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Periosteal Ewing sarcoma (ES) is an exceedingly rare topographic subtype of the ES. To our knowledge, only 60 patients have been reported in the medical English language literature. It predominantly affects men in the second decade of life and arises in the long tubular bone diaphysis. Periosteal ES rarely develops distant metastases. We report two patients of this rare ES location that were found on the distal tibial shaft and proximal femoral diaphysis of a 21-year-old man and an 8-year-old boy, respectively. Both patients were treated with neoadjuvant chemotherapy, wide resection, and adjuvant chemotherapy. One of our patients had lung metastases at the time of diagnosis and died 5 years later. The other patient presented intramedullary humeral bone metastasis 19 years after diagnosis. There has been no evidence of disease in the 26 years of follow-up. Close follow-up of periosteal ES is recommended because distant metastases may exceptionally occur, even several years after diagnosis., Competing Interests: Declaration of Conflicting InterestsThe authors declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Background and Objectives: Ewing's sarcoma (EWS) is a malignant round-cell tumor arising from the bone and soft tissue. It is a disease of children and young adults. EWS affecting the central nervous system (cranial and spinal column) is relatively rare with an annual incidence of approximately one case per million in the Western population. Due to their rarity, very few studies are available in the literature. We present our experience of managing 21 such cases, highlighting their clinical, and radiological findings, treatment strategy, and surgical outcomes in patients with primary EWS affecting the central nervous system., Materials and Methods: We retrospectively collected hospital records of patients with primary EWS affecting the CNS (cranial and spinal column), who had been surgically treated in our Neuroscience Center between 2015 and 2023. Patients' demographics, presentation, radiological findings, treatment strategy including surgery and biopsy followed by adjuvant therapy, and outcome at discharge, and the latest follow-up were analyzed from our database., Results: There were sixteen male and five female patients with a mean age of 18.22 ± 12.73 years (ranging from 6 months to 59 years). The commonest presentation was headache and vomiting in cranial lesions (5/13 patients, 38.46%), and back pain in spinal lesions (4/8 patients, 50%). The site of lesions was cranial in thirteen patients (61.9%) and spinal column in eight patients (38.1%). The commonest site was the frontal region in the cranial group (6 patients, 46.15%) and the lumbar region in the spinal group (4 patients, 50%). All patients underwent surgical intervention [tumor resection (18) and biopsy (3)]. Tumor resection was achieved in 18 patients (85.71%). The extent of resection was gross-total excision in 9 patients (42.86%), near-total excision in 5 patients (23.8%), and tumor decompression in 4 patients (19%). Four patients underwent spinal instrumentation. Fifteen patients (71.42%) received multiagent chemo-radiotherapy according to institute protocol. Five patients (23.8%) with poor KPS expired within 6 months of surgery and could not receive adjuvant therapy. Two patients (9.52%) improved symptomatically, and nine patients (42.86%) remained asymptomatic at a mean follow-up of 25.1 ± 29 months. One patient (4.76%) after receiving 2 cycles of adjuvant therapy had initial improvement but expired later due to disease progression. Four patients after adjuvant chemo-radiotherapy (19%) expired due to systemic spread., Conclusion: Primary EWS affecting the central nervous system is a rare variety. A detailed radiological assessment can aid in adequate planning for safe maximal resection. Timely tissue diagnosis is essential for initiating early treatment. Radical excision followed by adjuvant therapy offers a favorable outcome. Postoperative adjuvant chemo-radiotherapy aids in optimal disease control and surgical outcome. With the current treatment strategy, good surgical outcomes can be achieved. However, metastasis is not uncommon and should be evaluated regularly., Competing Interests: Declarations. Ethics approval: Consent to participate and consent for publication was taken from the patient using written informed consent to publish from the parent. Ethics committee approval was obtained. Ethics approval: approved by Institute Ethics Committee (ICE-965/13.01.2023, RP-02/2023). Conflict of interest: The authors declare no competing interests., (© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Introduction: Patients with high-risk or metastatic Ewing sarcoma (ES) and rhabdomyosarcoma (RMS) have a guarded prognosis. High-dose chemotherapy (HDT) with autologous stem cell transplant (ASCT) has been evaluated as a treatment option to improve outcomes. However, survival benefits remain unclear, and treatment is associated with severe toxicities., Methods: A systematic review was conducted, using the population, intervention, comparison outcome (PICO) model, to evaluate whether utilization of HDT/ASCT impacts the outcome of patients with ES and RMS compared to standard chemotherapy alone, as part of first line treatment or in the relapse setting. Medline, Embase and Cochrane Central were queried for publications from 1990 to October 2022 that evaluated event-free survival (EFS), overall survival (OS), and toxicities. Each study was screened by two independent reviewers for suitability. A qualitative synthesis of the results was performed., Results: Of 1,172 unique studies screened, 41 studies were eligible for inclusion with 29 studies considering ES, 10 studies considering RMS and 2 studies considering both. In ES patients with high-risk localised disease who received HDT/ASCT after VIDE chemotherapy, consolidation with melphalan-based HDT/ASCT as first line therapy conveyed an EFS and OS benefit over standard chemotherapy consolidation. Efficacy of HDT/ASCT using a VDC/IE backbone, which is now standard care, has not been established. Survival benefits are not confirmed for ES patients with metastatic disease at initial diagnosis. For relapsed/refractory ES, four retrospective studies report improvement in outcomes with HDT/ASCT with the greatest evidence in patients who demonstrate a treatment response before HDT, and in patients under the age of 14. In RMS, there is no proven survival benefit of HDT/ASCT in primary localised, metastatic or relapsed disease., Conclusion: Prospective randomised trials are required to determine the utility of HDT/ASCT in ES and RMS. Selected patients with relapsed ES could be considered for HDT/ASCT., Competing Interests: Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Angela M Hong: advisory board payment from Telix, other authors: None., (Copyright © 2024 The Author(s). Published by Elsevier Ltd.. All rights reserved.)

Melatonin (N-acetyl-5-methoxytryptamine) is a secretory product of the pineal gland. A great number of studies have been investigating the functions of this indoleamine in various diseases. Excessive proliferation, reduction in apoptosis, increased angiogenesis, invasion, and metastasis are all processes associated with cancerous tissues. In several cancer types, melatonin is reported to significantly impact these processes. Although bone cancer is relatively rare, it is a serious disease that often becomes metastatic, leading to an unsatisfactory prognosis. In recent decades, significant advances have been made in the therapeutic strategies for bone cancer. Nevertheless, few changes have occurred to patients' outcomes or therapeutic methods. Currently used therapeutic strategies including chemotherapy and radiotherapy often show serious side effects. Moreover, therapeutic options are not sufficient in certain cases, such as metastatic forms of the disease. Therefore, there is a need for a more precise definition of the molecular pathways and cellular functions associated with bone cancer to find novel therapeutic approaches. With such advances, the development of new effective therapies for patients with advanced stage or metastatic forms of the disease will be achieved, resulting in an improved prognosis. This review summarizes what is known about the functions of melatonin in osteosarcoma and Ewing's sarcoma. We explain the underlying mechanisms of action by which melatonin serves as an antitumor agent in bone cancer as well as provide an insight into its synergistic effects with other chemotherapeutic drugs., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)

