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Generalized monotonic functional mixed models with application to modelling normal tissue complications

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  • Matthew Schipper
  • Jeremy M. G. Taylor
  • Xihong Lin

Abstract

Normal tissue complications are a common side effect of radiation therapy. They are the consequence of the dose of radiation that is received by the normal tissue surrounding the site of the tumour. Within a specified organ each voxel receives a certain dose of radiation, leading to a distribution of doses over the organ. It is often not known what aspect of the dose distribution drives the presence and severity of the complications. A summary measure of the dose distribution can be obtained by integrating a weighting function of dose ("w"("d")) over the density of dose. For biological reasons the weight function should be monotonic. We propose a generalized monotonic functional mixed model to study the dose effect on a clinical outcome by estimating this weight function non-parametrically by using splines and subject to the monotonicity constraint, while allowing for overdispersion and correlation of multiple obervations within the same subject. We illustrate our method with data from a head and neck cancer study in which the irradiation of the parotid gland results in loss of saliva flow. Copyright (c) 2008 Royal Statistical Society.

Suggested Citation

  • Matthew Schipper & Jeremy M. G. Taylor & Xihong Lin, 2008. "Generalized monotonic functional mixed models with application to modelling normal tissue complications," Journal of the Royal Statistical Society Series C, Royal Statistical Society, vol. 57(2), pages 149-163.
  • Handle: RePEc:bla:jorssc:v:57:y:2008:i:2:p:149-163
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