# Craniopharyngioma

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

## TL;DR

Craniopharyngioma is a benign but destructive brain tumour growing from embryonic remnants beside the pituitary gland and hypothalamus. Surgery, or limited surgery plus radiotherapy, cures most people, but the price can be lifelong hormone deficiency and severe obesity. The adult (papillary) form carries a BRAF mutation and shrinks markedly with BRAF and MEK inhibitors, its first drug treatment.

## Summary

Craniopharyngioma is a WHO grade 1 epithelial tumour of the sellar and suprasellar region with two distinct types. Adamantinomatous craniopharyngioma (ACP), the childhood form, carries activating CTNNB1 (beta-catenin) mutations, forms cysts filled with motor-oil fluid, and invades the hypothalamus; papillary craniopharyngioma (PCP), almost exclusively adult, carries BRAF V600E in nearly every case. Neither metastasises, but both damage vision, pituitary function and the hypothalamic centres that control appetite, sleep and temperature.

Management has shifted from radical resection at any cost to preserving the hypothalamus. Gross total resection cures if achieved, but attempts to strip tumour from the hypothalamus cause hypothalamic obesity, which is refractory to diet and exercise and is the dominant determinant of quality of life in survivors. Hypothalamus-sparing subtotal resection followed by conformal or proton radiotherapy gives equivalent tumour control with fewer devastating sequelae, and is now the favoured approach for tumours with hypothalamic involvement (KRANIOPHARYNGEOM 2007 and St Jude data). Cysts can be managed with catheter drainage, intracystic interferon or bleomycin, or stereotactic radiosurgery. Lifelong endocrine replacement is the norm.

The molecular findings created two therapeutic openings. In papillary tumours, BRAF plus MEK inhibition (vemurafenib-cobimetinib in the Alliance A071601 phase 2, Lancet Oncology 2024) produced marked shrinkage in almost all treated patients, allowing surgery and radiotherapy to be reduced; dabrafenib-trametinib case series show the same. In adamantinomatous tumours, the inflammatory cyst fluid is rich in IL-6, and the IL-6 receptor antibody tocilizumab has shrunk cysts in children in case series and an early trial. Treatments for hypothalamic obesity itself (GLP-1 agonists, setmelanotide, oxytocin) are being studied.

## Fields

- Kind: Cancer
- Last checked: 2026-09-10
- Also known as: Adamantinomatous craniopharyngioma; Papillary craniopharyngioma; Childhood craniopharyngioma
- Tags: nci-coverage; paediatric; cns
- Group: paediatric
- Burden: Rare: a few percent of childhood brain tumours, with a second peak in adults in their fifties and sixties (NCI PDQ).
- Subtypes: Adamantinomatous (CTNNB1-mutant; children and adults); Papillary (BRAF V600E; adults)
- Biomarkers: CTNNB1 exon 3 mutation and nuclear beta-catenin (adamantinomatous); BRAF V600E (papillary); Hypothalamic involvement grade on MRI (Puget or Muller grading); Pituitary hormone panel and visual fields at baseline; Body-mass-index trajectory after treatment

## 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/craniopharyngioma/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/craniopharyngioma/#overview [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/craniopharyngioma/#what-it-is [2 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/craniopharyngioma/#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/craniopharyngioma/#treating-it [4 settings, 2 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/craniopharyngioma/#evidence [2 trials, 2 key papers, 6 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/craniopharyngioma/#science [1 target, 3 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/craniopharyngioma/where-you-are/ [1 centre]
- 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/craniopharyngioma/#living-with-it [14 questions, 4 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/craniopharyngioma/coming/ [6 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/craniopharyngioma/data/ [36 connected records]

## Standard of care

- Newly diagnosed, no or limited hypothalamic involvement: Gross total resection (transsphenoidal or craniotomy) with endocrine replacement; observation with serial MRI. ([MRI](https://onco.cc/technologies/mri/))
- Hypothalamic involvement: Hypothalamus-sparing subtotal resection or cyst drainage followed by conformal or proton radiotherapy; intracystic therapy for predominantly cystic tumours. ([Proton therapy](https://onco.cc/technologies/proton-therapy/), [IMRT / IGRT (modern external beam)](https://onco.cc/technologies/imrt-igrt/))
- Papillary craniopharyngioma, BRAF V600E: BRAF plus MEK inhibition (vemurafenib-cobimetinib per Alliance A071601, or dabrafenib-trametinib) before or instead of extensive surgery; radiotherapy after response. ([Dabrafenib + trametinib](https://onco.cc/drugs/dabrafenib-trametinib/), [Vemurafenib](https://onco.cc/drugs/vemurafenib/), [Cobimetinib](https://onco.cc/drugs/cobimetinib/))
- Survivorship: Lifelong endocrinology follow-up, management of hypothalamic obesity, sleep and behavioural sequelae; structured survivorship care. ([Survivorship care and late-effects surveillance](https://onco.cc/technologies/survivorship-care-plan/))

## State of the art

- The goal has shifted from radical removal to hypothalamus preservation: limited surgery plus radiotherapy controls the tumour with far less obesity and neuropsychological harm.
- Papillary craniopharyngioma is the first benign brain tumour treated by targeted therapy: BRAF/MEK inhibition shrinks nearly all tumours in the Alliance A071601 trial.
- IL-6 blockade with tocilizumab is an emerging cyst-directed therapy for adamantinomatous tumours in children.
- Proton therapy reduces dose to the temporal lobes and hypothalamus in children who need irradiation.

