{"entity":{"id":"chordoma","kind":"cancer","name":"Chordoma","aka":["Childhood chordoma","Clival chordoma","Sacral chordoma"],"tldr":"Chordoma is a slow-growing bone cancer (a sarcoma) of the skull base and spine that arises from leftover embryonic notochord cells. Complete surgery followed by high-dose proton or carbon-ion radiotherapy controls most tumours, and the whole disease depends on a single transcription factor, brachyury, which vaccines and degraders are now trying to hit.","summary":"Chordoma arises from notochordal remnants along the axial skeleton (clivus, mobile spine, sacrum). Nearly all tumours express the T-box transcription factor brachyury (TBXT), a lineage dependency rather than a mutation: a common germline TBXT variant raises risk, and germline TBXT duplication causes familial chordoma. Conventional and chondroid chordomas are indolent but locally destructive; dedifferentiated and poorly differentiated chordomas are aggressive. Poorly differentiated chordoma, seen mainly in children, is defined by SMARCB1 (INI1) loss, placing it in the SWI/SNF-deficient family with epithelioid sarcoma and ATRT.\n\nCurative treatment is en bloc resection with negative margins where anatomy permits, followed by high-dose radiotherapy, because the tumour is radioresistant at conventional doses and sits against the brainstem, cranial nerves or sacral roots. Proton and carbon-ion therapy deliver 70 Gy-equivalent or more while sparing neural tissue, and definitive particle therapy is used when resection is impossible. Systemic options are limited: imatinib (PDGFRB-expressing disease, phase 2 Stacchiotti 2012) and afatinib (EGFR) give disease stabilisation more often than shrinkage, and are not approved. Tazemetostat is being studied in INI1-negative poorly differentiated chordoma on the basis of its epithelioid sarcoma activity.\n\nThe frontier is brachyury itself: a yeast-based brachyury vaccine (GI-6301) and adenoviral brachyury vaccines have been tested with radiotherapy, and brachyury degraders and CDK7/9 inhibitors that lower TBXT expression are in preclinical or early clinical development. The Chordoma Foundation coordinates a global registry, biobank and drug-screening pipeline, a model for how a rare cancer community can run its own research programme.","asOf":"2026-09-10","wikipedia":"https://en.wikipedia.org/wiki/Chordoma","links":[{"label":"NCI PDQ: childhood chordoma (bone cancer)","url":"https://www.cancer.gov/types/bone"},{"label":"Chordoma Global Consensus Group recommendations (Lancet Oncol 2015)","url":"https://doi.org/10.1016/S1470-2045(14)71190-8"},{"label":"Chordoma Foundation","url":"https://www.chordomafoundation.org/"}],"tags":["nci-coverage","rare","sarcoma","paediatric"],"related":["chondrosarcoma","osteosarcoma","ewing-sarcoma"],"cancers":[],"sections":[],"technologies":["proton-therapy","carbon-ion","imrt-igrt","sbrt","kinase-inhibitors","epigenetic-drugs"],"targets":["ezh2","egfr","pdgfra"],"drugs":["imatinib","afatinib","sorafenib","tazemetostat","gi-6301"],"companies":[],"institutions":[],"pathways":["swi-snf-chromatin","transcription-addiction"],"terms":["rare-cancers"],"trials":["regobone"],"people":[],"bottlenecks":["b-rare-cancers","b-undruggable-targets"],"keyPapers":["paper-stacchiotti-lancet-oncol"],"journals":[],"dependsOn":[],"notes":[],"group":"sarcoma","burden":"About one case per million people per year, at any age; skull-base tumours are more common in children, sacral tumours in older adults.","subtypes":["Conventional chordoma","Chondroid chordoma","Dedifferentiated chordoma","Poorly differentiated chordoma (SMARCB1/INI1-deficient, mostly paediatric skull base)"],"biomarkers":["Brachyury (TBXT) nuclear immunostaining (diagnostic)","SMARCB1/INI1 loss (poorly differentiated