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首页> 外文期刊>Journal of Theoretical Biology >A mathematical model of brain tumour response to radiotherapy and chemotherapy considering radiobiological aspects.
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A mathematical model of brain tumour response to radiotherapy and chemotherapy considering radiobiological aspects.

机译：考虑放射生物学方面的脑肿瘤对放疗和化疗反应的数学模型。

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Glioblastoma is the most frequent and malignant brain tumour. For many years, the conventional treatment has been maximal surgical resection followed by radiotherapy (RT), with a median survival time of less than 10 months. Previously, the use of adjuvant chemotherapy (given after RT) has failed to demonstrate a statistically significant survival advantage. Recently, a randomized phase III trial has confirmed the benefit of temozolomide (TMZ) and has defined a new standard of care for the treatment of patients with high-grade brain tumours. The results showed an increase of 2.5 months in median survival, and 16.1% in 2 year survival, for patients receiving RT with TMZ compared with RT alone. It is not clear whether the major benefit of TMZ comes from either concomitant administration of TMZ with RT, or from six cycles of adjuvant TMZ, or both. The objectives were to develop our original model, which addressed survival after RT, to construct a new module to assess the potential role of TMZ from clinical data, and to explore its synergistic contribution in addition to radiation. The model has been extended to include radiobiological parameters. The addition of the linear quadratic equation to describe cellular response to treatment has enabled us to quantify the effects of radiation and TMZ in radiobiological terms. The results indicate that the model achieves an excellent fit to the clinical data, with the assumption that TMZ given concomitantly with RT synergistically increases radiosensitivity. The alternative, that the effect of TMZ is due only to direct cell killing, does not fit the clinical data so well. The addition of concomitant TMZ appears to change the radiobiological parameters. This aspect of our results suggests possible treatment developments. Our observations need further evaluations in real clinical trials, may suggest treatment strategies for new trials, and inform their design.
机译：胶质母细胞瘤是最常见和恶性的脑肿瘤。多年来，常规治疗一直是最大的手术切除，然后放疗（RT），中位生存时间少于10个月。以前，辅助化疗（在放疗后给予）的使用未能显示出统计学上显着的生存优势。最近，一项随机的III期临床试验证实了替莫唑胺（TMZ）的益处，并为治疗高级别脑肿瘤患者制定了新的护理标准。结果显示，与单纯放疗相比，接受TMZ放疗的患者中位生存期增加2.5个月，而2年生存期增加16.1％。尚不清楚TMZ的主要益处是来自于TMZ与RT的同时给药，还是来自六个佐剂TMZ，或两者兼而有之。目的是开发我们的原始模型，该模型解决了RT后的生存问题，构建了一个新模块，可根据临床数据评估TMZ的潜在作用，并探索其除辐射外的协同作用。该模型已扩展为包括放射生物学参数。线性二次方程式描述了细胞对治疗的反应，使我们能够以放射生物学术语量化辐射和TMZ的影响。结果表明，该模型达到了与临床数据的极佳拟合，并假设与RT一同给予的TMZ协同增加了放射敏感性。另一种选择是，TMZ的作用仅是直接杀伤细胞而引起的，并不完全符合临床数据。伴随的TMZ的加入似乎改变了放射生物学参数。我们结果的这一方面表明可能的治疗方法。我们的观察结果需要在实际临床试验中进行进一步评估，可能会建议新试验的治疗策略，并为他们的设计提供依据。

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