title: Statistical assessment of treatment response in a cancer patient based on pre-therapy and post-therapy FDG-PET scans.
abstract: This work arises from consideration of sarcoma patients in which fluorodeoxyglucose positron emission tomography (FDG-PET) imaging pre-therapy and post-chemotherapy is used to assess treatment response. Our focus is on methods for evaluation of the statistical uncertainty in the measured response for an individual patient. The gamma distribution is often used to describe data with constant coefficient of variation, but it can be adapted to describe the pseudo-Poisson character of PET measurements. We propose co-registering the pre-therapy and post- therapy images and modeling the approximately paired voxel-level data using the gamma statistics. Expressions for the estimation of the treatment effect and its variability are provided. Simulation studies explore the performance in the context of testing for a treatment effect. The impact of misregistration errors and how test power is affected by estimation of variability using simplified sampling assumptions, as might be produced by direct bootstrapping, is also clarified. The results illustrate a marked benefit in using a properly constructed paired approach. Remarkably, the power of the paired analysis is maintained even if the pre-image and post- image data are poorly registered. A theoretical explanation for this is indicated. The methodology is further illustrated in the context of a series of fluorodeoxyglucose-PET sarcoma patient studies. These data demonstrate the additional prognostic value of the proposed treatment effect test statistic. Copyright © 2016 John Wiley & Sons, Ltd.
authors.affiliation: School of Mathematical Sciences, University College Cork, Cork, Ireland.
authors.forename: E
authors.initials: E
authors.lastname: Wolsztynski
authors.affiliation: School of Mathematical Sciences, University College Cork, Cork, Ireland.
authors.forename: F
authors.initials: F
authors.lastname: O'Sullivan
authors.affiliation: School of Mathematical Sciences, University College Cork, Cork, Ireland.
authors.forename: J
authors.initials: J
authors.lastname: O'Sullivan
authors.affiliation: Department of Radiology, University of Alabama, Birmingham, U.S.A.
authors.forename: J F
authors.initials: JF
authors.lastname: Eary
mesh_terms: D000970:Antineoplastic Agents / Q000627:therapeutic use; D016001:Confidence Intervals; D003627:Data Interpretation, Statistical; D019788:Fluorodeoxyglucose F18; D006801:Humans; D053208:Kaplan-Meier Estimate; D016014:Linear Models; D015233:Models, Statistical; D015999:Multivariate Analysis; D049268:Positron-Emission Tomography / Q000379:methods; D011379:Prognosis; D015203:Reproducibility of Results; D012509:Sarcoma / Q000175:diagnosis / Q000000981:diagnostic imaging / Q000188:drug therapy*; D016896:Treatment Outcome
chemical_list: D000970:Antineoplastic Agents; D019788:Fluorodeoxyglucose F18
keywords: gamma distribution; paired analysis; patient-adaptive treatment; percentage change in mean; therapeutic effectiveness