Magnetic resonance imaging biomarkers in hepatocellular carcinoma: association with response and circulating biomarkers after sunitinib therapy

Dushyant V Sahani, Tao Jiang, Koichi Hayano, Dan G Duda, Onofrio A Catalano, Marek Ancukiewicz, Rakesh K Jain, Andrew X Zhu, Dushyant V Sahani, Tao Jiang, Koichi Hayano, Dan G Duda, Onofrio A Catalano, Marek Ancukiewicz, Rakesh K Jain, Andrew X Zhu

Abstract

Background: To investigate the hypothesis that MRI derived diffusion-weighted imaging (DWI) and perfusion (MRP) parameters are sensitive image biomarkers for monitoring early antiangiogenic effects and predicting progression free survival (PFS) in advanced hepatocellular carcinoma (HCC).

Methods: In this phase II clinical trial, 23 of 34 patients were included in the imaging and circulating biomarker study. DWI and MRP were performed at the baseline and at 2-weeks after initiation of sunitinib. The imaging protocol included an axial DWI sequence using b values of 50, 400 and 800 sec/mm2, and MRP using a series of coronal 3D-VIBE following 20 ml of Gd-DTPA at 2 ml/sec. These parameters were compared with clinical outcome and PFS at 6-months. Correlation between changes in MRI parameters and plasma biomarkers was also evaluated.

Results: After 2-week of sunitinib, substantial Ktrans changes in HCC were observed from median baseline value 2.15 min⁻¹ to 0.94 min⁻¹ (P = 0.0001) with increases in median apparent diffusion coefficient (ADC) from 0.88 × 10⁻³ mm²/s to 0.98 × 10⁻³ mm²/s (P = 0.0001). Tumor size remained unchanged by RECIST and mRECIST (both P > 0.05). Patients who showed larger drop in Ktrans and Kep at 2 weeks correlated with favorable clinical outcome, and higher baseline Ktrans and larger drop in EVF correlated with longer PFS (all P < 0.05). There was a significant association between a decrease in sVEGFR2 and the drop in Ktrans and Kep (P = 0.044, P = 0.030), and a significant and borderline association between decrease in TNF-α and the drop in Ktrans and Kep, respectively (P = 0.051, P = 0.035).

Conclusion: In HCC, MRP may be a more sensitive biomarker in predicting early response and PFS following sunitinib than RECIST and mRECIST.

Trial registration: ClinicalTrials.gov: NCT00361309.

Figures

Figure 1
Figure 1
Functional transfer constant map of HCC during sunitinib therapy. Coronal enhanced MR T1-weighted images (A, B) and functional transfer constant (Ktrans) maps from MR perfusion (C, D) at baseline and after 2-week of sunitinib therapy in a 47-year-old man with HCC (arrows). After two weeks of treatment with sunitinib, HCC showed a 96% drop of Ktrans, which presented a conspicuity of permeability change.
Figure 2
Figure 2
MR diffusion weighted images during sunitinib therapy. Transverse enhanced MR T1-weighted images (A, B) and MR diffusion weighted images (DWIs) for estimated apparent diffusion coefficient (ADC) (C, D) at baseline and after 2-week of sunitinib therapy in the same 47-year-old man with HCC (arrows). After two weeks of treatment with sunitinib, there was an increase in ADC value from 0.86 × 10-3 mm2/s to 0.94 × 10-3 mm2/s.

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