Dynamic Contrast-Enhanced and Intravoxel Incoherent Motion MRI Biomarkers Are Correlated to Survival Outcome in Advanced Hepatocellular Carcinoma.

Bang-Bin Chen,Tiffany Ting-Fang Shih,Yu-Yun Shao,Chih-Hung Hsu,Zhong-Zhe Lin,Chiun Hsu,Ann-Lii Cheng,Po-Chin Liang

doi:10.3390/diagnostics11081340

Abstract

Objective: This study assessed dynamic contrast-enhanced (DCE)-MRI and intravoxel incoherent motion diffusion-weighted imaging (IVIM DWI) parameters to prospectively predict survival outcomes in participants with advanced hepatocellular carcinoma (HCC) who received lenalidomide, a dual antiangiogenic and immunomodulatory agent, as second-line therapy in a Phase II clinical trial. Materials and methods: Forty-four participants with advanced HCC who had progression after sorafenib as first-line treatment were prospectively enrolled. Pretreatment MRI parameters—obtained from DCE-MRI (peak, slope, AUC, Ktrans, Kep, and Ve), apparent diffusion coefficient (ADC), and IVIM DWI (pure diffusion coefficient (D), pseudodiffusion coefficient (D*), and perfusion fraction (f))—were derived from the largest hepatic tumor. The Cox model was used to investigate the associations of the parameters with progression-free survival (PFS) and overall survival (OS). Results: Median PFS and OS were 2.3 and 8.0 months, respectively. Univariate analysis showed that participants with a high slope (p = 0.024), Kep (p < 0.001), and ADC (p = 0.018) values had longer PFS than those with low values; participants with a small tumor size (p = 0.006), high slope (p = 0.01), ADC (p = 0.015), and f (p = 0.012) values had longer OS than those with low values did. Cox multivariable analysis revealed that Kep (p < 0.001) and ADC (p = 0.009) remained independent predictors of PFS; slope (p = 0.003) and ADC (p = 0.009) remained independent predictors of OS. Moreover, Kep and slope were still significant after Bonferroni correction was performed (p < 0.005). Conclusion: Both pretreatment DCE-MRI and IVIM DWI parameters, especially slope and ADC, may predict PFS and OS in participants with HCC receiving lenalidomide as second-line therapy.

Highlights

Hepatocellular carcinoma (HCC) is the third highest cause of cancer-related death, with an increasing global incidence
Cox multivariable analysis revealed that Kep and apparent diffusion coefficient (ADC) remained independent predictors of progression-free survival (PFS); slope and ADC remained independent predictors of overall survival (OS)
In participants with advanced hepatocellular carcinoma (HCC) who received lenalidomide as second-line therapy, high baseline slope, Kep, and ADC values were associated with better PFS, while small tumor size, high baseline slope, ADC, and f values were associated with better OS

Summary

Introduction

Hepatocellular carcinoma (HCC) is the third highest cause of cancer-related death, with an increasing global incidence. Regorafenib, cabozantinib, and ramucirumab, and two checkpoint inhibitors, namely, nivolumab and pembrolizumab, were approved by the US Food and Drug Administration as second-line treatment options after prior sorafenib treatment [5]. Lenalidomide, which has both antiangiogenic and immunomodulatory effects, demonstrated efficacy as a second-line treatment for advanced HCC [6,7]. In several clinical trials of new targeted therapies for HCC, DCE-MRI biomarkers using conventional gadolinium-based contrast agents have been used as early surrogates to predict clinical response and survival outcome [7,9,10,11]. Vascular response determined by >40% Ktrans reduction at 2 weeks did not correlate with treatment response after lenalidomide [7] and vandetanib [10] treatments

Methods

Results

Conclusion