{"entity":{"id":"rhabdomyosarcoma","kind":"cancer","name":"Rhabdomyosarcoma","aka":[],"tldr":"A childhood soft-tissue sarcoma, a 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.","summary":"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.\n\nTherapy 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.","asOf":"2026-09-08","wikipedia":"https://en.wikipedia.org/wiki/Rhabdomyosarcoma","links":[{"label":"NCI PDQ: childhood rhabdomyosarcoma","url":"https://www.cancer.gov/types/soft-tissue-sarcoma/patient/rhabdomyosarcoma-treatment-pdq"},{"label":"EpSSG RMS 2005 maintenance (Lancet Oncol 2019)","url":"https://doi.org/10.1016/S1470-2045(19)30617-5"},{"label":"FaR-RMS trial","url":"https://clinicaltrials.gov/study/NCT04625907"}],"tags":["gap-fill","paediatric","sarcoma"],"related":["ewing-sarcoma","osteosarcoma","synovial-sarcoma","alveolar-soft-part-sarcoma"],"cancers":[],"sections":[],"technologies":["cytotoxic-chemotherapy","imrt-igrt","proton-therapy","brachytherapy","car-t","pet-ct"],"targets":["b7h3","cdk4-6","fgfr2","tp53"],"drugs":["vincristine","dactinomycin","cyclophosphamide","ifosfamide","irinotecan","vinorelbine","temsirolimus","etoposide","doxorubicin","temozolomide"],"companies":["pfizer","childrens-oncology-group"],"institutions":[],"pathways":["ras-mapk","pi3k-akt-mtor"],"terms":["gene-fusion","foxo1-fusion-status"],"trials":["ccss"],"people":[],"bottlenecks":[],"keyPapers":["paper-bisogno-lancet-oncol"],"journals":[],"dependsOn":[],"notes":[],"group":"paediatric","burden":"The most common soft-tissue sarcoma of childhood (~350 cases per year in the US, ~3% of childhood cancers); survival ~70% overall, >90% low risk, <30% metastatic.","subtypes":["Embryonal RMS (botryoid and spindle cell variants)","Alveolar RMS, PAX3/PAX7-FOXO1 fusion-positive","Fusion-negative alveolar RMS (behaves as embryonal)","Spindle cell / sclerosing RMS (MYOD1-mutant, aggressive; VGLL2-fused infantile, indolent)","Pleomorphic RMS (adults)"],"biomarkers":["PAX3/PAX7-FOXO1 fusion status (FISH/RT-PCR)","Site (favourable: orbit, non-parameningeal head and neck, GU non-bladder/prostate)","IRS group and TNM stage","Nodal status (PET-CT, biopsy for extremity/paratesticular)","MYOD1 L122R (poor)","Age (>10 years, <1 year unfavourable)"],"standardOfCare":[{"setting":"Low risk (embryonal, favourable site, complete resection)","approach":"VA ± reduced cyclophosphamide for 22-24 weeks; radiotherapy for microscopic residual disease.","refs":["vincristine","dactinomycin","cyclophosphamide"],"guideline":{"version":"COG ARST0331 / EpSSG RMS 2005","url":"https://doi.org/10.1016/S1470-2045(19)30617-5"}},{"setting":"Intermediate risk","approach":"VAC (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.","refs":["vincristine","dactinomycin","cyclophosphamide","ifosfamide","irinotecan","vinorelbine","temsirolimus","imrt-igrt"],"guideline":{"version":"COG ARST1431; EpSSG RMS 2005"}},{"setting":"High risk (metastatic)","approach":"Intensive multi-agent chemotherapy (VAC/IE, vincristine-irinotecan windows) with radiotherapy to primary and metastases; maintenance; FaR-RMS trial questions.","refs":["vincristine","irinotecan","ifosfamide","etoposide","doxorubicin","imrt-igrt"],"guideline":{"version":"COG ARST0431; FaR-RMS"}},{"setting":"Relapsed","approach":"Vinorelbine-cyclophosphamide, irinotecan-temozolomide, surgery/RT; trials (mTOR, FGFR4, CDK4/6, IGF-1R, B7-H3 CAR-T).","refs":["vinorelbine","cyclophosphamide","irinotecan","temozolomide","temsirolimus"]}],"stateOfArt":["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."],"history":[{"year":1972,"title":"Intergroup Rhabdomyosarcoma Study (IRS-I) begins","note":"Establishes VAC and cooperative-group model.","refs":[]},{"year":1993,"title":"PAX3-FOXO1 fusion identified (Galili, Barr)","refs":["gene-fusion"]},{"year":2010,"title":"Fusion-negative alveolar RMS behaves like embryonal (Williamson, JCO)","note":"Leads to fusion-based risk stratification.","refs":[]},{"year":2019,"title":"EpSSG RMS 2005: maintenance vinorelbine-cyclophosphamide improves survival (Lancet Oncol)","refs":["vinorelbine","cyclophosphamide"]},{"year":2019,"title":"ARST0531: irinotecan does not improve outcome but spares cyclophosphamide","refs":["irinotecan"]},{"year":2024,"title":"ARST1431: temsirolimus + chemotherapy improves EFS in intermediate risk","refs":["temsirolimus"]}],"pipeline":["temsirolimus","vinorelbine","car-t","b7h3","cobolimab"],"openProblems":["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."],"parent":"sarcoma"},"route":"/cancers/rhabdomyosarcoma/","neighbours":{"cancer":[{"id":"alveolar-soft-part-sarcoma","kind":"cancer","name":"Alveolar soft part