Comparison of clinical features and outcomes in patients with extraskeletal versus skeletal localized Ewing sarcoma: A report from the Children's Oncology Group.
The prognostic significance of having extraskeletal (EES) versus skeletal Ewing sarcoma (ES) 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 EES and skeletal ES.



Patients had localized ES and were treated on two consecutive protocols using five-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.



Patients with extraskeletal ES (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% confidence interval: 0.50-0.95; P = 0.02). Among patients with EES, age ≥18, nonwhite race, and elevated baseline erythrocyte sedimentation rate were independently associated with inferior EFS.



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.
Department of Pediatrics, Children's Healthcare of Atlanta, Emory University, Atlanta, Georgia.
Thomas
T
Cash
Department of Preventive Medicine, Keck School of Medicine, University of Southern California, Los Angeles, California.
Elizabeth
E
McIlvaine
Department of Preventive Medicine, Keck School of Medicine, University of Southern California, Los Angeles, California.
Mark D
MD
Krailo
Center for Childhood Cancer and Blood Disorders at Nationwide Children's Hospital, and the Division of Hematology, Oncology and BMT at The Ohio State University, Columbus, Ohio.
Stephen L
SL
Lessnick
Department of Pediatrics, University of Michigan, Ann Arbor, Michigan.
Elizabeth R
ER
Lawlor
Department of Radiation Oncology, Mayo Clinic, Rochester, Minnesota.
Nadia
N
Laack
Department of Orthopedics, Cincinnati Children's Hospital Medical Center, Cincinnati, Ohio.
Joel
J
Sorger
Department of Pediatrics, Stanford University School of Medicine and Lucille Packard Children's Hospital at Stanford, Palo Alto, California.
Neyssa
N
Marina
Department of Pediatrics, Children's Hospital Boston/Dana-Farber Cancer Institute and Harvard Medical School, Boston, Massachusetts.
Holcombe E
HE
Grier
Department of Pediatrics, NYU School of Medicine and NYU Langone Medical Center, New York.
Linda
L
Granowetter
Department of Pediatrics, University of Pennsylvania Perelman School of Medicine and Children's Hospital of Philadelphia, Philadelphia, Pennsylvania.
Richard B
RB
Womer
Department of Pediatrics, UCSF School of Medicine and UCSF Benioff Children's Hospital, San Francisco, California.
Steven G
SG
DuBois
D000293:Adolescent; D000328:Adult; D001799:Blood Sedimentation; D001859:Bone Neoplasms / Q000188:drug therapy* / Q000401:mortality; D002648:Child; D002675:Child, Preschool; D005260:Female; D006801:Humans; D007223:Infant; D007231:Infant, Newborn; D008297:Male; D016016:Proportional Hazards Models; D012512:Sarcoma, Ewing / Q000188:drug therapy* / Q000401:mortality; D059467:Transcriptome
extraosseous; extraskeletal Ewing sarcoma; gene expression; gene profiling; prognosis; soft-tissue Ewing sarcoma