目的 : 針對高雄長庚質子治療中心使用的筆尖式線性掃描(Pencil beam linear scanning, PBLS)提升單一照野最佳化(single-field optimization, SFO)技術與多照野最佳化(multi-field optimization, MFO)技術品質保證程序(Patient Specific Quality Assurance, PSQA)之效率。
材料與方法 : 本研究為回溯性研究自高雄長庚醫院質子治療中心收集389個質子放射治療的品質保證照野資料參數，執行PSQA程序包含照野監測單位校正、絕對劑量與深度劑量量測以及二維面劑量γ指數分析。使用MATLAB採監督式學習概念進行資料庫模型撰寫程式，建立PSQA資料庫並提出評估程序的重要參數，定義SFO與MFO兩者技術的擴展布拉格峰(Spread out bragg peak, SOBP)深度，評估定義後五個深度的Gamma index通過率，量測射束末端的二維劑量變化，量化質子射束位置的劑量差異，使用獨立T檢定來比較優化前後之二維劑量量測程序有無差異。導入粒子群演算法(Particle Swarm Optimization, PSO)執行最佳化程序作業(Operating point search, OPS)計算劑量工作點(Dose specification point, DSP)之座標，提供PSQA程序最佳化建議。
結果 : 經資料庫所提出的質子治療品質保證程序重要參數中照野監測單位校正、絕對劑量量測、深度劑量量測與二維面劑量γ指數分析，在SFO技術中結果分別為1.15%±0.88、-0.77%±1.30、0.25%±1.05、99.41%±0.67，而MFO技術結果分別為1.29%±1.09、-1.23%±1.13、0.67%±0.94、99.26%±0.62，兩者技術在各項參數皆於標準誤差±5%與Gamma index通過率≥85%內。射束末端Gamma index通過率在SFO與MFO技術結果分別為42.86%、70.8%。SFO技術未加裝質子降能器中建議移除Surface與Proximal量測；SFO技術加裝質子降能器中建議省略Proximal量測；頭頸部MFO技術建議移除Group2與Group4量測，使用獨立T檢定評估三者條件下的優化前後二維劑量量測比較之P值皆>0.05，無顯著差異。從PTW Verisoft輸入劑量矩陣至MATLAB執行OPS腳本並結合上述程序優化建議將可節省23.5%的作業時間。
結論 : PSQA程序中執行OPS可提升前置作業在搜尋量測工作點的效率；二維劑量量測結果分析，SFO技術加裝質子降能器中建議移除Surface與Proximal量測；SFO技術未裝質子降能器中建議省略Proximal量測；頭頸部MFO技術建議移除Group2與Group4量測，並建議SFO與MFO在Distal falloff區域無須量測，結合上述步驟後，可發揮PSQA程序最大效率。

Purpose: Improving single-field optimization (SFO) and multi-field optimization (MFO) of the patient-specific quality assurance (PSQA) process for the pencil beam linear scanning (PBLS) proton therapy..
Materials and methods: This study is a retrospective study from the Proton Therapy Center of Kaohsiung Chang Gung Hospital. The study collected 389 proton radiation treatment data quality assurance field parameters. The process of the PSQA program includes field monitoring unit calibration, absolute dose and depth dose measurement, and two-dimensional dose gamma index analysis. Using MATLAB to adopt the concept of supervised learning to write database models, researchers were able to establish a PSQA database and propose important parameters of the evaluation procedure, define the SOBP depth of both SFO and MFO technologies, measuring the two-dimensional dose change at the distal falloff area ,evaluate the Gamma index pass rate of the five defined depths, and quantify protons,using an independent T test to compare the difference between the two-dimensional dose measurement procedures before and after optimization. The dose difference at the beam position. Introduce Particle Swarm Optimization (PSO) to execute OPS, calculate the coordinates of Dose specification point (DSP), and provide PSQA program optimization suggestions.
