Perilesional edema in brain metastases: potential causes and implications for treatment with immune therapy

Journal for Immunotherapy of Cancer
Thuy T TranHarriet M Kluger

Abstract

Little is known about tumor-associated vasogenic edema in brain metastasis, yet it causes significant morbidity and mortality. Our purpose was to characterize edema in patients treated with anti-PD-1 and to study potential causes of vessel leakage in humans and in pre-clinical models. We analyzed tumor and edema volume in 18 non-small cell lung (NSCLC) and 18 melanoma patients with untreated brain metastases treated with pembrolizumab on a phase II clinical trial. Melanoma brain metastases were stained with anti-CD34 to assess vessel density and its association with edema. We employed an in vitro model of the blood-brain barrier using short-term cultures from melanoma brain and extracranial metastases to determine tight junction resistance as a measure of vessel leakiness. Edema volumes are similar in NSCLC and melanoma brain metastases. While larger tumors tended to have more edema, the correlation was weak (R2 = 0.30). Patients responding to pembrolizumab had concurrent shrinkage of edema volume and vice versa (R2 = 0.81). Vessel density was independent of the degree of edema (R2 = 0.037). Melanoma brain metastasis cells in culture caused loss of tight junction resistance in an in vitro blood-brain barrier model system in som...Continue Reading

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Citations

Oct 3, 2019·Current Opinion in Neurology·Thuy T TranHarriet M Kluger
Aug 28, 2020·Frontiers in Molecular Neuroscience·Roberta AndrejewHenning Ulrich
Dec 10, 2019·Journal of Cancer Research and Clinical Oncology·Wang Li, Hong Yu
Feb 9, 2021·Frontiers in Oncology·Dimitri G TrembathStergios J Moschos

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Methods Mentioned

BETA
xenografts

Clinical Trials Mentioned

NCT02085070
NCT02681549
NCT03175432

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