# Ewing sarcoma

Source: https://onco.cc/cancers/ewing-sarcoma/  
OnCo record `ewing-sarcoma` (Cancer). Data CC BY-NC 4.0, attribute "Data from OnCo (onco.cc)"; commercial use needs a licence.

## TL;DR

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 poor prognosis). It arises in bone (pelvis, femur, chest wall) or soft tissue in adolescents and young adults.

Treatment 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.

## Fields

- Kind: Cancer
- Last checked: 2026-09-08
- Tags: gap-fill; paediatric; sarcoma; aya
- 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 (poor prognosis); ctDNA fusion detection (emerging)

## Sections of this record

The page is a hub with ten sections in reading order; large sections have their own page. The same plan as JSON: https://onco.cc/api/v1/cancers/ewing-sarcoma/sections.json

- Overview (on the hub): The TL;DR, the family this cancer belongs to, the organ, who gets it and what the state of the art is. https://onco.cc/cancers/ewing-sarcoma/#overview [4 state-of-the-art points]
- What it is (on the hub): Anatomy, the subtypes and how they differ, how it is staged, and where advanced disease spreads. https://onco.cc/cancers/ewing-sarcoma/#what-it-is [4 subtypes]
- Finding it (on the hub): How it shows itself, how it is confirmed, what screening exists, and the biomarkers clinicians test for. https://onco.cc/cancers/ewing-sarcoma/#finding-it [6 biomarkers, 1 prevalence rows]
- Treating it (on the hub): The standard of care by setting, the medicines, surgery and radiotherapy named in it, and the regimens behind them. https://onco.cc/cancers/ewing-sarcoma/#treating-it [4 settings, 1 regimen, 4 decisions with options]
- Evidence (on the hub): Trials recruiting now, the landmark trials, the key papers and what they mean, the latest literature, and the milestones year by year. https://onco.cc/cancers/ewing-sarcoma/#evidence [10 trials, 1 key paper, 8 milestones]
- The science (on the hub): The molecular landscape: the targets and how often each appears, the pathways, the mechanics stages and the preclinical models. https://onco.cc/cancers/ewing-sarcoma/#science [8 targets, 2 pathways, 4 preclinical models]
- Where you are (own page): Cases by country, the UK and NHS pathway and other country lenses, and the expert centres with trials on record. https://onco.cc/cancers/ewing-sarcoma/where-you-are/ [1 centre]
- Living with it (on the hub): The decisions you may face, the aids that walk through them, the warnings on record, the first sixty days and the questions to ask. https://onco.cc/cancers/ewing-sarcoma/#living-with-it [18 questions, 6 red cards]
- What is coming (own page): Everything in development, the open problems and what is being done about them, the roadmaps, and what changed on this record. https://onco.cc/cancers/ewing-sarcoma/coming/ [14 medicines, 10 trials, 4 open problems]
- Data (own page): Every connected record, the notes, the JSON, Markdown and RDF twins, and where the record came from and when it was checked. https://onco.cc/cancers/ewing-sarcoma/data/ [76 connected records]

