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Blood–Brain Barrier Repair of Bevacizumab and Corticosteroid as Prediction of Clinical Improvement and Relapse Risk in Radiation-Induced Brain Necrosis: A Retrospective Observational Study

BACKGROUND: Blood–brain barrier (BBB) disruption after endothelial damage is a crucial part of radiation-induced brain necrosis (RN), but little is known of BBB disruption quantification and its role in the evaluation of therapeutic effect and prognosis for drug treatment. In this retrospective stud...

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Autores principales: Xue, Ruiqi, Chen, Meiwei, Cai, Jinhua, Deng, Zhenhong, Pan, Dong, Liu, Xiaohuan, Li, Yi, Rong, Xiaoming, Li, Honghong, Xu, Yongteng, Shen, Qingyu, Tang, Yamei
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8526720/
https://www.ncbi.nlm.nih.gov/pubmed/34692494
http://dx.doi.org/10.3389/fonc.2021.720417
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author Xue, Ruiqi
Chen, Meiwei
Cai, Jinhua
Deng, Zhenhong
Pan, Dong
Liu, Xiaohuan
Li, Yi
Rong, Xiaoming
Li, Honghong
Xu, Yongteng
Shen, Qingyu
Tang, Yamei
author_facet Xue, Ruiqi
Chen, Meiwei
Cai, Jinhua
Deng, Zhenhong
Pan, Dong
Liu, Xiaohuan
Li, Yi
Rong, Xiaoming
Li, Honghong
Xu, Yongteng
Shen, Qingyu
Tang, Yamei
author_sort Xue, Ruiqi
collection PubMed
description BACKGROUND: Blood–brain barrier (BBB) disruption after endothelial damage is a crucial part of radiation-induced brain necrosis (RN), but little is known of BBB disruption quantification and its role in the evaluation of therapeutic effect and prognosis for drug treatment. In this retrospective study, BBB repair by bevacizumab and corticosteroid and the correlation between BBB permeability and treatment response and relapse were evaluated by dynamic contrast-enhanced MRI (DCE-MRI). METHODS: Forty-one patients with RN after radiotherapy for nasopharyngeal carcinoma (NPC) (28 treated with bevacizumab and 13 with corticosteroid), 12 patients with no RN after NPC radiotherapy, and 12 patients with no radiotherapy history were included as RN, non-RN, and normal groups, respectively. DCE-MRI assessed BBB permeability in white matter of bilateral temporal lobe. DCE parameters were compared at baseline among the three groups. DCE parameters after treatment were compared and correlated with RN volume decrease, neurological improvement, and relapse. RESULTS: The extent of BBB leakage at baseline increased from the normal group and non-RN group and to RN necrosis lesions, especially K (trans) (Kruskal–Wallis test, P < 0.001). In the RN group, bevacizumab-induced K (trans) and v (e) decrease in radiation necrosis lesions (both P < 0.001), while corticosteroid showed no obvious effect on BBB. The treatment response rate of bevacizumab was significantly higher than that of corticosteroid [30/34 (88.2%) vs. 10/22 (45.4%), P < 0.001]. Spearman analysis showed baseline K (trans), K (ep), and v (p) positively correlated with RN volume decrease and improvement of cognition and quality of life in bevacizumab treatment. After a 6-month follow-up for treatment response cases, the relapse rate of bevacizumab and corticosteroid was 10/30 (33.3%) and 2/9 (22.2%), respectively, with no statistical difference. Post-bevacizumab K (trans) level predicted relapse in 6 months with AUC 0.745 (P < 0.05, 95% CI 0.546–0.943, sensitivity = 0.800, specificity = 0.631). CONCLUSIONS: Bevacizumab improved BBB leakage in RN necrosis. DCE parameters may be useful to predict therapeutic effect and relapse after bevacizumab.
