重离子束用于肿瘤放射治疗的基础理论

通过与低传能线密度辐射治疗对比分析建立了重离子束肿瘤放射治疗的基础理论,提出了一些提高重离子束放射治疗疗效和减少对正常组织损伤的技术措施,旨在为已开展的重离子治癌临床研究提供理论依据． The basic theory of tumor radiotherapy with heavy ion beam was introduced in contrast to low LET irradiation therapy. Some useful methods are also suggested to improve the curative effect of heavy ion therapy and to spare the normal tissue around the tumor.     

HIRFL的辐照治癌终端

为了进行重离子束流的肿瘤治疗和生物效应的研究,HIRFL正在建造一个辐照治癌终端.主要介绍了该终端的束流制备方法和束流线的布局、性能参数和束流光学设计计算结果. A new experimental terminal is being constructed at HIRFL for research program of proton and heavy ion therapies and irradiation effects of living things . The beam preparation method and the layout, performance and beam optics calculation of the beam line are presented.     

Progresses of heavy-ion cancer therapy

The status of heavy-ion cancer therapy has been reviewed. The existing and constructing heavy-ion beam facilities for cancer therapy in the world are introduced. The first clinical trials of superficially placed tumor therapy at heavy ion research facility in Lanzhou (HIRFL) are presented.     

重离子治癌相关研究

癌症是现代医学的难题, 一直危害着人类的健康。放射治疗是癌症治疗的有效手段之一。由于重离子束在物理学和生物学性质上所具有的优势, 它已成为放疗用的最佳射线。简述了重离子治癌的发展历程、 现状以及特点, 详细讨论了在医学物理和放射生物学研究领域值得关注的若干热点问题。Being a challenge to modern medicine, cancer endangers people’s health. Radiotherapy is one of the most successful means to treat cancer. Owing to their advantages in physics and biology, heavy ions have become the optimal particles used in radiotherapy. The features of heavy ion therapy are described, and several hot topics in medical physics and radiobiology are discussed in detail.     

重离子束治疗肿瘤临床研究

文章综述了重离子束在物理学、生物学、临床治疗等方面的优势,以及在放射生物学方面的基础实验研究内容。分析总结了国内外重离子束辐照治疗肿瘤的临床研究结果。其中,日本已接受治疗了约6 000 名不同类型的肿瘤患者,并取得较高的局部控制率和生存率;德国在头颈部肿瘤临床治疗方面取得了巨大的成功;在兰州重离子研究装置(HIRFL) 肿瘤治疗终端上,中国科学院近代物理研究所联合甘肃省肿瘤医院及兰州军区总医院对肿瘤患者的重离子治疗已进入临床试验阶段。甘肃省肿瘤医院治疗结果显示:43 例患者通过影像学检查评价疗效,客观有效率(CR+PR)为71.4%,主要急性放射损伤为1-2 级皮肤反应(红斑形成和脱皮),发生率为61.9%,治疗1 个月后随访结果显示重离子束(12C6+)对深部肿瘤具有较好的局部控制作用,且无严重不良反应发生。This article reviews the advantages of heavy ion in physical, biological and clinical aspects, discusses the radio-biological basis of experiment research, and summarizes clinical results of heavy ion beam treatment on tumor at home and abroad. Japan has accepted and treated about 6000 cancer patients of different types with high local control rates and survival ones. Germany has achieved great success in head and neck tumor clinical treatment. Institute of Modern Physics, Chinese Academy of Sciences (IMP-CAS), Tumor Hospital of Gansu Province and Lanzhou General Hospital of PLA have begun clinical trial on heavy ion treatment of deep-seated tumors after the shallow-seated tumor therapy has been done at HIRFL (Heavy Ion Research Facility in Lanzhou). The treatment results of Tumor Hospital of Gansu Province show that the objective response rate (CR+PR) is 71.4% and the rate of 1-2 levels radiation injury to skin reactions (erythema and desquamation) is 61.9% when we evaluate the 43 patients by means of maging. The results of case follow-up after treatment in 1 month indicate that the deep-seated tumor therapy with heavy ion beam has high local control rates without severe adverse effect.     

