肺癌精准放射治疗中呼吸运动解决方案

随着图像引导放疗技术的不断发展，摆位误差对肺癌三维适形调强放疗的影响明显减小，然而，影响肺癌精准放疗剂量提升的另一重要因素——呼吸运动，仍然困扰着肿瘤放疗工作者。目前，解决呼吸运动对肺癌放疗影响的方法大致包括个体化内靶体积（internal target volume，ITV）勾画、呼吸控制技术、呼吸门控放疗以及实时跟踪放疗等技术。     

主动呼吸控制系统在肝癌三维适形放疗中的应用研究

近年随计算机技术、放射生物学的发展，三维适形及调强放疗，立体定向外科手术开始应用于肝癌的治疗，为不能切除的患者提供了较好治疗效果，甚至获得二次根治切除的机会。然而，肿瘤随呼吸运动是影响精确放疗的主要问题。主动呼吸控制系统（ABC）是在放疗时将呼吸临时暂停在呼吸周期的某一阶段，有效减少放疗过程中靶区运动。笔者旨在初步探索ABC应用于肝癌三维适形放疗临床可行性，分析主动呼吸控制和自由呼吸状态下横膈和肝内靶区的动度。     

呼吸运动对食管癌靶区影响的研究

[目的]探索食管癌适形放疗中呼吸运动对靶区的影响,为靶区的勾画提供依据。[方法]对23例确诊食管癌患者分别于平静呼吸、平静吸气末、平静呼气末状态下对靶区行CT扫描,将扫描图像传输至治疗计划系统,进行图像融合,并测量靶区动度数据。[结果]肿瘤靶区几何中心在Y轴、X轴、Z轴方向上呼吸动度的平均值,10例中段食管癌患者分别为0.46±0.14cm,0.52±0.26cm,0.59±0.26cm;13例下段食管癌患者分别为1.17±0.69cm,0.95±0.74cm,0.82±0.35cm。取95%可信区间作为GTV外扩边界,23例食管癌靶区在三维方向上位移分别为上侧0.74cm,下侧1.62cm,左侧0.91cm,右侧0.66cm,前侧0.87cm,后侧0.59cm。[结论]受呼吸运动影响食管癌GTV几何中心在Y轴、X轴、Z轴方向均会发生不同程度的移位,勾画靶区时中应充分考虑这一因素。     

CT模拟确定肺癌靶区体积的影响因素研究

为准确确定肺癌的三维形状及体积,为三维适形放疗提供真实准确的影像信息,为实施精确放疗,笔者进行了CT模拟确定靶区体积的影响因素研究。一、材料与方法1.材料:通过一变速电机控制靶区运动速度,模拟靶区随呼吸运动的频率;通过一偏心轮的离心程度模拟肺呼吸时靶区的最大移动幅度。模体内一圆球形及以一正方体靶区     

功能影像在确定非小细胞肺癌生物靶区中的应用和展望

准确勾画非小细胞肺癌（NSCLC）的生物靶区对非小细胞肺癌（NSCLC）三维适形调强放疗有重要的作用。PET、SPECT等功能显像以及图像融合技术的发展为准确定位NSCLC生物靶区提供了可能。本文综述了功能影像技术在NSCLC的应用，并对各种功能显像的现状进行阐明，同时展望了功能影像在非小细胞肺癌生物靶区确定和适形调强放疗中的前景和挑战。     

模拟呼吸运动对三维放疗剂量分布的影响

目的 通过模拟呼吸运动来观察对三维适形放疗(3DCRT)和调强放疗(IMRT)剂量分布的影响。方法 将德国PTW 2D-ARRAY seven29剂量矩阵平板放在呼吸模拟机上,比较模拟呼吸运动和静止状态下的质量保证计划和治疗计划系统输出的等中心处水平面剂量分布。两组间数据行配对t检验。结果 呼吸运动均能降低靶区剂量分布和靶区剂量的适形度;3DCRT的γ通过率(3%3 mm)大于IMRT的\[(53.58±0.74)%、(30.71±1.00)%,t=57.91,P<0.01\]。呼吸运动对3DCRT的影响集中在靶区周边,对IMRT的影响分布与整个靶区。结论 对呼吸运动幅度较大处肿瘤采用3DCRT,若采用IMRT应根据情况对靶区及剂量均应适当修正。     

