肺部立体定向放疗对外周血淋巴细胞的影响

The effect of lung stereotactic body radiotherapy on peripheral blood lymphocytes

背景与目的:靶向程序性死亡[蛋白]-1(programmed death-1,PD-1)/程序性死亡[蛋白]配体-1(programmed death ligand-1,PD-L1)的免疫检查点抑制剂已被批准用于多种恶性肿瘤的治疗,其治疗效应的发挥取决于T淋巴细胞的活化。放射治疗诱导的免疫原性细胞死亡可促进免疫反应,但同时辐射诱发的淋巴结细胞减少可能会降低免疫检查点抑制剂的效应。目前不同放疗技术、放疗部位、放疗范围对淋巴细胞的影响都尚不明确。探讨肺部立体定向放疗(stereotactic body radiotherapy,SBRT)的不同分割方式及剂量等参数对患者外周血淋巴细胞的影响。方法:回顾性分析2016—2018年间在郑州大学附属肿瘤医院接受肺部立体定向放疗的64例患者的相关临床资料。SBRT采用90%等剂量线覆盖计划靶体积(planning target volume,PTV),PTV为40~65 Gy,分割次数4~13次,生物等效剂量(biological equivalent dose,BED)为60~116 Gy,每天1次,每周照射最多5次。通过收集患者放疗前1周、放疗后1周、放疗后1个月和放疗后3个月的血常规数据,分析SBRT的各项参数与患者外周血绝对淋巴细胞计数变化的相关性。结果:外周血淋巴细胞计数在放疗后1周和1个月均出现不同程度的降低,在放疗后3个月基本恢复到放疗前水平。SBRT的各项参数中分割次数对淋巴细胞计数的影响较为突出,在放疗后1周和1个月,分割次数≤5次组的外周血淋巴细胞计数降低程度均显著小于分割次数>5次组,分别为(1.68±0.63 vs 0.93±0.34,P=0.021)和(1.60±0.68 vs 0.95±0.41,P=0.004)。而不同分割剂量、总剂量、BED值在放疗前后各组对比淋巴细胞计数差异无统计学意义(P>0.05)。结论:SBRT治疗后1周和1个月,分割次数≤5次组的外周血淋巴细胞计数降低程度显著小于分割次数>5次组,在SBRT结束后3个月淋巴细计数基本恢复到放疗前水平。

Background and purpose:Immune checkpoint inhibitors targeting programmed death-1(PD-1)/programmed death ligand-1(PD-L1)have been approved for the treatment of a variety of malignant tumors,and their therapeutic effects depend on the activation of T lymphocytes.Radiotherapy-induced immunogenic cell death can promote immune response,but at the same time,radiation-induced lymph node cell reduction may reduce the effect of immune checkpoint inhibitors.At present,the effects of different radiotherapy techniques,radiotherapy sites and radiotherapy ranges on lymphocytes are still unclear.The purpose of this study was to investigate the effects of different segmentation methods and doses of lung stereotactic body radiotherapy(SBRT)on patients'peripheral blood lymphocytes.Methods:The clinical data of 64 patients receiving pulmonary SBRT at the Affiliated Cancer Hospital of Zhengzhou University from 2016 to 2018 were retrospectively analyzed.The total prescribed dosage ranging from 40 to 65 Gy was completed for no more than 5 times a week,with 4 to 13 fractions prescribed at the 90%isodose lines for planning target volume(PTV).The biological effective dose(biological equivalent dose,BED)was 60-116 Gy.The differences of absolute lymphocyte counts in peripheral blood of patients with different segmentation methods and doses in various parameters of SBRT were analyzed before radiotherapy,1 week,1 month and 3 months after radiotherapy.Results:The lymphocyte counts decreased at 1 week and 1 month after radiotherapy,and basically returned to the levels before radiotherapy at 3 months after radiotherapy.Among the various parameters of SBRT,the number of fractions had a prominent effect on lymphocyte counts.The the reduction of peripheral blood lymphocyte count was significantly less in the group of ≤5-fraction radiotherapy schedule than in the group of>5-fraction radiotherapy,respectively(1.68±0.63 vs 0.93±0.34,P=0.021;1.6±0.68 vs 0.95±0.41,P=0.004).However,there was no significant difference in lymphocyte counts between groups before and after radiotherapy for dose per fraction,total dose and BED values(P>0.05).Conclusion:The reduction of peripheral blood lymphocyte count was significantly less in the group with less than 5-fraction radiotherapy schedule than in the group with more than 5-fraction radiotherapy schedule 1 week and 1 month after SBRT.The lymphocyte count was basically restored to the level before radiotherapy at 3 months after the end of SBRT.