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TNFR1 and the TNFα axis as a targetable mediator of liver injury from stereotactic body radiation therapy

INTRODUCTION: Radiation therapy for the management of intrahepatic malignancies can adversely affect liver function. Liver damage has been associated with increased levels of inflammatory cytokines, including tumor necrosis factor alpha (TNFα). We hypothesized that an inflammatory state, characteriz...

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Autores principales: Cousins, Matthew M., Morris, Emily, Maurino, Christopher, Devasia, Theresa P., Karnak, David, Ray, Dipankar, Parikh, Neehar D., Owen, Dawn, Ten Haken, Randall K., Schipper, Matthew J., Lawrence, Theodore S., Cuneo, Kyle C.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Neoplasia Press 2020
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7744766/
https://www.ncbi.nlm.nih.gov/pubmed/33395747
http://dx.doi.org/10.1016/j.tranon.2020.100950
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author Cousins, Matthew M.
Morris, Emily
Maurino, Christopher
Devasia, Theresa P.
Karnak, David
Ray, Dipankar
Parikh, Neehar D.
Owen, Dawn
Ten Haken, Randall K.
Schipper, Matthew J.
Lawrence, Theodore S.
Cuneo, Kyle C.
author_facet Cousins, Matthew M.
Morris, Emily
Maurino, Christopher
Devasia, Theresa P.
Karnak, David
Ray, Dipankar
Parikh, Neehar D.
Owen, Dawn
Ten Haken, Randall K.
Schipper, Matthew J.
Lawrence, Theodore S.
Cuneo, Kyle C.
author_sort Cousins, Matthew M.
collection PubMed
description INTRODUCTION: Radiation therapy for the management of intrahepatic malignancies can adversely affect liver function. Liver damage has been associated with increased levels of inflammatory cytokines, including tumor necrosis factor alpha (TNFα). We hypothesized that an inflammatory state, characterized by increased soluble TNFα receptor (sTNFR1), mediates sensitivity of the liver to radiation. MATERIALS/METHODS: Plasma samples collected during 3 trials of liver radiation for liver malignancies were assayed for sTNFR1 level via enzyme-linked immunosorbent assay (ELISA). Univariate and multivariate logistic regression and longitudinal models were used to characterize associations between liver toxicity (defined as a ≥2-point increase in Child-Pugh [CP] score within 6 months of radiation treatment) and sTNFR1 levels, ALBI score, biocorrected mean liver dose (MLD), age, and baseline laboratory values. RESULTS: Samples from 78 patients given liver stereotactic body radiation therapy [SBRT] (92%) or hypofractionated radiation were examined. There was a significant association between liver toxicity and sTNFR1 levels, and higher values were associated with increased toxicity over a range of mean liver doses. When ALBI score and biocorrected dose were included in the model with sTNFR1, baseline ALBI score and change in ALBI (ΔALBI) were significantly associated with toxicity, but sTNFR1 was not. Baseline aminotransferase levels also predicted toxicity but not independently of ALBI score. CONCLUSIONS: Elevated plasma sTNFR1 levels are associated with liver injury after liver radiation, suggesting that elevated inflammatory cytokine activity is a predictor of radiation-induced liver dysfunction. Future studies should determine whether administration of agents that decrease inflammation prior to treatment is warranted.
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spelling pubmed-77447662020-12-22 TNFR1 and the TNFα axis as a targetable mediator of liver injury from stereotactic body radiation therapy Cousins, Matthew M. Morris, Emily Maurino, Christopher Devasia, Theresa P. Karnak, David Ray, Dipankar Parikh, Neehar D. Owen, Dawn Ten Haken, Randall K. Schipper, Matthew J. Lawrence, Theodore S. Cuneo, Kyle C. Transl Oncol Original article INTRODUCTION: Radiation therapy for the management of intrahepatic malignancies can adversely affect liver function. Liver damage has been associated with increased levels of inflammatory cytokines, including tumor necrosis factor alpha (TNFα). We hypothesized that an inflammatory state, characterized by increased soluble TNFα receptor (sTNFR1), mediates sensitivity of the liver to radiation. MATERIALS/METHODS: Plasma samples collected during 3 trials of liver radiation for liver malignancies were assayed for sTNFR1 level via enzyme-linked immunosorbent assay (ELISA). Univariate and multivariate logistic regression and longitudinal models were used to characterize associations between liver toxicity (defined as a ≥2-point increase in Child-Pugh [CP] score within 6 months of radiation treatment) and sTNFR1 levels, ALBI score, biocorrected mean liver dose (MLD), age, and baseline laboratory values. RESULTS: Samples from 78 patients given liver stereotactic body radiation therapy [SBRT] (92%) or hypofractionated radiation were examined. There was a significant association between liver toxicity and sTNFR1 levels, and higher values were associated with increased toxicity over a range of mean liver doses. When ALBI score and biocorrected dose were included in the model with sTNFR1, baseline ALBI score and change in ALBI (ΔALBI) were significantly associated with toxicity, but sTNFR1 was not. Baseline aminotransferase levels also predicted toxicity but not independently of ALBI score. CONCLUSIONS: Elevated plasma sTNFR1 levels are associated with liver injury after liver radiation, suggesting that elevated inflammatory cytokine activity is a predictor of radiation-induced liver dysfunction. Future studies should determine whether administration of agents that decrease inflammation prior to treatment is warranted. Neoplasia Press 2020-12-13 /pmc/articles/PMC7744766/ /pubmed/33395747 http://dx.doi.org/10.1016/j.tranon.2020.100950 Text en © 2020 The Authors http://creativecommons.org/licenses/by-nc-nd/4.0/ This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).
spellingShingle Original article
Cousins, Matthew M.
Morris, Emily
Maurino, Christopher
Devasia, Theresa P.
Karnak, David
Ray, Dipankar
Parikh, Neehar D.
Owen, Dawn
Ten Haken, Randall K.
Schipper, Matthew J.
Lawrence, Theodore S.
Cuneo, Kyle C.
TNFR1 and the TNFα axis as a targetable mediator of liver injury from stereotactic body radiation therapy
title TNFR1 and the TNFα axis as a targetable mediator of liver injury from stereotactic body radiation therapy
title_full TNFR1 and the TNFα axis as a targetable mediator of liver injury from stereotactic body radiation therapy
title_fullStr TNFR1 and the TNFα axis as a targetable mediator of liver injury from stereotactic body radiation therapy
title_full_unstemmed TNFR1 and the TNFα axis as a targetable mediator of liver injury from stereotactic body radiation therapy
title_short TNFR1 and the TNFα axis as a targetable mediator of liver injury from stereotactic body radiation therapy
title_sort tnfr1 and the tnfα axis as a targetable mediator of liver injury from stereotactic body radiation therapy
topic Original article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7744766/
https://www.ncbi.nlm.nih.gov/pubmed/33395747
http://dx.doi.org/10.1016/j.tranon.2020.100950
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