IMP重离子治癌中的剂量计算方法

针对深部肿瘤重离子治疗临床试验的需求,首先在水介质中进行生物有效剂量的优化计算,然后根据CT图像中像素CT值与水等效长度转换系数之间的关系, 结合水中的深度剂量分布曲线对每个像素进行积分得到CT图像上的生物有效剂量分布。同时介绍了基于被动式束流配送系统适形照射时的剂量确定方式, 并提出二维适形放疗也应使用分层照射方式以适应治疗时的不同要求。 这些方法适合目前及今后在IMP进行的重离子治癌临床试验研究中治疗计划系统的需要。Basic algorithms of biological effective dose optimization and dose distribution on CT image for the heavy ion therapy project at the Institute of Modern Physics (IMP), Chinese Academy of Sciences (CAS) are reported in this paper. Firstly, biological effective dose optimization is conducted in water. According to the relationship between CT number and water equivalent path length, an integral algorithm is used to calculate the average dose within a pixel and then the dose distribution in tissue is derived. Secondly, the dose determination of layer stacking conformal irradiation is described and the layer stacking method is proposed to be applied in two dimensional conformal irradiation. These methods are sufficient to the requirements of the ongoing and future heavy ion clinical trials conducted at IMP.     

面向HIRFL-CSR主动式点扫描技术的剂量标定方法研究(英文)

基于HIRFL-CSR肿瘤重离子治疗终端主动式束流配送系统发展了面向三维点扫描适形调强治疗技术的在线监测器点扫描剂量标定方法。为了验证点扫描剂量标定方法的稳定性和可靠性,利用HIRFL-CSR提供的C离子束考察了在线监测器剂量标定因子的能量依赖以及不同扫描步长的影响。结果表明:在线监测器剂量标定因子存在能量依赖;不同扫描步长对剂量标定因子影响较小（偏差小于1.8%）。证明了点扫描剂量标定方法的稳定性和可靠性。鉴于在三维点扫描适形调强治疗技术中影响在线监测器点扫描剂量标定因子的因素较多,建议今后续继续研究点扫描剂量标定因子影响因素,修正和完善点扫描剂量标定方法。As an important step of the application of spot scanning technique to heavy ion therapy, an experimental calibration procedure of online beam monitors based on standard of absorbed dose to water has recently been developed for scanned pencil like carbon ion beam in the deep seated tumor therapy terminal at the Heavy Ion Research Facility in Lanzhou (HIRFL). In this work, creating homogeneous irradiation field with steerable spot beam was tested using a 207 MeV/u penci like carbon ion beam. Then the verification of energy dependence of the calibration factors (CFs) and the influence of scanning step on the CF were also shown, as a part of the heavy ion clinic dosimetry researches. The results showd that the monitor CF presented energy dependence and performed stable response with deviation of 1.8% for the variation of scan steps. In this paper, the suitability and effectiveness of beam monitor calibration procedure for dynamic particle beam delivery were verified and the further research points to improve the calibration procedure were suggested.     

离子束治疗中的靶区运动补偿方法

相对于被动式束流配送系统,由患者呼吸因素而引起的肿瘤靶区运动会对主动式束流配送系统下的离子束放射治疗带来非常严重的影响,造成离子束辐射场剂量分布的严重畸变,甚至对肿瘤靶区周围的健康组织造成严重损伤,很大程度上影响离子束治疗的疗效。因此,在主动式束流配送系统下,建立针对由呼吸因素引起的运动肿瘤靶区的适形调强照射方法就显得必要,且具有重要意义。系统介绍了呼吸运动探测、4D-CT 以及目前主要的3 种运动补偿方法(多次扫描、呼吸门控和主动跟踪技术),并对这3 种方法在靶区适形度、稳健性以及技术复杂度等方面进行了比较。在靶区适形度方面主动跟踪技术优于门控技术,而门控技术又优于多次扫描技术;在稳健性方面多次扫描技术优于门控技术,而门控技术优于主动跟踪技术;在技术复杂度方面,多次扫描技术最简单,其次是门控技术,而主动跟踪技术最复杂。Active beam scanning results in serious distortion of ion-beam irradiation field in the presence of target motion and causes damage to healthy tissues round tumor target compared to passive beam shaping techniques. Therefore,it is necessary to establish suitable conformal irradiation methods for moving targets caused by the factor such as respiration in active ion beam scanning system. In this paper, motion detection, 4D-CT and three main ion beam specific mitigation techniques, namely rescanning, gating and beam tracking, are introduced. In addition, three motion mitigation techniques are compared comprehensively in terms of target conformation, robustness and mplementation complexity,respectively. For target conformation, the beam tracking is superior to gating, and gating is better than beam rescanning;the robustness decreases in the order rescanning-gating-beam tracking; for implementation complexity, beam rescanning is the most simple technology, followed by gating, while beam tracking is the most complex technique.     

