靶向EBV-LMP1脱氧核酶增强鼻咽癌放疗敏感性的临床实验研究
摘要
目的:
鼻咽癌是常见的头颈部恶性肿瘤,首选治疗方法是放射治疗,对于中晚期鼻咽癌5年生存率不足50%。放疗抵抗及复发、转移是导致放疗失败的主要原因。因此,寻找放疗增敏的新方法成为肿瘤治疗的热点。本课题研究目的是将靶向LMP1的脱氧核酶应用于临床上EBV-LMP1阳性的鼻咽癌患者,观察靶向EBV-LMP1脱氧核酶能否增强鼻咽癌患者对放疗的敏感性,同时观察其毒副作用。
方法:
将符合入组标准的20例鼻咽癌病人按双盲法随机分为两组,试验组(A组,放疗加靶向EBV-LMP1脱氧核酶)和对照组(B组,放疗加生理盐水),两组放射治疗方法完全相同,使用不规则铅挡块的体外常规放射治疗,鼻咽照射剂量D_T70～76Gy,7～7.5周完成,阳性颈淋巴结D_T66～70Gy,6～7周完成;颈淋巴结阴性预防照射D_T50～56Gy,5～6周完成。A组在每周一、四放疗前2小时,肿瘤局部注射脱氧核酶0.1ml,120mg/ml,共10次。B组予生理盐水0.1ml,其他治疗及处理A、B两组完全相同。每周内窥镜下观察肿瘤大小变化;通过导入放疗前、放疗50 Gy、放疗结束和放疗后3月复查的4次MRI图象精确测量肿瘤体积;采用实体肿瘤WHO客观疗效评价标准计算CR、PR:并按照RTOG急性放射损伤分级标准观察其使用过程中的毒副反应。
结果:
试验组与对照组患者的一般项目分组组间一致性好,说明试验组与对照组的同质性、均衡性都较高。根据MRI所示瘤体体积(cm~3)进行率的转换(RTR值)并行t检验,结果显示RTR_3即3月后复查与放疗前相比较试验组与对照组组间P值为0.04,有显著性差异,认为靶向EBV-LMP1脱氧核酶能够增强LMP1阳性的鼻咽癌病人的放疗敏感性。两组的CR、PR相比较,P值=0.092,因例数过少暂时未发现明显差别,无显著性差异。两组间造血系统、皮肤、粘膜、唾液腺、肝肾功能的损伤无显著性差异。
结论:
靶向EBV-LMP1脱氧核酶增强了LMP1阳性的鼻咽癌患者对放疗的敏感性,提高了肿瘤消退速率。在放疗过程中不会增加鼻咽癌放疗患者的急性放射损伤,具有良好的安全性。
Objective:
Nasopharyngeal carcinoma(NPC)is one of the common maligant tumors in China.Radiotherapy is the main method for its clinical therapy. It is reported that the five-year survival rate of intermediate-advanced stage is less than 50%.Resistance to the therapy,recurrence and metastasis are the main reasons duing to the fail of treatment.Now,to search a new method enhancing radiosensitivity become a hot spot.This study is to use the targeting EBV-LMP1 deoxyribozymes in clinical NPC patients who be diagnosed positive expression of LMP1,observe the effects and side effects of DNAzymes,and investigate targeting EBV-LMP1 DNAzymes may as potential radiosensitizers for NPC treatment.
Methods:
Divide 20 patients who match the selected conditions into 2 groups in random and double-blind,one is to be tested(Group A,radiotherapy plus the DNAzymes),one is contrast(Group B,radiotherapy alone).The methods of radiotherapy between groups is same:regular radiotherapy using the irregular lead block.The total doses of nasopharynx is DT70-76Gy,accomplished in 7-7.5weeks.The total doses of positive lymph node in cervical is Dr 66-70 Gy,accomplished in 6-7 weeks.2 hours before radiotherapy,Group A be injected the DNAzymes 0.1ml(120mg/ml)in the tumor local,,every Monday and Thursday,and total 10 times.Group B be injected Sodium Chloride 0.1ml the same time. Other treatments are same between 2 groups.Observe the tumor through the endoscope every week,measure the volume through 4 times MRI images rigorously at the point of before the radiotherapy,Dr 50 Gy,D_T70 Gy and return visit after 3 months,test the CR,PR using the solid tumor WHO objective curative effect standards and observe the side effects during the period.
Results:
The general data is consistency,which means well homogenicity and balanced between 2 groups.Accoding to the tumor volume(cm~3),we changed it into RTR,which means rate of tumor reduction,and carry out two-tailed t test for the values.The results of RTR~3 is P=0.04,which showed a significant difference between two treatments.The results of CR,PR is P=0.092,which can't showed a significant difference between two groups temporarily,as the reason of little cases.The results of the observation index,which from RTOG's acute radiotherapy injured,can't showed a significant difference between two groups.
Conclusions:
The result suggest that targeting EBV-LMP1 DNAzyme may represent as potential radiosensitizers for NPC treatment.During the period,this DNAzyme did any acute radiotherapy injured,which means well security.
