四維氟十八去氧葡萄糖正子暨電腦斷層攝影於放射治療之腫瘤體積規劃在食道癌之臨床應用

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题名:	四維氟十八去氧葡萄糖正子暨電腦斷層攝影於放射治療之腫瘤體積規劃在食道癌之臨床應用 The clinical application of 4D 18F-FDG PET/CT on gross tumor volume delineation for radiotherapy planning in esophageal squamous cell cancer
作者:	王耀慶
贡献者:	臨床醫學研究所碩士班
关键词:	四維氟十八去氧葡萄糖正子暨電腦斷層攝影;放射治療;食道癌 4D;18F-FDG PET/CT;radiotherapy;esophageal squamous cell cancer
日期:	2011-07-22
上传时间:	2011-10-17 16:55:17 (UTC+8)
出版者:	中國醫藥大學
摘要:	研究目的：文獻建議使用正子攝影到電腦斷層影像上在定義腫瘤體積(gross tumor volume)，減少觀察者之間的差異，及治療計畫的改變有一些影響。在肺部的腫瘤而言，包含食道癌，呼吸造成了器官及腫瘤的移動進而影響電腦斷層影像的準確度及品質。本文研究目的是評估結合四維電腦斷層暨四維正子攝影在食道癌規畫標靶腫瘤體積的可行性。並且我們假設可藉由使用從四維電腦斷層暨正子攝影獲得的生理標靶體積(biological target volume)可得到一些標準可作為食道癌的腫瘤體積規劃的依據。研究方法：本研究是一採用前瞻性的分析四維電腦斷層暨正子攝影在食道癌放射治療計畫的研究。經過本院醫學倫理委員會的認證許可(DMR 98-IRB-171-1及DMR 98-IRB-171-2)才執行。病患需有病理證實且將執行治癒性放射治療，同步化學及放射治療，或外科手術治療才收案。從西元2009年12月到2011年1月，共有18人進入研究。每一位病患在檢查時需先靜脈注射氟十八去氧葡萄糖370百萬貝克(MBq)[10毫居里(mCi)]然後在一個安靜且微暗的房間休息。病患採取仰躺及放射治療姿勢下，加上呼吸調控裝置(Real-time Position Management, Varian Medical System Inc)以進行攝影。四維電腦斷層攝影影像的厚度為2.5毫米，正子攝影收兩個單位(table position)，每一單位為七分鐘。所有呼吸期別影像經由自動影像疊合(fusion)。在所有呼吸期別的四維影像中，分析平均期（average phase）四維電腦斷層攝影影像與平均期正子攝影影像疊合一起，探討最佳標準攝取值(SUV)的閾值。正子攝影得到的腫瘤體積是由AW工作站(advantage SimTM 7.6.,GE,Healthcare)以自動畫輪廓方式，選取八種閾值來作進一步分析: SUV15%, SUV2, SUV2.5, SUV20%, SUV25%,SUV30%, SUV40% 及 SUV50%。根據有顯影劑的電腦斷層影像，食道內視鏡及超音波影像，在平均期四維電腦斷層影像上畫出標準參考的腫瘤體積。為了減少觀察者間的誤差，至少二位放射腫瘤科醫師對每位病人執行參考腫瘤體積規劃。從電腦斷層攝影及正子攝影得到的靶體積，以體積比率(volume ratio)及順型指數(conformality index)來比較彼此差異。順型指數是兩者體積的交集除以兩者體積的聯集。體積比率是兩者的體積相除，以電腦斷層的體積為分母。適合的標準攝取值閾值是指正子攝影的腫瘤體積與電腦斷層攝影參考的腫瘤體積來做比較，而定義出在長度，順型指數或體積比率最相似的標準攝取值閾值。研究結果：四維電腦斷層暨正子攝影經由自動影像融合成功的有十二位病人共十三個腫瘤體積。有六位病人無法得到疊合的影像。平均病患年齡為48.5歲(38-76歲)。所有病患皆為男性。十一個腫瘤的T分期為T3和T4。食道內視鏡共有九位病人(75%)執行。平均電腦斷層影像靶體積的長度為5.73 ± 2.40cm (1.75-10.01cm)。平均電腦斷層影像的腫瘤體積為29.41 ± 19.14mL (3.65-70.76 mL)。平均最大標準攝取值（SUVmax）為13.26 ± 2.78 (9.4-16.9)。腫瘤長度的決定係數(R2) 在閾值為SUV2.5, SUV20% 和SUV25% 各別是0.79,0.65 和0.54。平均體積比率從0.30到 1.48 (0.86±0.24)。最佳的體積比率為0.98 (最接近於1)是在SUV 20% 或 SUV 2.5。所有的SUV值與SUV2.5比較, P值在SUV15%, SUV40% 和 SUV50% 分別是0.007, 0.002, and 0.000。平均順行指數從0.28 到0.58。最好的順行指數在SUV 20%(0.58 ± 0.10)或SUV 2.5(0.57 ± 0.13)。所有的SUV值與 SUV20%比較, P值在SUV40%和SUV50%分別是0.014,和 0.000。研究結論：本篇研究顯示四維正子暨電腦斷層攝影在食道癌的腫瘤的體積規劃在放射腫瘤治療上是可行的。使用SUV 20% 或SUV 2.5 為閾值，可以獲得最佳的腫瘤長度，體積比率及順行指數。使用四維正子暨電腦斷層攝影在放射治療計畫的好處，需要更多的臨床經驗才能評估最後的臨床治療效果。 Purpose: Studies suggested PET overlay on CT has shown to have some impact on the definition of the gross tumor volume (GTV), decrease inter-observer variability and change the treatment planning. Organs or tumor motion always influenced the accuracy and quality of CT images in the thoracic malignancy, including esophageal cancer during free breathing cycle. To estimate the feasibility of the combined four-dimensional computed tomography with four-dimensional 18F-fluorodeoxyglucose positron emission tomography (4D PET/CT) in GTV delineation of esophageal cancer. We hypothesized that some standards can be obtained when defining GTV for esophageal cancer by using biological target volume from 4D-PET/CT images. Methods and Materials: This study was a prospective analysis, approved by local institutional review board (DMR98- IRB-171-1 and DMR98- IRB-171-2), of 4D-PET/CT in radiotherapy planning of esophageal cancer. Patients with histologically approved esophageal cancer who would undergo definitive radiotherapy, concurrent chemoradiotherapy or radical surgery were eligible for this