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Purpose The histological response to neoadjuvant chemotherapy is an important prognostic factor in patients with osteosarcoma (OS) and Ewing sarcoma (EWS). The aim of this study was to assess baseline primary tumour FDG uptake on PET/CT, and serum values of alkaline phosphatase (ALP) and lactate dehydrogenase (LDH), to establish whether these factors are correlated with tumour necrosis and prognosis. Methods Patients treated between 2009 and 2014 for localized EWS and OS, who underwent FDG PET/CT as part of their staging work-up, were included. The relationships between primary tumour SUVmax at baseline (SUV1), SUVmax after induction chemotherapy (SUV2), metabolic response calculated as [(SUV1 − SUV2)/SUV1)] × 100, LDH and ALP and tumour response/survival were analysed. A good response (GR) was defined as tumour necrosis >90 % in patients with OS, and grade II-III Picci necrosis (persitence of microscopic foci only or no viable tumor) in patients with Ewing sarcoma. Results The study included 77 patients, 45 with EWS and 32 with OS. A good histological response was achieved in 53 % of EWS patients, and 41 % of OS patients. The 3-year event-free survival (EFS) was 57 % in EWS patients and 48 % OS patients. The median SUV1 was 5.6 (range 0 – 17) in EWS patients and 7.9 (range 0 – 24) in OS patients ( p  = 0.006). In EWS patients the GR rate was 30 % in those with a high SUV1 (≥6) and 72 % in those with a lower SUV1 ( p  = 0.0004), and in OS patients the GR rate was 29 % in those with SUV1 ≥6 and 64 % in those with a lower SUV1 ( p  = 0.05). In the univariate analysis the 3-year EFS was significantly better in patients with a low ALP level (59 %) than in those with a high ALP level (22 %, p  = 0.02) and in patients with a low LDH level (62 %) than in those with a high LDH level (37 %, p  = 0.004). In EWS patients the 3-year EFS was 37 % in those with a high SUV1 and 75 % in those with a low SUV1 ( p  = 0.004), and in OS patients the 3-year EFS was 32 % in those with a high SUV1 and 66 % in those with a low SUV1 ( p  = 0.1). Histology, age and gender were not associated with survival. In the multivariate analysis, SUV1 was the only independent pretreatment prognostic factor to retain statistical significance ( p  = 0.017). SUV2 was assessed in 25 EWS patients: the median SUV2 was 1.9 (range 1 – 8). The GR rate was 20 % in patients with a high SUV2, and 67 % in those with a low SUV2 ( p  = 0.02). A good metabolic response (SUV reduction of ≥55 %) was associated with a 3-year EFS of 80 % and a poor metabolic response with a 3-year EFS of 20 % ( p  = 0.05). In the OS patients the median SUV2 was 2.7 (range 0 – 4.5). Neither SUV2 nor the metabolic response was associated with outcome in OS patients. Conclusion FDG PET/CT is a useful and noninvasive tool for identifying patients who are more likely to be resistant to chemotherapy. If this finding is confirmed in a larger series, SUV1, SUV2 and metabolic response could be proposed as factors for stratifying EWS patients to identify those with high-grade localized bone EWS who would benefit from risk-adapted induction chemotherapy.

Ewing's sarcoma, a highly malignant tumor of children, adolescents, and young adults, often responds to local excision plus a now-standard four-drug regimen of chemotherapy. This study shows that standard chemotherapy alternating with courses of ifosfamide plus etoposide significantly improves survival in patients with nonmetastatic disease at the time of diagnosis, but not in those with metastatic disease. Ewing's sarcoma is a highly malignant tumor of bone that occurs in children, adolescents, and young adults. When treated with local control measures only (surgery or radiation therapy), the disease has an extremely high fatality rate. 1 The use of adjuvant chemotherapy, which began in the early 1970s, resulted in a marked improvement in the outcome. Since the first Intergroup Ewing's Sarcoma Study demonstrated improved outcomes with the inclusion of doxorubicin, nearly every chemotherapy protocol for Ewing's sarcoma has been based on four drugs: doxorubicin, cyclophosphamide, vincristine, and dactinomycin. 2 – 4 In the early 1980s, treatment with ifosfamide, with or without etoposide, . . .