Background/aim: Ewing sarcoma is a common primary bone tumor, often located in the distal femur or pelvis. Acral Ewing sarcoma of the upper extremity is exceedingly rare. The aim of this study was to review our institution's experience with the management of rare acral Ewing sarcomas., Patients and Methods: We retrospectively reviewed the records of 10 patients with bony Ewing sarcomas located distal to the elbow joint. The group included 9 male and 1 female patient with a mean age at diagnosis of 20±12 years and a mean follow-up of 19 years., Results: All patients presented with a primary complaint of a painful mass. The most common location was the metacarpal (n=4). Patients were treated with chemotherapy and either surgery (n=7) or definitive radiotherapy (n=3). The mean tumor size and necrosis on the resected specimens were 4±1 cm and 87% (range=30-100%), respectively. There was one case of local progression in a patient treated with definitive radiotherapy, which led to an amputation. Four patients developed metastatic disease, most commonly to the lungs. The 5-year survival free of metastatic disease or death due to disease was 55% and 60%, respectively., Conclusion: Acral Ewing sarcoma is rare. Combined chemotherapy and surgery lead to definitive local control in all patients, with an acceptable functional outcome., (Copyright © 2022 International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.)

Background: Locally recurrent disease following surgical resection of Ewing sarcoma (ES) confers a poor prognosis. Limited evidence is available evaluating non-selective use of pre-operative radiotherapy (RT) for patients with pelvic ES and its effect on local control and survival., Patients and Methods: 49 consecutive patients with pelvic ES were identified retrospectively from a prospectively collated database. Patients either received non-selective pre-operative RT and surgery (n = 27), or selective post-operative RT (n = 22) (surgery alone (n = 11) or surgery and post-operative RT (n = 11))., Results: Patients who had non-selective pre-operative radiotherapy appeared to have a higher LRFS, 88.0% compared to 66.5% in the selective RT group (p = 0.096, Kaplan Meier; p = 0.028, Chi-squared). Administration of non-selective, pre-operative RT to all patients with pelvic ES elevates the LFRS to that of the good responder group (≥90% tumour necrosis and margins, p = 0.880). There was no difference in metastasis-free survival, 60.0% and 54.5% (p = 0.728) and overall survival (OS), 57.7% and 63.6% (p = 0.893). The majority of pre-operative RT patients had both good necrosis (≥90%) (p = 0.003) and widely excised tumours, 81.5% vs 59.1% (p = 0.080). Tumour volume ≥250 ml was associated with worse LRFS (p = 0.045) and post-operative complications (p = 0.017). There may be improved LRFS (p = 0.057) with pre-operative proton-beam RT compared to surgery and selective post-operative RT., Conclusion: Pre-operative photon or proton-beam RT to all pelvic ES may improve LRFS compared to the selective delivery of post-operative RT. Radiotherapy delivered to all patients results in a greater percentage of highly necrotic tumours at surgical excision, enabling a greater proportion of patients with wide resection margins., Competing Interests: Declaration of competing interest Each author certifies that he or she has no commercial associations (e.g. Consultancies, stock ownership, equity interest, patent/licensing arrangements, etc.) that might pose a conflict of interest in connection with the submitted article., (Crown Copyright © 2021. Published by Elsevier Ltd. All rights reserved.)

Background: Ewing's sarcoma (ES) is a kind of malignant tumor, which often occurs in the long bone, pelvis, and other bone tissues, as well as some soft tissues. It often occurs in children and adolescents, second only to osteosarcoma and rhabdomyosarcoma. In the past 30 years, little progress has been made on the genomic mechanism of ES metastasis., Methods: The gene expression sequence of ES metastasis samples was compared with that of primary tumor samples to obtain differentially expressed genes (DEGs). Subsequently, we annotated the gene functions and enriched pathways of DEGs. Additionally, the protein and protein interaction network were constructed to screen key genes that can lead to the metastasis in ES. Then, cell and molecular biology experiments were conducted to verify the results obtained from the bioinformatics analysis. Finally, we assessed the correlation of expression between the key genes EWSR and FLI1, and conducted a survival analysis of ICAM1., Results: Our study revealed 153 DEGs. Of these, 82 (53.59%) were upregulated and the remaining 71 (46.41%) were downregulated. The bioinformatics analysis showed that ICAM1 was the key gene leading to the invasion and metastasis of ES. Through cell biology and molecular biology experiments, inactivation of ICAM1 inhibited the metastasis of ES cells. The survival and correlation analyses showed that ICAM1 was a risk factor in patients with ES, and that ICAM1 expression was correlated with EWSR and FLI1 expression., Conclusion: Our study shows that inactivation of ICAM1 inhibits metastasis and improves the prognosis of ES. Additionally, our findings provide a better understanding of the underlying mechanisms of metastatic ES, a basis for an accurate diagnosis, and therapeutic targets for ES patients.

Oncogenesis of Ewing sarcoma (EwS), the second most common malignant bone tumor of childhood and adolescence, is dependent on the expression of chimeric EWSR1-ETS fusion oncogenes, most often EWSR1-FLI1 (E/F). E/F expression leads to dysregulation of focal adhesions (FAs) enhancing the migratory capacity of EwS cells. Here, we show that, in EwS cell lines and tissue samples, focal adhesion kinase (FAK) is expressed and phosphorylated at Y397 in an E/F-dependent way involving Ezrin. Employing different EwS cell lines as in vitro models, we found that key malignant properties of E/F are mediated via substrate-independent autophosphorylation of FAK on Y397. This phosphorylation results in enhanced FA formation, Rho-dependent cell migration, and impaired caspase-3-mediated apoptosis in vitro. Conversely, treatment with the FAK inhibitor 15 (1,2,4,5-benzenetetraamine tetrahydrochloride (Y15) enhanced caspase-mediated apoptosis and EwS cell migration, independent from the respective EWSR1-ETS fusion type, mimicking an anoikis-like phenotype and paralleling the effects of FAK siRNA knockdown. Our findings were confirmed in vivo using an avian chorioallantoic membrane model and provide a first rationale for the therapeutic use of FAK inhibitors to impair metastatic dissemination of EwS., (© 2019 The Authors. Published by FEBS Press and John Wiley & Sons Ltd.)

