{"entity":{"id":"ewing-sarcoma","kind":"cancer","name":"Ewing sarcoma","aka":[],"tldr":"Ewing sarcoma is a bone and soft-tissue cancer of teenagers driven by a single fusion gene, EWSR1-FLI1. Intensive chemotherapy with surgery or radiation cures most localised cases; disease that has spread at diagnosis, and relapse, remain hard to treat, and no drug against the fusion protein itself has yet succeeded.","summary":"Ewing sarcoma is defined by FET-ETS fusions, EWSR1-FLI1 in ~85% and EWSR1-ERG in ~10%, which act as aberrant transcription factors at GGAA microsatellites; the genome is otherwise quiet (STAG2, CDKN2A, TP53 alterations carry shorter survival). It arises in bone (pelvis, femur, chest wall) or soft tissue in adolescents and young adults.\n\nTreatment is multimodal: interval-compressed VDC/IE (vincristine, doxorubicin, cyclophosphamide alternating with ifosfamide, etoposide) every 2 weeks (AEWS0031), which Euro Ewing 2012 showed superior to VIDE; local control by surgery, radiotherapy or both; and metastatic disease treated with the same backbone plus whole-lung irradiation, with high-dose busulfan-melphalan benefiting selected high-risk patients (Euro-EWING 99 R2). Relapse is treated with irinotecan-temozolomide, high-dose ifosfamide or topotecan-cyclophosphamide, ranked by the rEECur adaptive trial (high-dose ifosfamide best). Targeted attempts (IGF-1R antibodies, TK216 against EWS-FLI1, PARP inhibitors) have not succeeded; lurbinectedin and combinations are in trials.","asOf":"2026-09-08","wikipedia":"https://en.wikipedia.org/wiki/Ewing_sarcoma","links":[{"label":"NCCN Guidelines: Bone Cancer","url":"https://www.nccn.org/guidelines/guidelines-detail?category=1&id=1418"},{"label":"NCI PDQ: Ewing sarcoma","url":"https://www.cancer.gov/types/bone/patient/ewing-treatment-pdq"}],"tags":["gap-fill","paediatric","sarcoma","aya"],"related":["osteosarcoma","rhabdomyosarcoma","chondrosarcoma","synovial-sarcoma"],"cancers":[],"sections":[],"technologies":["cytotoxic-chemotherapy","imrt-igrt","limb-salvage-surgery","proton-therapy","autologous-stem-cell-transplant","protac-degrader","car-t"],"targets":["ewsr1-fli1","tp53","parp"],"drugs":["vincristine","doxorubicin","cyclophosphamide","ifosfamide","etoposide","irinotecan","temozolomide","topotecan","lurbinectedin","docetaxel","tk216"],"companies":["pharmamar","jazz","childrens-oncology-group"],"institutions":[],"pathways":["p53-cell-cycle"],"terms":["gene-fusion","histological-response-induction"],"trials":["ccss","cabone","regobone","sarc028"],"people":[],"bottlenecks":[],"keyPapers":[],"journals":["journal-of-adolescent-and-young-adult-oncology"],"dependsOn":[],"notes":[],"group":"paediatric","burden":"Ewing sarcoma is the second most common bone cancer in children and young adults; ~200-250 cases per year in the US, rare in people of African or East Asian ancestry; survival ~75% localised, ~30% metastatic.","subtypes":["Skeletal Ewing sarcoma","Extraosseous Ewing sarcoma","EWSR1-FLI1 vs EWSR1-ERG fusion","Round cell sarcomas with EWSR1-non-ETS, CIC or BCOR fusions (separate WHO entities)"],"biomarkers":["EWSR1-FLI1 / EWSR1-ERG fusion (FISH, RT-PCR, RNA-seq)","CD99 membranous staining, NKX2-2","Metastatic status (lung vs bone/marrow)","Histologic response to induction","STAG2 loss, TP53 mutation, CDKN2A deletion (shorter survival)","ctDNA fusion detection (emerging)"],"standardOfCare":[{"setting":"Localised","approach":"Interval-compressed VDC/IE ×14 cycles (AEWS0031 / Euro Ewing 2012) with surgery ± radiotherapy (or definitive RT 55.8 Gy) after 6 induction cycles.","refs":["vincristine","doxorubicin","cyclophosphamide","ifosfamide","etoposide","imrt-igrt","limb-salvage-surgery","aews0031"],"guideline":{"nccn":"Category 1","version":"NCCN Guidelines: Bone Cancer","url":"https://www.nccn.org/guidelines/guidelines-detail?category=1&id=1418"}},{"setting":"Metastatic (lung only)","approach":"Same chemotherapy plus whole-lung irradiation; busulfan-melphalan high-dose therapy in selected patients (Euro-EWING 99 R2pulm equivocal).","refs":["vincristine","doxorubicin","cyclophosphamide","ifosfamide","etoposide","autologous-stem-cell-transplant"],"guideline":{"nccn":"Category 2A","version":"NCCN Guidelines: Bone Cancer"}},{"setting":"Metastatic (bone/marrow)","approach":"Chemotherapy with palliative-intent local therapy; survival <20%; trials strongly preferred.","refs":["vincristine","doxorubicin","cyclophosphamide"]},{"setting":"Relapsed","approach":"High-dose ifosfamide (rEECur), irinotecan-temozolomide, topotecan-cyclophosphamide, gemcitabine-docetaxel; local therapy; trials.","refs":["ifosfamide","irinotecan","temozolomide","topotecan","cyclophosphamide"],"guideline":{"nccn":"Category 2A","version":"NCCN Guidelines: Bone Cancer"}}],"stateOfArt":["Interval compression (chemotherapy every 2 rather than 3 weeks) improved survival without new drugs (AEWS0031, Euro Ewing 2012).","rEECur is the first randomised trial in relapsed Ewing sarcoma and ranked four regimens with high-dose ifosfamide on top.","EWSR1-FLI1 is an 'undruggable' transcription factor; degraders, LSD1 inhibitors and menin/EWS-FLI1 interactome drugs are the research directions.","International cooperation (COG, Euro Ewing) is the only way trials complete."],"history":[{"year":1921,"title":"James Ewing describes 'diffuse endothelioma of bone'","refs":[]},{"year":1974,"title":"IESS-I: adjuvant VAC + doxorubicin raises survival from ~10% to ~60%","refs":["vincristine","doxorubicin","cyclophosphamide"]},{"year":1992,"title":"EWSR1-FLI1 fusion cloned (Delattre, Nature)","refs":[]},{"year":2003,"title":"INT-0091: adding ifosfamide-etoposide improves survival (Grier, NEJM)","refs":["ifosfamide","etoposide"]},{"year":2012,"title":"AEWS0031: interval compression improves EFS (Womer, JCO)","refs":[]},{"year":2018,"title":"Euro-EWING 99 R2: busulfan-melphalan benefit in high-risk localised disease","refs":["autologous-stem-cell-transplant"]},{"year":2022,"title":"Euro Ewing 2012: VDC/IE superior to VIDE (Lancet)","refs":[]},{"year":2022,"title":"rEECur: high-dose ifosfamide best of four relapse regimens","refs":["ifosfamide"]}],"pipeline":["lurbinectedin","ifosfamide","car-t","kc1036"],"openProblems":["Metastatic-to-bone and relapsed disease: survival under 20-30%.","EWSR1-FLI1 remains undrugged after 30 years.","Late effects: cardiotoxicity, infertility, secondary leukaemia (etoposide, alkylators), radiation-induced sarcoma.","Ancestry-linked incidence differences (GGAA microsatellite polymorphism) unexplained."],"parent":"sarcoma"},"route":"/cancers/ewing-sarcoma/","neighbours":{"cancer":[{"id":"adamantinoma","kind":"cancer","name":"Adamantinoma of bone","route":"/cancers/adamantinoma/"},{"id":"aya-cancers","kind":"cancer","name":"Adolescent