重离子束治癌

本文回顾了辐射治癌的历史发展和国内外动态,讨论了重离子束与常规辐射相比在肿瘤治疗上的优势,提出了为治疗应用的重离子束的主要参数以及在兰州重离子研究装置（ＨＩＲＦＬ）拟建的冷却储存环（ＣＳＲ）上建立治疗实验室的初步考虑． Historical background and trends at home and abroad for radiation therapy arelooked back in the paper. The advantages of heavy ion beam in comparision with conventional radiation in tumour treatment are discussed. The main parameters of heavy ion beams fortherapy application and a tentative idea constructing treatment rooms at Cooling StorageRing(CSR) of Heavy Ion Research Facility in Lanzhou (HIRFL) are proposed.     

HIRFL-CSR电子冷却束流位置测量系统

高效率的电子冷却过程, 要求电子束与离子束位置平行且重叠。 为了同时测量电子束与离子束的位置, 在HIRFL CSR电子冷却装置上研发了以容性圆筒形极板为感应电极的束流位置探测系统。 系统测量束流通过探针时产生的脉冲感应信号, 并进行傅里叶变换得到频谱信号, 分析4个不同电极上频谱信号强度获取束流的位置信息。 测量结果表明, 该束流位置探测系统测量准确, 为定量研究储存环离子累积和电子冷却过程与两种束流相对位置及角度的依赖关系提供了条件。 The efficient electron cooling requires that the ion beam and electron beam are parallel and overlapped. In order to measure the positions of ion beam and electron beam simultaneously, a beam position monitor system is developed for the HIRFL-CSR electron cooler device, which probe consists of four capacitive cylinder linear cut poles. One can get the both beam positions from the picking up signals of four poles by using Fourier transform(FFT) method. The measurement results show that the beam position monitor system is accurate. This system is suitable for investigating the relation between electron cooling processing and the angle of ion beam and electron beam.     

Active spot-scanning test with heavy ions at HIRFL-CSR

An active spot beam delivery system for heavy ion therapy has been developed based on the Cooling Storage Ring at HIRFL-CSR, where the pencil carbon-ion beams were scanned within a target volume transversely by a pair of orthogonal (horizontal and vertical) dipole magnets to paint the slices of the target volume and longitudinally by active energy variation of the synchrotron slice by slice. The unique techniques such as dose shaping via active energy variation and magnetic deflection constitute a promising three-dimensional conformal even intensity-modulated radiotherapy with heavy ions at HIRFL-CSR. In this paper, the verification of active energy variation and the calibration of steerable beam deflection are shown, as the basic functionality components of the active spot-scanning system. Additionally, based on the capability of creating homogeneous irradiation fields with steerable pencil beams, a radiobiological experiment like cell survival measurement has been performed aiming at comparison of the radiobiological effects under active and passive beam deliveries.     

栅扫描重离子束治癌束流配送系统对运动靶区的适形放疗(Ⅱ)可行性实验

在栅扫描束流配送系统下, 进行了重离子束对运动靶体进行适形照射的可行性实验研究. 利用实时修正束流扫描参数的方法, 使得束流追踪靶体在横向上的运动; 在纵向上利用一个机械驱动的束流降能装置(称深度扫描器)迅速调节束流 能量, 使得重离子束高剂量的Bragg峰区落在运动靶体需治疗的断层之上. 实验结果表明: 栅扫描器主动补偿靶体横向运动及深度扫描器补偿靶体纵向运动是可行的.     

HIRFL浅层肿瘤重离子治疗终端束流配送系统性能的实验验证

详细介绍了兰州重离子研究装置(HIRFL)浅层肿瘤重离子治疗终端的被动式束流配送系统, 对该束流配送系统重要组成部件及其整体的性能进行了实验验证. Bragg峰展宽装置脊形过滤器及能量调节装置射程移位器测试结果显示该设备的性能指标达到设计要求. 为验证该被动式束流配送系统的整体性能, 进行了束流成形实验, 模拟对肿瘤靶区的三维适形照射. 结果表明: 利用该束流配送系统可实施对肿瘤的三维适形放射治疗. HIRFL浅层肿瘤治疗装置束流配送系统性能的验证为下一步开展肿瘤重离子束治疗临床试验奠定了基础.     