Bone sarcomas are rare cancers which often present with metastatic disease and are still associated with poor survival rates. Studies in the last decade have identified that exosomes, a type of extracellular vesicle released by cells, play an important role in tumour progression and dissemination. Through the transfer of their cargo (RNAs, proteins, and lipids) across cells, they are involved in cellular cross-talk and can induce changes in cellular behaviour. Exosomes have been shown to be important in metastasis organotropism, induction of angiogenesis and vascular permeability, the education of cells towards a pro-metastatic phenotype or the interaction between stromal and tumour cells. Due to the importance exosomes have in disease progression and the high incidence of metastasis in bone sarcomas, recent studies have evaluated the implications of these extracellular vesicles in bone sarcomas. In this review, we discuss the studies that evaluate the role of exosomes in osteosarcoma, Ewing sarcoma, and preliminary data on chondrosarcoma., Competing Interests: Abbreviations:

Background: Medical implications of 3-dimensional (3D) printing technology have evolved and are increasingly used. Surgical spine oncology involves at times complex resection using various surgical approaches and unique spinal reconstruction. As high general complication rates, including hardware failure, are reported, careful preoperative planning and optimized fixation techniques should be performed. 3D printing technology allows the improvement of preoperative planning, practice and exploration of various surgical approaches, and designing customized surgical tools and patient specific implants., Objective: To investigate the use of 3D printing technology in complex spine surgeries., Methods: Between 2015 and 2018, all complex spine oncological cases were evaluated and assessed for the possible benefit of use of 3D printing technology. Following high-quality imaging, a computerized integrated 3D model was created. Based on the planned procedure considering the various surgical steps, a customized 3D model was planned and printed, and in select cases a 3D custom-made implant was designed and printed in various sizes with matching trials., Results: A total of 7 cases were selected for the use of a 3D printing technology. For all, a custom-made model was created. In 3 of these cases, a customized 3D-printed implant was used. Special customized intraoperative instruments were made for 2 cases, and a simulated surgical approach was performed in 5 cases. In 2 cases, pre-bent rods were made based on the model created and were used in surgery later on., Conclusions: For complex spine oncology cases, the use of 3D printing allowed better preoperative planning, simplified the operative procedure, and enabled improved reconstruction., (Copyright © 2019 Elsevier Inc. All rights reserved.)

Purpose: The R2Pulm trial was conducted to evaluate the effect of busulfan-melphalan high-dose chemotherapy with autologous stem-cell rescue (BuMel) without whole-lung irradiation (WLI) on event-free survival (main end point) and overall survival, compared with standard chemotherapy with WLI in Ewing sarcoma (ES) presenting with pulmonary and/or pleural metastases., Methods: From 2000 to 2015, we enrolled patients younger than 50 years of age with newly diagnosed ES and with only pulmonary or pleural metastases. Patients received chemotherapy with six courses of vincristine, ifosfamide, doxorubicin, and etoposide (VIDE) and one course of vincristine, dactinomycin, and ifosfamide (VAI) before either BuMel or seven courses of VAI and WLI (VAI plus WLI) by randomized assignment. The analysis was conducted as intention to treat. The estimates of the hazard ratio (HR), 95% CI, and P value were corrected for the three previous interim analyses by the inverse normal method., Results: Of 543 potentially eligible patients, 287 were randomly assigned to VAI plus WLI (n = 143) or BuMel (n = 144). Selected patients requiring radiotherapy to an axial primary site were excluded from randomization to avoid excess organ toxicity from interaction between radiotherapy and busulfan. Median follow-up was 8.1 years. We did not observe any significant difference in survival outcomes between treatment groups. Event-free survival was 50.6% versus 56.6% at 3 years and 43.1% versus 52.9% at 8 years, for VAI plus WLI and BuMel patients, respectively, resulting in an HR of 0.79 (95% CI, 0.56 to 1.10; P = .16). For overall survival, the HR was 1.00 (95% CI, 0.70 to 1.44; P = .99). Four patients died as a result of BuMel-related toxicity, and none died after VAI plus WLI. Significantly more patients in the BuMel arm experienced severe acute toxicities than in the VAI plus WLI arm., Conclusion: In ES with pulmonary or pleural metastases, there is no clear benefit from BuMel compared with conventional VAI plus WLI.

Background: We investigated the effects of surgical margins, histological response, and radiotherapy on local recurrence (LR), distant metastasis (DM), and survival in Ewing sarcoma., Procedure: Disease evolution was retrospectively studied in 982 patients with Ewing sarcoma undergoing surgery after chemotherapy using a multistate model with initial state surgery, intermediate states LR, pulmonary metastasis (DMpulm), other DM ± LR (DMother), and final state death. Effect of risk factors was estimated using Cox proportional hazard models., Results: The median follow-up was 7.6 years (95% CI, 7.2-8.0). Risk factors for LR are pelvic location, HR 2.04 (1.10-3.80), marginal/intralesional resection, HR 2.28 (1.25-4.16), and radiotherapy, HR 0.52 (0.28-0.95); for DMpulm the risk factors are <90% necrosis, HR 2.13 (1.13-4.00), and previous pulmonary metastasis, HR 4.90 (2.28-8.52); for DMother are 90% to 99% necrosis, HR 1.56 (1.09-2.23), <90% necrosis, HR 2.66 (1.87-3.79), previous bone/other metastasis, HR 3.08 (2.03-4.70); and risk factors for death without LR/DM are pulmonary metastasis, HR 8.08 (4.01-16.29), bone/other metastasis, HR 10.23 (4.90-21.36), and <90% necrosis, HR 6.35 (3.18-12.69). Early LR (0-24 months) negatively influences survival, HR 3.79 (1.34-10.76). Once DMpulm/DMother arise only previous bone/other metastasis remain prognostic for death, HR 1.74 (1.10-2.75)., Conclusion: Disease extent and histological response are risk factors for progression to DM or death. Tumor site and surgical margins are risk factors for LR. If disease progression occurs, previous risk factors lose their relevance. In case of isolated LR, time to recurrence is important for decision-making. Radiotherapy seems protective for LR especially in pelvic/axial. Low percentages of LR in extremity tumors and associated toxicity question the need for radiotherapy in extremity Ewing sarcoma., (© 2019 The Authors. Pediatric Blood & Cancer Published byWiley Periodicals, Inc.)

Introduction: Paediatric soft tissue sarcoma treatments and outcomes have improved significantly in the last few decades. However, a significant number of patients still succumb to the disease. In low-middle income countries there are dual problems of advanced disease at presentation and financial burden leading to poor compliance to therapy. Hence, we designed a low-cost oral metronomic chemotherapy protocol for these patients and studied the responses and toxicities to therapy in a tertiary referral hospital., Patients and Methods: This is retrospective, single institutional, observational study. We retrospectively reviewed data of patients with relapsed, refractory or metastatic soft tissue sarcoma (STS) [ Ewing Sarcoma (ES); Rhabdomyosarcoma (RMS) or other STS] who were treated with the metronomic protocol of oral Tamoxifen, Etoposide and Cyclophosphamide (TEC) during the period April 1998 to September 2013, at the Tata Memorial Hospital, Parel, Mumbai. Patients with ES and RMS were primarily treated on our Institutional protocols. The patients included in the analysis were those who had relapsed after the primary protocols and then treated with metronomic TEC protocol; or those with primary refractory or metastatic disease (RMS, ES) and received metronomic TEC therapy., Results: 49 patients were enrolled. Among the 49 patients, 32 were diagnosed ES, 13 RMS and 4 other STS. For the whole cohort response rates (RR) were 59% and clinical benefit rate (CBR) was 79%. Patients in the study were grouped into the following subgroups. Systemic recurrent/relapsed disease (N=24), metastatic disease at presentation (N=15) and local disease (refractory/recurrent) (N=10). None of the patients required blood or platelet support or admission for supportive care. The PFS for the above groups were 16.8 months, 12.5 months and 126.68 months respectively. This compares favorably with other historical cohorts in a similar setting., Conclusions: This study provides a preliminary evidence efficacy and tolerability of metronomic chemotherapy in poor risk ES and RMS. It also demonstrates that with this low-cost low risk treatment few patients could go into long term remissions despite high disease burden.

