靶向抗肿瘤纳米药物研究进展

肿瘤是当今严重威胁人类健康的三大疾病之一。然而目前在临床肿瘤治疗和诊断中广泛应用的药物还多数为非选择性药物，体内分布广泛，尤其在一些正常组织和器官中也常有较多分布，常规治疗剂量即可对正常组织器官产生显著的毒副作用，导致患者不能耐受，降低药物疗效，所以提高药物的肿瘤选择性，减少其在非靶向部位的聚集是提高抗肿瘤药物疗效的关键。减少药物对非靶向部位的毒副作用，降低药物治疗剂量并减少给药次数，从而提高药物疗效，这种治疗方法即被称为肿瘤靶向治疗。现今在肿瘤靶向治疗领域，靶向抗肿瘤纳米药物研究正日益受到人们的普遍关注和重视，现就其近年来的研究进展综述如下。     

肺癌三维适形放疗和常规放疗的剂量分布比较分析

比较肺癌三维适形放疗和常规放疗的剂量分布.对40例首程放疗肺癌患者同时进行X线和CT模拟定位,每位患者设计3套治疗计划:即三维适形治疗计划、常规治疗计划和虚拟常规治疗计划,通过剂量-体积直方图(DVH)的分析来评价不同放疗方式对肿瘤的剂量分布和危及组织、器官的受照剂量差异.说明三维适形放疗能给予靶区均匀的剂量分布,并能有效地保护正常组织和器官.     

三维适形调强放疗的历史、现状和未来

三维适形调强放疗 (ｉｎｔｅｎｓｉｔｙｍｏｄｕｌａｔｅｄ 3-ｄｉｍｅｎｔｉｏｎａｌｃｏｎｆｏｒｍａｌｒａｄｉａｔｉｏｎｔｈｅｒａｐｙ ,本文简称适形放疗 ) ,是由 3Ｄ -ＣＲＴ和ＩＭＲＴ两部分组成 ,前者利用精确的固定和定位技术 ,不改变剂量场强度 ,使高剂量区的分布和肿瘤的形状在三维方向上基本一致 ;后者指在适形的前提下利用逆向计划系统计算 ,根据需要调节靶区内不同区域的照射量 ,使其在形态和剂量学分布上双重适形 ,更均匀 ,对正常组织的保护更好。这一肿瘤放疗史上的重大革新 ,经初步临床验证 ,能明显降低正常组织的放射损…     

肺癌肺内肿瘤不同能量三维适形放疗的比较

目的:研究6 MV和15 MV X射线对肺癌肺内肿瘤三维适形放疗肿瘤组织、危及器官及正常组织剂量的影响。方法:选择11例肺癌肺内肿瘤患者,对每例患者分别采用6 MV和15 MV X射线进行三维适形放疗计划设计,同一患者的两个计划均使用相同的布野方案和剂量体积约束。比较两组计划的计划靶区、危及器官及正常组织的剂量分布。结果:6MV和15 MV两种能量X线三维适形放疗计划计划靶区的剂量分布、均匀性、适形度的差异无显著性意义(P>0.05),危及器官脊髓、食管、心脏,正常组织肺的剂量分布无显著性意义(P>0.05)。结论:肺癌肺内肿瘤6 MV、15 MV三维适形放疗剂量分布无明显差异,三维适形放疗能量用6 MV,不主张用15 MV。     

T2000—ROT食道癌精确定位系统临床应用

目的：分析T2000－ROT食道癌精确定位系统的临床应用情况。材料与方法：采用带有N形标记柱的体部框架,内加真空负压垫。对病人身体进行固定和重复固定,服钡后,以3mm或5mm厚进行CT断层扫描,将病人图像数据舆到治疗计划工作站,通过CT图像信息以及标记点,计算出肿瘤的三维坐标。根据现有的长方形旋转照射野剂量模型,计算某一照射方案下体模中任意一点的剂量值及横断面上的等剂量分布。利用直线加速器对病人实施治疗。结果：利用该系统治疗40例病人,有效研究病例36例,一年局部控制率为100％。结论：T2000－ROT食道癌精确定位系统。定位精确,能够使高剂量区均匀准确分布于病灶及亚临床灶区,保护周围正常组织和重要器官,提高肿瘤局部控制率和病人生存质量。     

