Craniopharyngioma
Craniopharyngioma is a benign but destructive 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 dramatically with BRAF and MEK inhibitors, its first drug treatment.
Overview
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.
State of the art today
- 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.
Where it starts and where it drains
Gliomas infiltrate along white matter and can cross the corpus callosum, medulloblastoma sits in the cerebellum, and CNS lymphoma favours deep periventricular tissue; none spread through lymph nodes.
- Frontal lobe (glioblastoma commonest)
- Temporal lobe
- Corpus callosum (butterfly glioma)
- Lower-grade IDH-mutant glioma
- Cerebellum (medulloblastoma)
- Brainstem (diffuse midline glioma)
- Ventricles and ependymal lining (ependymoma)
- Sella and pituitary (pituitary tumours, craniopharyngioma)Adamantinomatous (CTNNB1-mutant; children and adults) · Papillary (BRAF V600E; adults)
- Deep periventricular tissue (CNS lymphoma)
No conventional lymphatics: gliomas spread along white matter tracts and, rarely, through cerebrospinal fluid; medulloblastoma can seed the spine.
Same organ: Glioma & glioblastoma, Primary CNS lymphoma, Medulloblastoma, Paediatric low-grade glioma, Diffuse midline glioma, H3 K27-altered (including DIPG), Atypical teratoid/rhabdoid tumour (ATRT), Ependymoma, Pituitary tumours (pituitary neuroendocrine tumours) and pituitary carcinoma
Rare: a few percent of childhood brain tumours, with a second peak in adults in their fifties and sixties (NCI PDQ).
- AI in radiologyEstablished
- cfDNA fragmentomicsEstablished
- Colorectal cancer screening (colonoscopy, FIT, stool DNA, blood)Standard of care
- DNA methylation profilingEstablished
- HCC surveillance in cirrhosis (ultrasound + AFP)Standard of care
- High-risk pancreatic surveillance (CAPS / PRECEDE)Established
- A 28-day national pathway for people with a positive multi-cancer blood test
- A breath test to rule out cancer in people with vague symptoms
- A cancer blood test for older people arriving at A&E with unexplained symptoms
- A legislated, publicly reported 28-day standard from urgent referral to diagnosis
- A live national dashboard of stage at diagnosis as the scorecard for early detection
- A single 'cancer check at 60' appointment bundling all screening tests
Background: Alpha-fetoprotein (AFP), Barrett's oesophagus, CA 19-9, Early detection, Faecal immunochemical test (FIT). Also on OnCo: Symptoms and red flags · Early detection roadmap.
Where the cases are
No country-level case numbers. This cancer is not mapped to a GLOBOCAN site.
Gross total resection (transsphenoidal or craniotomy) with endocrine replacement; observation with serial MRI.
Hypothalamus-sparing subtotal resection or cyst drainage followed by conformal or proton radiotherapy; intracystic therapy for predominantly cystic tumours.
BRAF plus MEK inhibition (vemurafenib-cobimetinib per Alliance A071601, or dabrafenib-trametinib) before or instead of extensive surgery; radiotherapy after response.
Lifelong endocrinology follow-up, management of hypothalamic obesity, sleep and behavioural sequelae; structured survivorship care.
Subtypes & biomarkers
top- Adamantinomatous (CTNNB1-mutant; children and adults)
- Papillary (BRAF V600E; adults)
- 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
Target prevalence in this cancer
- 1932Cushing names craniopharyngioma
- 2005Nuclear beta-catenin and CTNNB1 mutations define adamantinomatous tumours
- 2014BRAF V600E found in papillary craniopharyngioma
Brastianos and colleagues (Nature Genetics) show near-universal BRAF V600E in PCP and CTNNB1 in ACP.
- 2015First dramatic response to BRAF/MEK inhibition in papillary craniopharyngioma
Case report (JNCI) leads to the Alliance A071601 trial.
- 2016Hypothalamus-sparing surgery recommended
KRANIOPHARYNGEOM 2007 shows radical resection with hypothalamic injury worsens quality of life without improving control.
- 2024Alliance A071601 published
Vemurafenib plus cobimetinib produces responses in nearly all BRAF V600E papillary craniopharyngiomas (Lancet Oncology).
