Statistical Analysis of Occurrence of and Death from Oral Cancer with Multi-state Illness-Death Competing Risks Model
Date Issued
2014
Date
2014
Author(s)
Lee, Chia-Hsuan
Abstract
Background
An increasing trend of incidence of and mortality from oral cancer called for a nationwide secondary prevention through oral cancer screening with dental inspection in Taiwan. It is therefore of great interest to examine the survival of oral cancer while more proportion of early-detected oral cancer was noted. However, statistical analysis of early stage of oral cancer is subject to competing risks of death. In spite of wide applications of statistical competing risks model, very few studies were conducted to apply these statistical models to population-based cancer screening data. Moreover, it is also very rare to develop a multi-state illness-death model with the incorporation of competing risks of death as one of absorbing states. How to integrate the concept of cumulative incidence and subdistribution hazard into the illness-death competing risks model has been barely addressed.
Aims
The main purposes of this thesis were to develop a multi-state illness-death competing risks model so as to apply the proposed model to estimate cumulative incidence for occurrence of and death from oral cancer and also to estimate case-specific hazard (CSH) ratio and subdistribution hazard (SDH) ratio for the effect of betel quids on oral cancer death taking competing risks into account.
Data
Data on 2,332,430 Taiwanese residents aged 18 years or older attending the population-based screening for oral cancer with dental inspection from which 8009 oral cancer, and 2223 oral cancer deaths, together with 75582 and 667 deaths from competing causes among subjects free of oral cancer and patients of oral cancer, respectively, were ascertained. These data were exploited to estimate cumulative risk of occurrence of oral cancer and death from oral cancer. Information on betel quids chewing and smoking was also collected for assessing the CSH and SDH ratios for the effect of betel quids chewing.
Model Specification
A four-state illness-death model was proposed, including free of oral cancer (FOC) (State 1), oral cancer (State 2), oral cancer death (State 3), and competing risks of death (State 4). Both homogeneous (exponential) Markov model and non-homogeneous Weibull-based stochastic process were applied to estimating the parameters corresponding to each transition from state i to state j (i≤j, i, j=1, 2, 3, 4). Cumulative risks for each transition were estimated by using the corresponding transition probabilities.
The effect of betel quids on occurrence of oral cancer was assessed by cause-specific hazard (CSH) ratio and subdistribution hazard (SDH) ratio based on Gray and Fine idea.
Results
Cumulative risks with adjustment for competing risks of death for oral cancer and oral cancer death were slightly lower than those without considering competing risks of death. By using the proposed multi-state illness-death competing risks model, we predicted 10-year cumulative risks for occurrence of oral cancer were 0.20% and 0.27% with and without adjustment for competing risks of death, respectively. Both 10-year cumulative risk figures for oral cancer death were 67.4% and 81.98% for oral cancer patients, and 0.33% and 0.39% for the underlying screened population, respectively.
Using SDH ratio as opposed to cause-specific hazard (CSH) shows the effect of betel quids chewing varied with time of follow-up.
Conclusion
The proposed multi-state illness-death competing risks model permits one to predict long-term risk of multi-state outcome subject to presence of competing risks of death. Information provided from the results after the application of this model make contribution to the concern about overdiagnosis in population-based screen.
Subjects
瞬間風險比
多階段疾病-死亡競爭風險模式
口腔癌
SDGs
Type
thesis
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