title: Fractal analysis of contrast-enhanced CT images to predict survival of patients with hepatocellular carcinoma treated with sunitinib.
abstract: BACKGROUND
  Intratumoral heterogeneity is a well-recognized feature of malignancy.
  
  
  OBJECTIVE
  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.
  
  
  METHODS
  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.
  
  
  RESULTS
  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).
  
  
  CONCLUSIONS
  The FD of the tumor on CE-CT images may be a useful biomarker for HCC patients treated with sunitinib.
authors.affiliation: Division of Abdominal Imaging and Intervention, Department of Radiology, Massachusetts General Hospital, 55 Fruit Street, White 270, Boston, MA, 02114, USA, khayano@partners.org.
authors.forename: Koichi
authors.initials: K
authors.lastname: Hayano
authors.forename: Hiroyuki
authors.initials: H
authors.lastname: Yoshida
authors.forename: Andrew X
authors.initials: AX
authors.lastname: Zhu
authors.forename: Dushyant V
authors.initials: DV
authors.lastname: Sahani
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000970:Antineoplastic Agents / Q000627:therapeutic use*; D001900:Boston / Q000453:epidemiology; D006528:Carcinoma, Hepatocellular / Q000000981:diagnostic imaging* / Q000188:drug therapy / Q000401:mortality*; D018572:Disease-Free Survival; D005260:Female; D017709:Fractals; D006801:Humans; D007211:Indoles / Q000627:therapeutic use*; D053208:Kaplan-Meier Estimate; D008113:Liver Neoplasms / Q000000981:diagnostic imaging* / Q000188:drug therapy / Q000401:mortality*; D008297:Male; D008875:Middle Aged; D011758:Pyrroles / Q000627:therapeutic use*; D011859:Radiography; D000077210:Sunitinib
chemical_list: D000970:Antineoplastic Agents; D007211:Indoles; D011758:Pyrroles; D000077210:Sunitinib