Fractal Analysis of Contrast-Enhanced CT Images to Predict Survival of Patients with Hepatocellular Carcinoma Treated with Sunitinib

Abstract

Intratumoral heterogeneity is a well-recognized feature of malignancy. To assess the heterogeneity of tumor using fractal analysis of contrast-enhanced computed tomography (CE-CT) images for predicting survival of hepatocellular carcinoma (HCC) patients treated with sunitinib. The patient cohort comprised 23 patients (19 men, 4 women; mean age 61.5 years) with HCC who underwent CE-CT at baseline and after one cycle of sunitinib. Arterial-phase (AP) and portal-phase (PP) CE-CT images were analyzed using a plugin software for ImageJ (NIH, Bethesda, MD). A differential box-counting method was employed to calculate the fractal dimension (FD) of the tumor. Tumor FD, density, and size were compared with survival. Median progression-free survival (PFS) was 4.43 months. Patients were grouped into a favorable PFS (PFS >4.43 months; 9 patients) and an unfavorable PFS group (PFS ≤ 4.43; 13 patients). The baseline FD on both the AP and PP images was lower in the favorable PFS group than in the unfavorable PFS group (both P = 0.03). There was a significant difference in the change of the FD on the AP image between the favorable and unfavorable PFS groups (P = 0.02). Tumor density and size showed no significant correlations with PFS. In the Kaplan-Meier analysis, patients with tumors showing lower FD on the AP image at baseline showed longer PFS (P = 0.002). Patients with tumors showing a greater reduction in the FD on the PP image after one cycle of the therapy showed longer overall survival (P = 0.002). The FD of the tumor on CE-CT images may be a useful biomarker for HCC patients treated with sunitinib.