Balvasi Elnaz, Mahmoudi Farshid, Geraily Ghazale, Farnia Parastoo, Jafari Fatemeh
Department of Medical Physics and Biomedical Engineering, School of Medicine, Tehran University of Medical Sciences, Tehran, Iran.
School of Allied Medical Sciences, Lorestan University of Medical Sciences, Khorramabad, Iran.
Sci Rep. 2025 Aug 5;15(1):28592. doi: 10.1038/s41598-025-11937-4.
Spatially fractionated radiation therapy (SFRT) delivers heterogeneous dose distributions to enhance tumor control while reducing normal tissue toxicity. Since conventional models like the linear-quadratic (LQ) model overlook intercellular signaling, a key factor in non-uniform fields, this study uses an advanced mathematical model to assess its impact on SFRT plan evaluation. A volumetric-modulated arc therapy (VMAT)-based SFRT framework was developed, resulting in two treatment plans: VMAT-GRID and 3D lattice radiation therapy (3D-LRT). A kinetic model incorporating both direct radiation damage and intercellular signaling was implemented to simulate signal dynamics, DNA damage, and calculate the survival ratio across 3D voxelized volumes. Key dosimetric and biological indices, including mean dose, equivalent uniform dose (EUD), valley-to-peak dose ratio (VPDR), therapeutic ratio (TR), and normal tissue complication probability (NTCP), were computed using both physical and biological doses. Incorporating intercellular signaling led to increased EUD, mean dose, VPDR, and NTCP, particularly in 3D-LRT plans with steeper dose gradients. Additionally, signaling effects caused extra biological damage in non-irradiated cells within low-dose regions, which resulted in a decreased TR. This study highlights that accounting for radiation-induced signaling alters the evaluation of SFRT plans compared to models considering only direct radiation effects. Therefore, to achieve accurate assessment, particularly in complex techniques like 3D-LRT, it is advisable to employ models capable of capturing both direct and indirect radiation responses. Additionally, experimental validation is a crucial step toward translating this model into clinical practice.
空间分割放射治疗（SFRT）可提供不均匀的剂量分布，以增强肿瘤控制效果，同时降低正常组织毒性。由于传统模型（如线性二次模型）忽略了细胞间信号传导（这是不均匀照射野中的一个关键因素），本研究使用先进的数学模型来评估其对SFRT计划评估的影响。开发了一种基于容积调强弧形治疗（VMAT）的SFRT框架，产生了两个治疗计划：VMAT-网格和三维点阵放射治疗（3D-LRT）。实施了一个结合直接辐射损伤和细胞间信号传导的动力学模型，以模拟信号动态、DNA损伤，并计算三维体素化体积内的存活率。使用物理剂量和生物剂量计算关键的剂量学和生物学指标，包括平均剂量、等效均匀剂量（EUD）、谷峰剂量比（VPDR）、治疗比（TR）和正常组织并发症概率（NTCP）。纳入细胞间信号传导导致EUD、平均剂量、VPDR和NTCP增加，特别是在剂量梯度更陡的3D-LRT计划中。此外，信号传导效应在低剂量区域的未受照射细胞中造成额外的生物损伤，导致TR降低。本研究强调，与仅考虑直接辐射效应的模型相比，考虑辐射诱导的信号传导会改变SFRT计划的评估。因此，为了实现准确评估，特别是在像3D-LRT这样的复杂技术中，建议采用能够捕捉直接和间接辐射反应的模型。此外，实验验证是将该模型转化为临床实践的关键一步。
