立體定位放射手術(SRS)為多發性顱內轉移腫瘤主要的治療方式，但針對多個病灶使用多等中心點(multiple isocenter)技術製作治療計畫耗時且臨床操作效率低，病人長時間滯留在治療床也造成安全性的疑慮。近年來嘗試使用單等中心點(single isocenter)治療計畫不僅加速臨床效率也能有不錯的病灶劑量分布與治療效果，然而，單等中心點技術容易發生病灶外的劑量洩漏及散溢的現象，潛在著對危急器官的輻射生物效應，目前尚未有文獻探討此議題。另外，隨著診斷技術提升，能夠及早發現病灶及早治療，延長了病人的存活時間，因此在放射治療領域開始重視散射及洩漏劑量誘發正常組織二次癌症的風險。本研究目的即針對立體定位放射手術之兩種技術治療計畫比較生物效應與風險之差異，並建構一套完整的生物性治療計畫評估系統及操作平台。
評估對象取自美國休士頓衛理公會醫院(Houston Methodist Hospital)患有多發性腦腫瘤的案例資料，再分別以多等中心點及單等中心點技術建立兩種治療計畫。其中生物效應的評估以腫瘤控制率(TCP)和正常組織併發症機率(NTCP)模型，並結合Schneider發表之輻射誘發癌症風險模型做計算。從抓取DICOM資訊到模型計算分析，本研究使用MATLAB來建立完整的生物性治療計畫評估系統。
研究結果發現在大多數案例中，兩技術之腫瘤控制率較無明顯差異，而部分器官之正常組織併發症機率和誘發癌症風險與病灶數量、病灶分佈的位置距離以及兩種技術之計畫設計有關，因此仍需個別探討各生物模型之評估結果，以利臨床有更完善的計畫評估。然而單等中心點技術在整體的生物性評分模型(UCFCP)計算下，有近似甚至優於多等中心點技術的趨勢，病灶數目越多分數差越顯著。因此針對多發性腦瘤使用單等中心點技術不僅能提高治療效率，也有良好的物理劑量與合理的生物性評估表現。

Volumetric modulated arc therapy (VMAT) is commonly employed for stereotactic radiosurgery (SRS) treatment delivery. Especially the single isocenter techniques were introduced to multiple intracranial lesions for reducing the treatment time in recent years. The plan quality indices of single isocenter compared to multiple isocenter have been proposed, however, there has some potential biological effects in single isocenter. Therefore, the aim of this study is using biological model to compare single isocenter and multiple isocenter treatment plans and establishing the biological evaluation program for SRS plans.
Both multiple-isocenter and single-isocenter stereotactic treatment plans were created and exported by Varian Eclipse (Varian Medical Systems, Palo Alto, CA) treatment planning system for each multiple brain metastasis case. For defined critical organs in medium and high-dose regions, Schneider’s organ equivalent dose (OED) model was used, and the parameters of life attributable risk (LAR) for cancer risk assessment were according to the BEIR VII report. The biological effect models include the tumor control probability (TCP) and the normal tissue complication probability (NTCP) with parameters that are applicable for SRS.
An in-house MATLAB program imported DICOM and DICOM RT files from Eclipse planning system and all models were calculated by this program to establish a complete treatment plan evaluation system. The results show that the secondary cancer risk of critical organs was higher for most single isocenter plans, and the comparison of NTCP was not significantly different between the two types of plans. However, some multiple isocenter plans got worse TCP. Because those values were depending on lesion locations, we used the uncomplicated and cancer-free control probability (UCFCP) model which proposed by the Sánchez-Nieto to score the plans, and most single isocenter plans got a higher score.
The shortened treatment time of single isocenter plans improves efficiency and patient tolerance. However, there is still a biological effect difference between these two techniques, even if they give a similar physical dosimetric performance. This work gave the comprehensive system of biological evaluation for SRS plan to evaluate case by case that could give a help for choosing plan or re-optimization.

