Buffa F M, West C, Byrne K, Moore J V, Nahum A E
Department of Physics, Institute of Cancer Research and Royal Marsden NHS Trust, London, England, United Kingdom.
Int J Radiat Oncol Biol Phys. 2001 Mar 15;49(4):1109-18. doi: 10.1016/s0360-3016(00)01533-9.
To evaluate the adequacy of a Poisson tumor control probability (tcp) model and the impact of hypoxia on tumor cure.
A human colon adenocarcinoma cell line, WiDr, was grown as multicellular spheroids of different diameters. Measurements were made of cell survival and spheroid cure following 300-kV X-ray external beam irradiation in air and nitrogen. Cell survival data were fitted using a two-compartment and an oxygen diffusion model. Spheroid cure data were fitted using the tcp model.
Hypoxia was seen only for spheroids greater than 500 microm in diameter. For small spheroids tcp estimates of radiosensitivity and clonogenic number showed excellent agreement with experimentally derived values. For large spheroids, although tcp estimates of radiosensitivity were comparable with measurements, estimates of the clonogenic number were considerably lower than the experimental count. Reoxygenation of large spheroids before irradiation resulted in the tcp estimates of the number of clonogenic cells agreeing with measured values.
When hypoxia was absent, the tcp model accurately predicted cure from measured radiosensitivity and clonogen number. When hypoxia was present, the number of cells capable of regrowth in situ was considerably lower than the number of clonogenic cells that initially survived irradiation. As this counteracted the decreased radiosensitivity, hypoxia was less important for cure than predicted from cell survival assays. This finding suggests that chronic hypoxia may not limit directly the success of radiation therapy.
评估泊松肿瘤控制概率（tcp）模型的适用性以及缺氧对肿瘤治愈的影响。
将人结肠腺癌细胞系WiDr培养成不同直径的多细胞球体。在空气和氮气环境下，对300 kV X射线外照射后的细胞存活和球体治愈情况进行测量。细胞存活数据采用双室模型和氧扩散模型进行拟合。球体治愈数据采用tcp模型进行拟合。
仅在直径大于500微米的球体中观察到缺氧现象。对于小球体，tcp模型对放射敏感性和克隆源性细胞数量的估计与实验得出的值显示出极好的一致性。对于大球体，尽管tcp模型对放射敏感性的估计与测量值相当，但对克隆源性细胞数量的估计远低于实验计数。在照射前对大球体进行再氧合处理后，tcp模型对克隆源性细胞数量的估计与测量值相符。
当不存在缺氧情况时，tcp模型能够根据测量的放射敏感性和克隆源性细胞数量准确预测治愈情况。当存在缺氧情况时，能够原位再生长的细胞数量远低于最初照射后存活的克隆源性细胞数量。由于这抵消了放射敏感性的降低，缺氧对治愈的影响比细胞存活试验预测的要小。这一发现表明，慢性缺氧可能不会直接限制放射治疗的成功。