sarcoma","route":"/cancers/alveolar-soft-part-sarcoma/"},{"id":"childhood-cancers","kind":"cancer","name":"Childhood cancers (all types)","route":"/cancers/childhood-cancers/"},{"id":"pleuropulmonary-blastoma","kind":"cancer","name":"Childhood lung and airway tumours (pleuropulmonary blastoma, tracheobronchial tumours)","route":"/cancers/pleuropulmonary-blastoma/"},{"id":"desmoplastic-small-round-cell-tumour","kind":"cancer","name":"Desmoplastic small round cell tumour","route":"/cancers/desmoplastic-small-round-cell-tumour/"},{"id":"ewing-sarcoma","kind":"cancer","name":"Ewing sarcoma","route":"/cancers/ewing-sarcoma/"},{"id":"osteosarcoma","kind":"cancer","name":"Osteosarcoma","route":"/cancers/osteosarcoma/"},{"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/"},{"id":"vaginal","kind":"cancer","name":"Vaginal cancer","route":"/cancers/vaginal/"}],"technology":[{"id":"brachytherapy","kind":"technology","name":"Brachytherapy","route":"/technologies/brachytherapy/"},{"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":"imrt-igrt","kind":"technology","name":"IMRT / IGRT (modern external beam)","route":"/technologies/imrt-igrt/"},{"id":"sarcoma-methylation-classifier","kind":"technology","name":"Methylation classifier for sarcomas","route":"/technologies/sarcoma-methylation-classifier/"},{"id":"pet-ct","kind":"technology","name":"PET/CT","route":"/technologies/pet-ct/"},{"id":"proton-therapy","kind":"technology","name":"Proton therapy","route":"/technologies/proton-therapy/"},{"id":"rejuv-paed-teeth-and-face","kind":"technology","name":"Teeth, jaws and facial growth after treatment in childhood","route":"/technologies/rejuv-paed-teeth-and-face/"}],"target":[{"id":"b7h3","kind":"target","name":"B7-H3","route":"/targets/b7h3/"},{"id":"cdk4-6","kind":"target","name":"CDK4/6","route":"/targets/cdk4-6/"},{"id":"fgfr2","kind":"target","name":"FGFR2","route":"/targets/fgfr2/"},{"id":"foxo1","kind":"target","name":"FOXO1","route":"/targets/foxo1/"},{"id":"myod1","kind":"target","name":"MYOD1","route":"/targets/myod1/"},{"id":"pax3","kind":"target","name":"PAX3","route":"/targets/pax3/"},{"id":"pax7","kind":"target","name":"PAX7","route":"/targets/pax7/"},{"id":"tp53","kind":"target","name":"TP53","route":"/targets/tp53/"}],"drug":[{"id":"cobolimab","kind":"drug","name":"Cobolimab","route":"/drugs/cobolimab/"},{"id":"cyclophosphamide","kind":"drug","name":"Cyclophosphamide","route":"/drugs/cyclophosphamide/"},{"id":"dactinomycin","kind":"drug","name":"Dactinomycin (actinomycin D)","route":"/drugs/dactinomycin/"},{"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":"temozolomide","kind":"drug","name":"Temozolomide","route":"/drugs/temozolomide/"},{"id":"temsirolimus","kind":"drug","name":"Temsirolimus","route":"/drugs/temsirolimus/"},{"id":"vincristine","kind":"drug","name":"Vincristine","route":"/drugs/vincristine/"},{"id":"vinorelbine","kind":"drug","name":"Vinorelbine","route":"/drugs/vinorelbine/"}],"company":[{"id":"childrens-oncology-group","kind":"company","name":"Children's Oncology Group (COG)","route":"/companies/childrens-oncology-group/"},{"id":"itcc","kind":"company","name":"Innovative Therapies for Children with Cancer (ITCC)","route":"/companies/itcc/"},{"id":"pfizer","kind":"company","name":"Pfizer (incl. Seagen)","route":"/companies/pfizer/"}],"pathway":[{"id":"pi3k-akt-mtor","kind":"pathway","name":"PI3K / AKT / mTOR","route":"/pathways/pi3k-akt-mtor/"},{"id":"ras-mapk","kind":"pathway","name":"RAS / RAF / MEK / ERK (MAPK)","route":"/pathways/ras-mapk/"}],"term":[{"id":"foxo1-fusion-status","kind":"term","name":"FOXO1 fusion status and IRS group (rhabdomyosarcoma)","route":"/terms/foxo1-fusion-status/"},{"id":"gene-fusion","kind":"term","name":"Gene fusion","route":"/terms/gene-fusion/"},{"id":"li-fraumeni","kind":"term","name":"Li-Fraumeni syndrome (germline TP53)","route":"/terms/li-fraumeni/"}],"trial":[{"id":"ccss","kind":"trial","name":"Childhood Cancer Survivor Study (CCSS)","route":"/trials/ccss/"},{"id":"nct06277154","kind":"trial","name":"MASCT-I Combined With Doxorubicin and Ifosfamide for First-line Treatment of Advanced Soft Tissue Sarcoma","route":"/trials/nct06277154/"},{"id":"nct03709680","kind":"trial","name":"Study Of Palbociclib Combined With Chemotherapy In Pediatric Patients With Recurrent/Refractory Solid Tumors","route":"/trials/nct03709680/"}],"paper":[{"id":"paper-bisogno-lancet-oncol","kind":"paper","name":"Vinorelbine and continuous low-dose cyclophosphamide as maintenance chemotherapy in patients with high-risk rhabdomyosarcoma (RMS 2005): a multicentre, open-label, randomised, phase 3 trial","route":"/key-papers/paper-bisogno-lancet-oncol/"}],"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/"}]}}