Objectives: This study aims to evaluate the clinical characteristics and treatment outcomes of patients with primary malignant tumors located in the proximal fibula., Patients and Methods: This retrospective study included 23 patients (15 males, 8 females; mean age 22.1 years; range, 9 to 63 years) with primary malignant tumors located in the proximal fibula between May 2007 and May 2017. The anamnesis or medical history, physical examination, plain chest radiography, lung computed tomography, direct radiograph, and magnetic resonance imaging of the affected extremity and routine laboratory tests of all patients were evaluated., Results: Of the patients, 11 were diagnosed with osteosarcoma (47.8%), nine with Ewing's sarcoma (39.1%), two with chondrosarcoma (8.7%), and one was diagnosed with synovial sarcoma (4.3%). Pain and palpable mass were the most common symptoms. Six patients had lung metastases at the time of diagnosis. Of the patients, eight were performed Malawer type 1 resection (34.8%), nine type 2 resection (39.1%), four above knee amputation (17.4%), and two proximal tibia tumor resection prosthesis (8.6%). Mean follow-up duration was 36 months (range, 12 to 119 months). Local recurrence developed in three patients. Mean Musculoskeletal Tumor Society (MSTS) score of all patients was 62., Conclusion: Surgical treatment of primary malignant tumors of the proximal fibula is problematic. In appropriate indications, Malawer type 1 resection should be the treatment of choice due to lower local recurrence rates and higher MSTS scores.

Ewing Sarcoma is a highly lethal undifferentiated tumor of bone. ES is a small round cell tumor with etiological and characteristic chromosomal translocations between TET/FET (TLS/FUS, EWSR1, and TAF15) and ETS (E26 transformation-specific) family genes. Generally, therapeutic approach for metastatic Ewing Sarcoma includes both local (surgery and radiotherapy) and systemic (chemotherapy) disease control with an overall cure rate of 20%. For extra-osseous tumors, the most common primary sites of disease are trunk, extremities, head and neck, retroperitoneum. Among other sites, Ewing Sarcoma/PNET may also rarely arise in colon and rectum. Even if colonic Ewing Sarcoma/PNET have been previously reported in 5 cases, none of those reports came from right side of the colon. In this article, we report the first case of right-sided Ewing Sarcoma with synchronous liver metastases completely responding to first line chemotherapy. Furthermore, we provide a systematic qualitative review of the current literature on adult colorectal Ewing Sarcoma using the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA)., (Copyright © 2018. Published by Elsevier GmbH.)

Background: Malignant bone tumors of the pelvis in children are rare and knowledge of their behavior is limited., Methods: A total of 113 skeletally immature patients under 16 years of age, comprising 58 females and 55 males were treated between 1983 and 2014. Tumors comprised Ewing's sarcoma (ES) in 88 (77.9%) or osteosarcoma (OS) in 25 (22.1%). Metastases at diagnosis were present in 36 (31.9%). The mean follow-up was 5.2 years (2 to 16)., Results: For patients with ES, the overall survival was 37.1% at 5-years and 33.5% at 10-years and 31.7% at 5- and 10-years in patients with OS. Local recurrence occurred in 24 patients with ES (27.3%) and 7 patients with OS (43.7%). Chemotherapy response was a predictor of local recurrence in ES with the lowest incidence seen in those with a good response to chemotherapy treated with a combination of radiotherapy and surgery. In patients with OS, both surgical margin and chemotherapy response influenced local control., Conclusions: Attaining a wide surgical margin should be the aim of treatment for all children with primary bone tumors of the pelvis. In ES, chemotherapy response has a greater influence on disease free and overall survival. Patients who demonstrate a poor response to chemotherapy should be considered for subsequent radiotherapy. Effort should be directed toward identifying nonhistologic methods of assessing chemotherapy response., Level of Evidence: Level IV-retrospective case study.

A 39-year-old woman with primary spinal Ewing sarcoma and known lung metastases presented with painless bilateral decreased visual acuity over a 1-month period. Examination revealed bilateral disc edema. MRI of the brain/orbits showed metastatic lesions to the dura and bilateral orbits. Venous sinus thrombosis extending to the jugular vein was also noted. To the authors' knowledge, this is the first case of bilateral orbital metastasis and papilledema secondary to Ewing sarcoma and related hypercoagulability.

Ewing's sarcoma (ES) is an aggressive pediatric malignancy. We present a case of ES with thyroid metastasis. The patient was diagnosed with ES at age 8. Despite aggressive treatment, she suffered disease progression. Surveillance demonstrated a left thyroid lesion. This grew rapidly within 2 months, causing tracheal compression. She underwent hemi-thyroidectomy to prevent airway compromise. Due to her refractory ES, she was enrolled in the Vigil immunotherapy vaccine trial; thus, the specimen was used for vaccine development. This is the first reported case of skeletal ES with metastasis to the thyroid, requiring hemithyroidectomy to prevent airway compromise., (Copyright © 2018. Published by Elsevier B.V.)

The clinical efficacy and outcomes of pazopanib treatment for metastatic extraosseous Ewing sarcoma remain unclear. We herein report a case of heavily pre-treated metastatic extraosseous Ewing sarcoma in which pazopanib treatment achieved a significant improvement. A 17-year-old girl was referred to our hospital due to metastatic extraosseous Ewing sarcoma. The initial cytotoxic chemotherapy was temporarily effective, however, her disease eventually progressed, and she was subsequently treated with pazopanib. The recurrent tumor showed a marked response to pazopanib therapy; the therapeutic effect has lasted for more than 26 months. The present case suggests that pazopanib may be a therapeutic option for extraosseous Ewing sarcoma.

Background: The median age of patients with Ewing sarcoma (EwS) at diagnosis is around 14-15 years. Older age is associated with a worse outcome. The correlation of age at diagnosis on sites of disease has not been fully described., Objective: The goal of this study was to evaluate the differences in sites of primary tumor and metastatic tumor involvement according to age groups., Design/method: EwS data from the Gesellschaft für Pädiatrische Onkologie und Hämatology (GPOH) database of the Cooperative Ewing Sarcoma Study (CESS) 81/86 and the European Intergroup Cooperative Ewing's Sarcoma Study EICESS 92 and the EUROpean Ewing tumor Working Initiative of National Groups-99-Protocol (EURO-E.W.I.N.G.-99) study were analyzed. Patient and tumor characteristics were evaluated statistically using chi square tests., Results: The study population included 2,635 patients with bone EwS. Sites of primary and metastatic tumors differed according to the age groups of young children (0-9 years), early adolescence (10-14 years), late adolescence (15-19 years), young adults (20-24 years), and adults (more than 24 years). Young children demonstrated the most striking differences in site of disease with a lower proportion of pelvic primary and axial tumors. They presented less often with metastatic disease at diagnosis., Conclusions: Site of primary and metastatic tumor involvement in EwS differs according to patient age. The biological and developmental etiology for these differences requires further investigations., (© 2018 Wiley Periodicals, Inc.)

Renal Ewing sarcoma (RES) is an extremely rare disease. The standard treatment for this disease is lacking, and clinical experience needs to be accumulated. Here, we report a case of RES that rapidly developed to metastatic disease and was refractory to radiotherapy and chemotherapy; however, the case obtained a partial response based on Choi criteria by orally taking antiangiogenic drug apatinib. Our case suggests that apatinib may be a therapeutic option for RES.