subtype)","PDGFRB and EGFR expression (drug selection in trials)","Germline TBXT duplication (familial chordoma)","Surgical margin status and location (skull base vs sacrum)"],"standardOfCare":[{"setting":"Resectable, any site","approach":"En bloc resection with negative margins by a spine or skull-base team, followed by high-dose proton or carbon-ion radiotherapy; intralesional surgery is associated with early recurrence.","refs":["proton-therapy","carbon-ion","imrt-igrt"],"guideline":{"nccn":"Category 2A","version":"NCCN Guidelines: Bone Cancer; Chordoma Global Consensus Group (Lancet Oncol 2015)","url":"https://doi.org/10.1016/S1470-2045(14)71190-8"}},{"setting":"Unresectable or medically inoperable","approach":"Definitive particle therapy (proton or carbon-ion) to 70 Gy-equivalent or higher; stereotactic photon radiosurgery where particles are unavailable.","refs":["proton-therapy","carbon-ion","sbrt"]},{"setting":"Advanced or metastatic","approach":"Clinical trial preferred. Imatinib (PDGFRB-positive), afatinib or other EGFR inhibitors, or sorafenib give mainly disease stabilisation; tazemetostat was used for INI1-negative poorly differentiated chordoma until Ipsen withdrew it from all markets in March 2026.","refs":["imatinib","afatinib","sorafenib","tazemetostat","kinase-inhibitors"]}],"stateOfArt":["Particle therapy after maximal surgery has made long-term local control the expected outcome for skull-base chordoma, with less neurological injury than photon plans.","Brachyury is now recognised as the lineage dependency of the disease: TBXT knockdown is lethal to chordoma cells, and vaccines plus degraders that target it are the main mechanistic bets.","SMARCB1-deficient poorly differentiated chordoma in children is being treated with EZH2 inhibition borrowed from epithelioid sarcoma, an example of biology-based rather than histology-based drug repurposing.","Patient-led infrastructure (the Chordoma Foundation's registry, cell-line bank and prize-driven drug screens) has produced most of the field's preclinical models."],"history":[{"year":1857,"title":"Virchow describes chordoma","note":"First description of the notochord-derived tumour.","refs":[]},{"year":2006,"title":"Brachyury identified as a chordoma marker","note":"Vujovic and colleagues show near-universal nuclear brachyury expression.","refs":[]},{"year":2009,"title":"Germline TBXT duplication in familial chordoma","note":"Yang and colleagues (Nat Genet).","refs":[]},{"year":2012,"title":"Imatinib phase 2 in advanced chordoma","note":"Stacchiotti and colleagues: disease stabilisation in most patients, few objective responses.","refs":["imatinib"]},{"year":2015,"title":"Chordoma Global Consensus Group","note":"First international recommendations on surgery, radiotherapy and systemic therapy (Lancet Oncol).","refs":[]},{"year":2020,"title":"Poorly differentiated chordoma recognised as SMARCB1-deficient entity","note":"WHO classification of soft tissue and bone tumours, fifth edition.","refs":[]},{"year":2021,"title":"Brachyury vaccine plus radiotherapy tested","note":"Phase 2 of GI-6301 yeast-brachyury vaccine with radiation (NCT02383498).","refs":["proton-therapy"]}],"pipeline":["carbon-ion","proton-therapy","afatinib"],"openProblems":["No approved systemic therapy: trials of brachyury-directed vaccines, degraders and EGFR inhibitors are the response.","Recurrent skull-base disease after full-dose radiotherapy: re-irradiation with particles and salvage surgery are being studied.","Paediatric poorly differentiated chordoma: tazemetostat and SWI/SNF-directed trials.","Access to particle therapy, which remains concentrated in a few countries."],"parent":"sarcoma"},"route":"/cancers/chordoma/","neighbours":{"cancer":[{"id":"adamantinoma","kind":"cancer","name":"Adamantinoma