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

Background Metastatic Ewing sarcoma (EWS) has a poor prognosis. While metastasis-directed therapy (MDT) benefits oligometastatic disease, the role of comprehensive radiotherapy targeting all metastatic sites in widespread disease remains underexplored. This study aimed to provide a preliminary assessment of the short-term efficacy and safety of all-site radiotherapy in metastatic EWS. Methods This retrospective analysis included 21 consecutive metastatic EWS patients treated with helical tomotherapy (Aug 2024–Jun 2025). All known metastatic lesions and the primary tumor (if unresected) received radiotherapy. Prescription doses were 45–55 Gy in 20 fractions for most sites; lung/pleural metastases received adapted regimens (12–45 Gy). Systemic therapy regimens varied (chemotherapy, tyrosine kinase inhibitors [TKIs], immune checkpoint inhibitors [ICIs], or combinations). Primary endpoints were local objective response rate (ORR, RECIST 1.1) and acute toxicity (CTCAE 5.0). Secondary/exploratory endpoints included progression-free survival (PFS), overall survival (OS). Results Median follow-up was 6 months (range 2–11). Among 77 target lesions, the objective response rate (ORR, complete response [CR] + partial response [PR]) was 61.0% (47/77), including a CR rate of 48.1% (37/77). The disease control rate (DCR, CR + PR + stable disease [SD]) was 97.4%. A striking finding was the significantly higher complete response rate in soft tissue lesions compared to bone metastases (78.3% vs 3.2%, p < 0.001). The median PFS was 6.0 months (95% CI: 2.30–9.70), and the median OS was 8.0 months (95% CI: 6.69–9.31). Multivariate analysis identified "Combination Systemic Therapy" as associated with improved PFS (HR 3.94, 95%CI 1.32–11.78; p = 0.014), with chemotherapy-based regimens showing the best median PFS (8.5 months). An exploratory analysis suggested shorter PFS in patients receiving TKI-containing regimens (4.0 vs 8.5 months, p = 0.048); however, this finding is likely confounded by selection bias, as TKIs were often used in more heavily pretreated patients. Acute toxicity was manageable: grade 3 thrombocytopenia (19.0%, n = 4) and one case (4.7%) of grade 3 pneumonitis resolved with steroids. Conclusion All-site radiotherapy achieved promising short-term local control with manageable toxicity in metastatic EWS. These short-term data demonstrate the feasibility of this approach and highlight a marked differential response by lesion site, warranting further biological investigation. Systemic therapy, particularly chemotherapy, was associated with improved PFS in this cohort. The high rate of systemic progression observed shortly after treatment underscores that improving long-term outcomes will require integration with more effective systemic therapies. Our findings provide a rationale and specific hypotheses for future prospective trials.