调强放疗联合替吉奥治疗中晚期食管癌的疗效及对患者细胞免疫功能的影响

Effect of Intensity-Modulated Radiation Therapy Combined with Tegafur/Gimeracil/Oteracil in Treatment of Advanced Esophageal Cancer and Its Effect on Cellular Immune Function of Patients

目的分析调强放疗联合替吉奥治疗中晚期食管癌的疗效及对患者细胞免疫功能的影响。方法选择2016年1月至2018年5月上海中医药大学附属龙华医院收治的102例中晚期食管癌患者作为研究对象,根据治疗方法不同分为对照组和观察组,各51例。其中,对照组予以调强放疗进行治疗,观察组在对照组的基础上予以替吉奥进行治疗。比较两组患者治疗前后细胞免疫功能指标[CD4^(+)T细胞、CD8^(+)T细胞、CD4^(+)T/CD8^(+)T比值及自然杀伤细胞(NK细胞)]变化,近期疗效、毒性反应(白细胞下降、血小板下降和胃肠道反应)及放射性损伤(放射性肺损伤和放射性食管炎)发生情况。随访至2021年5月,评估两组远期疗效[无进展生存期(PFS)、总生存期(OS)及3年生存率]。结果外周血CD4^(+)T细胞、CD8^(+)T细胞、CD4^(+)T/CD8^(+)T比值及NK细胞水平组间、时点间的主效应差异有统计学意义(P<0.01),组间与时点间存在交互作用(P<0.01)。治疗后,两组外周血CD4^(+)T细胞、CD4^(+)T/CD8^(+)T比值及NK细胞水平均高于治疗前,且观察组高于对照组(P<0.05);CD8^(+)T细胞水平低于治疗前,且观察组低于对照组(P<0.05)。治疗后,观察组的总有效率、疾病控制率均高于对照组[74.51%(38/51)比54.90%(28/51)、94.12%(48/51)比76.47%(39/51)](P<0.05)。两组白细胞下降、血小板下降和胃肠道反应等毒性反应及放射性肺损伤、放射性食管炎等放射性损伤发生情况比较差异均无统计学意义(P>0.05)。随访至2021年5月,观察组中位PFS及OS分别为18.62个月、23.45个月,3年生存率为52.38%,对照组中位PFS及OS分别为14.58个月、19.36个月,3年生存率为31.43%,两组的3年PFS生存曲线、3年OS生存曲线比较差异有统计学意义(P<0.05)。结论采用调强放疗联合替吉奥治疗中晚期食管癌患者近远期疗效显著,可明显改善患者免疫功能,且不增加不良反应,安全可行。

Objective To analyze the efficacy of intensity-modulated radiation therapy combined with tegafur/gimeracil/oteracil(TGO)in the treatment of advanced esophageal cancer and its effect on the cellular immune function of the patients.Methods A total of 102 patients with advanced esophageal canceradmitted to Longhua Hospital Shanghai University of Traditional Chinese Medicine from Jan.2016 to May 2018 were included.According to different treatment methods,they were divided into a control group and an observation group,with 51 cases in each group.The control group was treated with intensity-modulated radiation therapy,and the observation group was treated with TGO on the basis of the control group′s regimen.The changes of cellular immune function indexes[CD4^(+)T cells,CD8^(+)T cells,CD4^(+)T/CD8^(+)T ratio and natural killer cells(NK cells)],and the short-term efficacy,toxicity(leukopenia,thrombocytopenia and gastrointestinal reactions)and radiation injury(radiation lung injury and radiation esophagitis)were compared between the two groups.Follow-up was done until May 2021,and the long-term efficacy[progression-free survival(PFS),overall survival(OS)and 3-year survival rate]of the two groups were assessed.Results There were significant differences in the main effect of peripheral blood CD4^(+)T cells,CD8^(+)T cells,CD4^(+)T/CD8^(+)T ratio and NK cell levels between groups and time points(P<0.01),and there were interactions between groups and time points(P<0.01).After treatment,the peripheral blood CD4^(+)T cells,CD4^(+)T/CD8^(+)T ratio and NK cell levels in the two groups were all higher than those before treatment,and the observation group was higher than the control group(P<0.05).The level of CD8^(+)T cells was lower than before treatment,and the observation group was lower than the control group(P<0.05).After treatment,the total effective rate and disease control rate of the observation group were higher than those of the control group[74.51%(38/51)vs 54.90%(28/51),94.12%(48/51)vs 76.47%(39/51)](P<0.05).There were no significant differences in the incidence of toxic reactions such as leukopenia,thrombocytopenia,and gastrointestinal reactions,as well as radiation-induced lung injury and radiation-induced esophagitis between the two groups(P>0.05).Followed up to May 2021,the median PFS and OS of the observation group were 18.62 months and 23.45 months,respectively,and the 3-year survival rate was 52.38%.The median PFS and OS in the control group were 14.58 months and 19.36 months,respectively,and the 3-year survival rate was 31.43%.There were significant differences in the 3-year PFS survival curve and 3-year OS survival curve between the two groups(P<0.05).Conclusion Intensity-modulated radiotherapy combined with TGO has significant short and long term efficacy in the treatment of advanced esophageal cancer,which can significantly improve the patients′immune function without increasing adverse reactions,thus is safe and feasible.