食管癌根治性放化疗后局部失败两种挽救方案的分析

Analysis of two salvage treatments for local failure of esophageal cancer after initial radical chemoradiotherapy

目的探讨再程调强放疗(IMRT)、程序性死亡受体1(PD-1)联合单药化疗用于根治性放化疗后局部失败的食管癌患者的有效性及安全性,并对相关因素进行分析。方法回顾性分析2014年6月—2023年6月,兴化市人民医院收治的80例根治性放化疗后局部失败的食管癌患者,其中40例进行再程IMRT(再程IMRT组),放疗剂量为45.0~60.0 Gy,1.8~2.0 Gy/次,5次/周。另40例进行PD-1免疫治疗联合单药化疗(免疫化疗联合组)。采用Kaplan-Meier法进行单因素分析并计算累积生存率,log-rank法行生存显著性检验,Cox比例风险回归模型进行总生存(OS)期、无进展生存(PFS)期和局部控制(LC)生存时间的影响因素多因素分析。结果随访截至2023年12月,随访率为100%。再程IMRT组l、2年OS率分别为66.1%、18.9%,中位OS期为10.1个月。免疫化疗联合组l、2年OS率分别为72.3%、36.9%,中位OS期为12.4个月。两组OS率差异有统计学意义(χ^(2)=3.89,P=0.049)。再程IMRT组l、2年PFS率分别为47.4%、31.6%,中位PFS期为8.5个月。免疫化疗联合组l、2年PFS率分别为70.0%、64.2%,中位PFS期为11.9个月。两组PFS率差异无统计学意义(χ^(2)=2.66,P=0.103)。再程IMRT组l、2年LC率分别为68.6%、62.3%,中位LC生存时间为8.9个月。免疫化疗联合组l、2年LC率分别为72.8%、66.7%,中位LC生存时间为12.0个月。两组LC率差异无统计学意义(χ^(2)=0.18,P=0.672)。再程IMRT组,2级放射性食管炎发生率为82.5%(33/40),2级放射性肺炎发生率为32.5%(13/40)。免疫化疗联合组,Ⅰ~Ⅱ度外周血白细胞减少40.0%(16/40),Ⅰ~Ⅱ度外周血血小板减少发生率为50.0%(20/40),中重度贫血发生率为27.5%(11/40),1~2级甲状腺功能异常发生率为20.0%(8/40)。单、多因素分析显示:失败部位(χ^(2)=9.01,P=0.011)、近期疗效(χ^(2)=7.78,P=0.005)分别是影响OS期的独立预后因素;近期疗效(χ^(2)=31.63,P<0.001)是影响PFS期的独立预后因素;近期疗效(χ^(2)=17.64,P=0.001)也是影响LC生存时间的独立预后因素。结论食管癌根治性放化疗后局部失败,采用PD-1免疫治疗联合单药化疗较单纯再程放疗具有更好的生存预后,但需关注相关药物不良反应。

Objective To evaluate the efficacy and safety of intensity modulated radiotherapy(IMRT)and programmed death-1(PD-1)immunotherapy combined with single-agent chemotherapy for patients with local failure of esophageal cancer after initial radical chemoradiotherapy.Methods Clinical data of 80 patients with local failure of esophageal cancer after initial radical chemoradiotherapy treated with IMRT or PD-1 immunotherapy combined with single-agent chemotherapy in People's Hospital of Xinghua between June 2014 and June 2023 were retrospectively analyzed.IMRT was delivered at 1.8-2.0 Gy per fraction,5 fractions per week,with a total dose of 45.0-60.0 Gy in 40 patients(IMRT group).The other 40 patients received PD-1 immunotherapy combined with single-agent chemotherapy(PD-1 immunotherapy combined with single-agent chemotherapy group).Kaplan-Meier method was used for univariate analysis and the cumulative survival probability.Log-rank test was used for survival significance test.Cox proportional hazards model was used for multivariate analysis of related factors affecting overall survival(OS),progression-free survival(PFS)and local control(LC).Results By December 2023,the follow-up rate was 100%.The 1-and 2-year OS rates in the IMRT group were 66.1%and 18.9%,with a median OS time of 10.1 months.In the PD-1 immunotherapy combined with single-agent chemotherapy group,the 1-and 2-year OS rates were 72.3% and 36.9%,with a median OS time of 12.4 months.There was a significant difference in OS rates between two groups(χ^(2)=3.89,P=0.049).The 1-and 2-year PFS rates in the IMRT group were 47.4%and 31.6%,with a median PFS time of 8.5 months.In the PD-1 immunotherapy combined with single-agent chemotherapy group,the 1-and 2-year PFS rates were 70.0% and 64.2%,with a median PFS time of 11.9 months.There was no significant difference in the PFS rates between two groups(χ^(2)=2.66,P=0.103).The 1-and 2-year LC rates in the IMRT group were 68.6% and 62.3%,with a median LC time of 8.9 months.In the PD-1 immunotherapy combined with single-agent chemotherapy group,the 1-and 2-year LC rates were 72.8%and 66.7%,with a median LC time of 12.0 months.There was no significant difference in LC rates between two groups(χ^(2)=0.18,P=0.672).Grade 2 radiation esophagitis and radiation pneumonitis developed in 82.5%(33/40)and 32.5%(13/40)in the IMRT group,respectively.The incidence of grade 1-2 peripheral blood leukopenia was 40.0%(16/40),50.0%(20/40)for grade 1-2 peripheral blood thrombocytopenia,27.5%(11/40)for moderate to severe anemia,and 20.0%(8/40)for grade 1-2 thyroid dysfunction in the PD-1 immunotherapy combined with single-agent chemotherapy,respectively.Single-and multi-factor analysis showed that the failure site(χ^(2)=9.01,P=0.011)and short-term efficacy(χ^(2)=7.78,P=0.005)were the independent prognostic factors affecting OS.The short-term efficacy was the independent prognostic factor for PFS(χ^(2)=31.63,P<0.001).The short-term efficacy was the independent prognostic factors affecting LCS(χ^(2)=17.64,P=0.001)too.Conclusion For the patients with local failure of esophageal cancer after initial radical chemoradiotherapy,the combination of PD-1 immunotherapy with single-agent chemotherapy yields better survival prognosis than re-irradiation alone,but it is still necessary to pay attention to the related drug toxicities.