免疫治疗相关性甲状腺功能异常与不可切除/晚期肝细胞癌患者预后改善相关

Association of immune-related thyroid dysfunction with improved prognosis in patients with unresectable/advanced hepatocellular carcinoma

目的:探讨免疫治疗相关性甲状腺功能异常与不可切除/晚期肝细胞癌(HCC)患者预后改善的相关性。方法:回顾性分析45例接受免疫检查点抑制剂(ICIs)治疗的不可切除/晚期HCC患者。根据ICIs治疗过程中是否出现免疫相关性甲状腺功能异常分为甲状腺功能正常组(28例)和异常组(17例),比较2组患者的预后和免疫应答情况,主要终点指标为中位总生存期(OS)、无进展生存期(PFS),次要终点指标为疾病控制率(DCR)。结果:所有患者的中位OS、PFS分别为10.8个月(95%CI:3.0~18.6)和5.0个月(95%CI:3.0~12.2)。正常组中位OS为5.8个月(95%CI:3.7~7.9),异常组中位OS尚未达到(P=0.026)。异常组中位PFS长于正常组(8.2个月vs.3.1个月,P=0.011),DCR高于正常组(52.9%vs.21.5%,P=0.030)。多因素Cox回归分析显示,甲状腺功能异常是达到6个月OS(HR=0.213,95%CI:0.048~0.944,P=0.042)和PFS(HR=0.383,95%CI:0.151~0.967,P=0.042)的独立影响因素;甲状腺功能异常(HR=0.403,95%CI:0.185~0.877,P=0.022)、基线无大血管侵犯(MVI)(HR=2.848,95%CI:1.406~5.768,P=0.004)、Child-Pugh A级(HR=2.404,95%:1.099~5.255,P=0.028)与12个月PFS相关。结论:免疫治疗相关性甲状腺功能异常的不可切除/晚期HCC患者预期生存和免疫应答效果更佳。治疗期间出现甲状腺功能异常、基线无MVI、Child-Pugh A级与患者预后改善相关。

Objective:To investigate the correlation between immune-related thyroid dysfunction and prognosis in patients with unresectable/advanced hepatocellular carcinoma(HCC).Methods:We retrospectively analyzed 45 patients with unresectable/advanced HCC who received immune checkpoint inhibitors(ICIs).The patients were divided into normal thyroid function group(n=28)and thyroid dysfunction group(n=17).The prognosis and immune response of the two groups were compared.The primary endpoint was median overall survival(OS)and progression-free survival(PFS),and the secondary endpoint was disease control rate(DCR).Results:The median OS and PFS of all patients were 10.8 months(95%CI:3.0-18.6)and 5.0 months(95%CI 3.0-12.2),respectively.The median OS of the normal group was 5.8 months(95%CI:3.7-7.9),and that of the dysfunction group was not yet reached(P=0.026).The median PFS of the dysfunction group was longer than that of the normal group(8.2 months vs.3.1 months,P=0.011),and the DCR of the dysfunction group was higher than that of the normal group(52.9%vs 21.5%,P=0.030).Multivariate Cox regression analysis showed that thyroid dysfunction was an independent prognostic factor for 6-month OS(HR=0.213,95%CI:0.048-0.944,P=0.042)and PFS(HR=0.383,95%CI:0.151-0.967,P=0.042).Thyroid dysfunction(HR=0.403,95%CI:0.185-0.877,P=0.022),no macrovascular invasion at baseline(HR=2.848,95%CI:1.406-5.768,P=0.004),Child-Pugh A grade(HR=2.404,95%CI:1.099-5.255,P=0.028)were independent prognostic factors for 12-month PFS.Conclusion:Unresectable/advanced HCC patients with thyroid dysfunction associated with immunotherapy have better expected survival and immune response,which can be used to predict the efficacy of immunotherapy in the early stage.Thyroid dysfunction,no macrovascular invasion and Child-Pugh A grade were associated with improved prognosis.