We report the clinical history of 2 female patients with Ewing sarcoma and microscopic ovarian infiltration. In both cases, the initial workup found no metastasis. However, the examination of cryopreserved ovarian tissues revealed the presence of CD99 positive tumor cells with rearrangement of EWS gene confirmed by FISH. Both children were treated as patients with localized tumor and are currently in remission. These reports underline that, in Ewing sarcoma patients, retransplantation of cryopreserved ovarian tissue is not harmless and could lead to cancer relapse. These observations question also on the significance of ovarian dissemination on Ewing sarcoma prognosis and therapy.

Rationale: Both acute lymphoblastic leukemia (ALL) and Ewing sarcoma (ES) are small round cell tumors, and it is difficult to differential diagnose them because of overlapping clinical, radiographic, histologic, and immunophenotypic features., Patient's Concerns: A 5-year-old boy was admitted to our hospital because of pains in his left leg without obvious inducement and lameness worsening with walking over a two 2-month period., Diagnoses: Based on the comprehensive analysis of radiography, magnetic resonance imaging (MRI), pathology biopsy and immunohistochemistry, the lesion was confirmed to be ES., Interventions: The patient received neoadjuvant chemotherapy with 2 cycles of VAC (vincristine 1 mg/m, adriamycin 50 mg/m, cyclophosphamide 800 mg/m) and 2 cycles of IE (ifosfamide 1.2 g/m, etoposide 70 mg/m, mesna 1.2 g/m) regimens., Outcomes: After 16 months, the results of routine blood tests showed reduced hemoglobin levels and decreased platelet counts. In addition, blast-like cells were found in a peripheral blood smear. All of the results suggested that the patient should undergo bone marrow aspiration and biopsy, which showed blast-like cells similar to that observed in cases of ES. Thus, a diagnosis of bone marrow metastasis of ES was established. However, when combined with immunohistochemistry data and medical history, the patient was eventually diagnosed as ALL arising after treatment of ES., Lessons: When there was an abnormality in peripheral blood, it was easily misdiagnosed as bone marrow metastasis of ES after ES patient received neoadjuvant chemotherapy. We should jointly analyze bone marrow aspiration smear, bone marrow biopsy, immunohistochemistry, analysis of the medical history, even cytogenetic and molecular analysis for differential diagnosis., (Copyright © 2017 The Authors. Published by Wolters Kluwer Health, Inc. All rights reserved.)

Purpose: To identify clinical and treatment variables associated with a higher risk of local failure in Ewing sarcoma patients treated on recent Children's Oncology Group protocols., Methods and Materials: Data for 956 patients treated with ifosfamide and etoposide-based chemotherapy on INT-0091, INT-0154, and AEWS0031 were analyzed. Local treatment modalities were defined as surgery, definitive radiation therapy (RT), or surgery plus radiation (S+RT). Five-year cumulative incidence of local failure was determined., Results: The local failure rate for the entire cohort was 7.3%, with a 3.9% rate for surgery, 15.3% for RT (P<.01), and 6.6% for S+RT (P=.12). The local failure incidence was 5.4% for extremity tumors, 13.2% for pelvis tumors (P<.01), 5.3% for axial non-spine tumors (P=.90), 9.1% for extraskeletal tumors (P=.08), and 3.6% for spine tumors (P=.49). The incidence of local failure was 14.8% for extremity tumors and 22.4% for pelvis tumors treated with RT, compared with 3.7% for extremity tumors and 3.9% for pelvis tumors treated with surgery (P≤.01). There was no difference in local failure incidence by local treatment modality for axial non-spine, spine, and extraskeletal tumors. The local failure incidence was 11.9% in patients aged ≥18 years versus 6.7% in patients aged <18 years (P=.02). Age ≥18 years (hazard ratio 1.9, P=.04) and treatment with RT (hazard ratio 2.40, P<.01) remained independent prognostic factors for higher local failure incidence on multivariate analysis. Tumor size (

Objective: To evaluate the frequency of bone marrow involvement with metastatic lung and bone sites in newly-diagnosed pediatric patients with Ewing sarcoma (ES)., Study Design: An observational study., Place and Duration of Study: Shaukat Khanum Memorial Cancer Hospital, Lahore, Pakistan, from January 2010 to October 2015., Methodology: Newly-diagnosed pediatric-age patients with ES were inducted. Ten patients were excluded because bone marrow aspiration/biopsy (BMAB) was not done. Patients'medical records were reviewed for data collection of age, diagnosis, tumor volume, bone marrow diagnosis, metastatic work-up and outcomes., Results: Atotal of 139 patients with median age of 12 years were identified. The median volume of tumors was 529 ml. Eleven patients had bone marrow (BM) disease involvement. Five (45.5%) had bone metastatic disease and 1 (9%) had both pulmonary and bone metastases. Four patients (31.1%) with positive BM had primary limb disease., Conclusion: Ewing sarcoma patients with bone metastatic disease have a higher frequency of BM involvement. However, BM can be involved without metastatic disease. BMAB should still be considered at staging for newly diagnosed pediatric patients with localized ES.

Purpose: Bilateral pulmonary radiotherapy in children and young adults aims to reduce the recurrence of lung metastases. The radiation field includes liver tissue, which is sensitive to even low radiation doses. We investigated the feasibility of respiratory gating radiotherapy using voluntary deep inspiration breath hold and its toxicity in these patients., Patients and Method: A retrospective clinical review was conducted for all patients who had undergone bilateral pulmonary radiotherapy, with or without deep inspiration breath hold, treated in our institution between October 1999 and May 2012. A dosimetric study was conducted on seven consecutive children using 4D-scan data on free-breathing and a SpiroDyn'RX-system-scan on deep inspiration breath hold. A radiation treatment of 20Gy was simulated., Results: Concerning the clinical study, seven patients of mean age 11.9 years (range: 4.9-21.1 years) were treated with free-breathing and ten patients of mean age 15.6 years (range: 8.6-19.7 years) were treated with deep inspiration breath hold for mainly Ewing sarcoma and nephroblastoma. Within six months of radiotherapy, all patients experienced mild liver toxicity (grade 1 or 2 altered levels of alanine/aspartate aminotransferase [n=8 of 9] or cholestasis [n=1 of 9]), which resolved completely with no difference between deep inspiration breath hold and free-breathing technique. Over a median follow-up of 2.6 years (range: 0.1-9.3 years), four patients died from disease progression (mean 1.5 years post-radiotherapy [range: 1.1-1.6 years]) and three experienced grade III-V lung toxicity. Concerning the dosimetric study, the irradiated liver volume was significantly lower with deep inspiration breath hold than free-breathing, for each isodose (V5: 73.80% versus 86.74%, P<0.05; V20: 5.70% versus 26.44%, P<0.05)., Conclusions: The dosimetric data of respiratory-gated bilateral pulmonary radiotherapy showed a significantly spare of normal liver tissue. Clinical data showed that this technique is feasible even in young children. However, no liver toxicity difference between deep inspiration breath hold and free-breathing was shown., (Copyright © 2017 Société française de radiothérapie oncologique (SFRO). Published by Elsevier SAS. All rights reserved.)

