Current Treatment Protocols Have Eliminated the Prognostic Advantage of Type 1 Fusions in Ewing Sarcoma: A Report From the Children's Oncology Group

Abstract

PURPOSE Ewing sarcoma family tumors (ESFTs) exhibit chromosomal translocations that lead to the creation of chimeric fusion oncogenes. Combinatorial diversity among chromosomal breakpoints produces varying fusions. The type 1 EWS-FLI1 transcript is created as a result of fusion between exons 7 of EWS and 6 of FLI1, and retrospective studies have reported that type 1 tumors are associated with an improved outcome. We have re-examined this association in a prospective cohort of patients with ESFT treated according to current Children's Oncology Group (COG) treatment protocols. METHODS Frozen tumor tissue was prospectively obtained from patients diagnosed with ESFT, and reverse transcriptase polymerase chain reaction (RT-PCR) was used to determine translocation status. Analysis was confined to patients with localized tumors who were diagnosed after 1994 and treated according to COG protocols. Translocation status was correlated with disease characteristics, event-free survival (EFS), and overall survival (OS). Results RT-PCR identified chimeric fusion oncogenes in 119 of 132 ESFTs. Eighty-nine percent of identified transcripts were EWS-FLI1, and of these, 58.8% were type 1. Five-year EFS and OS rates for patients with type 1 and non-type 1 fusions diagnosed between 2001 and 2005 were equivalent (type 1: EFS, 63% +/- 7%; OS, 83% +/- 6%; non-type 1: EFS, 71% +/- 9%; OS, 79% +/- 8%). CONCLUSION Current intensive treatment protocols for localized ESFT have erased the clinical disadvantage that was formerly observed in patients with non-type 1 EWS-FLI1 fusions.

Treatment and Outcomes of Ewing Sarcoma in Turkish Adults: A Single Centre Experience

“…But the results are conflicting (Oberlin et al, 2001;Grier et al, 2003;Kolb et al, 2003). Currently, the only evidence-based prognostic factor accepted by all authors is the presence of metastatic disease (Cotterill et al, 2000;van Doorninck et al, 2010;Shannon Orr et al, 2012). In our study, there was no correlation between gender, tumor size, and overall and disease-free survival.…”

Clinical heterogeneity of Xp11 translocation renal cell carcinoma: impact of fusion subtype, age, and stage

“…For example, among Ewing sarcomas, the type 1 EWS-FLI1 fusion (fusing exon 7 of EWS with exon 6 of FLI1) is associated with lower transcriptional activity, lower proliferative rate, and a more favorable outcome than are other variant EWS-FLI1 gene fusions, [52][53][54] although current treatment protocols have eliminated this prognostic advantage. 55 Among alveolar rhabdomyosarcomas, those tumors with the PAX7-FOXO1 gene fusion have a more favorable outcome than those with the PAX3-FOXO1 gene fusion. 56 Further differences include the fact that PAX7-FOXO1 fusion gene is amplified in the majority of alveolar rhabdomyosarcomas, whereas the PAX3-FOXO1 is not.…”

Common Musculoskeletal Tumors of Childhood and Adolescence

“…17 Fusion subtype is not known to be prognostically significant. 18,19 Rhabdomyosarcoma Although traditionally RMS has been considered to derive from primitive myoblasts, a large percentage of RMSs occur in locations normally lacking skeletal muscle (eg, bladder, prostate, vagina, bile ducts). 15 Rhabdomyosarcomas are usually grouped into 3 subtypes: embryonal (ERMS) (including botryoid and spindle cell variants), alveolar (ARMS), and pleomorphic.…”