基于调强放疗的鼻咽癌临床分期研究以及EB病毒miRNA-BART7在临床中的应用价值

发布时间：2018-03-13 16:32

本文选题：鼻咽肿瘤　切入点：肿瘤分期　出处：《福建医科大学》2014年博士论文　论文类型：学位论文

【摘要】：第一部分基于调强放疗的鼻咽癌AJCC分期研究背景与目的评估第七版AJCC分期标准对于接受根治性调强放疗的鼻咽癌患者的适用性。材料与方法收集1241例基于MRI扫描的首诊鼻咽癌患者临床数据,由两位头颈部专业影像学医师独立复阅全部MRI影像资料。对影响无局部复发生存(LRFS)、无远处转移生存(DMFS)、疾病相关生存(DSS)的预后因素进行分析。结果T1与T2、T2与T3间的LRFS差别无统计学意义(P=0.055、P=0.605)。T2与T3、T3与T4之间的DSS差别有统计学意义,但T1与T2之间的DSS差别无意义(P=0.070)。对于T1~T3期病人,虽然颅底骨质侵犯对局部复发无影响,却是远处转移和疾病相关死亡的独立预后因素。T3期伴有MRI诊断的颅神经侵犯患者生存好于T4期,而T3期伴或不伴MRI诊断的颅神经侵犯两组病人之间的生存差别均无统计学意义。III期伴或不伴MRI诊断的颅神经侵犯两组病人之间的生存差别也无统计学意义,而且均好于IV期。N0与N1、N1与N2之间的DMFS有差别,但N2与N3a、N3a与N3b之间的DMFS差别无统计学意义。结论鼻咽癌采用IMRT治疗后,N分期的预后作用变化不明显,但T1与T2之间的LRFS及DSS差距缩小,提示将现行T分期标准中T2与T1合并较为合理。T3/III期病人伴或不伴MRI诊断的颅神经侵犯生存相似,均好于T4/IV期,说明T3期伴有MRI诊断的颅神经侵犯患者不应归为T4期。第二部分:EB病毒mi RNA-BART7在临床中的应用价值背景与目的通过检测鼻咽癌患者与非鼻咽癌个体血浆中EB病毒编码的mi RNA-BART7的表达情况,评估mi RNA-BART7作为鼻咽癌肿瘤标志物在临床中的应用价值。材料与方法收集91例鼻咽癌、17例非鼻咽癌肿瘤患者治疗前血标本,以28例鼻咽癌高发区健康人体检血作为对照。另收集其中41例首诊鼻咽癌患者根治性放疗结束时的血标本。荧光定量PCR法检测血浆mi RNA-BART7的表达量,与患者的临床分期、肿瘤体积、治疗情况等临床信息进行相关性分析。同时检测患者血浆EBV DNA、血清EBV VCA-Ig A、EA-Ig A、Rta-Ig G的浓度,对比评估mi RNA-BART7对鼻咽癌诊断、疗效检测、预测预后的价值。结果mi RNA-BART7在鼻咽癌患者中高表达,而在非鼻咽癌肿瘤患者及健康对照者血浆中低表达。ROC曲线示mi RNA-BART7对鼻咽癌诊断的准确率为0.912(95%置信区间:0.863-0.962)。鼻咽癌患者治疗前血浆mi RNA-BART7表达量与T分期、N分期及临床分期、肿瘤体积相关,分期越晚体积越大,表达量越大。mi RNA-BART7相比于EBV DNA在鼻咽癌中有更高的阳性率(95.5%vs.51.3%),相比于EBV相关抗体的优点在与前者在治疗后表达显著下降,而抗体浓度在治疗后变化无规律。结论血浆mi RNA-BART7检测诊断鼻咽癌的准确性高,且与临床分期、肿瘤体积密切相关,并在治疗后下降至接近正常的水平,是较有前景的鼻咽癌肿瘤标志物。
[Abstract]:Part I background and objective to evaluate the applicability of 7th AJCC staging criteria for nasopharyngeal carcinoma patients undergoing radical intensity modulated radiotherapy (IMRT). Materials and methods A total of 1241 cases of nasopharyngeal carcinoma based on MRI scanning. Clinical data of patients with nasopharyngeal carcinoma, All MRI images were reviewed independently by two head and neck professional imaging physicians. The prognostic factors affecting survival without local recurrence, survival without distant metastasis and disease associated survival were analyzed. Results T1 and T _ 2T _ 2 were compared with T _ 3. There was no significant difference in DSS between T3 and T4, and there was no significant difference in DSS between T3T3 and T4. However, there was no significant difference in DSS between T1 and T2. For T _ 1 / T _ 3 patients, although the skull base bone invasion had no effect on local recurrence, there was no significant difference between T _ 1 and T _ 2. However, the patients with cranial nerve invasion diagnosed by MRI in stage T3 were better than those in stage T4, which were independent prognostic factors of distant metastasis and disease-related death. However, there was no significant difference in survival between the patients with or without MRI diagnosis in T3 stage. There was no significant difference in survival between the two groups with or without MRI diagnosis, and there was no significant difference in survival between the two groups, and there was no significant