Abstract

Objective

Deep-tissue localization of thermal doses is a long-standing challenge in magnetic field hyperthermia (MFH), and remains a limitation of the clinical application of MFH to date. Here, we show that pulse sequencing of MFH leads to a more persistent inhibition of tumor growth and less systemic impact than continuous MFH, even when delivering the same thermal dose.

Methods

We used an in vivo orthotopic murine model of pancreatic PANC-1 cancer, which was designed with a view to the forthcoming ‘NoCanTher’ clinical study, and featured MFH alongside systemic chemotherapy (SyC: gemcitabine and nab-paclitaxel). In parallel, in silico thermal modelling was implemented.

Results

Tumor volumes 27 days after the start of MFH/SyC treatment were 53% (of the initial volume) in the pulse MFH group, compared to 136% in the continuous MFH group, and 337% in the non-treated controls. Systemically, pulse MFH led to ca. 50% less core-temperature increase in the mice for a given injected dose of magnetic heating agent, and inflicted lower levels of the stress marker, as seen in the blood-borne neutrophil-to-lymphocyte ratio (1.7, compared to 3.2 for continuous MFH + SyC, and 1.2 for controls).

Conclusion

Our data provided insights into the influence of pulse sequencing on the observed biological outcomes, and validated the nature of the improved thermal dose localization, alongside significant lowering of the overall energy expenditure entailed in the treatment.

中文翻译：

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脉冲测序法对磁场热疗的深层组织定位

摘要

客观的

热剂量的深层组织定位是磁场热疗（MFH）的一项长期挑战，并且至今仍是MFH临床应用的局限性。在这里，我们显示，即使连续提供相同的热剂量，MFH的脉冲测序也比连续MFH导致对肿瘤生长的更持久的抑制和更少的系统性影响。

方法

我们使用了胰腺PANC-1癌症的体内原位鼠模型，该模型是针对即将进行的“ NoCanTher”临床研究而设计的，并以MFH和全身化疗（SyC：吉西他滨和纳布-紫杉醇）为特色。同时，实施了计算机模拟热建模。

结果

在开始MFH / SyC治疗后27天，脉冲MFH组的肿瘤体积为初始体积的53％，而连续MFH组为136％，而未治疗的对照组为337％。系统地，脉冲MFH导致约。在给定剂量的磁性加热剂中，小鼠的核心体温升高降低50％，并造成较低的应激标志物水平，如血源性中性粒细胞与淋巴细胞之比（1.7，连续的3.2相比） MFH + SyC，而对照则为1.2）。

结论

我们的数据提供了对脉冲测序对观察到的生物学结果的影响的见解，并验证了改进的热剂量定位的性质，以及显着降低了治疗所需的总能量消耗。