Results: According to the important parameters of the proton therapy quality assurance program proposed by the database, the results of SFO technology for the field monitoring unit calibration, absolute dose measurement, depth dose measurement, and two-dimensional dose gamma index analysis, were 1.15%±0.88, -0.77%±1.30, 0.25%±1.05, 99.41%±0.67, respectively; the MFO technical results were 1.29%±1.09, -1.23%±1.13, 0.67%±0.94, 99.26%±0.62, respectively. The two technologies are in various parameters All are within standard error ±5% and Gamma index pass rate ≥85%. The Gamma index pass rate at the end of the beam is 42.86% and 70.8% for the SFO and MFO technologies, respectively. The independent T test evaluates the P value of the two-dimensional dose measurement comparison before and after the optimization under the conditions of the three, and all the values are >0.05, no significant difference.From PTW Verisoft input dose matrix to MATLAB execution OPS script will save 23.5% of the operating time.
Conclusions: The implementation of OPS in the PSQA program can improve the efficiency of pre-operations in searching and measuring the working point; for two-dimensional dose measurement result analysis, it is recommended to remove the Surface and Proximal areas of the SFO without snout degrader technology ; Proximal areas of the SFO with snout degrader technology and Group 2 and Group 4 in the MFO technology into a single unit for measurement. Removal of the measurement of SFO and MFO in the distal falloff area, combined with the above steps, can maximize the efficiency of the PSQA program.

摘要
Abstract
致謝
目錄
表目錄
圖目錄
符號縮寫
符號說明
第一章 緒論
1.1 動機
1.2 目的
1.3 相關文獻探討
第二章 材料與方法
2.1 前言
2.2 樣本資料
2.3 病患品質保證程序(PSQA)前置作業
2.3.1 選擇假體尺寸
2.3.2 治療計畫系統上建立工作點
2.3.3 導入質子治療機每日輸出劑量校正
2.4 執行病患品質保證程序(PSQA)程序
2.4.1 步驟一 : 確認治療照野監測單位
2.4.2步驟二 : 驗證不同深度之絕對劑量
2.4.3步驟三 : 驗證二維劑量分佈
2.5 自動化資料彙整與資料庫建立
2.6 提出病患品質保證程序數據之特徵因子
2.6.1 MU diff.% (TCSC - TPS)
2.6.2 Dose diff.% (Chamber - TPS)
2.6.3 Depth dose diff.%
2.6.4 Gamma index(3mm/3%)
2.7 評估各項目量測之作業時間
2.8 縱向深度珈瑪指數分析
2.9 SFO技術縱向深度劑量曲線
2.10 MFO技術縱向深度劑量曲線
2.11 粒子群演算法最佳化工作點
第三章 結果
3.1 前言
3.2 照野監測單位校正
3.2.1 單一照野最佳化(single-field optimization, SFO)技術
3.2.2 多照野最佳化(multi-field optimization, MFO)技術
3.3 絕對劑量驗證
3.3.1 單一照野最佳化(single-field optimization, SFO)技術
3.3.2 多照野最佳化(multi-field optimization, MFO)技術
3.4 深度劑量驗證
3.4.1 單一照野最佳化(single-field optimization, SFO)技術
3.4.2 多照野最佳化(multi-field optimization, MFO)技術
3.5 二維面劑量γ指數分析
3.5.1 單一照野最佳化(single-field optimization, SFO)技術
3.5.2 多照野最佳化(multi-field optimization, MFO)技術
3.6 二維面劑量於射束末端之量測結果
3.7 腫瘤深度與面劑量量測分析結果
3.7.1 單一照野最佳化(single-field optimization, SFO)技術
3.7.2 多照野最佳化(multi-field optimization, MFO)技術
3.8 最佳化工作點執行結果
第四章 討論
4.1無質子降能器面劑量評估
4.2表淺位置的二維劑量分佈
4.3有無加裝質子降能器之比較
4.4空氣間隙與絕對劑量誤差之關係
第五章 結論
參考文獻
附件

[1]J. S. Loeffler and M. Durante, "Charged particle therapy—optimization, challenges and future directions," Nature reviews Clinical oncology, vol. 10, p. 411, 2013.
