復發事件存活時間分析-Thiotepa對膀胱癌病患復發療效之案例研究

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黃兆良(Chau-liang Huang) 查詢紙本館藏

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統計研究所

論文名稱

復發事件存活時間分析-Thiotepa對膀胱癌病患復發療效之案例研究
(Survival analysis for recurrent event data-a case study on the treatment effects of thiotepa to the bladder cancer patients’recurrence)

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摘要(中)

根據行政院衛生署2009年統計，膀胱癌為台灣地區最常見的泌尿系統癌症且為國人主要癌症死亡排名第十三位。表淺型膀胱癌多為低惡性度癌症，大部分可以經尿道切除術切除，並輔以膀胱內灌注法預防腫瘤復發。我們感興趣的是膀胱癌輔以膀胱內灌注Thiotepa對於膀胱癌病患復發事件之療效，本篇使用退伍軍人管理局合作泌尿學研究團隊86個膀胱癌病患資料，為研究膀胱內灌注Thiotepa療程，對於膀胱癌病患復發的次數以及存活時間的影響，探討比較多維事件存活時間的三種邊際模型（marginal model）：AG模型、PWP模型、WLW模型與脆弱模型（frailty model）。

摘要(英)

According to the Department of Health statistics in 2007, Bladder cancer is the most common genitourinary tumor ranked at the thirteenth important cancer in Taiwan. Most tumors of superficial bladder cancer are low grade cancers which can be removed by transurethral resection, supplemented by intravesical therapy in order to prevent the recurrence. We are interested in the treatment effects of thiotepa to the 86 bladder cancer patients’ recurrence from Vetrans Administration cooperative urological research group. To investigate this research problem, we focus on three marginal models (AG model, WLW model, and PWP model) and frailty models approaches of multivariate survival data analysis. In addition to studying the effect of thiotepa to bladder cancer patients’ recurrence and survival times under different models, we compare the performance of these approaches as well.

關鍵字(中)

★ 復發事件
★ 邊際模型
★ Thiotepa
★ 膀胱癌
★ 脆弱模型

關鍵字(英)

★ bladder cancer
★ frailty model
★ marginal model
★ thiotepa
★ repeated events

論文目次

Abstract i
摘要 ii
誌謝辭 iii
目錄 v
圖目次 vii
表目次 viii
第一章緒論 1
1.1 膀胱癌 1
1.2 研究方法文獻回顧 6
1.2.1 邊際模型 9
1.2.2 脆弱模型 10
1.3 研究架構 12
第二章模型方法 13
2.1 符號定義與基本假設 13
2.2 邊際模型（Marginal Model） 14
2.2.1 PWP邊際模型 18
2.2.2 AG邊際模型 19
2.2.3 WLW邊際模型 20
2.2.4 適當的模型配適 21
2.3 邊際模型參數估計 22
2.3.1 夾擠變異數估計量（Sandwich Variance Estimators） 24
2.4 脆弱模型(Frailty model) 25
2.4.1 脆弱模型參數估計 28
2.4.2 PPL（Penalized Partial Likelihood）演算法 29
2.4.3 脆弱參數分佈與懲罰函數 31
第三章模擬研究 32
3.1 模擬方法設定 32
3.2 模擬結果 35
3.2.1 每位觀測者事件發生之間相互獨立 35
3.2.2 每位觀測者事件發生之間具有相關性 38
3.2.3 總結 39
第四章實例分析 41
4.1 資料說明 41
4.2 敘述性資料分析 42
4.3 無母數方法分析 46
4.3.1 Kaplan-Meier 估計量 46
4.3.2 無母數假設檢定 53
4.4模型估計 54
4.4.1 PWP模型 55
4.4.2 脆弱模型 58
第五章結論與建議 61
5.1結論 61
5.2 建議 63
參考文獻 65
附錄A. 樣本數為100的模擬結果 69
附錄B. 樣本數為500的模擬結果 81

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指導教授

曾議寬(Yi-kuan Tseng)

審核日期

2010-7-6

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