Patterns of Translocation Testing in Patients Enrolling in a Cooperative Group Trial for Newly Diagnosed Metastatic Ewing Sarcoma

Abstract

Context.—: Molecular diagnostics play an increasing role in the diagnosis of Ewing sarcoma. The type of molecular testing used in clinical practice has been poorly described.

Objective.—: To describe patterns of translocation testing for newly diagnosed Ewing sarcoma.

Design.—: Children's Oncology Group (COG) trial AEWS1221 was a phase III randomized trial enrolling patients with newly diagnosed metastatic Ewing sarcoma from 2014 to 2019. Patients were required to have a histologic diagnosis of Ewing sarcoma, but translocation testing was not required. Sites provided types and results of any molecular diagnostics performed.

Results.—: Data from 305 enrolled patients were available. The most common type of molecular testing was fluorescence in situ hybridization (FISH) performed on the primary tumor (236 of 305 patients; 77.4%), with positive testing for an EWSR1 or FUS translocation in 211 (89.4%). Reverse transcription-polymerase chain reaction (RT-PCR) on the primary tumor was performed in 61 of 305 patients (20%), with positive results in 48 of 61 patients (78.7%). Next-generation sequencing was reported in 7 patients for the primary tumor and in 3 patients for metastatic sites. For all types of testing on either primary or metastatic tumor, 16 of 305 patients (5.2%) had no reported translocation testing. When evaluating all results from all testing, 44 of 305 patients (14.4%) lacked documentation of an abnormality consistent with a molecular diagnosis of Ewing sarcoma.

Conclusions.—: COG sites enrolling in a Ewing sarcoma trial have high rates of testing by FISH or PCR. A small proportion of patients have no translocation testing on either primary or metastatic sites. Next-generation sequencing techniques are not yet commonly used in this context.

A, Flow diagram of translocation testing performed accounting for all patients enrolled in AEWS1221 with submitted translocation testing data. B, Flow diagram of translocation test results for all patients enrolled in AEWS1221 with submitted translocation testing data. Diagrams consider each patient once, starting with testing by FISH on primary tumor. Only patients who did not have testing (A) or a positive test result (B) in the preceding boxes are considered in subsequent boxes. Abbreviations: FISH, fluorescence in situ hybridization; RT-PCR reverse transcription–polymerase chain reaction.