and young adult cancers (ages 15 to 39)","route":"/cancers/aya-cancers/"},{"id":"childhood-cancers","kind":"cancer","name":"Childhood cancers (all types)","route":"/cancers/childhood-cancers/"},{"id":"chondrosarcoma","kind":"cancer","name":"Chondrosarcoma","route":"/cancers/chondrosarcoma/"},{"id":"chordoma","kind":"cancer","name":"Chordoma","route":"/cancers/chordoma/"},{"id":"desmoplastic-small-round-cell-tumour","kind":"cancer","name":"Desmoplastic small round cell tumour","route":"/cancers/desmoplastic-small-round-cell-tumour/"},{"id":"osteosarcoma","kind":"cancer","name":"Osteosarcoma","route":"/cancers/osteosarcoma/"},{"id":"rhabdomyosarcoma","kind":"cancer","name":"Rhabdomyosarcoma","route":"/cancers/rhabdomyosarcoma/"},{"id":"sarcoma","kind":"cancer","name":"Sarcomas (soft tissue, bone, GIST)","route":"/cancers/sarcoma/"},{"id":"synovial-sarcoma","kind":"cancer","name":"Synovial sarcoma","route":"/cancers/synovial-sarcoma/"}],"technology":[{"id":"rejuv-ayac-distinct-group","kind":"technology","name":"Adolescents and young adults: a group with its own cancers, its own gap and its own needs","route":"/technologies/rejuv-ayac-distinct-group/"},{"id":"autologous-stem-cell-transplant","kind":"technology","name":"Autologous stem cell transplant (high-dose therapy)","route":"/technologies/autologous-stem-cell-transplant/"},{"id":"rejuv-paed-breast-after-chest-radiotherapy","kind":"technology","name":"Breast cancer after chest radiotherapy in childhood, and the screening that follows","route":"/technologies/rejuv-paed-breast-after-chest-radiotherapy/"},{"id":"car-t","kind":"technology","name":"CAR-T cell therapy","route":"/technologies/car-t/"},{"id":"cytotoxic-chemotherapy","kind":"technology","name":"Cytotoxic chemotherapy","route":"/technologies/cytotoxic-chemotherapy/"},{"id":"rejuv-paed-fertility-male","kind":"technology","name":"Fertility in boys and young men treated for cancer, including testicular tissue banking","route":"/technologies/rejuv-paed-fertility-male/"},{"id":"rejuv-paed-fertility-female","kind":"technology","name":"Fertility in girls and young women treated for cancer, including ovarian tissue freezing","route":"/technologies/rejuv-paed-fertility-female/"},{"id":"rejuv-ayac-diagnostic-delay","kind":"technology","name":"How long it takes to diagnose cancer in a young person, and what the evidence actually says","route":"/technologies/rejuv-ayac-diagnostic-delay/"},{"id":"rejuv-paed-chronic-disease-burden","kind":"technology","name":"How much illness childhood cancer survivors carry, and at what age","route":"/technologies/rejuv-paed-chronic-disease-burden/"},{"id":"imrt-igrt","kind":"technology","name":"IMRT / IGRT (modern external beam)","route":"/technologies/imrt-igrt/"},{"id":"rejuv-paed-kidneys","kind":"technology","name":"Kidneys after cisplatin, ifosfamide, radiotherapy and nephrectomy in childhood","route":"/technologies/rejuv-paed-kidneys/"},{"id":"rejuv-recon-limb","kind":"technology","name":"Limb salvage, amputation, and the rehabilitation that follows either","route":"/technologies/rejuv-recon-limb/"},{"id":"limb-salvage-surgery","kind":"technology","name":"Limb-salvage surgery and endoprosthetic reconstruction","route":"/technologies/limb-salvage-surgery/"},{"id":"sarcoma-methylation-classifier","kind":"technology","name":"Methylation