CT与MRI图像融合在头颈部肿瘤放疗靶区勾画中的应用

放射肿瘤学己逐步从常规外照射向立体定向放疗、三维适形放疗、调强放疗等精确放疗发展，而肿瘤靶区边界和正常组织轮廓定义的精确与否己成为肿瘤放疗计划优劣的基础和评估的依据。放疗计划系统解剖结构主要取自于CT，但是CT对软组织分辨率较低，如果仍简单地采用CT图像来定义靶区轮廓，就可能遗漏部分靶体积，增加了肿瘤复发概率。因此对常用CT和MRI利用图像融合配准技术得到融合图像，探讨两种图像在头颈部肿瘤放疗当中对GTV确定的优缺点。[第一段]     

非小细胞肺癌三维适形放疗的靶区确定

三维适形放疗(3DCRT)能够提高治疗比，使非小细胞肺癌(NSCLC)局部控制率的提高成为可能。在三维适形放疗中靶区的确定是重要的一步。目前临床医师在CT图像上逐层勾画肿瘤体积(GTV)，根据对肿瘤生物学的了解及临床经验在GTV外周加一定边界以包括亚，临床浸润病灶构成临床靶体积(CTV)，并根据肿瘤部位及患者具体情况，综合考虑呼吸动度、摆位误差等不确定因素在CTV外加0．5cm～2cm的边界构成计划靶体积(PTV)。CTV、PTV的范围尚无统一标准。现综述靶区确定方面的研究动态。     

肺癌合并纵隔淋巴结转移的三维适形放疗和调强放疗的剂量学研究

目的比较肺癌合并纵隔淋巴结转移的三维适形放疗（3 DCRT）和调强放疗（IMRT）的剂量学差异,为临床应用提供参考。方法选择2007年8月至2008年2月行IMRT放射治疗的11例肺癌纵隔转移患者,利用其CT模拟定位图像分别设计IMRT计划和3DCRT计划,结合等剂量曲线以及剂量体积直方图（DVH）对IMRT计划和3 DCRT计划进行适形性、靶区均匀性和对各关键器官受量进行比较。处方剂量66Gy／33次,治疗时间6周;要求95％靶区体积达到95％以上的处方剂量。SPSS14．0统计软件进行t检验。结果IMRT靶区的适形度优于3DCRT（P〈0．05）,IMRT靶区内超过处方剂量110％体积相比3DCRT放疗靶区内超过处方剂量110％体积减小;在对肺组织的保护上,IMRT肺V20、V30、V40数值均明显小于3 DCRT（P〈0．05）。结论对临床靶区体积大、形状不规则的肺癌合并纵隔淋巴结转移患者,IMRT治疗是较好的选择。     

肺癌三维适形放疗计划设计的剂量学分析

 目的 比较肺癌常规二维放疗和三维适形放疗计划的剂量学特征。方法 采用美国RAHD三维放疗计划系统对20例肺癌术后患者分别进行常规二维及三维适形放疗计划设计，根据剂量-体积直方图等参数对两者剂量学特征进行评估分析。结果 与常规二维计划相比较，三维适形放疗计划的靶区适形度好，剂量分布均匀；全肺受照体积V20及脊髓最大剂量均明显低于二维计划。结论 肺癌患者采用三维适形放疗技术，可提高靶区剂量，进而有助于提高肿瘤局部控制率，同时能有效地保护靶区周围正常组织和器官。     

Internal target volume determined with expansion margins beyond composite gross tumor volume in three-dimensional conformal radiotherapy for lung cancer

