title: 18F-FDG PET uptake characterization through texture analysis: investigating the complementary nature of heterogeneity and functional tumor volume in a multi-cancer site patient cohort.
abstract: Intratumoral uptake heterogeneity in (18)F-FDG PET has been associated with patient treatment outcomes in several cancer types. Textural feature analysis is a promising method for its quantification. An open issue associated with textural features for the quantification of intratumoral heterogeneity concerns its added contribution and dependence on the metabolically active tumor volume (MATV), which has already been shown to be a significant predictive and prognostic parameter. Our objective was to address this question using a larger cohort of patients covering different cancer types.
  
  
  METHODS
  A single database of 555 pretreatment (18)F-FDG PET images (breast, cervix, esophageal, head and neck, and lung cancer tumors) was assembled. Four robust and reproducible textural feature-derived parameters were considered. The issues associated with the calculation of textural features using co-occurrence matrices (such as the quantization and spatial directionality relationships) were also investigated. The relationship between these features and MATV, as well as among the features themselves, was investigated using Spearman rank coefficients for different volume ranges. The complementary prognostic value of MATV and textural features was assessed through multivariate Cox analysis in the esophageal and non-small cell lung cancer (NSCLC) cohorts.
  
  
  RESULTS
  A large range of MATVs was included in the population considered (3-415 cm(3); mean, 35; median, 19; SD, 50). The correlation between MATV and textural features varied greatly depending on the MATVs, with reduced correlation for increasing volumes. These findings were reproducible across the different cancer types. The quantization and calculation methods both had an impact on the correlation. Volume and heterogeneity were independent prognostic factors (P = 0.0053 and 0.0093, respectively) along with stage (P = 0.002) in non-small cell lung cancer, but in the esophageal tumors, volume and heterogeneity had less complementary value because of smaller overall volumes.
  
  
  CONCLUSIONS
  Our results suggest that heterogeneity quantification and volume may provide valuable complementary information for volumes above 10 cm(3), although the complementary information increases substantially with larger volumes.
authors.affiliation: INSERM, UMR 1101 LaTIM, Brest, FRANCE hatt@univ-brest.fr.
authors.forename: Mathieu
authors.initials: M
authors.lastname: Hatt
authors.affiliation: INSERM, UMR 1101 LaTIM, Brest, FRANCE.
authors.forename: Mohamed
authors.initials: M
authors.lastname: Majdoub
authors.affiliation: Department of Oncology, McGill University, Montreal, Canada.
authors.forename: Martin
authors.initials: M
authors.lastname: Vallières
authors.affiliation: INSERM, UMR 1101 LaTIM, Brest, FRANCE Nuclear Medicine, CHU Milétrie, Poitiers, France.
authors.forename: Florent
authors.initials: F
authors.lastname: Tixier
authors.affiliation: INSERM, UMR 1101 LaTIM, Brest, FRANCE Nuclear Medicine, CHU Milétrie, Poitiers, France.
authors.forename: Catherine Cheze
authors.initials: CC
authors.lastname: Le Rest
authors.affiliation: Nuclear Medicine, CHU Saint Louis, Paris, France.
authors.forename: David
authors.initials: D
authors.lastname: Groheux
authors.affiliation: Nuclear Medicine, CHU Saint Louis, Paris, France.
authors.forename: Elif
authors.initials: E
authors.lastname: Hindié
authors.affiliation: Nuclear Medicine, CHU Saint Louis, Paris, France.
authors.forename: Antoine
authors.initials: A
authors.lastname: Martineau
authors.affiliation: INSERM, UMR 1101 LaTIM, Brest, FRANCE Radiotherapy, CHRU Morvan, Brest, France.
authors.forename: Olivier
authors.initials: O
authors.lastname: Pradier
authors.affiliation: Nuclear Medicine, CHU Liège, Liège, Belgium; and.
authors.forename: Roland
authors.initials: R
authors.lastname: Hustinx
authors.affiliation: Nuclear Medicine, CHU Milétrie, Poitiers, France.
authors.forename: Remy
authors.initials: R
authors.lastname: Perdrisot
authors.affiliation: Radiology, CHU Milétrie, Poitiers, France.
authors.forename: Remy
authors.initials: R
authors.lastname: Guillevin
authors.affiliation: Department of Oncology, McGill University, Montreal, Canada.
authors.forename: Issam
authors.initials: I
authors.lastname: El Naqa
authors.affiliation: INSERM, UMR 1101 LaTIM, Brest, FRANCE.
authors.forename: Dimitris
authors.initials: D
authors.lastname: Visvikis
mesh_terms: D001692:Biological Transport; D015331:Cohort Studies; D019788:Fluorodeoxyglucose F18 / Q000378:metabolism*; D006801:Humans; D009369:Neoplasms / Q000000981:diagnostic imaging* / Q000378:metabolism / Q000473:pathology*; D049268:Positron-Emission Tomography; D011379:Prognosis; D012189:Retrospective Studies; D016019:Survival Analysis; D047368:Tumor Burden
chemical_list: D019788:Fluorodeoxyglucose F18
keywords: 18FDG PET/CT; heterogeneity; metabolically active tumor volume; prognosis; textural features