Lee Chern-Horng, Lin Yu-Jr, Lin Chen-Chun, Yen Cho-Li, Shen Chien-Heng, Chang Chee-Jen, Hsieh Sen-Yung
Department of General Medicine, Chang Gung Memorial Hospital, Linkou, Taoyuan, Taiwan.
Resource Center for Clinical Research, Chang Gung Memorial Hospital, Linkou, Taoyuan, Taiwan.
Liver Int. 2015 Oct;35(10):2327-36. doi: 10.1111/liv.12817. Epub 2015 Apr 10.
BACKGROUND & AIMS: Thrombocytosis is associated with metastasis in many human cancers. Most hepatocellular carcinomas (HCC) develop in cirrhotic livers, which are characterized by thrombocytopenia. We aimed to elucidate the pretreatment platelet count in prediction of extrahepatic metastasis of HCC during the follow-up.
Three cohorts containing 1660, 480 and 965 HCC patients enrolled from three hospitals were used for discovery and validation respectively. Pretreatment clinical factors associated with extrahepatic metastasis during follow-up up to 5 years were identified using multivariate Cox regression model.
In early-stage HCC (BCLC stage 0-A), pretreatment platelet count (hazard ratio [HR], 1.04 per 10,000/μl; 95% CI, 1.01-1.07; P = 0.010) and serum alpha-foetoprotein (AFP) >100 ng/ml (HR, 1.70; 95% CI, 1.04-2.78; P = 0.033) were the only two independent factors associated with extrahepatic metastasis. Receiver operating characteristic evidenced that pretreatment platelet count predicted metastasis better than AFP did. Survival tree analysis identified platelet counts <118,000/μl (HR, 0.49; 95% CI, 0.38-0.63; P < 0.001) or >212,000/μl (HR, 2.12; 95% CI, 1.67-2.70; P < 0.001) to categorize patients into low and high risk of metastasis subgroups, which were verified using both validation cohorts.
Pretreatment platelet count is a reliable marker to predict extrahepatic metastasis of early-stage HCC following curative treatment. Cirrhotic thrombocytopenia contributes to relatively low metastasis incidence of HCC than many other cancers. High platelet count identifies a subgroup of HCC patients at high risk of metastasis, who might benefit from adjuvant therapies following initial curative treatment.
血小板增多症与多种人类癌症的转移相关。大多数肝细胞癌（HCC）发生于肝硬化肝脏，其特征为血小板减少。我们旨在阐明随访期间HCC肝外转移预测中的预处理血小板计数情况。
分别来自三家医院的包含1660例、480例和965例HCC患者的三个队列用于发现和验证。使用多变量Cox回归模型确定随访长达5年期间与肝外转移相关的预处理临床因素。
在早期HCC（BCLC分期0 - A）中，预处理血小板计数（风险比[HR]，每10,000/μl为1.04；95%置信区间[CI]，1.01 - 1.07；P = 0.010）和血清甲胎蛋白（AFP）>100 ng/ml（HR，1.70；95% CI，1.04 - 2.78；P = 0.033）是与肝外转移相关的仅有的两个独立因素。受试者工作特征曲线表明预处理血小板计数比AFP能更好地预测转移。生存树分析确定血小板计数<118,000/μl（HR，0.49；95% CI，0.38 - 0.63；P < 0.001）或>212,000/μl（HR，2.12；95% CI，1.67 - 2.70；P < 0.001）可将患者分为转移低风险和高风险亚组，这在两个验证队列中均得到验证。
预处理血小板计数是预测根治性治疗后早期HCC肝外转移的可靠标志物。肝硬化性血小板减少导致HCC转移发生率相对低于许多其他癌症。高血小板计数确定了一组HCC转移高风险患者，他们可能从初始根治性治疗后的辅助治疗中获益。
