-timing chemotherapy [STC] group) vs once every 2 weeks (interval-compressed chemotherapy [ICC] group). At 5 years, patients who received interval-compressed chemotherapy had superior event-free survival, with no significant increase in toxicity.

Key Findings

At 10 years, the event-free survival rate was 70% in the ICC group vs 61% in the STC group (P = .03), and the 10-year overall survival rate was 76% vs 69% (P = .04). The 10-year cumulative incidence of second malignant neoplasms was 3.2% (95% confidence interval [CI] = 1.6%–6.3%) in the ICC group vs 4.2% (95% CI = 2.4%–7.5%) in the STC group (P = .5).

A test for interaction showed that interval-compressed chemotherapy was associated with a greater reduction in risk for event-free survival events among patients with a tumor volume of at least 200 mL (relative hazard rate = 0.45) vs those with a tumor volume less than 200 mL (relative hazard rate = 1.2, P = .04). No significant interactions were observed in subgroups according to age, primary tumor site, and histologic response.

The investigators concluded: “With longer-term follow-up, interval-compressed chemotherapy for localized Ewing sarcoma is associated with superior event-free survival and overall survival without an increased risk for second malignant neoplasms compared with standard-timing chemotherapy. Interval-compressed chemotherapy is associated with improved outcomes even in adverse-risk patient groups.”

Thomas Cash, MD, MSc, of the Department of Pediatrics, Emory University, Atlanta, is the corresponding author of the Journal of Clinical Oncology article.

Disclosure: The study was supported by grants from the National Cancer Institute, St. Baldrick’s Foundation, and Daniel P. Sullivan Fund. For full disclosures of the study authors, visit

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