# Chordoma

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

## TL;DR

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.

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.

The 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.

## Fields

- Kind: Cancer
- Last checked: 2026-09-10
- Also known as: Childhood chordoma; Clival chordoma; Sacral chordoma
- Tags: nci-coverage; rare; sarcoma; paediatric
- 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)

## 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/chordoma/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/chordoma/#overview [2 subtypes, 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/chordoma/#what-it-is [6 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/chordoma/#finding-it [5 biomarkers]
- 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/chordoma/#treating-it [3 settings, 3 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/chordoma/#evidence [2 trials, 1 key paper, 7 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/chordoma/#science [8 targets, 2 pathways]
- 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/chordoma/where-you-are/
- 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/chordoma/#living-with-it [13 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/chordoma/coming/ [5 medicines, 2 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/chordoma/data/ [38 connected records]

## Standard of care

- 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. ([Proton therapy](https://onco.cc/technologies/proton-therapy/), [Carbon-ion therapy](https://onco.cc/technologies/carbon-ion/), [IMRT / IGRT (modern external beam)](https://onco.cc/technologies/imrt-igrt/))
- Unresectable or medically inoperable: Definitive particle therapy (proton or carbon-ion) to 70 Gy-equivalent or higher; stereotactic photon radiosurgery where particles are unavailable. ([Proton therapy](https://onco.cc/technologies/proton-therapy/), [Carbon-ion therapy](https://onco.cc/technologies/carbon-ion/), [SBRT / SABR (stereotactic radiotherapy)](https://onco.cc/technologies/sbrt/))
- 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. ([Imatinib](https://onco.cc/drugs/imatinib/), [Afatinib](https://onco.cc/drugs/afatinib/), [Sorafenib](https://onco.cc/drugs/sorafenib/), [Tazemetostat](https://onco.cc/drugs/tazemetostat/), [Small-molecule kinase inhibitors](https://onco.cc/technologies/kinase-inhibitors/))

## State of the art

- 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.

## Open problems

- 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.

## Sources

- Wikipedia: https://en.wikipedia.org/wiki/Chordoma
- NCI PDQ: childhood chordoma (bone cancer): https://www.cancer.gov/types/bone
- Chordoma Global Consensus Group recommendations (Lancet Oncol 2015): https://doi.org/10.1016/S1470-2045(14)71190-8
- Chordoma Foundation: https://www.chordomafoundation.org/

## Connected records

- cancers: [Adamantinoma of bone](https://onco.cc/cancers/adamantinoma/), [Chondrosarcoma](https://onco.cc/cancers/chondrosarcoma/), [Dedifferentiated chordoma](https://onco.cc/cancers/dedifferentiated-chordoma/), [Ewing sarcoma](https://onco.cc/cancers/ewing-sarcoma/), [Osteosarcoma](https://onco.cc/cancers/osteosarcoma/), [Poorly differentiated chordoma (SMARCB1-deficient)](https://onco.cc/cancers/poorly-differentiated-chordoma/), [Sarcomas (soft tissue, bone, GIST)](https://onco.cc/cancers/sarcoma/)
- technologies: [Carbon-ion synchrotrons and facilities](https://onco.cc/technologies/carbon-ion-synchrotrons/), [Carbon-ion therapy](https://onco.cc/technologies/carbon-ion/), [Epigenetic drugs (HDAC, DNMT, EZH2, IDH, menin, BET)](https://onco.cc/technologies/epigenetic-drugs/), [IMRT / IGRT (modern external beam)](https://onco.cc/technologies/imrt-igrt/), [Proton therapy](https://onco.cc/technologies/proton-therapy/), [Proton therapy machines: cyclotrons, synchrotrons and single-room systems](https://onco.cc/technologies/proton-therapy-systems/), [SBRT / SABR (stereotactic radiotherapy)](https://onco.cc/technologies/sbrt/), [Small-molecule kinase inhibitors](https://onco.cc/technologies/kinase-inhibitors/)
- targets: [EGFR](https://onco.cc/targets/egfr/), [EZH2](https://onco.cc/targets/ezh2/), [PDGFRA](https://onco.cc/targets/pdgfra/), [TBXT](https://onco.cc/targets/tbxt/)
- drugs: [Afatinib](https://onco.cc/drugs/afatinib/), [GI-6301](https://onco.cc/drugs/gi-6301/), [Imatinib](https://onco.cc/drugs/imatinib/), [Sorafenib](https://onco.cc/drugs/sorafenib/), [Tazemetostat](https://onco.cc/drugs/tazemetostat/)
- pathways: [SWI/SNF chromatin remodelling](https://onco.cc/pathways/swi-snf-chromatin/), [Transcriptional machinery & addiction](https://onco.cc/pathways/transcription-addiction/)
- terms: [Rare cancers](https://onco.cc/terms/rare-cancers/)
- trials: [A Study of BL-B01D1 in Patients With Locally Advanced or Metastatic Chordoma](https://onco.cc/trials/nct06787664/), [REGOBONE](https://onco.cc/trials/regobone/)
- bottlenecks: [Rare and paediatric cancers without markets](https://onco.cc/bottlenecks/b-rare-cancers/), [The undruggable drivers](https://onco.cc/bottlenecks/b-undruggable-targets/)
- key papers: [Building a global consensus approach to chordoma: a position paper from the medical and patient community](https://onco.cc/key-papers/paper-stacchiotti-lancet-oncol/)
- pairings: [Caution: proton therapy vs IMRT](https://onco.cc/pairings/proton-vs-imrt/)

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JSON: https://onco.cc/api/v1/entities/chordoma.json