保定市肿瘤医院引进X-刀治疗肿瘤

一种治疗肿瘤不用麻醉、不用开刀、不流血、无创伤的治疗肿瘤高新设备Ｘ－刀，在保定肿瘤医院投入使用。Ｘ－刀是世界高科技成果，是２１世纪治疗肿瘤的重要手段。它利用电子直线加速器产生高能Ｘ线、通过非共面多弧度等中心旋转治疗、实现多野、多集束照射病变，使周围正常组织得到最低剂量的照射，而病变组织得到最大剂量照射，起到类似刀切的效果，免除手术之苦。保定市肿瘤医院现已发展成为集科研、医疗、教学、预防保健、急救、康复为一体的服务功能齐全的现代化综合医院。保定市肿瘤医院引进X-刀治疗肿瘤     

以蒙特卡洛方法建立组织中光剂量数学模型:分析激光对肝组织的损伤

背景:目前很难通过数学分析方法求出或临床直接监测激光能量在生物组织内的传输规律,因此常常采用数值模拟的方法进行预测。用蒙特卡罗方法研究激光光子在组织中的传输,是目前较为理想的研究方法。目的:采用蒙特卡罗方法建立组织中的光剂量数学模型,探讨激光照射对于肝组织的损伤情况。方法:采用蒙特卡罗方法,建立不同光学参数下正常组织和肿瘤组织的组织剂量数学模型,逐个计算大量光子迁移轨迹,统计嵌于正常组织和肿瘤组织中的光子宏观能量分布。结果及结论:通过数学模型得到光损伤随组织深度的增加呈指数衰减的结果,且光子在组织边缘会形成第2个峰值。组织损伤是阈值过程,每条剂量曲线可被视为阈值曲线。采用蒙特卡罗方法模拟激光在肝组织中的传播,得到了激光光子在肝肿瘤组织中的分布规律。结果表明,适量光照强度能引起浅薄全面的肿瘤组织光损伤,深层光损伤伴随正常组织损伤。     

周围型肺癌立体定向放射治疗中采用实体肿瘤靶区推量技术的可行性研究——基于剂量学分析

目的：通过研究周围型肺癌立体定向放射治疗中提高肿瘤靶区最高剂量对剂量限制参数和正常器官剂量的影响，探讨使用实体肿瘤靶区推量技术的可行性，为临床治疗提供剂量学参考依据。方法：收集19例周围型早期肺癌患者的CT图像资料，重新设计放射治疗计划，初始治疗计划在满足放射治疗肿瘤协作组（RTOG）0915号报告关于剂量限制参数的情况下，以2 Gy的剂量爬升梯度分别对肿瘤靶区进行提量，共得到5组治疗计划。结果：5组计划的剂量限制参数均能满足RTOG0915号报告要求。5组计划的剂量限制参数和正常器官剂量无显著差异，但是肿瘤靶区最高剂量存在显著差异（P<0.05），最高和最低剂量组剂量差异可达6.6 Gy。结论：提高肿瘤靶区最高剂量对剂量限制参数和正常器官剂量没有显著影响。由于提高靶区内最高剂量会直接影响肿瘤的局部控制率，因此在满足剂量限制参数的前提下，建议使用实体肿瘤靶区推量技术以提高肿瘤靶区内的最高剂量。     

早期鼻咽癌Rapid Arc和IMRT计划的剂量学对比

目的:分析和比较早期NPC患者IMRT和Rapid Arc两种治疗技术的剂量学差别。方法:选取10例早期NPC病例分别对10例病例做IMRT和Rapid Arc计划,肿瘤计划靶区分为PTVnx、PTV60。PTVnx处方剂量为70 Gy,PTV60为60 Gy。比较两种方法的DVH图,等剂量分布和治疗时间。结果:两种不同计划中的靶区分布,PTVnx分布差异不大,但是RapidArc计划中的PTV60高剂量区明显多于IMRT计划。对其它正常组织来说,脊髓、脑干、腮腺、颞叶、视神经有着显著性差异。结论:对于早期NPC病人,Rapid Arc技术在剂量学上比IMRT技术有其更多的优势,不仅可以缩短治疗时间,而且其它一些正常组织也可减少受照剂量。     

射束强度受调节的适形放射治疗

射束强度受调节的适形放疗法是一种先进的放射治疗方法，它使用一组强度可独立控制的笔射束，通过旋转或多野静态照射肿瘤靶，使射野内高剂量分布形状在三维方向上与肿瘤靶的形状一致，同时尽可能地减少了靶区周围健康组织的照射剂量，从而大大提高放射治疗的治疗增益比，促进肿瘤的局部控制。本文系统地阐述了强度受调节的适形放疗的优势与治疗计划理论。     

