Hankinson Lab Research
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Does pre-irradiation gross tumor volume predict the risk of progression after radiation therapy in pediatric patients with adamantinomatous craniopharyngioma?
9/27/2024CONCLUSIONS: The authors conclude that for most children and adolescents with ACP, the GTV at the initiation of RT is not associated with the risk of PD. This finding may influence surgical practice, because it suggests that aggressive tumor debulking for the purpose of improving the efficacy of RT may not be necessary. In the case of giant tumors, however, novel strategies may be needed for tumor control.
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Recurrent adamantinomatous craniopharyngiomas show MAPK pathway activation, clonal evolution and rare TP53-loss-mediated malignant progression
8/10/2024The two types of craniopharyngioma, adamantinomatous (ACP) and papillary (PCP), are clinically relevant tumours in children and adults. Although the biology of primary craniopharyngioma is starting to be unravelled, little is known about the biology of recurrence. To fill this gap in knowledge, we have analysed through methylation array, RNA sequencing and pERK1/2 immunohistochemistry a cohort of paired primary and recurrent samples (32 samples from 14 cases of ACP and 4 cases of PCP). We show...
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Unraveling the complexity of the senescence-associated secretory phenotype in adamantinomatous craniopharyngioma using multimodal machine learning analysis
2/9/2024CONCLUSIONS: A complex interplay between cellular senescence, cytokine signaling, and gene expression pathways underlies ACP development. Further research is crucial to understand how these elements interact to create novel therapeutic approaches for patients with ACP.
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Uncertainty-Aware Deep Learning Classification of Adamantinomatous Craniopharyngioma from Preoperative MRI
3/29/2023Diagnosis of adamantinomatous craniopharyngioma (ACP) is predominantly determined through invasive pathological examination of a neurosurgical biopsy specimen. Clinical experts can distinguish ACP from Magnetic Resonance Imaging (MRI) with an accuracy of 86%, and 9% of ACP cases are diagnosed this way. Classification using deep learning (DL) provides a solution to support a non-invasive diagnosis of ACP through neuroimaging, but it is still limited in implementation, a major reason being the...
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Contemporary Biological Insights and Clinical Management of Craniopharyngioma
12/27/2022Craniopharyngiomas (CPs) are clinically aggressive tumors because of their invasive behavior and recalcitrant tendency to recur after therapy. There are 2 types based on their distinct histology and molecular features: the papillary craniopharyngioma (PCP), which is associated with BRAF-V600E mutations and the adamantinomatous craniopharyngioma (ACP), characterized by mutations in CTNNB1 (encoding β-catenin). Patients with craniopharyngioma show symptoms linked to the location of the tumor close...
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Response assessment in pediatric craniopharyngioma: recommendations from the Response Assessment in Pediatric Neuro-Oncology (RAPNO) Working Group
9/20/2022CONCLUSIONS: Craniopharyngioma is a common pediatric central nervous system tumor for which standardized response parameters have not been defined. A RAPNO committee devised guidelines for craniopharyngioma assessment to uniformly define response in future prospective trials.
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Adamantinomatous craniopharyngioma associated with a compromised blood-brain barrier: patient series
7/20/2022BACKGROUND: Adamantinomatous craniopharyngioma (ACP) is a highly morbid adult and pediatric brain tumor derived from epithelial remnants of the craniopharyngeal canal (Rathke's pouch), which gives rise to the anterior pituitary gland. Standard therapy includes maximal safe resection with or without radiation therapy. Systemic antitumor therapy remains elusive. Immune-related paracrine signaling involving the interleukin-6 receptor (IL-6R) may contribute to ACP pathogenesis. Tocilizumab, a...
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Editorial: Characteristics and overall survival in pediatric versus adult craniopharyngioma: a population-based study
4/27/2021No abstract
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Robust deep learning classification of adamantinomatous craniopharyngioma from limited preoperative radiographic images
10/10/2020Deep learning (DL) is a widely applied mathematical modeling technique. Classically, DL models utilize large volumes of training data, which are not available in many healthcare contexts. For patients with brain tumors, non-invasive diagnosis would represent a substantial clinical advance, potentially sparing patients from the risks associated with surgical intervention on the brain. Such an approach will depend upon highly accurate models built using the limited datasets that are available....
