Treatment effect heterogeneity of radiotherapy in localized Ewing sarcoma: A secondary analysis of the EURO-E.W.I.N.G. 99 and Ewing 2008 trial - PubMed
3 hours ago
- #radiotherapy
- #Ewing sarcoma
- #individualized treatment effects
- Standard treatment for localized Ewing sarcoma includes chemotherapy and local therapy, but previous studies show no average benefit of combined local therapy (radiotherapy + surgery) versus surgery alone.
- This secondary analysis of two trials used causal survival forests to predict individualized treatment effects (ITEs) for 5-year event-free survival comparing combined therapy to surgery alone.
- 19.4% of patients derived clinically meaningful benefit (≥6-month increase in 5y EFS) from combined therapy, showing substantial heterogeneity in ITEs (range: -0.7 to 1.0 years).
- Patients predicted to benefit least had increased hazards by 53% when receiving combined therapy, while those predicted to benefit most had reduced hazards by 40%.
- Surgical margin status was not associated with treatment benefit in patients undergoing combined therapy, challenging current decision-making practices.
- Simulation analysis indicated that applying the personalized treatment rule could improve event-free survival.