PURPOSE: Gross tumor volume (GTV) of lung cancer defined by fast helical CT scan represents an image of moving tumor captured at a point in active respiratory movement. However, the method for defining internal margins beyond GTV to account for its expected physiologic movement and all variations in size and shape during the administration of radiation has not been established. The goal of this study was to determine the internal margins with expansion margins beyond individual GTVs defined with (1) fast scan at shallow free breathing, (2) breath-hold scans at the end of tidal volume inspiration and expiration, and (3) 4-s slow scan to approximate the composite GTV of all scans. METHODS AND MATERIALS: A series of sequential CT scans were acquired with (1) a fast helical scan at shallow free breathing and (2) breath-hold scans at the end of tidal volume expiration and inspiration for the first 6 patients, and (3) a 4-s slow scan at quiet free breathing, which was added for the latter 7 patients. We fused breath-hold scans and the 4-s slow scan to the fast scan at shallow free breathing to generate the composite GTV. Margins necessary to encompass the composite GTV beyond individual GTVs defined by either fast scan at quiet free breathing, breath-hold scans, or the 4-s slow scan at quiet free breathing were defined as expansion or internal margins and termed the internal target volumes. The centroid of the tumor volume was also used as another reference for tumor movement. RESULTS: Thirteen patients with 14 tumors were enrolled into the study. Substantial tumor movement was noted by either the extent of internal margins beyond each GTV or the movement of the centroid. Internal margins varied significantly according to the method of CT scanning for determination of GTV. Even for tumors in the same lobe of the lung, a wide range of internal margins and significant variation in the centroid movement in all directions (x, y, and z) were observed. The GTV of a single fast helical scan at free breathing (n = 14) required the largest internal margin (mean, 3.5 mm; maximum, 18 mm; standard deviation [SD], 4.2 mm) to match the composite GTV, compared with those of the 4-s slow scan (mean 2.7 mm, maximum 14 mm, SD 3.5 mm) or combined breath-hold scans (mean 1.1 mm, maximum 9 mm, SD 1.9 mm). Internal margins (expansion margins) required to approximate the composite GTV in 95% of cases were 13 mm, 10 mm, and 5 mm for the GTVs of a single fast scan, 4-s slow scan, and breath-hold scans at the end of tidal volume inspiration and expiration, respectively. CONCLUSIONS: The internal margins required to account for the internal tumor motion in three-dimensional conformal radiotherapy are substantial. For the use of symmetric and population-based margins to account for internal tumor motion, GTV defined with breath-hold scans at the end of tidal volume inspiration and expiration has a narrower range of internal margins in all directions than that of either a single fast scan or 4-s slow scan.     

呼吸门控技术在胸部肿瘤放射治疗中的研究进展

随着三维适型、调强、容积旋转等技术的发展,靶区剂量的适型度越来越高。但是由于人体器官的自身运动及充盈状态的变化,会引起靶区位置的变化。呼吸动度对胸部肿瘤放疗的影响目前是放疗界研究的热点,临床中控制呼吸动度的技术主要为呼吸门控技术,包括主动呼吸门控技术和被动呼吸门控技术,本文将详细介绍目前常用的应用于胸部肿瘤放疗过程中的呼吸控制技术,同时探讨呼吸门控技术的未来发展方向。     