Open problems, and what is being done about each
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.
and how the field plans to fix it →What is being done about thisRecurrence and residual diseaseAvailable now- Survivorship care and late-effects surveillanceEstablished
- Liquid biopsy (ctDNA)Standard of care
- MRD / molecular residual disease testingEstablished
- Multiparameter flow cytometry MRDStandard of care
- NGS-based MRD (clonoSEQ and molecular MRD)Standard of care
- SignateraEstablished
In trials- ADAURAPositive
- CAMBRIA-1 & CAMBRIA-2Recruiting
- CIRCULATE-Japan (GALAXY / VEGA / ALTAIR)Active
- ctDNA monitoring in lymphoma (PhasED-seq, clonoSEQ)Emerging
- DYNAMICPositive
- IMvigor011Positive
Ideas and roadmaps- A blood test for the pre-metastatic niche
- A bone marrow niche on a chip to study human dormancy
- A dedicated clinic for people whose blood test says the cancer is back
- A drug screen that only rewards killing sleeping cancer cells
- A national platform trial that every ctDNA-positive patient can join
- A national residual-disease weather service: serial blood tests for every curatively treated patient, pooled
Background: Circulating tumour DNA (ctDNA), Disseminated tumour cells (DTCs), Late recurrence, Minimal / molecular residual disease (MRD), MRD negativity (myeloma, 10⁻⁵ / 10⁻⁶). Also on OnCo: Treatment journeys · Survivorship planner.
Trials
topRecruiting now (live from ClinicalTrials.gov)
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Expert centres
topCentres linked to this cancer in OnCo
- via Proton therapy
- via Proton therapy
- via Proton therapy
- via Proton therapy
- via Proton therapy
- Aarhus University HospitalAarhus, DKvia Proton therapy, IMRT / IGRT (modern external beam)
- American Society for Radiation OncologyArlington, VA, USvia Proton therapy, IMRT / IGRT (modern external beam)
- Centre Antoine LacassagneNice, FRvia Proton therapy, IMRT / IGRT (modern external beam)
- Children's Oncology Group (COG)Monrovia, CA, USvia this cancer, Survivorship care and late-effects surveillance
- European Society for Radiotherapy and OncologyBrussels, BEvia Proton therapy, IMRT / IGRT (modern external beam)
- Hokkaido University HospitalSapporo, JPvia Proton therapy, IMRT / IGRT (modern external beam)
- via Proton therapy, IMRT / IGRT (modern external beam)
- via Proton therapy, IMRT / IGRT (modern external beam)
- Royal Adelaide HospitalAdelaide, AUvia Proton therapy, IMRT / IGRT (modern external beam)
- via Proton therapy, IMRT / IGRT (modern external beam)
- via this cancer, Proton therapy
- Zhejiang Cancer HospitalHangzhou, CNvia Proton therapy, IMRT / IGRT (modern external beam)
- via Proton therapy
- Alliance for Clinical Trials in OncologyChicago, IL, USvia this cancer
- Apollo Hospitals (Apollo Cancer Centres)Chennai, INvia Proton therapy
- via Proton therapy
- via Proton therapy
- Centre François BaclesseCaen, FRvia Proton therapy
- Centre Oscar LambretLille, FRvia IMRT / IGRT (modern external beam)
- Chang Gung Memorial HospitalTaoyuan, TWvia Proton therapy
- via IMRT / IGRT (modern external beam)
- via IMRT / IGRT (modern external beam)
- Children's Hospital of PhiladelphiaPhiladelphia, PA, USvia Proton therapy
- Cleveland Clinic Abu DhabiAbu Dhabi, AEvia Proton therapy
- Comprehensive Cancer Center Freiburg (CCCF)Freiburg im Breisgau, DEvia IMRT / IGRT (modern external beam)
- via Proton therapy
- Erasmus MC Cancer InstituteRotterdam, NLvia Proton therapy
- Geneva University Hospitals (HUG)Geneva, CHvia IMRT / IGRT (modern external beam)
- Groote Schuur Hospital / University of Cape TownCape Town, ZAvia IMRT / IGRT (modern external beam)
- via IMRT / IGRT (modern external beam)
- Hacettepe University Cancer InstituteAnkara, TRvia IMRT / IGRT (modern external beam)
- via IMRT / IGRT (modern external beam)
- Ho Chi Minh City Oncology HospitalHo Chi Minh City, VNvia IMRT / IGRT (modern external beam)
- Hunan Cancer HospitalChangsha, CNvia IMRT / IGRT (modern external beam)
