Interval-compressed chemotherapy in patients with Ewing’s sarcoma: report on feasibility and toxicity from a North African center

Background: Ewing'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. Methods: We 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. Results: We 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. Conclusion: This study highlights the challenges of implementing the EE2012 protocol in our practice. Adapting the regimen could optimize induction, particularly for localized forms.