title: Intratumoral heterogeneity of (18)F-FDG uptake predicts survival in patients with pancreatic ductal adenocarcinoma.
abstract: OBJECTIVE
  To assess whether intratumoral heterogeneity measured by (18)F-FDG PET texture analysis has potential as a prognostic imaging biomarker in patients with pancreatic ductal adenocarcinoma (PDAC).
  
  
  METHODS
  We evaluated a cohort of 137 patients with newly diagnosed PDAC who underwent pretreatment (18)F-FDG PET/CT from January 2008 to December 2010. First-order (histogram indices) and higher-order (grey-level run length, difference, size zone matrices) textural features of primary tumours were extracted by PET texture analysis. Conventional PET parameters including metabolic tumour volume (MTV), total lesion glycolysis (TLG), and standardized uptake value (SUV) were also measured. To assess and compare the predictive performance of imaging biomarkers, time-dependent receiver operating characteristic (ROC) curves for censored survival data and areas under the ROC curve (AUC) at 2 years after diagnosis were used. Associations between imaging biomarkers and overall survival were assessed using Cox proportional hazards regression models.
  
  
  RESULTS
  The best imaging biomarker for overall survival prediction was first-order entropy (AUC = 0.720), followed by TLG (AUC = 0.697), MTV (AUC = 0.692), and maximum SUV (AUC = 0.625). After adjusting for age, sex, clinical stage, tumour size and serum CA19-9 level, multivariable Cox analysis demonstrated that higher entropy (hazard ratio, HR, 5.59; P = 0.028) was independently associated with worse survival, whereas TLG (HR 0.98; P = 0.875) was not an independent prognostic factor.
  
  
  CONCLUSIONS
  Intratumoral heterogeneity of (18)F-FDG uptake measured by PET texture analysis is an independent predictor of survival along with tumour stage and serum CA19-9 level in patients with PDAC. In addition, first-order entropy as a measure of intratumoral metabolic heterogeneity is a better quantitative imaging biomarker of prognosis than conventional PET parameters.
authors.affiliation: Department of Nuclear Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, 81 Irwon-Ro, Gangnam-gu, Seoul, 06351, Republic of Korea.
authors.forename: Seung Hyup
authors.initials: SH
authors.lastname: Hyun
authors.affiliation: Department of Nuclear Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, 81 Irwon-Ro, Gangnam-gu, Seoul, 06351, Republic of Korea.
authors.forename: Ho Seong
authors.initials: HS
authors.lastname: Kim
authors.affiliation: Department of Surgery, Samsung Medical Center, Sungkyunkwan University School of Medicine, 81 Irwon-Ro, Gangnam-gu, Seoul, 06351, Republic of Korea.
authors.forename: Seong Ho
authors.initials: SH
authors.lastname: Choi
authors.affiliation: Department of Surgery, Samsung Medical Center, Sungkyunkwan University School of Medicine, 81 Irwon-Ro, Gangnam-gu, Seoul, 06351, Republic of Korea.
authors.forename: Dong Wook
authors.initials: DW
authors.lastname: Choi
authors.affiliation: Department of Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, 81 Irwon-Ro, Gangnam-gu, Seoul, 06351, Republic of Korea.
authors.forename: Jong Kyun
authors.initials: JK
authors.lastname: Lee
authors.affiliation: Department of Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, 81 Irwon-Ro, Gangnam-gu, Seoul, 06351, Republic of Korea.
authors.forename: Kwang Hyuck
authors.initials: KH
authors.lastname: Lee
authors.affiliation: Department of Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, 81 Irwon-Ro, Gangnam-gu, Seoul, 06351, Republic of Korea.
authors.forename: Joon Oh
authors.initials: JO
authors.lastname: Park
authors.affiliation: Department of Nuclear Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, 81 Irwon-Ro, Gangnam-gu, Seoul, 06351, Republic of Korea.
authors.forename: Kyung-Han
authors.initials: KH
authors.lastname: Lee
authors.affiliation: Department of Nuclear Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, 81 Irwon-Ro, Gangnam-gu, Seoul, 06351, Republic of Korea.
authors.forename: Byung-Tae
authors.initials: BT
authors.lastname: Kim
authors.affiliation: Department of Nuclear Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, 81 Irwon-Ro, Gangnam-gu, Seoul, 06351, Republic of Korea. jynm.choi@samsung.com.
authors.forename: Joon Young
authors.initials: JY
authors.lastname: Choi
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D001692:Biological Transport; D021441:Carcinoma, Pancreatic Ductal / Q000175:diagnosis* / Q000000981:diagnostic imaging / Q000378:metabolism* / Q000473:pathology; D005260:Female; D019788:Fluorodeoxyglucose F18 / Q000378:metabolism*; D006019:Glycolysis; D006801:Humans; D008297:Male; D008875:Middle Aged; D000072078:Positron Emission Tomography Computed Tomography; D011379:Prognosis; D012189:Retrospective Studies; D016019:Survival Analysis; D047368:Tumor Burden
chemical_list: D019788:Fluorodeoxyglucose F18
keywords: 18F-FDG PET/CT; Intratumoral heterogeneity; Pancreatic cancer; Prognosis; Texture analysis