現今質子治療計畫中以定量(constant)相對生物效應(relative biological effectiveness, RBE)來規劃治療計畫，然而RBE是會隨著分次劑量、直線能量轉移(linear energy transfer, LET)、細胞種類與生物終點而變動的，尤其在質子治療領域中，LET與RBE呈現正相關，會於質子射程遠端有升高的趨勢，此現象顯示考量變量(variable) RBE的必要性，透過將變量RBE納入治療計畫才可評估更準確之治療成效。本研究將熱發光劑量計(thermoluminescent dosimeter, TLD)量測LET之系統應用於質子治療攝護腺癌，以臨床射束條件對擬人假體中之TLD進行照射，分析假體內量測之劑量與LET，並透過RBE模型來將LET轉換為變量RBE，使TLD可作為體內(in-vivo)量測變量RBE之工具，未來亦可作為體內驗證RBE之工具來使用。
　　為了使用TLD量測LET，本研究首先比較高溫比值法與峰比值法所建立之LET量測系統對於臨床之適用性，藉由觀察TLD使用兩種方法下之量測結果與TOPAS蒙地卡羅模擬結果之相近程度來選擇一種較適合臨床使用的系統進行後續評估。對於臨床應用的部分，因攝護腺對輻射較敏感(α/β較小)，RBE較大，對於觀察RBE變化相對容易，因此選用質子治療攝護腺癌作為臨床應用案例。針對常規治療攝護腺方式(bilateral fields, BL)與新興照射方式(anterior oblique fields, AO)進行文獻回顧後，發現於靶深度、靶體積與組織不均性上兩者具有差異，因此對這三個因素進行LET依存性的評估。最後，以BL與AO射束照射擬人假體中之TLD，取得假體內之劑量與LET，透過RBE模型轉換為變量RBE與生物劑量，對兩種照射方式之結果進行分析。
　　採用變量RBE來優化質子治療計畫是未來趨勢，如何進行體內驗證為一重要議題，本研究透過將建立之LET量測系統應用於臨床質子治療攝護腺癌中，成功證明TLD量測LET系統適用於臨床，且TLD有能力作為劑量與變量RBE體內驗證之工具來使用。

　　Currently, the treatment planning systems (TPSs) in proton radiation therapy are based on the assumption of constant relative biological effectiveness (RBE) of 1.1. However, there is experimental evidence that proton RBE varies with the linear energy transfer (LET), dose per fraction, tissue type and biological endpoint. Due to the positive correlation between LET and RBE at the distal proton range, it is necessary to take the variable RBE into account for TPSs. The purpose of this study is to apply the LET measurement system with thermoluminescent dosimeters (TLD) to clinical prostate proton therapy, analyzing the dose and LET in anthropomorphic phantom by TLD and converting to variable RBE. In this way, TLD can be a useful tool for in-vivo verification of variable RBE.
　　In order to measure LET by TLD, the clinical applicability between high temperature method based and peak ratio method based LET measurement systems are accessed in this study. For selecting a proper system for LET analysis, we compare the TLD measurements and the TOPAS Monte Carlo simulation results in these two methods. For clinical application, due to the higher radiosensitivity (lower α/β ratio) of prostate, it is easier to observe the elevations of RBE in prostate cancer proton therapy. Therefore, we decide to compare the LET between standard bilateral (BL) fields and anterior oblique (AO) fields in treating prostate cancer. Because the target depth, target volume and tissue heterogeneity in these two fields are different, it is essential to evaluate the LET dependence on these factors. Lastly, TLDs are irradiated by BL and AO fields in an anthropomorphic phantom. In order to assess variable RBE weighted biological dose of BL and AO fields, the dose and LET measured by TLDs are converted to variable RBE through the RBE model.
　　The use of variable RBE to optimize proton therapy plans is a future trend. Therefore, how to measure the in-vivo variable RBE is a vital issue. The results of this study prove that TLD can be used as a tool for in-vivo dose and variable RBE verification.

摘要 i
Abstract ii
致謝 iv
目錄 v
表目錄 viii
圖目錄 ix
第一章 緒論 1
1.1 研究動機與目的 1
1.2 研究方法與步驟 2
1.3 研究範圍與限制 3
1.4 名詞解釋 4
第二章 介紹與文獻回顧 7
2.1 直線能量轉移之量測 7
2.1.1 阻擋本領與直線能量轉移 7
2.1.2 直線能量轉移偵檢器 8
2.1.3 熱發光劑量計原理 9
2.1.4 高溫比值法與峰比值法 12
2.1.5 直線能量轉移量測系統 14
2.2 相對生物效應 17
2.2.1 線性二次模型 17
2.2.2 相對生物效應模型 18
2.3 蒙地卡羅模擬 19
2.3.1 TOPAS簡介 20
2.3.2 模擬質子治療機 21
2.3.3 紀錄直線能量轉移之方法 22
2.4 質子治療攝護腺癌 23
2.4.1 質子治療技術簡介 23
2.4.2 質子治療攝護腺癌 24
2.4.3 質子治療之體內驗證 25
第三章 研究設計與方法 29
3.1 直線能量轉移量測系統 30
3.1.1 高溫比值法與峰比值法 30
3.1.2 直線能量轉移量測系統之優化 32
3.1.3 直線能量轉移量測系統之臨床適用性 32
3.2 直線能量轉移依存性 35
3.2.1 靶體積與靶深度 36
3.2.2 組織不均性 36
3.3 質子治療攝護腺癌之擬人假體量測 38
3.3.1 劑量與直線能量轉移量測 38
3.3.2 生物劑量評估 40
第四章 結果與討論 41
4.1 直線能量轉移量測系統之臨床適用性 41
4.1.1 高溫比值方法 41
4.1.2 峰比值方法 42
4.1.3 直線能量轉移量測系統之臨床適用性評比 45
4.2 直線能量轉移依存性 47
4.3 質子治療攝護腺癌之擬人假體量測 49
4.4 變量RBE加權之生物劑量評估 51
第五章 結論與未來展望 55
參考資料 56

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