Craniopharyngioma is a rare, WHO grade 1 epithelial neoplasm of the sellar/parasellar and suprasellar region, usually arising from Rathke pouch epithelial remnants. The two main entities, adamantinomatous craniopharyngioma and papillary craniopharyngioma, differ in age distribution, histology, imaging pattern, and molecular drivers. Morbidity is dominated by local mass effect and treatment injury involving the optic apparatus, hypothalamus, and pituitary gland, causing visual impairment, headache, hypopituitarism, diabetes insipidus, hypothalamic dysfunction, and long-term quality-of-life burden.
Ask a research question about Craniopharyngioma. OpenScientist will conduct autonomous deep research using the Disorder Mechanisms Knowledge Base and PubMed literature (typically 10-30 minutes).
Do not include personal health information in your question. Questions and results are cached in your browser's local storage.
name: Craniopharyngioma
creation_date: "2026-05-11T17:51:07Z"
updated_date: "2026-05-11T19:12:44Z"
synonyms:
- Rathke pouch tumor
- Rathke pouch neoplasm
- craniopharyngeal duct tumor
- adamantinomatous craniopharyngioma
- papillary craniopharyngioma
description: >-
Craniopharyngioma is a rare, WHO grade 1 epithelial neoplasm of the
sellar/parasellar and suprasellar region, usually arising from Rathke pouch
epithelial remnants. The two main entities, adamantinomatous
craniopharyngioma and papillary craniopharyngioma, differ in age distribution,
histology, imaging pattern, and molecular drivers. Morbidity is dominated by
local mass effect and treatment injury involving the optic apparatus,
hypothalamus, and pituitary gland, causing visual impairment, headache,
hypopituitarism, diabetes insipidus, hypothalamic dysfunction, and long-term
quality-of-life burden.
categories:
- Central Nervous System Neoplasm
- Pediatric Brain Tumor
- Sellar Region Tumor
- Endocrine Neoplasia
- Benign Epithelial Neoplasm
parents:
- central nervous system organ benign neoplasm
- sella turcica neoplasm
- benign epithelial neoplasm
disease_term:
preferred_term: craniopharyngioma
term:
id: MONDO:0018907
label: craniopharyngioma
definitions:
- name: Craniopharyngioma literature definition
definition_type: CASE_DEFINITION
description: >-
A rare intracranial epithelial tumor arising from Rathke pouch remnants in
the sellar/parasellar region, histologically low-grade but clinically
morbid because of its position near the optic, hypothalamic, and pituitary
structures.
evidence:
- reference: PMID:38961911
reference_title: "Craniopharyngioma: A comprehensive review of the clinical presentation, radiological findings, management, and future Perspective."
supports: SUPPORT
evidence_source: HUMAN_CLINICAL
snippet: >-
Craniopharyngioma (CP) is a rare intracranial tumor arising from the
epithelial remnants of Rathke's pouch, most frequently originating in the
sellar/parasellar region. Histologically, CP is a benign low-grade tumor
(WHO grade 1) with two distinct phenotypes: adamantinomatous CP (ACP) and
papillary CP (PCP).
explanation: >-
This clinical review directly defines the anatomic origin, benign WHO
grade, and two major craniopharyngioma entities.
has_subtypes:
- name: ACP
display_name: Adamantinomatous Craniopharyngioma
description: >-
Adamantinomatous craniopharyngioma is the CTNNB1/Wnt-driven subtype that
occurs in children and adults, often with cystic/solid components,
calcification, wet keratin, palisading epithelium, and a reactive
inflammatory/glial microenvironment.
evidence:
- reference: PMID:36979325
reference_title: "Current Advances in Papillary Craniopharyngioma: State-Of-The-Art Therapies and Overview of the Literature."
supports: SUPPORT
evidence_source: HUMAN_CLINICAL
snippet: >-
Craniopharyngiomas are classically distinguished into two histological
types (adamantinomatous and papillary), which have been recently considered
by the WHO classification of CNS tumors as two independent entities, due to
different epidemiological, radiological, histopathological, and genetic
patterns.
explanation: >-
This review supports adamantinomatous craniopharyngioma as one of the two
WHO-recognized clinicopathologic entities.
- reference: PMID:36748936
reference_title: The molecular pathogenesis of craniopharyngiomas.
supports: SUPPORT
evidence_source: HUMAN_CLINICAL
snippet: >-
ACP and PCP subtypes can be identified by the presence of mutations in
CTNNB1 and BRAF genes, with prevalence around 60% and 90%, respectively.
explanation: >-
This molecular review supports CTNNB1 mutation as the characteristic
marker for ACP.
- name: PCP
display_name: Papillary Craniopharyngioma
description: >-
Papillary craniopharyngioma is the BRAF V600E/MAPK-driven subtype, mainly
seen in adults, with a strong precision-oncology treatment signal from
BRAF/MEK inhibition.
evidence:
- reference: PMID:36979325
reference_title: "Current Advances in Papillary Craniopharyngioma: State-Of-The-Art Therapies and Overview of the Literature."
supports: SUPPORT
evidence_source: HUMAN_CLINICAL
snippet: "With regard to papillary craniopharyngioma, a BRAF V600 mutation is detected in 95% of cases."
explanation: >-
This review supports papillary craniopharyngioma as a BRAF V600-mutant
entity.
- reference: PMID:37437144
reference_title: BRAF-MEK Inhibition in Newly Diagnosed Papillary Craniopharyngiomas.
supports: SUPPORT
evidence_source: HUMAN_CLINICAL
snippet: "Genotyping has shown that more than 90% of papillary craniopharyngiomas carry BRAF V600E mutations"
explanation: >-
This phase 2 trial abstract supports the high prevalence of BRAF V600E in
papillary craniopharyngioma.
prevalence:
- population: General population
notes: >-
Craniopharyngioma is rare, with published incidence estimates in recent
reviews spanning roughly 0.13 to 2 per 100,000 population per year.
evidence:
- reference: PMID:38961911
reference_title: "Craniopharyngioma: A comprehensive review of the clinical presentation, radiological findings, management, and future Perspective."
supports: SUPPORT
evidence_source: HUMAN_CLINICAL
snippet: "The annual incidence ranges from 0.13 to 2 per 100,000 population per year with no gender predilection."
explanation: >-
The review provides the incidence range and notes absence of a strong
overall sex predilection.
progression:
- phase: Indolent local growth with high morbidity
notes: >-
Despite benign histology, recurrence and long-term morbidity are common
clinical problems because of the tumor's proximity to the
hypothalamic-pituitary and optic structures.
evidence:
- reference: PMID:36979325
reference_title: "Current Advances in Papillary Craniopharyngioma: State-Of-The-Art Therapies and Overview of the Literature."
supports: SUPPORT
evidence_source: HUMAN_CLINICAL
snippet: >-
Craniopharyngiomas are commonly classified as low-grade tumors, although
they may harbor a malignant behavior due to their high rate of recurrence
and long-term morbidity.
explanation: >-
This review supports modeling the disease course as locally recurrent and
morbidity-heavy despite low-grade classification.
- reference: PMID:37437144
reference_title: BRAF-MEK Inhibition in Newly Diagnosed Papillary Craniopharyngiomas.
supports: SUPPORT
evidence_source: HUMAN_CLINICAL
snippet: >-
Treatment with the use of surgery, radiation, or both is often associated
with substantial morbidity related to vision loss, neuroendocrine
dysfunction, and memory loss.
explanation: >-
The trial background summarizes the major long-term morbidity domains
associated with traditional local treatment.
pathophysiology:
- name: Sellar-Suprasellar Rathke Pouch Tumor Formation
description: >-
Craniopharyngioma arises from epithelial remnants of Rathke pouch in the
sellar/parasellar and suprasellar region, producing a slow-growing but
space-occupying epithelial mass near the pituitary gland and hypothalamus.
cell_types:
- preferred_term: Rathke pouch-derived epithelial cell
term:
id: CL:0000066
label: epithelial cell
locations:
- preferred_term: sella turcica
term:
id: UBERON:0003689
label: sella turcica
- preferred_term: Rathke pouch epithelium
term:
id: UBERON:0012287
label: Rathkes pouch epithelium
- preferred_term: pituitary gland
term:
id: UBERON:0000007
label: pituitary gland
biological_processes:
- preferred_term: tumor cell proliferation
modifier: INCREASED
term:
id: GO:0008283
label: cell population proliferation
evidence:
- reference: PMID:38961911
reference_title: "Craniopharyngioma: A comprehensive review of the clinical presentation, radiological findings, management, and future Perspective."
supports: SUPPORT
evidence_source: HUMAN_CLINICAL
snippet: >-
Craniopharyngioma (CP) is a rare intracranial tumor arising from the
epithelial remnants of Rathke's pouch, most frequently originating in the
sellar/parasellar region.
explanation: >-
The review directly anchors the tumor's origin and sellar/parasellar
localization.
downstream:
- target: Optic-Hypothalamic-Pituitary Mass Effect
causal_link_type: DIRECT
description: >-
Expansion in the sellar/suprasellar region compresses or injures nearby
optic, hypothalamic, pituitary, and third-ventricle structures.