- Institut BergoniéBordeaux, FRvia IMRT / IGRT (modern external beam)
- Institut National d'Oncologie, RabatRabat, MAvia IMRT / IGRT (modern external beam)
- Institut Salah AzaïezTunis, TNvia IMRT / IGRT (modern external beam)
- Institute of Oncology LjubljanaLjubljana, SIvia IMRT / IGRT (modern external beam)
- via IMRT / IGRT (modern external beam)
- via IMRT / IGRT (modern external beam)
- International Extranodal Lymphoma Study GroupBellinzona, CHvia IMRT / IGRT (modern external beam)
- IRCCS Humanitas Research HospitalRozzano (Milan), ITvia IMRT / IGRT (modern external beam)
- Istanbul University Institute of OncologyIstanbul, TRvia IMRT / IGRT (modern external beam)
- via IMRT / IGRT (modern external beam)
- Juravinski Cancer Centre / Escarpment Cancer Research InstituteHamilton, ON, CAvia IMRT / IGRT (modern external beam)
- Kenyatta National HospitalNairobi, KEvia IMRT / IGRT (modern external beam)
- via Proton therapy
- Koo Foundation Sun Yat-Sen Cancer CenterTaipei, TWvia Survivorship care and late-effects surveillance
- Korle Bu Teaching HospitalAccra, GHvia IMRT / IGRT (modern external beam)
- Lagos University Teaching HospitalLagos, NGvia IMRT / IGRT (modern external beam)
- via IMRT / IGRT (modern external beam)
- Leiden University Medical CenterLeiden, NLvia Proton therapy
- Maastricht UMC+ Comprehensive Cancer CenterMaastricht, NLvia Proton therapy
- via IMRT / IGRT (modern external beam)
- via Proton therapy
- via Proton therapy
- via Proton therapy
- National Cancer Center Hospital EastKashiwa, Chiba, JPvia Proton therapy
- National Cancer Center KoreaGoyang, KRvia Proton therapy
- National Cancer Centre SingaporeSingapore, SGvia Proton therapy
- via IMRT / IGRT (modern external beam)
- National Institute of Oncology, HungaryBudapest, HUvia IMRT / IGRT (modern external beam)
- National Taiwan University HospitalTaipei, TWvia Proton therapy
- via Proton therapy
- Ocean Road Cancer InstituteDar es Salaam, TZvia IMRT / IGRT (modern external beam)
- via Proton therapy
- via IMRT / IGRT (modern external beam)
- via Proton therapy
- Rajiv Gandhi Cancer Institute and Research CentreNew Delhi, INvia IMRT / IGRT (modern external beam)
- Rambam Health Care CampusHaifa, ILvia IMRT / IGRT (modern external beam)
- Rigshospitalet – Copenhagen University HospitalCopenhagen, DKvia IMRT / IGRT (modern external beam)
- Ruijin Hospital, Shanghai Jiao Tong UniversityShanghai, CNvia Proton therapy
- Shizuoka Cancer CenterNagaizumi, Shizuoka, JPvia Proton therapy
- Siriraj Hospital, Mahidol UniversityBangkok, THvia IMRT / IGRT (modern external beam)
- via Proton therapy
- Tata Medical Center, KolkataKolkata, INvia IMRT / IGRT (modern external beam)
- Tawam HospitalAl Ain, AEvia IMRT / IGRT (modern external beam)
- Tel Aviv Sourasky Medical CenterTel Aviv, ILvia IMRT / IGRT (modern external beam)
- The Clatterbridge Cancer Centre NHS Foundation TrustLiverpool, GBvia Proton therapy
- via IMRT / IGRT (modern external beam)
- TROG Cancer ResearchNewcastle, NSW, AUvia IMRT / IGRT (modern external beam)
- UMC Utrecht Cancer CenterUtrecht, NLvia IMRT / IGRT (modern external beam)
- via Proton therapy
- via Proton therapy
- via Proton therapy
- via Proton therapy
- University of Malaya Medical CentreKuala Lumpur, MYvia IMRT / IGRT (modern external beam)
- University of Maryland Marlene and Stewart Greenebaum Comprehensive Cancer CenterBaltimore, MD, USNCI comprehensivevia Proton therapy
- via IMRT / IGRT (modern external beam)
- via Proton therapy
- UZ Leuven / Leuven Cancer InstituteLeuven, BEvia Proton therapy
- Velindre Cancer CentreCardiff, GBvia IMRT / IGRT (modern external beam)
- via IMRT / IGRT (modern external beam)
- Wellcome Sanger InstituteHinxton, GBvia BRAF
- via Proton therapy
Questions to ask
topQuestions to ask your oncologist about Craniopharyngioma
Newly diagnosed
- What is my exact diagnosis, stage, and grade, and which tests established them?Why: Everything else follows from an accurate stage and subtype.
