摘要
目的 探讨体重指数(BMI)对接受免疫治疗的晚期肝细胞癌(HCC)患者预后的影响。方法 回顾性分析2016年11月至2020年1月在哈尔滨医科大学附属肿瘤医院消化内科接受靶向治疗(T队列)、免疫治疗(I队列)或靶向联合免疫治疗(T+I队列)的119例晚期HCC患者的临床资料。收集治疗前BMI,将患者分为两组:非超重组(BMI<23 kg/m^(2))和超重组(BMI≥23 kg/m^(2))。采用Kaplan-Meier生存曲线计算不同队列下各组患者的中位总生存期(OS)和中位无进展生存期(PFS),采用Logistic回归模型分析疾病控制率(DCR)。采用Cox比例风险回归模型分析预后的影响因素。I队列中纳入炎性指标中性粒细胞与淋巴细胞比值(NLR),通过受试者工作特征(ROC)曲线确定NLR的最佳截断值及其评估OS的灵敏度和特异度,比较NLR、BMI联合NLR与预后的关系。结果 共纳入119例患者,按照治疗方式分为3个队列,其中I队列41例,T队列41例,T+I队列37例。Kaplan-Meier分析结果显示,在整体人群中,超重组患者的中位OS和中位PFS依次在T队列、I队列、T+I队列中延长,组间差异有统计学意义(P=0.002,P=0.029);非超重组患者中位OS和中位PFS在I队列、T+I队列中均有延长趋势,但差异均无统计学意义(P>0.05)。对整体人群行Cox多因素分析显示,BMI、既往肝切除术、既往肝局部治疗为影响OS的独立因素(P<0.05),性别为影响PFS的独立因素(P<0.05)。进一步对BMI在各队列中进行分析,I队列:超重组和非超重组的患者OS之间的差异有统计学意义(HR=0.449,95%CI:0.207~0.970,P=0.041);T+I队列:超重组和非超重组的患者OS之间的差异有统计学意义(HR=0.393,95%CI:0.155~0.998,P=0.049);T队列:超重组和非超重组患者OS之间的差异无统计学意义(HR=1.020,95%CI:0.508~2.049,P=0.953)。在3个队列中,超重组和非超重组的患者PFS之间的差异均无统计学意义(P>0.05);I队列和T+I队列中超重组患者的PFS分别延长了2.0个月和5.1个月,疾病进展风险分别降低26.8%和41.0%。I队列中,ROC曲线显示NLR的最佳截断值为2.62,NLR<2.62组的患者中位OS较NLR≥2.62组显著延长(37.5个月vs.14.3个月,P=0.016);进一步分析发现OS在BMI≥23 kg/m^(2)且NLR<2.62组的患者中延长趋势最明显,在BMI<23 kg/m^(2)且NLR≥2.62组中最短(P=0.024)。Logistic回归分析显示BMI对各队列患者的DCR无显著影响(P>0.05)。结论 BMI对接受系统治疗的晚期HCC预后产生影响,结果可能因治疗方式不同而产生差异。超重组(BMI≥23 kg/m^(2))中接受含免疫治疗的患者OS改善、死亡风险降低,而患者的PFS、DCR与BMI未见相关性。BMI联合NLR检测更能够揭示与接受免疫治疗的晚期HCC患者预后的关系,即高BMI伴随低NLR预示更长的OS,而低BMI伴随高NLR预示OS更差。
Objective To evaluate the effect of body mass index(BMI)on the prognosis of patients with advanced hepatocellular carcinoma(HCC)who received immunotherapy.Methods Clinical data of 119 advanced HCC patients treated with immunotherapy(I cohort),targeted therapy(T cohort)or targeted combination immunotherapy(T+I cohort)in the Department of Gastroenterology,Affiliated Cancer Hospital of Harbin Medical University from November 2016 to January 2020 were retrospectively analyzed.BMI before treatment was calculated and patients were divided into two groups:non-overweight group(BMI<23 kg/m2)and overweight group(BMI≥23 kg/m2).The median overall survival(OS)and median progression-free survival(PFS)of patients were calculated using the Kaplan-Meier survival curve,and the disease control rate(DCR)was calculated using Logistic regression.Cox regression model was used for univariate and multivariate analysis.The inflammatory index of neutrophil to lymphocyte ratio(NLR)was included in the I cohort.The optimal cut-off value of NLR and sensitivity and specificity of OS were determined through the receiver operating characteristic(ROC)curve,and the relationship between NLR,BMI combined with NLR and prognosis was compared.Results A total of 119 patients were included and divided into three cohorts according to treatment methods,including 41 cases of I cohort,41 cases of T cohort and 37 cases of T+I cohort.Kaplan-Meier analysis showed that,in the whole population,median OS and median PFS of patients with overweight group were extended successively in T cohort,I cohot and T+I cohot,and