- name: Optic-Hypothalamic-Pituitary Mass Effect
description: >-
Local tumor extension and treatment effects injure the optic chiasma,
pituitary gland, hypothalamus, and adjacent ventricular pathways, explaining
visual impairment, headache, hypopituitarism, diabetes insipidus, and
hydrocephalus or raised intracranial pressure.
locations:
- preferred_term: optic chiasm
term:
id: UBERON:0000959
label: optic chiasma
- preferred_term: hypothalamus
term:
id: UBERON:0001898
label: hypothalamus
- preferred_term: pituitary gland
term:
id: UBERON:0000007
label: pituitary gland
- preferred_term: third ventricle
term:
id: UBERON:0002286
label: third ventricle
evidence:
- reference: PMID:38961911
reference_title: "Craniopharyngioma: A comprehensive review of the clinical presentation, radiological findings, management, and future Perspective."
supports: SUPPORT
evidence_source: HUMAN_CLINICAL
snippet: >-
Due to its unique anatomical locations, the most frequently reported
clinical manifestations are headache, visual impairment, nausea/vomiting,
and endocrine deficiencies resulting in sexual dysfunction in adults and
growth failure in children.
explanation: >-
The clinical manifestations are directly attributable to mass effect and
hypothalamic-pituitary involvement at the tumor site.
- name: CTNNB1-Wnt ACP Tumor Signaling
description: >-
In adamantinomatous craniopharyngioma, somatic CTNNB1 alterations stabilize
beta-catenin and activate Wnt signaling in tumor clusters. These clusters
act as signaling centers that support epithelial proliferation, cystic/solid
architecture, and paracrine interaction with surrounding glial and immune
tissue.
genes:
- preferred_term: CTNNB1
term:
id: hgnc:2514
label: CTNNB1
cell_types:
- preferred_term: tumor epithelial cell
term:
id: CL:0000066
label: epithelial cell
biological_processes:
- preferred_term: Wnt signaling pathway
modifier: INCREASED
term:
id: GO:0016055
label: Wnt signaling pathway
evidence:
- reference: PMID:29541918
reference_title: Tumour compartment transcriptomics demonstrates the activation of inflammatory and odontogenic programmes in human adamantinomatous craniopharyngioma and identifies the MAPK/ERK pathway as a novel therapeutic target.
supports: SUPPORT
evidence_source: HUMAN_CLINICAL
snippet: >-
Adamantinomatous craniopharyngiomas (ACPs) are clinically challenging
tumours, the majority of which have activating mutations in CTNNB1.
explanation: >-
This human tumor molecular study supports CTNNB1 activation as the main
upstream ACP driver.
- reference: PMID:37565822
reference_title: Multi-omics analysis of adamantinomatous craniopharyngiomas reveals distinct molecular subgroups with prognostic and treatment response significance.
supports: SUPPORT
evidence_source: HUMAN_CLINICAL
snippet: >-
The WNT subgroup showed higher Wnt/β-catenin pathway activity, with a
greater number of epithelial cells and more predominantly solid tumors.
explanation: >-
Multi-omics subgrouping links Wnt/beta-catenin activity to epithelial-rich
ACP tumor architecture.
downstream:
- target: ACP Inflammatory and MAPK Microenvironment
causal_link_type: DIRECT
description: >-
CTNNB1-mutant ACP cluster cells signal to adjacent tumor, glial, and
immune compartments through paracrine pathways.
- name: ACP Inflammatory and MAPK Microenvironment
description: >-
ACP contains a reactive glial and immune microenvironment with inflammatory,
interferon, cytokine, and MAPK/ERK signaling programs. These pathways shape
invasive front behavior, cystic tumor biology, and potential sensitivity to
MEK inhibition or other anti-inflammatory strategies.
cell_types:
- preferred_term: astrocyte
term:
id: CL:0000127
label: astrocyte
- preferred_term: macrophage
term:
id: CL:0000235
label: macrophage
- preferred_term: T cell
term:
id: CL:0000084
label: T cell
biological_processes:
- preferred_term: inflammatory response
modifier: INCREASED
term:
id: GO:0006954
label: inflammatory response
- preferred_term: cytokine-mediated signaling pathway
modifier: INCREASED
term:
id: GO:0019221
label: cytokine-mediated signaling pathway
- preferred_term: MAPK cascade
modifier: INCREASED
term:
id: GO:0000165
label: MAPK cascade
evidence:
- reference: PMID:29541918
reference_title: Tumour compartment transcriptomics demonstrates the activation of inflammatory and odontogenic programmes in human adamantinomatous craniopharyngioma and identifies the MAPK/ERK pathway as a novel therapeutic target.
supports: SUPPORT
evidence_source: HUMAN_CLINICAL
snippet: >-
We validate these results by immunostaining against immune cell markers,
cytokine ELISA and proteome analysis in both solid tumour and cystic fluid
from ACP patients.
explanation: >-
Human ACP tissue and cyst-fluid measurements support immune and cytokine
microenvironment involvement.
- reference: PMID:29541918
reference_title: Tumour compartment transcriptomics demonstrates the activation of inflammatory and odontogenic programmes in human adamantinomatous craniopharyngioma and identifies the MAPK/ERK pathway as a novel therapeutic target.
supports: SUPPORT
evidence_source: IN_VITRO
snippet: >-
We reveal that inhibiting the MAPK/ERK pathway with trametinib, a
clinically approved MEK inhibitor, results in reduced proliferation and
increased apoptosis in explant cultures of human and mouse ACP.
explanation: >-
Ex vivo explant evidence supports MAPK/ERK as a tractable ACP pathway.
- reference: PMID:37565822
reference_title: Multi-omics analysis of adamantinomatous craniopharyngiomas reveals distinct molecular subgroups with prognostic and treatment response significance.
supports: SUPPORT
evidence_source: HUMAN_CLINICAL
snippet: >-
The ImA and ImB subgroups had activated inflammatory and interferon
response pathways, with enhanced immune cell infiltration and more
predominantly cystic tumors.
explanation: >-
Multi-omics clustering supports inflammatory/immune ACP subgroups linked
to cystic tumor architecture.
downstream:
- target: Optic-Hypothalamic-Pituitary Mass Effect
causal_link_type: INDIRECT_KNOWN_INTERMEDIATES
description: >-
Inflammatory and invasive-front biology can intensify local tissue
reaction around critical hypothalamic and optic structures.
- name: BRAF V600E MAPK PCP Tumor Signaling
description: >-
Papillary craniopharyngioma is driven in most cases by BRAF V600E, which
activates MAPK/ERK signaling and creates a genotype-matched therapeutic
vulnerability to combined BRAF and MEK inhibition.
genes:
- preferred_term: BRAF
term:
id: hgnc:1097
label: BRAF
biological_processes:
- preferred_term: MAPK cascade
modifier: INCREASED
term:
id: GO:0000165
label: MAPK cascade
evidence:
- reference: PMID:37437144
reference_title: BRAF-MEK Inhibition in Newly Diagnosed Papillary Craniopharyngiomas.
supports: SUPPORT
evidence_source: HUMAN_CLINICAL
snippet: "Genotyping has shown that more than 90% of papillary craniopharyngiomas carry BRAF V600E mutations"
explanation: >-
This phase 2 trial background supports BRAF V600E as the defining PCP
driver lesion.
- reference: PMID:39634188
reference_title: Practical application of precision oncology in adult onset craniopharyngiomas.
supports: SUPPORT
evidence_source: HUMAN_CLINICAL
snippet: >-
Identification of specific molecular driver mutations in each type- BRAF
V600E in papillary craniopharyngiomas (PCP) and CTNNB1 in
adamantinomatous craniopharyngiomas (ACP) has resulted in a paradigm
shift in the management of adult CPs.
explanation: >-
This adult precision-oncology review links BRAF V600E and CTNNB1 to the
subtype-specific treatment paradigm.
downstream:
- target: Optic-Hypothalamic-Pituitary Mass Effect
causal_link_type: DIRECT
description: >-
BRAF V600E-driven MAPK activation leads to papillary craniopharyngioma
tumor growth in the sellar/suprasellar region, producing optic,
hypothalamic, and pituitary mass effect.
phenotypes:
- category: Neurological
name: Headache
description: >-
Headache is a common presenting manifestation from sellar/suprasellar mass
effect and raised intracranial pressure.
phenotype_term:
preferred_term: Headache
term:
id: HP:0002315
label: Headache
evidence:
- reference: PMID:38961911
reference_title: "Craniopharyngioma: A comprehensive review of the clinical presentation, radiological findings, management, and future Perspective."
supports: SUPPORT
evidence_source: HUMAN_CLINICAL
snippet: >-
Due to its unique anatomical locations, the most frequently reported
clinical manifestations are headache, visual impairment, nausea/vomiting,
and endocrine deficiencies resulting in sexual dysfunction in adults and
growth failure in children.
explanation: >-
The review names headache among the most frequently reported clinical
manifestations.
- category: Ophthalmologic
name: Visual Impairment
description: >-
Visual impairment and visual-field deficits reflect compression or injury of
the optic chiasma and nearby optic pathways.
phenotype_term:
preferred_term: Visual impairment
term:
id: HP:0000505
label: Visual impairment
evidence:
- reference: PMID:38961911
reference_title: "Craniopharyngioma: A comprehensive review of the clinical presentation, radiological findings, management, and future Perspective."
supports: SUPPORT
evidence_source: HUMAN_CLINICAL
snippet: >-
Due to its unique anatomical locations, the most frequently reported
clinical manifestations are headache, visual impairment, nausea/vomiting,
and endocrine deficiencies resulting in sexual dysfunction in adults and
growth failure in children.
explanation: >-
The review names visual impairment as a frequent manifestation.
