Ewing Sarcoma Research Articles

Real-world experiences in patients with Ewing sarcoma treated at a specialist centre in Turkey

ObjectivesThe present study evaluates the clinical outcomes of children, adolescents and adults with Ewing sarcoma and identifies the prognostic factors. MethodsIncluded in the study were 222 pediatric and adult patients diagnosed with Ewing sarcoma (EwS) who were followed up between 1992 and 2019, and whose data were analyzed retrospectively. ResultsThe median age of 131 male and 91 female patients included in the study was 13 (1–64). The median follow-up duration of the survivors was 79 months (range, 11–182 months). The 3-year EFS rate of the 222 patients was 34 % (Confidence Interval (CI) (0.158–0.242 %) and the OS rate was 54 % (CI, 0.289–0.590 %). For the non-metastatic patients, the 3-year EFS rate was 47 % and the OS was 68 %, while for the metastatic patients the 3-year EFS rate was 13 % and the OS was 30 %. Of the patient sample, 81 (36, 5 %) survived, of whom 72 were continuously free of disease while the disease persisted in nine, and three developed a secondary neoplasm (2 of whom subsequently died while one survived disease-free). Of the 129 patients who relapsed with metastases and/or local recurrence, eight survived and are disease-free, nine are alive with uncontrolled disease; five were lost to follow-up and 107 died. ConclusionThe findings of the present study suggest metastatic disease at presentation and positive margins after surgery to be of prognostic significance in EwS. Disruptions in aggressive local treatments may reduce the chances of cure in EwS.

Undifferentiated Round Cell Sarcoma With CRTC1::SS18 Fusion: Expanding Clinicopathologic Features of a Rare Translocation Sarcoma With Prominent Desmoplastic Stroma

Undifferentiated round cell sarcomas (URCS) represent a diverse group of tumors, including conventional Ewing sarcoma, round cell sarcoma with EWSR1/FUS–non-ETS fusions, CIC-rearranged sarcoma, and sarcoma with BCOR alterations. Since 2018, 3 cases of URCS with a novel CRTC1::SS18 gene fusion have been reported in the literature. Herein, we report 3 additional cases of CRTC1::SS18 sarcoma, thereby doubling the number of described cases and expanding the clinicopathologic features of this rare translocation sarcoma. Together with the previously reported cases, we show that the male-to-female ratio is 1:2 with a median age of 34 years (range, 12-42 years). Tumors occurred primarily in intramuscular locations involving the lower extremity. Histologically, all tumors contained uniform round-to-epithelioid cells with a moderate amount of eosinophilic cytoplasm growing in sheets and nests with prominent desmoplastic stroma reminiscent of desmoplastic small round cell tumor. Immunohistochemical results were nonspecific, demonstrating variable expression of CD99 (patchy), ALK, GATA3, and cyclin D1. RNA sequencing revealed CRTC1::SS18 gene fusions in all cases, involving exons 1 to 2 of CRTC1 (the 5′ partner gene) on chromosome 19 and either exon 2 or exon 4 of SS18 (the 3′ partner gene) on chromosome 18. The clinical course was variable. Although 1 previously reported case demonstrated aggressive behavior with a fatal outcome, 2 others had a relatively indolent course with gradual growth for 6 to 7 years prior to resection. Two cases developed metastatic disease, including 1 case with bilateral lung metastasis and 1 with locoregional spread to a lymph node. By analyzing the clinicopathologic features, we aimed to improve recognition of this rare translocation sarcoma to better understand its biologic potential, optimize patient management, and expand the current classification of URCS.

Neurotrophic tyrosine receptor kinase gene fusions in adult and pediatric patients with solid tumors: a clinicogenomic biobank and record linkage study of expression frequency and patient characteristics from Finland.

