Statistical assessment of treatment response in a cancer patient based on pre-therapy and post-therapy FDG-PET scans
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Accepted Version
Date
2016-12-18
Authors
Wolsztynski, Eric
O'Sullivan, Finbarr
O'Sullivan, Janet
Eary, Janet F.
Journal Title
Journal ISSN
Volume Title
Publisher
Wiley
Published Version
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.
Description
Keywords
Therapeutic effectiveness , Percentage change in mean , Paired analysis , Patient-adaptive treatment , Gamma distribution
Citation
Wolsztynski, E., O'Sullivan, F., O'Sullivan, J. and Eary, J. F. (2016) 'Statistical assessment of treatment response in a cancer patient based on pre-therapy and post-therapy FDG-PET scans', Statistics in Medicine, 36(7), pp. 1172-1200. doi:10.1002/sim.7198
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Copyright
© 2016 John Wiley & Sons, Ltd. This is the peer reviewed version of the following article: Wolsztynski, E., O'Sullivan, F., O'Sullivan, J. and Eary, J. F. (2016) 'Statistical assessment of treatment response in a cancer patient based on pre-therapy and post-therapy FDG-PET scans', Statistics in Medicine, 36(7), pp. 1172-1200, which has been published in final form at http://dx.doi.org/10.1002/sim.7198. This article may be used for non-commercial purposes in accordance with Wiley Terms and Conditions for Self-Archiving.