- category: Endocrine
name: Hypopituitarism
description: >-
Anterior pituitary hormone deficiencies can cause growth failure in
children and sexual dysfunction or other endocrine-axis failure in adults.
phenotype_term:
preferred_term: Hypopituitarism
term:
id: HP:0040075
label: Hypopituitarism
evidence:
- reference: PMID:38961911
reference_title: "Craniopharyngioma: A comprehensive review of the clinical presentation, radiological findings, management, and future Perspective."
supports: SUPPORT
evidence_source: HUMAN_CLINICAL
snippet: >-
Due to its unique anatomical locations, the most frequently reported
clinical manifestations are headache, visual impairment, nausea/vomiting,
and endocrine deficiencies resulting in sexual dysfunction in adults and
growth failure in children.
explanation: >-
This supports pituitary endocrine deficiency as a frequent disease
manifestation.
- category: Endocrine
name: Growth Hormone Deficiency
description: >-
Growth hormone deficiency is a specific and predominant endocrinological
disturbance in craniopharyngioma, reflecting pituitary and
hypothalamic-pituitary axis involvement.
phenotype_term:
preferred_term: Growth hormone deficiency
term:
id: HP:0000824
label: Decreased response to growth hormone stimulation test
evidence:
- reference: PMID:38961911
reference_title: "Craniopharyngioma: A comprehensive review of the clinical presentation, radiological findings, management, and future Perspective."
supports: SUPPORT
evidence_source: HUMAN_CLINICAL
snippet: "Growth hormone deficiency is the most predominant endocrinological disturbance associated with craniopharyngioma."
explanation: >-
The review specifically identifies growth hormone deficiency as the
predominant endocrine disturbance in craniopharyngioma.
- category: Endocrine
name: Diabetes Insipidus
description: >-
Posterior pituitary and hypothalamic injury can produce central diabetes
insipidus, especially after tumor growth or local therapy affects the
hypothalamic-pituitary axis.
phenotype_term:
preferred_term: Diabetes insipidus
term:
id: HP:0000873
label: Diabetes insipidus
evidence:
- reference: PMID:37437144
reference_title: BRAF-MEK Inhibition in Newly Diagnosed Papillary Craniopharyngiomas.
supports: PARTIAL
evidence_source: HUMAN_CLINICAL
snippet: >-
Treatment with the use of surgery, radiation, or both is often associated
with substantial morbidity related to vision loss, neuroendocrine
dysfunction, and memory loss.
explanation: >-
The abstract supports neuroendocrine dysfunction as a major morbidity
domain; the specific diabetes-insipidus mapping is a common
hypothalamic-pituitary manifestation rather than directly named in this
abstract.
- category: Neurological
name: Hydrocephalus or Raised Intracranial Pressure
description: >-
Large suprasellar tumors may obstruct ventricular pathways, producing
hydrocephalus or raised intracranial pressure with nausea, vomiting, and
headache.
phenotype_term:
preferred_term: Hydrocephalus
term:
id: HP:0000238
label: Hydrocephalus
evidence:
- reference: PMID:38961911
reference_title: "Craniopharyngioma: A comprehensive review of the clinical presentation, radiological findings, management, and future Perspective."
supports: PARTIAL
evidence_source: HUMAN_CLINICAL
snippet: >-
Due to its unique anatomical locations, the most frequently reported
clinical manifestations are headache, visual impairment, nausea/vomiting,
and endocrine deficiencies resulting in sexual dysfunction in adults and
growth failure in children.
explanation: >-
The review supports nausea/vomiting and headache among common
manifestations; hydrocephalus is retained as the mechanistic HPO mapping
for obstructive raised-pressure presentations but is not directly named in
this abstract snippet.
- category: Neurological
name: Memory Impairment
description: >-
Memory impairment can occur as part of craniopharyngioma morbidity,
especially when disease or local treatment affects hypothalamic and adjacent
brain structures.
phenotype_term:
preferred_term: Memory impairment
term:
id: HP:0002354
label: Memory impairment
evidence:
- reference: PMID:37437144
reference_title: BRAF-MEK Inhibition in Newly Diagnosed Papillary Craniopharyngiomas.
supports: SUPPORT
evidence_source: HUMAN_CLINICAL
snippet: >-
Treatment with the use of surgery, radiation, or both is often associated
with substantial morbidity related to vision loss, neuroendocrine
dysfunction, and memory loss.
explanation: >-
The phase 2 trial background explicitly names memory loss among major
morbidity domains associated with craniopharyngioma treatment.
genetic:
- name: CTNNB1
association: Somatic activating mutation in adamantinomatous craniopharyngioma
gene_term:
preferred_term: CTNNB1
term:
id: hgnc:2514
label: CTNNB1
notes: >-
Somatic CTNNB1 mutations are the core ACP driver and activate Wnt/beta-catenin
signaling.
evidence:
- reference: PMID:36748936
reference_title: The molecular pathogenesis of craniopharyngiomas.
supports: SUPPORT
evidence_source: HUMAN_CLINICAL
snippet: >-
ACP and PCP subtypes can be identified by the presence of mutations in
CTNNB1 and BRAF genes, with prevalence around 60% and 90%, respectively.
explanation: >-
This molecular review identifies CTNNB1 mutations as the ACP-defining
alteration.
- name: BRAF
association: Somatic BRAF V600E mutation in papillary craniopharyngioma
gene_term:
preferred_term: BRAF
term:
id: hgnc:1097
label: BRAF
notes: >-
BRAF V600E is present in most papillary craniopharyngiomas and predicts
sensitivity to BRAF/MEK inhibitor combinations.
evidence:
- reference: PMID:37437144
reference_title: BRAF-MEK Inhibition in Newly Diagnosed Papillary Craniopharyngiomas.
supports: SUPPORT
evidence_source: HUMAN_CLINICAL
snippet: "Genotyping has shown that more than 90% of papillary craniopharyngiomas carry BRAF V600E mutations"
explanation: >-
This trial background supports BRAF V600E as the dominant PCP alteration.
histopathology:
- name: Adamantinomatous Craniopharyngioma
finding_term:
preferred_term: Adamantinomatous Craniopharyngioma
term:
id: NCIT:C4726
label: Adamantinomatous Craniopharyngioma
diagnostic: true
description: >-
ACP is the adamantinomatous histologic entity, with CTNNB1-driven epithelial
clusters, cystic and solid components, palisading epithelium, and an
inflammatory/glial reaction.
evidence:
- reference: PMID:29541918
reference_title: Tumour compartment transcriptomics demonstrates the activation of inflammatory and odontogenic programmes in human adamantinomatous craniopharyngioma and identifies the MAPK/ERK pathway as a novel therapeutic target.
supports: SUPPORT
evidence_source: HUMAN_CLINICAL
snippet: >-
They are histologically complex, showing cystic and solid components, the
latter comprised of different morphological cell types (e.g.
β-catenin-accumulating cluster cells and palisading epithelium),
surrounded by a florid glial reaction with immune cells.
explanation: >-
This human ACP molecular-pathology study describes the diagnostic
histologic architecture and microenvironment.
- name: Papillary Craniopharyngioma
finding_term:
preferred_term: Papillary Craniopharyngioma
term:
id: NCIT:C4725
label: Papillary Craniopharyngioma
diagnostic: true
description: >-
PCP is the papillary histologic entity, distinguished from ACP by BRAF V600E
mutation status and integrated histologic, radiologic, and genetic features.
evidence:
- reference: PMID:36979325
reference_title: "Current Advances in Papillary Craniopharyngioma: State-Of-The-Art Therapies and Overview of the Literature."
supports: SUPPORT
evidence_source: HUMAN_CLINICAL
snippet: >-
Craniopharyngiomas are classically distinguished into two histological
types (adamantinomatous and papillary), which have been recently considered
by the WHO classification of CNS tumors as two independent entities, due to
different epidemiological, radiological, histopathological, and genetic
patterns.
explanation: >-
This review supports PCP as a distinct histologic and molecular entity.
diagnosis:
- name: MRI Sellar Region Imaging
description: >-
MRI characterizes the cystic and solid sellar/suprasellar mass and its
relationship to the optic chiasm, pituitary gland, hypothalamus, and third
ventricle.
diagnosis_term:
preferred_term: magnetic resonance imaging procedure
term:
id: MAXO:0000424
label: magnetic resonance imaging procedure
results: >-
Sellar/parasellar or suprasellar cystic-solid mass and anatomic relationship
to optic and hypothalamic-pituitary structures.
evidence:
- reference: PMID:38961911
reference_title: "Craniopharyngioma: A comprehensive review of the clinical presentation, radiological findings, management, and future Perspective."
supports: SUPPORT
evidence_source: HUMAN_CLINICAL
snippet: "Magnetic Resonance Imaging (MRI) further characterizes craniopharyngiomas and helps to narrow down the differential diagnoses."
explanation: >-
The review supports MRI as a key diagnostic characterization tool.
- name: CT Calcification Assessment
description: >-
CT is used to detect calcification within craniopharyngioma tissue, a common
imaging feature particularly relevant to ACP.
diagnosis_term:
preferred_term: computed tomography procedure
term:
id: MAXO:0000571
label: computed tomography procedure
results: Calcification in craniopharyngioma tissue when present.
evidence:
- reference: PMID:38961911
reference_title: "Craniopharyngioma: A comprehensive review of the clinical presentation, radiological findings, management, and future Perspective."
supports: SUPPORT
evidence_source: HUMAN_CLINICAL
snippet: "Computed tomography (CT) is gold standard to detect calcifications in CP tissue"
explanation: >-
The review specifically supports CT for identifying calcified
craniopharyngioma tissue.
