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研究生:李家誠
研究生(外文):Lee, Jia-Cheng
論文名稱:硼中子捕獲臨床治療之劑量評估研究
論文名稱(外文):Dose Evaluation of Clinical Boron Neutron Capture Treatment
指導教授:莊克士莊克士引用關係
指導教授(外文):Chuang, Keh-Shih
口試委員:劉鴻鳴顏上惠許芳裕周鳳英
口試委員(外文):Liu, Hong-MingYen, Sang-HueHsu, Fang-YuhChou, Fong-In
口試日期:2018-10-05
學位類別:博士
校院名稱:國立清華大學
系所名稱:生醫工程與環境科學系
學門:工程學門
學類:生醫工程學類
論文種類:學術論文
論文出版年:2018
畢業學年度:107
語文別:英文
論文頁數:71
中文關鍵詞:硼中子捕獲治療多照野位移劑量誤差強度調控放射治療
外文關鍵詞:Boron Neutron Capture TreatmentMulti-fieldPosition errorDosimetric errorIntensity modulated radiation therapy
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本論文有三個主題,第一個主題為多角度針對瀰漫型內因性橋腦神經膠細胞瘤病患在硼中子捕獲治療的初步劑量研究的可行性,第二個主題為硼中子捕獲治療中腦瘤病患在定位位移的劑量影響,第三個主題為頭頸癌之總腫瘤體積對於硼中子捕獲治療及合併硼中子捕獲治療及強度調控放射治療的劑量比較。
第一,瀰漫型內因性橋腦神經膠細胞瘤(diffuse intrinsic pontine glioma,DIPG)是一種非常難以治療的腫瘤。腫瘤對腦幹的浸潤不太可能手術切除,並且可能導致劑量的限制,阻礙常規放療中劑量遞增的嘗試。作為標靶放射治療方法,硼中子捕獲治療(boron neutron capture therapy,BNCT)提供了以足夠的劑量選擇性地照射腫瘤同時保留鄰近的正常組織的潛力。然而,由於中子束穿透不充分,先前要求在照射前進行開顱手術用單一照野BNCT治療DIPG的嘗試。在這劑量學研究中,我們研究了連續12例接受常規放療的患者,以評估無開顱術的多照野BNCT的可行性。1.1.44版的NCTPlan用於劑量計算,與兩個照野和三個照野照射相比,四個照野照射使平均最大劑量減少至正常大腦至7.35±0.72 Gy-Eq。通過四個照野照射,最小劑量與臨床靶體積和最大劑量與正常組織的平均比值為2.41±0.26。當使用多照野BNCT治療DIPG而不進行開顱手術時,可以預期治療益處,並且通過使用四照野設置可以最小化正常腦的最大劑量。
第二,與傳統的光子放射治療不同,複雜的患者定位工具不適用於硼中子捕獲治療(BNCT),因此BNCT仍易受擺位錯誤和分次內患者運動的影響,本研究的目的是評估定位偏差對清華水池式反應爐(Tsing Hua open-pool reactor,THOR)腦瘤BNCT傳遞劑量的影響,對於這些研究,基於患有腦腫瘤的患者的電腦斷層掃描(computed tomography,CT)影像形成模擬頭部模型,模擬直徑3cm、長5cm的圓柱型腦瘤且距離該頭部模型的後頭皮6.5cm和2.5cm的距離(分別為T6.5cm和T2.5cm),評估針對每個距離與定位誤差相關的輻射劑量,包括上、下、左、右位移,從照野中心軸的偏移以及從射束的表面向外移位,還評估了旋轉和傾斜效應。劑量處方為20 Gy-Eq至80%的腫瘤體積,治療計劃系統NCTPlan用於進行劑量計算。與給予初始腫瘤位置的劑量相比,在T6.5cm下1 cm、2 cm和3 cm位移(左側、右側、上側和下側)的平均腫瘤劑量分別下降約1%、6%和11%;在T6.5cm下對於1 cm、2 cm和3 cm向外移位的平均腫瘤劑量的分別降低約5%、11%和15%。對於T2.5cm的淺表腫瘤,在1 cm的橫向移位後未觀察到平均腫瘤劑量的顯著降低,旋轉和傾斜達15度下並不會導致腫瘤劑量的顯著差異。由於定位的變化,與正常組織的劑量差異也是最小的。總之,這些數據表明在THOR,在較大深度處給予腫瘤的平均劑量可能更容易受到定位偏差的影響,並且更大的移位距離導致平均腫瘤劑量減少,此外這些數據提供了在BNCT期間由擺位誤差或分次內運動引起的劑量差異的估計,並且這些可以促進在未來治療中更準確地預測患者實際劑量。
第三,九名患有復發性頭頸部(head and neck,H&N)癌症的患者使用THORplan治療計劃系統(treatment planning system,TPS)在清華水池式反應爐中一個分次接受硼中子捕獲治療(BNCT),本研究的目的是評估使用強度調控放射治療(intensity modulated radiation therapy,IMRT)來補償單獨使用單照野BNCT時通常觀察到的劑量異質性,並評估模擬BNCT+IMRT與單獨BNCT的計劃品質指數,所有IMRT計劃均使用Eclipse治療計畫系統生成,該治療計畫系統採用非均向解析演算法。對於BNCT+IMRT計劃,總腫瘤體積(gross tumor volume,GTV)的順形指數優於單獨BNCT計劃(p = 0.003),此外BNCT+IMRT計劃在GTV中提供了明顯更好的均勻度(p = 0.03),BNCT計劃中不均勻劑量分佈的劑量低點可能是頭頸癌症復發的關鍵因素,我們的研究結果表明,BNCT+IMRT改善了治療的均勻度和順形性,特別是腫瘤體積大於100 cm3,並可能增加局部腫瘤控制。
There are three parts in this thesis. The topic in first part was “Preliminary dosimetric study on feasibility of multi-beam boron neutron capture therapy in patients with diffuse intrinsic pontine glioma without craniotomy”. The second topic was “The dosimetric impact of shifts in patient positioning during boron neutron capture therapy for brain tumors”. The final topic of paper was “A comparison of dose distributions in gross tumor volume between boron neutron capture therapy alone and combined boron neutron capture therapy plus intensity modulation radiation therapy for head and neck cancer”.
In first part, diffuse intrinsic pontine glioma (DIPG) is a very difficult type of tumor to treat. Infiltration of the brain stem by the tumor can make surgical removal impossible and can lead to dose constraints that impede attempts at dose escalation in conventional radiotherapy. As a targeted radiotherapy approach, boron neutron capture therapy (BNCT) offers the potential to irradiate tumors selectively with an adequate dose while sparing adjacent normal tissue. However, due to inadequate penetration of the neutron beam, previous attempts at treating DIPG with single-field BNCT required that craniotomy be performed before irradiation. In this dosimetric study, 12 consecutive patients treated with conventional radiotherapy in our institute were reviewed to evaluate the feasibility of multi-field BNCT without craniotomy. NCTPlan Ver. 1.1.44 was used for dose calculations. Compared with two- and three-field irradiation, four-field irradiation reduced the average maximal dose to the normal brain to 7.35 ± 0.72 Gy-Eq. The mean ratio of minimal dose to clinical target volume and maximal dose to normal tissue was 2.41 ± 0.26 by four-field irradiation. A therapeutic benefit may be expected when using multi-field BNCT to treat DIPG without craniotomy, and the maximal dose to the normal brain would be minimized by using the four-field setting.