classifier for sarcomas","route":"/technologies/sarcoma-methylation-classifier/"},{"id":"protac-degrader","kind":"technology","name":"PROTACs & molecular glues (targeted protein degradation)","route":"/technologies/protac-degrader/"},{"id":"proton-therapy","kind":"technology","name":"Proton therapy","route":"/technologies/proton-therapy/"},{"id":"rejuv-paed-second-cancers","kind":"technology","name":"Second cancers after childhood cancer: the risk by treatment, and why it is falling","route":"/technologies/rejuv-paed-second-cancers/"},{"id":"rejuv-ayac-services","kind":"technology","name":"Services built for teenagers and young adults, and what the national evaluation found","route":"/technologies/rejuv-ayac-services/"},{"id":"rejuv-paed-heart","kind":"technology","name":"The heart after anthracyclines and chest radiotherapy in childhood","route":"/technologies/rejuv-paed-heart/"}],"target":[{"id":"cdkn2b","kind":"target","name":"CDKN2B","route":"/targets/cdkn2b/"},{"id":"ewsr1-fli1","kind":"target","name":"EWSR1-FLI1 fusion","route":"/targets/ewsr1-fli1/"},{"id":"igf1r","kind":"target","name":"IGF-1 receptor (IGF1R)","route":"/targets/igf1r/"},{"id":"parp","kind":"target","name":"PARP","route":"/targets/parp/"},{"id":"ptprd","kind":"target","name":"PTPRD","route":"/targets/ptprd/"},{"id":"slfn11","kind":"target","name":"SLFN11","route":"/targets/slfn11/"},{"id":"tp53","kind":"target","name":"TP53","route":"/targets/tp53/"}],"drug":[{"id":"cyclophosphamide","kind":"drug","name":"Cyclophosphamide","route":"/drugs/cyclophosphamide/"},{"id":"dactinomycin","kind":"drug","name":"Dactinomycin (actinomycin D)","route":"/drugs/dactinomycin/"},{"id":"docetaxel","kind":"drug","name":"Docetaxel","route":"/drugs/docetaxel/"},{"id":"doxorubicin","kind":"drug","name":"Doxorubicin","route":"/drugs/doxorubicin/"},{"id":"etoposide","kind":"drug","name":"Etoposide","route":"/drugs/etoposide/"},{"id":"ifosfamide","kind":"drug","name":"Ifosfamide","route":"/drugs/ifosfamide/"},{"id":"irinotecan","kind":"drug","name":"Irinotecan (and liposomal irinotecan)","route":"/drugs/irinotecan/"},{"id":"kc1036","kind":"drug","name":"KC1036","route":"/drugs/kc1036/"},{"id":"lurbinectedin","kind":"drug","name":"Lurbinectedin","route":"/drugs/lurbinectedin/"},{"id":"plicamycin","kind":"drug","name":"Plicamycin","route":"/drugs/plicamycin/"},{"id":"temozolomide","kind":"drug","name":"Temozolomide","route":"/drugs/temozolomide/"},{"id":"tk216","kind":"drug","name":"TK216","route":"/drugs/tk216/"},{"id":"topotecan","kind":"drug","name":"Topotecan","route":"/drugs/topotecan/"},{"id":"vincristine","kind":"drug","name":"Vincristine","route":"/drugs/vincristine/"}],"company":[{"id":"actuate-therapeutics","kind":"company","name":"Actuate Therapeutics","route":"/companies/actuate-therapeutics/"},{"id":"childrens-oncology-group","kind":"company","name":"Children's Oncology Group (COG)","route":"/companies/childrens-oncology-group/"},{"id":"french-sarcoma-group","kind":"company","name":"French Sarcoma Group","route":"/companies/french-sarcoma-group/"},{"id":"jazz","kind":"company","name":"Jazz Pharmaceuticals","route":"/companies/jazz/"},{"id":"pharmamar","kind":"company","name":"PharmaMar","route":"/companies/pharmamar/"},{"id":"sarc","kind":"company","name":"SARC (Sarcoma Alliance for Research through