清華大學水池式反應爐使用的硼中子捕獲治療之治療計畫系統共有三種，包含THORplan、NTHUplan和INSIGHT。三種治療計畫系統架構的整體是相似的，但於細節上仍有差異之處，導致即使使用相同參數條件進行計算，劑量結果也會有所差異，因此本研究的第一個目的是探討造成三個治療計畫系統所計算的劑量結果有所差異之可能原因。此外，硼中子捕獲治療的治療計畫評估方式，目前是採用劑量體積直方圖、平均劑量和最小劑量等物理性指標作為參考依據，但當不同的治療計畫在這些物理性指標的表現上相近時，會造成難以辨別治療計畫之優劣，因此本研究的第二個目的是嘗試將生物性指標應用於治療計畫評估，並比較物理性指標和生物性指標於硼中子捕獲治療之治療計畫評估的效益。
三個治療計畫系統間劑量差異之可能原因，針對治療計畫系統中劑量計算方式、感興趣區域填入的材料，以及器官特異性，包含器官體積和器官位置，以此四個方面分析是否與劑量差異具有關聯。治療計畫評估中，將計算各案例腫瘤之平均劑量、最小劑量、最大劑量、均勻度、廣義等效均勻劑量和腫瘤控制率共六項指標，並分析各項指標對於各案例之臨床後續追蹤結果是否有鑑別度。
治療計畫系統之間，THORplan與INSIGHT之平均劑量差異為-35% ~ +35%，NTHUplan與INSIGHT差異則為-20% ~ +10%。深入分析後得知，劑量計算邏輯與方式、感興趣區域所填入的材料，是主要影響劑量結果的因素，然而器官體積和器官位置對劑量差異並沒有顯著相關性。治療計畫評估可使用最小劑量和廣義等效均勻劑量，因為相較於其他指標，此二者最能夠辨別治療效益，建議硼中子捕獲治療計畫系統可將這兩項指標納入，以提供臨床治療選擇合適的治療計畫之參考。依據目前的案例分析，當最小劑量超過8 Gy-Eq或廣義等效均勻劑量超過15 Gy-Eq時，對於硼中子捕獲治療會有較好的生物效益。

Three boron neutron capture therapy (BNCT) treatment planning systems (TPS) can be used in Tsing Hua Open-pool reactor, namely THORplan, NTHUplan, and INSIGHT. The overall structure of these TPSs is similar, but there are still some differences in details, resulting in varied dose results even under the same treatment parameter conditions. Therefore, the first aim of this study is to quantify the differences in dose results between these TPSs. Furthermore, the physical indices are currently used to evaluate BNCT treatment plans. These physical indices are the dose-volume histogram, the average dose, the minimum dose, and the maximum dose. However, when different treatment plans are similar in the performance of these physical indices, it will be difficult to distinguish these treatment plans. Therefore, the second aim of this study is to apply biological indices to evaluate treatment plans and to compare the benefits of physical and biological indices in evaluating treatment plans for BNCT.
The possible reasons for the dose differences among these TPSs are based on the dose calculation method in the TPS, the materials filled in the region of interest (ROI) and the specificity of the organ, including organ volume and organ location. Analyze whether there is a correlation between these reasons and dose differences. In the evaluation of treatment plans, the average dose, minimum dose, maximum dose, homogeneity index, generalized equivalent uniform dose and tumor control probability of each case were calculated and analyzed, to determine which index has discrimination for the clinical follow-up results of each case.
The difference in the average doses compared between THORplan and INSIGHT was -35% ~ +35%, and the difference between NTHUplan and INSIGHT was -20% ~ +10%. The different dose calculation methods and the materials filled in the ROI between TPSs principally affect the BNCT dose results. However, there was no significant correlation between organ specificity and dose results. We suggest using a minimum dose and a generalized equivalent uniform dose as appropriate dose indices to evaluate BNCT plans because they have the best discrimination compared to other indices. Furthermore, BNCT is more beneficial when the minimum dose exceeds 8 Gy-Eq or the generalized equivalent uniform dose exceeds 15 Gy-Eq.

