Key result
Ewing sarcoma survivors treated with VDC plus IE had a higher risk of renal complications compared to VDC alone (3.2% vs 0.56%; HR 2.55; 95% CI 1.07-11.7), with no differences in late mortality.
Why the study?
Survivors of Ewing sarcoma are at significant long-term risk of complications, prompting this characterization of long-term outcomes according to treatment regimen.
Does the addition of ifosfamide and etoposide to VDC alter the risk of late mortality, subsequent malignant neoplasms, and chronic health conditions in Ewing sarcoma survivors?
Cohort (n=5,779)
Does the addition of ifosfamide and etoposide to VDC alter the risk of late mortality, subsequent malignant neoplasms, and chronic health conditions in Ewing sarcoma survivors?
Ewing sarcoma survivors face significantly elevated risks of late mortality and chronic health conditions compared to siblings and the general population, with similar risks between VDC and VDC/IE regimens except for increased renal complications with VDC/IE.
Answers are grounded in this paper and cite their sources.
May inform regimen-specific survivorship care in EWS; extends observational data but leaves optimal strategies open.
BACKGROUND: Survivors of Ewing sarcoma (EWS) are at significant long-term risk of treatment- and disease-related complications. The purpose of this study was to characterize long-term outcomes in EWS survivors according to treatment regimen. METHODS: Five-year survivors of EWS diagnosed between 1970 and 1999 from the Childhood Cancer Survivor Study were included. Late mortality (>5 years from diagnosis), subsequent malignant neoplasms (SMNs), and severe to fatal chronic health conditions (CHCs) by chemotherapy regimen were compared. Patients were compared to siblings via cumulative incidence and proportional hazards models. Standardized mortality ratios (SMRs) compared late mortality between survivors and the general population. RESULTS: Survivors (N = 739) had higher all-cause (SMR, 6.16; 95% CI, 5.36-7.05), SMN-related (SMR, 9.24; 95% CI, 6.92-12.08), cardiac-related (SMR, 4.53; 95% CI, 2.81-6.93), and noncardiopulmonary health-related (SMR, 2.04; 95% CI, 1.25-3.15) mortality compared with the general population. Compared with siblings (N = 5040), survivors had an increased risk of developing CHCs (any: hazard ratio [HR], 5.49; 95% CI, 4.58-6.59; cardiovascular: HR, 4.59; 95% CI, 3.67-5.74; neurological: HR, 2.82; 95% CI, 1.72-4.63; respiratory: HR, 5.37; 95% CI, 2.76-10.5; renal: HR, 4.61; 95% CI, 2.26-9.40). Between chemotherapy groups within EWS, there were no statistically significant differences in all-cause, SMN-caused, or health-related late mortality and the risk of developing SMNs or CHCs (any, cardiovascular, neurological, or respiratory), except that the vincristine, doxorubicin, and cyclophosphamide (VDC) plus ifosfamide and etoposide (IE) group had a higher risk of renal complications (HR, 2.55; 95% CI, 1.07-11.7; 30-year incidence was 0.56% for VDC and 3.2% for VDC/IE). CONCLUSIONS: No differences in late mortality, SMNs, and most CHCs were observed between patients who received VDC versus VDC/IE. Aging EWS survivors' elevated risk of morbidity and mortality underscores the need for lifelong survivorship care and therapies that reduce the risk for late effects.
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Ramsey et al. (2026) conducted a cohort in Ewing sarcoma (n=5,779). VDC plus ifosfamide and etoposide (IE) vs. VDC (vincristine, doxorubicin, and cyclophosphamide) was evaluated on Renal complications (HR 2.55, 95% CI 1.07-11.7). Ewing sarcoma survivors treated with VDC plus IE had a higher risk of renal complications compared to VDC alone (3.2% vs 0.56%; HR 2.55; 95% CI 1.07-11.7), with no differences in late mortality.
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