Background
Retrospective cohort study and outcomes analysis. 171 patients with disseminated (metastatic) Ewing sarcoma treated at multiple European centers. Evaluated impact of whole lung irradiation (WLI), total body irradiation (TBI), and high-dose chemotherapy with autologous stem cell rescue on outcomes in disseminated disease. Aimed to identify prognostic factors and role of RT in the curative-intent treatment of metastatic Ewing sarcoma.
Interventions and follow up
Arm A: Conventional chemotherapy (VDC/IE-based induction) + local RT ± WLI 15–18 Gy ± consolidation HDCT with PBSC rescue
Primary endpoint: 3-year OS, prognostic factor analysi
mFollow up: 5.0 year
Primary endpoint: 3-year OS, prognostic factor analysi
mFollow up: 5.0 year
Results
Arm B (comparison): Same induction without WLI or HDCT
3-yr OS (lung metastases only): 32% with WLI vs 17% without, P=.02
3-yr OS (bone/BM metastases): ~10% regardless of consolidation
Prognostic factors: Lung-only metastases, age <14, fewer metastatic sites — favorable
3-yr OS (lung metastases only): 32% with WLI vs 17% without, P=.02
3-yr OS (bone/BM metastases): ~10% regardless of consolidation
Prognostic factors: Lung-only metastases, age <14, fewer metastatic sites — favorable
Adverse events
Main adverse events: WLI: pneumonitis grade ≥2 in 18%, pulmonary fibrosis long-term. HDCT consolidation: treatment-related mortality 5–8%. TBI: significant late effects (endocrine, secondary malignancy, growth). Combined WLI + HDCT: additive pulmonary toxicity.
Conclusions
Whole lung irradiation improves outcomes in patients with lung-only metastatic Ewing sarcoma, particularly when combined with HDCT consolidation. Bone/BM metastatic disease has uniformly poor prognosis regardless of intensification. Lung-only metastases represent the most curable subset of disseminated Ewing sarcoma.
Key Limitations
Key Limitations: Retrospective with selection bias. Heterogeneous treatment across centers. Patient selection for WLI vs no-WLI not randomized. Small subgroup numbers limit statistical power for subset analyses. Era effects limit generalizability to current molecular staging era.
Clinical Context
WLI 15–18 Gy is recommended for patients with Ewing sarcoma with lung metastases who respond to induction chemotherapy. COG protocols (AEWS1221) incorporate WLI in this setting. Proton therapy is explored to reduce cardiac and pulmonary late effects in patients receiving WLI with HDCT.
References