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Teaching pack: Rhabdomyosarcoma

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9 slides generated from the cancer page, with a quiz from the open benchmark and speaker notes that cite the sources. Arrow keys move between slides; Print gives one slide per page.

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  1. Teaching pack · Cancer · paediatric

    Rhabdomyosarcoma

    A childhood soft-tissue cancer of muscle-like cells found anywhere from the eye socket to the bladder. Most children are cured with chemotherapy, surgery and radiation, and a fusion gene (PAX-FOXO1) now decides how intensively to treat.

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  2. What it is

    In two paragraphs

    Rhabdomyosarcoma (RMS) has two main types: embryonal (~70%, younger children, RAS-pathway mutations, favourable) and alveolar (~25%, adolescents, PAX3- or PAX7-FOXO1 fusion in ~80%, unfavourable). Fusion status has replaced histology in risk stratification since fusion-negative alveolar RMS behaves like embryonal. Sites range from orbit and parameningeal head and neck to genitourinary and extremity; risk groups combine site, size, nodal status, metastases, age and fusion status.

    Therapy is VAC (vincristine, actinomycin D, cyclophosphamide) in North America or IVA (ifosfamide) in Europe, with local control by surgery and/or radiotherapy at week ~13. Key trial results: adding irinotecan (VAC/VI, ARST0531) did not improve outcomes but reduced cyclophosphamide exposure; maintenance vinorelbine-cyclophosphamide after standard therapy improved survival in high-risk localised disease (EpSSG RMS 2005, Lancet Oncol 2019); temsirolimus added to chemotherapy improved event-free survival in intermediate-risk disease (ARST1431, reported 2024). Metastatic disease (especially bone/marrow, age >10) has survival under 30% and is the target of the FaR-RMS international trial. Relapse is usually fatal outside low-risk cases.

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  3. Standard of care

    What is given today, by setting

    SettingApproachGuideline
    Low risk (embryonal, favourable site, complete resection)VA ± reduced cyclophosphamide for 22-24 weeks; radiotherapy for microscopic residual disease.not mapped
    Intermediate riskVAC (or VAC/VI) 42 weeks with radiotherapy at week 13 (COG); IVA with maintenance vinorelbine-cyclophosphamide 6 months (EpSSG); temsirolimus-VAC/VI per ARST1431 where adopted.not mapped
    High risk (metastatic)Intensive multi-agent chemotherapy (VAC/IE, vincristine-irinotecan windows) with radiotherapy to primary and metastases; maintenance; FaR-RMS trial questions.not mapped
    RelapsedVinorelbine-cyclophosphamide, irinotecan-temozolomide, surgery/RT; trials (mTOR, FGFR4, CDK4/6, IGF-1R, B7-H3 CAR-T).not mapped
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  4. State of the art

    Where the field stands

    • Fusion status has replaced histology in risk stratification in both COG and European protocols.
    • Maintenance chemotherapy (EpSSG RMS 2005) is the first survival gain in decades for high-risk localised disease.
    • Temsirolimus is the first targeted agent to improve event-free survival in a randomised RMS trial (ARST1431).
    • Metastatic disease remains the unsolved problem; international FaR-RMS trial pools patients across continents.
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  5. History

    How we got here

    1. 1972Intergroup Rhabdomyosarcoma Study (IRS-I) begins
    2. 1993PAX3-FOXO1 fusion identified (Galili, Barr)
    3. 2010Fusion-negative alveolar RMS behaves like embryonal (Williamson, JCO)
    4. 2019EpSSG RMS 2005: maintenance vinorelbine-cyclophosphamide improves survival (Lancet Oncol)
    5. 2019ARST0531: irinotecan does not improve outcome but spares cyclophosphamide
    6. 2024ARST1431: temsirolimus + chemotherapy improves EFS in intermediate risk
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  6. Pipeline

    What is coming

    • Temsirolimus (product)
    • Vinorelbine (product)
    • CAR-T cell therapy (technology)
    • B7-H3 (target)
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  7. Open problems

    What nobody has solved

    • Metastatic alveolar RMS: survival <30% for 30 years.
    • PAX3-FOXO1 is an undrugged fusion transcription factor.
    • Local-control morbidity in young children (orbit, bladder, prostate).
    • Relapse after intermediate-risk therapy is rarely curable.
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  8. Quiz

    Check understanding

    1. What is CAR-T and which cancers is it approved for?
      Answer
      A patient's T cells are engineered with a synthetic receptor, multiplied, and returned. Approved CD19 products treat B-cell lymphomas and leukaemias; BCMA products treat multiple myeloma; the first solid-tumour approval (Claudin 18.2, gastric) is in China.
    2. What is in vivo CAR-T and why is it exciting?
      Answer
      Targeted lipid nanoparticles or viral vectors deliver CAR-encoding mRNA or DNA to T cells inside the patient, avoiding manufacturing, lymphodepletion, and wait time and allowing redosing; first-in-human data in 2025-26 show B-cell depletion. AbbVie bought Capstan for up to $2.1B.
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  9. Sources

    Read the primary sources

    • NCI PDQ: childhood rhabdomyosarcoma: https://www.cancer.gov/types/soft-tissue-sarcoma/patient/rhabdomyosarcoma-treatment-pdq
    • EpSSG RMS 2005 maintenance (Lancet Oncol 2019): https://doi.org/10.1016/S1470-2045(19)30617-5
    • FaR-RMS trial: https://clinicaltrials.gov/study/NCT04625907
    • Wikipedia: https://en.wikipedia.org/wiki/Rhabdomyosarcoma
    • Guideline: https://doi.org/10.1016/S1470-2045(19)30617-5
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