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

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 o...

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Veröffentlicht in:Applied statistics 2008-04, Vol.57 (2), p.149-163
Hauptverfasser: Schipper, Matthew, Taylor, Jeremy M. G., Lin, Xihong
Format: Artikel
Sprache:eng
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Zusammenfassung: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.
ISSN:0035-9254
1467-9876
DOI:10.1111/j.1467-9876.2007.00606.x