Geographic difference in survival outcome for advanced hepatocellular carcinoma: Implications on future clinical trial design
Geographic difference in survival outcome for advanced hepatocellular carcinoma: Implications on future clinical trial design
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DOI：
10.1016/j.cct.2009.08.002
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发表时间：
2010-01-01
影响因子：
2.2
通讯作者：
Cheng, Ann-Lii
中科院分区：
文献类型：
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作者：
Hsu, Chiun;Shen, Ying-Chun;Cheng, Ann-Lii
在晚期肝细胞癌 (HCC) 全身治疗的临床试验中，亚洲试验几乎总是报告生存率低于非亚洲试验。本研究试图找出造成这种地理差异的因素。对不可切除的 HCC 随机试验进行了系统评价，该试验使用全身治疗作为实验组，安慰剂或支持性护理作为对照。进行荟萃分析时考虑了固定效应和随机效应。然后，进行荟萃回归以确定对照组患者生存的预测因素和治疗效果（中位生存的改善）。 14 项试验（6 项亚洲人，8 项非亚洲人）符合荟萃分析条件。对照组患者的中位生存期（表明晚期 HCC 患者的自然史）在亚洲试验中为 3.57 +/- 1.88 个月，在非亚洲试验中为 5.96 +/- 1.46 个月 (p=0.02)。更好生存的独立预测因素包括非亚洲试验 (p=0.0007)、较高比例的儿童 A 型肝硬化 (p=0.01) 和乙型肝炎 (HBV) 相关的 HCC (p=0.02)。亚组分析表明，亚洲试验倾向于招募患有更晚期疾病的患者。更好治疗效果的独立预测因素包括非亚洲试验、肝外转移比例较高、HBV 相关 HCC 以及较差的试验质量。地理差异的定量估计有助于设计未来晚期 HCC 的临床试验。 (C) 2009 Elsevier Inc. 保留所有权利。
In clinical trials of systemic therapy for advanced hepatocellular carcinoma (HCC), Asian trials almost always reported poorer survival than non-Asian trials. This study sought to identify contributory factors for this geographic difference. A systematic review was done on randomized trials for unresectable HCC that used systemic therapy as an experimental arm and placebo or supportive care as control. Meta-analysis was performed with the consideration of fixed and random effects. Then, meta-regression was performed to identify predictors of patient survival in the control arm and the treatment effects (improvement in median survival). Fourteen trials (6 Asians, 8 non-Asians) were eligible for meta-analysis. The median survival of patients in the control arm, which indicated natural history of advanced HCC patients, was 3.57 +/- 1.88 months in Asian trials and 5.96 +/- 1.46 months in non-Asian trials (p=0.02). Independent predictors of better survival included non-Asian trials (p=0.0007), higher percentage of Child A cirrhosis (p=0.01) and hepatitis B (HBV)-related HCC (p=0.02). Sub-group analysis suggested that Asian trials tended to enroll patients with more advanced diseases. Independent predictors of better treatment effect included non-Asian trials, higher percentage of extra-hepatic metastasis, HBV-related HCC, and poorer trial quality. The quantitative estimation of the geographic difference can help design of future clinical trials of advanced HCC. (C) 2009 Elsevier Inc. All rights reserved.