title: Current measures of metabolic heterogeneity within cervical cancer do not predict disease outcome.
abstract: BACKGROUND
  A previous study evaluated the intra-tumoral heterogeneity observed in the uptake of F-18 fluorodeoxyglucose (FDG) in pre-treatment positron emission tomography (PET) scans of cancers of the uterine cervix as an indicator of disease outcome. This was done via a novel statistic which ostensibly measured the spatial variations in intra-tumoral metabolic activity. In this work, we argue that statistic is intrinsically non-spatial, and that the apparent delineation between unsuccessfully- and successfully-treated patient groups via that statistic is spurious.
  
  
  METHODS
  We first offer a straightforward mathematical demonstration of our argument. Next, we recapitulate an assiduous re-analysis of the originally published data which was derived from FDG-PET imagery. Finally, we present the results of a principal component analysis of FDG-PET images similar to those previously analyzed.
  
  
  RESULTS
  We find that the previously published measure of intra-tumoral heterogeneity is intrinsically non-spatial, and actually is only a surrogate for tumor volume. We also find that an optimized linear combination of more canonical heterogeneity quantifiers does not predict disease outcome.
  
  
  CONCLUSIONS
  Current measures of intra-tumoral metabolic activity are not predictive of disease outcome as has been claimed previously. The implications of this finding are: clinical categorization of patients based upon these statistics is invalid; more sophisticated, and perhaps innately-geometric, quantifications of metabolic activity are required for predicting disease outcome.
authors.affiliation: Department of Radiation Oncology, Washington University School of Medicine, 4921 Parkview Place, Saint Louis MO 63110, USA. fbrooks@radonc.wustl.edu
authors.forename: Frank J
authors.initials: FJ
authors.lastname: Brooks
authors.forename: Perry W
authors.initials: PW
authors.lastname: Grigsby
mesh_terms: D002584:Cervix Uteri / Q000000981:diagnostic imaging / Q000528:radiation effects; D003287:Contrast Media; D003627:Data Interpretation, Statistical; D005260:Female; D019788:Fluorodeoxyglucose F18; D006801:Humans; D008962:Models, Theoretical; D009362:Neoplasm Metastasis; D049268:Positron-Emission Tomography / Q000379:methods; D011237:Predictive Value of Tests; D015203:Reproducibility of Results; D016896:Treatment Outcome; D002583:Uterine Cervical Neoplasms / Q000628:therapy*
chemical_list: D003287:Contrast Media; D019788:Fluorodeoxyglucose F18