Metastasis is the most powerful predictor of poor outcome of Ewing sarcoma (ES). Thus, identification of new molecules involved in tumor metastasis is of crucial importance to reduce morbidity and mortality of this devastating disease. In this study, we found that miR-124, a highly conserved miRNA, was suppressed in ES tissues and might be associated with tumor metastasis through suppressing its mesenchymal features. Overexpression of miR-124 suppressed the invasion of ES cells in vitro and tumor metastasis in vivo, which might be achieved through suppressing its mesenchymal features, as overexpression of miR-124 could repress the mesenchymal genes expression, and inhibit cell differentiation to mesenchymal lineages in ES cells. However, when SLUG was experimentally restored in these cells, mesenchymal features including suppressed expression of mesenchymal genes and decreased invasive ability were observed. We also found that cyclin D2 (CCND2) was a novel target gene of miR-124, and was directly involved in miR-124-mediated suppressive effects on cell growth. Lastly, we found that treatment with 5-Aza-CdR restored the expression of miR-124, accompanied with suppressed cell proliferation, invasion and mesenchymal features of ES cells, which demonstrated that hypermethylation might be involved in the regulation of miR-124 expression. Collectively, our data suggest that hypermethylation-mediated suppression of miR-124 might be involved in the tumor initiation and metastasis through suppressing the mesenchymal features of ES cells.

PURPOSE OF THE STUDY Ewing sarcomas (ES) are the second most common solid malignant bone tumors in both, children and adolescents, and systemic chemotherapy protocols were established during the last 3 decades which proved to be a successful approach in addition to local treatment. The purpose of the present study is (i) to provide survival rates and prognostic factors for patients with ES which received treatment in a single center and (ii) to compare data with results of multicenter studies. MATERIALS AND METHODS Patients (n = 38) were treated by the same surgeon whereas surgery was combined with radiotherapy in 55.3% of the patients (n = 21). Median age at diagnosis was 17.5 years (4.7-60) and the median follow-up time for all patients was 8.2 years (9.8 years for survivors, 3.2 years for non-survivors). RESULTS The survival rate for metastasis free sarcoma decreases from 90.5% to 50% for patients diagnosed with disseminated disease stage. Patients with a good response to chemotherapy survived in 83.3% of the cases. In addition, a higher OS was found for patients younger than 15 years (82.4%) when compared to patients older than 15 years (73.3%). In contrast, multicenter studies reported lower survival rates for metastasis free (~60%) and metastasis stages (< 40%). DISCUSSION The survival rates in the present single center study are higher than the rates reported from multi-center studies although same chemotherapy protocols were used and no substantially difference are apparent for patient population. CONCLUSIONS Based on the present data we re-emphasize that patients with Ewing sarcoma receive appropriate treatment in a large and qualified center particularly considering the survival rates. In addition, our data underline that a close collaboration between the oncological team and the experienced surgeon is crucial for patient's care. Key words: Ewing sarcoma, survival rate, single center, prognostic factors, chemotherapy, surgery, multi center, single center.

Background: To examine national imaging strategies regarding the use of F-18-FDG PET-CT in patients with Ewing sarcoma and study factors that might influence the use of PET-CT, such as tumour biology (Picci grade of operation specimen), clinical disease stage and age., Methods: We examined the medical records including pathology and imaging of all patients below 30 years diagnosed with Ewing sarcoma in Norway in 2005-2012., Results: Of 61 patients treated at one of the two national sarcoma treatment service centres (Oslo: 35, Bergen: 26), 29 patients had localized disease, 8 had tumour extending to organs nearby and 24 had metastases. Among 35 operated patients with neoadjuvant chemotherapy, 15 had Picci grades II and III (good responders) and 20 grade I (poor responders). We found a significant difference in the use of PET-CT (Oslo/Bergen 0·9 versus 2·0 scans per patient, P = 0·010) and in the use of MRI (Oslo/Bergen: eight versus 13, P = 0·006). No differences were proven for ultrasound, radiography, CT or skeletal scintigraphy. The number of PET-CTs was associated with clinical disease stage at diagnosis (P = 0·041) but not with Picci grade or age. The number of PET studies was not correlated to the number of MR studies., Conclusions: The use of PET-CT in children and young adults diagnosed with Ewing sarcoma in Norway during 2005-2012 at the two national sarcoma treatment service centres differed significantly. The use of PET-CT imaging was related to the clinical disease stage at diagnosis but unrelated to patient age and tumour biology (Picci grade)., (© 2015 Scandinavian Society of Clinical Physiology and Nuclear Medicine. Published by John Wiley & Sons Ltd.)

Despite the advances in oncology, the survival of children with Ewing Sarcoma metastatic at diagnosis continues to be 27% 3-year event-free survival and 34% 3-year overall survival. In other words, 7 of 10 children die within 3 years of their initial diagnosis despite intense chemotherapy, local treatment (radiation/surgery), and/or high dose busulfan-melphalan and autologous stem-cell transplantation. A chief contributor to this morbidity and mortality is the difficulty eradicating the tumor using present therapeutic modalities. Despite the extensive surgery, intensive chemotherapy and radiation, those left with a significant bulk of residual tumor relapse within a year of completing treatment. This case report suggests that in children left with a significant tumor burden after completing chemotherapy, a prolonged period of stability can be achieved with biological agents targeting the underlying molecular drivers. In this particular case we used figitumumab, an antibody targeting the insulin-like growth factor type 1 receptor pathway, a documented target in Ewing Sarcoma. Although not curative, these agents provide a better quality of life.

Ewing sarcoma is the second most prevalent malignant primary bone tumor but constitutes only a small proportion of cardiac metastases. We present a case of asymptomatic Ewing sarcoma metastatic to the right ventricle. A 36-year-old man presented for evaluation and resection of a pedunculated right ventricular cardiac tumor. Three years before, he had been diagnosed with translocation-negative Ewing sarcoma, for which he had undergone chemotherapy and amputation of the left leg below the knee. We resected the right ventricular tumor. Analysis of the resected mass supported the diagnosis of metastatic Ewing sarcoma. Postoperative transthoracic echocardiograms showed normal biventricular size and function. One year later, the patient had no recurrence of the sarcoma. In addition to discussing this case, we review the relevant medical literature.

Background: The choice of a local control (LC) modality for Ewing sarcoma (EWS) of the femur is controversial. This study aimed to determine the effect of LC modality on tumor LC and patient outcomes., Methods: The study reviewed the treatment and outcomes for 115 patients who had EWS of the femur treated with similar chemotherapy in three cooperative group trials. Patient outcomes were analyzed according to the LC modality using the log-rank test and the cumulative incidence of local or distant failure using competing risks regression., Results: The median age of the patients was 13 years. The most common tumor location was the proximal femur followed by the mid femur. For 55 patients with available data, the tumor was larger than 8 cm in 29 patients and 8 cm or smaller in 26 patients. For 84 patients (73 %), surgery only was performed, whereas 17 patients (15 %) had surgery plus radiation, and 14 patients (12 %) had radiation only. The 5-year event-free survival (EFS) rate was 65 % (95 % confidence interval [CI], 55-73 %), and the 5-year overall survival (OS) rate was 70 % (95 % CI, 61-78 %). Patient outcomes did not differ significantly according to tumor location within the femur (proximal, mid or distal) or tumor size (<8 vs ≥8 cm). The findings showed no statistically significant differences in EFS, OS, cumulative incidence of local failure, or cumulative incidence of distant failure according to LC modality (surgery, surgery plus radiation, or radiation)., Conclusions: The LC modality did not significantly affect disease outcome for EWS of the femur. Further study of treatment complications and functional outcome may help to define the optimal LC modality., Competing Interests: There are no conflicts of interest.