- name: Integrated Histologic and Molecular Subtyping
description: >-
Diagnosis and treatment planning integrate clinical, endocrine, imaging,
histologic, and molecular evidence, including BRAF V600E testing in PCP and
CTNNB1/Wnt evidence in ACP.
diagnosis_term:
preferred_term: clinical assessment
term:
id: MAXO:0000487
label: clinical assessment
markers: CTNNB1 mutation, BRAF V600E mutation, beta-catenin localization
evidence:
- reference: PMID:36979325
reference_title: "Current Advances in Papillary Craniopharyngioma: State-Of-The-Art Therapies and Overview of the Literature."
supports: SUPPORT
evidence_source: HUMAN_CLINICAL
snippet: >-
Based on our research and experience, we strongly suggest a multimodal
approach combining clinical, endocrinological, radiological, histological,
and oncological findings in both preoperative workup and postoperative
follow up to define a roadmap integrating every aspect of this challenging
condition.
explanation: >-
The review supports an integrated diagnostic and management approach that
combines clinical, endocrine, radiologic, histologic, and oncologic data.
- reference: PMID:39634188
reference_title: Practical application of precision oncology in adult onset craniopharyngiomas.
supports: SUPPORT
evidence_source: HUMAN_CLINICAL
snippet: >-
Identification of specific molecular driver mutations in each type- BRAF
V600E in papillary craniopharyngiomas (PCP) and CTNNB1 in
adamantinomatous craniopharyngiomas (ACP) has resulted in a paradigm
shift in the management of adult CPs.
explanation: >-
This supports molecular subtype testing as clinically actionable.
treatments:
- name: Maximal Safe Surgical Resection
description: >-
Surgery is used to establish diagnosis, decompress symptomatic mass effect,
and remove as much tumor as safely possible while limiting hypothalamic,
optic, and pituitary injury.
treatment_term:
preferred_term: surgical procedure
term:
id: MAXO:0000004
label: surgical procedure
target_mechanisms:
- target: Sellar-Suprasellar Rathke Pouch Tumor Formation
treatment_effect: INHIBITS
description: >-
Surgical cytoreduction removes tumor tissue and reduces the local
space-occupying lesion.
- target: Optic-Hypothalamic-Pituitary Mass Effect
treatment_effect: INHIBITS
description: >-
Decompression aims to relieve mass-related symptoms affecting optic,
pituitary, hypothalamic, and ventricular structures.
evidence:
- reference: PMID:38961911
reference_title: "Craniopharyngioma: A comprehensive review of the clinical presentation, radiological findings, management, and future Perspective."
supports: SUPPORT
evidence_source: HUMAN_CLINICAL
snippet: >-
In almost all craniopharyngioma cases, surgery is indicated to: establish
the diagnosis, relieve mass-related symptoms, and remove as much tumor as
is safely possible.
explanation: >-
The review directly states the diagnostic, decompressive, and cytoreductive
rationale for surgery.
- name: Radiation Therapy for Local Tumor Control
description: >-
Radiation therapy is used with or after surgery for local disease control,
but must be balanced against morbidity involving the optic,
hypothalamic-pituitary, and adjacent brain structures.
treatment_term:
preferred_term: radiation therapy
term:
id: MAXO:0000014
label: radiation therapy
target_mechanisms:
- target: Sellar-Suprasellar Rathke Pouch Tumor Formation
treatment_effect: INHIBITS
description: >-
Radiation therapy aims to control residual or recurrent local tumor growth.
evidence:
- reference: PMID:37437144
reference_title: BRAF-MEK Inhibition in Newly Diagnosed Papillary Craniopharyngiomas.
supports: SUPPORT
evidence_source: HUMAN_CLINICAL
snippet: >-
Treatment with the use of surgery, radiation, or both is often associated
with substantial morbidity related to vision loss, neuroendocrine
dysfunction, and memory loss.
explanation: >-
The phase 2 trial background identifies radiation, alone or with surgery,
as part of traditional craniopharyngioma treatment and notes associated
morbidity.
- reference: PMID:38961911
reference_title: "Craniopharyngioma: A comprehensive review of the clinical presentation, radiological findings, management, and future Perspective."
supports: SUPPORT
evidence_source: HUMAN_CLINICAL
snippet: >-
Recent neurosurgical technical advances, including innovative surgical
approaches, detailed radiotherapy protocols, targeted therapy, replacement
of lost hormonal functions and quality of life all have the potential to
improve the outcome of patients with craniopharyngioma.
explanation: >-
This review supports radiotherapy protocols as part of contemporary
craniopharyngioma management.
- name: BRAF/MEK Inhibition for BRAF V600E Papillary Craniopharyngioma
description: >-
Combined BRAF and MEK inhibition, such as vemurafenib plus cobimetinib or
dabrafenib plus trametinib, is a genotype-matched treatment strategy for
BRAF V600E papillary craniopharyngioma and may reduce the need for morbid
local therapy.
treatment_term:
preferred_term: Pharmacotherapy
term:
id: NCIT:C15986
label: Pharmacotherapy
therapeutic_agent:
- preferred_term: vemurafenib
term:
id: CHEBI:63637
label: vemurafenib
- preferred_term: cobimetinib
term:
id: CHEBI:90851
label: cobimetinib
- preferred_term: dabrafenib
term:
id: CHEBI:75045
label: dabrafenib
- preferred_term: trametinib
term:
id: CHEBI:75998
label: trametinib
target_mechanisms:
- target: BRAF V600E MAPK PCP Tumor Signaling
treatment_effect: INHIBITS
description: >-
Combined BRAF and MEK inhibition targets the genotype-matched MAPK driver
pathway in papillary craniopharyngioma.
evidence:
- reference: PMID:37437144
reference_title: BRAF-MEK Inhibition in Newly Diagnosed Papillary Craniopharyngiomas.
supports: SUPPORT
evidence_source: HUMAN_CLINICAL
snippet: >-
The median reduction in the volume of the tumor was 91% (range, 68 to 99).
explanation: >-
This phase 2 trial supports high objective response to
vemurafenib-cobimetinib in BRAF-mutant PCP.
- reference: PMID:39456573
reference_title: "Update on Neoadjuvant and Adjuvant BRAF Inhibitors in Papillary Craniopharyngioma: A Systematic Review."
supports: SUPPORT
evidence_source: HUMAN_CLINICAL
snippet: >-
Treatment is shifting to a wider multidisciplinary management, where a key
role is played by targeted therapies, to improve outcomes and quality of
life for patients with BRAF-mutated craniopharyngiomas.
explanation: >-
The systematic review supports targeted therapy as an increasingly central
component of BRAF-mutated PCP management.
- name: Binimetinib for Recurrent Adamantinomatous Craniopharyngioma
description: >-
Binimetinib MEK inhibition is under phase 2 clinical investigation for
pediatric and young-adult recurrent ACP, supported by ACP MAPK pathway
biology but not yet established as standard care.
treatment_term:
preferred_term: Pharmacotherapy
term:
id: NCIT:C15986
label: Pharmacotherapy
therapeutic_agent:
- preferred_term: binimetinib
term:
id: CHEBI:145371
label: binimetinib
target_mechanisms:
- target: ACP Inflammatory and MAPK Microenvironment
treatment_effect: INHIBITS
description: >-
MEK inhibition is intended to inhibit MAPK signaling active in ACP
microenvironmental compartments.
evidence:
- reference: clinicaltrials:NCT05286788
reference_title: Phase 2 Study of the MEK Inhibitor MEKTOVI® (Binimetinib) for the Treatment of Pediatric Adamantinomatous Craniopharyngioma
supports: SUPPORT
evidence_source: HUMAN_CLINICAL
snippet: >-
In this Phase II, the drug will be used to treat pediatric patients
diagnosed with recurrent Adamantinomatous Craniopharyngioma including
patients who have undergone surgery and/or radiation therapy.
explanation: >-
The ClinicalTrials.gov summary supports binimetinib as an investigational
treatment for recurrent pediatric ACP.
- reference: PMID:29541918
reference_title: Tumour compartment transcriptomics demonstrates the activation of inflammatory and odontogenic programmes in human adamantinomatous craniopharyngioma and identifies the MAPK/ERK pathway as a novel therapeutic target.
supports: PARTIAL
evidence_source: IN_VITRO
snippet: >-
We reveal that inhibiting the MAPK/ERK pathway with trametinib, a
clinically approved MEK inhibitor, results in reduced proliferation and
increased apoptosis in explant cultures of human and mouse ACP.
explanation: >-
Ex vivo ACP explant data support MEK inhibition as a mechanistic rationale,
but not yet as proven clinical efficacy.
- name: Brachytherapy for Cystic Craniopharyngioma
description: >-
Intracystic or local brachytherapy is an alternative radiation-based
strategy for selected cystic craniopharyngiomas, with long-term
progression-free-survival evidence from pooled clinical trials.
treatment_term:
preferred_term: radiation therapy
term:
id: MAXO:0000014
label: radiation therapy
target_mechanisms:
- target: Sellar-Suprasellar Rathke Pouch Tumor Formation
treatment_effect: INHIBITS
description: >-
Local radiation delivered to the cystic tumor compartment aims to control
tumor progression while limiting broader exposure.
evidence:
- reference: PMID:38790011
reference_title: "Brachytherapy in craniopharyngiomas: a systematic review and meta-analysis of long-term follow-up."
supports: SUPPORT
evidence_source: HUMAN_CLINICAL
snippet: >-
Brachytherapy has been indicated as an alternative option for treating
cystic craniopharyngiomas (CPs).
explanation: >-
This systematic review and meta-analysis supports brachytherapy as an
option for cystic craniopharyngioma.