Neurotrophic tyrosine receptor kinase (NTRK) gene fusions are oncogenic drivers. Using the Auria Biobank in Finland, we aimed to identify and characterize patients with these gene fusions, and describe their clinical and tumor characteristics, treatments received, and outcomes. We evaluated pediatrics with any solid tumor type and adults with colorectal cancer (CRC), non-small cell lung cancer (NSCLC), sarcoma, or salivary gland cancer. We determined tropomyosin receptor kinase (TRK) protein expression by pan-TRK immunohistochemistry (IHC) staining of tumor samples from the Auria Biobank, scored by a certified pathologist. NTRK gene fusion was confirmed by next generation sequencing (NGS). All 2,059 patients were followed-up starting 1 year before their cancer diagnosis. Frequency of NTRK gene fusion tumors was 3.1% (4/127) in pediatrics, 0.7% (8/1,151) for CRC, 0.3% (1/288) for NSCLC, 0.9% (1/114) for salivary gland cancer, and 0% (0/379) for sarcoma. Among pediatrics there was one case each of fibrosarcoma (TPM3::NTRK1), Ewing's sarcoma (LPPR1::NTRK2), primitive neuroectodermal tumor (DAB2IP::NTRK2), and papillary thyroid carcinoma (RAD51B::NTRK3). Among CRC patients, six harbored tumors with NTRK1 fusions (three fused with TPM3), one harbored a NTRK3::GABRG1 fusion, and the other a NTRK2::FXN/LPPR1 fusion. Microsatellite instability was higher in CRC patients with NTRK gene fusion tumors versus wild-type tumors (50.0% vs. 4.4%). Other detected fusions were SGCZ::NTRK3 (NSCLC) and ETV6::NTRK3 (salivary gland cancer). Four patients (three CRC, one NSCLC) received chemotherapy; one patient (with CRC) received radiotherapy. NTRK gene fusions are rare in adult CRC, NSCLC, salivary tumors, sarcoma, and pediatric solid tumors.

P-346 A systematic review of the gonadotoxicity of osteoscarcoma and Ewinǵs sarcoma chemotherapies in postpubertal females and males

Abstract Study question What is the postpubertal gonadotoxicity of osteosarcoma (OS) and Ewing’s sarcoma (ES) chemotherapies to better counsel females and males about the risk of infertility? Summary answer Limited data indicate a risk of infertility in OS in 5.1% of females and 52.2% of males and in ES in 13.0% and 89.5% respectively. What is known already Data on the gonadotoxicity of different chemotherapies are essential to better advise young women and men about the risk of treatment-related infertility and to better assess the need for fertility preservation measures prior to cancer treatment. Such data specific to bone-cancer have not yet been systematically reviewed. This review is part of the FertiTOX project (www.fertitox.com) which aims to close the gap of data regarding gonadotoxicity of cancer therapies to enable more accurate counselling regarding fertility preservation. Study design, size, duration A systematic review was conducted to address the issue of gonadotoxicity of bone-cancer specific chemotherapies. Combined search topics included 1) bone-cancer, 2) cancer therapies and 3) fertility parameters after cancer therapy. All relevant documents published between 09/2000 and 08/2022 from the information sources MEDLINE, Embase, and Cochrane Library were included. Participants/materials, setting, methods Only post-pubertal women and men aged < 40 years without recurrent or metastatic disease were included. Due to the inconsistent description of post-treatment fertility parameters, the parameter “suspected infertility” was introduced to summarise and interpret the results. “Suspected infertility” was defined as follows: in women, any menstrual cycle disorder, gonadotropin or anti-mullerian hormone outside the reference range and a diagnosis of premature ovarian failure; in men, the presence of azoospermia or oligozoospermia. Main results and the role of chance A total of 11 out of 831 trials were included in the review. All studies were registry or observational studies. The rate of suspected infertility varied considerably in both OS and ES. Suspected infertility was found in 10/190 (5.1%, range 0-66%) female patients with OS (6 studies), 24/46 (52.2%, range 46-100%) male patients with OS (3 studies), 18/138 (13.0%, range 3-18%) female patients with ES (3 studies) and 34/38 (89.5%) male patients with ES (1 study). It was not possible to calculate the risk associated with specific chemotherapies. The risk of suspected infertility tended to be higher in ES, where all (100%) patients received alkylating chemotherapy, compared with 40% of women and 90% of men in OS. In both OS and ES, the overall rate of suspected infertility appeared to be higher in men than in women. Limitations, reasons for caution The limited data and heterogeneity of fertility-related outcomes in most trials made it necessary to define the rather vague outcome “suspected infertility”. Wider implications of the findings Our data suggest a moderate to high risk of infertility due to chemotherapies in bone cancer. This appears to be more pronounced in males than in females, although precise information cannot be given due to limited data. However, even though the study emphasizes the importance to consider fertility preservation measures. Trial registration number not applicable