主动呼吸控制技术(ABC)在肺癌放射治疗中的应用

目的：使用主动呼吸控制技术（aetive brething control,ABC）治疗非小细胞肺癌患者，评价呼吸运动时肺部肿瘤动度的影响及ABC技术的优势和可行性，并评价近期疗效和急性放射反应。方法：选择9例使用ABC技术联合三维造型放疗技术治疗的非小细胞系癌患者进行分析。CT定位扫描时分别采集ABC和自由呼吸（free breath.FB）状态下的图像，评价呼吸运动对肺部肿瘤动度和PTV边界的影响唾弃；并比较两种计划的DVH，放疗剂量为54-60Gy/18-20次。3Gy/次，1次/天，5天/周，定期随访，评价近期疗效及急性放射反应。结果：应用ABC技术后，隔肌的平均位移从FB时的43.5mm（20.0-32.0mm）降低为3.6mm（0.5-72.mm）,胸壁的侧方位移从FB时的3.2mm（2.8-4.0mm）降低为1.2mm（0.5-1.6mm）.PTV边界可以从FB时的1.5mm减少为0.75cm;肺的V20从21.8%降低为15.0%,减少了30.6%.中位随访6个月时,9例患者中有6例CR,3例PR.急性放射副反应都很轻微,仅为I-II.结论：在肺癌的精确放射治疗中,呼吸动度的影响不可忽视.而ABC系统可以有效的降低呼吸运动时治疗的影响,提高放疗的精确性,减少副反应.,但该系统使用较为复杂,延长了治疗的时间,个别患者不能忍受.     

Assessing respiration-induced tumor motion and internal target volume using four-dimensional computed tomography for radiotherapy of lung cancer

PURPOSE: To assess three-dimensional tumor motion caused by respiration and internal target volume (ITV) for radiotherapy of lung cancer. METHODS AND MATERIALS: Respiration-induced tumor motion was analyzed for 166 tumors from 152 lung cancer patients, 57.2% of whom had Stage III or IV non-small-cell lung cancer. All patients underwent four-dimensional computed tomography (4DCT) during normal breathing before treatment. The expiratory phase of 4DCT images was used as the reference set to delineate gross tumor volume (GTV). Gross tumor volumes on other respiratory phases and resulting ITVs were determined using rigid-body registration of 4DCT images. The association of GTV motion with various clinical and anatomic factors was analyzed statistically. RESULTS: The proportions of tumors that moved >0.5 cm along the superior-inferior (SI), lateral, and anterior-posterior (AP) axes during normal breathing were 39.2%, 1.8%, and 5.4%, respectively. For 95% of the tumors, the magnitude of motion was less than 1.34 cm, 0.40 cm, and 0.59 cm along the SI, lateral, and AP directions. The principal component of tumor motion was in the SI direction, with only 10.8% of tumors moving >1.0 cm. The tumor motion was found to be associated with diaphragm motion, the SI tumor location in the lung, size of the GTV, and disease T stage. CONCLUSIONS: Lung tumor motion is primarily driven by diaphragm motion. The motion of locally advanced lung tumors is unlikely to exceed 1.0 cm during quiet normal breathing except for small lesions located in the lower half of the lung.     

左乳腺癌保乳术后不同放疗方式的剂量学比较

目的:评价左乳腺癌保乳术后三种放疗方式（3DCRT,IMRT,VMAT）的剂量学特点。方法:选取本院2015年5月至2016年2月期间20例早期左乳腺癌保乳术后放疗患者,所有靶区及危及器官均由同一高级放疗医师勾画,包括临床靶区（CTV）、计划靶区（PTV）及危及器官（OAR）,并由同一高级放疗物理师分别设计3DCRT、IMRT、VMAT 三种治疗计划,处方剂量为50 Gy。比较三种计划的计划靶区（PTV）的靶区均匀性指数（HI）及适形度指数（CI）,最大剂量（Dmax）、平均剂量（Dmean）、最小剂量（Dmin）;肺、心脏的V5,V10,V20,V30,V40,Dmax,Dmean及Dmin等。结果:3DCRT、IMRT、VMAT三种放疗计划适形度指数（CI）分别为 0.75±0.08、0.84±0.04和0.89±0.04(P＜0.05),均匀性指数(HI)分别为 0.11±0.12、0.11±0.08 和0.10±0.09。VMAT与IMRT计划降低了危及器官高剂量区体积,但相应增加了低剂量区体积,尤其VMAT计划的心脏、患侧肺V5、V10明显增加(P＜0.05)。结论:IMRT计划不仅提高了靶区的适形度,而且降低了心脏和肺的低剂量受照体积及平均剂量。因此,IMRT计划更适用于左乳腺癌保乳术后的放射治疗。     

CT and F-deoxyglucose (FDG) image fusion for optimization of conformal radiotherapy of lung cancers

Purpose: To validate a computed tomography (CT) and ¹⁸F-deoxyglucose (FDG) image fusion procedure and to evaluate its usefulness to facilitate target definition and treatment planning in three-dimensional conformal radiation therapy (3D-CRT) for non–small-cell lung cancer.