X刀系统物理参数的测量方法和结果

本文以安装在ＢＪ／６Ｂ直线加速器上的ＪＸ－１００Ｘ刀系统为例,系统地介绍了总散射输出因子、组织最大比、离轴比、等中心定位精度和剂量分布等参数的测量方法,并给出了部分测量结果。     

JX—100X刀系统安全联锁装置设计

介绍一种应用于Ｘ刀系统防止加速器机架旋转照射过程中与治疗床和病人发生碰撞的安全装置的设计方法，并详细给出了其安装调试步骤。该装置已成功应用于第一军医大学研制的ＪＸ－１００Ｘ刀系统。     

X刀的剂量计算

本文提出一种Ｘ刀快速计算剂量算法，根据立体定向放射外科中使用的高能Ｘ射线特性和窄束射线剂量分布数学模型，通过改变步长的搜索，快速并精确地计算出剂量分布。     

旋转照射与X刀照射剂量分布的理论分析

本文利用理想线束的概念分析旋转治疗及Ｘ刀剂量分布的规律。分析了受照射的时间对剂量分布的影响。这时任何线束的剂量分布关系相对于照射野的宽度基本相同。多平面旋转治疗的剂量分布随平面数增加剂量更集中于靶区，但是，在轴区的剂量分布不变。重叠区大小随平面数增加而迅速变大，不重叠区剂量随平面数增加而减少。     

Dose verification of single shot gamma knife applications using VIPAR polymer gel and MRI

This work describes an experimental procedure with potential to assess the overall accuracy associated with gamma knife clinical applications, from patient imaging and dosimetry planning to patient positioning and dose delivery using the automated positioning system of a Leksell Gamma Knife model C. The VIPAR polymer gel-MRI dosimetry method is employed due to its inherent three-dimensional feature and linear dose response over the range of gamma knife applications. Different polymer gel vials were irradiated with single shot gamma knife treatment plans using each of the four available collimator helmets to deliver a maximum dose of 30 Gy. Percentage relative dose results are presented not only in the form of one-dimensional profiles but also planar isocontours and isosurfaces in three dimensions. Experimental results are compared with corresponding Gammaplan treatment planning system calculations as well as acceptance test radiochromic film measurements. A good agreement, within the experimental uncertainty, is observed between measured and expected dose distributions. This experimental uncertainty is of the order of one imaging pixel in the MRI gel readout session (<1 mm) and allows for the verification of single shot gamma knife applications in terms of acceptance specifications for precision in beam alignment and accuracy. Averaging net R(2) results in the dose plateau of the 4 mm and 18 mm collimator irradiated gel vials, which were MR scanned in the same session, provides a crude estimate of the 4 mm output factor which agrees within errors with the default value of 0.870.     

胰腺癌伽玛刀和加速器治疗计划剂量学比较

目的:比较分析OUR-QGD型γ刀和两种加速器治疗技术胰腺癌治疗计划的剂量学数据,为临床选择放疗技术提供参考。方法:选取20例胰腺癌病例,每例设计靶中靶(Target in Target,TIT)、调强(IMRT)和γ刀三种治疗计划。处方剂量为50 Gy包绕95%的PTV。计算比较三种计划的PTV靶区适形指数和均匀性指数,通过DVH计算靶区剂量和周围要害器官剂量。结果:IMRT计划的PTV靶区适形度最好,TIT计划次之,γ刀计划最差,均匀性指数γ刀计划也要劣于IMRT和TIT计划,但γ刀计划周围正常组织的剂量相对较低,而靶区剂量比TIT和IMRT计划要高得多。结论:根据物理剂量学数据,γ刀治疗胰腺癌可显著提高靶区剂量,同时很好地保护周围正常组织;TIT和IMRT也是治疗胰腺癌的有效方法。     

