首次疗效评估中肿瘤最长径之和变化对晚期肝内胆管癌化疗患者生存预后的预测价值

Predictive value of changes in the sum of longest diameters for initial response evaluation and survival in patients with advanced intrahepatic cholangiocarcinoma received chemotherapy

关键词:  晚期肝内胆管癌  化疗  首次疗效  预后

Key words:  advanced intrahepatic cholangiocarcinoma  chemotherapy  first response evaluation  prognosis

摘要:

目的 探讨晚期肝内胆管癌患者接受一线化疗后首次疗效评估结果对生存预后价值。方法 回顾性纳入2018年10月—2022年12月在海军军医大学附属东方肝胆外科医院接受化疗方案治疗的107例晚期肝内胆管癌患者。基于实体瘤疗效评价标准1.1，对比化疗前后最长径之和(sum of the largest tumor diameters, SLD)变化将疗效分为3组，将肿瘤SLD缩小至少超过30%为SLD(1)组；SLD增加至少超过20%纳入SLD(3)组；介于两者之间的为SLD(2)组。Kaplan-Meier曲线分析3组患者的总生存期(overall survival, OS)。单因素和多因素Cox风险回归分析明确疗效与生存时间的预后价值。结果 Kaplan-Meier曲线分析结果表明SLD(1)组、SLD(2)组和SLD(3)组患者的中位OS分别为16.3、13.2、7.4个月(P<0.001)，以及6、12和24个月OS率依次递减。SLD(1)组中6、12、24个月的生存率分别为100%、72.2%和16.7%；SLD(2)组中6、12、24个月的生存率分别为90.7%、53.7%和7.4%；SLD(3)组中6、12、24个月的生存率分别为57.1%、20%和0%。为进一步分析SLD增大或缩小的程度对患者预后的影响，我们在SLD(2)组中将SLD增大的患者纳入SLD(2+)组，将SLD减小的患者纳入到SLD(2-)组。SLD(2+)和SLD(3)组的中位OS分别为11.3个月和7.4个月，P=0.012。然而，SLD(2-)和SLD(1)组的中位OS分别为13.9个月和16.4个月，P=0.053。单因素和多因素Cox风险回归分析表明SLD缩小＞30%(HR=0.564，95%CI: 0.3210.991，P=0.046)、SLD增加＞20%(HR=3.012，95%CI: 1.8734.842，P<0.001)是晚期肝内胆管癌总体生存时间的独立预后因素。结论 晚期肝内胆管癌一线化疗患者，首次疗效结果对患者生存预后有重要的意义: 肿瘤SLD增长越大，生存预后越差，但在肿瘤SLD缩小部分中，SLD(1)与SDL(2-)对患者的生存预后没有明显差异性。

Abstract:

Objective To investigate the predictive value of the initial response evaluation for prognosis of patients with advanced intrahepatic cholangiocarcinoma(iCCA) after first-line chemotherapy. Methods A retrospective analysis was conducted on a cohort of 107 patients diagnosed with advanced iCCA, who received chemotherapy at the Eastern Hepatobiliary Surgery Hospital Affiliated to Naval Medical University between October 2018 and December 2022. According to the RECIST1.1 criteria, the sum of the largest tumor diameters(SLD) before and after chemotherapy were compared to divide into three groups. The SLD(1) group included cases reduction in SLD by at least 30%. Cases with an increased in SLD by more than 20% were classified as the SLD(3) group. The intermediate category was referred to as the SLD(2) group. Kaplan-Meier curve was used to analyze the overall survival(OS) of the three groups. Prognostic value of efficacy and survival time were determined through univariate and multivariate Cox risk regression analyses. Results Kaplan-Meier curve analysis revealed that the median OS in SLD(1) group, SLD(2) group and SLD(3) group were 16.3 months, 13.2 months, and 7.4 months respectively(P<0.001). Furthermore, the OS rates progressively decreased at 6, 12, and 24 months. The 6-month, 12-month and 24-month survival rates in SLD(1) group were 100%, 72.2% and 16.7%, respectively. The 6-month, 12-month and 24-month survival rates of SLD(2) were 90.7%, 53.7% and 7.4%, respectively. The 6-month, 12-month and 24-month survival rates in the SLD(3) group were 57.1%, 20% and 0%, respectively. To further investigate the impact of changes in the degree of SLD enlargement or contraction on patient prognosis, we categorized patients with increased SLD into the SLD(2+) group and those with reduced SLD into the SLD(2-) group. The median overall survival(OS) for the SLD(2+) and SLD(3) groups were 11.3 months and 7.4 months, respectively, with a statistically significant difference(P=0.012). However, the median OS in the SLD(2-) and SLD(1) groups were 13.9 months and 16.4 months, respectively, P=0.053. Univariate and multivariate Cox regression analyses were demonstrated that both SLD(1) [hazard ratio(HR)=0.564; 95% confidence interval: 0.321-0.991; P=0.046] and SLD(3) [HR=3.012; 95%CI: 1.873-4.842; P<0 .001] were independent prognostic factors for overall survival in patients with advanced intrahepatic cholangiocarcinoma. Conclusion The initial therapeutic response played a crucial role in the survival prognosis of patients with advanced iCCA received first-line chemotherapy. Specifically, a greater increase in tumor SLD was associated with a poorer survival prognosis. However, in the reduction of tumor SLD, there was no significant difference between SLD(1) and SDL(2-) in the survival prognosis of patients.