title: (18)F-FDG PET/CT imaging in rectal cancer: relationship with the RAS mutational status.
abstract: OBJECTIVE
  Treating metastatic colorectal cancer with anti-EGFR monoclonal antibodies is recommended only for patients whose tumour does not harbour mutations of KRAS or NRAS. The aim of this study was to investigate the biology of rectal cancers and specifically to evaluate the relationship between fluorine-18 fludeoxyglucose ((18)F-FDG) positron emission tomography (PET) intensity and heterogeneity parameters and their mutational status.
  
  
  METHODS
  151 patients with newly diagnosed rectal cancer were included in this retrospective study. All patients underwent a baseline (18)F-FDG PET/CT within a median time interval of 27 days of tumour tissue sampling, which was performed before any treatment. Standardized uptake values (SUVs), volume-based parameters and texture analysis were studied. We retrospectively performed KRAS genotyping on codons 12, 13, 61, 117 and 146, NRAS genotyping on codons 12, 13 and 61 and BRAF on codon 600. Associations between PET/CT parameters and the mutational status were assessed using univariate and multivariate analysis.
  
  
  RESULTS
  83 (55%) patients had an RAS mutation: 74 KRAS and 9 NRAS, while 68 patients had no mutation (wild-type tumours). No patient had BRAF mutation. First-order features based on intensity histogram analysis were significantly associated with RAS mutations: maximum SUV (SUVmax) (p-value = 0.002), mean SUV (p-value = 0.006), skewness (p-value = 0.049), SUV standard deviation (p-value = 0.001) and SUV coefficient of variation (SUVcov) (p-value = 0.001). Both SUVcov and SUVmax showed an area under the curve of 0.65 with sensitivity of 56% and 69%, respectively, and specificity of 64% and 52%, respectively. None of the volume-based (metabolic tumour volume and total lesion glycolysis), nor local or regional textural features were associated with the presence of RAS mutations.
  
  
  CONCLUSIONS
  Although rectal cancers with KRAS or NRAS mutations display a significantly higher glucose metabolism than wild-type cancers, the accuracy of the currently proposed quantitative metrics extracted from (18)F-FDG PET/CT is not sufficiently high for playing a meaningful clinical role.
  
  
  CONCLUSIONS
  RAS-mutated rectal cancers have a significantly higher glucose metabolism. However, the accuracy of (18)F-FDG PET/CT quantitative metrics is not as such as the technique could play a clinical role.
authors.affiliation: 1 Nuclear Medicine and Oncological Imaging Division, Medical Physics Department, Centre Hospitalier Universitaire de Liège, Liège, Belgium.
authors.forename: Pierre
authors.initials: P
authors.lastname: Lovinfosse
authors.affiliation: 2 Center for Human Genetic, Molecular Haemato-Oncology Unit, UniLab Lg, Centre Hospitalier Universitaire de Liège, Liège, Belgium.
authors.forename: Benjamin
authors.initials: B
authors.lastname: Koopmansch
authors.affiliation: 2 Center for Human Genetic, Molecular Haemato-Oncology Unit, UniLab Lg, Centre Hospitalier Universitaire de Liège, Liège, Belgium.
authors.forename: Frederic
authors.initials: F
authors.lastname: Lambert
authors.affiliation: 3 Department of Medical Physics, Centre Hospitalier Universitaire de Liège, Liège, Belgium.
authors.forename: Sébastien
authors.initials: S
authors.lastname: Jodogne
authors.affiliation: 4 Department of Pathology, Centre Hospitalier Universitaire de Liège, Liège, Belgium.
authors.forename: Gaelle
authors.initials: G
authors.lastname: Kustermans
authors.affiliation: 5 LaTIM, INSERM UMR 1101, IBSAM, University of Brest, France.
authors.forename: Mathieu
authors.initials: M
authors.lastname: Hatt
authors.affiliation: 5 LaTIM, INSERM UMR 1101, IBSAM, University of Brest, France.
authors.forename: Dimitris
authors.initials: D
authors.lastname: Visvikis
authors.affiliation: 6 Department of Biostatistics and Medico-economic Information, Centre Hospitalier Universitaire de Liège, Liège, Belgium.
authors.forename: Laurence
authors.initials: L
authors.lastname: Seidel
authors.affiliation: 7 Department of Gastro-enterology, Centre Hospitalier Universitaire de Liège, Belgium.
authors.forename: Marc
authors.initials: M
authors.lastname: Polus
authors.affiliation: 6 Department of Biostatistics and Medico-economic Information, Centre Hospitalier Universitaire de Liège, Liège, Belgium.
authors.forename: Adelin
authors.initials: A
authors.lastname: Albert
authors.affiliation: 4 Department of Pathology, Centre Hospitalier Universitaire de Liège, Liège, Belgium.
authors.forename: Philippe
authors.initials: P
authors.lastname: Delvenne
authors.affiliation: 1 Nuclear Medicine and Oncological Imaging Division, Medical Physics Department, Centre Hospitalier Universitaire de Liège, Liège, Belgium.
authors.forename: Roland
authors.initials: R
authors.lastname: Hustinx
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D005260:Female; D019788:Fluorodeoxyglucose F18; D011905:Genes, ras / Q000235:genetics*; D006801:Humans; D008297:Male; D008875:Middle Aged; D009154:Mutation; D000072078:Positron Emission Tomography Computed Tomography; D019275:Radiopharmaceuticals; D012004:Rectal Neoplasms / Q000000981:diagnostic imaging* / Q000235:genetics*; D012007:Rectum / Q000000981:diagnostic imaging; D012189:Retrospective Studies
chemical_list: D019275:Radiopharmaceuticals; D019788:Fluorodeoxyglucose F18