High-Dose Chemotherapy Compared With Standard Chemotherapy and Lung Radiation in Ewing Sarcoma With Pulmonary Metastases: Results of the European Ewing Tumour Working Initiative of National Groups, 99 Trial and EWING 2008.

PURPOSE: The R2Pulm trial was conducted to evaluate the effect of busulfan-melphalan high-dose chemotherapy with autologous stem-cell rescue (BuMel) without whole-lung irradiation (WLI) on event-free survival (main end point) and overall survival, compared with standard chemotherapy with WLI in Ewing sarcoma (ES) presenting with pulmonary and/or pleural metastases. METHODS: From 2000 to 2015, we enrolled patients younger than 50 years of age with newly diagnosed ES and with only pulmonary or pleural metastases. Patients received chemotherapy with six courses of vincristine, ifosfamide, doxorubicin, and etoposide (VIDE) and one course of vincristine, dactinomycin, and ifosfamide (VAI) before either BuMel or seven courses of VAI and WLI (VAI plus WLI) by randomized assignment. The analysis was conducted as intention to treat. The estimates of the hazard ratio (HR), 95% CI, and P value were corrected for the three previous interim analyses by the inverse normal method. RESULTS: Of 543 potentially eligible patients, 287 were randomly assigned to VAI plus WLI (n = 143) or BuMel (n = 144). Selected patients requiring radiotherapy to an axial primary site were excluded from randomization to avoid excess organ toxicity from interaction between radiotherapy and busulfan. Median follow-up was 8.1 years. We did not observe any significant difference in survival outcomes between treatment groups. Event-free survival was 50.6% versus 56.6% at 3 years and 43.1% versus 52.9% at 8 years, for VAI plus WLI and BuMel patients, respectively, resulting in an HR of 0.79 (95% CI, 0.56 to 1.10; P = .16). For overall survival, the HR was 1.00 (95% CI, 0.70 to 1.44; P = .99). Four patients died as a result of BuMel-related toxicity, and none died after VAI plus WLI. Significantly more patients in the BuMel arm experienced severe acute toxicities than in the VAI plus WLI arm. CONCLUSION: In ES with pulmonary or pleural metastases, there is no clear benefit from BuMel compared with conventional VAI plus WLI.

Percutaneous Computed Tomography-Guided Thermal Ablation of Pulmonary Osteosarcoma Metastases in Children.

INTRODUCTION: The role of percutaneous thermal ablation as a minimally-invasive treatment has not been evaluated in children under 18 years of age with pulmonary osteosarcoma metastases. METHODS: This was a retrospective review of children treated with percutaneous thermal ablation for pulmonary osteosarcoma metastasis after prior surgical metastasectomy and chemotherapy. Selection criteria included number of pulmonary nodules <5 and nodule size smaller than 2 cm. Indications were discussed at multidisciplinary meetings. The goal was to achieve complete remission using percutaneous thermal ablation, thereby avoiding additional thoracotomies. RESULTS: A total of 26 pulmonary nodules (mean size 6.7 mm, range 2-16 mm) were successfully treated by percutaneous computed tomography (CT)-guided thermal ablation in 11 children with osteosarcoma between the ages of 7 and 17 years (median 12.5). Patients denied post-procedure pain. Complications were limited to three pneumothoraxes (two minor, one major), and median hospitalization duration was 2.0 days. One patient died of rapidly progressive lumbar metastasis discovered 20 days post-ablation. Of the remaining 10 patients, local control at the ablation site was achieved, with median follow up of 16.7 months (range 4.1-41.8). Five patients remained in complete remission after median follow-up of 37.5 months, and five patients developed new metastases (one osseous, four pulmonary), of which two are in remission after subsequent treatment. CONCLUSION: Percutaneous thermal ablation is a safe and effective minimally-invasive curative local treatment alternative for children with oligometastatic pulmonary osteosarcoma in whom surgical intervention is clinically contraindicated or unappealing.