Background: Ewing sarcoma (ES) is the second most common pediatric malignant bone tumor with a wide spectrum of clinical presentations. Although metastatic disease to the lungs is often the cause of death, isolated lung metastases at diagnosis are not frequent. The specific role of chemotherapy, surgery, and lung radiation has not been clearly defined. We investigated prognostic factors and the impact of the different treatment modalities in a cohort of patients with ES with isolated lung metastases., Materials and Methods: Thirty-eight patients with ES and isolated lung metastases were treated using modern multimodal therapy during the period 2000-2014. According to the imaging characteristics of lung nodules patients were allocated into one of four treatment groups: "0" without nodules, "1" one solitary nodule of <0.5cm or several nodules of <0.3cm, "2" solitary nodule of 0.5-1cm or multiple nodules of 0.3-0.5cm, "3" one pulmonary/pleural nodule of >1cm, or more than one nodule of >0.5cm. Factors predictive of outcome were analyzed. Overall survival was estimated by Kaplan-Meier methods and compared using long-rank test and Cox models., Results: Treatment of the lung metastases was performed in 23 cases (60.5%): twenty patients underwent lung surgery, 6 of them received additional postoperative whole lung radiation; three patients received lung radiation only. Malignant cells were found in all lung nodules of patients from group "3", in 5 (62.5%) patients from group "2", and none of the group "1". There was a correlation between histological response of the primary tumor and outcome. Three-year estimates of EFS and OS were 45.19% and 60.7%, respectively. Patients with good response measured by chest CT had significantly better EFS than patients with poor response (81% vs. 27.66%, respectively, p=0.006)., Conclusions: Metastatectomy may have a role in the treatment of highly selected patients with ES and isolated lung metastases depending on the histologic response to therapy. Further studies are needed to better define the use of surgery and the response-adapted criteria in the upfront management of this population., (Copyright © 2016 Elsevier Inc. All rights reserved.)

Purpose: To evaluate the results of radiotherapy and the prognostic factors affecting local control in nonextremity Ewing sarcomas., Methods: Between 1995 and 2011, 44 patients with nonextremity Ewing sarcomas were treated with radiotherapy. Tumor localizations were pelvis in 23, spine in 13, thoracic region in 5, and cranium in 3 patients. Tumor size was ≥8 cm in 56.8% of patients. Distant metastases were present in 19 of the patients at the time of diagnosis (43.1%). All patients were treated with 12 weeks of neoadjuvant chemotherapy followed by surgery and radiotherapy (45-54 Gy) or radiotherapy alone (54-64.8 Gy). Radiotherapy was applied due to microscopic residue (R1) in 5 patients after the operation and macroscopic tumor in 39 patients (macroscopic residue [R2] and nonresectable tumor)., Results: Median follow-up was 49 months (range 9-195). Local failures developed in 7 patients (15.9%) and local control at 5 years was 81.4%. Local recurrence was detected in 6 patients (6/38) who did not have residual tumor after RT. Progression was detected in 1 patient (1/6) who had residual tumor. All those patients with local failure experienced further distant metastases. Possible prognostic factors such as age (≤17 vs &gt;17), tumor localization, tumor volume (≤8 cm vs &gt;8 cm), and M status at diagnosis (0 vs 1) were not related to local control., Conclusions: Radiotherapy, either alone or adjuvant to surgery, provides local control in 80% of nonextremity Ewing sarcomas and plays an important role in treatment.

Introduction: Local control, either with surgery, radiation (RT) or both, is essential in the management of localised Ewing sarcoma; however, the relative role of RT remains controversial., Methods: Using the Surveillance, Epidemiology, and End Results database, 612 patients treated for non-metastatic skeletal Ewing sarcoma between the years 1988 and 2010 were identified., Results: Median age and follow-up were 13 years (range: 0-21) and 56 months (range: 0-287), respectively. Five-year overall survival (OS) for the cohort was 74.4 ± 2.0%. Patients received surgery alone (51.3%), RT alone (21.6%) or both (27.1%). Patients with skeletal Ewing sarcoma had improved OS with surgery alone compared with other treatments. However, in subset analyses, RT was not inferior to surgery alone for appendicular (5-year OS: 80.0% vs. 79.3%), non-pelvic (84.3% vs. 79.9%) or localised disease (confined to cortex or periosteum; 79.7% vs. 80.6%). After controlling for stage and site, no increase in mortality was observed with RT versus surgery alone (hazard ratio = 0.77 (95% confidence interval: 0.49-1.19))., Conclusions: In regard to survival, RT did not appear to be inferior to surgery alone for most patients, particularly those with disease at favourable sites (localised, appendicular, non-pelvic). In select patients with Ewing sarcoma, RT may be an appropriate strategy for local control that does not necessarily compromise survival outcomes., (© 2015 The Royal Australian and New Zealand College of Radiologists.)

Background: It is challenging for neurosurgeons to remove huge tumors involving the skull that may possibly invade the dura or intracranial neural tissue. In this situation, excision of the tumor may cause profound blood loss, unexpected opening of the dura, or neurological injury. We describe a technique of craniotomy in a pediatric patient to avoid surgical complications., Methods: A 15-year-old boy had a huge metastatic calvarial Ewing's sarcoma. We removed the tumor successfully with modified concentric craniotomy. First, two oval burr holes are made on both sides of the tumor. The inner craniotomy uses the internal margin of the oval holes, while the outer cut uses the outer margins. The skull bone in between the two craniotomies is removed easily in two pieces and the dura surrounding the tumor can be exposed early in the procedure. In this way, the huge skull tumor can be removed en bloc under direct vision to avoid unwanted complications. Minimal blood and bone loss can be achieved., Results: Blood transfusion was not necessary during the surgery. The patient did not have new neurological symptoms and signs after surgery., Conclusions: The goal of the modified concentric craniotomy is to develop an accessible margin of the dura surrounding the bulky tumor in the early phase of surgery. Blood and bone loss can be reduced significantly.

In this article, we report the case of a woman in whom was found an abdominal mass during pregnancy and who underwent nephrectomy and extraction of the emboli after delivery. The kidney had a volume of 15 × 10 × 8 cm and pathological diagnosis was primary Ewing's sarcoma. The patient was treated with conventional chemotherapy for 1 year after surgery, at which time multiple metastases were found. From this case, we surmise that hormonal changes that occur during pregnancy may accelerate the growth of Ewing's sarcoma of the kidney, suggesting that renal tumors in pregnant women demand serious attention and that anti-cancer treatment should begin as soon as possible., (© 2016 S. Karger AG, Basel.)

