鼻咽癌处理的调强放疗

本文从物理学的观点介绍鼻咽癌处理中调强放疗临床实践的有关概况。文中对于处理过程中挑战性的问题以及临床处理流程，尤其是保证几何和计量计算的精度问题进行了讨论。对那些用于治疗计划和剂量优化计算的技术和策略、处理计划的评价、剂量验证和病人的移动等问题和处理的质量保证和检测问题一起进行了讨论。对调强放疗虚拟剂量验证的原理和邮电进行了介绍和描述。我们用35个鼻咽癌病人处理的初步结果表明：和常规的放疗技术相比，这里介绍的调强技术能够改进处理时的复杂性。     

Intensity modulated radiotherapy: advantages, limitations and future developments

Intensity modulated radiotherapy (IMRT) is widely used in clinical applications in developed countries, for the treatment of malignant and non-malignant diseases. This technique uses multiple radiation beams of non-uniform intensities. The beams are modulated to the required intensity maps for delivering highly conformal doses of radiation to the treatment targets, while sparing the adjacent normal tissue structures. This treatment technique has superior dosimetric advantages over 2-dimensional (2D) and conventional 3-dimensional conformal radiotherapy (3DCRT) treatments. It can potentially benefit the patient in three ways. First, by improving conformity with target dose it can reduce the probability of in-field recurrence. Second, by reducing irradiation of normal tissue it can minimise the degree of morbidity associated with treatment. Third, by facilitating escalation of dose it can improve local control. Early clinical results are promising, particularly in the treatment of nasopharyngeal carcinoma (NPC). However, as the IMRT is a sophisticated treatment involving high conformity and high precision, it has specific requirements. Therefore, tight tolerance levels for random and systematic errors, compared with conventional 2D and 3D treatments, must be applied in all treatment and pre-treatment procedures. For this reason, a large-scale routine clinical implementation of the treatment modality demands major resources and, in some cases, is impractical. This paper will provide an overview of the potential advantages of the IMRT, methods of treatment delivery, and equipment currently available for facilitating the treatment modality. It will also discuss the limitations of the equipment and the ongoing development work to improve the efficiency of the equipment and the treatment techniques and procedures.     

组织等效补偿膜对调强放射治疗的剂量影响

目的研究组织等效补偿膜对调强放射治疗（IMRT）的剂量影响。方法选择12例浅表鼻腔癌患者,其中男性7例,女性5例,年龄26～66岁,平均年龄47.7岁。将传统扇形束CT加有虚拟组织等效补偿膜,形成调强计划planA;将调强计划planA移植到做过电子密度刻度的、加有实物组织等效补偿膜的相应锥形束CT（cone-beam CT）,直接剂量计算形成planB;将planA复制并去掉虚拟组织等效补偿膜,以同样的靶区处方剂量和目标函数进行优化后剂量计算形成planC。最后将3组计划的剂量体积直方图（DVH）及其统计数据进行对比定量分析。结果①不加组织等效补偿膜的浅表肿瘤调强治疗计划planC中临床靶区（CTV）受量很差,平均V95%为91.4%,且重要器官严重超过耐受剂量,相应的治疗计划根本不能用于临床。②对于IMRTplanA加系统虚拟组织等效补偿膜确实可以增加浅表肿瘤靶区剂量,其CTV平均V95%为99.8%,且能消除计划内高剂量区。③IMRT计划执行时planB中实物组织等效补偿膜虽与虚拟组织等效补偿膜有一定差异,但确实能使肿瘤靶区受到充分的照射剂量,其CTV平均V95%为99.1%,对浅表肿瘤靶区所受的剂量影响较小,对重要器官所受的剂量影响稍较大且不存确定性。结论正确合理地使用组织等效补偿膜进行逆向调强计划优化确实能得到满意的浅表肿瘤剂量分布,并也能使浅表的肿瘤得到很好的放射治疗,但对重要器官所受的剂量影响稍较大且存不确定性。     