摘要 i
Abstract ii
致謝 iv
目錄 v
表目錄 vii
圖目錄 viii
第一章 緒論 1
1.1 研究目的及動機 1
1.2 研究方法與步驟 1
1.3 名詞解釋 3
第二章 介紹與文獻回顧 8
2.1 立體定位放射手術 8
2.1.1 特性與臨床應用 9
2.1.2 基於直線加速器之技術發展 10
2.1.3 立體定位治療計畫 13
2.2 治療計畫評估 16
2.2.1 物理劑量與評估指標 17
2.2.2 生物有效劑量與評估模型 20
2.2.3 輻射誘發癌症風險評估 21
第三章 研究設計與方法 24
3.1 臨床資料 24
3.1.1 治療機器與設備 24
3.1.2 治療計畫系統與劑量限值 25
3.1.3 案例資料 27
3.2 治療計畫評估模型 28
3.2.1 物理性劑量評估指標 28
3.2.2 生物性評估模型 30
3.2.3 輻射誘發癌症風險模型 33
3.2.4 複合性評分模型 37
3.3 評估系統程式建構 37
第四章 結果與討論 41
4.1 物理性劑量指標評估 41
4.1.1 結果分析與探討 41
4.1.2 影響單等中心點劑量指標因素 44
4.2 生物性模型評估結果與模型探討 50
4.2.1 生物性計畫評估結果 51
4.2.2 生物性模型探討 60
4.3 系統驗證 63
第五章 結論與未來工作 67
5.1 研究結論 67
5.2 未來工作 67
參考資料 69
附錄 生物性治療計畫評估系統之MATLAB程式碼 82

[1] W.Lutz, K.Winston, andN.Maleki, “A system for stereotactic radiosurgery with a linear accelerator and its performance evaluation,” Int. J. Radiat. Oncol., vol. 12, p. 100, 1986.
[2] L.Leksell, “The stereotaxic method and radiosurgery of the brain,” Acta Chir. Scand., vol. 102, no. 4, pp. 316–319, 1951.
[3] A.Niranjan, S.Sirin, J. C.Flickinger, A.Maitz, D.Kondziolka, andL. D.Lunsford, “Gamma Knife Radiosurgery,” in Principles and Practice of Stereotactic Radiosurgery, Springer New York, 2008.
[4] O. O.Betti andV. E.Derechinsky, “Hyperselective Encephalic Irradiation with Linear Accelerator,” in Advances in Stereotactic and Functional Neurosurgery 6, pp. 385–390., 1984
[5] F.Colombo et al., “External Stereotactic Irradiation by Linear Accelerator,” Neurosurgery, vol. 16, no. 2, pp. 154–160, 1985.
[6] J. S.Kuo et al., “The Cyberknife Stereotactic Radiosurgery System: Description Installation, and an Initial Evaluation of Use and Functionality,” Neurosurgery, vol. 53, no. 5, pp. 1235–1239, 2003.
[7] S. H.Benedict et al., Stereotactic Radiation Therapy, vol. 9. Elsevier B.V., 2014.
[8] J. M.Buatti, W. A.Friedman, S. L.Meeks, andF. J.Bova, “RTOG 90-05: The real conclusion,” International Journal of Radiation Oncology Biology Physics, vol. 47, no. 2. Elsevier, pp. 269–271, May 01, 2000.
[9] S.Kim andJ.Palta, “The Physics of Stereotactic Radiosurgery,” in Principles and Practice of Stereotactic Radiosurgery, Springer New York, pp. 33–50, 2008.
[10] D. D.Leavitt, “Beam shaping for SRT/SRS,” Med. Dosim., vol. 23, no. 3, pp. 229–236, 1998.
[11] C.Yu andD.Shepard, “Treatment Planning for Stereotactic Radiosurgery with Photon Beams,” Technol. Cancer Res. Treat., vol. 2, no. 2, pp. 93–104, 2003, Accessed: Feb.23, 2020.
[12] K.Stelzer, “Epidemiology and prognosis of brain metastases,” Surg. Neurol. Int., vol. 4, no. SUPPL4, 2013.
[13] D. C.Shrieve, J. S.Loeffler, M. W.Mcdermott, andD. A.Larson, “25 - Radiosurgery,” in Leibel and Phillips Textbook of Radiation Oncology (Third Edition), vol. 487–508, 2010.
