Cutting-edge options

Prepared 4 September 2026 by Kya at a friend's request, for her partner and the patient. Two questions were asked: what is genuinely cutting edge for chordoma and its lookalike chondrosarcoma in September 2026, including trials of related tumour types; and which treatments with roots in ancient or traditional medicine have reached modern clinical evidence. Every claim is sourced in research thread 12, with trial registry numbers. No prognosis figures. Nothing here argues for changing the standard plan of biopsy, surgery and proton therapy; most of it depends on that plan being done well.

The four levers

In chordoma the enemy is local regrowth at the skull base, far more than spread elsewhere. Everything in this document and the others points at the same four levers, in order: get as much out as is safe the first time, at a unit that does this often, because the amount left behind is the strongest predictor of regrowth; full-dose protons to what is left, because that is what holds the remainder; surveillance scans on a schedule afterwards, so that any regrowth is found small, when a second operation or re-irradiation is still possible; and, fourth, the drugs and trials below, for the case where the first three have not been enough. Get the first two right and the fourth may never be needed. That is the whole argument for the national MDT and for the tissue.

The short answer

• The single most useful cutting-edge step is within the family's power now: get the tissue handled right. Fresh frozen tumour and blood at biopsy or surgery for NHS whole genome sequencing on the sarcoma pathway, plus the stains that define the subtype (brachyury, INI1, p16, IDH1, PD-L1). Every drug and every trial below is gated on that result.
• No drug is licensed for chordoma, and every drug trial has been in disease that has progressed after surgery and radiotherapy. The best published numbers are for afatinib (a UK-site phase 2). CDK inhibitors, the brachyury vaccine, tazemetostat and checkpoint immunotherapy have each produced a handful of responses in small trials and no more. The most promising biology, a SHP2 inhibitor, is closed to new patients.

[Correction 11 Oct 2026: tazemetostat was withdrawn from all markets in March 2026 (Ipsen, after SYMPHONY-1 showed second blood cancers in 5.7% vs 0); trials and compassionate access stopped. PMID 42599162; research 12 A3. Read anything above or below about it as history, not an option.] - Carbon ions are not better than protons on the only randomised comparison, and are not NHS-funded. The Christie already gives the top of the international proton dose range. - From the ancient side, the things that survived trials are for symptoms, not the tumour: acupuncture for pain and opioid sparing, music around surgery and radiotherapy, mindfulness, yoga and tai chi for sleep and fatigue, melatonin instead of a sedative before surgery, and frankincense (Boswellia) as a steroid-sparing agent for brain swelling, which has a placebo-controlled trial. - Leave alone: ketogenic diets and fasting (two randomised trials negative, and she is losing weight), private hyperthermia or "immunotherapy" clinics, Chinese formula decoctions, ashwagandha and berberine at supplement doses, psilocybin outside a trial, and private "sequence and treat" offers that would consume the tissue the NHS test needs.

Track A: what is cutting edge for chordoma now

Disease-directed options, ranked by what could change her outcome

1. Tissue. Whole genome sequencing and the subtype stains, requested at the time of biopsy or surgery. Ask who is responsible for sending it.
2. Surgery at a high-volume unit, planned jointly with the proton centre. Intraoperative MRI is the one operating-theatre innovation with chordoma evidence of changing the operation; fluorescence guidance does not. The national chordoma MDT exists to make the joint plan; the referral should go in before surgery.
3. Protons at the Christie or UCLH at full dose. Only a specific dosimetric problem at the brainstem or basilar artery would justify self-funded carbon ions abroad, and the proton centre should be asked that question directly.
4. If histology is chondrosarcoma: IDH testing opens CHONQUER (ivosidenib, a UK phase 3 for advanced IDH-mutant chondrosarcoma) and ozekibart expanded access, the only related-type trials with UK access and a positive randomised signal.
5. If the disease ever progresses: afatinib or imatinib off-label through a UK sarcoma centre; DETERMINE (the UK precision-medicine platform, Southampton is a site) or MegaMOST in Lyon if sequencing shows a matching alteration; US trials via the Chordoma Foundation's navigators. These are treatments for progression, not cures.
6. If histology shows INI1 loss (unlikely at her age but tested for): tazemetostat combinations and chemotherapy enter the conversation.

   [Update 13 Oct 2026: the surgeon reported INI1 "not present" on 6 Oct, so this branch is now live, not unlikely. Tazemetostat is withdrawn (note above). Current branch-by-branch picture: em-ini1-result.md and research 37/38.]

7. Brachyury vaccines and degraders, CDK9 inhibitors, immunotherapy with radiotherapy, radiosensitisers: real science, no open trial she can join today. Worth a standing question to the Chordoma Foundation every six months.