Ewing sarcoma (ES) is rare in Japanese people, and only 30-40 patients develop the disease annually. To diagnose ES, molecular techniques that aim to detect characteristic fusion genes are commonly used in combination with conventional histological and immunohistochemical examinations. The treatment strategy for ES is characterized by multi-disciplinary collaboration between pediatric oncologists, medical oncologists, radiation oncologists, and orthopedic surgeons. In recent years, numerous large-scale national or international multi-institutional studies of ES have been performed. Pre- and postoperative intensive systemic chemotherapy with multiple anticancer drugs is the standard treatment method for ES. Depending on the obtained surgical margin, postoperative radiation might also be performed. If preoperative radiological examinations indicate that surgical excision would be difficult, preoperative radiation can be administered. As the treatment outcomes of ES have improved, late complications and secondary malignancies have become a problem. After treatment, patients with ES require very long-term follow-up in order to detect secondary malignancies and growth-related musculoskeletal complications.

Ewing's Sarcoma (ES) is a rare malignant tumor that commonly arises from skeletal bone but rarely has an extraskeletal origin. Intradural ES is rare in childhood and adulthood. Intradural metastasis is very rarely encountered in clinical observations. There are only two reports of intradural ES skip metastasis in the literature to date. Here we present the case of a 39-year-old female who was admitted to our hospital with complaints of left upper limb pain and numbness for one year. Cervical magnetic resonance imaging showed a C4-C6 primary intradural and extramedullary Ewing's sarcoma. Skip metastasis to cauda equina was observed three years following the first surgery and chemoradiotherapy.

Background: This retrospective multicenter study assessed the clinical, radiological and pathological presentation, treatment and outcome of 26 patients with Ewing-like sarcoma harboring BCOR-CCNB3 gene fusion transcript. Tumor samples had been collected between 1994 and April 2012., Procedure: Eligibility criteria included assessment of a BCOR-CCNB3 transcript-positive tumor after molecular analysis and availability of minimal clinical and pathological data. Radiological data were also retrieved when possible. Data were analyzed by descriptive statistics and methods for survival analysis., Results: Median age at diagnosis was 13.1 years (5.9 to 25.6 years). Most patients (24/26) had localized tumors. All tumors but five were localized to bone. CCNB3 immunochemistry showed strong nuclear staining on all samples. No specific radiological features were found. Most patients received chemotherapy (15 according to protocols designed for Ewing tumors), before and/or after local treatment (surgery and/or radiotherapy, with 46.2% receiving both). Local and metastatic relapses were of poor prognosis. Induction chemotherapy and treatment according to an Ewing protocol might influence survival for patients with localized tumors. Sixteen patients are alive in complete remission with a median follow-up of 86 months. Five year overall survival and disease-free survival were respectively 76.5% (95% CI, 58%-95%) and 67.9% (95% CI, 48%-88%)., Conclusions: BCOR-CCNB3 transcript-positive Ewing-like sarcoma diagnosis should be discussed for a transcript-negative small round cell sarcoma in a child, adolescent or young adult patient. Diagnosis needs to be stated through CCNB3 immunochemistry or transcript identification. The exquisite chemosensitivity of these tumors should encourage the use of polychemotherapy for appropriate care, associated with best local tumor control., (© 2014 Wiley Periodicals, Inc.)

Background: Data on extraosseous Ewing sarcoma (EES) with uniform chemotherapy protocol are minimal. We aimed to examine this aspect in our patients, identify prognostic factors and compare the same with osseous Ewing sarcoma., Procedures: A single institutional data review of patients with EES treated between June 2003 and November 2011 with uniform chemotherapy and evaluated on intent-to-treat analysis was done., Results: Of 374 patients with Ewing sarcoma, 60 (16%) were EES with median age 16 years; 20 (33%) had metastases. After median follow-up of 25 months (range: 1.7-104.4), 5-year event free survival (EFS), OS, and local-control-rate were 47.1 ± 7.9%, 61.6 ± 7.8%, and 77.9 ± 8.6%, respectively for entire EES cohort. In multivariate analysis, hemoglobin ≤ 10 g/dl (P = 0.03), and white blood cell count (WBC) >11 × 10(9) /L (P = 0.009) predicted inferior EFS for the entire EES cohort. Low hemoglobin (P = 0.05) and high LDH (P = 0.01) predicted inferior OS for the entire EES cohort on multivariate analysis. As compared to the cohort of skeletal primary (n = 314), higher proportion of patients underwent surgery in the cohort of EES (P =  .003); EFS (P = 0.004) and OS (P = 0.08) were superior for patients with EES than patients with skeletal Ewing sarcoma., Conclusion: These data of EES suggests that low hemoglobin and high WBC count adversely affect EFS. Overall outcome was significantly better for EES than skeletal primary tumors., (© 2014 Wiley Periodicals, Inc.)

BCOR-CCNB3 fusion transcripts resulting from an X-chromosomal paracentric inversion were recently identified in a series of unclassifiable soft tissue and bone sarcomas with Ewing sarcoma-like morphology. The morphologic and clinical features of these sarcomas are, as yet, not well characterized. Here we describe the clinicopathologic features of 10 cases of BCOR-CCNB3 sarcoma and compare their clinical course with typical Ewing sarcoma. Nine of 10 patients were male, and all were 11 to 18 years of age. Seven tumors were located in the bone and 3 in the deep soft tissues. The histomorphologic spectrum was quite wide, with 7 tumors predominately showing small primitive cell morphology with angulated nuclei simulating so-called atypical Ewing sarcoma and 3 predominately showing spindle cell morphology. Recurrent and metastatic lesions showed increased cellularity and marked pleomorphism. Immunohistochemistry showed expression of CCNB3 (100%), bcl2 (90%), CD99 (60%), and CD117 (60%). Reverse transcription polymerase chain reaction for BCOR-CCNB3 fusion transcripts was positive in all 9 cases, which yielded sufficient extracted RNA. Five- and 10-year survival rates were 75% and 56%, respectively. BCOR-CCNB3 sarcomas located in axial skeleton and soft tissues showed a significantly shorter survival. The Ewing sarcoma overall survival was not statistically different, although there was a trend for longer survival of patients with BCOR-CCNB3 sarcomas in the extremities. In conclusion, this study provides a detailed description of the histologic spectrum, immunohistochemical features, and clinical characteristic of BCOR-CCNB3 sarcoma justifying distinction from Ewing sarcoma with its typical EWS/FUS-ETS translocations. Ideally immunohistochemistry is used in combination with reverse transcription polymerase chain reaction for definitive diagnosis.

Ewing sarcoma (EWS) is a primary bone tumor that most often occurs in the long bones of young patients. EWS is typically an aggressive tumor that is highly sensitive to radiation therapy; recurrences often occur, usually within a year of treatment. We present a case of EWS that first presented in a patient at the age of 40 with extraosseous disease. The patient was treated initially with radiation and surgery. Over the following 36-year period, the tumor recurred once and metastasized twice. The morphologic, immunohistochemical, and cytogenetic features of this tumor were typical of EWS, and the tumor was highly responsive to radiation therapy. The unusually prolonged course in this patient demonstrates significant heterogeneity in the biological behavior of EWS, and the importance of randomized trials in cancer therapy.