[14] M. J.Moravan et al., “Current multidisciplinary management of brain metastases,” Am. Cancer Soc., pp. 1–17, 2020.
[15] S.Shi et al., “Stereotactic Radiosurgery for Resected Brain Metastases: Single-Institutional Experience of Over 500 Cavities,” Int. J. Radiat. Oncol., vol. 106, no. 4, pp. 764–771, 2020.
[16] M.Rahman, G. J. A.Murad, F.Bova, W. A.Friedman, andJ.Mocco, “Stereotactic radiosurgery and the linear accelerator: accelerating electrons in neurosurgery,” Neurosurg. Focus FOC, vol. 27, no. 3, 2009.
[17] S. H.Benedict, R. M.Cardinale, Q.Wu, R. D.Zwicker, W. C.Broaddus, andR.Mohan, “Intensity-modulated stereotactic radiosurgery using dynamic micro-multileaf collimation,” Int. J. Radiat. Oncol. Biol. Phys., vol. 50, no. 3, pp. 751–758, 2001.
[18] D.Roberge, R.Ruo, Souhami, andLuis, “Killing Two Birds with One Stone: A Dosimetric Study of Dual Target Radiosurgery Using a Single Isocenter,” Technol. Cancer Res. Treat., vol. 5, pp. 613–617, 2006, Accessed: Feb.07, 2020. [Online]. Available: www.tcrt.org.
[19] A. M.Bergman, E.Gete, C.Duzenli, andT.Teke, “Monte Carlo modeling of HD120 multileaf collimator on Varian TrueBeam linear accelerator for verification of 6X and 6X FFF VMAT SABR treatment plans,” J. Appl. Clin. Med. Phys., vol. 15, no. 3, pp. 148–163, 2014.
[20] S. B.French, S.Bhagroo, D. P.Nazareth, andM. B.Podgorsak, “Adapting VMAT plans optimized for an HD120 MLC for delivery with a Millennium MLC,” J. Appl. Clin. Med. Phys., vol. 18, no. 5, pp. 143–151, 2017.
[21] R. M.Cardinale, S. H.Benedict, Q.Wu, R. D.Zwicker, H. E.Gaballa, andR.Mohan, “A comparison of three stereotactic radiotherapy techniques; arcs vs. noncoplanar fixed fields vs. intensity modulation,” Int. J. Radiat. Oncol. Biol. Phys., vol. 42, no. 2, pp. 431–436, 1998.
[22] S. A.Hanna, A.Mancini, A. H.Dal Col, R. N.Asso, andW. F. P.Neves-Junior, “Frameless Image-Guided Radiosurgery for Multiple Brain Metastasis Using VMAT: A Review and an Institutional Experience,” Front. Oncol., vol. 9, p. 703, 2019.
[23] L. J.Hazard et al., “Conformity of LINAC-Based Stereotactic Radiosurgery Using Dynamic Conformal Arcs and Micro-Multileaf Collimator,” Int. J. Radiat. Oncol. Biol. Phys., vol. 73, no. 2, pp. 562–570, 2009.
[24] J.Molinier et al., “Comparison of volumetric-modulated arc therapy and dynamic conformal arc treatment planning for cranial stereotactic radiosurgery,” J. Appl. Clin. Med. Phys., vol. 17, no. 1, pp. 92–101, 2016.
[25] M. W.Münter et al., “Inverse Treatment Planning and Stereotactic Intensity-Modulated Radiation Therapy (IMRT) of the Tumor and Lymph Node Levels for Nasopharyngeal CarcinomasDescription of Treatment Technique, Plan Comparison, and Case Study,” Strahlentherapie und Onkol., vol. 178, no. 9, pp. 517–523, 2002.
[26] T. J.St John, T. H.Wagner, F. J.Bova, W. A.Friedman, andS. L.Meeks, “A geometrically based method of step and shoot stereotactic radiosurgery with a miniature multileaf collimator,” Phys. Med. Biol., vol. 50, no. 14, pp. 3263–3276, 2005.
