Gd-EOB-DTPA-Enhanced Magnetic Resonance Imaging for Predicting Immunotherapy Response in Hepatocellular Carcinoma: A
Wenbo Xie1,2,3, Linmao Sun1,2,3, Yumin Fu1,2,3
1Department of Hepatobiliary Surgery, Centre for Leading Medicine and Advanced Technologies of IHM, The First Affiliated Hospital of USTC, Division of Life Sciences and Medicine, University of Science and Technology of China, Hefei, China.
Introduction:
Hepatocellular carcinoma (HCC) harboring CTNNB1 mutations that activate the Wnt/β-catenin pathway demonstrates increased gadoxetic acid (Gd-EOB-DTPA) uptake due to overexpressed organic anion transporting polypeptide 1B3 (OATP1B3) and exhibits immune checkpoint inhibitor (ICI) resistance attributed to an immune-excluded tumor microenvironment and tumor immune barriers. This systematic review investigated Gd-EOB-DTPA-enhanced magnetic resonance imaging (MRI) for predicting immunotherapy response in HCC.
Methods:
A systematic search of PubMed, Web of Science, and Cochrane was conducted up to September 10, 2025. Studies linking relative enhancement ratio (RER) >0.9 on Gd-EOB-DTPA-enhanced MRI to progression-free survival (RECIST 1.1) in immunotherapy-treated patients were included. Following PRISMA 2020/SWiM guidelines, risk of bias was assessed via QUADAS-2. Meta-analysis was performed using JASP (v0.95.4) via a random-effects model with restricted maximum likelihood estimation. Heterogeneity was assessed using I 2 and τ 2. Notably, the Knapp-Hartung adjustment was applied to calculate 95% confidence interval (CI) to ensure robust inference despite the limited study number. Sources of heterogeneity and robustness were explored using subgroup analyses, meta-regression, and sensitivity analyses.
Results:
Five studies (n = 253; published 2021-2025) were analyzed. RER ≥0.9 was identified as a significant predictor of poor response across diverse ICI regimens, with a pooled hazard ratios (HR) of 5.79 (95% CI: 1.56-21.50; p = 0.020) and individual estimates ranging from 1.58 to 22.04. However, further analysis indicated that anti-VEGF therapy might mitigate this resistance and partially restore ICI efficacy; the association between high RER and poor survival was not statistically significant in the anti-VEGF cohort (HR = 3.39; 95% CI: 0.39-29.14; p = 0.135).
Conclusions:
To the best of our knowledge, this is the first systematic review evaluating the predictive utility of Gd-EOB-DTPA-enhanced MRI for HCC immunotherapy. Our findings suggest that an RER ≥0.9 serves as a potential noninvasive marker for poor treatment response. Notably, the observation that anti-VEGF combination therapy might mitigate this imaging-defined resistance is hypothesis-generating, underscoring the need for prospective studies to validate optimal strategies for patients with high-RER tumors.
