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 (20%), with positive results in 48 of 61 patients (78.7%). Next-generation sequencing was reported in 7 patients on primary tumor and in 3 patients on metastatic sites. Evaluating all types of testing on either primary or metastatic tumor, 16 of 305 patients (5.2%) had no reported translocation testing. 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.

Randomized Phase III Trial of Ganitumab With Interval-Compressed Chemotherapy for Patients With Newly Diagnosed Metastatic Ewing Sarcoma: A Report From the Children's Oncology Group

“…A prior analysis of institutional translocation testing from this trial showed that 14% of patients lacked molecular data supporting the diagnosis. 33 As such, it is possible that patients with histologic mimics of Ewing sarcoma without an established role for IGF-1R inhibition may have enrolled, further diluting any beneficial effect of ganitumab in bona fide Ewing sarcoma (ie, tumors with FET / ETS translocations). Second, there are no validated biomarkers predictive of benefit from IGF-1R inhibition and therefore no enrichment could be performed in our trial.…”

Cutaneous Ewing Sarcoma Presenting as a Second Primary Malignancy in a Child

“…10 Multiple studies of sarcomas have demonstrated a significant percent of cases demonstrating discordance between initial pathologic diagnoses and the diagnosis upon second opinion. [11][12][13][14] In the present case, the diagnosis of Ewing sarcoma still relies heavily on EWSR1 translocation detection by FISH, 15 which in the case of cutaneous Ewing sarcoma, can be problematic as it: (1) does not identify the EWSR1 binding partner and (2) can be negative when non-FLI1 Ewing fusion types are present, such as EWSR1-ERG. 16 Cutaneous Ewing sarcomas harboring an EWSR1-ERG fusion are reported in the literature.…”

Features of Metastatic Ewing Sarcoma

“…FISH was carried out on the primary tumor in three-fourths of the patients. Dubois et al (24) found positive testing for an EWSR1 or FUS translocation in 211, which equates almost 90% of the patients. A reverse transcriptionpolymerase chain reaction (RT-PCR) was carried out in one fifth of the patients.…”

“…is not yet fully studied in detail. In a recent study involving the Children' s Oncology Group (COG) trial AEWS1221, the patterns of translocation testing for newly diagnosed ES were described (24). The AEWS1221 trial was a phase III randomized study enrolling patients with newly diagnosed metastatic ES/ PNET from 2014 to 2019.…”