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Adamantinomatous craniopharyngioma associated with a compromised blood–brain barrier: patient series

BACKGROUND: 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...

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Autores principales: Prince, Eric W., Hoffman, Lindsey M., Vijmasi, Trinka, Dorris, Kathleen, McWilliams, Jennifer A., Jordan, Kimberly R., Mirsky, David M., Hankinson, Todd C.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: American Association of Neurological Surgeons 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9245763/
https://www.ncbi.nlm.nih.gov/pubmed/35854837
http://dx.doi.org/10.3171/CASE2150
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author Prince, Eric W.
Hoffman, Lindsey M.
Vijmasi, Trinka
Dorris, Kathleen
McWilliams, Jennifer A.
Jordan, Kimberly R.
Mirsky, David M.
Hankinson, Todd C.
author_facet Prince, Eric W.
Hoffman, Lindsey M.
Vijmasi, Trinka
Dorris, Kathleen
McWilliams, Jennifer A.
Jordan, Kimberly R.
Mirsky, David M.
Hankinson, Todd C.
author_sort Prince, Eric W.
collection PubMed
description BACKGROUND: 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 recombinant humanized monoclonal antibody against IL-6R, is approved by the US Food and Drug Administration but does not cross an intact blood–brain barrier. OBSERVATIONS: In a phase 0 trial design, a single dose of tocilizumab was delivered intravenously before clinically indicated surgical intervention in 3 children with ACP. The presence of tocilizumab was assayed in plasma, tumor tissue, tumor cyst fluid, and cerebrospinal fluid (n = 1) using a novel enzyme-linked immunosorbent assay. Tocilizumab reached ACP tumor tissue and/or cyst fluid after one systemic dose in every patient. LESSONS: This finding helps explain extant data that indicate tocilizumab may contribute to ACP therapy. It further indicates that ACP does not reside behind an intact blood–brain barrier, dramatically broadening the range of potential antitumor therapies against this tumor. This has substantial implications for the design of future clinical trials for novel therapies against ACP in both children and adults.
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spelling pubmed-92457632022-07-18 Adamantinomatous craniopharyngioma associated with a compromised blood–brain barrier: patient series Prince, Eric W. Hoffman, Lindsey M. Vijmasi, Trinka Dorris, Kathleen McWilliams, Jennifer A. Jordan, Kimberly R. Mirsky, David M. Hankinson, Todd C. J Neurosurg Case Lessons Case Lesson BACKGROUND: 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 recombinant humanized monoclonal antibody against IL-6R, is approved by the US Food and Drug Administration but does not cross an intact blood–brain barrier. OBSERVATIONS: In a phase 0 trial design, a single dose of tocilizumab was delivered intravenously before clinically indicated surgical intervention in 3 children with ACP. The presence of tocilizumab was assayed in plasma, tumor tissue, tumor cyst fluid, and cerebrospinal fluid (n = 1) using a novel enzyme-linked immunosorbent assay. Tocilizumab reached ACP tumor tissue and/or cyst fluid after one systemic dose in every patient. LESSONS: This finding helps explain extant data that indicate tocilizumab may contribute to ACP therapy. It further indicates that ACP does not reside behind an intact blood–brain barrier, dramatically broadening the range of potential antitumor therapies against this tumor. This has substantial implications for the design of future clinical trials for novel therapies against ACP in both children and adults. American Association of Neurological Surgeons 2021-05-10 /pmc/articles/PMC9245763/ /pubmed/35854837 http://dx.doi.org/10.3171/CASE2150 Text en © 2021 The authors https://creativecommons.org/licenses/by-nc-nd/4.0/CC BY-NC-ND 4.0 (http://creativecommons.org/licenses/by-nc-nd/4.0/ (https://creativecommons.org/licenses/by-nc-nd/4.0/) ).
spellingShingle Case Lesson
Prince, Eric W.
Hoffman, Lindsey M.
Vijmasi, Trinka
Dorris, Kathleen
McWilliams, Jennifer A.
Jordan, Kimberly R.
Mirsky, David M.
Hankinson, Todd C.
Adamantinomatous craniopharyngioma associated with a compromised blood–brain barrier: patient series
title Adamantinomatous craniopharyngioma associated with a compromised blood–brain barrier: patient series
title_full Adamantinomatous craniopharyngioma associated with a compromised blood–brain barrier: patient series
title_fullStr Adamantinomatous craniopharyngioma associated with a compromised blood–brain barrier: patient series
title_full_unstemmed Adamantinomatous craniopharyngioma associated with a compromised blood–brain barrier: patient series
title_short Adamantinomatous craniopharyngioma associated with a compromised blood–brain barrier: patient series
title_sort adamantinomatous craniopharyngioma associated with a compromised blood–brain barrier: patient series
topic Case Lesson
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9245763/
https://www.ncbi.nlm.nih.gov/pubmed/35854837
http://dx.doi.org/10.3171/CASE2150
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