Bottiglieri Anna, Yadav Poonam, Mandal Santosh K, Williams Malea, McWatters Amanda, Sheth Rahul A, Prakash Punit
Department of Electrical and Computer Engineering, Kansas State University, Manhattan, KS, USA.
Department of Biomedical Engineering, The George Washington University, Washington, DC, USA.
Int J Hyperthermia. 2025 Dec;42(1):2492766. doi: 10.1080/02656736.2025.2492766. Epub 2025 Apr 23.
Increased intratumoral pressure and stiffening of the extracellular matrix are biophysical barriers to effective drug delivery in hepatocellular carcinoma (HCC). Local thermal interventions alter these biophysical characteristics of the tumor.
To characterize time-dependent and thermal dose-related effects of radiofrequency hyperthermic (RFHT) interventions on intratumoral pressure and tumor stiffness.
Two treatment protocols (high input power > 1 W and low input power < 1 W) were investigated using a computational modeling approach and a syngeneic rat HCC tumor model with a customized monopolar RFHT system. Intratumoral pressure and stiffness were assessed using piezo-electric sensors and ultrasound shear wave elastography (SWE), respectively, across three groups (untreated tumors, tumors treated with high and low RFHT) and time points (immediately after treatment, at 24 h, and 48 h).
The developed RFHT system maintained electrode-tip temperatures of 74.1 ± 5.2 °C (high RFHT) and 45.9 ± 1.6 °C (low RFHT) for 15 min. Histological analysis confirmed larger necrotic areas in the high RFHT group compared with low RFHT ( < 0.01) and control groups ( < 0.001). The initial intratumoral hypertension significantly decreased in both treated groups at 24 h and 48 h ( < 0.01 high RFHT, < 0.05 low RFHT). Tumor stiffness significantly decreased ( < 0.05) only in the low RFHT group at the end of treatment. This change was spatially-dependent within the tumor and a recovery toward initial conditions was observed at 48 h ( < 0.01).
Local RFHT induces time- and heating profile-dependent alterations in intratumoral pressure and stiffness in a rat model of HCC, suggesting that RFHT interventions may modulate tumor biophysics and influence drug delivery.
肿瘤内压力升高和细胞外基质硬化是肝细胞癌（HCC）有效药物递送的生物物理屏障。局部热干预会改变肿瘤的这些生物物理特性。
描述射频热疗（RFHT）干预对肿瘤内压力和肿瘤硬度的时间依赖性和热剂量相关效应。
使用计算建模方法和定制的单极RFHT系统的同基因大鼠HCC肿瘤模型，研究了两种治疗方案（高输入功率>1W和低输入功率<1W）。分别使用压电传感器和超声剪切波弹性成像（SWE），在三组（未治疗的肿瘤、接受高和低RFHT治疗的肿瘤）和时间点（治疗后立即、24小时和48小时）评估肿瘤内压力和硬度。
开发的RFHT系统在15分钟内将电极尖端温度维持在74.1±5.2°C（高RFHT）和45.9±1.6°C（低RFHT）。组织学分析证实，与低RFHT组（<0.01）和对照组（<0.001）相比，高RFHT组的坏死面积更大。在24小时和48小时时，两个治疗组的初始肿瘤内高血压均显著降低（高RFHT<0.01，低RFHT<0.05）。仅在治疗结束时，低RFHT组的肿瘤硬度显著降低（<0.05）。这种变化在肿瘤内具有空间依赖性，并且在48小时时观察到向初始状态的恢复（<0.01）。
局部RFHT在HCC大鼠模型中诱导肿瘤内压力和硬度的时间和加热曲线依赖性改变，表明RFHT干预可能调节肿瘤生物物理学并影响药物递送。
