The Evolution of Tumour Composition During Fractionated Radiotherapy: Implications for Outcome
The Evolution of Tumour Composition During Fractionated Radiotherapy: Implications for Outcome
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DOI：
10.1007/s11538-018-0391-9
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发表时间：
2018-05-01
影响因子：
3.5
通讯作者：
Byrne, Helen M.
中科院分区：
文献类型：
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作者：
Lewin, Thomas D.;Maini, Philip K.;Byrne, Helen M.
目前用于提供放射治疗的方案主要基于肿瘤阶段以及淋巴结和转移状态，尽管众所周知肿瘤及其微环境是高度异质性的。众所周知，局部氧张力在辐射诱导的细胞死亡中起着重要作用，缺氧肿瘤区域对辐射的反应很差。因此，为了改善辐射反应，重要的是要更充分地了解在分割辐射之前和期间生长的肿瘤内的氧的时空分布。为此，我们扩展了由Greenspan（Stud Appl Math 51：317-340，1972）首次提出的肿瘤生长的空间分辨数学模型，以研究氧异质性对辐射诱导的细胞死亡的影响。更详细地，假设在肿瘤中的每个位置处由于辐射引起的细胞死亡（如由公知的线性二次模型确定的）也取决于局部氧浓度。氧浓度由反应扩散方程控制，该反应扩散方程耦合到确定假定的球对称肿瘤的大小的积分微分方程。我们结合联合收割机的数值和分析技术来研究不同的肿瘤内氧分布的肿瘤的辐射反应。模型模拟揭示了一个快速的短暂增加，缺氧后再生长的肿瘤球体照射后。我们研究了对不同放射分割时间表的反应，并确定了分割间时间和每分割剂量之间的肿瘤特异性关系，以实现治愈。该模型所表现出的丰富的动力学表明，空间异质性可能是重要的预测肿瘤放射治疗的临床应用。
Current protocols for delivering radiotherapy are based primarily on tumour stage and nodal and metastases status, even though it is well known that tumours and their microenvironments are highly heterogeneous. It is well established that the local oxygen tension plays an important role in radiation-induced cell death, with hypoxic tumour regions responding poorly to irradiation. Therefore, to improve radiation response, it is important to understand more fully the spatiotemporal distribution of oxygen within a growing tumour before and during fractionated radiation. To this end, we have extended a spatially resolved mathematical model of tumour growth, first proposed by Greenspan (Stud Appl Math 51:317-340, 1972), to investigate the effects of oxygen heterogeneity on radiation-induced cell death. In more detail, cell death due to radiation at each location in the tumour, as determined by the well-known linear-quadratic model, is assumed also to depend on the local oxygen concentration. The oxygen concentration is governed by a reaction-diffusion equation that is coupled to an integro-differential equation that determines the size of the assumed spherically symmetric tumour. We combine numerical and analytical techniques to investigate radiation response of tumours with different intratumoral oxygen distribution profiles. Model simulations reveal a rapid transient increase in hypoxia upon regrowth of the tumour spheroid post-irradiation. We investigate the response to different radiation fractionation schedules and identify a tumour-specific relationship between inter-fraction time and dose per fraction to achieve cure. The rich dynamics exhibited by the model suggest that spatial heterogeneity may be important for predicting tumour response to radiotherapy for clinical applications.