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10 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.
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.
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.
Curative 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.
| Setting | Approach | Guideline |
|---|---|---|
| Resectable, any site | 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. | NCCN Category 2A |
| Unresectable or medically inoperable | Definitive particle therapy (proton or carbon-ion) to 70 Gy-equivalent or higher; stereotactic photon radiosurgery where particles are unavailable. | not mapped |
| Advanced or metastatic | 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. | not mapped |