Bayesian Spatial Analysis of Cholangiocarcinoma in Northeast Thailand

Abstract

Background Cholangiocarcinoma (CCA) is a malignant neoplasm of the biliary tract. Infection with the liver flukes, Opisthorchis viverrini has been identified as an aetiological agent of CCA. Thailand reports the highest incidence of CCA in the world. The aim of this study was to map the distribution of CAA and identify spatial disease clusters in Northeast Thailand. Methods Individual-level data of patients with histopathologically confirmed CCA, aggregated at the sub-district level, were obtained from the Cholangiocarcinoma Screening and Care Program (CASCAP) between February 2013 and December 2017. A multivariate Zero-inflated, Poisson (ZIP) regression model was developed with a conditional autoregressive (CAR) prior structure and with posterior parameters estimated using Bayesian Markov chain Monte Carlo (MCMC) simulation with Gibbs sampling. Covariates included in the models were age, sex, normalized vegetation index (NDVI), and distance to water body. Findings There was a total of 1,299 cases out of 358,981 participants. CCA incidence increased 2.94 fold (95% credible interval [CrI] 2.62, 3.31) in patients >60 years as compared to ≤60 years. Males were 2.53 fold (95% CrI: 2.24, 2.85) more likely to have CCA when compared to females. CCA decreased with a 1 unit increase of NDVI (Relative Risk = 0.06; 95% CrI: 0.01, 0.63). The maps of the posterior means demonstrated evidence of spatial clustering after accounting for the model covariates. Interpretation Age, sex and environmental variables were associated with an increase in the incidence of CCA. The maps of the posterior means of the spatially structured random effects demonstrated evidence of spatial clustering after accounting for these covariates. Funding Khon Kaen University (KKU) through CASCAP (Grant No. CASCAP 1/60), the National Research Council of Thailand through the Medical Research Network of the Consortium of Thai Medical Schools (Grant No. MRF.59-076) and National Research Council of Thailand (NRCT/2559-134). Declaration of Interest: The authors declare that they have no competing interests. Ethical Approval: The use of Cholangiocarcinoma Screening and Care Program (CASCAP) data for this study was approved by the Khon Kaen University Ethics Committee for Human Research (HE611035). The CASCAP was conducted according to the principles of Good Clinical Practice, the Declaration of Helsinki, and national laws and regulations about clinical studies, and was approved by the Khon Kaen University Ethics Committee for Human Research under the reference number HE591067. All patients gave written informed consent for the CASCAP study.