Oncology ·
ctDNA Alterations Identify a High-Risk Ewing Sarcoma Subgroup
A prospective ctDNA analysis across two first-line Ewing sarcoma trials included 347 patients and 991 blood, tumor, and bone marrow samples. At diagnosis, alterations in TP53, STAG2, or CDKN2A were associated with substantially worse event-free and overall survival, independently of several established clinical factors.
- 347 patients were included across two first-line trials.
- Three ctDNA alteration groups marked higher-risk disease.
- High-risk status was associated with worse survival.
- Clinical benefit from ctDNA-guided treatment was not assessed.
Ewing sarcoma risk stratification currently relies on clinicoradiologic features, and evidence for molecular risk assessment has been limited. Researchers prospectively integrated serial circulating tumor DNA (ctDNA) sampling into the phase II/III Euro Ewing 2012 and CombinaiR3 trials, with additional relapse studies. Across 347 patients, 991 blood, tumor, and bone marrow samples underwent targeted sequencing and shallow whole-genome sequencing.
At diagnosis, ctDNA detection of TP53 and/or STAG2 loss-of-function mutations or focal CDKN2A deletions identified an independent high-risk subgroup in Euro Ewing 2012. After adjustment for metastatic status, tumor volume, age, and treatment, this subgroup had inferior event-free survival (hazard ratio [HR], 3.6; 95% CI, 2.2–5.8) and overall survival (HR, 4.3; 95% CI, 2.5–7.3); both associations had P < .001. ctDNA profiles also captured heterogeneity relative to tumor biopsies, and serial sampling showed selection of TP53-altered clones at relapse.
The findings support further evaluation of ctDNA for molecular risk stratification in Ewing sarcoma. The source does not report a ctDNA-guided treatment strategy or evidence that changing management based on these results improves outcomes; the findings alone do not establish a new standard of care.
In practice
In patients with Ewing sarcoma, diagnosis-time ctDNA detection of TP53 or STAG2 loss-of-function mutations or focal CDKN2A deletions was associated with poorer event-free and overall survival, independently of metastatic status, tumor volume, age, and treatment in the Euro Ewing 2012 analysis. These results suggest potential use in molecular risk stratification, but the source does not show that ctDNA-guided treatment improves outcomes or establish a management change. The findings should therefore be viewed as prognostic evidence rather than a basis for changing care.
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Journal of Clinical Oncology: Circulating Tumor DNA Profiling Across Phase II/III Ewing Sarcoma Trials Identifies High-Risk Patients With TP53 , STAG2 , and CDKN2A Alterations ↗This is an automated AI-condensed summary that has not yet been reviewed by an editor. Always consult the full item at the original source.