Interval-compressed VDC/IE protocol feasibility and outcomes in 27 Ewing's sarcoma patients at a North African center

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Frontiers in Medicine Published June 4, 2026 Medically reviewed June 4, 2026 DOI ↗ By Dr. Julia Lee, PhD · Oncology, Genomics & Drug Development

Key Takeaway

Note high-grade toxicity in 89% of patients on interval-compressed VDC/IE for Ewing's sarcoma; real-world data limited.

This retrospective, single-institutional cohort study assessed the feasibility, tolerance, and effectiveness of an interval-compressed VDC/IE protocol in 27 patients with Ewing's sarcoma treated at a North African center between January 2018 and April 2024. The population included patients with a median age of 18.3 years at diagnosis, 89% of whom had skeletal tumors, and 41% presenting with metastatic disease. The median delay to neoadjuvant chemotherapy was 36 days.

Treatment duration averaged 22 weeks, with a mean interval between cycles of 19.8 days. The mean relative dose intensity (RDI) was 70%, though only 11% of patients achieved an RDI greater than 85%. Notably, RDI was lower in adults (p=0.011) and in patients with metastatic stage disease (p=0.011). High-grade toxicities occurred in 89% of patients, primarily neutropenia, while 11 patients achieved a good pathologic response.

Outcomes included a median overall survival (OS) of 32 months, with 3-year OS rates of 36.9% and 3-year event-free survival (EFS) rates of 19.9%. The relapse rate was 67%, with a median relapse time of 13 months. Tolerability was assessed, but discontinuations were not reported. The study acknowledges that real-world data remain limited due to its retrospective, single-institutional nature. Adapting the regimen could optimize induction, particularly for localized forms, though the high toxicity burden and low RDI in specific subgroups warrant careful consideration.

Study Details

Study typeCohort

EvidenceLevel 3

PublishedApr 2026

View Original Abstract ↓

BackgroundEwing’s sarcoma (ES) is the second most common malignant bone tumor in patients under 20 years of age. The “Euro-Ewing 2012” trial established induction therapy with the 2-week-interval VDC/IE (Vincristine-Doxorubicine-Cyclophosphamide/Ifosfamide-Etoposide) as the standard of care. However, real-world data remain limited. We aimed to determine the feasibility, tolerance, and effectiveness of this protocol.MethodsWe conducted a retrospective, single-institutional cohort study, including patients with ES treated between January 2018 and April 2024 using the interval-compressed VDC/IE protocol. Data were collected on feasibility, toxicity, and outcomes.ResultsWe included 27 patients. Median age at diagnosis was 18.3 years. Sekeletal tumors predominated (89%), mainly in the pelvis and lower limbs. Metastatic disease was present at diagnosis in 41%. Neoadjuvant chemotherapy was initiated after a median delay of 36 days post-biopsy, with a median duration of 22 weeks and a mean interval of 19.8 days. The mean relative dose intensity (RDI) was 70%, with only 11% of patients achieving an RDI >85%. A lower RDI was observed in adults (p=0.011) and metastatic stage patients (p=0.011). High-grade toxicities were reported in 89% of patients, primarily neutropenia. Good pathologic response was reported in 11 patients. After a median follow-up of 26 months, the median OS was 32 months, with 3-year OS and EFS rates of 36.9% and 19.9%, respectively. The relapse rate was 67%, with a median relapse time of 13 months.ConclusionThis study highlights the challenges of implementing the EE2012 protocol in our practice. Adapting the regimen could optimize induction, particularly for localized forms.