of bone","route":"/cancers/adamantinoma/"},{"id":"chondrosarcoma","kind":"cancer","name":"Chondrosarcoma","route":"/cancers/chondrosarcoma/"},{"id":"dedifferentiated-chordoma","kind":"cancer","name":"Dedifferentiated chordoma","route":"/cancers/dedifferentiated-chordoma/"},{"id":"ewing-sarcoma","kind":"cancer","name":"Ewing sarcoma","route":"/cancers/ewing-sarcoma/"},{"id":"osteosarcoma","kind":"cancer","name":"Osteosarcoma","route":"/cancers/osteosarcoma/"},{"id":"poorly-differentiated-chordoma","kind":"cancer","name":"Poorly differentiated chordoma (SMARCB1-deficient)","route":"/cancers/poorly-differentiated-chordoma/"},{"id":"sarcoma","kind":"cancer","name":"Sarcomas (soft tissue, bone, GIST)","route":"/cancers/sarcoma/"}],"technology":[{"id":"carbon-ion-synchrotrons","kind":"technology","name":"Carbon-ion synchrotrons and facilities","route":"/technologies/carbon-ion-synchrotrons/"},{"id":"carbon-ion","kind":"technology","name":"Carbon-ion therapy","route":"/technologies/carbon-ion/"},{"id":"epigenetic-drugs","kind":"technology","name":"Epigenetic drugs (HDAC, DNMT, EZH2, IDH, menin, BET)","route":"/technologies/epigenetic-drugs/"},{"id":"imrt-igrt","kind":"technology","name":"IMRT / IGRT (modern external beam)","route":"/technologies/imrt-igrt/"},{"id":"proton-therapy","kind":"technology","name":"Proton therapy","route":"/technologies/proton-therapy/"},{"id":"proton-therapy-systems","kind":"technology","name":"Proton therapy machines: cyclotrons, synchrotrons and single-room systems","route":"/technologies/proton-therapy-systems/"},{"id":"sbrt","kind":"technology","name":"SBRT / SABR (stereotactic radiotherapy)","route":"/technologies/sbrt/"},{"id":"kinase-inhibitors","kind":"technology","name":"Small-molecule kinase inhibitors","route":"/technologies/kinase-inhibitors/"}],"target":[{"id":"egfr","kind":"target","name":"EGFR","route":"/targets/egfr/"},{"id":"ezh2","kind":"target","name":"EZH2","route":"/targets/ezh2/"},{"id":"pdgfra","kind":"target","name":"PDGFRA","route":"/targets/pdgfra/"},{"id":"tbxt","kind":"target","name":"TBXT","route":"/targets/tbxt/"}],"drug":[{"id":"afatinib","kind":"drug","name":"Afatinib","route":"/drugs/afatinib/"},{"id":"gi-6301","kind":"drug","name":"GI-6301","route":"/drugs/gi-6301/"},{"id":"imatinib","kind":"drug","name":"Imatinib","route":"/drugs/imatinib/"},{"id":"sorafenib","kind":"drug","name":"Sorafenib","route":"/drugs/sorafenib/"},{"id":"tazemetostat","kind":"drug","name":"Tazemetostat","route":"/drugs/tazemetostat/"}],"pathway":[{"id":"swi-snf-chromatin","kind":"pathway","name":"SWI/SNF chromatin remodelling","route":"/pathways/swi-snf-chromatin/"},{"id":"transcription-addiction","kind":"pathway","name":"Transcriptional machinery & addiction","route":"/pathways/transcription-addiction/"}],"term":[{"id":"rare-cancers","kind":"term","name":"Rare cancers","route":"/terms/rare-cancers/"}],"trial":[{"id":"nct06787664","kind":"trial","name":"A Study of BL-B01D1 in Patients With Locally Advanced or Metastatic Chordoma","route":"/trials/nct06787664/"},{"id":"regobone","kind":"trial","name":"REGOBONE","route":"/trials/regobone/"}],"bottleneck":[{"id":"b-rare-cancers","kind":"bottleneck","name":"Rare and paediatric cancers without markets","route":"/bottlenecks/b-rare-cancers/"},{"id":"b-undruggable-targets","kind":"bottleneck","name":"The undruggable drivers","route":"/bottlenecks/b-undruggable-targets/"}],"paper":[{"id":"paper-stacchiotti-lancet-oncol","kind":"paper","name":"Building a global consensus approach to chordoma: a position paper from the medical and patient community","route":"/key-papers/paper-stacchiotti-lancet-oncol/"}],"pairing":[{"id":"proton-vs-imrt","kind":"pairing","name":"Caution: proton therapy vs IMRT","route":"/pairings/proton-vs-imrt/"}]}}