- reference: PMID:38790011
reference_title: "Brachytherapy in craniopharyngiomas: a systematic review and meta-analysis of long-term follow-up."
supports: SUPPORT
evidence_source: HUMAN_CLINICAL
snippet: >-
The results of the meta-analysis showed that 1-year, 2-3 years and 5 years
progression free survival rates (PFS) are 75% (95%CI: 66-84%), 62%
(95%CI: 52-72%) and 57% (95%CI: 22-92%), respectively.
explanation: >-
The pooled clinical-trial analysis provides long-term PFS estimates for
brachytherapy.
clinical_trials:
- name: NCT03224767
phase: PHASE_II
description: >-
Phase 2 Alliance study of vemurafenib plus cobimetinib for BRAF V600E
mutation-positive papillary craniopharyngioma.
evidence:
- reference: clinicaltrials:NCT03224767
reference_title: Phase II Trial of BRAF/MEK Inhibitors in Papillary Craniopharyngiomas
supports: SUPPORT
evidence_source: HUMAN_CLINICAL
snippet: >-
This phase II trial studies how well vemurafenib and cobimetinib work in
treating patients with BRAF V600E mutation positive craniopharyngioma.
explanation: >-
The trial summary directly describes the BRAF/MEK inhibitor intervention
and disease genotype.
- name: NCT05525273
phase: PHASE_II
description: >-
Phase 2 study of neoadjuvant and postoperative dabrafenib plus trametinib
for BRAF-mutated papillary craniopharyngioma.
evidence:
- reference: clinicaltrials:NCT05525273
reference_title: Neoadjuvant and Postoperative Treatment With Dabrafenib and Trametinib in BRAF Mutated Papillary Craniopharyngioma
supports: SUPPORT
evidence_source: HUMAN_CLINICAL
snippet: >-
Subjects with papillary craniopharyngioma harboring a BRAF mutation will
be treated with a BRAF + MEK inhibitor (dabrafenib + trametinib) after
informed consent.
explanation: >-
The trial summary supports ongoing genotype-matched dabrafenib/trametinib
evaluation in papillary craniopharyngioma.
- name: NCT05286788
phase: PHASE_II
description: >-
Phase 2 study of the MEK inhibitor binimetinib in recurrent pediatric
adamantinomatous craniopharyngioma after surgery and/or radiation therapy.
evidence:
- reference: clinicaltrials:NCT05286788
reference_title: Phase 2 Study of the MEK Inhibitor MEKTOVI® (Binimetinib) for the Treatment of Pediatric Adamantinomatous Craniopharyngioma
supports: SUPPORT
evidence_source: HUMAN_CLINICAL
snippet: >-
In this Phase II, the drug will be used to treat pediatric patients
diagnosed with recurrent Adamantinomatous Craniopharyngioma including
patients who have undergone surgery and/or radiation therapy.
explanation: >-
The trial summary supports binimetinib as an active investigational ACP
treatment strategy.
notes: >-
Falcon research and the fetched abstracts did not identify established
environmental, infectious, lifestyle, or inherited familial risk factors for
craniopharyngioma. Differential diagnosis of sellar/suprasellar masses was
not curated here because the Falcon report explicitly marked that evidence as
incomplete for this run.
Craniopharyngiomas are rare epithelial intracranial neoplasms that arise along the craniopharyngeal duct / from remnants of Rathke’s pouch, typically in the sellar and suprasellar region, often extending toward the third ventricle (neto2025recentadvancesin pages 1-2, campanini2023themolecularpathogenesis pages 1-2, campanini2023themolecularpathogenesis pages 2-3). Their clinical impact is largely due to proximity to the optic apparatus, pituitary gland, and hypothalamus, causing visual and endocrine morbidity (biswas2024practicalapplicationof pages 1-2, brastianos2023brafmekinhibitionin pages 1-4).
The WHO classifies craniopharyngiomas as histologically benign WHO grade 1 tumors, but they can behave aggressively via adherence/invasion of adjacent critical structures (campanini2023themolecularpathogenesis pages 1-2, neto2025recentadvancesin pages 1-2).
Commonly used names include adamantinomatous craniopharyngioma (ACP) and papillary craniopharyngioma (PCP), which the 2021 WHO CNS classification treats as separate tumor entities (biswas2024practicalapplicationof pages 1-2, jannelli2023currentadvancesin pages 1-2).
Most information in this report is derived from aggregated disease-level resources (systematic reviews, narrative reviews, population registries) and clinical trials; some mechanistic claims are supported by primary molecular studies using human tissue and model systems (brastianos2023brafmekinhibitionin pages 1-4, apps2018tumourcompartmenttranscriptomics pages 1-2, wang2024multiomicsanalysisof pages 1-2).
Primary causal factors are molecular drivers that define two biologically distinct entities: - Adamantinomatous craniopharyngioma (ACP): driven by somatic CTNNB1 mutations (β‑catenin), with Wnt/β‑catenin pathway activation and β‑catenin accumulation in characteristic cell clusters (campanini2023themolecularpathogenesis pages 1-2, campanini2023themolecularpathogenesis pages 4-6). - Papillary craniopharyngioma (PCP): driven by BRAF p.(V600E) in ~90–95% (or higher) of cases, activating MAPK/ERK signaling (jannelli2023currentadvancesin pages 1-2, campanini2023themolecularpathogenesis pages 1-2, campanini2023themolecularpathogenesis pages 2-3).
No clear environmental or lifestyle risk factors were identified in the retrieved evidence; CPs are generally considered sporadic tumors with age‑related incidence peaks (an2025molecularsubtypesof pages 1-2, javidialsaadi2025advancesinthe pages 2-4).
No protective factors or gene–environment interactions were identified in the retrieved evidence.
Craniopharyngiomas typically have insidious onset with symptoms driven by mass effect and hypothalamic–pituitary involvement (javidialsaadi2025advancesinthe pages 4-6, alboqami2024craniopharyngiomaacomprehensive pages 2-5).
Frequent manifestations include: - Headache: reported as 83.6% in one synthesis, and commonly 50–80% across reviews (javidialsaadi2025advancesinthe pages 4-6, gonzalezgallego2025moderntreatmentof pages 2-4). - Visual deficits: reported as 81.6% in one synthesis; classic bitemporal hemianopia due to optic chiasm compression, and decreased visual acuity (javidialsaadi2025advancesinthe pages 4-6, alboqami2024craniopharyngiomaacomprehensive pages 2-5, gonzalezgallego2025moderntreatmentof pages 2-4). - Endocrine dysfunction (pituitary axis deficits): endocrine deficits are common (e.g., 75–90% in one review synthesis), including central hypothyroidism, hypogonadism, adrenal insufficiency, and diabetes insipidus (gonzalezgallego2025moderntreatmentof pages 2-4, alboqami2024craniopharyngiomaacomprehensive pages 2-5). - Hydrocephalus / raised intracranial pressure: obstruction of the third ventricle can cause hydrocephalus; reported ranges include 10–30% for obstructive hydrocephalus in one synthesis (alboqami2024craniopharyngiomaacomprehensive pages 2-5, gonzalezgallego2025moderntreatmentof pages 2-4).
Additional phenotype frequencies reported in one review synthesis include endocrine deficit subtypes such as growth hormone deficiency (~85%), gonadotroph deficiency (~40%), ACTH (~25%), TSH (~25%), and diabetes insipidus (~20%) (javidialsaadi2025advancesinthe pages 6-8).
High overall survival contrasts with long‑term morbidity, driven by visual loss, neuroendocrine deficits, and hypothalamic dysfunction (brastianos2023brafmekinhibitionin pages 1-4, biswas2024practicalapplicationof pages 1-2).
(HPO identifiers are provided as ontology suggestions; specific term mapping may be refined for local database standards.)
A 2024 multi‑omics study profiled a large cohort (119 ACP and 23 PCP among 142 cases) using WES/RNA‑seq/DNA methylation and defined three ACP molecular subgroups—WNT, ImA, and ImB—with distinct pathway activation and imaging/histologic correlates (wang2024multiomicsanalysisof pages 1-2). The WNT subgroup showed stronger Wnt/β‑catenin activity and more epithelial/solid tumors, whereas ImA/ImB showed inflammatory and interferon responses with more cystic tumors and immune infiltration (wang2024multiomicsanalysisof pages 1-2). Prognostically, WNT had better event‑free survival than ImB, and ImA/ImB were predicted more likely to respond to immune checkpoint blockade than WNT (wang2024multiomicsanalysisof pages 1-2, wang2024multiomicsanalysisof pages 8-10).
Mechanistic tissue studies support that ACP contains a prominent inflammatory microenvironment; tumor clusters are surrounded by gliosis/inflammatory reaction, and inflammatory programs (including inflammasome activation) have been described in transcriptomic/proteomic studies (campanini2023themolecularpathogenesis pages 4-6, apps2018tumourcompartmenttranscriptomics pages 1-2).
No specific environmental, lifestyle, or infectious causal agents were identified in the retrieved evidence.
ACP causal chain (simplified): Somatic CTNNB1 mutation → stabilization/nuclear accumulation of β‑catenin in discrete tumor clusters → Wnt/β‑catenin hyperactivation with cluster cells acting as signaling centers → secretion of growth factors/cytokines/chemokines and remodeling of surrounding tissue with gliosis/inflammation → locally invasive behavior with cyst formation and adherence to hypothalamus/optic pathways → clinical syndrome of visual deficits and endocrine/hypothalamic dysfunction (campanini2023themolecularpathogenesis pages 4-6, apps2018tumourcompartmenttranscriptomics pages 1-2, alboqami2024craniopharyngiomaacomprehensive pages 2-5).