IntroductionEwing sarcoma is a rare paediatric cancer. Currently, there is no way of accurately predicting these patients’ survival at diagnosis. Disease type (ie, localised disease, lung/pleuropulmonary metastases and other metastases) is used to guide treatment decisions, with metastatic patients generally having worse outcomes than localised disease patients. However, not all patients fit this trend. An accurate prognostic model could be used to guide treatment decisions in clinical practice to avoid patients being incorrectly under or overtreated.Methods and analysisThis study aims to develop and internally validate prognostic models in newly diagnosed Ewing sarcoma patients, using the EE2012 clinical trial data set. The models will incorporate prognostic factors, identified from a literature review, to predict patients’ probability of event-free survival at clinically important time points. Three models will be developed, for comparison of their performance and stability, using different methods of model selection and penalisation for overfitting (full model or backwards selection applying uniform shrinkage; and lasso variable selection). The models will be internally validated using bootstrapping to give optimism-adjusted performance statistics (calibration and discrimination) and model stability results. Patient and clinical user groups will be asked to determine risk thresholds to guide treatment decisions in clinical practice based on the model. Decision curve analyses will examine clinical utility at these thresholds.Ethics and disseminationThis study is a secondary analysis of EE2012 clinical trial data. The EE2012 trial received ethical approval from the competent authorities (UK ethics reference approval number 12/NW/0827). This study is covered by the trial ethics in place. The results from this study will be published in peer-reviewed journals to act as a benchmark for future studies.Trial registration numberEudraCT number 2012-002107-17. ISRCTN number 92192408.

Background Primary Ewing sarcoma (ES) can sometimes present as a chest-wall tumor. Multidisciplinary management, including chemotherapy and local treatment consisting of surgery, radiotherapy (RT), or both, has improved the survival of patients with localized ES; however, the best approach to achieving local control remains controversial. Methods We retrospectively analyzed data from 198 patients with non-metastatic ES of the chest wall, who were registered in the database of the German Society of Pediatric Hematology and Oncology between July 1998 and April 2009. The majority of patients ( n  = 130) presented with rib tumors; 7 patients received RT only, 85 patients underwent surgery alone, and 106 patients were treated with a combination of surgery and RT. Results Overall survival in all patients was 78 and 71 % at 3 and 5 years, respectively. Event-free survival at 5 years (5-year EFS) was 57 % in the RT group, 73 % in the surgery group and 63 % in the surgery + RT group. In patients with complete resections, 5-year EFS did not improve with the addition of RT compared with surgery alone. There was no difference in the 5-year EFS in patients with partial (63 %) or total (64 %) resection of the affected ribs, and median follow-up was 4.71 years (range 0.40–13.48). Conclusions Complete tumor resection is the best way to achieve local control of ES of the chest wall; additional RT is only useful in patients with incomplete resection. The main limitation of this study was its retrospective nature, and the benefit of total resection of the affected ribs could not be proved.

Background Though relatively rare, bone tumors significantly impact patient health and treatment outcomes. Objective This systematic review analyzes the incidence, types, survival rates, and risk factors associated with bone tumors, including both benign and malignant forms. Methods This systematic review was conducted using the keywords “bone tumors,” “epidemiology,” “benign bone tumors,” “malignant bone tumors,” “osteosarcoma,” “Ewing sarcoma,” “chondrosarcoma,” “risk factors,” and “survival” in electronic databases including PubMed, Scopus, Web of Science, and Google Scholar from 2000 to 2024. The search strategy was based on the PRISMA statement. Finally, 9 articles were selected for inclusion in the study. Results The systematic review highlights that primary bone tumors can be classified into benign and malignant types, with osteosarcoma being the most prevalent malignant form, particularly among adolescents and young adults. The epidemiology of bone tumors is influenced by factors such as age, gender, geographic location, and genetic predispositions. Recent advancements in imaging techniques have improved the detection of these tumors, contributing to an increasing recognition of their prevalence. Data shows that the limited-duration prevalence of malignant bone tumors has increased significantly. This increase is from 0.00069% in 2000 to 0.00749% in 2018, indicating an increasing recognition and diagnosis of these rare tumors over time. Survival rates vary significantly by tumor type, with approximately 50–60% for osteosarcoma and around 70% for Ewing’s sarcoma, though these rates decrease with metastasis. Key risk factors identified include genetic predispositions such as Li-Fraumeni syndrome and TP53 mutations, environmental exposures like radiation, and growth patterns related to height. Conclusion The review highlights the importance of early diagnosis and treatment intervention, as survival rates are significantly better for patients with localized disease compared to those with metastatic conditions. The observed variations in survival rates across different tumor types underscore the need for tailored treatment strategies. Key risk factors include genetic predispositions and environmental exposures, highlighting the need for targeted screening and ongoing research to enhance diagnostic accuracy and treatment strategies.