[2]H. M. Kooy, M. Schaefer, S. Rosenthal, and T. Bortfeld, "Monitor unit calculations for range-modulated spread-out Bragg peak fields," Physics in Medicine & Biology, vol. 48, p. 2797, 2003.
[3]U. Schneider and E. Pedroni, "Proton radiography as a tool for quality control in proton therapy," Medical physics, vol. 22, pp. 353-363, 1995.
[4]M. Yang, X. R. Zhu, P. C. Park, U. Titt, R. Mohan, G. Virshup, et al., "Comprehensive analysis of proton range uncertainties related to patient stopping-power-ratio estimation using the stoichiometric calibration," Physics in Medicine & Biology, vol. 57, p. 4095, 2012.
[5]A.-C. Knopf and A. Lomax, "In vivo proton range verification: a review," Physics in Medicine & Biology, vol. 58, p. R131, 2013.
[6]J. Van Dyk, R. Barnett, J. Cygler, and P. Shragge, "Commissioning and quality assurance of treatment planning computers," International Journal of Radiation Oncology* Biology* Physics, vol. 26, pp. 261-273, 1993.
[7]D. Mackin, Y. Li, M. B. Taylor, M. Kerr, C. Holmes, N. Sahoo, et al., "Improving spot‐scanning proton therapy patient specific quality assurance with HPlusQA, a second‐check dose calculation engine," Medical physics, vol. 40, p. 121708, 2013.
[8]E. Pedroni, S. Scheib, T. Böhringer, A. Coray, M. Grossmann, S. Lin, et al., "Experimental characterization and physical modelling of the dose distribution of scanned proton pencil beams," Physics in Medicine & Biology, vol. 50, p. 541, 2005.
[9]M. C. Mesias, E. Troost, S. Appold, M. Krause, C. Richter, and K. Stützer, "8 Evaluation of robust and non-robust proton treatment plans using single-field and multifield optimization for unilateral head and neck targets," Würzburg, p. 25, 2014.
[10]F. Tommasino, M. Durante, V. D'Avino, R. Liuzzi, M. Conson, P. Farace, et al., "Model-based approach for quantitative estimates of skin, heart, and lung toxicity risk for left-side photon and proton irradiation after breast-conserving surgery," Acta Oncologica, vol. 56, pp. 730-736, 2017.
[11]T. Pfeiler, D. A. Khalil, M. Ayadi, C. Bäumer, O. Blanck, M. Chan, et al., "Motion effects in proton treatments of hepatocellular carcinoma—4D robustly optimised pencil beam scanning plans versus double scattering plans," Physics in Medicine & Biology, vol. 63, p. 235006, 2018.
[12]W. Liu, S. J. Frank, X. Li, Y. Li, P. C. Park, L. Dong, et al., "Effectiveness of robust optimization in intensity‐modulated proton therapy planning for head and neck cancers," Medical physics, vol. 40, p. 051711, 2013.
[13]S. J. Frank, J. D. Cox, M. Gillin, R. Mohan, A. S. Garden, D. I. Rosenthal, et al., "Multifield optimization intensity modulated proton therapy for head and neck tumors: a translation to practice," International Journal of Radiation Oncology* Biology* Physics, vol. 89, pp. 846-853, 2014.
[14]K. Chung, "A pilot study of the scanning beam quality assurance using machine log files in proton beam therapy," Progress in Medical Physics, vol. 28, pp. 129-133, 2017.
[15]M. Filippi, M. Horsfield, H. Ader, F. Barkhof, P. Bruzzi, A. Evans, et al., "Guidelines for using quantitative measures of brain magnetic resonance imaging abnormalities in monitoring the treatment of multiple sclerosis," Annals of neurology, vol. 43, pp. 499-506, 1998.
[16]T. F. De Laney and H. M. Kooy, Proton and charged particle radiotherapy: Lippincott Williams & Wilkins, 2008.
[17]K. Jo, S. H. Ahn, K. Chung, S. Cho, E. H. Shin, S. Park, et al., "Initial Experience of Patient-Specific QA for Wobbling and Line-Scanning Proton Therapy at Samsung Medical Center," Progress in Medical Physics, vol. 30, pp. 14-21, 2019.
