Lee Sang Ho, Hayano Koichi, Zhu Andrew X, Sahani Dushyant V, Yoshida Hiroyuki
3D Imaging Research, Department of Radiology, Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts, United States of America.
Division of Abdominal Imaging and Intervention, Department of Radiology, Massachusetts General Hospital, Boston, Massachusetts, United States of America.
PLoS One. 2015 Sep 14;10(9):e0136725. doi: 10.1371/journal.pone.0136725. eCollection 2015.
To find prognostic biomarkers in pretreatment dynamic contrast-enhanced MRI (DCE-MRI) water-exchange-modified (WX) kinetic parameters for advanced hepatocellular carcinoma (HCC) treated with antiangiogenic monotherapy.
Twenty patients with advanced HCC underwent DCE-MRI and were subsequently treated with sunitinib. Pretreatment DCE-MRI data on advanced HCC were analyzed using five different WX kinetic models: the Tofts-Kety (WX-TK), extended TK (WX-ETK), two compartment exchange, adiabatic approximation to tissue homogeneity (WX-AATH), and distributed parameter (WX-DP) models. The total hepatic blood flow, arterial flow fraction (γ), arterial blood flow (BFA), portal blood flow, blood volume, mean transit time, permeability-surface area product, fractional interstitial volume (vI), extraction fraction, mean intracellular water molecule lifetime (τC), and fractional intracellular volume (vC) were calculated. After receiver operating characteristic analysis with leave-one-out cross-validation, individual parameters for each model were assessed in terms of 1-year-survival (1YS) discrimination using Kaplan-Meier analysis, and association with overall survival (OS) using univariate Cox regression analysis with permutation testing.
The WX-TK-model-derived γ (P = 0.022) and vI (P = 0.010), and WX-ETK-model-derived τC (P = 0.023) and vC (P = 0.042) were statistically significant prognostic biomarkers for 1YS. Increase in the WX-DP-model-derived BFA (P = 0.025) and decrease in the WX-TK, WX-ETK, WX-AATH, and WX-DP-model-derived vC (P = 0.034, P = 0.038, P = 0.028, P = 0.041, respectively) were significantly associated with an increase in OS.
The WX-ETK-model-derived vC was an effective prognostic biomarker for advanced HCC treated with sunitinib.
寻找抗血管生成单药治疗晚期肝细胞癌（HCC）时，治疗前动态对比增强磁共振成像（DCE-MRI）水交换修正（WX）动力学参数中的预后生物标志物。
20例晚期HCC患者接受了DCE-MRI检查，随后接受舒尼替尼治疗。使用五种不同的WX动力学模型分析晚期HCC的治疗前DCE-MRI数据：Tofts-Kety（WX-TK）模型、扩展Tofts-Kety（WX-ETK）模型、双室交换模型、组织均匀性绝热近似（WX-AATH）模型和分布参数（WX-DP）模型。计算全肝血流量、动脉血流分数（γ）、动脉血流量（BFA）、门静脉血流量、血容量、平均通过时间、通透性-表面积乘积、间质容积分数（vI）、提取分数、平均细胞内水分子寿命（τC）和细胞内容积分数（vC）。在采用留一法交叉验证的受试者工作特征分析后，使用Kaplan-Meier分析评估每个模型的个体参数对1年生存率（1YS）的判别能力，并使用带有置换检验的单变量Cox回归分析评估其与总生存期（OS）的相关性。
WX-TK模型得出的γ（P = 0.022）和vI（P = 0.010），以及WX-ETK模型得出的τC（P = 0.023）和vC（P = 0.042）是1YS的统计学显著预后生物标志物。WX-DP模型得出的BFA增加（P = 0.025），以及WX-TK、WX-ETK、WX-AATH和WX-DP模型得出的vC降低（分别为P = 0.034、P = 0.038、P = 0.028、P = 0.041）与OS增加显著相关。
WX-ETK模型得出的vC是舒尼替尼治疗晚期HCC的有效预后生物标志物。
