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

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 3.03 min-1 to 1.06 min-1 (P=0.009) with modest increases in median apparent diffusion coefficient (ADC) from 0.88x10-3 mm2/s to 0.98x10-3 mm2/s (P=0.027). Tumor size remained unchanged by RECIST and mRECIST (P=0.230, P=0.741). Patients who showed higher baseline tumor Ktrans and Kep and larger drop in Ktrans at 2 weeks correlated with favorable clinical outcome and longer PFS (all P<0.05). There was a significant association between a decrease in sVEGFR2 or TNF-alpha and the drop in Kep (P=0.031, P=0.046) and a trend for association with Ktrans. 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

via Journal of Hematology & Oncology