difference in survival between the patients with or without cranial nerve invasion diagnosed by MRI. All of them were better than those of stage IV. N0 and N1N 1 and N 2, but there was no significant difference in DMFS between N 2 and N 3a N 3a and N 3b. Conclusion the prognostic effect of N staging in patients with nasopharyngeal carcinoma treated with IMRT is not significant. However, the difference of LRFS and DSS between T 1 and T 2 was narrowed, which suggested that T 2 and T 1 were more reasonable in T 3 / III stage patients than in T 4 / IV stage patients with or without MRI, and the survival of the patients with cranial nerve invasion was similar, which was better than that of T 4 / IV stage. The results showed that the patients with cranial nerve invasion diagnosed by MRI in T3 stage should not be classified as stage T4. Part two: Epstein-Barr virus mi RNA-BART7 in clinical application background and objective to detect Epstein-Barr virus coding in plasma of patients with nasopharyngeal carcinoma and non-nasopharyngeal carcinoma patients. The expression of the mi RNA-BART7 of the code, To evaluate the clinical value of mi RNA-BART7 as a tumor marker for nasopharyngeal carcinoma (NPC). Materials and methods Blood samples were collected from 91 patients with nasopharyngeal carcinoma (NPC) and 17 patients with nonnasopharyngeal carcinoma (NNPC) before treatment. The blood samples of 41 patients with nasopharyngeal carcinoma at the end of radical radiotherapy were collected. The expression of plasma mi RNA-BART7 was detected by fluorescence quantitative PCR, and compared with the clinical stage of the patients. The clinical information of tumor volume and treatment were analyzed, and the plasma EBV DNA and serum EBV VCA-Ig Amita-Ig Rta-Ig G were detected, and the diagnosis and curative effect of mi RNA-BART7 on nasopharyngeal carcinoma were compared and evaluated. Results the expression of mi RNA-BART7 was highly expressed in patients with nasopharyngeal carcinoma. The accuracy of mi RNA-BART7 in the diagnosis of nasopharyngeal carcinoma was 0.912 ~ 95% confidence interval: 0.863-0.9620.The expression of RNA-BART7 in plasma of patients with nasopharyngeal carcinoma before treatment and T stage N stage and clinical stage were higher than those in normal controls. Compared with EBV DNA, the tumor volume was significantly higher than that of EBV DNA. Compared with the former, the positive rate of the tumor volume was significantly higher than that of EBV DNA. Compared with the former, the expression of EBV related antibodies decreased significantly. Conclusion the accuracy of plasma mi RNA-BART7 in the diagnosis of nasopharyngeal carcinoma is high, which is closely related to clinical stage and tumor volume, and decreases to the normal level after treatment. It is a promising tumor marker for nasopharyngeal carcinoma.
【学位授予单位】：福建医科大学
【学位级别】：博士
【学位授予年份】：2014
【分类号】：R739.63

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