摘要 i
Abstract iii
致謝 v
目錄 vii
表目錄 x
圖目錄 xi
第一章 緒論 1
1.1 研究目的 1
1.2 研究架構與方法 1
1.3 名詞解釋 3
第二章 介紹與文獻回顧 4
2.1 硼中子捕獲治療 4
2.1.1 原理與臨床應用 4
2.1.2 治療計畫系統之簡介 5
2.1.3 清華水池式反應爐使用之治療計畫系統 7
2.2 治療計畫評估 14
2.2.1 治療計畫之設計 14
2.2.2 傳統光子治療之治療計畫評估指標 15
第三章 材料與方法 17
3.1 治療計畫系統之比較 17
3.1.1 案例資料 17
3.1.2 治療計畫參數設定 20
3.1.3 劑量結果分析 23
3.2 治療計畫評估之計算 23
3.2.1 案例資料 23
3.2.2 物理性指標之計算 24
3.2.3 生物性指標之計算 25
第四章 結果與討論 29
4.1 治療計畫系統之劑量結果比較 29
4.1.1 劑量結果分析 29
4.1.2 劑量計算方式對於劑量差異之影響 31
4.1.3 感興趣區域材料對於劑量差異之影響 36
4.1.4 器官體積對於劑量差異之影響 38
4.1.5 器官位置對於劑量差異之影響 39
4.2 驗證治療計畫評估 41
4.2.1 治療計畫評估指標之結果 41
4.2.2 治療計畫評估指標之鑑別度 42
第五章 結論與未來工作 47
5.1 研究結論 47
5.2 未來工作 47
參考資料 49
附錄 52
I. 各個ROI在三個治療計畫系統的平均劑量值(單位：Gy-Eq) 52
I. 各個ROI在三個治療計畫系統的平均劑量值(單位：Gy-Eq) (續) 53
II. THORplan、NTHUplan與INSIGHT之間的平均劑量差異(單位：%) 54
II. THORplan、NTHUplan與INSIGHT之間的平均劑量差異(單位：%) (續) 55
III. 眼球材料為Eye-Lens與材料為Avg-soft-tissue的平均劑量比值 56
IV. 未定義區域材料為Avg-soft-tissue與材料依據CT值的平均劑量比值 57
V. 四位案例各ROI的體積(單位：c.c.) 58
VI. ICRU 46提供之人體組織元素組成(單位：重量百分比) 59

Bland, J.M., Altman, D.G., 2004. The logrank test. BMJ 328, 1073. https://doi.org/10.1136/bmj.328.7447.1073
Bland, J.M., Altman, D.G., 1998. Survival probabilities (the Kaplan-Meier method). BMJ 317, 1572. https://doi.org/10.1136/bmj.317.7172.1572
Caswell, R.S., Coyne, J.J., Randolph, M.L., 1982. Kerma Factors of Elements and Compounds for Neutron Energies Below 30 MeV. Int. J. Appl. Radiat. Isot. 33, 1227–1262. https://doi.org/10.1016/0020-708X(82)90246-0
Coderre, J.A., Turcotte, J.C., Riley, K.J., Binns, P.J., Harling, O.K., Kiger, W.S., 2003. Boron Neutron Capture Therapy : Cellular Targeting of High Linear Energy Transfer Radiation. Technol. Cancer Res. Treat. 2, 355–375. https://doi.org/10.1177/153303460300200502
Drzymala, R.E., Mohan, R., Brewster, L., Chu, J., Goitein, M., Harms, W., Urie, M., 1991. Dose-Volume Histograms. Int. J. Radiat. Oncol. Biol. Phys. 21, 71–78. https://doi.org/10.1016/0360-3016(91)90168-4
Durisi, E., Koivunoro, H., Visca, L., Borla, O., Zanini, A., 2010. Comparison of Different MC Techniques to Evaluate BNCT Dose Profiles in Phantom Exposed to Various Neutron Fields. Radiat. Prot. Dosimetry 138, 213–222. https://doi.org/10.1093/rpd/ncp263
Dymova, M.A., Taskaev, S.Y., Richter, V.A., Kuligina, E.V., 2020. Boron neutron capture therapy: Current status and future perspectives. Cancer Commun. 1–16. https://doi.org/10.1002/cac2.12089
Gay, H.A., Niemierko, A., 2007. A free program for calculating EUD-based NTCP and TCP in external beam radiotherapy. Phys. Medica 23, 115–125. https://doi.org/10.1016/j.ejmp.2007.07.001
Hall, E.J., Giaccia, A.J., 2019. Radiobiology for the Radiologist, Eighth Edition., Wolters Kluwer.