[...]we filtered for those genes whose overexpression was significantly negatively correlated with patients’ overall survival in a dataset of matched gene expression and survival data of 166 EwS patients [5] that covered 280 of the 292 overexpressed genes (96%) (Fig. 1c), identifying 22 candidates (Supplementary Table 1). [...]we focused on druggable targets possessing kinase or other enzymatic functions for which specific inhibitors and their pharmacokinetic data were available, but were still not (pre)clinically tested in EwS. [...]differential effect on sensitivity towards triapine was not observed in A-637 cells expressing a non-targeting control shRNA. [...]we observed an ~ twofold increase of RRM2 expression in triapine-resistant A-673 (A-673/TR) compared to parental A-673 EwS cells, suggesting that RRM2 upregulation can be a potential mechanism for acquiring triapine-resistance in A-673 EwS cells (Supplementary Fig. 3d). [...]despite our data strongly support RRM2 as an actionable and valuable drug target in EwS, and triapine as a potential lead candidate drug for preferential RRM2 inhibition, the development of even more specific RRM2 inhibitors is desirable.

Osteosarcoma and Ewing sarcoma are the most common malignant primary bone tumors mainly occurring in children, adolescents and young adults. Current standard therapy includes multidrug chemotherapy and/or radiation specifically for Ewing sarcoma, associated with tumor resection. However, patient survival has not evolved for the past decade and remains closely related to the response of tumor cells to chemotherapy, reaching around 75% at 5 years for patients with localized forms of osteosarcoma or Ewing sarcoma but less than 30% in metastatic diseases and patients resistant to initial chemotherapy. Despite Ewing sarcoma being characterized by specific EWSR1-ETS gene fusions resulting in oncogenic transcription factors, currently, no targeted therapy could be implemented. It seems even more difficult to develop a targeted therapeutic strategy in osteosarcoma which is characterized by high complexity and heterogeneity in genomic alterations. Nevertheless, the common point between these different bone tumors is their ability to deregulate bone homeostasis and remodeling and divert them to their benefit. Therefore, targeting different actors of the bone tumor microenvironment has been hypothesized to develop new therapeutic strategies. In this context, it is well known that the Wnt/β-catenin signaling pathway plays a key role in cancer development, including osteosarcoma and Ewing sarcoma as well as in bone remodeling. Moreover, recent studies highlight the implication of the Wnt/β-catenin pathway in angiogenesis and immuno-surveillance, two key mechanisms involved in metastatic dissemination. This review focuses on the role played by this signaling pathway in the development of primary bone tumors and the modulation of their specific microenvironment.

Ewing sarcoma (EWS) is a rare bone cancer that is most usually detected in children. Neutrophil extracellular traps (NETs) are closely related to the prognosis of cancer, but the significance of NET-related features in EWS remains uncertain. We constructed a NET signature utilizing four crucial NET-related genes in EWS to forecast prognosis and investigate the potential immunological value of this signature in EWS. EWS data were collected from the International Cancer Genome Consortium and Gene Expression Omnibus databases. We identified the subtypes mediated by NET-related genes in EWS and analyzed the function infiltration and immune signature of NET-related subtypes in EWS. The expression levels of proteins in EWS cells were detected via western blotting analysis. NET could distinguish EWS patients into two NET-related subtypes: C1 and C2. EWS patients with the C1 subtype exhibited a more unfavorable prognosis and higher levels of TIDE and T cell dysfunction when compared to individuals with the C2 subtype. C1 and C2 subtypes had different immune characteristics. A NET-related prognostic model including AKT1, MAPK3, ATG7, and SELPLG was established to predict the prognosis of EWS patients. The risk score model was an independent prognostic factor for EWS, and high-risk EWS patients exhibited significantly inferior prognosis. AKT1 and ATG7 expression was significantly increased in EWS samples. The protein levels of AKT1 and ATG7 were increased in EWS cells, while the protein levels of SELPLG was decreased. The NET-related prognostic model is a critical biomarker for predicting prognosis, defining molecular subtypes, and describing immune signatures in patients with EWS.

