【摘要】 目的 观察ⅢC1～ⅣA期宫颈癌患者根治性同步放化疗同期联合免疫检查点抑制剂信迪利单抗治疗的效果，探讨其安全性。方法 2019年10月—2022年10月郑州大学附属肿瘤医院诊治的盆腔淋巴结短径≥1.5 cm或阳性淋巴结数≥4个或有腹主动脉旁淋巴结转移的ⅢC1～ⅣA期宫颈癌患者70例，其中35例行根治性同步放化疗者为同步放化疗组，35例根治性同步放化疗同期联合信迪利单抗治疗者为联合免疫治疗组。同步放化疗组放疗采用体外适形放疗并腔内照射，放疗第1周给予顺铂增敏化疗，连续5周。联合免疫治疗组在同步放化疗组治疗基础上给予信迪利单抗，治疗6个疗程。2组治疗结束后每4～6周行盆腔平扫和动态增强MRI,颈部、胸部和腹部增强CT检查评估疗效，随访1年，记录客观缓解率、无进展生存率及3级以上药物不良反应发生情况。采用单因素及多因素Cox回归分析宫颈癌患者治疗后疾病进展的影响因素。结果 (1)2组年龄、组织病理类型、肿瘤最大径、合并症、ECOG评分、阳性淋巴结数、淋巴结短径及程序性死亡受体配体1表达、鳞状细胞癌相关抗原表达、腹主动脉旁淋巴结转移情况比较差异均无统计学意义(P>0.05)。(2)随访至2023年5月，2组均无死亡病例，联合免疫治疗组完全缓解16例，部分缓解10例，疾病稳定5例，疾病进展4例；同步放化疗组完全缓解11例，部分缓解7例，疾病稳定5例，疾病进展12例。联合免疫治疗组1年无进展生存率(88.6%)及客观缓解率(74.3%)均高于同步放化疗组(65.7%、51.4%)(χ~2=6.293,P=0.012;χ~2=3.916,P=0.048)。(3)肿瘤最大径≥4 cm(HR=3.442,95%CI:1.310～9.039,P=0.0121)、未应用信迪利单抗(HR=2.511,95%CI:1.006～6.266,P=0.049)是宫颈癌患者治疗后疾病进展的危险因素。(4)联合免疫治疗组3级以上白细胞减少(45.7%)、血小板减少(17.1%)、乏力(2.9%)、恶心呕吐(2.9%)、腹泻(2.9%)发生率与同步放化疗组(51.4%、8.6%、2.9%、5.7%、0)比较差异均无统计学意义(P>0.05)。结论 盆腔淋巴结短径≥1.5 cm或阳性淋巴结数≥4个或有腹主动脉旁淋巴结转移的ⅢC1～ⅣA期宫颈癌患者根治性同步放化疗同期联合信迪利单抗可延长无进展生存期，不增加药物不良反应。更多还原

【Abstract】 Objective To observe the efficacy and safety of radical concurrent chemoradiotherapy combined with sintilimab in patients with stageⅢC1-ⅣA cervical cancer.Methods In 70stageⅢC1-ⅣA cervical cancer patients with pelvic lymph node short-axis diameter≥1.5cm,positive lymph nodes≥4,or para-aortic lymph node metastasis,35patients received radical concurrent chemoradiotherapy combined with sintilimab(combined immunotherapy group),and35patients received radical concurrent chemoradiotherapy alone(concurrent chemoradiotherapy group)in the Affiliated Cancer Hospital of Zhengzhou University from October 2019to October 2022.In concurrent chemoradiotherapy group,external beam radiotherapy and intracavitary irradiation were administered,with concurrent cisplatin sensitization chemotherapy for 5 weeks starting from the first week of radiotherapy.In combined immunotherapy group,after concurrent chemoradiotherapy,sintilimab was administered for 6cycles.The patients were followed up for 1year after treatment,and pelvic plain scan,dynamic contrast-enhanced MRI and contrast-enhanced CT scans of the neck,chest and abdomen were done for evaluation every 4to 6weeks.The objective response rate,progression-free survival rate,and adverse drug reactions of grade 3or above were recorded.Univariate and multivariate Cox regression analyses were conducted to identify the influencing factors of the disease progression of patients with cervical cancer.Results(1)There were no significant differences in the age,histopathological classification,maximal tumor diameter,comorbidities,ECOG performance status,number of positive lymph nodes,lymph node short-axis diameter,programmed cell death ligand 1expression,squamous cell carcinoma antigen expression,and para-aortic lymph node metastasis between two groups(P>0.05).(2)Till May 2023,there were no deaths during the follow-up period in two group.The therapeutic results were complete response in 16patients,partial response in 10,stable disease in 5,and disease progression in 4in combined immunotherapy group;complete response in 11patients,partial response in 7,stable disease in 5,and disease progression in 12in concurrent chemoradiotherapy group.The one-year progression-free survival rate and objective response rate were higher in combined immunotherapy group (88.6%,74.3%)than those in concurrent chemoradiotherapy group(65.7%,51.4%）（χ~2=6.293,P=0.012；χ~2=3.916,P=0.048).(3)The maximal tumor diameter（≥4cm)(HR=3.442,95%CI:1.310-9.039,P=0.0121)and no administration of sintilimab(HR=2.511,95%CI:1.006-6.266,P=0.049)were the risk factors of disease progression in patients with cervical cancer after concurrent chemoradiotherapy.(4)There were no significant differences in the incidence rates of grade 3or above leukopenia,thrombocytopenia,fatigue,nausea/vomiting and diarrhea between combined immunotherapy group(45.7%,17.1%,2.9%,2.9%,2.9%)and concurrent chemoradiotherapy group (51.4%,8.6%,2.9%,5.7%,0)(P>0.05).Conclusion Concurrent chemoradiotherapy combined with sintilimab can prolong the progression-free survival without increasing the incidence of adverse drug reactions in patients with stageⅢC1-Ⅳa cervical cancer when pelvic lymph node short-axis diameter is≥1.5cm,number of positive lymph nodes is≥4,or para-aortic lymph node is metastatic.更多还原