放射性肺损伤的预测和危险因素的临床研究
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摘要
目的第一部分研究放射治疗前后肺脏的2—F~(18)—脱氧-D-葡萄糖的摄取变化与急性放射性肺炎的相关性；第二部分研究合并糖尿病的肺癌病人在接受放射治疗后是否易罹患放射性肺炎；第三部分研究研究糖尿病对大鼠的急性放射性肺损伤的影响作用。
方法第一部分的材料和方法：41名肺癌患者在进行三维适形放射治疗前后都进FDG-PET／CT扫描。分别对肺部吸收剂量为0～10G y，10～20Gy，20～30Gy，30～40Gy，40～50Gy剂量区进行2-F~(18)-脱氧-D-葡萄糖标准摄取值的测定。将患者放射治疗前后的平均标准摄取值进行比较，并将随访观察中患放射性肺炎的病人和未患放射性肺炎的病人放射治疗前后的平均标准摄取值的变化幅度进行比较。统计学差异使用配对t检验。放射性肺炎的诊断和分级标准参照美国放射治疗肿瘤学会所制定的标准。第二部分的材料和方法：收集我院2006．1—2007．3年收治的非小细胞肺癌病例，住院期间均接受三维适形放射治疗，其中合并糖尿病的病例52例，另外设立对照组104例，随访观察一年，比较两组的放射性肺炎的发病情况。计算糖尿病肺癌患者发病的相对危险度。第三部分动物实验验证的材料和方法：用60只Wistar大鼠随机分为3组(A、B、C组)，试验组(A组)应用链脲佐菌素(50mg／kg)腹腔内注射，成功建立2型糖尿病大鼠模型，同时给予对照组(B组)和空白对照组(C组)的大鼠生理盐水腹腔注射。应用clinac600c型加速器6MV x线对A、B组的大鼠右侧肺部进行单分割15Gy照射，除右侧肺部其他部位均给予挡铅。照射后六周进行对3组大鼠进行CT扫描，并对大鼠的肺组织进行病理切片检查，比较3组大鼠的影像学改变。
结果第一部分的结果：所有患者中位随访期为12个月，41人中有12人(26．8％)罹患2级或2级以上的急性放射性肺炎。41例病人的平均2-F~(18)-脱氧-D-葡萄糖标准摄取值均较放疗前升高，这种升高在发生肺炎的病人中尤其明显(P＜0．001)。患放射性肺炎的病人的平均标准摄取值在肺脏接受10Gy或更高剂量的区域增加明显。第二部分的临床资料显示：糖尿病组和对照组的患者的放射性肺炎的发病率为(40．38％Vs 21．35％，P＜0．05)，罹患有糖尿病的肺癌患者的放射性肺炎的发病危险是没患有糖尿病的肺癌患者的2．05倍。，其总体相对危险度的95％的可信区间为(1．17，3．58)。第三部分实验室动物模型的验证结果显示患有糖尿病的大鼠的肺部放射线损伤的影像学检出率较对照组为高(62．5％vs30％，P＜0．05)。
结论肺脏的平均标准摄取值的变化可作为急性放射性肺炎的预测指标。FDG-PET／CT在预测放射性肺损伤可以有新的应用。糖尿病为放射性肺炎发病的危险因素。糖尿病可以加重放射性肺损伤。
Objective Part one:to investigate if [~(18)F]2-fluoro-2-deoxyglucose (FDG) uptakechanges in the lung after radiotherapy can be used as a new predictor for acuteradiation pneumonitis.Part two:the purpose of this study was to investigate if thediabetics are more vulnerable to radiation induced pulmonary damage.Part three:toinvestigate the effect of diabetes mellitus on radiation induced lung injury.