Peripheral doses in CyberKnife radiosurgery

The purpose of this work is to measure the dose outside the treatment field for conformal CyberKnife treatments, to compare the results to those obtained for similar treatments delivered with gamma knife or intensity-modulated radiation therapy (IMRT), and to investigate the sources of peripheral dose in CyberKnife radiosurgery. CyberKnife treatment plans were developed for two hypothetical lesions in an anthropomorphic phantom, one in the thorax and another in the brain, and measurements were made with LiF thermoluminescent dosimeters (TLD-100 capsules) placed within the phantom at various depths and distances from the irradiated volume. For the brain lesion, gamma knife and 6-MV IMRT treatment plans were also developed, and peripheral doses were measured at the same locations as for the CyberKnife plan. The relative contribution to the CyberKnife peripheral dose from inferior- or superior-oblique beams entering or exiting through the body, internally scattered radiation, and leakage radiation was assessed through additional experiments using the single-isocenter option of the CyberKnife treatment-planning program with different size collimators. CyberKnife peripheral doses (in cGy) ranged from 0.16 to 0.041% (+/- 0.003%) of the delivered number of monitor units (MU) at distances between 18 and 71 cm from the field edge. These values are two to five times larger than those measured for the comparable gamma knife brain treatment, and up to a factor of four times larger those measured in the IMRT experiment. Our results indicate that the CyberKnife peripheral dose is due largely to leakage radiation, however at distances less than 40 cm from the field edge, entrance, or exit dose from inferior- or superior-oblique beams can also contribute significantly. For distances larger than 40 cm from the field edge, the CyberKnife peripheral dose is directly related to the number of MU delivered, since leakage radiation is the dominant component.     

Buildup/surface dose and exit dose measurements for a 6-MV linear accelerator

The central axis dose distribution in the buildup region for the Varian Clinac 6/100 6-MV x-ray beam was measured in a polystyrene phantom using a fixed volume (0.5 cm3) parallel-plate ionization chamber (2.4-mm plate separation). Results for the surface dose measurements ranged from approximately 8% of the maximum dose for a 5 X 5 cm field, up to 36% for a 40 X 40 cm field, 100-cm source-skin distance. The effect of a 0.6-cm-thick polycarbonate blocking tray and metal filters on the surface and buildup dose is also reported. In addition, ionization measurements were made to document the dose perturbations caused by the absence of backscattering material at the exit surface of a polystyrene phantom. Exit dose measurements showed a 15% reduction in dose with essentially no scattering material beyond the measurement point. Near full scatter condition could be restored by placing 5-10 mm (depending on field size) of unit density material directly behind the ion chamber's distal surface.     

An evaluation of the TSE MR sequence for time efficient data acquisition in polymer gel dosimetry of applications involving high doses and steep dose gradients

The use of magnetic resonance imaging as a readout method for polymer gel dosimetry commonly involves long imaging sessions, particularly when high spatial resolution is required in all three dimensions, for the investigation of dose distributions with steep dose gradients and stringent dose delivery specifications. In this work, a volume selective turbo spin echo (TSE) pulse sequence is compared to the established Carr-Purcell-Meiboom-Gill (CPMG) multiecho acquisition with regard to providing accurate dosimetric results in significantly reduced imaging times. Polyethylene glycol diacrylate based (PABIG) gels were irradiated and subsequently scanned to obtain R2 relaxation rate measurements, using a CPMG multiecho sequence and a dual echo TSE utilizing an acceleration (turbo) factor of 64. R2 values, plotted against corresponding Monte Carlo dose calculations, provided calibration data of PABIG gels dose response over a wide dose range. A linear R2 versus dose relationship was demonstrated for both sequences with TSE results presenting reduced dose sensitivity. Although TSE data were found to deviate from linearity at lower doses compared to CPMG data, a relatively wide dynamic dose range of response extending up to approximately 100 Gy was observed for both sequences. The TSE and CPMG sequences were evaluated with a brachytherapy irradiation using a high dose rate 192Ir source and a gamma knife stereotactic radiosurgery irradiation with a single 4 mm collimator helmet shot. Dosimetric results obtained with the TSE and CPMG are shown to compare equally well with the expected dose distributions for these irradiations. The 60-fold scan time reduction achieved with TSE implies that this sequence could prove to be a useful tool for the introduction of polymer gel dosimetry in clinical radiation therapy applications involving high doses and steep dose gradients.     

Absorbed dose from secondary electrons in high energy photon beams.

The absorbed dose in high energy photon beams due to scattered electrons from the irradiated air volume and from beam-shaping platforms has been calculated using the Fermi-Eyges theory of multiple scattering. The results are presented as lateral surface absorbed dose distributions across the field for three different radiation qualities, namely 60Co, 6 MV and 21 MV X-rays. For 60Co the relative absorbed dose due to electrons expelled in air reaches a value as high as 30% of the absorbed dose at dose maximum at a field size 40 X 40 cm2 and an SSD of 100 cm. The absorbed dose from electrons emanating from beam-shaping platforms contribute significantly to the absorbed dose at the surface when the platform is placed closer than 20--40 cm from the surface for field sizes greater than 10 X 10 cm2 to 40 X 40 cm2 respectively.