title: Heterogeneity of Glucose Metabolism in Esophageal Cancer Measured by Fractal Analysis of Fluorodeoxyglucose Positron Emission Tomography Image: Correlation between Metabolic Heterogeneity and Survival.
abstract: BACKGROUND
  Intratumoral heterogeneity is a well-recognized characteristic feature of cancer. The purpose of this study is to assess the heterogeneity of the intratumoral glucose metabolism using fractal analysis, and evaluate its prognostic value in patients with esophageal squamous cell carcinoma (ESCC).
  
  
  METHODS
  18F-fluorodeoxyglucose positron emission tomography (FDG-PET) studies of 79 patients who received curative surgery were evaluated. FDG-PET images were analyzed using fractal analysis software, where differential box-counting method was employed to calculate the fractal dimension (FD) of the tumor lesion. Maximum standardized uptake value (SUVmax) and FD were compared with overall survival (OS).
  
  
  RESULTS
  The median SUVmax and FD of ESCCs in this cohort were 13.8 and 1.95, respectively. In univariate analysis performed using Cox's proportional hazard model, T stage and FD showed significant associations with OS (p = 0.04, p < 0.0001, respectively), while SUVmax did not (p = 0.1). In Kaplan-Meier analysis, the low FD tumor (<1.95) showed a significant association with favorable OS (p < 0.0001). In wthe multivariate analysis among TNM staging, serum tumor markers, FD, and SUVmax, the FD was identified as the only independent prognostic factor for OS (p = 0.0006; hazards ratio 0.251, 95% CI 0.104-0.562).
  
  
  CONCLUSIONS
  Metabolic heterogeneity measured by fractal analysis can be a novel imaging biomarker for survival in patients with ESCC.
authors.affiliation: Department of Frontier Surgery, Chiba University Graduate School of Medicine, Chiba, Japan.
authors.forename: Toru
authors.initials: T
authors.lastname: Tochigi
authors.forename: Kiyohiko
authors.initials: K
authors.lastname: Shuto
authors.forename: Tsuguaki
authors.initials: T
authors.lastname: Kono
authors.forename: Gaku
authors.initials: G
authors.lastname: Ohira
authors.forename: Takayuki
authors.initials: T
authors.lastname: Tohma
authors.forename: Hisashi
authors.initials: H
authors.lastname: Gunji
authors.forename: Koichi
authors.initials: K
authors.lastname: Hayano
authors.forename: Kazuo
authors.initials: K
authors.lastname: Narushima
authors.forename: Takeshi
authors.initials: T
authors.lastname: Fujishiro
authors.forename: Toshiharu
authors.initials: T
authors.lastname: Hanaoka
authors.forename: Yasunori
authors.initials: Y
authors.lastname: Akutsu
authors.forename: Shinichi
authors.initials: S
authors.lastname: Okazumi
authors.forename: Hisahiro
authors.initials: H
authors.lastname: Matsubara
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D014408:Biomarkers, Tumor / Q000097:blood; D002294:Carcinoma, Squamous Cell / Q000378:metabolism* / Q000473:pathology / Q000628:therapy*; D059186:Chemoradiotherapy, Adjuvant; D017024:Chemotherapy, Adjuvant; D004938:Esophageal Neoplasms / Q000378:metabolism* / Q000473:pathology / Q000628:therapy*; D016629:Esophagectomy; D005260:Female; D019788:Fluorodeoxyglucose F18 / Q000378:metabolism; D017709:Fractals; D005947:Glucose / Q000378:metabolism*; D006801:Humans; D053208:Kaplan-Meier Estimate; D008297:Male; D008875:Middle Aged; D020360:Neoadjuvant Therapy; D009367:Neoplasm Staging; D049268:Positron-Emission Tomography; D016016:Proportional Hazards Models; D019275:Radiopharmaceuticals / Q000378:metabolism; D012189:Retrospective Studies; D015996:Survival Rate
chemical_list: D014408:Biomarkers, Tumor; D019275:Radiopharmaceuticals; D019788:Fluorodeoxyglucose F18; D005947:Glucose
keywords: 18F-fluorodeoxyglucose positron emission tomography; Esophageal cancer; Fractal analysis; Heterogeneity; Overall survival