Keall Paul J, Lammering Guido, Lin Peck-Sun, Winter David S, Chung Theodore D, Mohan Radhe, Schmidt-Ullrich Rupert K
Department of Radiation Oncology, Virginia Commonwealth University, Richmond, VA 23298-0058, USA.
Int J Radiat Oncol Biol Phys. 2003 Sep 1;57(1):255-63. doi: 10.1016/s0360-3016(03)00500-5.
Genetic radiotherapy, the combination of gene therapy and radiation therapy, for cancer treatment is evolving from laboratory studies to clinical trials. Genetic radiotherapy involves the viral infection of cells that change the sensitivity of transduced cells to radiation. Because there is no patient outcome data for genetic radiotherapy, prospective models are needed to determine the expected benefit of this new modality. Such a prospective model has been developed in this work.
An existing tumor control probability (TCP) calculation model developed for external beam radiotherapy was modified for genetic radiotherapy. Specifically, the (1) transduced fraction and (2) enhancement factor of the transduced cells were included in the model. Parametric studies of the effects of these two variables on TCP for head-and-neck cancer were performed.
Using reasonable transduction fraction and enhancement factor values (0.8 and 1.4, respectively), the model predicts an increase in the TCP for genetic radiotherapy over radiotherapy alone by up to 15% for the same radiotherapy dose. The theoretical limit of TCP increase was calculated to be near 70%, which may occur with improved techniques that increase the transduced fraction or because of a strong bystander effect. To maintain existing TCP, dose reductions from 5 Gy (reasonable values) to >30 Gy (ideal case) are predicted for genetic radiotherapy over radiotherapy alone.
Our results indicate that genetic radiotherapy has the potential to significantly improve tumor control over radiotherapy alone.
基因放射疗法，即基因治疗与放射治疗相结合用于癌症治疗，正从实验室研究发展到临床试验阶段。基因放射疗法涉及对细胞进行病毒感染，从而改变转导细胞对辐射的敏感性。由于目前尚无基因放射疗法的患者预后数据，因此需要前瞻性模型来确定这种新疗法的预期获益。本研究开发了这样一种前瞻性模型。
对现有的用于外照射放疗的肿瘤控制概率（TCP）计算模型进行修改，以用于基因放射疗法。具体而言，该模型纳入了（1）转导分数和（2）转导细胞的增强因子。对这两个变量对头颈部癌TCP的影响进行了参数研究。
使用合理的转导分数和增强因子值（分别为0.8和1.4），该模型预测，在相同放疗剂量下，基因放射疗法的TCP比单纯放疗最多可提高15%。计算得出TCP增加的理论极限接近70%，这可能会随着提高转导分数的技术改进或由于强烈的旁观者效应而出现。为维持现有的TCP，预计基因放射疗法相对于单纯放疗的剂量可从5 Gy（合理值）降低至>30 Gy（理想情况）。
我们的结果表明，基因放射疗法有可能比单纯放疗显著提高肿瘤控制率。