Methods and Materials: Twelve patients were assessed by CT and FDG-coincidence mode dual-head gamma camera (CDET) before radiotherapy. The patients were placed in a similar position during CT and FDG-CDET. Matching was achieved by minimizing the cost function by 3D translation and rotation between four landmarks drawn on the patient’s skin. Virtual simulation was performed from image fusion and estimated dose–volume histograms (DVH) were calculated.

Results: Quantitative analysis indicated that the matching error was < 5 mm. Fusion of anatomic and metabolic data corrected staging of lymph nodes (N) for 4 patients and staging of metastases for 1 patient. In these 5 patients, DVH revealed that the lung volume irradiated at 20 Gy (Vl₂₀) was decreased by an average of 22.8%, and tumor volume irradiated at the 95% isodose (V₉₅) was increased by 22% and 8% for 2 patients, respectively, and was decreased by an average of 59% for 3 patients after fusion. No difference in terms of Vl₂₀ and V₉₅ was observed for the other 7 patients.

Conclusion: We have validated CT and FDG-CDET lung image fusion to facilitate determination of lung cancer volumes, which improved the accuracy of 3D-CRT.     

PET-CT在三维适形放射治疗晚期胰腺癌中的应用

目的:评价PET-CT在三维适形放射治疗晚期胰腺癌中靶区勾画的价值及放疗后评价疗效的意义。方法:对13例晚期胰腺癌患者,采用PET-CT检查并定位,分别勾画出大体肿瘤体积CT-GTV和PET-CT-GTV,并分别制定出三维适形放射治疗的GTV进行比较。放疗后3个月行PET-CT复查。结果:13例患者的PET-CT-GTV和CT-GTV均不同,其中5例患者PET-CT-GTV较CT-GTV平均减少10.9cm3(25.7%)。CT-GTV平均42.4 cm3,PET-CT-GTV平均为31.5cm3(P=0.0045);8例患者的PET-CT-GTV较CT-GTV增加45.3%(27.4 cm3),CT-GTV平均为60.4 cm3,PET-CT-GTV平均为87.8 cm3(P=0.0000)。治疗后3个月PET-CT复查示:7例胰腺病灶较前明显缩小,局部FDG代谢明显减低或消失。其余6例病灶略缩小,FDG不同程度减低。治疗后的SUVmax变化范围为1.6-6.0,SUVmean变化范围为1.4-2.2。结论:采用PET-CT融合图像能够更好地提高靶区确定的精度及不确定性,最大限度减少不同勾画者之间的差异性。治疗前后局部病灶代谢活性的不同程度改变,对评价放疗疗效具有一定的指导意义。     

多靶区三维适形放疗在胸部肿瘤的临床应用

目的 研究胸部多病灶肿瘤行多靶区三维适形放射治疗的可行性及应用价值。方法 对36例胸部原发肿瘤肺内纵隔转移或双肺多发转移瘤等晚期肿瘤,采用多靶区三维适形放射治疗,优化指标：照射靶区尽可能采用PET/CT定位，靶区以2～4个为宜,采用共面或非共面多野照射，每次剂量2Gy,5次/周,或5～8Gy/次,3次/周，均为90%剂量曲线包绕PTV，总照射剂量或生物等效剂量70～80Gy，在放疗结束后2月行胸部CT或PET/CT进行评价。结果 36例患者中，2例病灶完全消失（CR），23例病灶明显缩小（PR），有效率（CR＋PR）69.4%,放疗中未出现明显放射性肺炎、放射性食管炎。结论晚期胸部肿瘤或转移瘤应用三维适形放射治疗采用多靶区治疗，局部控制率高，有较好的近期疗效，早期并发症低，患者可耐受。     

