放化疗联合免疫治疗复发转移性食管鳞癌患者的初步分析

Preliminary analysis of chemoradiotherapy combined with immunotherapy in patients with recurrent or metastatic esophageal squamous cell carcinoma

目的评估一线根治性治疗后局部区域复发或和远处转移食管鳞癌(LR/M ESCC)患者在接受放/化疗联合免疫检查点抑制剂(ICIs)后的疗效。方法对符合入组条件的116例LR/M ESCC患者进行回顾性分析,主要分析影响患者预后的因素,并对患者二线治疗前中性粒细胞淋巴细胞比值(NLR)和血小板淋巴细胞比值(PLR)等炎性指标、放射治疗介入时机及范围和治疗疗效等指标对患者预后的影响进行了分层分析,同时分析≥2级治疗相关不良反应及患者二线治疗后的失败模式等情况。结果全组患者二线治疗后的中位总生存(OS)和无进展生存(PFS)时间分别为19.4个月和12.0个月、总客观缓解率和疾病控制率分别为38.8%和86.2%。NLR和PLR数值较小组患者的OS率(χ^(2)=14.93、11.60,P<0.05)和PFS率(χ^(2)=17.55、8.95,P<0.05)均优于较大组患者。放疗可以显著提高患者的OS率(χ^(2)=5.93,P<0.05),但对PFS率影响不显著(P>0.05);接受全部病灶放疗患者的OS和PFS率优于接受部分病灶照射组患者(χ^(2)=8.88、4.93,P<0.05);放疗介入的时间对患者的OS和PFS均无明显影响(P>0.05)。疗效完全缓解(CR)+部分缓解(PR)组患者的预后优于疾病稳定(SD)+疾病进展(PD)组患者(χ^(2)=8.97、10.67,P<0.05)。COX多因素分析结果显示复发类型、PLR、免疫周期数、局部放疗介入和近期疗效为影响患者OS的独立性危险因素(HR=2.67、4.63、0.39、2.10、3.35,P<0.05);NLR、PLR、免疫周期数和近期疗效为影响患者PFS的独立性危险因素(HR=1.79、1.89、0.54、2.50,P<0.05)。二线治疗后再次出现进展的患者为38例(32.8%);总体治疗不良反应患者可以耐受,其≥2级治疗相关不良反应者为36例(31.0%)。结论免疫检查点抑制剂联合放(化)疗二线治疗可以改善局部区域复发或和远处转移食管鳞癌患者的预后,其中放射治疗的介入时机和范围值得临床进一步探索。

Objective To evaluate the efficacy of radiotherapy/chemotherapy combined with immune checkpoint inhibitors(ICIs)in patients with locally recurrent or metastatic esophageal squamous cell carcinoma(LR/M ESCC)after first-line radical treatment.Methods A retrospective analysis was conducted on 116 enrolled patients with LR/M ESCC.Factors influencing patient prognosis were analyzed,and a stratified analysis was performed focusing on inflammatory markers such as neutrophil-to-lymphocyte ratio(NLR)and platelet-to-lymphocyte ratio(PLR)before second-line treatment,the intervention timing and extent of radiotherapy,and treatment efficacy.Additionally,treatment-related adverse effects with grade≥2 and failure patterns of the patients after second-line treatment were examined.Results After second-line treatment,the median OS and PFS were 19.4 and 12.0 months,respectively,and the overall objective response rate and disease control rate were 38.8%and 86.2%,respectively.Patients with lower NLR and PLR values exhibited significantly higher OS(χ^(2)=14.93,11.60,P<0.05)and PFS rates(χ^(2)=17.55,8.95,P<0.05)compared to those with higher NLR and PLR values.Radiotherapy significantly improved the OS rates(χ^(2)=5.93,P<0.05)of the patients,but produced insignificant effects on their PFS rates(P>0.05).Patients receiving whole-field radiotherapy exhibited superior OS and PFS rates compared to those treated with partial-field radiotherapy(χ^(2)=8.88,4.93,P<0.05).The intervention time of radiotherapy had no significant effects on the OS and PFS of the patients(P>0.05).The prognosis of the CR+PR group was significantly better than that of the SD+PD group(χ^(2)=8.97,10.67,P>0.05).The Cox multivariate analysis result identified the recurrence type,PLR,the number of immunotherapy cycles,local radiotherapy intervention,and recent efficacy as independent risk factors in the patients'OS(HR=2.67,4.63,0.39,2.10,3.35,P<0.05)and determined that NLR,PLR,the number of immunotherapy cycles,and recent efficacy were independent risk factors affecting the patients'PFS(HR=1.79,1.88,0.54,2.50,P<0.05).Among the patients,38(32.8%)experienced disease progression after second-line treatment,and 36(31.0%)suffered from treatment-related adverse effects of grades≥2,which were generally tolerable.Conclusions Second-line treatment with ICIs combined with radiotherapy/chemotherapy can improve the prognosis of patients with LR/M ESCC.Further clinical exploration is warranted regarding the intervention timing and extent of radiotherapy.