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.

Meiwei Chen,Jinhua Cai,Yamei Tang,Xiaohuan Liu,Yongteng Xu,Ruiqi Xue,Yi Li,Honghong Li,Xiaoming Rong,Dong Pan,Qingyu Shen,Zhenhong Deng

doi:10.3389/fonc.2021.720417

Meiwei Chen, Jinhua Cai

Open Access

https://doi.org/10.3389/fonc.2021.720417

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Abstract

BackgroundBlood–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).MethodsForty-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.ResultsThe 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).ConclusionsBevacizumab improved BBB leakage in RN necrosis. DCE parameters may be useful to predict therapeutic effect and relapse after bevacizumab.

Highlights

Radiation-induced brain necrosis (RN) is a major adverse event in patients after radiotherapy for head and neck tumor
One previous study has demonstrated that based on the degree of RN volume decrease, bevacizumab shows superiority to corticosteroid with higher treatment response rate and lower relapse rate [12]
The inclusion criteria were as follows: 1) age >18 years old, 2) radiographic evidence to support the diagnosis of RN in temporal lobe without tumor recurrence or metastases, 3) patients who received standard routine treatment of bevacizumab or corticosteroid for the first time, 4) patients with complete baseline and radiotherapy information, 5) patients who completed clinical score evaluation and DCEMRI examination before and after the treatment course, and 6) routine laboratory studies including urinalysis, complete blood count, liver function, renal function, and coagulation test within a normal range

Summary

Introduction

Radiation-induced brain necrosis (RN) is a major adverse event in patients after radiotherapy for head and neck tumor. Previous studies have mainly focused on the treatment effect of bevacizumab and corticosteroid on volume decrease of RN necrosis and edema on MRI and clinical improvement of neurological symptoms [11,12,13,14]. 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)

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