111例初治鼻咽癌调强放射治疗临床疗效分析

目的分析调强放射治疗（IMRT）鼻咽癌的初步临床结果。方法选择111例初治鼻咽癌患者进行IMRT．其中男性76例,女性35例：年龄22～71岁,中位年龄47岁。根据国际抗癌联盟2002年分期标准,Ⅰ期19例．Ⅱ期58例．Ⅲ期32例,Ⅳa期2例。对鼻咽肿瘤计划靶区（PTV）放射治疗至60～65Gy时根据肿瘤退缩情况,缩野加量至70～75Gy。中下颈65～70Gv,锁骨上区52Gy,危及器官剂量在安全限制范围内,脑干、脊髓平均剂量36．5Gv,左、有视神经47．2Gv、43.4Gy,左、右腮腺剂量40．1Gy,39．6Gy,50％腮腺体积平均受照剂量在30Gy以下。结果中位随访期38个月,22例出现局部或淋巴结复发,局部复发率1年、2年分别为5．4％、14．4％。1年、2年、3年总生存率分别为98.2％、94．6％和85．6％。急性反应主要以口腔黏膜放射性损伤、骨髓抑制和口干为主。口腔黏膜Ⅰ度损伤为22．5％,Ⅱ度、Ⅲ度损伤分别为44．1％、33-3％。骨髓抑制Ⅰ级发生率为31．5％．Ⅱ级3412％．Ⅲ级14．4％。未发现放射性脑损伤后遗症。结论IMRT对于鼻咽癌各区均有较好的剂量分布,局部控制率和2年、3年总生存率有明显提高．且可较好地保护正常组织免受照射,IMRT逐渐成为鼻咽癌标7佯的治疗方式     

Equivalent dose and effective dose from stray radiation during passively scattered proton radiotherapy for prostate cancer

Proton therapy reduces the integral therapeutic dose required for local control in prostate patients compared to intensity-modulated radiotherapy. One proposed benefit of this reduction is an associated decrease in the incidence of radiogenic secondary cancers. However, patients are also exposed to stray radiation during the course of treatment. The purpose of this study was to quantify the stray radiation dose received by patients during proton therapy for prostate cancer. Using a Monte Carlo model of a proton therapy nozzle and a computerized anthropomorphic phantom, we determined that the effective dose from stray radiation per therapeutic dose (E/D) for a typical prostate patient was approximately 5.5 mSv Gy(-1). Sensitivity analysis revealed that E/D varied by +/-30% over the interval of treatment parameter values used for proton therapy of the prostate. Equivalent doses per therapeutic dose (HT/D) in specific organs at risk were found to decrease with distance from the isocenter, with a maximum of 12 mSv Gy(-1) in the organ closest to the treatment volume (bladder) and 1.9 mSv Gy(-1) in the furthest (esophagus). Neutrons created in the nozzle predominated effective dose, though neutrons created in the patient contributed substantially to the equivalent dose in organs near the proton field. Photons contributed less than 15% to equivalent doses.     

Application of coloring theory to reduce intensity modulated radiotherapy dose calculations

Coloring theory is applied to reduce the dose calculations under intensity modulated radiotherapy. Intensity modulated radiotherapy varies the intensity profile across the beam. The beam face is divided into a panel of small squares or "bixels." Each square may be opened or closed for different lengths of time by moving collimator leaves in and out of the beam. It has been shown that the distribution of dose from radiation directed through any open square depends on whether the adjacent squares are opened or closed. Taking the states of neighboring bixels into account greatly increases the required dose calculations. There are 2(8) possible ways to select open or closed states for the eight neighbors of a given bixel. Each combination represents one coloring of a 3 x 3 panel, and each coloring demands a separate dose calculation. The number of calculations is reduced by considering the symmetries of a square. The 256 possible colorings can be divided into 51 distinct patterns through application of Burnside's theorem. Each pattern consists of selections of closed bixels that are the same except for a symmetric transformation of coordinates. If the symmetry between x and y coordinates is broken by collimator leaves whose ends and sides have different effects on bordering bixels, the number of patterns increases to 84. The theoretic gain in the number of calculations through the application of Burnside's theorem is fivefold if bixel borders are symmetric, and threefold if the borders are asymmetric. The results are applied to examples of generated intensity maps. The symmetry rules divide the bixel arrangements into proportionately fewer patterns as the intensity maps become larger, allowing computational gains to be achieved.     

Contamination dose from photoneutron processes in bodily tissues during therapeutic radiation delivery

Dose to the total body from induced radiation resulting from primary exposure to radiotherapeutic beams is not detailed in routine treatment planning though this information is potentially important for better estimates of health risks including secondary cancers. This information can also allow better management of patient treatment logistics, suggesting better timing, sequencing, and conduct of treatment. Monte Carlo simulations capable of taking into account all interactions contributing to the dose to the total body, including neutron scattering and induced radioactivity, provide the most versatile and accurate tool for investigating these effects. MCNPX code version 2.2.6 with full IAEA library of photoneutron cross sections is particularly suited to trace not only photoneutrons but also protons and heavy ion particles that result from photoneutron interactions. Specifically, the MCNPX code is applied here to the problem of dose calculations in traditional (non-IMRT) photon beam therapy. Points of calculation are located in the head, where the primary irradiation has been directed, but also in the superior portion of the torso of the ORNL Mathematical Human Phantom. We calculated dose contributions from neutrons, protons, deutrons, tritons and He-3 that are produced at the time of photoneutron interactions in the body and that would not have been accounted for by conventional radiation oncology dosimetry.     