[27] G. M.Clark, R. A.Popple, P. E. of S.-I. V. M. A. R. for T. of M. B. M.Young, andJ. B.Fiveash, “Feasibility of Single-Isocenter Volumetric Modulated Arc Radiosurgery for Treatment of Multiple Brain Metastases,” Int. J. Radiat. Oncol. Biol. Phys., vol. 76, no. 1, pp. 296–302, 2010.
[28] J. Z.Wang et al., “Intensity-modulated radiosurgery with rapidarc for multiple brain metastases and comparison with static approach,” Med. Dosim., vol. 37, no. 1, pp. 31–36, 2012.
[29] I.Iftimia, E. T.Cirino, L.Xiong, andH. W.Mower, “Quality assurance methodology for Varian RapidArc treatment plans,” J. Appl. Clin. Med. Phys., vol. 11, no. 4, pp. 130–143, 2010.
[30] D. M.Shepard, C.Yu, M.Murphy, M. R.Bussière, andF. J.Bova, “Treatment Planning for Stereotactic Radiosurgery,” in Principles and Practice of Stereotactic Radiosurgery, L. S.Chin andW. F.Regine, Eds.New York, NY: Springer New York, 2008, pp. 69–90.
[31] R.Ruggieri et al., “Linac-based VMAT radiosurgery for multiple brain lesions: Comparison between a conventional multi-isocenter approach and a new dedicated mono-isocenter technique,” Radiat. Oncol., vol. 13, no. 1, pp. 1–9, 2018.
[32] R.Ruggieri et al., “Linac-based radiosurgery for multiple brain metastases: Comparison between two mono-isocenter techniques with multiple non-coplanar arcs,” Radiother. Oncol., vol. 132, pp. 70–78, 2019.
[33] L.VanderSpek, J.Wang, J.Alksne, andK. T.Murphy, “Single Fraction, Single Isocenter Intensity Modulated Radiosurgery (IMRS) for Multiple Brain Metastases: Dosimetric and Early Clinical Experience,” Int. J. Radiat. Oncol., vol. 69, no. 3, Supplement, p. S265, 2007.
[34] S. K. M.Lau et al., “Single-Isocenter Frameless Volumetric Modulated Arc Radiosurgery for Multiple Intracranial Metastases,” Neurosurgery, vol. 77, no. 2, pp. 233–240, 2015.
[35] S. K.Nath et al., “Single-isocenter frameless intensity-modulated stereotactic radiosurgery for simultaneous treatment of multiple brain metastases: Clinical experience,” Int. J. Radiat. Oncol. Biol. Phys., vol. 78, no. 1, pp. 91–97, 2010.
[36] Q.Wu et al., “Optimization of treatment geometry to reduce normal brain dose in radiosurgery of multiple brain metastases with single-isocenter volumetric modulated Arc therapy,” Sci. Rep., vol. 6, no. September, pp. 1–8, 2016.
[37] M. D.Posner, J. M.Quivey, P. F.Akazawa, P.Xia, C.Akazawa, andL. J.Verhey, “Dose optimization for the treatment of anaplastic thyroid carcinoma: A comparison of treatment planning techniques,” Int. J. Radiat. Oncol. Biol. Phys., vol. 48, no. 2, pp. 475–483, 2000.
[38] M.Zarepisheh et al., “A moment-based approach for {DVH}-guided radiotherapy treatment plan optimization,” Phys. Med. Biol., vol. 58, no. 6, pp. 1869–1887, 2013.
[39] R.Prabhakar andG. K.Rath, “Slice-based plan evaluation methods for three dimensional conformai radiotherapy treatment planning,” Australas. Phys. Eng. Sci. Med., vol. 32, no. 4, pp. 233–239, 2009.
[40] B.Warkentin, P.Stavrev, N.Stavreva, C.Field, andB. G.Fallone, “A TCP-NTCP estimation module using DVHs and known radiobiological models and parameter sets,” J. Appl. Clin. Med. Phys., vol. 5, no. 1, pp. 50–63, 2004.
[41] E.Shaw et al., “Radiation therapy oncology group: Radiosurgery quality assurance guidelines,” Int. J. Radiat. Oncol. • Biol. • Phys., vol. 27, no. 5, pp. 1231–1239, 1993.
