{"entity":{"id":"craniopharyngioma","kind":"cancer","name":"Craniopharyngioma","aka":["Adamantinomatous craniopharyngioma","Papillary craniopharyngioma","Childhood craniopharyngioma"],"tldr":"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.\n\nManagement 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 severe late effects, 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.\n\nThe 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.","asOf":"2026-09-10","wikipedia":"https://en.wikipedia.org/wiki/Craniopharyngioma","links":[{"label":"NCI PDQ: childhood craniopharyngioma","url":"https://www.cancer.gov/types/brain/hp/child-cranio-treatment-pdq"},{"label":"Alliance A071601: BRAF/MEK inhibition in papillary craniopharyngioma (Lancet Oncology 2024)","url":"https://doi.org/10.1016/S1470-2045(23)00492-9"},{"label":"Brastianos 2014: exome sequencing of craniopharyngioma (Nature Genetics)","url":"https://doi.org/10.1038/ng.2868"}],"tags":["nci-coverage","paediatric","cns"],"related":["pituitary-tumours","paediatric-low-grade-glioma","cns-germ-cell-tumours","meningioma"],"cancers":[],"sections":[],"technologies":["proton-therapy","imrt-igrt","mri","survivorship-care-plan"],"targets":["braf"],"drugs":["dabrafenib-trametinib","vemurafenib","cobimetinib","interferon-alfa","bleomycin","setmelanotide"],"companies":["childrens-oncology-group","alliance-oncology"],"institutions":["st-jude"],"pathways":["wnt","ras-mapk","inflammation-nfkb"],"terms":["late-effects"],"trials":[],"people":[],"bottlenecks":["b-survivorship","b-rare-cancers"],"keyPapers":["paper-brastianos-nat-genet"],"journals":[],"dependsOn":[],"notes":[],"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"],"standardOfCare":[{"setting":"Newly diagnosed, no or limited hypothalamic involvement","approach":"Gross total resection (transsphenoidal or craniotomy) with endocrine replacement; observation with serial MRI.","refs":["mri"],"guideline":{"version":"NCI PDQ: childhood craniopharyngioma","url":"https://www.cancer.gov/types/brain/hp/child-cranio-treatment-pdq"}},{"setting":"Hypothalamic involvement","approach":"Hypothalamus-sparing subtotal resection or cyst drainage followed by conformal or proton radiotherapy; intracystic therapy for predominantly cystic tumours.","refs":["proton-therapy","imrt-igrt"],"guideline":{"version":"KRANIOPHARYNGEOM 2007; NCI PDQ","url":"https://www.cancer.gov/types/brain/hp/child-cranio-treatment-pdq"}},{"setting":"Papillary craniopharyngioma, BRAF V600E","approach":"BRAF plus MEK inhibition (vemurafenib-cobimetinib per Alliance A071601, or dabrafenib-trametinib) before or instead of extensive surgery; radiotherapy after response.","refs":["dabrafenib-trametinib","vemurafenib","cobimetinib"],"guideline":{"version":"Alliance A071601 (Lancet Oncology 2024)","url":"https://doi.org/10.1016/S1470-2045(23)00492-9"}},{"setting":"Survivorship","approach":"Lifelong endocrinology follow-up, management of hypothalamic obesity, sleep and behavioural sequelae; structured survivorship care.","refs":["survivorship-care-plan"]}],"stateOfArt":["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."],"history":[{"year":1932,"title":"Cushing names craniopharyngioma","refs":[]},{"year":2005,"title":"Nuclear beta-catenin and CTNNB1 mutations define adamantinomatous tumours","refs":[]},{"year":2014,"title":"BRAF V600E found in papillary craniopharyngioma","note":"Brastianos and colleagues (Nature Genetics) show near-universal BRAF V600E in PCP and CTNNB1 in ACP.","refs":["braf"]},{"year":2015,"title":"First dramatic response to BRAF/MEK inhibition in papillary craniopharyngioma","note":"Case report (JNCI) leads to the Alliance A071601 trial.","refs":["dabrafenib-trametinib"]},{"year":2016,"title":"Hypothalamus-sparing surgery recommended","note":"KRANIOPHARYNGEOM 2007 shows radical resection with hypothalamic injury worsens quality of life without improving control.","refs":[]},{"year":2024,"title":"Alliance A071601 published","note":"Vemurafenib plus cobimetinib produces responses in nearly all BRAF V600E papillary craniopharyngiomas (Lancet Oncology).","refs":["vemurafenib","cobimetinib"]}],"pipeline":["dabrafenib-trametinib","proton-therapy","glp1-agonists-cancer-risk"],"openProblems":["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."],"parent":"brain-tumours"},"route":"/cancers/craniopharyngioma/","neighbours":{"cancer":[{"id":"brain-tumours","kind":"cancer","name":"Brain