Whole Lung Irradiation after High-Dose Busulfan/Melphalan in Ewing Sarcoma with Lung Metastases: An Italian Sarcoma Group and Associazione Italiana Ematologia Oncologia Pediatrica Joint Study

SIMPLE SUMMARY: The lung is the most frequent site of metastasis in Ewing sarcoma, the second most common bone cancer affecting children, adolescents and young adults. The five-year overall survival of patients with isolated lung metastasis is approximately 50% after multimodal treatments including chemotherapy, surgery and radiotherapy. This retrospective study aimed to investigate the feasibility and the predictors of survival in 68 Ewing sarcoma patients with lung metastases who received high-dose chemotherapy with busulfan and melphalan, followed by reduced dose whole-lung irradiation, as part of two prospective and consecutive treatment protocols. This combined treatment strategy is feasible and might contribute to the disease control in lung metastatic Ewing sarcoma with responsive disease. Furthermore, the results of this study provide support to explore the treatment stratification for lung metastatic Ewing sarcoma based on the histological response of the primary tumor. ABSTRACT: Purpose: To analyze toxicity and outcome predictors in Ewing sarcoma patients with lung metastases treated with busulfan and melphalan (BU-MEL) followed by whole-lung irradiation (WLI). Methods: This retrospective study included 68 lung metastatic Ewing Sarcoma patients who underwent WLI after BU-MEL with autologous stem cell transplantation, as part of two prospective and consecutive treatment protocols. WLI 12 Gy for <14 years old and 15 Gy for ≥14 years old patients were applied at least eight weeks after BU-MEL. Toxicity, overall survival (OS), event-free survival (EFS) and pulmonary relapse-free survival (PRFS) were estimated and analyzed. Results: After WLI, grade 1–2 and grade 3 clinical toxicity was reported in 16.2% and 5.9% patients, respectively. The five-year OS, EFS and PRFS with 95% confidence interval (CI) were 69.8% (57.1–79.3), 61.2% (48.4–71.7) and 70.5% (56.3–80.8), respectively. Patients with good histological necrosis of the primary tumor after neoadjuvant chemotherapy showed a significant decreased risk of pulmonary relapse or death compared to patients with poor histological necrosis. Conclusions: WLI at recommended doses and time interval after BU-MEL is feasible and might contribute to the disease control in Ewing sarcoma with lung metastases and responsive disease. Further studies are needed to explore the treatment stratification based on the histological response of the primary tumor.