Open-Label, Multicenter, Phase I/II, First-in-Human Trial of TK216: A First-Generation EWS::FLI1 Fusion Protein Antagonist in Ewing Sarcoma.

Ewing Sarcoma (ES), a rare cancer with a pathognomonic translocation resulting in the Ewing sarcoma gene (EWS)::FLI1 oncoprotein, has a poor prognosis in the relapsed/refractory (R/R) setting. Tokalas (TK)216 was designed to bind EWS::FLI1 proteins directly, disrupt protein-protein interactions, and inhibit transcription factor function. TK216 plus vincristine showed synergistic activity in preclinical tumor models. To our knowledge, we report the results of a first-in-class, first-in-human phase I/II trial of TK216 in R/R ES. TK216 was administered intravenously as a continuous infusion to patients with R/R ES in 11 cohorts. The dosing duration of 7 days was later extended to 10, 14, and 28 days. Vincristine could be added on day 1 after cycle 2, per investigators' choice. The trial used a 3 + 3 design with an expansion cohort at the recommended phase II dose (RP2D). A total of 85 patients with a median age of 27 years (range, 11-77) were enrolled. The maximum tolerated dose for the 14-day infusion of TK216, 200 mg/m2 once daily, was determined in cohort 9 and selected as the RP2D. The median previous number of systemic therapies regimens was three (range, 1-10). The most frequent-related adverse events in patients treated at the RP2D included neutropenia (44.7%), anemia (29.4%), leukopenia (29.4%), febrile neutropenia (15.3%), thrombocytopenia (11.8%), and infections (17.6%). In cohorts 9 and 10, two patients had a complete response, one had a partial response, and 14 had stable disease; the 6-month progression-free survival was 11.9%. There were no responses among the eight patients in cohort 11. TK216 administered as 14-day continuous infusion with or without vincristine was well tolerated and showed limited activity at the RP2D in R/R ES.

High Expression of miR-218-5p in the Peripheral Blood Stream and Tumor Tissues of Pediatric Patients with Sarcomas.

Sarcomas are malignant tumors that may metastasize and the course of the disease is highly aggressive in children and young adults. Because of the rare incidence of sarcomas and the heterogeneity of tumors, there is a need for non-invasive diagnostic and prognostic biomarkers in sarcomas. The aim of the study was to investigate the level of miR-218-5p in peripheral blood and tumor tissue samples of Ewing's sarcoma, osteosarcoma, spindle cell sarcoma patients, and healthy controls, and assessed whether the corresponding molecule was a diagnostic and prognostic biomarker. The study was performed patients (n = 22) diagnosed and treated with Ewing's sarcoma and osteosarcoma and in a control group of 22 healthy children who were matched for age, gender, and ethnicity with the patient group. The expression level of miR-218-5p in RNA samples from peripheral blood and tissue samples were analyzed using the RT-PCR and the expression level of miR-218-5p was evaluated by comparison with the levels in patients and healthy controls. The expression level of miR-218-5p was found to be statistically higher (3.33-fold, p = 0.006) in pediatric patients with sarcomas and when the target genes of miR-218-5p were investigated using the bioinformatics tools, the miR-218-5p was found as an important miRNA in cancer. In this study, the miR-218-5p was shown for the first time to have been highly expressed in the peripheral blood and tumor tissue of sarcoma patients. The results suggest that miR-218-5p can be used as a diagnostic and prognostic biomarker in sarcomas and will be evaluated as an important therapeutic target.