and spinal cord tumours (all types)","route":"/cancers/brain-tumours/"},{"id":"cns-germ-cell-tumours","kind":"cancer","name":"Central nervous system germ cell tumours (germinoma and non-germinomatous)","route":"/cancers/cns-germ-cell-tumours/"},{"id":"gonadotroph-pitnet","kind":"cancer","name":"Gonadotroph pituitary neuroendocrine tumour (non-functioning adenoma)","route":"/cancers/gonadotroph-pitnet/"},{"id":"meningioma","kind":"cancer","name":"Meningioma","route":"/cancers/meningioma/"},{"id":"paediatric-low-grade-glioma","kind":"cancer","name":"Paediatric low-grade glioma","route":"/cancers/paediatric-low-grade-glioma/"},{"id":"pituitary-tumours","kind":"cancer","name":"Pituitary tumours (pituitary neuroendocrine tumours) and pituitary carcinoma","route":"/cancers/pituitary-tumours/"}],"technology":[{"id":"glp1-agonists-cancer-risk","kind":"technology","name":"GLP-1 receptor agonists and obesity-related cancer risk","route":"/technologies/glp1-agonists-cancer-risk/"},{"id":"imrt-igrt","kind":"technology","name":"IMRT / IGRT (modern external beam)","route":"/technologies/imrt-igrt/"},{"id":"mri","kind":"technology","name":"MRI","route":"/technologies/mri/"},{"id":"proton-therapy","kind":"technology","name":"Proton therapy","route":"/technologies/proton-therapy/"},{"id":"survivorship-care-plan","kind":"technology","name":"Survivorship care and late-effects surveillance","route":"/technologies/survivorship-care-plan/"}],"target":[{"id":"braf","kind":"target","name":"BRAF","route":"/targets/braf/"}],"drug":[{"id":"bleomycin","kind":"drug","name":"Bleomycin","route":"/drugs/bleomycin/"},{"id":"cobimetinib","kind":"drug","name":"Cobimetinib","route":"/drugs/cobimetinib/"},{"id":"dabrafenib-trametinib","kind":"drug","name":"Dabrafenib + trametinib","route":"/drugs/dabrafenib-trametinib/"},{"id":"interferon-alfa","kind":"drug","name":"Interferon alfa-2a/2b","route":"/drugs/interferon-alfa/"},{"id":"setmelanotide","kind":"drug","name":"Setmelanotide","route":"/drugs/setmelanotide/"},{"id":"vemurafenib","kind":"drug","name":"Vemurafenib","route":"/drugs/vemurafenib/"}],"company":[{"id":"alliance-oncology","kind":"company","name":"Alliance for Clinical Trials in Oncology","route":"/companies/alliance-oncology/"},{"id":"childrens-oncology-group","kind":"company","name":"Children's Oncology Group (COG)","route":"/companies/childrens-oncology-group/"}],"institution":[{"id":"st-jude","kind":"institution","name":"St. Jude Children's Research Hospital","route":"/institutions/st-jude/"}],"pathway":[{"id":"inflammation-nfkb","kind":"pathway","name":"Inflammation & NF-κB","route":"/pathways/inflammation-nfkb/"},{"id":"ras-mapk","kind":"pathway","name":"RAS / RAF / MEK / ERK (MAPK)","route":"/pathways/ras-mapk/"},{"id":"wnt","kind":"pathway","name":"Wnt / β-catenin","route":"/pathways/wnt/"}],"term":[{"id":"late-effects","kind":"term","name":"Late effects and survivorship toxicity","route":"/terms/late-effects/"}],"bottleneck":[{"id":"b-rare-cancers","kind":"bottleneck","name":"Rare and paediatric cancers without markets","route":"/bottlenecks/b-rare-cancers/"},{"id":"b-survivorship","kind":"bottleneck","name":"Survivorship and late effects are neglected","route":"/bottlenecks/b-survivorship/"}],"paper":[{"id":"paper-brastianos-nat-genet","kind":"paper","name":"Exome sequencing identifies BRAF mutations in papillary craniopharyngiomas","route":"/key-papers/paper-brastianos-nat-genet/"},{"id":"paper-transcend-miller-nejm-2026","kind":"paper","name":"Setmelanotide for the treatment of acquired hypothalamic obesity (TRANSCEND)","route":"/key-papers/paper-transcend-miller-nejm-2026/"}],"journal":[{"id":"brain-tumor-pathology","kind":"journal","name":"Brain tumor pathology","route":"/journals/brain-tumor-pathology/"},{"id":"cns-oncology","kind":"journal","name":"CNS oncology","route":"/journals/cns-oncology/"},{"id":"journal-of-neuro-oncology","kind":"journal","name":"Journal of neuro-oncology","route":"/journals/journal-of-neuro-oncology/"}],"trial":[{"id":"nct05919264","kind":"trial","name":"FOG-001 in Locally Advanced or Metastatic Solid Tumors","route":"/trials/nct05919264/"},{"id":"transcend","kind":"trial","name":"TRANSCEND","route":"/trials/transcend/"}]}}