Dosimetric evaluation of radiation dose rate effect in respiratory gated intensity modulated radiation therapy

Purpose:

To investigate the dosimetric accuracy of the sliding window gated IMRT compared with the static treatment, using varying dose rates.

Materials and methods:

This study measured changes in output and diode array response with changing dose rate, verified the precision of the motion table, and measured changes in dose distribution accuracy with film and diodes at two depths with changing dose rate. During 4DCT (4 Dimensional Computed Tomography), the patient’s respiratory signals and target motion were recorded and imported to the XY4D simulation table of SUN NUCLEAR Corporation to simulate the patient’s respiration and tumour motion. A single field of each sliding window IMRT plan with 30º wedge and one for lung cancer were used in this study. Three irradiating conditions, static and moving target with and without gating, were applied to both plans.

Results:

The standard deviations of output, with the dose rates changing from 300–600 MU/min, were 0.065 cGy and 0.169 cGy for the ionisation chamber and diode, respectively. The verification of the motion table shows very good precision with 9.98 ± 0.02 cm (true value = 10.0 cm). The measurements by MapCheck show the gamma index of the planned absolute dose distribution in static and moving targets with gating, resulting in more than 96% passing for all dose rates. The absolute dose distribution measured by film for the static target was agreeable with the value of moving target with gating.

Conclusion:

The sliding window gated IMRT technique is able to deliver an accurate dose to a moving target with the dose rate of 300–600 MU/min that is suitable for clinical treatment.     

Implementing multiple static field delivery for intensity modulated beams.

A clinically oriented two-dimensional intensity-modulated beam delivery method is implemented using multiple static segmented fields, i.e., the "step-and-shoot" approach. Starting with a desired al" intensity distribution, it creates a multiple-level intensity approximation, and then constructs a sequence of segmented fields to deliver the multiple-level intensities using multileaf collimator (MLC) and independent backup jaws. The approach starts with a simple grouping of all the nonzero intensity values into a minimum number of clusters for a user specified deviation tolerance for the ideal plan. The k-means clustering algorithm is then employed to find the optimal levels of intensity that minimize the discrepancies between the ideal and the approximated intensities, without violating the user specified deviation tolerance. The multiple-level intensities are then decomposed into a sequence of machine deliverable segments. Apart from the first segment for each gantry angle, all the other segments are arranged to minimize the total travel distance of the leaves. The first segment covers the entire irradiated area and is used for treatment verification by electronic portal imaging. The implementation issues due to the physical constraints of the MLCs are also addressed.     

数字模拟机对适形调强放射治疗患者进行射野核对的应用

目的 应用数字模拟定位机核对适形调强放射治疗计划,验证需要治疗的区域是否与靶区吻合.方法 收集头颈部、胸部、腹部肿瘤患者各30例,分别进行射野核对.将治疗计划系统（TPS）重建的0°和90°的数字重建图像（DRR）传至数字模拟机,移床从定位时的参考点移动到治疗时的等中心点,分别采集0°和90°的X射线影像;调用数字模拟机2D/2D matching程序,调整感兴趣区域（ROI）,设定10 cm×10 cm的射野区域为ROI,将0°DRR图与0°X射线影像、90°DRR图与90°X射线影像分别进行自动或手动分析匹配,查看ROI内的两组图像的骨性结构是否吻合,最后得出两组图像匹配后的误差.结果 分析头颈部、胸部、腹部各30例肿瘤患者进行射野核对后的误差以及校正后的误差,头颈部肿瘤在X、Y、Z方向误差均≤3 mm,胸腹部肿瘤在X、Y、Z方向误差均≤5 mm.结论 数字模拟机能够通过DRR图与X射线影像分析匹配的方式对适形调强放射治疗的计划进行核对,验证治疗区域,从而保证治疗的准确性,满足了临床需要.     

