The impact of whole lung irradiation in lung metastatic rhabdomyosarcoma: A pooled analysis of two European trials and one European registry

Background: Lung metastases in patients with metastatic rhabdomyosarcoma (RMS) have not been treated uniformly across Europe. This provides comparison of the impact of whole lung irradiation (WLI). Methods: Lung-metastatic patients included in the Cooperative Weichteilsarkom Studiengruppe-IV 2002, European Pediatric Soft Tissue Sarcoma Study Group MTS 2008 or the Soft Tissue Sarcoma Registry received four- or six-drug chemotherapy, surgery, and/or irradiation (radiotherapy) of the primary tumor. Treatment of lung lesions consisted of metastasectomy, WLI, or no local treatment according to protocols. Results: A total of 238 patients with lung-metastatic RMS were included. Half of these patients (n = 119/238) had lung metastases only (median age, 6.6 years), mainly classified as embryonal RMS (n = 93/119, 78%). Lung-only patients underwent metastasectomy (n = 17) and/or WLI (n = 31) or no local treatment of lung metastases (n = 71). Early complete response of lung metastases was associated with favorable 3-year overall survival (p =.009). A trend toward improved event-free survival after WLI could be identified in patients ≥10 years old (hazard ratio [HR], 2.7; 95% CI, 0.8–9.6), but not in patients under 10 years old (HR, 0.86; 95% CI, 0.44–1.66). Lung–relapse-free survival (lung-RFS) was not influenced by WLI or metastasectomy in the univariable and multivariable analyses. When analyzing all lung-metastatic patients (including those with metastases in other sites, n = 238), WLI in patients older than 10 years was a significant prognostic factor (HR, 2.2; 95% CI, 1.0–4.9). Conclusions: The analysis failed to show a significant benefit of WLI in patients with lung-metastatic RMS, apart from the subgroup of patients older than 10 years. Lung-RFS was not influenced by WLI.