## Standard of care

- Localised: Interval-compressed VDC/IE ×14 cycles (AEWS0031 / Euro Ewing 2012) with surgery ± radiotherapy (or definitive RT 55.8 Gy) after 6 induction cycles. ([Vincristine](https://onco.cc/drugs/vincristine/), [Doxorubicin](https://onco.cc/drugs/doxorubicin/), [Cyclophosphamide](https://onco.cc/drugs/cyclophosphamide/), [Ifosfamide](https://onco.cc/drugs/ifosfamide/), [Etoposide](https://onco.cc/drugs/etoposide/), [IMRT / IGRT (modern external beam)](https://onco.cc/technologies/imrt-igrt/), [Limb-salvage surgery and endoprosthetic reconstruction](https://onco.cc/technologies/limb-salvage-surgery/), [AEWS0031](https://onco.cc/trials/aews0031/))
- Metastatic (lung only): Same chemotherapy plus whole-lung irradiation; busulfan-melphalan high-dose therapy in selected patients (Euro-EWING 99 R2pulm equivocal). ([Vincristine](https://onco.cc/drugs/vincristine/), [Doxorubicin](https://onco.cc/drugs/doxorubicin/), [Cyclophosphamide](https://onco.cc/drugs/cyclophosphamide/), [Ifosfamide](https://onco.cc/drugs/ifosfamide/), [Etoposide](https://onco.cc/drugs/etoposide/), [Autologous stem cell transplant (high-dose therapy)](https://onco.cc/technologies/autologous-stem-cell-transplant/))
- Metastatic (bone/marrow): Chemotherapy with palliative-intent local therapy; survival <20%; trials strongly preferred. ([Vincristine](https://onco.cc/drugs/vincristine/), [Doxorubicin](https://onco.cc/drugs/doxorubicin/), [Cyclophosphamide](https://onco.cc/drugs/cyclophosphamide/))
- Relapsed: High-dose ifosfamide (rEECur), irinotecan-temozolomide, topotecan-cyclophosphamide, gemcitabine-docetaxel; local therapy; trials. ([Ifosfamide](https://onco.cc/drugs/ifosfamide/), [Irinotecan (and liposomal irinotecan)](https://onco.cc/drugs/irinotecan/), [Temozolomide](https://onco.cc/drugs/temozolomide/), [Topotecan](https://onco.cc/drugs/topotecan/), [Cyclophosphamide](https://onco.cc/drugs/cyclophosphamide/))

## State of the art

- 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.

## Open problems

- 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.

## Sources

- Wikipedia: https://en.wikipedia.org/wiki/Ewing_sarcoma
- NCCN Guidelines: Bone Cancer: https://www.nccn.org/guidelines/guidelines-detail?category=1&id=1418
- NCI PDQ: Ewing sarcoma: https://www.cancer.gov/types/bone/patient/ewing-treatment-pdq

