Department of Health Data Science, Liverpool Health Partners, University of Liverpool, UK.
NIHR Birmingham Biomedical Research Centre, University Hospitals Birmingham NHS Foundation Trust and University of Birmingham, UK; Institute of Applied Health Research, University of Birmingham, UK.
J Hepatol. 2021 Oct;75(4):879-887. doi: 10.1016/j.jhep.2021.05.015. Epub 2021 May 27.
BACKGROUND & AIMS: Sorafenib has been the standard of care for patients with advanced hepatocellular carcinoma and although immunotherapeutic approaches are now challenging this position, it retains an advantage in HCV-seropositive patients. We aimed to quantify the rate of tumour progression in patients receiving sorafenib and relate this figure to survival, both overall, and according to viral status.
Using serial data from an international clinical trial we applied a joint model to combine survival and progression over time in order to estimate the rate of tumour growth as assessed by tumour burden and serum alpha-fetoprotein, and the impact of treatment on liver function.
High tumour burden at baseline was associated with an increased risk of death. In patients still alive at the end of the study, the progression in relation to tumour burden was very low compared to those who died within the study. Overall, the change in mean tumour burden was 0.12 mm per day or an absolute growth rate of 3.6 mm/month. Median doubling time was 665 days. For those who progressed above 0.12 mm per day or the 12% rate, median survival was 234 days compared to 384 days if the rate was below 12%. Tumour growth rate and serum alpha-fetoprotein rise were significantly lower in those who were HCV seropositive as was the rate of decline in liver function. These results were replicated in 2 independent patient groups.
Our analysis suggests that sorafenib treatment is associated with improved survival in patients with advanced hepatocellular carcinoma mainly by decreasing the rate of tumour growth and liver function deterioration among patients with HCV infection.
Among patients receiving sorafenib for advanced hepatocellular carcinoma the rate of tumour growth (as assessed by changes in tumour size and the biomarker alpha-fetoprotein) and the deterioration of liver function is less in those who have the hepatitis C virus, than in those who do not.
索拉非尼一直是晚期肝细胞癌患者的标准治疗方法，尽管免疫治疗方法目前正在挑战这一地位，但它在 HCV 血清阳性患者中仍具有优势。我们旨在量化接受索拉非尼治疗的患者的肿瘤进展率，并根据总体生存率和病毒状态来比较这一数字。
利用一项国际临床试验的连续数据，我们应用联合模型来结合随时间推移的生存和进展，以评估肿瘤负担和血清甲胎蛋白评估的肿瘤生长速度，以及治疗对肝功能的影响。
基线时高肿瘤负担与死亡风险增加相关。在研究结束时仍存活的患者中，与肿瘤负担相关的进展速度与研究期间内死亡的患者相比非常低。总体而言，平均肿瘤负担的变化为每天 0.12 毫米或绝对生长速度为每月 3.6 毫米。中位倍增时间为 665 天。对于那些进展速度超过每天 0.12 毫米或 12%的患者，中位生存期为 234 天，而进展速度低于 12%的患者为 384 天。对于肿瘤生长速度和血清甲胎蛋白升高的患者，HCV 血清阳性患者的发生率明显较低，肝功能下降的发生率也较低。这些结果在另外两个独立的患者群体中得到了复制。
我们的分析表明，索拉非尼治疗与晚期肝细胞癌患者的生存率提高有关，主要是通过降低 HCV 感染患者的肿瘤生长速度和肝功能恶化速度。
在接受索拉非尼治疗的晚期肝细胞癌患者中，肿瘤生长速度（通过肿瘤大小和生物标志物甲胎蛋白的变化来评估）和肝功能恶化速度在患有丙型肝炎病毒的患者中比在不患有丙型肝炎病毒的患者中要低。
