title: The asphericity of the metabolic tumour volume in NSCLC: correlation with histopathology and molecular markers.
abstract: OBJECTIVE
  Asphericity (ASP) is a tumour shape descriptor based on the PET image. It quantitates the deviation from spherical of the shape of the metabolic tumour volume (MTV). In order to identify its biological correlates, we investigated the relationship between ASP and clinically relevant histopathological and molecular signatures in non-small-cell lung cancer (NSCLC).
  
  
  METHODS
  The study included 83 consecutive patients (18 women, aged 66.4 ± 8.9 years) with newly diagnosed NSCLC in whom PET/CT with18F-FDG had been performed prior to therapy. Primary tumour resection specimens and core biopsies were used for basic histopathology and determination of the Ki-67 proliferation index. EGFR status, VEGF, p53 and ALK expression were obtained in a subgroup of 44 patients. The FDG PET images of the primary tumours were delineated using an automatic algorithm based on adaptive thresholding taking into account local background. In addition to ASP, SUVmax, MTV and some further descriptors of shape and intratumour heterogeneity were assessed as semiquantitative PET measures.
  
  
  RESULTS
  SUVmax, MTV and ASP were associated with pathological T stage (Kruskal-Wallis, p = 0.001, p < 0.0005 and p < 0.0005, respectively) and N stage (p = 0.017, p = 0.003 and p = 0.002, respectively). Only ASP was associated with M stage (p = 0.026). SUVmax, MTV and ASP were correlated with Ki-67 index (Spearman's rho = 0.326/p = 0.003, rho = 0.302/p = 0.006 and rho = 0.271/p = 0.015, respectively). The latter correlations were considerably stronger in adenocarcinomas than in squamous cell carcinomas. ASP, but not SUVmax or MTV, showed a tendency for a significant association with the extent of VEGF expression (p = 0.058). In multivariate Cox regression analysis, ASP (p < 0.0005) and the presence of distant metastases (p = 0.023) were significantly associated with progression-free survival. ASP (p = 0.006), the presence of distant metastases (p = 0.010), and Ki-67 index (p = 0.062) were significantly associated with overall survival.
  
  
  CONCLUSIONS
  The ASP of primary NSCLCs on FDG PET images is associated with tumour dimensions and molecular markers of proliferation and angiogenesis.
authors.affiliation: Clinic of Radiology and Nuclear Medicine, University Hospital, Otto-von-Guericke University Magdeburg, Leipziger Strasse 44, 39120, Magdeburg, Germany. Ivayla.apostolova@med.ovgu.de.
authors.forename: Ivayla
authors.initials: I
authors.lastname: Apostolova
authors.affiliation: Clinic of Radiology and Nuclear Medicine, University Hospital, Otto-von-Guericke University Magdeburg, Leipziger Strasse 44, 39120, Magdeburg, Germany.
authors.forename: Kilian
authors.initials: K
authors.lastname: Ego
authors.affiliation: Clinic of Radiology and Nuclear Medicine, University Hospital, Otto-von-Guericke University Magdeburg, Leipziger Strasse 44, 39120, Magdeburg, Germany.
authors.forename: Ingo G
authors.initials: IG
authors.lastname: Steffen
authors.affiliation: Clinic of Nuclear Medicine, University Medicine Charité, Berlin, Germany.
authors.forename: Ralph
authors.initials: R
authors.lastname: Buchert
authors.affiliation: Lung Clinic Lostau GmbH, Lostau, Germany.
authors.forename: Heinz
authors.initials: H
authors.lastname: Wertzel
authors.affiliation: Lung Clinic Lostau GmbH, Lostau, Germany.
authors.forename: H Jost
authors.initials: HJ
authors.lastname: Achenbach
authors.affiliation: Clinic of Pneumology, University Hospital, Otto-von-Guericke University Magdeburg, Magdeburg, Germany.
authors.forename: Sandra
authors.initials: S
authors.lastname: Riedel
authors.affiliation: Clinic of Pneumology, University Hospital, Otto-von-Guericke University Magdeburg, Magdeburg, Germany.
authors.forename: Jens
authors.initials: J
authors.lastname: Schreiber
authors.affiliation: Institute of Pathology Stendal, Straße der Demokratie 1, Stendal, Germany.
authors.forename: Meinald
authors.initials: M
authors.lastname: Schultz
authors.affiliation: Clinic of Radiology and Nuclear Medicine, University Hospital, Otto-von-Guericke University Magdeburg, Leipziger Strasse 44, 39120, Magdeburg, Germany.|Clinic of Nuclear Medicine, University Medicine Charité, Berlin, Germany.
authors.forename: Christian
authors.initials: C
authors.lastname: Furth
authors.affiliation: Department of Nuclear Medicine, Hannover Medical School, Hannover, Germany.
authors.forename: Thorsten
authors.initials: T
authors.lastname: Derlin
authors.affiliation: Clinic of Radiology and Nuclear Medicine, University Hospital, Otto-von-Guericke University Magdeburg, Leipziger Strasse 44, 39120, Magdeburg, Germany.|Clinic of Nuclear Medicine, University Medicine Charité, Berlin, Germany.
authors.forename: Holger
authors.initials: H
authors.lastname: Amthauer
authors.affiliation: Helmholtz-Center Dresden-Rossendorf, Dresden, Germany.
authors.forename: Frank
authors.initials: F
authors.lastname: Hofheinz
authors.affiliation: Institute for Pathology, University Hospital Magdeburg, Otto-von-Guericke University Magdeburg, Magdeburg, Germany.|Institute for Pathology Lademannbogen, Hamburg, Germany.
authors.forename: Thomas
authors.initials: T
authors.lastname: Kalinski
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D000465:Algorithms; D014408:Biomarkers, Tumor / Q000378:metabolism*; D002289:Carcinoma, Non-Small-Cell Lung / Q000000981:diagnostic imaging / Q000378:metabolism* / Q000473:pathology*; D005260:Female; D019788:Fluorodeoxyglucose F18 / Q000493:pharmacokinetics; D006801:Humans; D007090:Image Interpretation, Computer-Assisted / Q000379:methods; D008175:Lung Neoplasms / Q000000981:diagnostic imaging / Q000378:metabolism* / Q000473:pathology*; D008297:Male; D008875:Middle Aged; D009367:Neoplasm Staging; D049268:Positron-Emission Tomography / Q000379:methods*; D019275:Radiopharmaceuticals / Q000493:pharmacokinetics; D015203:Reproducibility of Results; D012680:Sensitivity and Specificity; D047368:Tumor Burden
chemical_list: D014408:Biomarkers, Tumor; D019275:Radiopharmaceuticals; D019788:Fluorodeoxyglucose F18
keywords: Asphericity; FDG PET/CT; Histopathology; Intratumour heterogeneity; Molecular markers; Non-small cell lung cancer