We present the first French case of uterine transposition for fertility preservation in a 25-year-old nulligravida patient with rectovaginal extra-skeletal Ewing sarcoma. After receiving induction chemotherapy, the uterus was transposed to the upper abdomen via laparotomy. During the same procedure, a posterior pelvectomy was performed to achieve wide surgical margins for tumor removal. To mitigate digestive toxicity from subsequent pelvic radiotherapy, a breast expansion prosthesis was placed. The patient experienced regular menstruation postoperatively, indicating preserved uterine function. After completing radiochemotherapy, we successfully repositioned the uterus into the pelvis. Menstruation resumed within months of reimplantation, and a clinical examination revealed a normal-appearing cervix. This case demonstrates the feasibility and potential benefits of uterine transposition for preserving fertility in women with pelvic malignancies who require radiotherapy. Further research is needed to evaluate the long-term outcomes and reproductive potential of this procedure.

To develop a predictive model for estimating the histological response to preoperative chemotherapy based on imaging data in patients with Ewing sarcoma. We included 133 patients with Enneking stage IIB or IIIB Ewing sarcoma who underwent chemotherapy and definitive surgery between 2003 and 2020. We analyzed various radiological parameters before and after preoperative chemotherapy. The necrotic area was evaluated using gadolinium-contrasted magnetic resonance imaging (radiological necrotic grade). Patients were classified as good histological responders if > 95% of their resected specimens showed necrosis; otherwise, they were classified as poor responders. Radiological parameters were assessed using the least absolute shrinkage and selection operator (LASSO) with cross-validation. Optimal regularization parameters were identified as those minimizing cross-validation error. The area under the curve (AUC) was calculated based on the predictive model with the selected parameters for training and test data using receiver operating characteristic (ROC) curve. LASSO models identified key parameters including volume change, radiological necrotic grade, complete regression of the extraskeletal component, and the disappearance of peritumoral gadolinium-enhancement after preoperative chemotherapy. ROC curve analysis showed that the predictive model achieved measurable discrimination ability on both training and test datasets (AUC = 0.89 [95% confidence interval (95%CI); 0.83-0.95] on training data, 0.77 [95%CI; 0.58-0.95] on test data). The developed model may facilitate accurate monitoring of the efficacy of preoperative chemotherapy in patients with Ewing sarcoma. Identifying patients with a poor histological response to preoperative chemotherapy can aid in the planning of secure surgical margins and effective treatment strategies.

Extra skeletal Ewing sarcoma (EES) has less clearly defined clinical behaviour and treatment strategies. We report the clinical profile, outcomes and prognostic factors of children with EES treated at a single centre over a decade on a non-dose chemotherapy backbone. Children ≤15 years of age with EES treated from January 2012 to December 2021 were retrospectively analysed. All received EFT-2001, a non-dose chemotherapy protocol. Local therapy was planned after 9-12 weeks of chemotherapy. One hundred and six patients formed the study cohort. The majority of the primary was axial in location. Metastasis was present in 25.5%, mainly in the lungs. Local therapy was definitive radiotherapy in 59.1% (n = 58), surgery only in 3% (n = 3) and surgery and radiotherapy in 37.9% (n = 37). At a median follow-up of 43 months (range, 33-52 months), 4-year event-free survival (EFS) and overall survival (OS) of the whole cohort were 70.4% (95% CI: 60.8%-85.3%) and 86.5% (95% CI: 79.3%-94.1%). Four-year EFS and OS of the localised cohort were 73.8% (95% CI: 60%-83.3%) and 88.6% (95% CI: 87.4%-90.2%) and those of the metastatic cohort were 32.4% (95% CI: 21.4%-86.5%) and 61.9% (95% CI: 54.1%-86.3%), respectively. On multivariate analysis, EFS was affected by albumin ≤ 3 g/dL (p = 0.01) and delay in any type of local therapy from initiation of chemotherapy ≥12 weeks (p = 0.01), whereas OS was affected by male gender (p = 0.02). Survival of children with EES treated on a strategy based on non-dose dense chemotherapy with inclusion of radiotherapy as local control modality is comparable to the Western cohorts, especially in the localised setting. Timely delivery of local therapy is imperative for optimal outcomes.

Several studies have shown that the intensity of treatment in Ewing sarcoma has an impact on outcome. The present trial tested the non-inferiority of intensive, shorter, induction chemotherapy (25 weeks total treatment time) compared to the standard treatment (37 weeks) in non-metastatic Ewing sarcoma (ES) at onset. This national, multicenter, parallel, randomized, controlled, open-label, non-inferiority, phase III trial was conducted in 14 specialized hospitals in Italy. Patients aged 2-40 years with newly diagnosed localized ES were randomized to receive four courses of induction therapy (one every 21 days) either with a standard arm (Arm A) or with an intensive arm (Arm B). For consolidation therapy, good responders (GRs) in Arm A received nine courses (37 weeks), while Arm B patients received five courses (25 weeks). Poor responders for both arms received four courses followed by high-dose busulfan/melphalan + autologous stem cell rescue. Follow-up was 5 years. In the study period 2009-2018, 274 patients with ES at onset were screened, 248 were eligible, 15 refused randomization, and 233 were randomized (Arm A: 113; Arm B: 120). Median age was 14 years. Arm B was not inferior to Arm A: 5-year EFS was 77.5% and 71.6%, respectively (HR vs. Arm A: 0.74, 90% CI: 0.49-1.14). GRs were 54.9% in Arm A and 62.5% in Arm B. Hematological, gastrointestinal, and cardiovascular Grade ≥3 toxicities had higher frequencies in Arm B. Intensive induction therapy showed non-inferiority in 5-year EFS when compared with the standard induction therapy. Higher toxicity was reported in Arm B with similar outcome, counterbalanced in GRs with a shorter treatment plan. gov Identifier: NCT02063022.

Ewing sarcoma is a rare, highly aggressive small round cell tumor that primarily affects the bones of adolescents and young adults, with extra skeletal involvement being particularly uncommon. We present the case of an 18-year-old male with a progressively enlarging, painful swelling in the right posterior neck, ultimately diagnosed as Extra skeletal Ewing sarcoma involving the occipital bone and C1 vertebra. Imaging revealed extensive intracranial, intraspinal, and paravertebral extension with multiple skeletal metastases. Histopathological and immunohistochemical analysis confirmed the diagnosis, showing NKX 2.2 positivity. The patient was initiated on systemic chemotherapy using the VDC/IE regimen, leading to significant clinical and radiological improvement. This case underscores the importance of considering Ewing sarcoma in atypical paraspinal and cranial presentations and highlights the critical role of early multimodal imaging and chemotherapy in managing aggressive disease.