[18]O. Jäkel, G. Hartmann, C. Karger, P. Heeg, and J. Rassow, "Quality assurance for a treatment planning system in scanned ion beam therapy," Medical physics, vol. 27, pp. 1588-1600, 2000.
[19]P. Trnková, A. Bolsi, F. Albertini, D. C. Weber, and A. J. Lomax, "Factors influencing the performance of patient specific quality assurance for pencil beam scanning IMPT fields," Medical physics, vol. 43, pp. 5998-6008, 2016.
[20]H. Paganetti, "Monte Carlo calculations for absolute dosimetry to determine machine outputs for proton therapy fields," Physics in Medicine & Biology, vol. 51, p. 2801, 2006.
[21]J. E. Bekelman, J. A. Deye, B. Vikram, S. M. Bentzen, D. Bruner, W. J. Curran Jr, et al., "Redesigning radiotherapy quality assurance: opportunities to develop an efficient, evidence-based system to support clinical trials—report of the National Cancer Institute work group on radiotherapy quality assurance," International Journal of Radiation Oncology* Biology* Physics, vol. 83, pp. 782-790, 2012.
[22]R. Glick, R. Gupta, J. Sauer, and A. Woodward, "Proton magnetic resonance of irradiated polyethylene," Polymer, vol. 1, pp. 340-350, 1960.
[23]W. D. Newhauser and R. Zhang, "The physics of proton therapy," Physics in Medicine & Biology, vol. 60, p. R155, 2015.
[24]M. J. Butson, K. Peter, T. Cheung, and P. Metcalfe, "Radiochromic film for medical radiation dosimetry," Materials Science and Engineering: R: Reports, vol. 41, pp. 61-120, 2003.
[25]T. Marusic, "Ray Cast/Dose Superposition algorithm for proton grid therapy," ed, 2017.
[26]A. Anand, N. Sahoo, X. R. Zhu, G. O. Sawakuchi, F. Poenisch, R. A. Amos, et al., "A procedure to determine the planar integral spot dose values of proton pencil beam spots," Medical physics, vol. 39, pp. 891-900, 2012.
[27]K. Chung, Y. Han, S. H. Ahn, J. S. Kim, and H. Nonaka, "Commissioning and validation of a dedicated scanning nozzle at Samsung Proton Therapy Center," Progress in Medical Physics, vol. 27, pp. 267-271, 2016.
[28]N. Wen, S. Lu, J. Kim, Y. Qin, Y. Huang, B. Zhao, et al., "Precise film dosimetry for stereotactic radiosurgery and stereotactic body radiotherapy quality assurance using Gafchromic™ EBT3 films," Radiation Oncology, vol. 11, pp. 1-11, 2016.
[29]C. Bäumer, B. Ackermann, M. Hillbrand, F.-J. Kaiser, B. Koska, H. Latzel, et al., "Dosimetry intercomparison of four proton therapy institutions in Germany employing spot scanning," Zeitschrift für Medizinische Physik, vol. 27, pp. 80-85, 2017.
[30]B. Clasie, N. Depauw, M. Fransen, C. Gomà, H. R. Panahandeh, J. Seco, et al., "Golden beam data for proton pencil-beam scanning," Physics in Medicine & Biology, vol. 57, p. 1147, 2012.
[31]L. Dong and X. R. Zhu, "Clinical Implementation of Pencil Beam Scanning (PBS) Proton Therapy," in Medical Physics, 2017, pp. 3031-3032.
[32]S. A. Vora, W. W. Wong, S. E. Schild, G. A. Ezzell, and M. Y. Halyard, "Analysis of biochemical control and prognostic factors in patients treated with either low-dose three-dimensional conformal radiation therapy or high-dose intensity-modulated radiotherapy for localized prostate cancer," International Journal of Radiation Oncology* Biology* Physics, vol. 68, pp. 1053-1058, 2007.
[33]F.-J. Kaiser, N. Bassler, and O. Jäkel, "COTS Silicon diodes as radiation detectors in proton and heavy charged particle radiotherapy 1," Radiation and environmental biophysics, vol. 49, pp. 365-371, 2010.