In second part, unlike conventional photon radiotherapy, sophisticated patient positioning tools are not available for boron neutron capture therapy (BNCT). Thus, BNCT remains vulnerable to setup errors and intra-fractional patient motion. The aim of this study was to estimate the impact of deviations in positioning on the dose administered by BNCT for brain tumors at the Tsing Hua open-pool reactor (THOR). For these studies, a simulated head model was generated based on computed tomography (CT) images of a patient with a brain tumor. A cylindrical brain tumor 3 cm in diameter and 5 cm in length was modeled at distances of 6.5 cm and 2.5 cm from the posterior scalp of this head model (T6.5 cm and T2.5 cm, respectively). Radiation doses associated with positioning errors were evaluated for each distance, including left and right shifts, superior and inferior shifts, shifts from the central axis of the beam aperture, and outward shifts from the surface of the beam aperture. Rotational and tilting effects were also evaluated. The dose prescription was 20 Gray-equivalent (Gy-Eq) to 80 % of the tumor. The treatment planning system, NCTPlan, was used to perform dose calculations. The average decreases in mean tumor dose for T6.5 cm for the 1 cm, 2 cm, and 3 cm lateral shifts composed by left, right, superior, and inferior sides, were approximately 1 %, 6 %, and 11 %, respectively, compared to the dose administered to the initial tumor position. The decreases in mean tumor dose for T6.5 cm were approximately 5 %, 11 %, and 15 % for the 1 cm, 2 cm, and 3 cm outward shifts, respectively. For a superficial tumor at T2.5cm, no significant decrease in average mean tumor dose was observed following lateral shifts of 1 cm. Rotational and tilting up to 15° did not result in significant difference to the tumor dose. Dose differences to the normal tissues as a result of the shifts in positioning were also minimal. Taken together, these data demonstrate that the mean dose administered to tumors at greater depths is potentially more vulnerable to deviations in positioning, and greater shift distances resulted in reduced mean tumor doses at the THOR. Moreover, these data provide an estimation of dose differences that are caused by setup error or intra-fractional motion during BNCT, and these may facilitate more accurate predictions of actual patient dose in future treatments.
In third part, nine patients with recurrent head and neck (H&N) cancer received boron neutron capture therapy (BNCT) in one fraction at the Tsing-Hua Open pool reactor (THOR) utilizing the THORplan treatment planning system (TPS). The aims of the present study were to evaluate the use of intensity modulated radiation therapy (IMRT) to compensate for the dose heterogeneity generally observed with single-field BNCT alone, and to evaluate planning quality indices of simulated BNCT+IMRT versus BNCT alone. All IMRT plans were generated using the Eclipse TPS which employs the analytical anisotropic algorithm. The conformity index for the gross tumor volume (GTV) was better for the BNCT+IMRT plan than for the BNCT-alone plan (p = 0.003). In addition, the BNCT+IMRT plan provided significantly better homogeneity in the GTV (p = 0.03). The cold spots in inhomogeneous dose distribution in the BNCT plan may be a key factor for H&N cancer recurrence. Our results suggest that BNCT+IMRT improves treatment homogeneity and conformity, especially for tumor volumes >100 cm3, and possibly increases local tumor control.
Content