Intensity and energy modulated radiotherapy with proton beams: variables affecting optimal prostate plan

Inverse planning for intensity- and energy-modulated radiotherapy (IEMRT) with proton beams involves the selection of (i) the relative importance factors to control the relative importance of the target and sensitive structures, (ii) an appropriate energy resolution to achieve an acceptable depth modulation, (iii) an appropriate beamlet width to modulate the beam laterally, and (iv) a sufficient number of beams and their orientations. In this article we investigate the influence of these variables on the optimized dose distribution of a simulated prostate cancer IEMRT treatment. Good dose conformation for this prostate case was achieved using a constellation of I factors for the target, rectum, bladder, and normal tissues of 500, 50, 15, and 1, respectively. It was found that for an active beam delivery system, the energy resolution should be selected on the basis of the incident beams' energy spread (sigmaE) and the appropriate energy resolution varied from 1 MeV at sigmaE = 0.0 to 5 MeV at sigmaE= 2.0 MeV. For a passive beam delivery system the value of the appropriate depth resolution for inverse planning may not be critical as long as the value chosen is at least equal to one-half the FWHM of the primary beam Bragg peak. Results indicate that the dose grid element dimension should be equal to or no less than 70% of the beamlet width. For this prostate case, we found that a maximum of three to four beam ports is required since there was no significant advantage to using a larger number of beams. However for a small number (< or = 4) of beams the selection of beam orientations, while having only a minor effect on target coverage, strongly influenced the sensitive structure sparing and normal tissue integral dose.     

Intensity modulated radiation therapy using laser-accelerated protons: a Monte Carlo dosimetric study

In this paper we present Monte Carlo studies of intensity modulated radiation therapy using laser-accelerated proton beams. Laser-accelerated protons coming out of a solid high-density target have broad energy and angular spectra leading to dose distributions that cannot be directly used for therapeutic applications. Through the introduction of a spectrometer-like particle selection system that delivers small pencil beams of protons with desired energy spectra it is feasible to use laser-accelerated protons for intensity modulated radiotherapy. The method presented in this paper is a three-dimensional modulation in which the proton energy spectrum and intensity of each individual beamlet are modulated to yield a homogeneous dose in both the longitudinal and lateral directions. As an evaluation of the efficacy of this method, it has been applied to two prostate cases using a variety of beam arrangements. We have performed a comparison study between intensity modulated photon plans and those for laser-accelerated protons. For identical beam arrangements and the same optimization parameters, proton plans exhibit superior coverage of the target and sparing of neighbouring critical structures. Dose-volume histogram analysis of the resulting dose distributions shows up to 50% reduction of dose to the critical structures. As the number of fields is decreased, the proton modality exhibits a better preservation of the optimization requirements on the target and critical structures. It is shown that for a two-beam arrangement (parallel-opposed) it is possible to achieve both superior target coverage with 5% dose inhomogeneity within the target and excellent sparing of surrounding tissue.     

Exploring the limits of spatial resolution in radiation dose delivery

Flexibility and complexity in patient treatment due to advances in radiotherapy techniques necessitates a simple method for evaluating spatial resolution capabilities of the dose delivery device. Our purpose in this investigation is to evaluate a model that describes the ability of a radiation therapy device to deliver a desired dose distribution. The model is based on linear systems theory and is analogous to methods used to describe resolution degradation in imaging systems. A qualitative analysis of spatial resolution degradation using the model is presented in the spatial and spatial frequency domains. The ability of the model to predict the effects of geometric dose conformity to treatment volumes is evaluated by varying multileaf collimator leaf width and magnitude of dose spreading. Dose distributions for three clinical treatment shapes, circular shapes of varying diameter and one intensity modulated shape are used in the evaluation. We show that the model accurately predicts the dependence of dose conformity on these parameters. The spatial resolution capabilities of different radiation therapy devices can be quantified using the model, providing a simple method for comparing different treatment machine characteristics. Also, as different treatment sites have different resolution requirements this model may be used to tailor machine characteristics to the specific site.     