the differences between groups were statistically significant(P=0.002,P=0.017).In the non-overweight group,median OS and median PFS were prolonged in the I cohort and T+I cohort,but the difference was not statistically significant(P>0.05).Univariate and multivariate analysis showed that BMI,hepatectomy,locoregional treatment were independent factors affecting OS in the whole population(P<0.05),and gender was an independent factor affecting PFS in the whole population(P<0.05).Further analysis of BMI in each cohort showed that there was significant difference in OS between patients with overweight group and non-overweight group in I cohort(HR=0.449,95%CI:0.207-0.970,P=0.041).T+I cohort:patients with overweight group and non-overweight group had statistical difference in OS(HR=0.393,95%CI:0.155-0.998,P=0.049).T cohort:there was no statistical difference in OS between patients with overweight group and non-overweight group(HR=1.020,95%CI:0.508-2.049,P=0.953).In the three cohorts,there was no significant difference in PFS between patients with overweight group and non-overweight group(P>0.05).PFS of patients with overweight group in I cohort and T+I cohort were prolonged by 2.0 months and 5.1 months respectively,and the risk of disease progression was reduced by 26.8%and 41.0%,respectively.In the I cohort,the best cut-off value of NLR calculated according to the ROC curve was 2.62,and the median OS of patients with NLR<2.62 was significantly longer than that of patients with NLR≥2.62(37.5 months vs.14.3 months,P=0.016).Further analysis showed that the extension trend of median OS was most obvious in the patients with BMI≥23 kg/m2 and NLR<2.62,and the median OS was the shortest in the patients with BMI<23 kg/m2 and NLR≥2.62(P=0.024).Logistic regression showed that BMI had no significant effect on DCR of patients in all cohorts(P>0.05).Conclusion The effect of BMI on the prognosis of patients with advanced HCC receiving systematic treatment may be different due to different treatment methods.Overweight group(BMI≥23 kg/m2)can improve the long-term prognosis of patients receiving immunotherapy,and reduce the risk of death,and it has no correlation with the short-term efficacy of patients,including PFS and DCR.BMI combined with NLR can better reveal the relationship with the prognosis of patients with advanced HCC receiving immunotherapy,that is,the high BMI with low NLR group has longer OS,while the low BMI with high NLR group has worse OS.
作者
刘菲
隋红
王凯冰
LIU Fei;SUI Hong;WANG Kaibing(Department of Gastroenterology, the Affiliated Cancer Hospital of Harbin Medical University, Harbin 150081,China)
出处
《临床肿瘤学杂志》
CAS
2022年第5期393-404,共12页
Chinese Clinical Oncology
基金
哈尔滨医科大学附属肿瘤医院海燕科研基金项目(JJZD2019-08)
吴阶平基金会临床科研专项资助基金项目(320.6750.18555)。
关键词
晚期肝细胞癌
免疫治疗
体重指数
中性粒细胞/淋巴细胞比值
预后
Advanced hepatocellular carcinoma
Immunotherapy
Body mass index
Neutrophil to lymphocyte ratio
Prognosis
作者简介
通讯作者:隋红,E⁃mail:doctorsui2003@126.com。