PCP causal chain (simplified): BRAF p.(V600E) mutation → MAPK/ERK pathway activation → growth of predominantly solid suprasellar tumor mass → optic chiasm compression and pituitary stalk/gland dysfunction → visual field loss and hypopituitarism; importantly, the dominant oncogenic driver yields high sensitivity to BRAF/MEK inhibitors (campanini2023themolecularpathogenesis pages 2-3, brastianos2023brafmekinhibitionin pages 1-4).
Although ACP is classically Wnt‑driven, MAPK/ERK pathway activation has been observed in compartments of ACP, and MEK inhibition with trametinib in ex vivo ACP tissue reduced pERK1/2, increased apoptosis, and decreased proliferation (campanini2023themolecularpathogenesis pages 4-6). This provides biological rationale for MEK‑inhibitor trials in ACP (NCT05286788 chunk 1).
Craniopharyngiomas arise in the sellar/suprasellar region, near the pituitary–hypothalamic axis (campanini2023themolecularpathogenesis pages 1-2, brastianos2023brafmekinhibitionin pages 1-4).
Commonly impacted structures include the optic chiasm/optic apparatus, pituitary stalk, hypothalamus, and sometimes the third ventricle (alboqami2024craniopharyngiomaacomprehensive pages 2-5, campanini2023themolecularpathogenesis pages 2-3).
Craniopharyngiomas show a bimodal age distribution with a pediatric peak (~5–14/15 years) and an adult peak (variously reported ~45–60 or ~50–74 years) (an2025molecularsubtypesof pages 1-2, javidialsaadi2025advancesinthe pages 2-4, neto2025recentadvancesin pages 1-2).
They are slow-growing but often chronic due to recurrence and long-term morbidity after treatment in this anatomically constrained region (brastianos2023brafmekinhibitionin pages 1-4, neto2025recentadvancesin pages 1-2).
Some reviews report no gender predilection overall (neto2025recentadvancesin pages 1-2). Subtype distribution is age-skewed: ACP occurs in both children and adults; PCP is largely adult (neto2025recentadvancesin pages 1-2, jannelli2023currentadvancesin pages 1-2).
Diagnosis is suggested by a sellar/suprasellar mass with cystic and/or solid components on MRI/CT; CT is particularly useful for calcifications, while MRI delineates soft tissue, cystic components, and relationships to the optic chiasm, pituitary stalk/gland, and hypothalamus (gonzalezgallego2025moderntreatmentof pages 2-4, javidialsaadi2025advancesinthe pages 6-8).
Calcifications are emphasized as frequent (reported ~90% in one review synthesis) (alboqami2024craniopharyngiomaacomprehensive pages 2-5).
Molecular testing is clinically actionable in PCP: identifying BRAF V600E enables use of BRAF/MEK inhibition (brastianos2023brafmekinhibitionin pages 1-4, NCT05525273 chunk 1).
Differential diagnosis is not comprehensively extracted from the available evidence snippets in this run; however, in practice it typically includes other sellar/suprasellar masses (e.g., pituitary adenomas, Rathke cleft cyst, germ cell tumors). A dedicated diagnostic radiology/pathology source would be needed for a fully cited differential list.
Overall survival is generally favorable compared with malignant brain tumors, but long-term morbidity is high due to location and treatment effects (brastianos2023brafmekinhibitionin pages 1-4, biswas2024practicalapplicationof pages 1-2). A narrative review reports wide 10‑year survival ranges (40–95%) reflecting heterogeneity and treatment era differences (javidialsaadi2025advancesinthe pages 4-6).
Major long-term morbidities include persistent endocrine deficits and hypothalamic dysfunction; hypothalamic injury is a key driver of severe sequelae (gonzalezgallego2025moderntreatmentof pages 2-4, brastianos2023brafmekinhibitionin pages 1-4).
Standard management historically relies on maximal safe resection with adjuvant radiotherapy when necessary, balanced against risk of hypothalamic/optic injury (brastianos2023brafmekinhibitionin pages 1-4, biswas2024practicalapplicationof pages 1-2).
A pivotal 2023 phase II study (papillary CP, BRAF‑mutant, no prior radiation) treated 16 patients with vemurafenib + cobimetinib and reported: 15/16 (94%) durable partial response or better, median tumor volume reduction 91%, and 12‑month PFS 87% (24‑month PFS 58%) (brastianos2023brafmekinhibitionin pages 1-4).
Direct abstract quotes supporting this include: - “Genotyping has shown that more than 90% of papillary craniopharyngiomas carry BRAF V600E mutations” (Brastianos et al., 2023) (brastianos2023brafmekinhibitionin pages 1-4). - “15 (94% …) had a durable objective partial response or better… The median reduction in the volume of the tumor was 91%” (brastianos2023brafmekinhibitionin pages 1-4).
A 2024 systematic review summarizing neoadjuvant/adjuvant BRAF±MEK inhibitor use in PCP found volumetric reductions ranging 24–100%, with ≥80% reductions reported in 64% of adjuvant cases, and near‑complete responses common in neoadjuvant settings (cossu2024updateonneoadjuvant pages 1-2).
Real-world implementation pattern: targeted therapy is increasingly used to de‑escalate morbid surgery/radiation in BRAF‑mutant PCP, while emphasizing multidisciplinary planning and close toxicity monitoring (biswas2024practicalapplicationof pages 2-3, NCT05525273 chunk 1).
A 2024 retrospective case series evaluated intracystic peginterferon alfa‑2a delivered weekly ×6 via Ommaya reservoir in 5 patients with cystic CP, reporting cyst shrinkage in all five and good tolerability ().
A 2024 systematic review/meta-analysis of brachytherapy in cystic CP (6 trials, 266 patients; ≥5-year follow-up) reported pooled PFS: 75% at 1 year, 62% at 2–3 years, and 57% at 5 years (zhang2024brachytherapyincraniopharyngiomas pages 1-2).
(MAXO identifiers are provided as ontology suggestions; mapping may require local curation.)
No established primary prevention strategies exist because CPs are not linked to modifiable exposures in the retrieved evidence. Secondary/tertiary “prevention” in practice centers on early diagnosis and hypothalamus/optic-sparing treatment strategies to reduce long-term morbidity (brastianos2023brafmekinhibitionin pages 1-4).
No naturally occurring non-human species disease evidence was retrieved in this run.
Mouse genetic models targeting oncogenic β‑catenin to pituitary embryonic precursors or adult stem cells have been used to model ACP tumorigenesis and support a paracrine mechanism in which cluster cells act as signaling centers (apps2017geneticallyengineeredmouse pages 3-5, apps2018tumourcompartmenttranscriptomics pages 1-2).
Human and mouse ACP explant cultures treated with the MEK inhibitor trametinib showed reduced proliferation and increased apoptosis, providing a preclinical platform for therapy development (apps2018tumourcompartmenttranscriptomics pages 1-2, campanini2023themolecularpathogenesis pages 4-6).
Open pediatric cancer multi‑omics initiatives (e.g., OpenPBTA/OpenPedCan) are expanding integrated diagnoses and methylation-based subtyping for pediatric brain tumors including craniopharyngioma ().
| Subtype | Relative frequency | Key driver mutation(s) | Typical age distribution | Imaging / histopathology | Therapy implications |
|---|---|---|---|---|---|
| Adamantinomatous craniopharyngioma (ACP) | ~90% of craniopharyngiomas (jannelli2023currentadvancesin pages 1-2, campanini2023themolecularpathogenesis pages 2-3, campanini2023themolecularpathogenesis pages 1-2) | Somatic CTNNB1 exon 3 mutation; reported prevalence ranges include ~60%, 59%, and ~69-100% across studies/reviews; causes nuclear/cytoplasmic β-catenin accumulation and Wnt/β-catenin activation (an2025molecularsubtypesof pages 1-2, neubecker2026systemicmolecularlytargeted pages 1-2, campanini2023themolecularpathogenesis pages 1-2, wang2024multiomicsanalysisof pages 3-5) | Bimodal peaks in childhood and later adulthood: 5-15 years and 45-60 years; other reviews report 5-14 and 55-74 years (an2025molecularsubtypesof pages 1-2, neto2025recentadvancesin pages 1-2, campanini2023themolecularpathogenesis pages 2-3, javidialsaadi2025advancesinthe pages 2-4) | Often multicystic or mixed solid-cystic; calcifications common (~90%); CT often shows hypodense cystic uni-/multilocular lesion; cyst fluid may resemble “motor oil.” Histology: palisading epithelium, stellate reticulum, finger-like infiltrative protrusions, wet keratin, epithelial whorls, gliosis/inflammation (alboqami2024craniopharyngiomaacomprehensive pages 2-5, javidialsaadi2025advancesinthe pages 6-8, gonzalezgallego2025moderntreatmentof pages 2-4, campanini2023themolecularpathogenesis pages 4-6) | Standard management remains maximal safe surgery ± radiotherapy. No single established targeted therapy yet. Emerging/experimental strategies include MEK inhibition (especially inflammatory/ImA subtype), IL-6/IL-6R blockade (e.g., tocilizumab), bevacizumab combinations, immunotherapy for inflammatory subgroups, and intracystic interferon/peginterferon for cystic disease (wang2024multiomicsanalysisof pages 8-10, wang2024multiomicsanalysisof pages 1-2, NCT05286788 chunk 1, wang2024multiomicsanalysisof pages 3-5) |
| Papillary craniopharyngioma (PCP) | ~10% of craniopharyngiomas (jannelli2023currentadvancesin pages 1-2, campanini2023themolecularpathogenesis pages 2-3) | BRAF p.V600E in ~90-95% of cases; reviews also report 81-100% or near-universal prevalence; activates MAPK/ERK signaling (jannelli2023currentadvancesin pages 1-2, campanini2023themolecularpathogenesis pages 2-3, campanini2023themolecularpathogenesis pages 1-2, NCT05525273 chunk 1) | Predominantly adult-onset; typically 4th-6th decade / 40-53 years, mean ~44.7 years; often 5th-6th decades (neto2025recentadvancesin pages 1-2, jannelli2023currentadvancesin pages 1-2, campanini2023themolecularpathogenesis pages 2-3, NCT05525273 chunk 1) | Typically solid or uniloculated, non-calcified suprasellar/tuberoinfundibular mass; CT/MRI often isodense and noncalcified with hyperintense T2 signal. Histology: mature squamous epithelium over fibrovascular cores; lacks ACP palisading, stellate reticulum, and wet keratin (alboqami2024craniopharyngiomaacomprehensive pages 2-5, javidialsaadi2025advancesinthe pages 6-8, gonzalezgallego2025moderntreatmentof pages 2-4) | Strong precision-oncology signal: BRAF/MEK inhibition produces major shrinkage. In prospective phase 2 data, 15/16 (94%) responded, median tumor-volume reduction 91%, 12-month PFS 87%, 24-month PFS 58% with vemurafenib+cobimetinib; neoadjuvant/adjuvant regimens often allow less morbid surgery/radiation and in some cases no further therapy (brastianos2023brafmekinhibitionin pages 1-4, cossu2024updateonneoadjuvant pages 1-2, NCT03224767 chunk 1, NCT05525273 chunk 1) |
Table: This table compares adamantinomatous and papillary craniopharyngioma across frequency, molecular drivers, age distribution, imaging and histopathologic features, and current therapeutic implications. It is useful for quickly linking subtype biology to diagnostic expectations and treatment strategy.