## Connected records

- cancers: [Adamantinoma of bone](https://onco.cc/cancers/adamantinoma/), [Adolescent and young adult cancers (ages 15 to 39)](https://onco.cc/cancers/aya-cancers/), [Childhood cancers (all types)](https://onco.cc/cancers/childhood-cancers/), [Chondrosarcoma](https://onco.cc/cancers/chondrosarcoma/), [Chordoma](https://onco.cc/cancers/chordoma/), [Desmoplastic small round cell tumour](https://onco.cc/cancers/desmoplastic-small-round-cell-tumour/), [Osteosarcoma](https://onco.cc/cancers/osteosarcoma/), [Rhabdomyosarcoma](https://onco.cc/cancers/rhabdomyosarcoma/), [Sarcomas (soft tissue, bone, GIST)](https://onco.cc/cancers/sarcoma/), [Synovial sarcoma](https://onco.cc/cancers/synovial-sarcoma/)
- technologies: [Autologous stem cell transplant (high-dose therapy)](https://onco.cc/technologies/autologous-stem-cell-transplant/), [CAR-T cell therapy](https://onco.cc/technologies/car-t/), [Cytotoxic chemotherapy](https://onco.cc/technologies/cytotoxic-chemotherapy/), [IMRT / IGRT (modern external beam)](https://onco.cc/technologies/imrt-igrt/), [Limb-salvage surgery and endoprosthetic reconstruction](https://onco.cc/technologies/limb-salvage-surgery/), [Methylation classifier for sarcomas](https://onco.cc/technologies/sarcoma-methylation-classifier/), [PROTACs & molecular glues (targeted protein degradation)](https://onco.cc/technologies/protac-degrader/), [Proton therapy](https://onco.cc/technologies/proton-therapy/)
- targets: [CDKN2B](https://onco.cc/targets/cdkn2b/), [EWSR1-FLI1 fusion](https://onco.cc/targets/ewsr1-fli1/), [IGF-1 receptor (IGF1R)](https://onco.cc/targets/igf1r/), [PARP](https://onco.cc/targets/parp/), [PTPRD](https://onco.cc/targets/ptprd/), [SLFN11](https://onco.cc/targets/slfn11/), [TP53](https://onco.cc/targets/tp53/)
- drugs: [Cyclophosphamide](https://onco.cc/drugs/cyclophosphamide/), [Dactinomycin (actinomycin D)](https://onco.cc/drugs/dactinomycin/), [Docetaxel](https://onco.cc/drugs/docetaxel/), [Doxorubicin](https://onco.cc/drugs/doxorubicin/), [Etoposide](https://onco.cc/drugs/etoposide/), [Ifosfamide](https://onco.cc/drugs/ifosfamide/), [Irinotecan (and liposomal irinotecan)](https://onco.cc/drugs/irinotecan/), [KC1036](https://onco.cc/drugs/kc1036/), [Lurbinectedin](https://onco.cc/drugs/lurbinectedin/), [Plicamycin](https://onco.cc/drugs/plicamycin/), [Temozolomide](https://onco.cc/drugs/temozolomide/), [TK216](https://onco.cc/drugs/tk216/), [Topotecan](https://onco.cc/drugs/topotecan/), [Vincristine](https://onco.cc/drugs/vincristine/)
- companies: [Actuate Therapeutics](https://onco.cc/companies/actuate-therapeutics/), [Children's Oncology Group (COG)](https://onco.cc/companies/childrens-oncology-group/), [French Sarcoma Group](https://onco.cc/companies/french-sarcoma-group/), [Jazz Pharmaceuticals](https://onco.cc/companies/jazz/), [PharmaMar](https://onco.cc/companies/pharmamar/), [SARC (Sarcoma Alliance for Research through Collaboration)](https://onco.cc/companies/sarc/)
- pathways: [p53 / RB / cell-cycle checkpoint](https://onco.cc/pathways/p53-cell-cycle/), [Transcriptional machinery & addiction](https://onco.cc/pathways/transcription-addiction/)
- terms: [Adolescent and young adult (AYA) oncology](https://onco.cc/terms/aya-oncology/), [CDKN2A/B homozygous deletion](https://onco.cc/terms/cdkn2a-homozygous-deletion/), [Gene fusion](https://onco.cc/terms/gene-fusion/), [Histological response to induction chemotherapy (osteosarcoma and Ewing sarcoma)](https://onco.cc/terms/histological-response-induction/)
- trials: [A Study of KC1036 in Adolescents With Advanced Ewing Sarcoma](https://onco.cc/trials/nct06564272/), [AEWS0031](https://onco.cc/trials/aews0031/), [CABONE](https://onco.cc/trials/cabone/), [CAMPFIRE: A Study of Abemaciclib (LY2835219) in Participants With Ewing's Sarcoma](https://onco.cc/trials/nct05440786/), [Childhood Cancer Survivor Study (CCSS)](https://onco.cc/trials/ccss/), [REGOBONE](https://onco.cc/trials/regobone/), [SARC028](https://onco.cc/trials/sarc028/), [Study of Lurbinectedin Monotherapy in Pediatric and Young Adult Participants With Relapsed/Refractory Ewing Sarcoma](https://onco.cc/trials/nct05734066/), [Study Of Palbociclib Combined With Chemotherapy In Pediatric Patients With Recurrent/Refractory Solid Tumors](https://onco.cc/trials/nct03709680/), [Substudy 01A: Zilovertamab Vedotin in Pediatric and Young Adult Participants With Hematologic Malignancies or Solid Tumors (MK-9999-01A/LIGHTBEAM-U01)](https://onco.cc/trials/nct06395103/)
- journals: [Journal of adolescent and young adult oncology](https://onco.cc/journals/journal-of-adolescent-and-young-adult-oncology/)
- people: [Antoine Italiano](https://onco.cc/people/antoine-italiano/), [Florence Duffaud](https://onco.cc/people/florence-duffaud/), [Uta Dirksen](https://onco.cc/people/uta-dirksen/)
- collections: [Alex's Lemonade Stand Foundation (ALSF)](https://onco.cc/collections/alexs-lemonade-stand/), [St. Baldrick's Foundation](https://onco.cc/collections/st-baldricks/)
- institutions: [Nationwide Children's Hospital](https://onco.cc/institutions/nationwide-childrens/)
- key papers: [AEWS0031: randomised trial of interval-compressed chemotherapy for localised Ewing sarcoma](https://onco.cc/key-papers/paper-aews0031-interval-compressed-chemotherapy-ewing-womer-jco-2012/)

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JSON: https://onco.cc/api/v1/entities/ewing-sarcoma.json