Trials of related tumour types, checked on the registries today

• UK: DETERMINE (precision medicine, seven arms, needs a matching alteration from sequencing); CHONQUER (chondrosarcoma only, IDH-mutant); ozekibart expanded access via a sarcoma centre.
• Europe: MegaMOST (Lyon; cohorts by alteration, including CDKN2A and PDGFR); Institut Bergonie profiling. The carbon-ion trial in France excludes skull base.
• USA: abemaciclib (chordoma explicitly eligible), pembrolizumab plus pemetrexed, a tazemetostat combination for INI1 loss, and the NCI natural history study.
• No European or UK sarcoma trial currently names chordoma in its inclusion list.

Track B: what ancient medicine has actually proved

Use, with the team's agreement

• Acupuncture for cancer pain and to reduce opioid need: a 2020 meta-analysis and a 360-patient randomised trial. Safe. After biopsy. Via the pain clinic, a hospice service or privately.
• Music before, during and after surgery and during proton sessions: 73 randomised trials in a Lancet meta-analysis. Free. Ask the gantry team.
• Mindfulness, gentle yoga now; tai chi or qigong after surgery; CBT for insomnia (Sleepio on the NHS) instead of a sleeping tablet. Cochrane-level evidence for sleep, fatigue and anxiety, none of it sedating.
• Melatonin on prescription as the pre-operative calming and sleep aid that does not cloud thinking. Ask the anaesthetist.
• Frankincense (Boswellia serrata) at about 4,200 mg a day as a steroid-sparing agent if brain swelling or dexamethasone becomes an issue during or after protons: a placebo-controlled trial in brain tumour patients showed oedema reduction in 60 percent against 26 percent. Only with the oncologist's agreement, and stopped two weeks before any surgery.
• A dietitian rather than a diet. Energy and protein for a 51 kg patient facing seven weeks of radiotherapy; ginger for opioid nausea.
• Hypnosis or psychology support for the radiotherapy mask if needed; the proton centres provide it.

Looked at and set aside

• Hyperthermia: real randomised evidence in limb and trunk sarcoma, but the clivus cannot be heated, skull base was excluded from the head and neck trial, and there is no UK service. Private "oncothermia" is not the trialled technology.
• Fasting and ketogenic diets: two randomised glioma trials negative; harmful at her weight.
• Chinese and Ayurvedic compounds: homoharringtonine became a leukaemia drug and triptolide is in early trials, which shows the tradition can yield medicines, but nothing applies to chordoma, and formula decoctions, ashwagandha and berberine carry sedation, liver and drug-interaction risks with her medicines.
• Psilocybin: genuine randomised trials for cancer-related distress, but illegal outside a trial, no UK cancer trial open, and a brain mass is a standard exclusion.

Questions for the national chordoma MDT

1. Will you take the case before surgery, and make the surgical and proton plans together?
2. Will fresh frozen tissue and blood be taken for NHS whole genome sequencing, and who requests it?
3. Which stains will be done: brachyury, INI1, p16, IDH1, PD-L1?
4. Does the operating unit have intraoperative MRI, and what is the protocol for early post-operative MRI and second-look surgery?
5. Is there any UK or European trial she could enter now or at progression, and who tracks that for her? Is she registered with the Chordoma Foundation and Chordoma UK?
6. If chondrosarcoma: IDH status and CHONQUER eligibility. If poorly differentiated: INI1 status and what changes.
7. Who is her named sarcoma medical oncologist?

Questions for the proton centre

1. What dose will you give, and does the basilar artery or brainstem force a compromise? Would carbon ions change that, honestly?
2. Music in the gantry, and psychology support for the mask?
3. Supplement policy during radiotherapy, and specifically Boswellia if dexamethasone is needed?
4. Rules on acupuncture, yoga and exercise during the seven weeks?
5. Any radiosensitiser or immunotherapy-plus-radiotherapy trial for chordoma?
6. Will you bank the planning data in case of a future trial?

Where to look for trials

Chordoma Foundation trial finder and Patient Navigation Service; ClinicalTrials.gov (search chordoma, chondrosarcoma, sarcoma with United Kingdom); the EU Clinical Trials Information System; NIHR Be Part of Research; Cancer Research UK's trial finder and the DETERMINE pages; Sarcoma UK; Chordoma UK; EORTC sarcoma; SARC in the USA. Links are in research thread 12.

Key sources

Afatinib phase 2 (NCT03083678); palbociclib in chordoma (Teleanu, ESMO Open 2025); tazemetostat basket (Gounder, Nature Communications 2026); BN-Brachyury vaccine with radiotherapy (Cote, Cancer 2024); carbon versus proton randomised comparison (Shanghai 2025); CHONQUER (ivosidenib); DETERMINE (Cancer Research UK); MegaMOST (Lyon); hyperthermia in sarcoma (Issels 2018); ketogenic diet in glioma (ERGO, ERGO2); acupuncture for cancer pain (He 2020 JAMA Oncology; PEACE 2021); music (Hole 2015 Lancet; Bradt 2021 Cochrane); Boswellia for brain oedema (Kirste 2011); melatonin pre-operatively (Cochrane). Full list with links: research thread 12, em-research/12-cutting-edge-and-traditional.md.