Impact of computed tomography and F-deoxyglucose coincidence detection emission tomography image fusion for optimization of conformal radiotherapy in non–small-cell lung cancer

PURPOSE: To report a retrospective study concerning the impact of fused 18F-fluoro-deoxy-D-glucose (FDG)-hybrid positron emission tomography (PET) and CT images on three-dimensional conformal radiotherapy planning for patients with non-small-cell lung cancer. METHODS AND MATERIALS: A total of 101 patients consecutively treated for Stage I-III non-small-cell lung cancer were studied. Each patient underwent CT and FDG-hybrid PET for simulation treatment in the same treatment position. Images were coregistered using five fiducial markers. Target volume delineation was initially performed on the CT images, and the corresponding FDG-PET data were subsequently used as an overlay to the CT data to define the target volume. RESULTS: 18F-fluoro-deoxy-D-glucose-PET identified previously undetected distant metastatic disease in 8 patients, making them ineligible for curative conformal radiotherapy (1 patient presented with some positive uptake corresponding to concomitant pulmonary tuberculosis). Another patient was ineligible for curative treatment because the fused PET-CT images demonstrated excessively extensive intrathoracic disease. The gross tumor volume (GTV) was decreased by CT-PET image fusion in 21 patients (23%) and was increased in 24 patients (26%). The GTV reduction was > or = 25% in 7 patients because CT-PET image fusion reduced the pulmonary GTV in 6 patients (3 patients with atelectasis) and the mediastinal nodal GTV in 1 patient. The GTV increase was > or = 25% in 14 patients owing to an increase in the pulmonary GTV in 11 patients (4 patients with atelectasis) and detection of occult mediastinal lymph node involvement in 3 patients. Of 81 patients receiving a total dose of > or = 60 Gy at the International Commission on Radiation Units and Measurements point, after CT-PET image fusion, the percentage of total lung volume receiving >20 Gy increased in 15 cases and decreased in 22. The percentage of total heart volume receiving >36 Gy increased in 8 patients and decreased in 14. The spinal cord volume receiving at least 45 Gy (2 patients) decreased. Multivariate analysis showed that tumor with atelectasis was the single independent factor that resulted in a significant effect on the modification of the size of the GTV by FDG-PET: tumor with atelectasis (with vs. without atelectasis, p = 0.0001). CONCLUSION: The results of our study have confirmed that integrated hybrid PET/CT in the treatment position and coregistered images have an impact on treatment planning and management of non-small-cell lung cancer. However, FDG images using dedicated PET scanners and respiration-gated acquisition protocols could improve the PET-CT image coregistration. Furthermore, the impact on treatment outcome remains to be demonstrated.     

20例鼻咽癌自适应放疗应用探讨

目的:使用我院Elekta Synergy医用直线加速器自带XIO三维适形调强放射治疗计划系统计算在不同放疗阶段及不同影像条件下对放疗计划的影响，探讨自适应放射治疗（ART）的可行性及实用性。方法:收集2013年8月至2014年10月共20例鼻咽癌患者资料，获取每例患者的第1次放射治疗时、放疗至17次时的千伏级锥形束CT(kV-cone beam)kV-实时CT(CBCT)影像。同时，获取在同一治疗条件下的传统扇形束CT(FBCT)图像。使用XIO三维适形调强放射治疗计划系统行三维的剂量显示、剂量体积直方图（DVH）及TPC/NTCP计划评估工具，在不同视野面进行放疗计划实时比较。进行不同放疗阶段下两种影像系统的放疗计划差异比较。结果:在不同放疗阶段下，两种影像系统的放疗计划差异性小（P＜0.05），它们在同一放疗阶段的靶区及危及器官剂量差异均在1.5%以内、DVH显示两者有较好的一致性。结论:我院Elekta Synergy医用直线加速器的kV-CBCT影像可以用来做放疗计划设计，ART在我院有可行性及一定的实用性。