[34]J. Sorriaux, M. Testa, H. Paganetti, D. Bertrand, J. A. Lee, H. Palmans, et al., "Consistency in quality correction factors for ionization chamber dosimetry in scanned proton beam therapy," Medical Physics, vol. 44, pp. 4919-4927, 2017.
[35]X. R. Zhu, Y. Li, D. Mackin, H. Li, F. Poenisch, A. K. Lee, et al., "Towards effective and efficient patient-specific quality assurance for spot scanning proton therapy," Cancers, vol. 7, pp. 631-647, 2015.
[36]F. P. N. S. H. Li and Y. Hojo, "Physics Quality Assurance," Proton Therapy E-Book: Indications, Techniques, and Outcomes, p. 80, 2020.
[37]G. Sahani, P. Tandon, and A. Sonawane, "Radiation safety assessment of proton therapy facility in India," Journal of Medical Physics, vol. 42, p. 66, 2017.
[38]S. T. Karris, Numerical analysis using MATLAB and Excel: Orchard Publications, 2007.
[39]G. A. Abers and B. R. Hacker, "A MATLAB toolbox and E xcel workbook for calculating the densities, seismic wave speeds, and major element composition of minerals and rocks at pressure and temperature," Geochemistry, Geophysics, Geosystems, vol. 17, pp. 616-624, 2016.
[40]J. Price and S. Student, "Design of an Automatic Speech Recognition System Using MATLAB," Dept. of Engineering and Aviation Sciences, University of Maryland Eastern Shore Princess Ann, 2005.
[41]Y.-H. Chen, H.-H. Fu, Y.-Y. Zhao, W. Meng, and D.-R. Ye, "Automatic Processing of Experimental Data Based on Matlab and Excel [J]," Computer Engineering, vol. 23, 2007.
[42]D. Mackin, X. R. Zhu, F. Poenisch, H. Li, N. Sahoo, M. Kerr, et al., "Spot-scanning proton therapy patient-specific quality assurance: results from 309 treatment plans," International Journal of Particle Therapy, vol. 1, pp. 711-720, 2014.
[43]D. Hernandez Morales, J. Shan, W. Liu, K. E. Augustine, M. Bues, M. J. Davis, et al., "Automation of routine elements for spot‐scanning proton patient‐specific quality assurance," Medical physics, vol. 46, pp. 5-14, 2019.
[44]R. Thiyagarajan, D. S. Sharma, S. Kaushik, M. Sawant, G. Krishnan, A. Nambiraj, et al., "Leaf Open Time Sinogram (LOTS): A novel approach for Patient specific quality assurance of Total marrow irradiation," 2020.
[45]F. Albertini, H. Damoune, A. Imboden, S. Lang, V. Maiwald, L. Negretti, et al., "Index of First Authors," Strahlenther Onkol, vol. 187, pp. 513-540, 2011.
[46]M. Chen, P. Yepes, Y. Hojo, F. Poenisch, Y. Li, J. Chen, et al., "Transitioning from measurement-based to combined patient-specific quality assurance for intensity-modulated proton therapy," The British journal of radiology, vol. 93, p. 20190669, 2020.
[47]F. Fracchiolla, F. Fellin, M. Innocenzi, M. Lipparini, S. Lorentini, L. Widesott, et al., "A pre-absorber optimization technique for pencil beam scanning proton therapy treatments," Physica Medica, vol. 57, pp. 145-152, 2019.
[48]T. A. Trikalinos, T. Terasawa, S. Ip, G. Raman, and J. Lau, "Particle beam radiation therapies for cancer," 2010.
[49]M. Engelsman, C. Bert, and H. Paganetti, "Precision and uncertainties in proton therapy for moving targets," Proton Therapy Physics. Series in Medical Physics and Biomedical Engineering, vol. 1, pp. 435-60, 2011.
[50]B. Arjomandy, T. Schultz, S. Park, and H. Gayar, "A comparative study of single verses 2-field daily fraction for treatment of prostate cancer using IMPT, double-scattered, and SFUD delivery technique," International Journal of Radiation Oncology• Biology• Physics, vol. 84, p. S843, 2012.
