Hyperthermic Laser Ablation of Recurrent Glioblastoma Leads to Temporary Disruption of the Peritumoral Blood Brain Barrier.
Hyperthermic Laser Ablation of Recurrent Glioblastoma Leads to Temporary Disruption of the Peritumoral Blood Brain Barrier.
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DOI：
10.1371/journal.pone.0148613
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发表时间：
2016
期刊：
影响因子：
3.7
通讯作者：
Tran DD
中科院分区：
文献类型：
--
作者：
Leuthardt EC;Duan C;Kim MJ;Campian JL;Kim AH;Miller-Thomas MM;Shimony JS;Tran DD
由于血脑屏障（BBB），细胞毒性药物的中枢神经系统渗透性差是脑肿瘤治疗的主要限制因素。大多数复发性胶质母细胞瘤（GBM）发生在肿瘤周围区域。在这项研究中，我们描述了一种高热方法，以诱导暂时中断的肿瘤周围血脑屏障，可以潜在地用于增强药物输送。本研究纳入了20例可能复发GBM的患者。14例患者可评价。MRI引导下的激光间质热治疗被应用于实现肿瘤细胞减少和肿瘤周围血脑屏障的破坏。为了确定肿瘤周围血脑屏障破坏的程度和时间，使用动态对比增强脑MRI计算肿瘤周围区域的血管转移常数（Ktranss），作为激光消融前后血脑屏障通透性的直接测量。还测量了脑特异性烯醇化酶（也称为神经元特异性烯醇化酶）的血清水平，并将其用作BBB破坏的独立定量。在所有14例可评价患者中，Ktranss水平在激光消融后立即达到峰值，随后在接下来的4周内逐渐下降。血清BSE浓度在激光消融后不久增加，并在1-3周达到峰值，然后在6周时降至基线。来自我们的初步研究的数据支持肿瘤周围血脑屏障的破坏是由高温诱导的，高渗透性的峰值在激光消融后1-2周内出现，并在4-6周消退。这提供了治疗机会窗口，在此期间可以增强BBB不渗透治疗剂的递送。ClinicalTrials.gov www.example.com
Poor central nervous system penetration of cytotoxic drugs due to the blood brain barrier (BBB) is a major limiting factor in the treatment of brain tumors. Most recurrent glioblastomas (GBM) occur within the peritumoral region. In this study, we describe a hyperthemic method to induce temporary disruption of the peritumoral BBB that can potentially be used to enhance drug delivery. Twenty patients with probable recurrent GBM were enrolled in this study. Fourteen patients were evaluable. MRI-guided laser interstitial thermal therapy was applied to achieve both tumor cytoreduction and disruption of the peritumoral BBB. To determine the degree and timing of peritumoral BBB disruption, dynamic contrast-enhancement brain MRI was used to calculate the vascular transfer constant (Ktrans) in the peritumoral region as direct measures of BBB permeability before and after laser ablation. Serum levels of brain-specific enolase, also known as neuron-specific enolase, were also measured and used as an independent quantification of BBB disruption. In all 14 evaluable patients, Ktrans levels peaked immediately post laser ablation, followed by a gradual decline over the following 4 weeks. Serum BSE concentrations increased shortly after laser ablation and peaked in 1–3 weeks before decreasing to baseline by 6 weeks. The data from our pilot research support that disruption of the peritumoral BBB was induced by hyperthemia with the peak of high permeability occurring within 1–2 weeks after laser ablation and resolving by 4–6 weeks. This provides a therapeutic window of opportunity during which delivery of BBB-impermeant therapeutic agents may be enhanced. ClinicalTrials.gov NCT01851733