肿瘤形态特征对肝细胞癌免疫治疗效果的预测价值

Predictive value of tumor morphology in hepatocellular carcinoma immunotherapy

  • 摘要:
    目的 探讨肿瘤形态特征对肝细胞癌(以下简称肝癌)免疫治疗效果的预测价值。
    方法 采用倾向评分匹配及回顾性队列研究方法。收集2021年1月至2023年12月中国科学技术大学附属第一医院收治的227例行肝癌免疫治疗患者的临床资料;男203例,女24例;年龄为(57±11)岁。227例患者中,93例CT或磁共振成像(MRI)检查结果显示肝肿瘤形态规则,设为形态规则组;134例CT或MRI检查结果显示肝肿瘤形态不规则,设为形态不规则组。观察指标:(1)倾向评分匹配情况及匹配后两组患者一般资料比较。(2)影响患者预后的因素分析。(3)倾向评分匹配后患者预后情况。正态分布的计量资料组间比较采用独立样本t检验。计数资料组间比较采用χ2检验。等级资料采用Mann-Whitney U检验。采用Kaplan-Meier法计算生存率并绘制生存曲线,Log-rank检验进行生存分析,采用Cox风险比例回归模型进行单因素和多因素分析。倾向评分匹配按1∶1最近邻匹配法匹配,卡钳值为0.02。
    结果 (1)倾向评分匹配情况及匹配后两组患者一般资料比较。227例行肝癌免疫治疗患者中,164例匹配成功,形态规则组和不规则组各82例。倾向评分匹配后消除既往根治性手术切除、肿瘤数目、甲胎蛋白因素混杂偏移,两组具有可比性。(2)影响患者预后的因素分析。多因素分析结果显示:体质量指数≥25 kg/m2、肿瘤形态不规则均是影响患者总生存时间的独立危险因素风险比=0.891、1.870,95%可信区间(CI)为0.825~0.963、1.151~3.038,P < 0.05。(3)倾向评分匹配后患者预后情况。倾向评分匹配后,形态规则组和形态不规则组患者的中位无进展生存时间分别为11.9(95%CI为9.2~16.1)个月和6.4(95%CI为4.4~8.1)个月,1年无进展生存率分别为48.48%和22.25%,两组患者无进展生存情况比较,差异有统计学意义(χ2=16.000,P < 0.05)。形态规则组和形态不规则组患者的中位总生存时间分别为27.2(95%CI为23.7~未达到)个月和18.1(95%CI为15.8~20.8)个月,1年总生存率分别为83.27%和66.98%,两组患者总生存情况比较,差异有统计学意义(χ2=13.400,P < 0.05)。
    结论 肿瘤形态特征对肝癌免疫治疗效果具有预测价值。与肿瘤形态规则比较,肿瘤形态不规则患者免疫治疗效果更差。

     

    Abstract:
    Objective To investigate the predictive value of tumor morphology in hepatocellular carcinoma (HCC) immunotherapy.
    Methods The propensity score matching and retrospective cohort study was conducted. The clinical data of 227 HCC patients who underwent immunotherapy in The First Affiliated Hospital of University of Science and Technology of China from January 2021 to December 2023 were collected. There were 203 males and 24 females, aged (57±11)years. Of the 227 patients, 93 patients with regular tumor morphology of HCC evaluated by computed tomography (CT) or magnetic resonance imaging (MRI) were divided into the regular morphology group, and 134 patients with irregular tumor morphology of HCC evaluated by CT or MRI were divided into the irregular morphology group. Observation indicators: (1) propensity score matching and comparison of general data of patients between the two groups after matching; (2) analysis of factors affecting prognosis of patients; (3) prognosis of patients after propensity score matching. Comparison of measurement data with normal distribution between groups was conducted using the independent sample t test. Comparison of count data between groups was conducted using the chi-square test. Comparison of ordinal data was conducted using the Mann-Whitney U test. The Kaplan-Meier method was used to calculate survival rate and draw survival curve. The Log-rank test was used for survival analysis. The Cox proportional hazards regression model was used for univariate and multivariate analyses. Propensity score matching was done by the 1∶1 nearest neighbor matching method, with a caliper value of 0.02.
    Results (1) Propensity score matching and comparison of general data of patients between the two groups after matching. Of 227 HCC patients undergoing immunotherapy, 164 cases were successfully matched, including 82 cases in the regular morphology group and 82 cases in the irregular morphology group. After propensity score matching, the elimination of patients who underwent radical surgical resection in the past, tumor number and alpha fetoprotein confounding bias ensured comparability between the two groups. (2) Analysis of factors affecting prognosis of patients. Results of multivariate analysis showed that body mass index ≥25 kg/m2 and irregular tumor morphology were independent risk factors affecting overall survival time of patients (hazard ratio=0.891, 1.870, 95% confidence interval as 0.825-0.963, 1.151-3.038, P < 0.05). (3) Prognosis of patients after propensity score matching. After propensity score matching, the median progression-free survival time was 11.9(95% confidence interval as 9.2-16.1)months for patients in the regular tumor morphology group and 6.4(95% confidence interval as 4.4-8.1)months for patients in the irregular tumor morphology group, the 1-year progress-free survival rate was 48.48% for patients in the regular tumor morphology group and 22.25% for patients in the irregular tumor morphology group. There was a significant difference in progress-free survival between patients in the regular tumor morphology group and the irregular tumor morphology group (χ2=16.000, P < 0.05). The median overall survival time was 27.2(95% confidence interval as 23.7-not reached)months for patients in the regular tumor morphology group and 18.1 (95% confidence interval as 15.8-20.8)months for patients in the regular tumor morphology group, the 1-year overall survival rate was 83.27% for patients in the regular tumor morphology group and 66.98% for patients in the irregular tumor morphology group. There was a significant difference in overall survival between patients in the regular tumor morphology group and the irregular tumor morphology group (χ2=13.400, P < 0.05).
    Conclusions Tumor morphology has a predictive value for the efficacy of immunotherapy for HCC. Compared with HCC patients of regular tumor morphology, immunotherapy is less effective in patients with irregular tumor morphology.

     

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