ClinicalTrials.gov URLs: - NCT03224767: https://clinicaltrials.gov/study/NCT03224767 (NCT03224767 chunk 1) - NCT05525273: https://clinicaltrials.gov/study/NCT05525273 (NCT05525273 chunk 1) - NCT05286788: https://clinicaltrials.gov/study/NCT05286788 (NCT05286788 chunk 1)
1) Ontology identifier codes (MONDO, Orphanet, ICD-10/11, MeSH, OMIM) were not accessible through the current scholarly-literature and ClinicalTrials.gov toolchain and therefore are not included as authoritative code assertions in this report. 2) Some requested elements (detailed differential diagnosis list; population prevalence; long-term endocrine/visual outcome rates by treatment modality) require additional dedicated sources or full-text extraction beyond the available evidence snippets.
The citations above already embed URLs and publication months/years in the evidence source metadata; key recent/high-authority sources include: - Brastianos PK et al. N Engl J Med. July 2023. DOI: https://doi.org/10.1056/NEJMoa2213329 (brastianos2023brafmekinhibitionin pages 1-4) - Alboqami MN et al. Heliyon. June 2024. DOI: https://doi.org/10.1016/j.heliyon.2024.e32112 (alboqami2024craniopharyngiomaacomprehensive pages 2-5) - Biswas C et al. Front Endocrinol. Nov 2024. DOI: https://doi.org/10.3389/fendo.2024.1488958 (biswas2024practicalapplicationof pages 1-2) - Cossu G et al. Cancers (Basel). Oct 2024. DOI: https://doi.org/10.3390/cancers16203479 (cossu2024updateonneoadjuvant pages 1-2) - Wang X et al. Chinese Medical Journal. Aug 2024. DOI: https://doi.org/10.1097/CM9.0000000000002774 (wang2024multiomicsanalysisof pages 1-2) - Campanini ML et al. Arch Endocrinol Metab. Feb 2023. DOI: https://doi.org/10.20945/2359-3997000000600 (campanini2023themolecularpathogenesis pages 1-2)
References
(campanini2023themolecularpathogenesis pages 1-2): Marina Lanciotti Campanini, João Paulo Almeida, Clarissa Silva Martins, and Margaret de Castro. The molecular pathogenesis of craniopharyngiomas. Archives of Endocrinology and Metabolism, 67:266-275, Feb 2023. URL: https://doi.org/10.20945/2359-3997000000600, doi:10.20945/2359-3997000000600. This article has 13 citations.
(jannelli2023currentadvancesin pages 1-2): Gianpaolo Jannelli, Francesco Calvanese, Luca Paun, Gerald Raverot, and Emmanuel Jouanneau. Current advances in papillary craniopharyngioma: state-of-the-art therapies and overview of the literature. Brain Sciences, 13:515, Mar 2023. URL: https://doi.org/10.3390/brainsci13030515, doi:10.3390/brainsci13030515. This article has 28 citations.
(neto2025recentadvancesin pages 1-2): Clariano Pires de Oliveira Neto, Gilvan Cortês Nascimento, Sabrina da Silva Pereira Damianse, and Manuel dos Santos Faria. Recent advances in craniopharyngioma pathophysiology and emerging therapeutic approaches. Frontiers in Endocrinology, May 2025. URL: https://doi.org/10.3389/fendo.2025.1562942, doi:10.3389/fendo.2025.1562942. This article has 2 citations.
(neubecker2026systemicmolecularlytargeted pages 1-2): Joseph J. Neubecker, Daniel W. Griepp, Jeffrey P. Turnbull, Joshua Caskey, Shivum Desai, Adam Mansour, Rabia Ahmed, Andrew Beggs, Annie T. K. Griepp, Heather Heitkotter, Chad F. Claus, Boyd F. Richards, and Prashant S. Kelkar. Systemic molecularly targeted therapies for neoadjuvant and salvage craniopharyngioma: a contemporary narrative review. Biomedicines, 14:499, Feb 2026. URL: https://doi.org/10.3390/biomedicines14030499, doi:10.3390/biomedicines14030499. This article has 0 citations.
(campanini2023themolecularpathogenesis pages 2-3): Marina Lanciotti Campanini, João Paulo Almeida, Clarissa Silva Martins, and Margaret de Castro. The molecular pathogenesis of craniopharyngiomas. Archives of Endocrinology and Metabolism, 67:266-275, Feb 2023. URL: https://doi.org/10.20945/2359-3997000000600, doi:10.20945/2359-3997000000600. This article has 13 citations.
(biswas2024practicalapplicationof pages 1-2): Chandrima Biswas, Guilherme Mansur, Kyle C. Wu, Daniel M. Prevedello, and Luma Ghalib. Practical application of precision oncology in adult onset craniopharyngiomas. Frontiers in Endocrinology, Nov 2024. URL: https://doi.org/10.3389/fendo.2024.1488958, doi:10.3389/fendo.2024.1488958. This article has 4 citations.
(brastianos2023brafmekinhibitionin pages 1-4): Priscilla K. Brastianos, Erin Twohy, Susan Geyer, Elizabeth R. Gerstner, Timothy J. Kaufmann, Shervin Tabrizi, Brian Kabat, Julia Thierauf, Michael W. Ruff, Daniela A. Bota, David A. Reardon, Adam L. Cohen, Macarena I. De La Fuente, Glenn J. Lesser, Jian Campian, Pankaj K. Agarwalla, Priya Kumthekar, Bhupinder Mann, Shivangi Vora, Michael Knopp, A. John Iafrate, William T. Curry, Daniel P. Cahill, Helen A. Shih, Paul D. Brown, Sandro Santagata, Fred G. Barker, and Evanthia Galanis. Braf-mek inhibition in newly diagnosed papillary craniopharyngiomas. The New England journal of medicine, 389 2:118-126, Jul 2023. URL: https://doi.org/10.1056/nejmoa2213329, doi:10.1056/nejmoa2213329. This article has 127 citations and is from a highest quality peer-reviewed journal.
(apps2018tumourcompartmenttranscriptomics pages 1-2): John R. Apps, Gabriela Carreno, Jose Mario Gonzalez-Meljem, Scott Haston, Romain Guiho, Julie E. Cooper, Saba Manshaei, Nital Jani, Annett Hölsken, Benedetta Pettorini, Robert J. Beynon, Deborah M. Simpson, Helen C. Fraser, Ying Hong, Shirleen Hallang, Thomas J. Stone, Alex Virasami, Andrew M. Donson, David Jones, Kristian Aquilina, Helen Spoudeas, Abhijit R. Joshi, Richard Grundy, Lisa C. D. Storer, Márta Korbonits, David A. Hilton, Kyoko Tossell, Selvam Thavaraj, Mark A. Ungless, Jesus Gil, Rolf Buslei, Todd Hankinson, Darren Hargrave, Colin Goding, Cynthia L. Andoniadou, Paul Brogan, Thomas S. Jacques, Hywel J. Williams, and Juan Pedro Martinez-Barbera. Tumour compartment transcriptomics demonstrates the activation of inflammatory and odontogenic programmes in human adamantinomatous craniopharyngioma and identifies the mapk/erk pathway as a novel therapeutic target. Acta Neuropathologica, 135:757-777, Mar 2018. URL: https://doi.org/10.1007/s00401-018-1830-2, doi:10.1007/s00401-018-1830-2. This article has 169 citations and is from a highest quality peer-reviewed journal.