Ewings sarcoma in pediatric population of North India: Demographics, outcome & prognostic factors

BackgroundEwings sarcoma is relatively rare and accounts for a 3–4% of childhood cancer. The data of Ewings sarcoma is scarce in North India and so the study was planned to find out the demographics, outcome and prognostic factors of Ewings sarcoma. MethodsThis is a retrospective study conducted in the Department of Pediatrics, Pediatric Oncology unit at a tertiary care centre (KGMC, Lucknow) in North India. All patients of age 1–16 years with biopsy and IHC proven Ewings sarcoma during 2015–2020 were included in the study. Parameters were noted and follow up was done till December 2021. Statistical analysis was done by Microsoft Excel and GraphPad Prism 10. Overall survival was assessed using Kaplan Meir Survival Analysis. P value < 0.05 was considered significant. Results75 patients i.e.4.1 % of the total were diagnosed with ES. Median age of patients was 10 years. 37.35 % had metastasis at presentation. 32 % were defaulters (abandoned and not taking treatment). Extremity ES constituted 46.7 % of the patient. 29.4 % patients relapsed. The overall survival of the whole cohort was 23.5 % and OS of localised disease was 42.3 %. OS of patients with respect to various sites failed to show any significance. Staging of disease have shown to be affecting outcome. ConclusionProportion of Ewings sarcoma was in accordance with the world's data but the survival outcome was low at our centre primarily due to delayed presentation translating to metastatic disease at diagnosis and abandonment issues along with defaults in treatment. Conducting focussed group discussions, awareness sessions, caregivers counselling and educating them about disease might help in curbing these factors.

Pediatric Axial Ewing Sarcoma: A Retrospective Population-Based Survival Analysis.

Ewing sarcomas of the axial skeleton represent a notable challenge for clinicians because of their aggressive presentation and tendency to obstruct neurovascular structures; however, little data exist regarding axial tumors in children. This study is the first population-based analysis assessing treatment regimens for axial Ewing sarcomas and their effects on cancer-specific survival and overall survival (OS). Data from 2004 to 2019 were collected for all patients aged 1 to 24 years from the Surveillance, Epidemiology, and End Results (SEER) database. Primary groups included pelvic tumors, thoracic tumors, and vertebral tumors. Chi-squared and Kaplan-Meier tests were used to assess associations between demographic variables, clinical and treatment characteristics, and patient survival. Pelvic tumors were most common, and 49.7% received chemotherapy/radiation. Vertebral tumors were least common, and 56.7% received chemotherapy/surgery/radiation. 53.5% of thoracic tumors received chemotherapy/surgery. Surgery was most common for thoracic tumors (80.2%) and rare for pelvic tumors (38.9%). Radiation therapy was most common for vertebral tumors (83.6%) and least common for thoracic tumors (36.0%). Pelvic tumors exhibited the lowest OS (1-year, 5-year, and 10-year OS: 96%, 70%, and 59%), followed by thoracic tumors (1-year, 5-year, and 10-year OS: 97%, 79%, and 66%) and vertebral tumors (1-year, 5-year, and 10-year OS: 92%, 77%, and 68%). This study underpins the importance of both early detection and chemotherapy-based multimodal therapy in the treatment of axial Ewing sarcoma in a pediatric population. A comparatively large decline in OS was observed between 5 and 10 years for patients with thoracic tumors, and this cohort's 10-year OS has not improved when compared with a similar SEER cohort from 1973 to 2011. Despite a growing body of research supporting definitive radiation therapy, a notable portion of patients with pelvic Ewing sarcoma did not receive radiation, representing an unmet need for this population.

Human EWS-FLI protein levels and neomorphic functions show a complex, function-specific dose-response relationship in Drosophila.