Collaboration)","route":"/companies/sarc/"}],"pathway":[{"id":"p53-cell-cycle","kind":"pathway","name":"p53 / RB / cell-cycle checkpoint","route":"/pathways/p53-cell-cycle/"},{"id":"transcription-addiction","kind":"pathway","name":"Transcriptional machinery & addiction","route":"/pathways/transcription-addiction/"}],"term":[{"id":"aya-oncology","kind":"term","name":"Adolescent and young adult (AYA) oncology","route":"/terms/aya-oncology/"},{"id":"cdkn2a-homozygous-deletion","kind":"term","name":"CDKN2A/B homozygous deletion","route":"/terms/cdkn2a-homozygous-deletion/"},{"id":"gene-fusion","kind":"term","name":"Gene fusion","route":"/terms/gene-fusion/"},{"id":"histological-response-induction","kind":"term","name":"Histological response to induction chemotherapy (osteosarcoma and Ewing sarcoma)","route":"/terms/histological-response-induction/"}],"trial":[{"id":"nct06564272","kind":"trial","name":"A Study of KC1036 in Adolescents With Advanced Ewing Sarcoma","route":"/trials/nct06564272/"},{"id":"aews0031","kind":"trial","name":"AEWS0031","route":"/trials/aews0031/"},{"id":"cabone","kind":"trial","name":"CABONE","route":"/trials/cabone/"},{"id":"nct05440786","kind":"trial","name":"CAMPFIRE: A Study of Abemaciclib (LY2835219) in Participants With Ewing's Sarcoma","route":"/trials/nct05440786/"},{"id":"ccss","kind":"trial","name":"Childhood Cancer Survivor Study (CCSS)","route":"/trials/ccss/"},{"id":"regobone","kind":"trial","name":"REGOBONE","route":"/trials/regobone/"},{"id":"sarc028","kind":"trial","name":"SARC028","route":"/trials/sarc028/"},{"id":"nct05734066","kind":"trial","name":"Study of Lurbinectedin Monotherapy in Pediatric and Young Adult Participants With Relapsed/Refractory Ewing Sarcoma","route":"/trials/nct05734066/"},{"id":"nct03709680","kind":"trial","name":"Study Of Palbociclib Combined With Chemotherapy In Pediatric Patients With Recurrent/Refractory Solid Tumors","route":"/trials/nct03709680/"},{"id":"nct06395103","kind":"trial","name":"Substudy 01A: Zilovertamab Vedotin in Pediatric and Young Adult Participants With Hematologic Malignancies or Solid Tumors (MK-9999-01A/LIGHTBEAM-U01)","route":"/trials/nct06395103/"}],"journal":[{"id":"journal-of-adolescent-and-young-adult-oncology","kind":"journal","name":"Journal of adolescent and young adult oncology","route":"/journals/journal-of-adolescent-and-young-adult-oncology/"}],"person":[{"id":"antoine-italiano","kind":"person","name":"Antoine Italiano","route":"/people/antoine-italiano/"},{"id":"florence-duffaud","kind":"person","name":"Florence Duffaud","route":"/people/florence-duffaud/"},{"id":"uta-dirksen","kind":"person","name":"Uta Dirksen","route":"/people/uta-dirksen/"}],"collection":[{"id":"alexs-lemonade-stand","kind":"collection","name":"Alex's Lemonade Stand Foundation (ALSF)","route":"/collections/alexs-lemonade-stand/"},{"id":"st-baldricks","kind":"collection","name":"St. Baldrick's Foundation","route":"/collections/st-baldricks/"}],"institution":[{"id":"nationwide-childrens","kind":"institution","name":"Nationwide Children's Hospital","route":"/institutions/nationwide-childrens/"}],"paper":[{"id":"paper-aews0031-interval-compressed-chemotherapy-ewing-womer-jco-2012","kind":"paper","name":"AEWS0031: randomised trial of interval-compressed chemotherapy for localised Ewing sarcoma","route":"/key-papers/paper-aews0031-interval-compressed-chemotherapy-ewing-womer-jco-2012/"}]}}