Division of Digestive and Liver Diseases, Department of Internal Medicine, University of Texas Southwestern Medical Center, Dallas, TX.
Division of Gastroenterology and Hepatology, McGuire VA Medical Center, Richmond, VA.
Hepatology. 2020 Nov;72(5):1654-1665. doi: 10.1002/hep.31159. Epub 2020 Oct 25.
BACKGROUND AND AIMS: There are limited data on hepatocellular carcinoma (HCC) growth patterns, particularly in Western cohorts, despite implications for surveillance, prognosis, and treatment. Our study's aim was to quantify tumor doubling time (TDT) and identify correlates associated with indolent and rapid growth. APPROACH AND RESULTS: We performed a retrospective multicenter cohort study of patients with cirrhosis diagnosed with HCC from 2008 to 2017 at six US and European health systems with two or more contrast-enhanced imaging studies performed ≥ 30 days apart prior to HCC treatment. Radiologists independently measured tumors in three dimensions to calculate TDT and specific growth rate (SGR). We used multivariable ordinal logistic regression to identify factors associated with indolent (TDT > 365 days) and rapid (TDT < 90 days) tumor growth. In the primary cohort (n = 242 patients from four centers), median TDT was 229 days (interquartile range [IQR], 89-627) and median SGR was 0.3% per day (IQR, 0.1%-0.8%). Over one-third (38%) of HCCs had indolent growth, 36.8% intermediate growth, and 25.2% rapid growth. In multivariable analysis, indolent growth was associated with larger tumor diameter (odds ratio [OR], 1.15, 95% confidence interval [CI], 1.03-1.30) and alpha-fetoprotein < 20 ng/mL (OR, 1.90; 95% CI, 1.12-3.21). Indolent growth was more common in nonviral than viral cirrhosis (50.9% versus 32.1%), particularly in patients with T1 HCC (OR, 3.41; 95% CI, 1.08-10.80). Median TDT (169 days; IQR 74-408 days) and SGR (0.4% per day) were similar in an independent cohort (n = 176 patients from two centers). CONCLUSIONS: In a large Western cohort of patients with HCC, we found heterogeneous tumor growth patterns, with one-fourth exhibiting rapid growth and over one-third having indolent growth. Better understanding different tumor growth patterns may facilitate a precision approach to prognostication and treatment.
背景与目的:尽管肝癌(HCC)的生长模式对监测、预后和治疗有影响,但在西方队列中,关于 HCC 生长模式的数据有限。本研究的目的是量化肿瘤倍增时间(TDT),并确定与惰性和快速生长相关的因素。
方法和结果:我们进行了一项回顾性多中心队列研究,纳入了 2008 年至 2017 年间在美国和欧洲的六个医疗系统中诊断为 HCC 且有肝硬化的患者,这些患者在 HCC 治疗前至少有两次间隔≥30 天的增强影像学检查。放射科医生独立地在三个维度上测量肿瘤,以计算 TDT 和特定生长率(SGR)。我们使用多变量有序逻辑回归来确定与惰性(TDT>365 天)和快速(TDT<90 天)肿瘤生长相关的因素。在主要队列(来自四个中心的 242 例患者)中,中位 TDT 为 229 天(IQR,89-627),中位 SGR 为 0.3%/天(IQR,0.1%-0.8%)。超过三分之一(38%)的 HCC 生长缓慢,36.8%生长速度中等,25.2%生长速度较快。在多变量分析中,惰性生长与肿瘤直径较大(比值比[OR],1.15,95%置信区间[CI],1.03-1.30)和甲胎蛋白<20ng/mL(OR,1.90;95%CI,1.12-3.21)相关。非病毒性肝硬化(50.9%)比病毒性肝硬化(32.1%)中更常见惰性生长,尤其是 T1 期 HCC(OR,3.41;95%CI,1.08-10.80)。在一个独立的队列(来自两个中心的 176 例患者)中,中位 TDT(169 天;IQR 74-408 天)和 SGR(0.4%/天)相似。
结论:在西方队列中,我们发现 HCC 患者的肿瘤生长模式存在异质性,四分之一的患者肿瘤生长较快,三分之一以上的患者肿瘤生长较慢。更好地了解不同的肿瘤生长模式可能有助于预测和治疗。
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