Ewing sarcoma (EwS) is a cancer that arises in the bones and soft tissues, typically driven by the Ewing's sarcoma breakpoint region 1-Friend leukemia virus integration 1 (EWS-FLI) oncogene. Implementation of genetically modified animal models of EwS has proved difficult largely owing to EWS-FLI's high toxicity. The EWS-FLI1FS frameshift variant that circumvents toxicity but is still able to perform key oncogenic functions provided the first study model in Drosophila. However, the quest for Drosophila lines expressing full-length, unmodified EWS-FLI remained open. Here, we show that EWS-FLI1FS's lower toxicity is owed to reduced protein levels caused by its frameshifted C-terminal peptide, and report new strategies through which we have generated Drosophila lines that express full-length, unmodified EWS-FLI. Using these lines, we have found that the upregulation of transcription from GGAA-microsatellites (GGAAμSats) presents a positive linear correlation within a wide range of EWS-FLI protein concentrations. In contrast, rather counterintuitively, GGAAμSats-independent transcriptomic dysregulation presents relatively minor differences across the same range, suggesting that GGAAμSat-dependent and -independent transcriptional upregulation present different kinetics of response with regards to changing EWS-FLI protein concentration. Our results underpin the functional relevance of varying EWS-FLI expression levels and provide experimental tools to investigate, in Drosophila, the effect of the EWS-FLI 'high' and 'low' states that have been reported and are suspected to be important for EwS in humans.

To determine the overall survival rate of patients with Ewing sarcoma after pre and post radiation treatment

To determine the overall survival rate of patients with Ewing sarcoma after pre and post radiation treatment

Unlocking epigenetics for precision treatment of Ewing's sarcoma.

Ewing's sarcoma (EWS) is a highly aggressive malignant bone tumor primarily affecting adolescents and young adults. Despite the efficacy of chemoradiotherapy in some cases, the cure rate for patients with metastatic and recurrent disease remains low. Therefore, there is an urgent need for innovative therapeutic approaches to address the challenges associated with EWS treatment. Epigenetic regulation, a crucial factor in physiological processes, plays a significant role in controlling cell proliferation, maintaining gene integrity, and regulating transcription. Recent studies highlight the importance of abnormal epigenetic regulation in the initiation and progression of EWS. A comprehensive understanding of the intricate interactions between EWS and aberrant epigenetic regulation is essential for advancing clinical drug development. This review aims to provide a comprehensive overview of both epigenetic targets implicated in EWS, integrating various therapeutic modalities to offer innovative perspectives for the clinical diagnosis and treatment of EWS.

Intestinal Ewing Sarcoma Misdiagnosed as an Adnexal Mass in a Young Woman

Intestinal Ewing Sarcoma Misdiagnosed as an Adnexal Mass in a Young Woman

Ewing's Sarcoma of Maxillary Sinus.

Ewing's sarcoma is a small round cell tumor commonly involving long bones. Head and neck involvement is seen less frequently with maxillary sinus being the rarest site. Here we report a case of a12-year-old female patient presented with left side facial swelling for 3 weeks duration which was diffuse and hard on palpation. CT and MRI of Nose & para nasal sinus revealed a mass lesion in the left maxillary sinus infiltrating and eroding the orbital wall and extending intracranially. Biopsy from the lesion revealed Ewing's sarcoma with strong positivity for CD-99 marker. Patient was referred to radiotherapy due to extensive disease at younger age. The CT and MRI along with HPE and IHC markers enables early diagnosis and prompt treatment that leads to better survival and prognosis, as unlike Ewing's sarcoma of long bones, that metastasize early. The combined chemoradiotherapy is now the standard line of treatment along with close follow up for at least 2 years.

Optimizing ATR Inhibition and Cisplatin Synergy in Ewing Sarcoma.

EWSR1::FLI1-mediated dysregulation of cellular machinery opens up potential new avenues for Ewing sarcoma treatment. A recent study demonstrates that pharmacologic ATR kinase inhibition dramatically synergizes with low-dose cisplatin through EWSR1::FLI1-dependent rewiring of transcription, DNA repair, and translation machinery, which could maximize the therapeutic window of the combinatory therapy. See related article by Jess et al., p. 3533.