study. Eighteen patients with esophageal squamous cell cancer were enrolled between December 2009 and January 2011. Each of them was administered intravenously with 370 MBq (10 mCi) of 18F-FDG and rested supine in a quiet and dimly room. Patients were positioned and simulated in a radiotherapy planning position using the Real-time Position Management system respiratory gating hardware (Varian Medical Systems Inc). Four-dimensional CT images with 2.50-mm slice thickness, and 4D PET images with two table positions, 7 minutes per position, were acquired. All phases of CT images and PET images were automatically fused for this gating study. In 4D images during respiratory cycle, an average phase of CT images was fused with average phase of FDG PETs for analysis of optimal threshold or standardized uptake values (SUV). PET-based GTV (GTVPET) was determined with 8 different threshold methods by autocontouring function at the AW workstation (Advantage SimTM 7.6.0, GE, Healthcare): SUV15%, SUV 2, SUV 2.5, SUV 20%, SUV 25%, SUV 30%, SUV 40% and SUV 50%. The information of tumor extent from the contrast CT scan, panendoscopy and endoscopic ultrasonography (EUS) were used when delineating the CT-based GTV (GTVCT). Excluding the adjacent metastatic lymph nodes, the volume of GTVCT was contoured as a reference tumor volume. To reduce inter-observer variations, at least 2 different radiation oncologists carried out the contouring of the tumors for each patient. GTVPET was compared with GTVCT by volume ratio (VR) and conformality index (CI). CI is the ratio of the volume of intersection of two volumes compared with the volume of union of the two volumes under comparison. VR is the ratio of two volumes, and the denominator is the volume of GTVCT. A suitable threshold level could be defined when GTVPET was observed to be the best fitness of the length, CI or VR from the GTVCT. Results: Automatic co-registrations of 4D CT-FDG PET were successful in 12 patients with 13 GTVCT. The fused images were not available in the other 6 patients. The median age was 48.5years (range, 38-76 years). All patients were men. Eleven lesions (85%) were T3 and T4 stage. EUS was performed for 9 patients (75%). The mean length of GTVCT was 5.73 ± 2.40cm (range, 1.75-10.01cm). The mean volume of GTVCT was 29.41 ± 19.14mL (range, 3.65-70.76 mL). The mean SUVmax was 13.26 ± 2. 78 (range, 9.4-16.9). The decision coefficient (R2) of tumor length difference at the threshold levels of SUV2.5, SUV20% and SUV25% were 0.79, 0.65 and 0.54, respectively. The mean VR ranged from 0.30 to 1.48 (0.86±0.24). The optimal VR, 0.98, close to 1, was at SUV 20% or SUV 2.5. All SUV thresholds compare with SUV 2.5, the p values of SUV15%, SUV40% and SUV50% are 0.007, 0.002, and 0.000, respectively. The mean CI ranged from 0.28 to 0.58. The best fitness for CI was at SUV 20% (0.58 ± 0.10) or SUV 2.5 (0.57 ± 0.13). All SUV thresholds compare with SUV20%, the p values of SUV40% and SUV50% are 0.014, and 0.000, respectively. Conclusions: This study demonstrated that 4D-PET/CT is applicable when contouring the GTV in radiation planning for esophageal cancer. The use of threshold levels of SUV 20% or SUV 2.5 achieves the optimal correlation with tumor length, VR and CI. To assess final treatment outcome, the benefits of RT planning using 4D-PET/CT need more clinical investigations.
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