[42] R.Yaparpalvi et al., “Evaluating which plan quality metrics are appropriate for use in lung SBRT,” Br. J. Radiol., p. 20170393, 2018.
[43] I.Paddick, “A simple scoring ratio to index the conformity of radiosurgical treatment plans.,” J. Neurosurg., vol. 93, pp. 219–222, 2000.
[44] N. J.Lomax andS. G.Scheib, “Quantifying the degree of conformity in radiosurgery treatment planning,” Int. J. Radiat. Oncol. Biol. Phys., vol. 55, no. 5, pp. 1409–1419, 2003.
[45] L.Feuvret, G.Noël, J. J.Mazeron, andP.Bey, “Conformity index: A review,” International Journal of Radiation Oncology Biology Physics, vol. 64, no. 2. pp. 333–342, Feb.01, 2006.
[46] T.Knöös, I.Kristensen, andP.Nilsson, “Volumetric and dosimetric evaluation of radiation treatment plans: radiation conformity index,” Int. J. Radiat. Oncol. • Biol. • Phys., vol. 42, no. 5, pp. 1169–1176, 1998.
[47] I.Paddick andB.Lippitz, “A simple dose gradient measurement tool to complement the conformity index.,” J. Neurosurg., vol. 105 Suppl, pp. 194–201, 2006.
[48] R. D.Stewart andX. A.Li, “BGRT: Biologically guided radiation therapy—The future is fast approaching!,” Med. Phys., vol. 34, no. 10, pp. 3739–3751, 2007.
[49] V.Smith, L.Verhey, andC. F.Serago, “Comparison of radiosurgery treatment modalities based on complication and control probabilities,” Int. J. Radiat. Oncol. Biol. Phys., vol. 40, no. 2, pp. 507–513, 1998.
[50] B. G.Douglas andJ. F.Fowler, “The effect of multiple small doses of x rays on skin reactions in the mouse and a basic interpretation.,” Radiat. Res., vol. 66, no. 2, pp. 401–426, 1976.
[51] J. F.Fowler, “The first James Kirk memorial lecture. What next in fractionated radiotherapy?,” Br. J. Cancer. Suppl., vol. 6, pp. 285–300, 1984.
[52] T. R.Munro andC. W.Gilbert, “The relation between tumour lethal doses and the radiosensitivity of tumour cells.,” Br. J. Radiol., vol. 34, pp. 246–251, 1961.
[53] RaySearchLaboratories, “Biological Optimization and Evaluation in Raystation,” RaySearch White Pap., 2017.
[54] A.Dasu andI.Toma-Dasu, “Models for the risk of secondary cancers from radiation therapy,” Phys. Medica, vol. 42, pp. 232–238, 2017.
[55] D. L.Preston et al., “Solid Cancer Incidence in Atomic Bomb Survivors: 1958–1998,” Radiat. Res., vol. 168, no. 1, pp. 1–64, 2007.
[56] ICRP, “Annals of the ICRP PUBLICATION 103 The 2007 Recommendations of the International Commission on Radiological Protection.,” Ann. ICRP, vol. 37, pp. 1–332, 2007.
[57] National Research Council, “Health Risks from Exposure to Low Levels of Ionizing Radiation: BEIR VII Phase 2,” Natl. Acad. Press, 2006.
[58] E. J.Hall, D.Phil, andD.SC, “Intensity-modulated radiation therapy, protons, and the risk of second cancers,” Int. J. Radiat. Oncol. Biol. Physics., vol. 66, no. 5, pp. 1593–1594, 2006.
[59] B.Welte et al., “Second malignancies in high dose areas of previous tumor radiotherapy.,” Strahlentherapie und Onkol., vol. 186, no. 3, pp. 174–179, 2010.
[60] U.Schneider, “Dose response relationship for radiation-induced cancer decrease or plateau at high dose: In regard to Davis,” Int. J. Radiat. Oncol. Biol. Physics., vol. 61, no. 1, p. 312, 2004.
[61] U.Schneider, “Mechanistic model of radiation-induced cancer after fractionated radiotherapy using the linear-quadratic formula,” Med. Phys., vol. 36, no. 4, pp. 1138–1143, 2009.
