Whole Lung Irradiation in Ewing Sarcoma with Pulmonary Metastases: Critical Appraisal of Evolution, Evidence, and Future Pathways in Precision Oncology

Based on the cumulative evidence, we advocate for the continued use of whole lung irradiation (WLI) as an integral component of multimodal therapy for Ewing sarcoma patients with pulmonary metastases, particularly in those with isolated lung involvement. Modern cardiac-sparing techniques, such as intensity-modulated radiotherapy and proton therapy, should be prioritized to mitigate acute cardiopulmonary toxicity, despite the unknown long-term implications of the low-dose bath. Dose prescription should be individualized according to age, risk stratification, and response to chemotherapy, with 15–18 Gy in 1.5 Gy fractions representing the current standard. For patients achieving a rapid complete radiographic response, the decision to omit WLI must be balanced against the proven survival benefit and should ideally be guided by emerging biomarkers, pending prospective validation. Concurrent administration of WLI with novel systemic agents, including tyrosine kinase inhibitors and immune checkpoint inhibitors, is not recommended outside clinical trials due to the risk of synergistic pulmonary toxicity. Lifelong surveillance for secondary malignancies and cardiopulmonary late effects is mandatory. We believe that the field must now move beyond empirical application toward biologically adapted, risk-adapted precision radiotherapy.