Faculty of Science, University of Oradea, Oradea 410087, Romania; Division of Health Sciences, University of South Australia, SA 5005, Australia.
Faculty of Science, University of Oradea, Oradea 410087, Romania.
J Theor Biol. 2019 Dec 7;482:109998. doi: 10.1016/j.jtbi.2019.109998. Epub 2019 Sep 4.
Cancer stem cells (CSCs) and hypoxia are key contributors towards radioresistance and they influence the choice of radiotherapy schedule for optimal tumour control. Since hypofractionation is becoming more popular in head and neck cancer (HNC) management, the aim of this work is to use a modelling approach to evaluate the efficacy of hypofractionated radiotherapy on both early stage and advanced tumours.
An in silico HNC was developed starting from one CSC. For a biologically indorsed tumour, CSCs generate all heterogeneous cell lineages with a 1.9% probability of symmetrical division, 33 h mean cell cycle time and 52 days volume doubling time. The simulated schedules include conventional, hyperfractionated, and hypofractionated radiotherapy and they target tumours with various oxygenation levels.
Oxic and mildly hypoxic tumours can benefit from hypofractionation, which reduces treatment time without increasing adverse events. Advanced tumours are only controlled by hyperfractionation, however a tumour with oxygen levels below 6 mmHg and 5.9% pre-treatment CSCs, needs either a dose greater than 81.6 Gy to be eradicated or the addition of adjuvant therapies.
Hypofractionation is suited for early stage tumours, whereas aggressive HNC require hyperfractionation. The interplay between CSCs and hypoxia dictates the optimal treatment strategy.
癌症干细胞（CSCs）和缺氧是导致放射抵抗的关键因素，它们影响着为实现最佳肿瘤控制而选择的放疗方案。由于在头颈部癌症（HNC）管理中，分次剂量降低越来越受欢迎，本研究旨在采用建模方法评估在早期和晚期肿瘤中分次剂量降低放疗的疗效。
从一个 CSC 开始开发了一个虚拟的 HNC。对于一个生物学上被认可的肿瘤，CSC 以 1.9%的对称分裂概率产生所有异质细胞谱系，平均细胞周期时间为 33 小时，体积倍增时间为 52 天。模拟的方案包括常规、超分割和分次剂量降低放疗，并针对不同氧合水平的肿瘤。
氧合良好和轻度缺氧的肿瘤可以从分次剂量降低中获益，这可以减少治疗时间而不增加不良反应。晚期肿瘤只能通过超分割来控制，但是，氧水平低于 6mmHg 和 5.9%的治疗前 CSC 的肿瘤，需要大于 81.6Gy 的剂量才能根除，或者需要辅助治疗。
分次剂量降低适用于早期肿瘤，而侵袭性 HNC 需要超分割。CSC 和缺氧之间的相互作用决定了最佳的治疗策略。
