129 - A Multi-Institutional Study of Dose-Escalated Definitive Radiotherapy in Children with Pelvic Ewing Sarcomas
Presenter(s)
T. M. Weiskittel1, D. J. Indelicato2, R. O. Kowalchuk1, S. K. Ahmed3, R. J. Brisson1, C. G. Morris4, and N. N. Laack II1; 1Department of Radiation Oncology, Mayo Clinic, Rochester, MN, 2Department of Radiation Oncology, University of Florida, Jacksonville, FL, 3Department of Radiation Oncology, Mayo Clinic, Phoenix, AZ, 4Department of Radiation Oncology, University of Florida College of Medicine, Jacksonville, FL
Purpose/Objective(s): Historically, unresectable pelvic Ewing sarcoma has been associated with poor local control (LC) relative to other sites, with a 5-year local failure rate of approximately 25% for large tumors treated with definitive radiation (RT). Small, prospective single-institution data suggests that local control may be improved through dose-escalation. However, concerns remain about the efficacy and safety of high dose chemoradiation amongst critical developing pelvic organs in children. Therefore, we performed a multi-institutional retrospective review to assess the therapeutic ratio of dose-escalated radiation (DE-RT) in pediatric patients with pelvic Ewing sarcoma.
Materials/Methods: Fifty-six patients with a median age of 16 years (range, 3.4-21.8) and newly diagnosed unresectable Ewing sarcoma of the pelvis were treated with definitive RT at XX (n=49) and YY (n=7) between 2006 and 2025. All patients received contemporary multiagent chemotherapy for localized disease or limited pulmonary metastases. Median maximum diameter of the primary tumor at diagnosis was 10 cm (1-24 cm). All patients were treated with standard fractionation of 1.8 Gy/fx and 53 patients (95%) were treated with a component of proton therapy. Fourteen patients with tumors < 8 cm were treated to 55.8 Gy and one received 54 Gy. Of the 41 patients with tumors = 8 cm, 20 were treated with 64.8 Gy DE-RT and 21 were treated with standard dose radiation (SD-RT) [(mean dose 55.8 Gy (range, 54-59.4 Gy)]. Clinical characteristics, oncologic outcomes, and treatment-related toxicities were analyzed with JMP version 18.2.2. Time-dependent endpoints including overall survival, LC, and disease-free survival were assessed with the cumulative incidence method. Due to strong interaction between large size and DE-RT, tumor diameter and dose were analyzed as a three-level variable: SD-RT and <8 cm tumor, SD-RT and =8 cm, and DE-RT and =8 cm.
Results: With a median follow-up of 5.4 years (range, 0.2-14.9), the 5-year overall survival, progression free survival, and LC was 75% [95% confidence interval (CI) 60-85], 59% (95% CI 46-73%), and 84% (95% CI 73-93) for the whole cohort, respectively. For patients with tumors < 8 cm, the LC was 91%. For patients with tumors = 8 cm, the LC was 76% following SD-RT and 88% following DE-RT (p=0.4). Among survivors with a median follow-up of 7.7 years (range, 0.4-14.9), 3 patients developed second malignancies: 2 with acute myeloid leukemia following 64.8 Gy and one with osteosarcoma following 55.8 Gy. Other serious toxicity was observed in 3/20 (15%) patients treated with 64.8 Gy and 9/36 (25%) patients treated with <64.8 Gy.
Conclusion: Proton-based DE-RT can be safely delivered in children with unresectable pelvic Ewing sarcoma and may improve local control for large tumors. This data supports broader prospective study of DE-RT in select patients within the cooperative group setting.