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spelling pubmed-85267202021-10-21 Blood–Brain Barrier Repair of Bevacizumab and Corticosteroid as Prediction of Clinical Improvement and Relapse Risk in Radiation-Induced Brain Necrosis: A Retrospective Observational Study Xue, Ruiqi Chen, Meiwei Cai, Jinhua Deng, Zhenhong Pan, Dong Liu, Xiaohuan Li, Yi Rong, Xiaoming Li, Honghong Xu, Yongteng Shen, Qingyu Tang, Yamei Front Oncol Oncology BACKGROUND: Blood–brain barrier (BBB) disruption after endothelial damage is a crucial part of radiation-induced brain necrosis (RN), but little is known of BBB disruption quantification and its role in the evaluation of therapeutic effect and prognosis for drug treatment. In this retrospective study, BBB repair by bevacizumab and corticosteroid and the correlation between BBB permeability and treatment response and relapse were evaluated by dynamic contrast-enhanced MRI (DCE-MRI). METHODS: Forty-one patients with RN after radiotherapy for nasopharyngeal carcinoma (NPC) (28 treated with bevacizumab and 13 with corticosteroid), 12 patients with no RN after NPC radiotherapy, and 12 patients with no radiotherapy history were included as RN, non-RN, and normal groups, respectively. DCE-MRI assessed BBB permeability in white matter of bilateral temporal lobe. DCE parameters were compared at baseline among the three groups. DCE parameters after treatment were compared and correlated with RN volume decrease, neurological improvement, and relapse. RESULTS: The extent of BBB leakage at baseline increased from the normal group and non-RN group and to RN necrosis lesions, especially K (trans) (Kruskal–Wallis test, P < 0.001). In the RN group, bevacizumab-induced K (trans) and v (e) decrease in radiation necrosis lesions (both P < 0.001), while corticosteroid showed no obvious effect on BBB. The treatment response rate of bevacizumab was significantly higher than that of corticosteroid [30/34 (88.2%) vs. 10/22 (45.4%), P < 0.001]. Spearman analysis showed baseline K (trans), K (ep), and v (p) positively correlated with RN volume decrease and improvement of cognition and quality of life in bevacizumab treatment. After a 6-month follow-up for treatment response cases, the relapse rate of bevacizumab and corticosteroid was 10/30 (33.3%) and 2/9 (22.2%), respectively, with no statistical difference. Post-bevacizumab K (trans) level predicted relapse in 6 months with AUC 0.745 (P < 0.05, 95% CI 0.546–0.943, sensitivity = 0.800, specificity = 0.631). CONCLUSIONS: Bevacizumab improved BBB leakage in RN necrosis. DCE parameters may be useful to predict therapeutic effect and relapse after bevacizumab. Frontiers Media S.A. 2021-10-06 /pmc/articles/PMC8526720/ /pubmed/34692494 http://dx.doi.org/10.3389/fonc.2021.720417 Text en Copyright © 2021 Xue, Chen, Cai, Deng, Pan, Liu, Li, Rong, Li, Xu, Shen and Tang https://creativecommons.org/licenses/by/4.0/This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
spellingShingle Oncology
Xue, Ruiqi
Chen, Meiwei
Cai, Jinhua
Deng, Zhenhong
Pan, Dong
Liu, Xiaohuan
Li, Yi
Rong, Xiaoming
Li, Honghong
Xu, Yongteng
Shen, Qingyu
Tang, Yamei
Blood–Brain Barrier Repair of Bevacizumab and Corticosteroid as Prediction of Clinical Improvement and Relapse Risk in Radiation-Induced Brain Necrosis: A Retrospective Observational Study
title Blood–Brain Barrier Repair of Bevacizumab and Corticosteroid as Prediction of Clinical Improvement and Relapse Risk in Radiation-Induced Brain Necrosis: A Retrospective Observational Study
title_full Blood–Brain Barrier Repair of Bevacizumab and Corticosteroid as Prediction of Clinical Improvement and Relapse Risk in Radiation-Induced Brain Necrosis: A Retrospective Observational Study
title_fullStr Blood–Brain Barrier Repair of Bevacizumab and Corticosteroid as Prediction of Clinical Improvement and Relapse Risk in Radiation-Induced Brain Necrosis: A Retrospective Observational Study
title_full_unstemmed Blood–Brain Barrier Repair of Bevacizumab and Corticosteroid as Prediction of Clinical Improvement and Relapse Risk in Radiation-Induced Brain Necrosis: A Retrospective Observational Study
title_short Blood–Brain Barrier Repair of Bevacizumab and Corticosteroid as Prediction of Clinical Improvement and Relapse Risk in Radiation-Induced Brain Necrosis: A Retrospective Observational Study
title_sort blood–brain barrier repair of bevacizumab and corticosteroid as prediction of clinical improvement and relapse risk in radiation-induced brain necrosis: a retrospective observational study
topic Oncology
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8526720/
https://www.ncbi.nlm.nih.gov/pubmed/34692494
http://dx.doi.org/10.3389/fonc.2021.720417
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