Methods Part one:Forty-one patients with lung cancer underwent FDG positronemission tomography/computed tomography (FDG-PET/CT) imaging before andafter radiotherapy.The mean standardized uptake value (SUV) were measured for theisodose regions of 0～10Gy,10～20Gy,20～30Gy,30～40Gy,40～50Gy.The mean SUVof these regions after radiotherapy were compared with baseline.The range of themean SUV in patients developed from radiation pneumonitis (RP) was also comparedto those who did not.The statistic difference was determined by matched pair t-test.Radiation Therapy Oncology Group (RTOG) Criteria was used for diagnosis andgrading of RP.Part two:52 diabetics with non small cell lung cancer were selectedand 104 non small cell lung cancer patients without diabetes mellitus were registeredin control group.All the patients have undergone three-dimension conformalradiation therapy between January 2006 and March 2007.A follow-up study wasperformed.Radiation pneumonitis was diagnosed according to the criteria ofRadiation Therapy Oncology Group.The statistical difference was determined bychi-square test.Part three:sixty Wistar mice were randomized into three groups(group A,B and C).Type 2 diabetes mellitus mice models were established byintraperitoneal injection (STZ 50mg/Kg) in treatment groups (Group A).Meanwhilethe control groups (group B and group C)were injected intraperitoneally with normalsodium.The group A and B received a single dose 15Gy to the right lung.The otherparts of the mouse were all shielded by 8cm lead blocks.Group C received 0Gy to theright lung.Six weeks later all mice underwent CT scan and the findings werecompared.Morphological changes of the lung tissue were observed under light.
Results result of part one:with a median follow-up of 12 months,eleven of 41patients (26.8%) have developed grade 2 and above acute radiation pneumonitis.Themean SUV of regions (10～20Gy,20～30Gy,30～40Gy,40～50Gy) increased afterradiation therapy in all 41 patients,these patients had significantly higher FDGactivity in regions reveived 10Gy or more(P＜0.001).Compared to their counterparts,the elevation was significantly greater in those patients who developed acute RP subsequently.Result of part two:Twenty-one of 52 (40.38%) patients with diabeteswere diagnosed as radiation pneumonitis (grade 2 or greater).In the control group theratio was 21.35 %(22/104).The morbidity of the radiation pneumonitis in patientswith diabetes mellitus is higher than those without diabetes mellitus (40.38% vs.21.35%,P＜0.05).The value of the relative risk is 2.05.The confidence interval is(1.17,3.58).Result of part three:The detection rate of the radiation induced lunginjury of the Group A was higher than the group B (62.5% vs 30%),P＜0.05).
Conclusion The mean SUV of the lung tissue may be a useful predictor for theacute RP.FDG-PET/CT may play a new role in study of the radiation damage oflung.
方法第一部分的材料和方法：41名肺癌患者在进行三维适形放射治疗前后都进FDG-PET／CT扫描。分别对肺部吸收剂量为0～10G y，10～20Gy，20～30Gy，30～40Gy，40～50Gy剂量区进行2-F~(18)-脱氧-D-葡萄糖标准摄取值的测定。将患者放射治疗前后的平均标准摄取值进行比较，并将随访观察中患放射性肺炎的病人和未患放射性肺炎的病人放射治疗前后的平均标准摄取值的变化幅度进行比较。统计学差异使用配对t检验。放射性肺炎的诊断和分级标准参照美国放射治疗肿瘤学会所制定的标准。第二部分的材料和方法：收集我院2006．1—2007．3年收治的非小细胞肺癌病例，住院期间均接受三维适形放射治疗，其中合并糖尿病的病例52例，另外设立对照组104例，随访观察一年，比较两组的放射性肺炎的发病情况。计算糖尿病肺癌患者发病的相对危险度。第三部分动物实验验证的材料和方法：用60只Wistar大鼠随机分为3组(A、B、C组)，试验组(A组)应用链脲佐菌素(50mg／kg)腹腔内注射，成功建立2型糖尿病大鼠模型，同时给予对照组(B组)和空白对照组(C组)的大鼠生理盐水腹腔注射。应用clinac600c型加速器6MV x线对A、B组的大鼠右侧肺部进行单分割15Gy照射，除右侧肺部其他部位均给予挡铅。照射后六周进行对3组大鼠进行CT扫描，并对大鼠的肺组织进行病理切片检查，比较3组大鼠的影像学改变。