International Commission on Radiation Units and Measurements, 1992. Photon, Electron, Proton and Neutron Interaction Data for Body Tissues. (ICRU Report 46)
Jiang, S.H., Hsueh Liu, Y.W., Chou, F.I., Liu, H.M., Peir, J.J., Liu, Y.H., Huang, Y.S., Wang, L.W., Chen, Y.W., Yen, S.H., Wu, Y.H., Liu, C.S., Lee, J.C., Chang, C.W., Wang, S.J., Huang, W.S., Kai, J.J., 2020. The overview and prospects of BNCT facility at Tsing Hua Open-pool reactor. Appl. Radiat. Isot. 161, 109143. https://doi.org/10.1016/j.apradiso.2020.109143
Kumada, H., Takada, K., 2018. Treatment planning system and patient positioning for boron neutron capture therapy. Ther. Radiol. Oncol. 2, 50. https://doi.org/10.21037/tro.2018.10.12
Lee, S., Cao, Y.J., Kim, C.Y., 2015. Physical and Radiobiological Evaluation of Radiotherapy Treatment Plan, in: Evolution of Ionizing Radiation Research. https://doi.org/10.5772/60846
Li, X.A., Alber, M., Deasy, J.O., Jackson, A., Jee, K.-W.K., Marks, L.B., Martel, M.K., Mayo, C., Moiseenko, V., Nahum, A.E., Niemierko, A., Semenenko, V.A., Yorke, E.D., 2012. The Use and QA of Biologically Related Models for Treatment Planning, short report of the TG-166 of the therapy physics committee of the AAPM. Medical physics, 39(3), 1386–1409. https://doi.org/10.1118/1.3685447
Lin, T.Y., Liu, Y.W.H., 2011. Development and verification of THORplan-A BNCT treatment planning system for THOR. Appl. Radiat. Isot. 69, 1878–1881. https://doi.org/10.1016/j.apradiso.2011.03.025
Marks, L.B., Yorke, E.D., Jackson, A., Haken, R.K.Ten, Constine, L.S., Eisbruch, A., Bentzen, S.M., Nam, J., Deasy, J.O., 2010. The Use of Normal Tissue Complication Probability (NTCP) Models in the Clinic. Int. J. Radiat. Oncol. Biol. Phys. 76. https://doi.org/10.1016/j.ijrobp.2009.07.1754.
Niemierko, A., 1999. A Generalized Concept of Equivalent Uniform Dose 26, 1100.
Niemierko, A., 1997. Reporting and analyzing dose distributions: A concept of equivalent uniform dose. Med. Phys. 24, 103–110. https://doi.org/10.1118/1.598063
Patel, G., Mandal, A., Choudhary, S., Mishra, R., Shende, R., 2020. Plan evaluation indices: A journey of evolution. Reports Pract. Oncol. Radiother. 25, 336–344. https://doi.org/10.1016/j.rpor.2020.03.002
Taghian, A., DuBois, W., Budach, W., Baumann, M., Freeman, J., Suit, H., 1995. In Vivo Radiation Sensitivity of Glioblastoma Multiforme. Int. J. Radiat. Oncol. Biol. Phys. 32, 99–104. https://doi.org/10.1016/0360-3016(94)00494-6
Wen, P.Y., Macdonald, D.R., Reardon, D.A., Cloughesy, T.F., Sorensen, A.G., Galanis, E., DeGroot, J., Wick, W., Gilbert, M.R., Lassman, A.B., Tsien, C., Mikkelsen, T., Wong, E.T., Chamberlain, M.C., Stupp, R., Lamborn, K.R., Vogelbaum, M.A., Van DenBent, M.J., Chang, S.M., 2010. Updated Response Assessment Criteria for High-Grade Gliomas: Response Assessment in Neuro-Oncology Working Group. J. Clin. Oncol. 28, 1963–1972. https://doi.org/10.1200/JCO.2009.26.3541
Zamenhof, R.G., Clement, S.D., Harling, O.K., Brenner, J.F., Wazer, D.E., Madoc-Jones, H., Yanch, J.C., 1990. Monte Carlo Based Dosimetry and Treatment Planning for Neutron Capture Therapy of Brain Tumors. Basic Life Sci. 54, 283–305.
李敏, 葉宗洸, 劉鴻鳴, 裴晉哲, 王美雅, 2021. 國立清華大學水池式反應器Tsing Hua Open - Pool Reactor醫療設施認證 - SERA治療計畫程式及NTHUplan使用手冊. 清華大學.