Co-targeting JAK1/STAT6/GAS6/TAM signaling improves chemotherapy efficacy in Ewing sarcoma

Ewing sarcoma is a pediatric bone and soft tissue tumor treated with chemotherapy, radiation, and surgery. Despite intensive multimodality therapy, ~50% patients eventually relapse and die of the disease due to chemoresistance. Here, using phospho-profiling, we find Ewing sarcoma cells treated with chemotherapeutic agents activate TAM (TYRO3, AXL, MERTK) kinases to augment Akt and ERK signaling facilitating chemoresistance. Mechanistically, chemotherapy-induced JAK1-SQ phosphorylation releases JAK1 pseudokinase domain inhibition allowing for JAK1 activation. This alternative JAK1 activation mechanism leads to STAT6 nuclear translocation triggering transcription and secretion of the TAM kinase ligand GAS6 with autocrine/paracrine consequences. Importantly, pharmacological inhibition of either JAK1 by filgotinib or TAM kinases by UNC2025 sensitizes Ewing sarcoma to chemotherapy in vitro and in vivo. Excitingly, the TAM kinase inhibitor MRX-2843 currently in human clinical trials to treat AML and advanced solid tumors, enhances chemotherapy efficacy to further suppress Ewing sarcoma tumor growth in vivo. Our findings reveal an Ewing sarcoma chemoresistance mechanism with an immediate translational value.

Effectiveness and safety of primary prophylaxis with G-CSF for patients with Ewing sarcomas: a systematic review for the Clinical Practice Guidelines for the Use of G-CSF 2022 of the Japan Society of Clinical Oncology.

Multidrug chemotherapy for Ewing sarcoma can lead to severe myelosuppression. We proposed two clinical questions (CQ): CQ #1, "Does primary prophylaxis with G-CSF benefit chemotherapy for Ewing sarcoma?" and CQ #2, "Does G-CSF-based intensified chemotherapy improve Ewing sarcoma treatment outcomes?". A comprehensive literature search was conducted in PubMed, Cochrane Library, and Ichushi web databases, including English and Japanese articles published from 1990 to 2019. Two reviewers assessed the extracted papers and analyzed overall survival (OS), febrile neutropenia (FN) incidence, infection-related mortality, quality of life (QOL), and pain. Twenty-five English and five Japanese articles were identified for CQ #1. After screening, a cohort study of vincristine, ifosfamide, doxorubicin, and etoposide chemotherapy with 851 patients was selected. Incidence of FN was 60.8% with G-CSF and 65.8% without; statistical tests were not conducted. Data on OS, infection-related mortality, QOL, or pain was unavailable. Consequently, CQ #1 was redefined as a future research question. As for CQ #2, we found two English and five Japanese papers, of which one high-quality randomized controlled trial on G-CSF use in intensified chemotherapy was included. This trial showed trends toward lower mortality and a significant increase in event-free survival for 2-week interval regimen with the G-CSF primary prophylactic use compared with 3-week interval. This review indicated that G-CSF's efficacy as primary prophylaxis in Ewing sarcoma, except in children, is uncertain despite its common use. This review tentatively endorses intensified chemotherapy with G-CSF primary prophylaxis for Ewing sarcoma.

A case of extraosseous Ewing sarcoma diagnosed by EUS-FNA for a pancreatic tail mass

A case of extraosseous Ewing sarcoma diagnosed by EUS-FNA for a pancreatic tail mass

Myeloid sarcoma: Experience from a tertiary care center in southern India - A series of eight unusual cases.