[62] M.Moteabbed, T. I.Yock, andH.Paganetti, “The risk of radiation-induced second cancers in the high to medium dose region: A comparison between passive and scanned proton therapy, IMRT and VMAT for pediatric patients with brain tumors,” Phys. Med. Biol., vol. 59, no. 12, pp. 2883–2899, 2014.
[63] M.Mazonakis, C.Varveris, E.Lyraraki, andJ.Damilakis, “Radiotherapy for stage i seminoma of the testis: Organ equivalent dose to partially in-field structures and second cancer risk estimates on the basis of a mechanistic, bell-shaped, and plateau model,” Med. Phys., vol. 42, no. 11, pp. 6309–6316, 2015.
[64] C.Geng, M.Moteabbed, Y.Xie, J.Schuemann, T.Yock, andH.Paganetti, “Assessing the radiation-induced second cancer risk in proton therapy for pediatric brain tumors: The impact of employing a patient-specific aperture in pencil beam scanning,” Phys. Med. Biol., vol. 61, no. 1, pp. 12–22, 2015.
[65] H. F.Lee et al., “Radiation-induced secondary malignancies for nasopharyngeal carcinoma: A pilot study of patients treated via IMRT or VMAT,” Cancer Manag. Res., vol. 10, pp. 131–141, 2018.
[66] E. M.Thomas et al., “Comparison of plan quality and delivery time between volumetric arc therapy (rapidarc) and gamma knife radiosurgery for multiple cranial metastases,” Neurosurgery, vol. 75, no. 4, pp. 409–417, 2014.
[67] G. W.Barendsen, “Dose fractionation, dose rate and iso-effect relationships for normal tissue responses.,” Int. J. Radiat. Oncol. Biol. Phys., vol. 8, no. 11, pp. 1981–1997, 1982.
[68] J. F.Fowler, “The linear-quadratic formula and progress in fractionated radiotherapy,” Br. J. Radiol., vol. 62, no. 740, pp. 679–694, 1989.
[69] L.Hlatky, R. K.Sachs, M.Vazquez, andM. N.Cornforth, “Radiation-induced chromosome aberrations: Insights gained from biophysical modeling,” BioEssays, vol. 24, no. 8, pp. 714–723, 2002.
[70] J. F.Fowler andR. G.Dale, “When is a ‘bED’ not a ‘bED’? - When it is an EQD2: In regard to Buyyounouski et al.,” International Journal of Radiation Oncology Biology Physics, vol. 78, no. 2. Elsevier, pp. 640–641, Oct.01, 2010.
[71] S.Baliga et al., “Fractionated stereotactic radiation therapy for brain metastases: a systematic review with tumour control probability modelling,” Br. J. Radiol., vol. 90, no. 1070, p. 20160666, 2017.
[72] P.Okunieff, D.Morgan, A.Niemierko, andH. D.Suit, “Radiation dose-response of human tumors,” Int. J. Radiat. Oncol. Biol. Phys., vol. 32, no. 4, pp. 1227–1237, 1995.
[73] P.Rubin andG.Casarett, “A Direction for Clinical Radiation Pathology,” in Frontiers of Radiation Therapy and Oncology, 1972, pp. 1–16.
[74] J. T.Lyman, “Complication Probability as Assessed from Dose-Volume Histograms,” Radiat. Res. Suppl., vol. 8, pp. S13–S19, 1985.
[75] L.DeMarzi et al., “Use of gEUD for predicting ear and pituitary gland damage following proton and photon radiation therapy,” Br. J. Radiol., vol. 88, no. 1048, 2015.
[76] M.Lambrecht et al., “Radiation dose constraints for organs at risk in neuro-oncology; the European Particle Therapy Network consensus,” Radiother. Oncol., vol. 128, no. 1, pp. 26–36, 2018.
[77] S. M.Bentzen et al., “Quantitative Analyses of Normal Tissue Effects in the Clinic (QUANTEC): An Introduction to the Scientific Issues,” Int. J. Radiat. Oncol. Biol. Phys., vol. 76, no. 3 SUPPL., pp. 3–9, 2010.
