A Bayesian hierarchical mixture model for platelet-derived growth factor receptor phosphorylation to improve estimation of progression-free survival in prostate cancer

Abstract

Advances in understanding the biological underpinnings of many cancers have led increasingly to the use of molecularly targeted anticancer therapies. Because the platelet-derived growth factor receptor (PDGFR) has been implicated in the progression of prostate cancer bone metastases, it is of great interest to examine possible relationships between PDGFR inhibition and therapeutic outcomes. We analyse the association between change in activated PDGFR (phosphorylated PDGFR) and progression-free survival time based on large within-patient samples of cell-specific phosphorylated PDGFR values taken before and after treatment from each of 88 prostate cancer patients. To utilize these paired samples as covariate data in a regression model for progression-free survival time, and be cause the phosphorylated PDGFR distributions are bimodal, we first employ a Bayesian hierarchical mixture model to obtain a deconvolution of the pretreatment and post-treatment within-patient phosphorylated PDGFR distributions. We evaluate fits of the mixture model and a non-mixture model that ignores the bimodality by using a supnorm metric to compare the empirical distribution of each phosphorylated PDGFR data set with the corresponding fitted distribution under each model. Our results show that first using the mixture model to account for the bimodality of the within-patient phosphorylated PDGFR distributions, and then using the posterior within-patient component mean changes in phosphorylated PDGFR so obtained as covariates in the regression model for progression-free survival time, provides an improved estimation. © 2010 Royal Statistical Society.