臺灣博碩士論文加值系統

過去這幾年在台灣，大腸直腸癌的發生率已經快速地增加，目前已經是台灣第一常見的惡性腫瘤同時也是因癌症而死亡的第三個常見的原因。臨床上針對第Ⅱ及Ⅲ期的直腸癌病患，手術前同步化學放射治療不僅能降低術後局部復發率還可以有較高的機率保留肛門。化學放射治療後的病理分期與病患的無病存活率及總體存活率有相關，特別是在化學放射治療後癌細胞完全消失的病患，他們有很低的局部及遠端復發率。這幾年來我們仍然以原發性腫瘤侵犯的深度；局部淋巴結侵犯與否；以及是否出現轉移(TNM分期)來做為直腸癌病人術前接受同步化學放射治療的決定因子。本研究計畫的目的就是找出能夠預測化學放射治療後療效的相關因子，讓臨床醫師與病患選擇最適當的治療。這樣的個人化醫療相信能更進一步地提升直腸癌病人的預後。

The incidence of colorectal cancer (CRC) in Taiwan has been rapidly increasing in the past few years, and CRC is the second most common cancer and also the third leading cause of cancer death in Taiwan. For locally advanced rectal cancer (T3-4 or N1-2), preoperative chemoradiotherapy (CCRT) has been demonstrated to achieve a lower local recurrence rate and good sphincter preservation rate. Several prospective and retrospective analyses suggest that pathological stage of disease after preoperative CCRT has a significant prognostic impact on disease-free and overall survival. In particular, the subgroup of patients who achieve a complete pathological response has a very low risk of local or distant recurrence. Traditionally, it is usually depends on TNM stage to determine whether patient receives preoperative CCRT or not. This proposal is aimed to discover clinical factors that can increase the power to predict the efficacy of preoperative CCRT.

中文摘要…………………………………………………………………i
英文摘要…………………………………………………………………ii
致謝辭...................................................iii
目錄………………………………………………………………………iv
圖目錄……………………………………………………………………vi
表目錄…………………………………………………………………vii
附錄....................................................viii
第一章緒論
1.1 直腸癌概述...........................................1
1.1.1 流行病學概況.....................................1
1.1.2 臨床症狀與診斷...................................1
1.1.3 直腸癌的病理結構以及分期.........................1
1.1.4 直腸癌的治療.....................................4
1.1.5 直腸癌的預後.....................................6
1.1.6 治療的副作用.....................................6
1.2放射線治療的技術........................................6
1.2.1 什麼是放射線治療.................................6
1.2.2 放射線治療是如何發生作用的.......................6
1.2.3 放射線治療的目標好處是什麼.......................7
1.2.4 放射線治療的進展.................................7
1.3 直腸癌的化學治療......................................9
1.3.1直腸癌化學治療的目的..............................9
1.3.2 5-FU的作用機轉及臨床應用.........................9
1.3.3 Capecitabine的作用機轉及臨床應用...............10
1.3.4 Oxaliplatin的作用機轉及臨床應用................10
第二章研究目標............................................12
第三章材料與方法..........................................13
3.1 病患族群與診斷檢查...................................13
3.2 手術術式與病理分析..................................14
3.3 放射線治療..........................................14
3.4 化學治療............................................15
3.5 統計方法............................................15
第四章結果................................................17
4.1 臨床分期 vs. 病理分期...............................17
4.2 總體存活率與無病存活率..............................18
4.3接受不同的放射線治療方式的病例有不同的臨床特徵分布...19
4.4局部復發與遠端轉移復發...............................20
4.5 預測病理完全反應（pathologic complete response）的臨床
因素................................................20
4.6 手術術式與肛門的保留................................21
4.7 治療相關的毒性......................................22
第五章討論................................................23
第六章結論................................................28
6.1 現今臨床應用之管見....................................28
6.2 未來研究之方向........................................28
參考文獻..................................................30

圖目錄
圖一、局部進行期或低位直腸癌病患總體存活率................40
圖二、局部進行期或低位直腸癌病患無病存活率................41
圖三、病理上沒有殘存任何癌細胞者有較佳的總體存活率........42
圖四、病理上沒有殘存任何癌細胞者有較佳的無病存活率........43
圖五、分化較差的腫瘤相較於分化較好的腫瘤有較差的總體存活率........................................................44
圖六、接受Tomotherapy的直腸癌病患相較於另外兩種治療技術有較好的總體存活率............................................45
圖七、腫瘤有神經旁的侵犯相較於無神經旁侵犯的腫瘤有較差的5年總體存活率................................................46
圖八、腫瘤有血管淋巴管旁的侵犯相較於無血管淋巴管旁侵犯的腫瘤有較差的4年總體存活率.....................................47
圖九、腫瘤有神經旁的侵犯相較於無神經旁侵犯的腫瘤有較差的無病存活率的趨勢..............................................48
圖十、腫瘤有血管淋巴管旁的侵犯相較於無血管淋巴管旁侵犯的腫瘤有較差的無病存活率的趨勢..................................49
圖十一、病理的腫瘤分期與無病存活率的相關..................50
圖十二、病理的淋巴分期與無病存活率的相關..................51
圖十三、病理的總分期與無病存活率的相關....................52
圖十四、病理的淋巴分期與總體存活率的相關..................53
圖十五、病理的總分期與總體存活率的相關....................54

表目錄
表一、本研究所有個案的病患與腫瘤特徵......................55
表二、臨床vs. 病理腫瘤分期................................56
表三、同步化放療後整體癌症分期下降的情形..................57
表四、個案的病患與腫瘤特徵（依據病患接受不同的放射線療法來分組）......................................................58
表五、以單變數分析來找出與局部復發有關的因子..............59
表六、以多變數分析來找出與局部復發有關的因子..............61
表七、以單變數分析來找出與遠端復發有關的因子..............62
表八、以多變數分析來找出與遠端復發有關的因子..............64
表九、以單變數分析來找出與病理完全反應有關的因子..........65
表十、病患接受的治療方式與藥物............................66
表十一、肛門保留率........................................67
表十二、CTCAE第三或第四級與手術後的副作用發生率...........68
表十三、與文獻發表之臨床研究比較肛門保留的比率............69

附錄
附錄一、直腸癌TNM分期（TNM與Duke’s，MAC系統的對照表）總表........................................................70
附錄二、5-fluorouracil的代謝..............................71
附錄三、5-fluorouracil抑制thymidylate synthase的作用機轉..72
附錄四、5-fluorouracil活性的調控..........................73

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