剂量异质性对迷你束放射治疗抗肿瘤反应的意义。

IF 4.9 1区 医学 Q1 ONCOLOGY Radiotherapy and Oncology Pub Date : 2024-10-10 DOI:10.1016/j.radonc.2024.110577
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引用次数: 0

摘要

背景和目的:质子微束放射治疗(pMBRT)是一种基于强剂量沉积调制的非常规放射技术。由于其特殊的模式,质子微束放射治疗涉及多个剂量测定(峰值和谷值剂量、峰谷剂量比(PVDR))和几何参数(束宽、间距),这些都会影响生物反应。本研究旨在加深对各种参数与中心生物机制(尤其是抗肿瘤免疫)之间的关系,以及这些关系如何影响治疗效果的理解,以充分发挥 pMBRT 的潜力。我们还评估了 X 射线 MBRT 的效果,以进一步阐明峰值剂量和剂量异质性的影响:方法和材料:对胶质母细胞瘤正位大鼠模型进行了多种 pMBRT 配置。研究了不同剂量参数对存活率的影响以及对 pMBRT 关键机制(如免疫反应)的调节。后者通过放射后7天的免疫组化和流式细胞术进行评估:结果:各种pMBRT方案通过保持最低谷剂量和更高的剂量异质性(由峰值剂量驱动)提高了生存率。虽然平均剂量对免疫浸润没有影响,但较高的PVDR可减少免疫抑制微环境:我们的研究结果表明,肿瘤根除和免疫浸润都与较高的剂量异质性有关。通过优化峰值剂量和保持最小谷值剂量,可以实现更高的剂量异质性。这些参数有助于直接根除肿瘤和减少免疫抑制,这与传统质子治疗中的均匀剂量分布所带来的免疫抑制性更强的肿瘤环境不同。
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The significance of dose heterogeneity on the anti-tumor response of minibeam radiation therapy

Background and purpose

Proton Minibeam Radiation Therapy (pMBRT) is an unconventional radiation technique based on a strong modulation of the dose deposition. Due to its specific pattern, pMBRT involves several dosimetry (peak and valley doses, peak-to-valley dose ratio (PVDR)) and geometrical parameters (beam width, spacing) that can influence the biological response. This study aims at contributing to the efforts to deepen the comprehension of how the various parameters relate to central biological mechanisms, particularly anti-tumor immunity, and how these correlations affect treatment outcomes with the goal to fully unleash the potential of pMBRT. We also evaluated the effects of X-ray MBRT to further elucidate the influence of peak dose and dose heterogeneity.

Methods and Materials

An orthotopic rat model of glioblastoma underwent several pMBRT configurations. The impact of different dosimetric parameters on survival and on the modulation of crucial mechanisms for pMBRT, such as immune response, was investigated. The latter was assessed by immunohistochemistry and flow cytometry at 7 days post-irradiation.

Results

Survival was improved across the various pMBRT regimens via maintaining a minimum valley dose as well as a higher dose heterogeneity, which is driven by peak dose. While the mean dose did not impact immune infiltration, a higher PVDR promoted a less immunosuppressive microenvironment.

Conclusions

Our results suggest that both tumor eradication, and immune infiltration are associated with higher dose heterogeneity. Higher dose heterogeneity was achieved by optimizing the peak dose, as well as maintaining a minimum valley dose. These parameters contributed to direct tumor eradication as well as reduction of immunosuppression, which is a departure from the more immunosuppressive tumor environment found in conventional proton therapy that delivers uniform dose distributions.
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来源期刊
Radiotherapy and Oncology
Radiotherapy and Oncology 医学-核医学
CiteScore
10.30
自引率
10.50%
发文量
2445
审稿时长
45 days
期刊介绍: Radiotherapy and Oncology publishes papers describing original research as well as review articles. It covers areas of interest relating to radiation oncology. This includes: clinical radiotherapy, combined modality treatment, translational studies, epidemiological outcomes, imaging, dosimetry, and radiation therapy planning, experimental work in radiobiology, chemobiology, hyperthermia and tumour biology, as well as data science in radiation oncology and physics aspects relevant to oncology.Papers on more general aspects of interest to the radiation oncologist including chemotherapy, surgery and immunology are also published.
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