## Open problems

- Hypothalamic obesity in survivors has no reliable treatment; GLP-1 agonists, setmelanotide and oxytocin are in trials.
- No systemic therapy is established for adamantinomatous tumours; IL-6 blockade and MEK inhibition (downstream of the beta-catenin-driven inflammatory programme) are being tested.
- How long BRAF/MEK inhibition should continue in papillary tumours and whether radiotherapy can be omitted after response.
- Recurrence after subtotal resection in children too young for radiotherapy.

## Sources

- Wikipedia: https://en.wikipedia.org/wiki/Craniopharyngioma
- NCI PDQ: childhood craniopharyngioma: https://www.cancer.gov/types/brain/hp/child-cranio-treatment-pdq
- Alliance A071601: BRAF/MEK inhibition in papillary craniopharyngioma (Lancet Oncology 2024): https://doi.org/10.1016/S1470-2045(23)00492-9
- Brastianos 2014: exome sequencing of craniopharyngioma (Nature Genetics): https://doi.org/10.1038/ng.2868

## Connected records

- cancers: [Brain and spinal cord tumours (all types)](https://onco.cc/cancers/brain-tumours/), [Central nervous system germ cell tumours (germinoma and non-germinomatous)](https://onco.cc/cancers/cns-germ-cell-tumours/), [Gonadotroph pituitary neuroendocrine tumour (non-functioning adenoma)](https://onco.cc/cancers/gonadotroph-pitnet/), [Meningioma](https://onco.cc/cancers/meningioma/), [Paediatric low-grade glioma](https://onco.cc/cancers/paediatric-low-grade-glioma/), [Pituitary tumours (pituitary neuroendocrine tumours) and pituitary carcinoma](https://onco.cc/cancers/pituitary-tumours/)
- technologies: [GLP-1 receptor agonists and obesity-related cancer risk](https://onco.cc/technologies/glp1-agonists-cancer-risk/), [IMRT / IGRT (modern external beam)](https://onco.cc/technologies/imrt-igrt/), [MRI](https://onco.cc/technologies/mri/), [Proton therapy](https://onco.cc/technologies/proton-therapy/), [Survivorship care and late-effects surveillance](https://onco.cc/technologies/survivorship-care-plan/)
- targets: [BRAF](https://onco.cc/targets/braf/)
- drugs: [Bleomycin](https://onco.cc/drugs/bleomycin/), [Cobimetinib](https://onco.cc/drugs/cobimetinib/), [Dabrafenib + trametinib](https://onco.cc/drugs/dabrafenib-trametinib/), [Interferon alfa-2a/2b](https://onco.cc/drugs/interferon-alfa/), [Setmelanotide](https://onco.cc/drugs/setmelanotide/), [Vemurafenib](https://onco.cc/drugs/vemurafenib/)
- companies: [Alliance for Clinical Trials in Oncology](https://onco.cc/companies/alliance-oncology/), [Children's Oncology Group (COG)](https://onco.cc/companies/childrens-oncology-group/)
- institutions: [St. Jude Children's Research Hospital](https://onco.cc/institutions/st-jude/)
- pathways: [Inflammation & NF-κB](https://onco.cc/pathways/inflammation-nfkb/), [RAS / RAF / MEK / ERK (MAPK)](https://onco.cc/pathways/ras-mapk/), [Wnt / β-catenin](https://onco.cc/pathways/wnt/)
- terms: [Late effects and survivorship toxicity](https://onco.cc/terms/late-effects/)
- bottlenecks: [Rare and paediatric cancers without markets](https://onco.cc/bottlenecks/b-rare-cancers/), [Survivorship and late effects are neglected](https://onco.cc/bottlenecks/b-survivorship/)
- key papers: [Exome sequencing identifies BRAF mutations in papillary craniopharyngiomas](https://onco.cc/key-papers/paper-brastianos-nat-genet/), [Setmelanotide for the treatment of acquired hypothalamic obesity (TRANSCEND)](https://onco.cc/key-papers/paper-transcend-miller-nejm-2026/)
- journals: [Brain tumor pathology](https://onco.cc/journals/brain-tumor-pathology/), [CNS oncology](https://onco.cc/journals/cns-oncology/), [Journal of neuro-oncology](https://onco.cc/journals/journal-of-neuro-oncology/)
- trials: [FOG-001 in Locally Advanced or Metastatic Solid Tumors](https://onco.cc/trials/nct05919264/), [TRANSCEND](https://onco.cc/trials/transcend/)

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