结果第一部分的结果：所有患者中位随访期为12个月，41人中有12人(26．8％)罹患2级或2级以上的急性放射性肺炎。41例病人的平均2-F~(18)-脱氧-D-葡萄糖标准摄取值均较放疗前升高，这种升高在发生肺炎的病人中尤其明显(P＜0．001)。患放射性肺炎的病人的平均标准摄取值在肺脏接受10Gy或更高剂量的区域增加明显。第二部分的临床资料显示：糖尿病组和对照组的患者的放射性肺炎的发病率为(40．38％Vs 21．35％，P＜0．05)，罹患有糖尿病的肺癌患者的放射性肺炎的发病危险是没患有糖尿病的肺癌患者的2．05倍。，其总体相对危险度的95％的可信区间为(1．17，3．58)。第三部分实验室动物模型的验证结果显示患有糖尿病的大鼠的肺部放射线损伤的影像学检出率较对照组为高(62．5％vs30％，P＜0．05)。
结论肺脏的平均标准摄取值的变化可作为急性放射性肺炎的预测指标。FDG-PET／CT在预测放射性肺损伤可以有新的应用。糖尿病为放射性肺炎发病的危险因素。糖尿病可以加重放射性肺损伤。
Objective Part one:to investigate if [~(18)F]2-fluoro-2-deoxyglucose (FDG) uptakechanges in the lung after radiotherapy can be used as a new predictor for acuteradiation pneumonitis.Part two:the purpose of this study was to investigate if thediabetics are more vulnerable to radiation induced pulmonary damage.Part three:toinvestigate the effect of diabetes mellitus on radiation induced lung injury.
Methods Part one:Forty-one patients with lung cancer underwent FDG positronemission tomography/computed tomography (FDG-PET/CT) imaging before andafter radiotherapy.The mean standardized uptake value (SUV) were measured for theisodose regions of 0～10Gy,10～20Gy,20～30Gy,30～40Gy,40～50Gy.The mean SUVof these regions after radiotherapy were compared with baseline.The range of themean SUV in patients developed from radiation pneumonitis (RP) was also comparedto those who did not.The statistic difference was determined by matched pair t-test.Radiation Therapy Oncology Group (RTOG) Criteria was used for diagnosis andgrading of RP.Part two:52 diabetics with non small cell lung cancer were selectedand 104 non small cell lung cancer patients without diabetes mellitus were registeredin control group.All the patients have undergone three-dimension conformalradiation therapy between January 2006 and March 2007.A follow-up study wasperformed.Radiation pneumonitis was diagnosed according to the criteria ofRadiation Therapy Oncology Group.The statistical difference was determined bychi-square test.Part three:sixty Wistar mice were randomized into three groups(group A,B and C).Type 2 diabetes mellitus mice models were established byintraperitoneal injection (STZ 50mg/Kg) in treatment groups (Group A).Meanwhilethe control groups (group B and group C)were injected intraperitoneally with normalsodium.The group A and B received a single dose 15Gy to the right lung.The otherparts of the mouse were all shielded by 8cm lead blocks.Group C received 0Gy to theright lung.Six weeks later all mice underwent CT scan and the findings werecompared.Morphological changes of the lung tissue were observed under light.
Results result of part one:with a median follow-up of 12 months,eleven of 41patients (26.8%) have developed grade 2 and above acute radiation pneumonitis.Themean SUV of regions (10～20Gy,20～30Gy,30～40Gy,40～50Gy) increased afterradiation therapy in all 41 patients,these patients had significantly higher FDGactivity in regions reveived 10Gy or more(P＜0.001).Compared to their counterparts,the elevation was significantly greater in those patients who developed acute RP subsequently.Result of part two:Twenty-one of 52 (40.38%) patients with diabeteswere diagnosed as radiation pneumonitis (grade 2 or greater).In the control group theratio was 21.35 %(22/104).The morbidity of the radiation pneumonitis in patientswith diabetes mellitus is higher than those without diabetes mellitus (40.38% vs.21.35%,P＜0.05).The value of the relative risk is 2.05.The confidence interval is(1.17,3.58).Result of part three:The detection rate of the radiation induced lunginjury of the Group A was higher than the group B (62.5% vs 30%),P＜0.05).
Conclusion The mean SUV of the lung tissue may be a useful predictor for theacute RP.FDG-PET/CT may play a new role in study of the radiation damage oflung.
引文
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