Intensified Induction Therapy for Newly Diagnosed, Localized Skeletal Ewing Sarcoma (ISG/AIEOP EW-1): A Randomized, Open-Label, Phase 3, Non-Inferiority Trial.

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Abstract

[Indexed for MEDLINE] 15. Radiother Oncol. 2024 Jun;195:110270. doi: 10.1016/j.radonc.2024.110270. Epub 2024 Apr 5. Comprehensive radiotherapy for pediatric Ewing Sarcoma: Outcomes of a prospective proton study. Bronk JK(1), McAleer MF(2), McGovern SL(2), Lassen-Ramshad Y(3), Safwat A(3), Daw NC(4), Rainusso N(5), Mahajan A(6), Grosshans DR(2), Paulino AC(7). Author information: (1)Department of Radiation Oncology, University of Texas MD Anderson Cancer Center, Houston, TX, United States. Electronic address: jkedwards@mdanderson.org. (2)Department of Radiation Oncology, University of Texas MD Anderson Cancer Center, Houston, TX, United States. (3)Danish Centre for Particle Therapy, Aarhus University Hospital, Aarhus, Denmark. (4)Department of Pediatrics, University of Texas MD Anderson Cancer Center, Houston, TX, United States. (5)Department of Pediatrics, Division of Hematology-Oncology, Baylor College of Medicine and Texas Children's Hospital Cancer and Hematology Centers, Houston, TX, United States. (6)Department of Radiation Oncology, Mayo Clinic, Rochester, MN, United States. (7)Department of Radiation Oncology, University of Texas MD Anderson Cancer Center, Houston, TX, United States. Electronic address: APaulino@mdanderson.org. BACKGROUND AND PURPOSE: Patients with Ewing Sarcoma (EWS) are treated with multimodality therapy which includes radiation therapy (RT) as an option for local control. We report on the efficacy after proton radiation therapy (PRT) to the primary site for localized and metastatic EWS. MATERIALS AND METHODS: Forty-two children with EWS (33 localized, 9 metastatic) treated between 2007 and 2020 were enrolled on 2 prospective registry protocols for pediatric patients undergoing PRT. PRT was delivered by passive scatter (74 %), pencil-beam scanning (12 %) or mixed technique (14 %). Treated sites included the spine (45 %), pelvis/sacrum (26 %), skull/cranium (14 %), extraosseous (10 %), and chest wall (5 %). Median radiation dose was 54 Gy-RBE (range 39.6-55.8 Gy-RBE). Patients with metastatic disease received consolidative RT to metastatic sites (4 at the time of PRT to the primary site, 5 after completion of chemotherapy). Median follow-up time was 47 months after PRT. RESULTS: The 4-year local control (LC), progression-free survival (PFS), and overall survival (OS) rates were 83 %, 71 %, and 86 %, respectively. All local failures (n = 6) were in-field failures. Tumor size ≥ 8 cm predicted for inferior 4-year LC (69 % vs 95 %, p = 0.04). 4-year PFS and OS rates were not statistically different in patients with localized versus metastatic disease (72 % vs 67 %, p = 0.70; 89 % vs 78 %, p = 0.38, respectively). CONCLUSION: In conclusion, LC for pediatric patients with EWS treated with PRT was comparable to that of historical patients who received photon-RT. Tumor size ≥ 8 cm predicted increased risk of local failure. Patients with metastatic disease, including non-pulmonary only metastases, received radiation therapy to all metastatic sites and had favorable survival outcomes. Copyright © 2024 Elsevier B.V. All rights reserved. DOI: 10.1016/j.radonc.2024.110270