Chinese Abstract……………………………………………………..…………………i
Abstract…………………………………………………………...…………………..iii
Acknowledgement…………………………………………………………………….vi
Content………………………………………………………………………………viii
Table list……………………………………………………………………..……….xii
Figures list…………………………………………………………………..……….xiv

Chapter 1 General introduction………………………………………………………..1
 1.1 Preliminary dosimetric study on feasibility of multi-beam boron neutron
capture therapy in patients with diffuse intrinsic pontine glioma without
craniotomy……………………………………………………………..……..1
 1.2 The dosimetric impact of shifts in patient positioning during boron neutron
capture therapy for brain tumors……………………………………………..5
 1.3 A comparison of dose distributions in gross tumor volume between boron
neutron capture therapy alone and combined boron neutron capture therapy
plus intensity modulation radiation therapy treatment planning for head and
neck cancer……………………………………………………………...……7
 1.4 Structure of thesis……………………………………………………….……9

Chapter 2 Preliminary dosimetric study on feasibility of multi-beam boron neutron
capture therapy in patients with diffuse intrinsic pontine glioma without
craniotomy…………………………………………………………………11
 2.1 Neutron source…………………………………………………………11
 2.2 Patient selection……………………………………………………….11
 2.3 Treatment planning systems…………………………………………...12
 2.4 Delineation of target volume and normal tissue……………………….15
 2.5 Dosimetric evaluation…………………………………………………15
 2.6 Statistical analysis……………………………………………………..16

Chapter 3 The dosimetric impact of shifts in patient positioning during boron neutron
capture therapy for brain tumors…………………………………………..17
 3.1 Homogeneous cylindrical phantom model…………………………….17
 3.2 Patient head model…………………………………………………….18
 3.3 Neutron source………………………………………………………...19
 3.4 Overview of NCTPlan…………………………………………………20
 3.5 Dose calculation parameters…………………………………………...21
 3.6 Statistical analysis……………………………………………………..22

Chapter 4 A comparison of dose distributions in gross tumor volume between boron
neutron capture therapy alone and combined boron neutron capture therapy
plus intensity modulation radiation therapy treatment planning for head and
neck cancer………………………………………………………………...24
 4.1 Patient selection………………………………………………………..24
 4.2 Treatment planning systems…………………………………………...25
 4.3 Dosimetric evaluation…………………………………………………28
 4.4 Statistical analysis……………………………………………………..30

Chapter 5 Results…………………………………………………………………….31
 5.1 Preliminary dosimetric study on feasibility of multi-beam boron neutron
capture therapy in patients with diffuse intrinsic pontine glioma without
craniotomy…………………………………………………………………..31
 5.1.1 Maximal tumor depths and dose distributions………………………31
 5.1.2 Target dosimetric evaluation………………………………………..33
 5.1.3 Radiation exposure to at-risk organs…………………………..…...35
 5.2 The dosimetric impact of shifts in patient positioning during boron neutron
capture therapy for brain tumors……………………………………………37
 5.2.1 Tumor dose for the cylindrical phantom…………………………….37
 5.2.2 Tumor dose for the patient head model……………………………...37
 5.2.3 Dose robustness for tumors at different depths……………………...42
 5.2.4 Normalized dose profile for the cylindrical phantom and patient head
models………………………………………………………………..43
 5.2.5 Isodose curves for the cylindrical phantom and patient head models
with lateral shifts……………………………………………………..43
 5.2.6 Changes in percent mean tumor dose compared to BMRR…………44
 5.2.7 Normal tissue dose with positioning shifts………………………….45
 5.3 A comparison of dose distributions in gross tumor volume between boron
neutron capture therapy alone and combined boron neutron capture therapy
plus intensity modulation radiation therapy treatment planning for head and
neck cancer………………………………………………………………….48
 5.3.1 Isodose curve and dose-volume histogram………………………….48
 5.3.2 Target dosimetric evaluation…………………………………………52
 5.3.3 Radiation exposure to at-risk organs……………………………….55

Chapter 6 Discussion……………………….………………………………………57
 6.1 Preliminary dosimetric study on feasibility of multi-beam boron neutron
capture therapy in patients with diffuse intrinsic pontine glioma without
craniotomy………………………………………………………………..57
 6.2 The dosimetric impact of shifts in patient positioning during boron neutron
capture therapy for brain tumors…………………………………………59
 6.3 A comparison of dose distributions in gross tumor volume between boron
neutron capture therapy alone and combined boron neutron capture
therapy plus intensity modulation radiation therapy treatment planning for
head and neck cancer…………………………………………………...63

Chapter 7 Summary and conclusion…………………………………………..……66

References……………………………………………………………………………67
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