Comparison of clinical features and outcomes in patients with extraskeletal versus skeletal localized Ewing sarcoma: A report from the Children's Oncology Group

• Type of Material: Article
• Authors: William T. Cash, Emory University; Elizabeth McIlvaine, University of Southern California; Mark D. Krailo, University of Southern California; Stephen L. Lessnick, Ohio State University; Elizabeth R. Lawlor, University of Michigan; Nadia Laack, Mayo Clinic; Joel Sorger, Cincinnati Children’s Hospital Medical Center; Neyssa Marina, Stanford University; Holcombe E. Grier, Children's Hospital Boston; Linda Granowetter, NYU School of Medicine and NYU Langone Medical Center; Richard B. Womer, University of Pennsylvania; Steven G. DuBois, University of California San Francisco
• Language: English
• Date: 2016-10-01
• Publisher: Wiley
• Publication Version: Author Accepted Manuscript (After Peer Review)
• Copyright Statement: © 2016 Wiley Periodicals, Inc.
• Final Published Version (URL): http://dx.doi.org/10.1002/pbc.26096
• Title of Journal or Parent Work: Pediatric Blood and Cancer
• ISSN: 1545-5009
• Volume: 63
• Issue: 10
• Start Page: 1771
• End Page: 1779
• Grant/Funding Information: Supported by the Nick Currey Fund and NIH/NCI U10 CA98543.
• Keywords: TUMORS; extraosseous; Oncology; PEDIATRIC-ONCOLOGY; CANCER; Hematology; FRENCH-SOCIETY; GENE FUSION; PROGNOSTIC-FACTORS; Science & Technology; soft-tissue Ewing sarcoma; ROUND-CELL SARCOMAS; BONE; SINGLE INSTITUTION; extraskeletal Ewing sarcoma; Pediatrics; ERYTHROCYTE SEDIMENTATION-RATE; prognosis; Life Sciences & Biomedicine; gene profiling; gene expression

Abstract

BACKGROUND: The prognostic significance of having extraskeletal vs. skeletal Ewing sarcoma in the setting of modern chemotherapy protocols is unknown. The purpose of this study was to compare the clinical characteristics, biologic features, and outcomes for patients with extraskeletal and skeletal Ewing sarcoma. METHODS: Patients had localized Ewing sarcoma (ES) and were treated on two consecutive protocols using 5-drug chemotherapy (INT-0154 and AEWS0031). Patients were analyzed based on having an extraskeletal (n=213) or skeletal (n=826) site of tumor origin. Event-free survival (EFS) was estimated using the Kaplan-Meier method, compared using the log-rank test, and modeled using Cox multivariate regression. RESULTS: Patients with extraskeletal Ewing Sarcoma (EES) were more likely to have axial tumors (72% vs. 55%; P < 0.001), less likely to have tumors > 8 cm (9% vs. 17%; P < 0.01), and less likely to be white (81% vs. 87%; P < 0.001) compared to patients with skeletal ES. There was no difference in key genomic features (type of EWSR1 translocation, TP53 mutation, CDKN2A mutation/loss) between groups. After controlling for age, race, and primary site, EES was associated with superior EFS [hazard ratio = 0.69; 95% CI: 0.50–0.95; P = 0.02]. Among patients with EES, age ≥ 18 years, non-white race, and elevated baseline erythrocyte sedimentation rate (ESR) were independently associated with inferior EFS. CONCLUSION: Clinical characteristics, but not key tumor genomic features, differ between EES and skeletal ES. Extraskeletal origin is a favorable prognostic factor, independent of age, race, and primary site.