Department of Radiation Oncology, S. Cuore-don Calabria Hospital, Negrar (VR), Italy.
Int J Radiat Oncol Biol Phys. 2012 Aug 1;83(5):1603-8. doi: 10.1016/j.ijrobp.2011.10.015. Epub 2012 Jan 21.
To verify whether a tumor control probability (TCP) model which mechanistically incorporates acute and chronic hypoxia is able to describe animal in vivo dose-response data, exhibiting tumor reoxygenation.
The investigated TCP model accounts for tumor repopulation, reoxygenation of chronic hypoxia, and fluctuating oxygenation of acute hypoxia. Using the maximum likelihood method, the model is fitted to Fischer-Moulder data on Wag/Rij rats, inoculated with rat rhabdomyosarcoma BA1112, and irradiated in vivo using different fractionation schemes. This data set is chosen because two of the experimental dose-response curves exhibit an inverse dose behavior, which is interpreted as due to reoxygenation. The tested TCP model is complex, and therefore, in vivo cell survival data on the same BA1112 cell line from Reinhold were added to Fischer-Moulder data and fitted simultaneously with a corresponding cell survival function.
The obtained fit to the combined Fischer-Moulder-Reinhold data was statistically acceptable. The best-fit values of the model parameters for which information exists were in the range of published values. The cell survival curves of well-oxygenated and hypoxic cells, computed using the best-fit values of the radiosensitivities and the initial number of clonogens, were in good agreement with the corresponding in vitro and in situ experiments of Reinhold. The best-fit values of most of the hypoxia-related parameters were used to recompute the TCP for non-small cell lung cancer patients as a function of the number of fractions, TCP(n).
The investigated TCP model adequately describes animal in vivo data exhibiting tumor reoxygenation. The TCP(n) curve computed for non-small cell lung cancer patients with the best-fit values of most of the hypoxia-related parameters confirms previously obtained abrupt reduction in TCP for n < 10, thus warning against the adoption of severely hypofractionated schedules.
验证一种肿瘤控制概率（TCP）模型是否能够描述具有肿瘤再氧合作用的动物体内剂量-反应数据，该模型机制上纳入了急性和慢性缺氧。
所研究的 TCP 模型考虑了肿瘤再增殖、慢性缺氧的再氧合以及急性缺氧的波动氧合。使用最大似然法，将模型拟合到 Fischer-Moulder 关于 Wag/Rij 大鼠的数据中，这些大鼠接种了大鼠横纹肌肉瘤 BA1112，并使用不同的分割方案进行体内照射。选择这个数据集是因为两个实验剂量-反应曲线中的两个表现出反剂量行为，这被解释为再氧合的结果。所测试的 TCP 模型很复杂，因此，来自 Reinhold 的相同 BA1112 细胞系的体内细胞存活数据被添加到 Fischer-Moulder 数据中，并与相应的细胞存活函数同时拟合。
对合并的 Fischer-Moulder-Reinhold 数据的拟合在统计学上是可接受的。对于存在信息的模型参数的最佳拟合值，其范围在已发表的值范围内。使用放射敏感性和初始克隆数的最佳拟合值计算的富氧细胞和缺氧细胞的细胞存活曲线与 Reinhold 的相应体外和原位实验非常吻合。大多数与缺氧相关的参数的最佳拟合值用于重新计算非小细胞肺癌患者的 TCP 作为分数（TCP(n)）的函数。
所研究的 TCP 模型充分描述了具有肿瘤再氧合作用的动物体内数据。使用大多数与缺氧相关的参数的最佳拟合值计算的非小细胞肺癌患者的 TCP(n)曲线证实了之前获得的 n < 10 时 TCP 急剧下降，从而警告不要采用严重低分割方案。