(wang2024multiomicsanalysisof pages 1-2): Xianlong Wang, Chuan Zhao, Jincheng Lin, Hongxing Liu, Qiuhong Zeng, Hua-Qing Chen, Ye Wang, Dapeng Xu, Wen Chen, Moping Xu, En Zhang, Da Lin, and Zhixiong Lin. Multi-omics analysis of adamantinomatous craniopharyngiomas reveals distinct molecular subgroups with prognostic and treatment response significance. Chinese Medical Journal, 137:859-870, Aug 2024. URL: https://doi.org/10.1097/cm9.0000000000002774, doi:10.1097/cm9.0000000000002774. This article has 21 citations and is from a peer-reviewed journal.
(campanini2023themolecularpathogenesis pages 4-6): Marina Lanciotti Campanini, João Paulo Almeida, Clarissa Silva Martins, and Margaret de Castro. The molecular pathogenesis of craniopharyngiomas. Archives of Endocrinology and Metabolism, 67:266-275, Feb 2023. URL: https://doi.org/10.20945/2359-3997000000600, doi:10.20945/2359-3997000000600. This article has 13 citations.
(an2025molecularsubtypesof pages 1-2): Wenhao An, Shouwei Li, Yihua An, and Zhixiong Lin. Molecular subtypes of adamantinomatous craniopharyngiomas. Neuro-Oncology, 27:1180-1192, Feb 2025. URL: https://doi.org/10.1093/neuonc/noaf030, doi:10.1093/neuonc/noaf030. This article has 9 citations and is from a domain leading peer-reviewed journal.
(javidialsaadi2025advancesinthe pages 2-4): Mousa Javidialsaadi, Diego D. Luy, Heather L. Smith, Arba Cecia, Seunghyuk Daniel Yang, and Anand V. Germanwala. Advances in the management of craniopharyngioma: a narrative review of recent developments and clinical strategies. Journal of Clinical Medicine, 14:1101, Feb 2025. URL: https://doi.org/10.3390/jcm14041101, doi:10.3390/jcm14041101. This article has 7 citations.
(javidialsaadi2025advancesinthe pages 4-6): Mousa Javidialsaadi, Diego D. Luy, Heather L. Smith, Arba Cecia, Seunghyuk Daniel Yang, and Anand V. Germanwala. Advances in the management of craniopharyngioma: a narrative review of recent developments and clinical strategies. Journal of Clinical Medicine, 14:1101, Feb 2025. URL: https://doi.org/10.3390/jcm14041101, doi:10.3390/jcm14041101. This article has 7 citations.
(alboqami2024craniopharyngiomaacomprehensive pages 2-5): Maryam Nashi Alboqami, Arwa Khalid S Albaiahy, Bushra Hatim Bukhari, Ali Alkhaibary, Ahoud Alharbi, Sami Khairy, Ali H. Alassiri, Fahd AlSufiani, Ahmed Alkhani, and Ahmed Aloraidi. Craniopharyngioma: a comprehensive review of the clinical presentation, radiological findings, management, and future perspective. Heliyon, 10:e32112, Jun 2024. URL: https://doi.org/10.1016/j.heliyon.2024.e32112, doi:10.1016/j.heliyon.2024.e32112. This article has 33 citations.
(gonzalezgallego2025moderntreatmentof pages 2-4): Carlos González-Gallego, Pedro Molina, Cristina Hostalot, Anna Oliva, Alberto Blanco, Paloma Puyalto de Pablo, Silvia Comas, Cristina Carrato, Elena Valassi, and Manel Puig-Domingo. Modern treatment of craniopharyngioma to improve outcomes: evidence of a change of paradigm. Endocrine, 89:20-29, May 2025. URL: https://doi.org/10.1007/s12020-025-04216-9, doi:10.1007/s12020-025-04216-9. This article has 3 citations and is from a peer-reviewed journal.
(javidialsaadi2025advancesinthe pages 6-8): Mousa Javidialsaadi, Diego D. Luy, Heather L. Smith, Arba Cecia, Seunghyuk Daniel Yang, and Anand V. Germanwala. Advances in the management of craniopharyngioma: a narrative review of recent developments and clinical strategies. Journal of Clinical Medicine, 14:1101, Feb 2025. URL: https://doi.org/10.3390/jcm14041101, doi:10.3390/jcm14041101. This article has 7 citations.
(wang2024multiomicsanalysisof pages 8-10): Xianlong Wang, Chuan Zhao, Jincheng Lin, Hongxing Liu, Qiuhong Zeng, Hua-Qing Chen, Ye Wang, Dapeng Xu, Wen Chen, Moping Xu, En Zhang, Da Lin, and Zhixiong Lin. Multi-omics analysis of adamantinomatous craniopharyngiomas reveals distinct molecular subgroups with prognostic and treatment response significance. Chinese Medical Journal, 137:859-870, Aug 2024. URL: https://doi.org/10.1097/cm9.0000000000002774, doi:10.1097/cm9.0000000000002774. This article has 21 citations and is from a peer-reviewed journal.
(NCT05286788 chunk 1): MEKTOVI® for the Treatment of Pediatric Adamantinomatous Craniopharyngioma. Nationwide Children's Hospital. 2023. ClinicalTrials.gov Identifier: NCT05286788
(ng2020anepidemiologyreport pages 8-9): Sam Ng, Sonia Zouaoui, Faiza Bessaoud, Valérie Rigau, Alexandre Roux, Amélie Darlix, Fabienne Bauchet, Hélène Mathieu-Daudé, Brigitte Trétarre, Dominique Figarella-Branger, Johan Pallud, Didier Frappaz, Thomas Roujeau, and Luc Bauchet. An epidemiology report for primary central nervous system tumors in adolescents and young adults: a nationwide population-based study in france, 2008-2013. Neuro-oncology, 22:851-863, Dec 2020. URL: https://doi.org/10.1093/neuonc/noz227, doi:10.1093/neuonc/noz227. This article has 28 citations and is from a domain leading peer-reviewed journal.
(NCT05525273 chunk 1): Eva Marie Erfurth, MD, PhD. Treatment of BRAF ( B-Rapidly Accelerated Fibrosarcoma) Mutated Papillary Craniopharyngioma. Eva Marie Erfurth, MD, PhD. 2023. ClinicalTrials.gov Identifier: NCT05525273
(cossu2024updateonneoadjuvant pages 1-2): Giulia Cossu, Daniele S. C. Ramsay, Roy T. Daniel, Ahmed El Cadhi, Luc Kerherve, Edouard Morlaix, Sayda A. Houidi, Clément Millot-Piccoli, Renan Chapon, Tuan Le Van, Catherine Cao, Walid Farah, Maxime Lleu, Olivier Baland, Jacques Beaurain, Jean Michel Petit, Brivaël Lemogne, Mahmoud Messerer, and Moncef Berhouma. Update on neoadjuvant and adjuvant braf inhibitors in papillary craniopharyngioma: a systematic review. Cancers, 16:3479, Oct 2024. URL: https://doi.org/10.3390/cancers16203479, doi:10.3390/cancers16203479. This article has 4 citations.
(biswas2024practicalapplicationof pages 2-3): Chandrima Biswas, Guilherme Mansur, Kyle C. Wu, Daniel M. Prevedello, and Luma Ghalib. Practical application of precision oncology in adult onset craniopharyngiomas. Frontiers in Endocrinology, Nov 2024. URL: https://doi.org/10.3389/fendo.2024.1488958, doi:10.3389/fendo.2024.1488958. This article has 4 citations.
(zhang2024brachytherapyincraniopharyngiomas pages 1-2): Li-Yuan Zhang, Wei Guo, Han-Ze Du, Hui Pan, Yun-Chuan Sun, Hui-Juan Zhu, Shuai-Hua Song, Xiao-Yuan Guo, Yue Jiang, and Qian-Qian Sun. Brachytherapy in craniopharyngiomas: a systematic review and meta-analysis of long-term follow-up. BMC Cancer, May 2024. URL: https://doi.org/10.1186/s12885-024-12397-1, doi:10.1186/s12885-024-12397-1. This article has 4 citations and is from a peer-reviewed journal.
(apps2017geneticallyengineeredmouse pages 3-5): John Richard Apps and Juan Pedro Martinez‐Barbera. Genetically engineered mouse models of craniopharyngioma: an opportunity for therapy development and understanding of tumor biology. Brain Pathology, 27:364-369, Apr 2017. URL: https://doi.org/10.1111/bpa.12501, doi:10.1111/bpa.12501. This article has 17 citations and is from a domain leading peer-reviewed journal.
(wang2024multiomicsanalysisof pages 3-5): Xianlong Wang, Chuan Zhao, Jincheng Lin, Hongxing Liu, Qiuhong Zeng, Hua-Qing Chen, Ye Wang, Dapeng Xu, Wen Chen, Moping Xu, En Zhang, Da Lin, and Zhixiong Lin. Multi-omics analysis of adamantinomatous craniopharyngiomas reveals distinct molecular subgroups with prognostic and treatment response significance. Chinese Medical Journal, 137:859-870, Aug 2024. URL: https://doi.org/10.1097/cm9.0000000000002774, doi:10.1097/cm9.0000000000002774. This article has 21 citations and is from a peer-reviewed journal.
(NCT03224767 chunk 1): Vemurafenib and Cobimetinib in Treating Patients With BRAF V600E Mutation Positive Craniopharyngioma. Alliance for Clinical Trials in Oncology. 2018. ClinicalTrials.gov Identifier: NCT03224767