广西医学

目的基于真实世界数据探讨瑞戈非尼联合治疗方案在晚期肝癌患者中的应用效果，以及疗效和患者预后的影响因素。方法回顾性分析71例一线治疗失败后接受瑞戈非尼联合治疗方案的晚期肝癌患者的临床资料，比较不同临床特征患者的疗效和预后。采用多因素Logistic 回归模型分析瑞戈非尼联合治疗方案疗效的影响因素。绘制受试者工作特征曲线评估治疗前血小板计数与淋巴细胞计数比值（PLR）、中性粒细胞计数与淋巴细胞计数比值（NLR）、C反应蛋白（CRP）水平、系统免疫炎症指数（SII）预测瑞戈非尼联合治疗方案疗效的效能。采用单因素和多因素COX回归模型分析瑞戈非尼联合治疗后晚期肝癌患者预后的影响因素。结果 71例晚期肝癌患者接受瑞戈非尼联合治疗方案后的客观缓解率（ORR）为5.63%，疾病控制率（DCR）为60.56%，中位无进展生存期（PFS）为6.77个月，中位总生存期（OS）为14.62个月。不同临床特征晚期肝癌患者的ORR和DCR差异无统计学意义（P>0.05）。甲胎蛋白（AFP）水平<400 ng/mL的晚期肝癌患者的中位PFS更长，既往接受免疫治疗、AFP水平<400 ng/mL的晚期肝癌患者的中位OS更长（P<0.05）。CRP水平为晚期肝癌患者瑞戈非尼联合治疗方案疗效的独立影响因素（P<0.05）。NLR、PLR、CRP、SII预测瑞戈非尼联合治疗方案疗效的曲线下面积分别为0.639、0.624、0.704、0.618。多因素COX回归分析结果显示，既往接受免疫治疗、AFP水平为采用瑞戈非尼联合治疗方案的晚期肝癌患者OS的影响因素（P<0.05）。大多数不良反应为轻度至中度，患者对治疗的耐受性良好。结论瑞戈非尼联合治疗方案对于经一线治疗失败的晚期肝癌患者而言安全、有效，不良反应可控，可带来良好的生存获益。CRP、AFP等血清学指标和既往治疗情况对该方案的疗效或患者预后有一定影响，应个性化调整治疗策略。

Objective To investigate the application effect of regorafenib combination therapy regimen in patients with advanced hepatocellular carcinoma based on real⁃world data, as well as the factors influencing efficacy and patients' prognosis. Methods The clinical data of 71 patients with advanced hepatocellular carcinoma who received regorafenib combination therapy regimen after first⁃line treatment failure were retrospectively analyzed. Efficacy and prognosis were compared between patients with different clinical characteristics. Multivariate Logistic regression model analysis was used to identify factors influencing the efficacy of regorafenib combination therapy regimen. Receiver operating characteristic (ROC) curve was plotted to evaluate the efficiency of the platelet⁃to⁃lymphocyte ratio (PLR), neutrophil⁃to⁃lymphocyte ratio (NLR), C⁃reactive protein (CRP) level, and systemic immune⁃inflammation index (SII) before treatment in predicting the efficacy of regorafenib combination therapy regimen. Univariate and multivariate COX regression models were employed to analyze factors influencing the prognosis of advanced hepatocellular carcinoma patients after regorafenib combination therapy. Results Among the 71 patients with advanced hepatocellular carcinoma treated with regorafenib combination therapy regimen, the objective response rate (ORR) was 5.63%, and the disease control rate (DCR) was 60.56%. The median progression⁃free survival (PFS) was 6.77 months, and the median overall survival (OS) was 14.62 months. No statistically significant difference in ORR or DCR was observed between advanced hepatocellular carcinoma patients with different clinical characteristics (P>0.05). Advanced hepatocellular carcinoma patients with alpha⁃fetoprotein (AFP) levels <400 ng/mL had a longer median PFS, while those with a history of immunotherapy and AFP levels <400 ng/mL exhibited a longer median OS (P<0.05). The CRP level was identified as an independent factor influencing the efficacy of regorafenib combination therapy regimen (P<0.05). The areas under the curve for predicting efficacy of regorafenib combination therapy regimen using NLR, PLR, CRP, and SII were 0.639, 0.624, 0.704, and 0.618, respectively. The results of multivariate COX regression analysis indicated that a history of immunotherapy and AFP level were factors influencing OS in advanced hepatocellular carcinoma patients treated with the regorafenib combination therapy regimen (P<0.05). Most adverse reactions were mild to moderate, and the treatment was well tolerated by patients. Conclusion The regorafenib combination therapy regimen is safe, effective, and manageable in terms of adverse reactions for patients with advanced hepatocellular carcinoma who have failed first⁃line treatment, and it provides significant survival benefits. Serological indices such as CRP and AFP, as well as prior treatment history, may influence the efficacy of this regimen or patients' prognosis to a certain extent, suggesting that treatment strategies should be tailored individually.