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Adamantinomatous craniopharyngioma in the molecular age and the potential of targeted therapies: a review
5/23/2020Pediatric adamantinomatous craniopharyngiomas (ACPs) are histologically benign brain tumors that often follow an aggressive clinical course. Arising in the sellar/suprasellar region, they grow in close proximity to critical neurological and vascular structures and can result in significant neuroendocrine morbidity. First-line treatment often involves surgical resection with or without radiotherapy and has been associated with significant morbidity and poor quality of life outcomes. As a result,...
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Transcriptional analyses of adult and pediatric adamantinomatous craniopharyngioma reveals similar expression signatures regarding potential therapeutic targets
5/15/2020Adamantinomatous craniopharyngioma (ACP) is a biologically benign but clinically aggressive lesion that has a significant impact on quality of life. The incidence of the disease has a bimodal distribution, with peaks occurring in children and older adults. Our group previously published the results of a transcriptome analysis of pediatric ACPs that identified several genes that were consistently overexpressed relative to other pediatric brain tumors and normal tissue. We now present the results...
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The Inflammatory Milieu of Adamantinomatous Craniopharyngioma and Its Implications for Treatment
2/21/2020Pediatric Adamantinomatous Craniopharyngiomas (ACPs) are histologically benign brain tumors that often follow an aggressive clinical course. Their suprasellar location leaves them in close proximity to critical neurological and vascular structures and often results in significant neuroendocrine morbidity. Current treatment paradigms, involving surgical resection and radiotherapy, confer significant morbidity to patients and there is an obvious need to discover effective and safe alternative...
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Adamantinomatous craniopharyngioma: moving toward targeted therapies
1/3/2020The evolving characterization of the biological basis of adamantinomatous craniopharyngioma (ACP) has provided insights critical for novel systemically delivered therapies. While current treatment strategies for ACP are associated with low mortality rates, patients experience severely lowered quality of life due to high recurrence rates and chronic sequelae, presenting a need for novel effective treatment regimens. The identification of various dysregulated pathways that play roles in the...
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Interrater reliability of a method to assess hypothalamic involvement in pediatric adamantinomatous craniopharyngioma
10/12/2019CONCLUSIONS: Interrater reliability for the system as defined is moderate. Slight refinements of the Puget MRI grading system, such as collapsing the 3 grades into 2, may improve its reliability, making the system more generalizable.
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Targeting IL-6 Is a Potential Treatment for Primary Cystic Craniopharyngioma
9/10/2019Adamantinomatous craniopharyngioma (ACP) makes up between 6 and 8% of pediatric brain tumors and is the most common pediatric tumor arising in the sellar/suprasellar region of the brain. The 10-year survival for patients diagnosed with craniopharyngioma ranges between 64 and 92%, but complicating factors such as location, common cyst formation, and potential hypothalamic infiltration cause significant morbidity in this population. There are a number of therapeutic options for children with ACP,...
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Pediatric craniopharyngioma in association with familial adenomatous polyposis
3/29/2019Familial adenomatous polyposis (FAP) is a cancer predisposition syndrome driven by germline loss-of-function of the APC gene and phenotypically manifests with intestinal polyposis and a variety of extra-intestinal bone and soft tissue tumors. Craniopharyngioma is not a well-described FAP-associated tumor, however, six cases have been reported in adults, all demonstrating ectopic location and adamantinomatous histology. We report the first case of craniopharyngioma associated with FAP in a...
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Diagnostic accuracy of neuroimaging in pediatric optic chiasm/sellar/suprasellar tumors
3/9/2019Preoperative diagnosis for tumors arising in the optic chiasm/sellar/suprasellar region in children is helpful to determine surgical necessity and approach, given the high operative risk in this area. We evaluated the ability to differentiate tumor type by preoperative neuroimaging. Thirty-eight of 53 tumors were correctly diagnosed by neuroimaging based on final pathologic diagnosis (prediction accuracy 72%). Prediction accuracies were 87% (20/23) for craniopharyngioma, 79% (11/14) for optic...