[78] L. B.Marks et al., “Use of Normal Tissue Complication Probability Models in the Clinic,” Int. J. Radiat. Oncol. Biol. Phys., vol. 76, no. 3 SUPPL., 2010.
[79] C.Mayo, E.Yorke, andT. E.Merchant, “Radiation Associated Brainstem Injury,” Int. J. Radiat. Oncol. Biol. Phys., vol. 76, no. 3 SUPPL., pp. 36–41, 2010.
[80] N.Bhandare et al., “Radiation Therapy and Hearing Loss,” Int. J. Radiat. Oncol. Biol. Phys., vol. 76, no. 3 SUPPL., 2010.
[81] Y. R.Lawrence et al., “Radiation Dose-Volume Effects in the Brain,” Int. J. Radiat. Oncol. Biol. Phys., vol. 76, no. 3 SUPPL., pp. 20–27, 2010.
[82] C.Mayo, M. K.Martel, L. B.Marks, J.Flickinger, J.Nam, andJ.Kirkpatrick, “Radiation Dose-Volume Effects of Optic Nerves and Chiasm,” Int. J. Radiat. Oncol. Biol. Phys., vol. 76, no. 3 SUPPL., pp. 28–35, 2010.
[83] C.Burman, G. J.Kutcher, B.Emami, andM.Goitein, “Fitting of normal tissue tolerance data to an analytic function,” Int. J. Radiat. Oncol. Biol. Phys., vol. 21, no. 1, pp. 123–135, 1991.
[84] U.Schneider, M.Sumila, andJ.Robotka, “Site-specific dose-response relationships for cancer induction from the combined Japanese A-bomb and Hodgkin cohorts for doses relevant to radiotherapy,” Theor. Biol. Med. Model., vol. 8, no. 1, pp. 1–21, 2011.
[85] U.Schneider, D.Zwahlen, D.Ross, andB.Kaser-Hotz, “Estimation of radiation-induced cancer from three-dimensional dose distributions: Concept of organ equivalent dose,” Int. J. Radiat. Oncol. Biol. Phys., vol. 61, no. 5, pp. 1510–1515, 2005.
[86] B.Sánchez-Nieto, M.Romero-Expósito, J. A.Terrón, andF.Sánchez-Doblado, “Uncomplicated and Cancer-Free Control Probability (UCFCP): A new integral approach to treatment plan optimization in photon radiation therapy,” Phys. Medica, vol. 42, pp. 277–284, 2017.
[87] B.Sánchez-Nieto et al., “External photon radiation treatment for prostate cancer: Uncomplicated and cancer-free control probability assessment of 36 plans,” Phys. Medica, vol. 66, pp. 88–96, 2019.
[88] S. K. M.Lau et al., “Single-Isocenter Frameless Volumetric Modulated Arc Radiosurgery for Multiple Intracranial Metastases,” Neurosurgery, vol. 77, no. 2, pp. 233–240, 2015.
[89] M.Uto et al., “Dosimetric comparison between dual-isocentric dynamic conformal arc therapy and mono-isocentric volumetric-modulated arc therapy for two large brain metastases,” J. Radiat. Res., vol. 59, no. 6, pp. 774–781, 2018.
[90] T.Gevaert et al., “Evaluation of a dedicated brain metastases treatment planning optimization for radiosurgery: A new treatment paradigm?,” Radiat. Oncol., vol. 11, no. 1, pp. 1–7, 2016.
[91] Å.Ballangrud et al., “Institutional experience with SRS VMAT planning for multiple cranial metastases,” J. Appl. Clin. Med. Phys., vol. 19, no. 2, pp. 176–183, 2018.
[92] G.Narayanasamy et al., “A Systematic Analysis of 2 Monoisocentric Techniques for the Treatment of Multiple Brain Metastases,” Technol. Cancer Res. Treat., vol. 16, no. 5, pp. 639–644, 2017.
[93] H.Liu et al., “Interinstitutional Plan Quality Assessment of 2 Linac-Based, Single-Isocenter, Multiple Metastasis Radiosurgery Techniques,” Adv. Radiat. Oncol., pp. 1–10, 2020.