- Which biomarkers have been tested on my tumour (for example CTNNB1 exon 3 mutation and nuclear beta-catenin, BRAF V600E, Hypothalamic involvement grade on MRI, Pituitary hormone panel and visual fields at baseline, Body-mass-index trajectory after treatment), and what were the results?Why: These results decide eligibility for targeted therapy, immunotherapy, and trials.
- Which subtype is my cancer, and does that change the recommended treatment?Why: Recognised subtypes for this cancer include Adamantinomatous, Papillary.
- Is germline (inherited) genetic testing recommended for me or my family?Why: Inherited variants can change treatment and matter for relatives.
Newly diagnosed, no or limited hypothalamic involvement
- For my situation (newly diagnosed, no or limited hypothalamic involvement), which of the standard options do you recommend and why?Why: Guideline options include: Gross total resection (transsphenoidal or craniotomy) with endocrine replacement; observation with serial MRI.
Hypothalamic involvement
- For my situation (hypothalamic involvement), which of the standard options do you recommend and why?Why: Guideline options include: Hypothalamus-sparing subtotal resection or cyst drainage followed by conformal or proton radiotherapy; intracystic therapy for predominantly cystic tumours.
Papillary craniopharyngioma, BRAF V600E
- For my situation (papillary craniopharyngioma, braf v600e), which of the standard options do you recommend and why?Why: Guideline options include: BRAF plus MEK inhibition (vemurafenib-cobimetinib per Alliance A071601, or dabrafenib-trametinib) before or instead of extensive surgery; radiotherapy after response.
- Am I a candidate for Dabrafenib + trametinib, Vemurafenib, Cobimetinib, and what side effects should I expect?Why: Knowing the expected toxicities helps you plan work, family, and supportive care.
Survivorship
- For my situation (survivorship), which of the standard options do you recommend and why?Why: Guideline options include: Lifelong endocrinology follow-up, management of hypothalamic obesity, sleep and behavioural sequelae; structured survivorship care.
Any stage
- Are there clinical trials I could join, for example of Dabrafenib + trametinib, Proton therapy, GLP-1 receptor agonists and obesity-related cancer risk?Why: Trials are how the next standard of care is set; asking early keeps options open.
- Would a second opinion at a high-volume centre change anything, and can you help arrange it?Why: Rare or high-stakes decisions benefit from a centre that treats many similar patients.
- What supportive care (symptom control, nutrition, exercise, mental health, financial help) is available from the start?Why: Supportive care improves quality of life and helps patients complete treatment.
- I read that “Hypothalamic obesity in survivors has no reliable treatment; GLP-1 agonists, setmelanotide and oxytocin are in trials”. How does that affect my plan?Why: Open problems are where trials and second opinions matter most.
- I read that “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 does that affect my plan?Why: Open problems are where trials and second opinions matter most.
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Direct links plus the targets, companies, and technologies of this cancer's products.
technologies
9targets
1drugs
5companies
2institutions
3pathways
3terms
1bottlenecks
2Latest papers
topQuery for this cancer: (TITLE:"Craniopharyngioma" OR ABSTRACT:"Craniopharyngioma" OR TITLE:"Adamantinomatous craniopharyngioma" OR ABSTRACT:"Adamantinomatous craniopharyngioma" OR TITLE:"Papillary craniopharyngioma" OR ABSTRACT:"Papillary craniopharyngioma" OR TITLE:"Childhood craniopharyngioma" OR ABSTRACT:"Childhood craniopharyngioma") AND (treatment OR therapy OR trial OR survival OR diagnosis). Results are unfiltered search hits about Craniopharyngioma, not a curated reading list.
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