宫颈癌不同照射剂量模式生物学效应研究

Cervical cancer is the most common gynecological malignancies in China. Radiation therapy is one of the major treatments for cervical cancer. In the past decade, there was a rapid development of radiotherapy technology .New IMRT technology improves the average dose of target, but clinical practice showed that it did not significantly improve local control rate. Relative researches suggest that this may be partly due to the special fractionated radiation dose delivery pattern of IMRT. VMAT, TomoTherapy, and other new technologies have brought new radiation dose delivery patterns, but there is no systemic and basic research on the efficacy of different radiation dose delivery patterns. This study is designed to analyze the characteristics of radiation dose delivery patterns of conventional radiotherapy, IMRT, VMAT, TomoTherapy and other commonly used patterns, and then a physical modeling process is done based on the result. Then evaluation of biological effectiveness among different radiation dose delivery patterns is made on cellular level, and a biological model of radiation dose delivery pattern is established. Possible mechanism causing the difference is discussed from the molecular and cellular level to provide a theoretical basis for further research. And we hope to find a more rational radiation dose delivery pattern to provide a theoretical basis for the improvement of clinical radiation dose pattern.

宫颈癌是中国最常见的妇科恶性肿瘤。放射治疗是宫颈癌主要的治疗手段之一。近十余年，放疗技术发展迅速，以适形调强放疗（IMRT）为代表的新技术提高了靶区平均剂量，但临床实践表明其并未显著提高疗效，研究提示这可能与IMRT分次内特殊的照射剂量模式相关。容积弧形调强放疗（VMAT）、螺旋断层调强放疗（Helical TomoTherapy）等新技术又带来了新的照射剂量模式，但目前尚无对不同照射剂量模式疗效的系统、基础研究。本研究拟通过对常规放疗、IMRT、VMAT、Tomotherapy等临床常用的照射剂量模式的特点进行分析，在此基础上将不同照射剂量模式进行物理建模；从细胞水平比较评价各照射剂量模式的生物学效应区别，建立照射剂量模式生物效应模型；从分子、细胞水平探讨造成区别的可能机理，为进一步研究提供理论基础；寻找更合理的照射剂量模式，为改进临床现有照射剂量模式提供理论依据。

本研究拟通过对常规放疗、IMRT、VMAT、Tomotherapy等临床常用的照射剂量模式的特点进行分析，在此基础上将不同照射剂量模式进行物理建模；选取三种宫颈癌细胞株：CaSki、HeLa和SiHa细胞株，建立3种细胞放射敏感性模型，运用克隆形成实验分析不同剂量和剂量率照射下三种细胞的放射敏感性及其差别，结果显示CaSki的细胞存活分数（SF2 ，Survival Fraction at 2Gy）为57.37%，HeLa为70.62%，SiHa为74.77%，三者差异具有统计学意义（P=0.002）。CaSki、HeLa、SiHa细胞在不同剂量率200、400、600 cGy/min照射时的生存分数差异不具有统计学意义（P>0.05）。从细胞水平比较评价各照射剂量模式的生物学效应区别，建立照射剂量模式生物效应模型；细胞水平探讨造成区别的可能机理，为进一步分子生物学的研究提供前期的实验基础；同时也为进一步寻找更合理的照射剂量模式，为改进临床现有照射剂量模式提供了一定的理论依据。