[51]朱家賢, "一個新的全域最佳化演算法: 禁制搜尋加強式粒子群最佳化," 暨南大學資訊管理學系學位論文, pp. 1-50, 2008.
[52]U. Titt, K. Suzuki, Y. Li, N. Sahoo, M. T. Gillin, and X. R. Zhu, "Dosimetric characteristics of the ocular beam line and commissioning data for an ocular proton therapy planning system at the Proton Therapy Center Houston," Medical physics, vol. 44, pp. 6661-6671, 2017.
[53]J. Saini, D. Maes, A. Egan, S. R. Bowen, S. St James, M. Janson, et al., "Dosimetric evaluation of a commercial proton spot scanning Monte-Carlo dose algorithm: comparisons against measurements and simulations," Physics in Medicine & Biology, vol. 62, p. 7659, 2017.
[54]J. C. Buchsbaum, M. W. McDonald, P. A. Johnstone, T. Hoene, M. Mendonca, C.-W. Cheng, et al., "Range modulation in proton therapy planning: a simple method for mitigating effects of increased relative biological effectiveness at the end-of-range of clinical proton beams," Radiation Oncology, vol. 9, p. 2, 2014.
[55]B. G. Baumert, I. A. Norton, A. J. Lomax, and J. B. Davis, "Dose conformation of intensity-modulated stereotactic photon beams, proton beams, and intensity-modulated proton beams for intracranial lesions," International Journal of Radiation Oncology* Biology* Physics, vol. 60, pp. 1314-1324, 2004.
[56]Y. Han, "Current status of proton therapy techniques for lung cancer," Radiation Oncology Journal, vol. 37, pp. 232-248, 2019.
[57]R. J. Shirey and H. T. Wu, "Quantifying the effect of air gap, depth, and range shifter thickness on TPS dosimetric accuracy in superficial PBS proton therapy," Journal of applied clinical medical physics, vol. 19, pp. 164-173, 2018.
[58]A. N. Schreuder, D. S. Bridges, L. Rigsby, M. Blakey, M. Janson, S. G. Hedrick, et al., "Validation of the RayStation Monte Carlo dose calculation algorithm using a realistic lung phantom," Journal of applied clinical medical physics, vol. 20, pp. 127-137, 2019.
[59]D. Wang, H. Daniel, and B. Dirksen, "Close-proximity range shifting device for proton radiosurgery," ed: Google Patents, 2018.
[60]F. Tommasino, F. Fellin, S. Lorentini, and P. Farace, "Impact of dose engine algorithm in pencil beam scanning proton therapy for breast cancer," Physica Medica, vol. 50, pp. 7-12, 2018.
[61]U. W. Langner, M. Mundis, D. Strauss, M. Zhu, and S. Mossahebi, "A comparison of two pencil beam scanning treatment planning systems for proton therapy," Journal of applied clinical medical physics, vol. 19, pp. 156-163, 2018.
[62]S. Michiels, A. M. Barragán, K. Souris, K. Poels, W. Crijns, J. A. Lee, et al., "Patient-specific bolus for range shifter air gap reduction in intensity-modulated proton therapy of head-and-neck cancer studied with Monte Carlo based plan optimization," Radiotherapy and Oncology, vol. 128, pp. 161-166, 2018.
[63]S. Rana and E. J. J. Samuel, "Measurements of in-air spot size of pencil proton beam for various air gaps in conjunction with a range shifter on a ProteusPLUS PBS dedicated machine and comparison to the proton dose calculation algorithms," Australasian Physical & Engineering Sciences in Medicine, vol. 42, pp. 853-862, 2019.
[64]L. Widesott, S. Lorentini, F. Fracchiolla, P. Farace, and M. Schwarz, "Improvements in pencil beam scanning proton therapy dose calculation accuracy in brain tumor cases with a commercial Monte Carlo algorithm," Physics in Medicine & Biology, vol. 63, p. 145016, 2018.