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Background <p>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.</p> Methods <p>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&#xa0;Gy in 20 fractions for most sites; 12–45&#xa0;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&#xa0;months post-radiotherapy and acute toxicity (CTCAE 5.0). Systemic therapy subgroup analyses were exploratory.</p> Results <p>Median follow-up was 6&#xa0;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 &lt; 0.001), potentially influenced by RECIST 1.1 limitations and treatment heterogeneity. Median progression-free survival (PFS) was 6.0&#xa0;months (95% CI: 2.30–9.70), and median overall survival (OS) was 8.0&#xa0;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&#xa0;months). TKI-containing regimens were linked to shorter PFS (4.0 vs 8.5&#xa0;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.</p> Conclusion <p>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.</p>

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

  • 期刊论文

  • 出版模式：

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  • 发表日期：

    2026年4月27日

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  • YuanYou Yang,
  • Lu Xie,
  • Xin Sun,
  • Jie Xu,
  • Gang Ren

摘要

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.