[94] Y.Cui, H.Gao, J.Zhang, J. P.Kirkpatrick, andF. F.Yin, “Retrospective quality metrics review of stereotactic radiosurgery plans treating multiple targets using single-isocenter volumetric modulated arc therapy,” J. Appl. Clin. Med. Phys., no. June 2019, 2020.
[95] Y.Yuan, E. M.Thomas, G. A.Clark, J. M.Markert, J. B.Fiveash, andR. A.Popple, “Evaluation of multiple factors affecting normal brain dose in single-isocenter multiple target radiosurgery,” J. Radiosurgery SBRT, vol. 5, no. 2, pp. 131–144, 2018.
[96] I.Vergalasova et al., “Multi-institutional dosimetric evaluation of modern day stereotactic radiosurgery (SRS) treatment options for multiple brain metastases,” Front. Oncol., vol. 9, pp. 1–12, 2019.
[97] J.Hofmaier et al., “Single isocenter stereotactic radiosurgery for patients with multiple brain metastases: Dosimetric comparison of VMAT and a dedicated DCAT planning tool,” Radiat. Oncol., vol. 14, no. 1, p. 103, 2019.
[98] K.Yoshio et al., “Plan quality comparison between 4-arc and 6-arc noncoplanar volumetric modulated arc stereotactic radiotherapy for the treatment of multiple brain metastases,” Med. Dosim., vol. 43, no. 4, pp. 358–362, 2018.
[99] J.Kang, E. C.Ford, K.Smith, J.Wong, andT. R.McNutt, “A method for optimizing LINAC treatment geometry for volumetric modulated arc therapy of multiple brain metastases.,” Med. Phys., vol. 37, no. 8, pp. 4146–4154, 2010.
[100] Z.Abisheva et al., “The effect of MLC leaf width in single-isocenter multi-target radiosurgery with volumetric modulated arc therapy,” J. radiosurgery SBRT, vol. 6, no. 2, pp. 131–138, 2019, [Online]. Available: https://pubmed.ncbi.nlm.nih.gov/31641549.
[101] X. A.Li et al., The Use and QA of Biologically Related Models for Treatment Planning Report of AAPM Task Group 166, no. 166. 2012.
[102] S. J.McMahon andK. M.Prise, “Mechanistic modelling of radiation responses,” Cancers (Basel)., vol. 11, no. 2, 2019.
[103] C.Park, L.Papiez, S.Zhang, M.Story, andR. D.Timmerman, “Universal Survival Curve and Single Fraction Equivalent Dose: Useful Tools in Understanding Potency of Ablative Radiotherapy,” Int. J. Radiat. Oncol. Biol. Phys., vol. 70, no. 3, pp. 847–852, 2008.
[104] R.Wiggenraad, A. V.DeKanter, H. B.Kal, M.Taphoorn, T.Vissers, andH.Struikmans, “Dose-effect relation in stereotactic radiotherapy for brain metastases. A systematic review,” Radiother. Oncol., vol. 98, no. 3, pp. 292–297, 2011.
[105] A.Fogliata et al., “Critical Appraisal of the Risk of Secondary Cancer Induction From Breast Radiation Therapy With Volumetric Modulated Arc Therapy Relative to 3D Conformal Therapy,” Int. J. Radiat. Oncol. Biol. Phys., vol. 100, no. 3, pp. 785–793, 2018.
[106] A.Joosten, O.Matzinger, W.Jeanneret-Sozzi, F.Bochud, andR.Moeckli, “Evaluation of organ-specific peripheral doses after 2-dimensional, 3-dimensional and hybrid intensity modulated radiation therapy for breast cancer based on Monte Carlo and convolution/superposition algorithms: Implications for secondary cancer risk asses,” Radiother. Oncol., vol. 106, no. 1, pp. 33–41, 2013.
[107] L.Wang andG. X.Ding, “Estimating the uncertainty of calculated out-of-field organ dose from a commercial treatment planning system,” J. Appl. Clin. Med. Phys., vol. 19, no. 4, pp. 319–324, 2018.
[108] K.H.V Medical Physics at Institute of Radiooncology, “Modelling the HD120 Out-of-Field Dose with Eclipse 13,” [online]. Available: https://www.wienkav.at /kav/kfj/91033454/, 2014.