鼻咽癌是常见的头颈部恶性肿瘤,首选治疗方法是放射治疗,对于中晚期鼻咽癌5年生存率不足50%。放疗抵抗及复发、转移是导致放疗失败的主要原因。因此,寻找放疗增敏的新方法成为肿瘤治疗的热点。本课题研究目的是将靶向LMP1的脱氧核酶应用于临床上EBV-LMP1阳性的鼻咽癌患者,观察靶向EBV-LMP1脱氧核酶能否增强鼻咽癌患者对放疗的敏感性,同时观察其毒副作用。
方法:
将符合入组标准的20例鼻咽癌病人按双盲法随机分为两组,试验组(A组,放疗加靶向EBV-LMP1脱氧核酶)和对照组(B组,放疗加生理盐水),两组放射治疗方法完全相同,使用不规则铅挡块的体外常规放射治疗,鼻咽照射剂量D_T70～76Gy,7～7.5周完成,阳性颈淋巴结D_T66～70Gy,6～7周完成;颈淋巴结阴性预防照射D_T50～56Gy,5～6周完成。A组在每周一、四放疗前2小时,肿瘤局部注射脱氧核酶0.1ml,120mg/ml,共10次。B组予生理盐水0.1ml,其他治疗及处理A、B两组完全相同。每周内窥镜下观察肿瘤大小变化;通过导入放疗前、放疗50 Gy、放疗结束和放疗后3月复查的4次MRI图象精确测量肿瘤体积;采用实体肿瘤WHO客观疗效评价标准计算CR、PR:并按照RTOG急性放射损伤分级标准观察其使用过程中的毒副反应。
结果:
试验组与对照组患者的一般项目分组组间一致性好,说明试验组与对照组的同质性、均衡性都较高。根据MRI所示瘤体体积(cm~3)进行率的转换(RTR值)并行t检验,结果显示RTR_3即3月后复查与放疗前相比较试验组与对照组组间P值为0.04,有显著性差异,认为靶向EBV-LMP1脱氧核酶能够增强LMP1阳性的鼻咽癌病人的放疗敏感性。两组的CR、PR相比较,P值=0.092,因例数过少暂时未发现明显差别,无显著性差异。两组间造血系统、皮肤、粘膜、唾液腺、肝肾功能的损伤无显著性差异。
结论:
靶向EBV-LMP1脱氧核酶增强了LMP1阳性的鼻咽癌患者对放疗的敏感性,提高了肿瘤消退速率。在放疗过程中不会增加鼻咽癌放疗患者的急性放射损伤,具有良好的安全性。
Objective:
Nasopharyngeal carcinoma(NPC)is one of the common maligant tumors in China.Radiotherapy is the main method for its clinical therapy. It is reported that the five-year survival rate of intermediate-advanced stage is less than 50%.Resistance to the therapy,recurrence and metastasis are the main reasons duing to the fail of treatment.Now,to search a new method enhancing radiosensitivity become a hot spot.This study is to use the targeting EBV-LMP1 deoxyribozymes in clinical NPC patients who be diagnosed positive expression of LMP1,observe the effects and side effects of DNAzymes,and investigate targeting EBV-LMP1 DNAzymes may as potential radiosensitizers for NPC treatment.
Methods:
Divide 20 patients who match the selected conditions into 2 groups in random and double-blind,one is to be tested(Group A,radiotherapy plus the DNAzymes),one is contrast(Group B,radiotherapy alone).The methods of radiotherapy between groups is same:regular radiotherapy using the irregular lead block.The total doses of nasopharynx is DT70-76Gy,accomplished in 7-7.5weeks.The total doses of positive lymph node in cervical is Dr 66-70 Gy,accomplished in 6-7 weeks.2 hours before radiotherapy,Group A be injected the DNAzymes 0.1ml(120mg/ml)in the tumor local,,every Monday and Thursday,and total 10 times.Group B be injected Sodium Chloride 0.1ml the same time. Other treatments are same between 2 groups.Observe the tumor through the endoscope every week,measure the volume through 4 times MRI images rigorously at the point of before the radiotherapy,Dr 50 Gy,D_T70 Gy and return visit after 3 months,test the CR,PR using the solid tumor WHO objective curative effect standards and observe the side effects during the period.
Results:
The general data is consistency,which means well homogenicity and balanced between 2 groups.Accoding to the tumor volume(cm~3),we changed it into RTR,which means rate of tumor reduction,and carry out two-tailed t test for the values.The results of RTR~3 is P=0.04,which showed a significant difference between two treatments.The results of CR,PR is P=0.092,which can't showed a significant difference between two groups temporarily,as the reason of little cases.The results of the observation index,which from RTOG's acute radiotherapy injured,can't showed a significant difference between two groups.
Conclusions:
The result suggest that targeting EBV-LMP1 DNAzyme may represent as potential radiosensitizers for NPC treatment.During the period,this DNAzyme did any acute radiotherapy injured,which means well security.
引文
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