All-site radiotherapy for metastatic ewing's sarcoma: a short-term analysis of feasibility, response, and safety.

Clinical Snapshot

Key Findings

• P Value: Soft tissue vs bone CR rate p < 0.001; combination therapy PFS benefit p = 0.014

• Effect Size: Complete response rate 48.1%, disease control rate 97.4%

• Primary Outcome: Local objective response rate 61.0% at 2 months

• Nnt Or Sensitivity: Median PFS 6.0 months, median OS 8.0 months

• Confidence Interval: PFS: 95% CI 2.30-9.70 months, OS: 95% CI 6.69-9.31 months

Clinical Application

Requires advanced radiotherapy facilities (helical tomotherapy) and multidisciplinary expertise Limited applicability given resource requirements; would need TGA approval for off-label systemic agents; not currently supported by PBS for this indication Highly selected metastatic Ewing sarcoma patients with good performance status and limited disease burden

Abstract

BACKGROUND: Metastatic Ewing sarcoma (EWS) has a poor prognosis. While metastasis-directed therapy benefits oligometastatic disease, the role of comprehensive all-site radiotherapy in widespread disease remains underexplored. This study aimed to preliminarily assess its short-term efficacy and safety. METHODS: This retrospective analysis included 21 consecutive metastatic EWS patients treated with helical tomotherapy (Aug 2024-Jun 2025). All known metastases and unresected primary tumors received radiotherapy (45-55 Gy in 20 fractions for most sites; 12-45 Gy for lung/pleural metastases). Concurrent systemic therapies included chemotherapy, tyrosine kinase inhibitors (TKIs), immune checkpoint inhibitors (ICIs), or combinations. Primary endpoints were local objective response rate (ORR, RECIST 1.1) at 2 months post-radiotherapy and acute toxicity (CTCAE 5.0). Systemic therapy subgroup analyses were exploratory. RESULTS: Median follow-up was 6 months (range 2-11). Among 77 target lesions, ORR was 61.0% (CR 48.1%), and disease control rate (DCR) was 97.4%. Soft tissue lesions had a significantly higher CR rate than bone metastases (78.3% vs 3.2%, p < 0.001), potentially influenced by RECIST 1.1 limitations and treatment heterogeneity. Median progression-free survival (PFS) was 6.0 months (95% CI: 2.30-9.70), and median overall survival (OS) was 8.0 months (95% CI: 6.69-9.31). Combination systemic therapy was associated with improved PFS (HR 3.94, 95%CI 1.32-11.78; p = 0.014), with chemotherapy-based regimens yielding the best PFS (8.5 months). TKI-containing regimens were linked to shorter PFS (4.0 vs 8.5 months, p = 0.048) due to selection bias. Acute toxicity was manageable, with grade 3 thrombocytopenia (19.0%) and pneumonitis (4.7%) resolving with treatment. CONCLUSION: All-site radiotherapy achieves promising short-term local control with manageable toxicity in metastatic EWS, demonstrating feasibility and a lesion site-specific response warranting further investigation. Systemic therapy, particularly chemotherapy, correlates with improved PFS. Given high systemic progression rates, long-term outcomes may benefit from integration with more effective systemic therapies, supporting future prospective trials.

References

1. 1.Yang, Y., Xie, L., Sun, X., Xu, J., & Ren, G. (2026). All-site radiotherapy for metastatic ewing's sarcoma: a short-term analysis of feasibility, response, and safety. Clinical & Experimental Metastasis. https://doi.org/10.2147/OTT.S89755