磁共振弥散加权成像技术预测鼻咽癌放射敏感性的价值及其机制研究

发布时间：2019-01-21 10:09

【摘要】：背景与目的鼻咽癌的疗效与放射敏感性密切相关，但目前缺乏预测其放射敏感性的有效方法。磁共振弥散加权成像（MR-DWI）技术具有分子功能影像的特点，且能提供定量参数表观弥散系数（ADC），它与宫颈癌、肝癌、头颈部癌的放化疗反应性有一定的相关性。本研究拟从动物模型和患者两个层面探讨MR-DWI技术预测鼻咽癌放射敏感性的价值及其作用机制，为其应用于临床提供依据。材料与方法①将荷人鼻咽癌裸鼠随机分成对照组和照射组（单次照射剂量15Gy）。分别测量照射前的ADC值（ADC0）和照射后第二天的ADC值（ADC1），ΔADC=(ADC1-ADC0)/ADC0*100%。照射后第X天移植瘤的体积变化ΔVx=（Vx-V0）/VO*100%；第X天对照组与照射组体积变化的差值定义为辐射相关体积变化δVX=ΔVxc-ΔVxt。②以SPECT进行鼻咽癌裸鼠移植瘤99mTc-HL91乏氧显像，分析肿瘤组织与正常组织的放射性计数比值（T/NT）与ADC值的相关性。③另外将荷瘤裸鼠随机分为未照射组、照射后第1、2、3、5和7天组，比较移植瘤的ADC值和HIF-1α表达动态变化的相关性。④收集2010年4月至2011年11月间本单位鼻咽癌患者，采用调强放疗±化疗。分别测量治疗前鼻咽原发灶的ADC值（ADC0）和放疗两周时ADC值（ADC1），△ADC=（ADC1-ADC0）/ADC0*100%。放疗结束后3个月按WHO实体瘤疗效评价标准评价近期疗效。结果①CNE1组和CNE2组间移植瘤ADC0无显著差异，ADC1及△ADC差异有统计学意义。△ADC与δVX从照射后第2天开始即存在负相关关系，多元线性回归分析发现ΔADC是照射后第14天δVx的独立影响因素。②移植瘤的ADC值和HL-91乏氧显像后4h移植瘤与对侧正常组织放射性计数比值成负相关关系。③移植瘤照射后ADC值的变化与HIF-1α的蛋白和mRNA表达水平呈明显负相关。④共有134例鼻咽癌患者符合条件，其中合并化疗121例。放疗后三个月时鼻咽局部有残留者23例（17.2%），无残留患者111例（82.8%），，两组的△ADC分别为49.77%±31.02%和68.35%±34.22%，差别有统计学意义（t=-2.406，P=0.017）。Logistic回归分析结果表明△ADC是鼻咽癌调强放疗近期疗效的独立预后因素。结论 MR-DWI技术具有应用于预测鼻咽癌放射敏感性的潜在能力，作用机制可能与乏氧有关。
[Abstract]:Background and objective the efficacy of nasopharyngeal carcinoma is closely related to its radiosensitivity, but there is no effective method to predict its radiosensitivity. Magnetic Resonance Diffusion-weighted Imaging (MR-DWI) has the characteristics of molecular functional imaging and can provide quantitative parameter apparent diffusion coefficient (ADC),) which is related to the radiochemotherapeutic reactivity of cervical carcinoma liver cancer and head and neck cancer. The purpose of this study was to explore the value and mechanism of MR-DWI in predicting radiosensitivity of nasopharyngeal carcinoma (NPC) from animal model and patient level, and to provide evidence for its clinical application. Materials and methods 1 Nude mice bearing human nasopharyngeal carcinoma were randomly divided into control group and irradiation group (single dose of 15Gy). ADC value (ADC0) before irradiation and ADC value (ADC1), 螖 ADC= (ADC1-ADC0) / ADC0*100%. on the second day after irradiation were measured, respectively. Volume change of transplanted tumor 螖 Vx= (Vx-V0) / VO*100%; on day X after irradiation On day X, the difference of volume changes between the control group and the irradiation group was defined as radiation-related volume change 未 VX= 螖 Vxc- 螖 Vxt.2 using SPECT to perform 99mTc-HL91 hypoxia imaging of transplanted tumor of nasopharyngeal carcinoma in nude mice. The correlation between the radioactivity count ratio (T/NT) of tumor tissue to normal tissue and the ADC value was analyzed. 3 in addition, the nude mice were randomly divided into two groups: the non-irradiated group, the 5th and 7th day groups after irradiation. To compare the correlation between ADC value and HIF-1 伪 expression in transplanted tumor. 4 patients with nasopharyngeal carcinoma were collected from April 2010 to November 2011 and received intensity modulated radiotherapy + chemotherapy. ADC value (ADC0) and ADC value (ADC1), ADC= (ADC1-ADC0) / ADC0*100%. of nasopharyngeal primary focus were measured before treatment and two weeks after radiotherapy, respectively. Three months after radiotherapy, the short-term efficacy was evaluated according to the criteria for evaluating the efficacy of WHO solid tumor. Results there was no significant difference in ADC0 between 1CNE1 group and CNE2 group, but there was significant difference in ADC1 and ADC. There was a negative correlation between ADC and 未 VX from the second day after irradiation. Multiple linear regression analysis showed that 螖 ADC was the independent factor of 未 Vx on the 14th day after irradiation. (2) there was a negative correlation between the ADC value of transplanted tumor and the radioactivity count ratio of contralateral normal tissue at 4h after HL-91 hypoxia imaging. The change of ADC value after irradiation was negatively correlated with the expression of HIF-1 伪 protein and mRNA. 4 A total of 134 patients with nasopharyngeal carcinoma were eligible. Among them 121 cases were complicated with chemotherapy. Three months after radiotherapy, there were 23 cases (17.2%) with residual nasopharynx and 111 cases (82.8%) with no residual nasopharynx. The ADC of the two groups was 49.77% 卤31.02% and 68.35% 卤34.22%, respectively. The difference was statistically significant (twe-2.406). Logistic regression analysis showed that ADC was an independent prognostic factor for the short-term therapeutic effect of intensity-modulated radiotherapy for nasopharyngeal carcinoma (NPC). Conclusion MR-DWI has the potential to predict radiosensitivity of nasopharyngeal carcinoma, and the mechanism may be related to hypoxia.
【学位授予单位】：福建医科大学
【学位级别】：博士
【学位授予年份】：2012
【分类号】：R445.2;R739.63

【参考文献】