Myeloid sarcoma (MS) is a tumor mass comprising myeloid blasts with or without maturation occurring in any site other than bone marrow. It is a rare and distinct clinical presentation of myeloid neoplasm. This is a retrospective study over 7 years (2015-2022) comprising a series of eight cases, which includes clinical details, morphology, immunohistochemistry (IHC) markers, cytogenetics, and molecular details. These cases showed up as an isolated MS (3/8), as an initial clinical presentation in acute myeloid leukemia (1/8), as acute myeloid leukemia (1/8), as a disease progression in primary myelofibrosis (1/8), as chronic myeloid leukemia (1/8), and as BCR-ABL-negative myelodysplastic syndrome/myeloproliferative neoplasm (1/8). One of the three isolated MS was incorrectly identified as having Ewing's sarcoma. One case each presented at the cervical lymph node, mediastinum, skin, sacral soft tissue, maxillary sinus, and perinephric fat, and two cases presented at the hard palate. Four of the cases in our study were clinically thought of as lymphoma/sarcoma, which was a major diagnostic challenge. All but one case succumbed to their disease. Without adequate clinical history and appropriate use of ancillary techniques such as IHC in tissue biopsies, flow cytometry, cytogenetics, and molecular studies, these cases have a high chance of being misdiagnosed as non-Hodgkin lymphoma, small round blue cell tumor, or undifferentiated carcinomas, which can complicate patient management and prognosis.

Characterization of transcriptional heterogeneity and novel therapeutic targets using single cell RNA-sequencing of primary and circulating Ewing sarcoma cells.

Ewing sarcoma is the second most common bone cancer in children, accounting for 2% of pediatric cancer diagnoses. Patients who present with metastatic disease at the time of diagnosis have a dismal prognosis, compared to the >70% 5-year survival of those with localized disease. Here, we utilized single cell RNA-sequencing to characterize the transcriptional landscape of primary Ewing sarcoma tumors and surrounding tumor microenvironment (TME). Copy-number analysis identified subclonal evolution within patients prior to treatment. Primary tumor samples demonstrate a heterogenous transcriptional landscape with several conserved gene expression programs, including those composed of genes related to proliferation and EWS targets. Single cell RNA-sequencing and immunofluorescence of circulating tumor cells at the time of diagnosis identified TSPAN8 as a novel therapeutic target.

ETMR-29. PRIMARY CNS SARCOMAS IN CHILDREN AND ADOLESCENTS: EXPERIENCE OF AN INSTITUTION

Abstract BACKGROUND Soft tissue sarcomas represent 6% of childhood cancers, less than 0.2% of CNS tumors are primary intracranial sarcomas. Their origin is pluripotential primitive mesenchymal cells. OBJECTIVE to evaluate clinical and genetic characteristics and report the experience of a rare CNS tumor. METHODS review of CNS tumors database at IOP/GRAACC/UNIFESP for the period 2008-2024, searching for all types of sarcomas that involved the CNS. RESULTS case series included 7 male, 2 female patients; average age at diagnosis 11.3 years. Supratentorial was the most common site of occurrence (66.6%), posterior fossa and intramedulary (2 and 1 cases, respectively) were found. One PF sarcoma presented as a second neoplasm after 2 years finished treatment for medulloblastoma, the other was diagnosed just after metilation. The presenting symptoms varied with tumor location, specially hemiparesis, seizure and headache. Gross total resection was achieved in 7 cases (77.7%), 1 after second look surgery. Histology and immunohistochemistry studies revealed: spinocellular sarcoma, fusocellular and myxoid sarcoma, gliosarcoma, meningeal sarcoma, Ewing sarcoma, condrosarcoma and synovial sarcoma. Work-up excluded other primary tumor origin outside CNS. Analyses for genetic characteristics were performed by Next Generation Sequencing in 6 patients (66.6%) and the following alterations were found: NRAS, TP53, JAK3, NF2, C11orf95-RELA fusion, PDGFRA. Some of these, by now, with no significant meaning for the disease. All patients underwent multimodal treatment. Chemotherapy involved mainly ICE Protocol (55.5%), but also Head Start Protocol and Ewing Sarcoma Protocol. Follow-up ranged from 13 months to 12 years, 90% of patients are alive, 2 (28.5%) dealing with endocrinal issues after focal radiotherapy. The mean overall survival was 61.4 months. CONCLUSION CNS primary sarcomas were mostly observed in the supratentorial region and in older children, with male predilection. Multimodal treatment seems to benefit patients’ outcomes. More patients and longer follow-up periods are needed to further elucidate the biological features of these tumors.