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.
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.
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DOI：
10.3389/fonc.2021.720417
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发表时间：
2021
影响因子：
4.7
通讯作者：
Tang Y
中科院分区：
文献类型：
--
作者：
Xue R;Chen M;Cai J;Deng Z;Pan D;Liu X;Li Y;Rong X;Li H;Xu Y;Shen Q;Tang Y
内皮损伤后血脑屏障（BBB）的破坏是放射性脑坏死（RN）的重要组成部分，但BBB破坏的定量及其在药物治疗疗效和预后评估中的作用尚不清楚。在这项回顾性研究中，通过动态对比增强MRI（DCE-MRI）评价了贝伐单抗和皮质类固醇对BBB的修复以及BBB通透性与治疗反应和复发之间的相关性。将41例鼻咽癌放疗后RN患者（28例接受贝伐单抗治疗，13例接受皮质类固醇治疗）、12例鼻咽癌放疗后无RN患者和12例无放疗史患者分别纳入RN、非RN和正常组。DCE-MRI评估双侧颞叶白色物质中的BBB通透性。比较三组基线时的DCE参数。比较治疗后DCE参数与RN体积减少、神经功能改善和复发的相关性。从正常组和非RN组到RN坏死病变，尤其是K-T，基线时BBB渗漏的程度增加（Kruskal-Wallis检验，P <0.001）。在RN组，Bevacizumab可使放射性坏死灶的K_（transm）和V_（e）降低（均P <0.001），而激素对血脑屏障无明显影响。贝伐单抗组有效率为30/34（88.2%），显著高于皮质类固醇组10/22（45.4%）（P <0.001）。斯皮尔曼分析显示，基线K trans、K ep和v p与贝伐珠单抗治疗中RN体积减少以及认知和生活质量的改善正相关。治疗缓解病例随访6个月后，贝伐珠单抗和皮质类固醇的复发率分别为10/30（33.3%）和2/9（22.2%），无统计学差异。贝伐珠单抗治疗后的K-trans水平预测6个月内的复发，AUC为0.745（P <0.05，95%CI为0.546 - 0.943，敏感性= 0.800，特异性= 0.631）。贝伐单抗改善RN坏死中的BBB渗漏。VCE参数可能有助于预测贝伐珠单抗后的治疗效果和复发。
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). 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. 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). Bevacizumab improved BBB leakage in RN necrosis. DCE parameters may be useful to predict therapeutic effect and relapse after bevacizumab.
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影响因子：
1.9
作者：
Miyatake S;Nonoguchi N;Furuse M;Yoritsune E;Miyata T;Kawabata S;Kuroiwa T
通讯作者：
Kuroiwa T
DOI：
10.1158/1078-0432.ccr-08-1420
发表时间：
2009-03-01
期刊：
Clinical cancer research : an official journal of the American Association for Cancer Research
影响因子：
--
作者：
Cao Y;Tsien CI;Sundgren PC;Nagesh V;Normolle D;Buchtel H;Junck L;Lawrence TS
通讯作者：
Lawrence TS
DOI：
10.1016/j.ijrobp.2009.12.061
发表时间：
2011-04-01
影响因子：
7
作者：
Levin, Victor A.;Bidaut, Luc;Hou, Ping;Kumar, Ashok J.;Wefel, Jeffrey S.;Bekele, B. Nebiyou;Prabhu, Sujit;Loghin, Monica;Gilbert, Mark R.;Jackson, Edward F.
通讯作者：
Jackson, Edward F.
DOI：
10.1097/00005072-199906000-00006
发表时间：
1999-06-01
影响因子：
3.2
作者：
Proescholdt, MA;Heiss, JD;Merrill, MJ
通讯作者：
Merrill, MJ
影响因子：
5.9
作者：
Fu, Fan;Sun, Xuefei;Sun, Shengjun
通讯作者：
Sun, Shengjun