A flexible multivariate random effects proportional odds model with application to adverse effects during radiation therapy

DOI10.1002/BIMJ.201600142zbMATH Open1379.62064arXiv1602.08360OpenAlexW2273999248WikidataQ38686278 ScholiaQ38686278MaRDI QIDQ4597945FDOQ4597945

Authors: Nicole H. Augustin, Sung Won Kim, Annemarie Uhlig, Christina Hanser, Michael Henke, Martin Schumacher 

Publication date: 14 December 2017

Published in: Biometrical Journal (Search for Journal in Brave)

Abstract: Radiation therapy in patients with head and neck cancer has a toxic effect on mucosa, the soft tissue in and around the mouth. Hence mucositis is a serious common side effect and is a condition characterized by pain and inflammation of the surface of the mucosa. Although the mucosa recovers during breaks of and following the radiotherapy course the recovery will depend on the type of tissue involved and on its location. We present a novel flexible multivariate random effects proportional odds model which takes account of the longitudinal course of oral mucositis at different mouth sites and of the radiation dosage (in terms of cumulative dose). The model is an extension of the {em proportional odds model} which is used for ordinal response variables. Our model includes the ordinal multivariate response of the mucositis score by location, random intercepts for individuals and includes a non-linear function of cumulative radiation dose. The model allows to test whether sensitivity differs by mouth sites after having adjusted for site specific cumulative radiation dose. The model also allows to check whether and how the (non-linear) effect of site specific dose differs by site. We fit the model to longitudinal patient data from a prospective observation and find that after adjusting for cumulative dose, upper, lower lips and mouth floor are associated with the lowest mucositis scores and hard and soft palate are associated with the highest mucositis scores. This implies the possibility that tissues at different mouth locations differ in their sensitivity to the toxic effect of radiation. We also find that cumulative dose followed by mouth site are the strongest predictors of mucositis, and the effects of age and gender are negligible.

Full work available at URL: https://arxiv.org/abs/1602.08360

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zbMATH Keywords

proportional odds modelradiation therapymultivariate repeated measuresgeneralized additive mixed modelordered categorical responsecumulative threshold modelmucositis

Mathematics Subject Classification ID

Applications of statistics to biology and medical sciences; meta analysis (62P10) Estimation in multivariate analysis (62H12)

Cited In (4)

• Generalized Monotonic Functional Mixed Models with Application to Modelling Normal Tissue Complications
• A shared frailty model for multivariate longitudinal data on adverse event of radiation therapy
• Statistical models for multivariate longitudinal data with application to the development of side effects during radiation therapy
• A Bayesian mixture model relating dose to critical organs and functional complication in 3D conformal radiation therapy

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