替雷利珠单抗联合放化疗治疗局部晚期食管鳞癌的疗效和不良反应分析

Efficacy and Adverse Effects of Tislelizumab plus Chemoradiotherapy in Locally Advanced Esophageal Squamous Cell Carcinoma

目的:分析替雷利珠单抗联合放化疗在一线治疗局部晚期食管鳞癌中的疗效和不良反应。方法:回顾性分析我院2019年2月至2021年12月期间入院诊治的不可手术切除或者不愿手术切除的局部晚期食管鳞癌患者的临床资料,根据放化疗过程中是否联合替雷利珠单抗,分为联合治疗组和单纯放化疗组。联合治疗组接受替雷利珠单抗联合白蛋白结合型紫杉醇及铂类化疗4~6周期,之后口服替吉奥并同步放疗;单纯放化疗组仅接受白蛋白结合型紫杉醇联合铂类化疗4~6周期,然后口服替吉奥并同步放疗,初步评估替雷利珠单抗联合放化疗的疗效和安全性。结果:共入组31例患者,联合治疗组18例,单纯放化疗组13例,其中男性21例、女性10例;年龄55~79岁,中位年龄67岁;T_(3)N_(+)9例、T_(4)N_(0~3)22例;肿瘤部位位于颈段5例、胸上段8例、胸中段8例、胸下段7例、胃食管交界处3例。截止到2023年10月,患者最短随访时间为20.3个月。联合治疗组完全缓解(complete response,CR)4例、部分缓解(partial response,PR)11例、稳定(stable disease,SD)3例;单纯放化疗组CR 1例、PR 4例、SD 7例、进展1例,联合治疗组的客观缓解率83.33%(15/18)明显高于单纯放化疗组38.46%(5/13),差异有统计学意义(P=0.020)。联合治疗组中位无进展生存期为36.5个月(95%CI:25.75~47.25),远高于单纯放化疗组24.0个月(95%CI:21.05~26.95),差异有统计学意义(P=0.021);联合治疗组1年无进展生存率为100%,单纯放化疗组为92.3%,差异无统计学意义(OR=1.08,95%CI:0.93~1.27,P=0.419);联合治疗组2年无进展生存率为77.0%,单纯放化疗组为39.2%,差异有统计学意义(OR=5.85,95%CI:1.22~27.99,P=0.033)。治疗前联合治疗组和单纯放化疗组之间外周血中CD3^(+)T细胞、CD4^(+)T细胞、CD8^(+)T细胞和CD4^(+)/CD8^(+)T比值的差异均无统计学意义(均P>0.05);治疗后联合治疗组的CD4^(+)T细胞和CD4^(+)/CD8^(+)T比值高于单纯放化疗组,差异有统计学意义(P=0.036,P=0.002),联合治疗组CD8^(+)T低于单纯放化疗组,差异有统计学意义(P=0.048)。联合治疗组与单纯放化疗组在放射性食管炎、骨髓抑制、食欲减退、放射性肺炎方面差异均无统计学意义;联合治疗组甲状腺功能减退发生率为55.56%,单纯放化疗组发生率15.38%,均为1~2级,差异有统计学意义(P=0.032)。结论:替雷利珠单抗联合白蛋白结合型紫杉醇及铂类一线用于局部晚期食管鳞癌放化疗表现出有潜力的生存优势,不良反应较为可控,可能为食管鳞癌患者带来生存获益。

Objective:To analyze the efficacy and adverse effects of tislelizumab plus chemoradiotherapy in the first⁃line treatment of locally advanced esophageal squamous cell carcinoma(ESCC).Methods:We retrospectively analyzed the clin⁃ical data of patients admitted to our hospital from February 2019 to December 2021 with locally advanced ESCC who were surgically unresectable or unwilling to undergo surgical resection.The patients whether or not were administrated with tisleli⁃zumab during chemoradiotherapy were assigned to combination group and chemoradiotherapy group.The combination group(18 patients)received 4 to 6 cycles of albumin⁃conjugated paclitaxel and platinum⁃based chemotherapy before being admin⁃istrated with tislelizumab followed by concomitant chemoradiotherapy.The chemoradiotherapy group(13 patients)received 4 to 6 cycles of albumin⁃conjugated paclitaxel and platinum⁃based chemotherapy before being administrated tegafur followed by radiotherapy.Efficacy and safety of tislelizumab combined with chemoradiotherapy was initially evaluated.Results:Thirty⁃one patients were enrolled,18 in the combination group and 13 in the chemoradiotherapy group,including 21 men and 10 women aged from 55 to 79 years,with median age of 67 years.Of the 31 patients,9 cases were in T_(3)N_(+)stage and 22 cases in T_(4)N_(0~3) stage;5 cases were in the cervical segment,8 cases in the upper thoracic segment,8 cases in the middle thoracic segment,7 cases in the lower thoracic segment,and 3 cases in the gastroesophageal junction.As of October 2023,the mini⁃mum follow⁃up for patients was 20.3 months.There were 4 cases of complete response(CR),11 cases of partial response(PR),and 3 cases of stable disease(SD)in the combination group,and 1 case of CR,4 cases of PR,7 cases of SD,and 1 case of progressive disease(PD)in the chemoradiotherapy group.Objective response rate was 83.33%(15/18)in com⁃bination group,and 38.46%(5/13)in the chemoradiotherapy group,and the difference was statistically significant(P=0.20);the mPFS was 36.5 months(95%CI:25.75~47.25)in the former,and 24.0 months(95%CI:21.05~26.95)in the latter,and the difference was statistically significant(P=0.021);the rates of 1⁃year progression⁃free survival were 100%in the former and 92.3%in the latter,and the difference was statistically significant(OR=1.08,95%CI:0.93~1.27,P=0.419);the rates of 2⁃year progression⁃free survival were 77.0%in the former and 39.2%in the latter,and the difference was statistically significant(OR=5.85,95%CI:1.22~27.99,P=0.033).There were no statistically signifi⁃cant differences in CD3^(+)T cells,CD4^(+)T cells,CD8^(+)T cells,and the CD4^(+)/CD8^(+)T ratio between the two groups before treatment(both P>0.05).After treatment,the rate of CD4^(+)T and the CD4^(+)/CD8^(+)T ratio in the combination group were significantly higher than those in the chemoradiotherapy group(P=0.036,P=0.002);and the rate of CD8^(+)T was signifi⁃cantly lower in the former than that in the latter(P=0.048).There were no significant differences between the two groups in terms of radioactive esophagitis,bone marrow suppression,loss of appetite,and radioactive pneumonia.The incidence of hypothyroidism,ranging from grade 1 to 2,was 55.56%in the combination group and 15.38%in the chemoradiotherapy group,and the difference was statistically significant(P=0.032).Conclusion:The first⁃line chemoradiotherapy of tisleli⁃zumab combined with albumin⁃conjugated paclitaxel and platinum for locally advanced ESCC is relatively effective,and the adverse effects are controllable,which is profitable for the survival of ESCC patients.