目的：癌症病患確診年齡逐年降低，對於預後較佳的病患，需要考慮其晚期反應對於生活品質之影響。本研究分析鼻咽癌和乳癌病患經過強度調控放射治療 (Intensity modulation radiation therapy, IMRT)和動態弧形強度調控放射治療 (Volumetric-modulated arc therapy, VMAT)後發生二次癌症風險 (Secondary cancer risk, SCR)，幫助臨床對於放射治療決策參考之依據。
材料與方法：本論文收集回溯性病人資料分別為112位鼻咽癌 (Nasopharyngeal carcinoma , NPC)病患和90位乳癌 (Breast cancer, BC)病患，使用強度調控治療和動態弧形強度調控放射治療。鼻咽癌和乳癌病患分別以1：1的傾向分數配對(Propensity score-matched analysis, PSM)進行資料匹配，得到IMRT與VMAT之病患各為20位。分析目標器官的劑量-體積直方圖 (Dose-volume histogram, DVH)，導入線性 (Linear)、線性指數 (Linear-exponential, Lin-exp)、高原 (Plateau)和Schneider之風險等效劑量 (Risk equivalent dose, RED)反應模型，計算各器官等效劑量 (Organ equivalent dose, OED)。考慮病患之照射年紀，得到額外絕對危險度 (Excess absolute risk, EAR)。代入群體之生存曲線，得到終身歸因危險度 (Lifetime attributable risk, LAR)評估，建立二次癌症的風險評估模型。
結果：本研究比較四種二次癌症風險評估模型，線性模型明顯高估二次癌症風險，放射治療之不均勻劑量分佈對二次癌症風險評估有明顯之影響。在鼻咽癌病患中，兩種治療技術對增加二次癌症機會並未有顯著之差異，但VMAT有較高的累積風險。在乳癌病患中，IMRT對增加二次癌症機會有較顯著之影響，但須注意VMAT有對側肺部有增加二次癌症風險之慮。本研究結果顯示，除了治療時的吸收劑量會影響二次癌症風險結果，照射年齡與存活期亦會影響病患的二次癌症終生風險，但依據各器官對於輻射敏感度不同，不同部位會產生不同程度的二次癌症風險。本研究發現，無論照射範圍與器官吸收劑量，肺部是最容易被誘發二次癌症之器官，亦不隨病患照射年紀而改變。
結論：研究顯示VMAT有較優勢地劑量表現，但所增加的低劑量分佈，並未顯著地影響鼻咽癌和乳癌病患罹患二次癌症風險，但對於輻射較敏感的肺部，尤其是治療乳癌病患時，仍須注意VMAT對於患側之對側肺部可能產生的潛在風險。

Purpose: The age of cancer patients is decreasing year by year. For patients with better prognosis, the influence of late response on quality of life needs to be considered. This study analyzed the risk of secondary cancer after intensity modulated radiation therapy (IMRT) and volume-modulated arc therapy (VMAT) in patients with nasopharyngeal and breast cancers, helping the clinical radiation therapy decision-making.
Materials and methods: The retrospective patient data collected were 112 patients with nasopharyngeal carcinoma (NPC) and 90 breast cancer patients, using IMRT and VMAT. Patients with NPC and breast cancer were matched by the 1:1 propensity score matched evaluation, and 20 patients with IMRT and VMAT were obtained, respectively. For analysis of dose-volume histograms (DVHs), we used linear, linear-exponential, plateau and Schneider’s full response models, and calculated the organ equivalent dose (OED). Considering the patient's age of exposure, an excess absolute risk (EAR) is obtained. Substituting into the survival curve of the group, Lifetime attributable risk (LAR) assessment was conducted to establish the secondary cancer risk model for assessment.
Results: In this study, four secondary cancer risk (SCR) assessment models were compared. The linear model was significantly higher in SCR. The non-uniform dose distribution of radiation therapy had a significantly important on SCR assessment. In NPC patients, there is no significant difference in the two treatment techniques for increasing the chance of secondary cancer, but VMAT has a higher cumulative risk. In breast cancer patients, IMRT has a significant impact on increasing the chance of secondary cancer, but it should be noted that VMAT has an increased SCR in the contralateral lung. The results of this study show that the EAR after radiotherapy will affect the SCR. The age of exposure and survival will also affect the patient's LAR of secondary cancer. According to different organs for radiation sensitivity, different parts will produce varying degrees of SCR. This study found that regardless of the irradiation area and the absorbed dose of the organ, the lung is the most sensitive to SCR, and does not change with the age of the patient.
Conclusions: The results have shown that VMAT has superior dose performance, but the increased low-dose distribution does not significantly affect the SCR in NPC and breast cancer patients, but it is more sensitive to radiation in the lungs, especially in breast cancer patients. Contralateral lungs still have to pay attention to the potential risk of VMAT.

摘要 i
Abstract iii
致謝 v
目錄 vi
表目錄 viii
圖目錄 ix
符號縮寫 x
符號說明 xi
第一章 緒論 1
1.1 動機 1
1.2 目的 4
1.3 相關文獻探討 6
第二章 材料與方法 9
2.1 前言 9
2.2 病患資料 11
2.2.1 傾向分數配對 11
2.2.2 鼻咽癌病患之資料 14
2.2.3 乳癌病患之資料 15
2.3 治療技術 16
2.3.1 強度調控放射線治療 (Intensity-modulated Radiotherapy, IMRT) 16
2.3.2 動態弧形強度調控放射線治療 (Volumetric-modulated Arc Radiotherapy, VMAT) 17
2.3.3 鼻咽癌放射治療技術 18
2.3.4 乳癌放射治療技術 20
2.4 二次癌症風險預測模型介紹 22
2.4.1 前言 22
2.4.2 風險等效劑量 (Risk equivalent dose, RED) 23
2.4.3 器官等效劑量 (Organ equivalent dose, OED) 28
2.4.4 額外絕對風險 (Excess absolute risk, EAR) 30
2.4.5 終身歸因危險度 (Lifetime attributable risk, LAR) 31
2.5 統計方法介紹 32
第三章 結果 33
3.1 章節概述 33
3.2 前言 33
3.3 鼻咽癌放射治療誘發二次癌症之預測 34
3.3.1 鼻咽癌之器官等效劑量 36
3.3.2 鼻咽癌之額外絕對風險 43
3.3.3 鼻咽癌之終身歸因危險度評估 49
3.3 乳癌放射治療誘發二次癌症之預測 55
3.3.1 乳癌之器官等效劑量 56
3.3.2 乳癌之額外絕對風險 62
3.3.3 乳癌之終身歸因危險度評估 66
第四章 討論 70
4.1 章節概述 70
4.2 傾向分數配對對於分析二次癌症之影響 71
4.3 鼻咽癌患者經過放射治療後發生二次癌症之分析 72
4.4 乳癌患者經過放射治療後發生二次癌症之分析 73
4.5 放射治療時間點對於誘發二次癌症之影響 74
4.6 各器官之輻射敏感度對於二次癌症的影響 75
4.7 各器官之劑量分佈對於二次癌症的影響 76
4.8 二次癌症風險評估模型之差異 78
第五章 結論 80
5.1 研究總結 80
5.2 研究貢獻 80
5.3 未來研究目標 81
參考文獻 82

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