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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
3/16/2018Adamantinomatous craniopharyngiomas (ACPs) are clinically challenging tumours, the majority of which have activating mutations in CTNNB1. 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. Here, we have carried out RNA sequencing on 18 ACP samples and integrated these data with an existing ACP...
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Multiplexed immunofluorescence reveals potential PD-1/PD-L1 pathway vulnerabilities in craniopharyngioma
3/7/2018CONCLUSIONS: ACP exhibit PD-L1 expression in the tumor cyst lining and intrinsic PD-1 expression in cells proposed to comprise an oncogenic stem-like population. In PCP, proliferative tumor cells express PD-L1 in a continuous band at the stromal-epithelial interface. Targeting PD-L1 and/or PD-1 in both subtypes of craniopharyngioma might therefore be an effective therapeutic strategy.
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Molecular Analyses Reveal Inflammatory Mediators in the Solid Component and Cyst Fluid of Human Adamantinomatous Craniopharyngioma
9/2/2017Pediatric adamantinomatous craniopharyngioma (ACP) is a highly solid and cystic tumor, often causing substantial damage to critical neuroendocrine structures such as the hypothalamus, pituitary gland, and optic apparatus. Paracrine signaling mechanisms driving tumor behavior have been hypothesized, with IL-6R overexpression identified as a potential therapeutic target. To identify potential novel therapies, we characterized inflammatory and immunomodulatory factors in ACP cyst fluid and solid...
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Review of xanthomatous lesions of the sella
2/26/2017Xanthomatous lesions of the sellar region have traditionally been divided into two separate categories, xanthomatous hypophysitis (XH) and xanthogranuloma (XG) of the sellar region. The seminal article on XH, a condition typified by foamy histiocytes and lymphoplasmacytic infiltrates in the pituitary gland/sellar region, but usually little or no hemosiderin pigment, detailed three patients. However, most reports since that time have been single cases, making understanding of the entity...
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Adamantinomatous craniopharyngioma and xanthomatous lesions of the sella
2/26/2017No abstract
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Potential evolution of neurosurgical treatment paradigms for craniopharyngioma based on genomic and transcriptomic characteristics
12/2/2016The recent genomic and transcriptomic characterization of human craniopharyngiomas has provided important insights into the pathogenesis of these tumors and supports that these tumor types are distinct entities. Critically, the insights provided by these data offer the potential for the introduction of novel therapies and surgical treatment paradigms for these tumors, which are associated with high morbidity rates and morbid conditions. Mutations in the CTNNB1 gene are primary drivers of...
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Identification of targets for rational pharmacological therapy in childhood craniopharyngioma
5/21/2015CONCLUSIONS: We report here the first published transcriptome for ACP and the identification of targets for rational therapy. Experimental drugs targeting each of these gene products are currently being tested clinically and pre-clinically for the treatment of other tumor types. This study provides a rationale for further pre-clinical and clinical studies of novel pharmacological treatments for ACP. Development of mouse and cell culture models for ACP will further enable the translation of these...
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Patterns of care for craniopharyngioma: survey of members of the american association of neurological surgeons
3/1/2014CONCLUSIONS: This survey verifies that a deviation from established algorithms is common, underscoring the clinical complexity of these patients and recent secondary data analyses. This should influence clinical researchers to investigate outcomes for patients treated using alternative methods. It will lend insight into appropriate treatment options and contribute to quality of life outcomes studies for craniopharyngioma.
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Limited utility despite accuracy of the national SEER dataset for the study of craniopharyngioma
8/24/2012Craniopharyngioma is histologically benign and associated with high survival rates but poor quality of life. The SEER Program is among the most cited data sources regarding malignancies in the United States. SEER began collecting data regarding craniopharyngiomain 2004. SEER-STAT v7.0.5 was utilized to identify patients (January 1, 2004-December 31, 2008) with ICD-O-3 codes for craniopharyngioma. Age was categorized into 3 groups: ≤19, 20-34, and ≥35 years, as was surgical intervention: none,...