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An imaging-based tumour growth and treatment response model: Investigating the effect of tumour oxygenation on radiation therapy response

机译:基于影像的肿瘤生长和治疗反应模型:研究肿瘤氧合对放射治疗反应的影响

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摘要

A multiscale tumour simulation model employing cell-line-specific biological parameters and functional information derived from pre-therapy PET/CT imaging data was developed to investigate effects of different oxygenation levels on the response to radiation therapy. For each tumour voxel, stochastic simulations were performed to model cellular growth and therapeutic response. Model parameters were fitted to published preclinical experiments of head and neck squamous cell carcinoma (HNSCC). Using the obtained parameters, the model was applied to a human HNSCC case to investigate effects of different uniform and non-uniform oxygenation levels and results were compared for treatment efficacy. Simulations of the preclinical studies showed excellent agreement with published data and underlined the model’s ability to quantitatively reproduce tumour behaviour within experimental uncertainties. When using a simplified transformation to derive non-uniform oxygenation levels from molecular imaging data, simulations of the clinical case showed heterogeneous tumour response and variability in radioresistance with decreasing oxygen levels. Once clinically validated, this model could be used to transform patient-specific data into voxel-based biological objectives for treatment planning and to investigate biologically optimized dose prescriptions.
机译:建立了一种多尺度肿瘤模拟模型,该模型利用细胞系特定的生物学参数和从治疗前的PET / CT成像数据得出的功能信息来研究不同氧合水平对放射治疗反应的影响。对于每个肿瘤体素,进行随机模拟以模拟细胞生长和治疗反应。模型参数适合于已发表的头颈部鳞状细胞癌(HNSCC)的临床前实验。使用获得的参数,将该模型应用于人类HNSCC病例,以研究不同均匀和不均匀充氧水平的影响,并比较治疗效果的结果。临床前研究的模拟显示与已发表的数据极好的一致性,并强调了该模型在实验不确定性范围内定量再现肿瘤行为的能力。当使用简化的转换从分子成像数据中得出不均匀的氧合水平时,临床病例的模拟显示出异质性肿瘤反应和放射抵抗性随氧水平的降低而变化。一旦经过临床验证,该模型可用于将患者的特定数据转换为基于体素的生物学目标,以进行治疗计划并研究生物学优化的剂量处方。

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