Intensity modulated radiation therapy with irregular multileaf collimated field: a dosimetric study on the penumbra region with different leaf stepping patterns

Using a Varian 21 EX linear accelerator with a multileaf collimator (MLC) of 120 leaves, the penumbra regions of beam profiles within an irregular multileaf collimated fields were studied. MLC fields with different leaf stepping angles from 21.8 degrees to 68.2 degrees were used. Beam profiles in different directions: (1) along the cross-line and in-line axis, (2) along the leaf stepping edges of the field, and (3) parallel to the stepping edges but in the middle of the field, were measured and calculated using Kodak XV radiographic film and Pinnacle3 treatment planning system version 7.4f. These beam profiles were measured and calculated at source to axis distance= 100 cm with 5 cm of solid water slab on top. On the one hand, for both cross-line and in-line beam profiles, the penumbra widths of 20%-80% did not vary with the leaf stepping angles and were about 0.4 cm. On the other hand, the penumbra widths of 10%-90% of the above two profiles varied with the stepping angles and had maximum widths of about 1.9 cm (cross-line) and 1.65 cm (in-line) for stepping angles of 38.7 degrees and 51.3 degrees , respectively. For profiles crossing the "rippled" stepping edges of the field, the penumbra widths (10%-90%) at the regions between two opposite leaves (i.e., profile end at the Y1/Y2 jaw position) decreased with the stepping angles. At the penumbra regions between two leaf edges with the tongue-and-groove structure of the same bank (i.e., profile end at the X1/X2 jaw position), the penumbra widths increased with the stepping angles. When the penumbra widths were measured between two opposite leaf edges and at corners between two leaves, the widths first decreased with the stepping angles and then increased beyond the minimum width point at stepping angle of 45 degrees. The penumbra width (10%-90%) measured at the leaf edge was larger than that at the corner. For the beam profiles calculated using Pinnacle3, it is found that the results agreed well with the measurements along the cross-line and in-line axis, while there was a deviation for the profiles along the leaf stepping edge of the field compared to the film measurements. The measured results in this study can help us to understand the dosimetric effect of the leaf stepping (due to finite leaf width), tongue-and-groove and rounded leaf end structure in the penumbra region of an irregular MLC field. A more dedicated penumbra model can be developed for the treatment planning system.     

The effect of optimization on surface dose in intensity modulated radiotherapy (IMRT)

Although IMRT has been shown clinically to increase skin doses for some patients, it has also been shown that intensity modulated delivery does not, of itself, increase skin doses. The reason for this apparent difference is that inverse planning can result in solutions that give high fluence to tangential beam segments near the skin surface, in an attempt to counter the build-up region. In cases where the clinical target volume (CTV) stops short of the skin surface, but the planning target volume (PTV) does not, there is no clinical reason to treat the skin. The CTV-PTV margin exists purely to ensure that fields are large enough to allow for geometrical uncertainties. With an objective function based on the doses to the PTV, it is possible for a plan that gives excess fluence to the skin to have a lower objective function, and hence to be preferred in an optimization. We describe a technique of plan evaluation, based on analysis of a plan by recalculating several plans in which the isocentre has been offset by a distance equal to the CTV-PTV margin. We demonstrate that changes to a plan that reduce a PTV-based objective can give a worse dose distribution to the CTV when systematic and random set-up errors are accounted for, and increase skin dose. Several possible strategies for avoiding this problem are discussed, including the use of the skin as an organ at risk, modification of the PTV to avoid the skin, and the use of 'pretend bolus' applied in planning but not in treatment. The latter gave the best results. The possibility of using the evaluation method itself, as the basis of an objective function for optimization, is discussed.     

Optimization of intensity modulated radiotherapy under constraints for static and dynamic MLC delivery.

Multi-leaf collimators (MLCs) are emerging as the prevalent modality to apply intensity modulated radiotherapy (IMRT). Both the principle and the particular design of MLCs stipulate complex constraints on the practically applicable intensity modulated radiation fields. Most consequentially, the distribution of exposure times across the maximum field outline is either a piecewise constant function in the static mode or a piecewise linear function in the dynamic mode of driving an MLC. In view of clinical utility, the total leaf movement should be minimized, which requires that MLC-related constraints be considered in the dose optimization process. A method is proposed to achieve this for both static MLC fields and dynamic leaf close-in application. The method is an amendment to a generic gradient-based IMRT dose optimization algorithm and solves numerical problems related to the non-convexity of the MLC constraints, which can cause erratic behaviour of a gradient-based algorithm. It employs bistable penalty functions to select preferrable leaf configurations from the configuration space of the MLC, which is limited by specific design features. Together with an 'annealing' escape mechanism from local minima, the algorithm is capable of finding the optimum of an IMRT problem as leaf sequences with minimized leaf travel. In particular, the efficiency of static IMRT can be raised to the levels of unmodulated fields with very few field segments, thereby increasing the utility of IMRT in clinical practice.     

A device for measuring ionizing radiation dose field nonuniformity

Moscow Scientific Research Institute of Roentgenoradiology. Translated from Meditsinskaya Tekhnika, No. 2, pp. 6–8, March–April, 1992.