Purpose Osteosarcoma (OSC) and Ewing sarcoma (EWS) of the skull are rare malignancies in children and adolescents. This study aimed to analyze the demographic, clinical, treatment, and survival characteristics of these tumors using a population-based approach. Methods Data from the Surveillance, Epidemiology, and End Results (SEER) database were used to identify pediatric and adolescent patients (aged 0–19 years) diagnosed with OSC or EWS of the skull from 2000 to 2019. Demographic, clinical, and treatment variables were analyzed. Kaplan–Meier survival analysis and Cox proportional hazards regression models were used to evaluate prognostic factors for overall survival (OS). Results A total of 124 patients were included, with 46% diagnosed with OSC and 54% with EWS. At diagnosis, 43.6% had localized disease, 42.6% had regional disease, and 13.8% presented with distant metastases. Surgical resection was the primary treatment (84.6%), with 84.6% of patients receiving chemotherapy and 43.6% undergoing radiotherapy. The OS rates for the entire cohort were 90.3% at 1 year, 77.9% at 3 years, and 75.6% at 5 years. Younger patients (0–14 years) demonstrated significantly better survival outcomes compared to older adolescents ( P  = 0.003). EWS was associated with higher survival rates than OSC ( P  = 0.004). Patients with localized disease had significantly better survival outcomes compared to those with distant metastases ( P  = 0.003). Multivariable Cox regression analysis identified age, histological subtype, and SEER stage as independent prognostic factors. Older patients had higher mortality risk (HR 2.58; 95% CI, 1.28–5.19; P  = 0.008), as did those with distant-stage disease (HR 4.11; 95% CI, 1.67–10.11; P  = 0.002). EWS was associated with better survival compared to OSC (HR 0.36; 95% CI, 0.13–0.99; P  = 0.048). Conclusions This study highlights significant differences in survival outcomes for OSC and EWS of the skull in children and adolescents. Younger age, localized disease, and EWS subtype were associated with better prognosis. These findings underscore the need for early diagnosis and tailored treatment strategies to improve outcomes in this population.

Introduction The management of spinal sarcomas is complex, given their widespread involvement and high recurrence rates. Despite consensus on the need for a multidisciplinary approach with surgery at its core, there is a lack of definitive guidelines for clinical decision-making. This study examines a case series of primary spinal sarcomas, focusing on the surgical strategies, clinical results, and survival data to inform and guide therapeutic practices. Methods We conducted a retrospective analysis of patients who underwent surgical resection for primary spinal sarcomas between 2005 and 2022. The study focused on gathering data on patient demographics, surgical details, postoperative complications, overall hospital stay, and mortality within 90 days post-surgery. Results The study included 14 patients with a primary diagnosis of spinal sarcoma, with an average age of 48.6 ± 12.6 years. Chondrosarcoma emerged as the most common tumor type, representing 57.1% of cases, followed by Ewing sarcoma at 35.7%, and synovial sarcoma at 7.1%. Patients with chondrosarcoma were treated with en-bloc resection, while the patient with synovial sarcoma underwent intra-lesional excision and those with Ewing sarcoma received decompression and tumor debulking. Postoperative assessments revealed significant improvements in neurological conditions. Notably, functional status as measured by the Karnofski Performance Index (KPI), improved substantially post-surgery (from 61.4 to 80.0%) The mean follow-up was 34.9 ± 9.2 months. During this time period one patient experienced fatal bleeding after en-bloc resection complications involving the vena cava. None of the patient needed further surgery. Conclusions Our 16-year study offers vital insights into managing primary spinal sarcomas, showcasing the effectiveness of surgical intervention, particularly en-bloc resection. Despite their rarity and complexity, our multidisciplinary treatment approach yields improved outcomes and highlights the potential for refined surgical strategies to become standardized care in this challenging domain.