Statistical assessment of treatment response in a cancer patient based on pre-therapy and post-therapy FDG-PET scans

dc.contributor.authorWolsztynski, Eric
dc.contributor.authorO'Sullivan, Finbarr
dc.contributor.authorO'Sullivan, Janet
dc.contributor.authorEary, Janet F.
dc.contributor.funderNational Institutes of Healthen
dc.contributor.funderScience Foundation Irelanden
dc.date.accessioned2017-01-20T12:12:29Z
dc.date.available2017-01-20T12:12:29Z
dc.date.issued2016-12-18
dc.date.updated2017-01-20T11:53:52Z
dc.description.abstractThis 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.en
dc.description.sponsorshipNational Institutes of Health, USA (CA-65537 and CA-42045); Science Foundation Ireland (11/PI/1027)en
dc.description.statusPeer revieweden
dc.description.versionAccepted Versionen
dc.format.mimetypeapplication/pdfen
dc.identifier.citationWolsztynski, 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.7198en
dc.identifier.doi10.1002/sim.7198
dc.identifier.endpage1200
dc.identifier.issn1097-0258
dc.identifier.issued7
dc.identifier.journaltitleStatistics In Medicineen
dc.identifier.startpage1172
dc.identifier.urihttps://hdl.handle.net/10468/3486
dc.identifier.volume36
dc.language.isoenen
dc.publisherWileyen
dc.rights© 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.en
dc.subjectTherapeutic effectivenessen
dc.subjectPercentage change in meanen
dc.subjectPaired analysisen
dc.subjectPatient-adaptive treatmenten
dc.subjectGamma distributionen
dc.titleStatistical assessment of treatment response in a cancer patient based on pre-therapy and post-therapy FDG-PET scansen
dc.typeArticle (peer-reviewed)en
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