重离子放射治疗双微小展宽峰组合照射方法

在基于被动式束流配送系统的分层适形重离子治疗当中,需要利用微型脊形过滤器（mini ridge filter,mini-RF）将单能重离子束Bragg峰展宽为峰区近似高斯分布的微小展宽峰（mini spread-out Bragg peak,mini-SOBP）,从而达到减少照射分层数及照射时间的目的。采用较宽的mini-SOBP可以有效减少照射分层数,但会增大展宽Bragg峰（SOBP）远端剂量跌落距离,增加对靶区后方正常组织或危及器官的辐照剂量。这一问题可以通过双mini-SOBP的组合照射方法来解决。使用2种mini-RF对单能重离子束Bragg峰略微展宽得到2种半高宽（FWHM）且剂量分布近似高斯分布的mini-SOBP,通过基于放射生物学模型的剂量优化,证实了在SOBP平顶区按生物有效剂量均匀和物理吸收剂量均匀的展宽情况下,双mini-SOBP组合照射方法均可以在减少照射分层数的同时较大幅度地减小SOBP远端剂量跌落距离。In layer-stacking conformal heavy-ion therapy based on passive beam delivery system,it is necessary to minimize the layer numbers and reduce irradiation time for layer-stacking conformal heavy-ion therapy.Gaussian shaped mini spread-out Bragg peaks (mini-SOBP) were generated by mini ridge filters (mini-RF) for monoenergetic heavy ion beams.It is effective to minimize the layer number by using mini-SOBPs with the bigger full width at the half maximum (FWHM),but in this way the distal dose fall-off distance of a spread-out Bragg peak (SOBP) will be enlarged,increasing the radiation damage to normal tissue or organ at risk behind the target volume.This issue could be solved by using mini-SOBPs based combinatorial irradiation method.In this study,Gaussian shaped mini-SOBPs with two different FWHMs were generated by two different mini-RFs for monoenergetic heavy ion beams.Based on radiobiological model calculations and dose optimizations,the mini-SOBPs based combinatorial irradiation method was confirmed to reduce the distal dose fall-off distances of SOBPs while minimizing the layer numbers for layer-stacking conformal heavy-ion therapy.     

软调制双散射质子治疗束流配送系统

质子治疗是一种新兴的放射治疗方法,它的主要优点是剂量分布特性优良,可以使高辐射剂量集中于肿瘤部位,减少对周围正常组织的损伤.这一优点的实现主要依靠束流配送系统,它包含质子能量调节与调制、束流扩展和准直等功能.现提出一种新的软调制双散射质子治疗束流配送系统.其特点是利用程序控制质子能量变化以改变质子在体内的射程从而展宽Bragg峰,同时利用两次散射获得较大面积的均匀照射野.它的优点是运行可靠、调节灵活,并特别有利于实现适形治疗.     

重离子治疗计划系统的构想

对重离子柬治癌的优势进行简要的回顾，并着重介绍了用于重离子放射治疗的治疗计划系统。治疗计划系统是一套软件系统，不同的硬件设施应有与其相匹配的软件系统，即治疗计划系统。在此基础上，针对兰州重离子加速器的特点提出一些关于治疗计划系统方面的构想。After a brief review concerning the advantages of heavy ions in radiotherapy, more interests are concentrated on treatment planning system （TPS） for heavy ion radiotherapy. Compared to the hardware devices such as accelerator and beam delivery system, the TPS is a set of software system, and different therapy facilities require their corresponding TPSs. Based on the specialities of the Heavy Ion Research Facility in Lanzhou （HIIRFL）, some suggestions on the TPS for tumor therapy at HIRFL finally are given.     

12C6+ 离子束辐照对大鼠离体主动脉环内皮依赖性舒张功能的影响

利用兰州重离子研究装置(HIRFL) 提供的高能12C6+离子束(能量为300 MeV/u,剂量率为0.5 Gy/min) 辐照大鼠离体胸主动脉环,考察了12C6+离子束辐照对主动脉环内皮依赖性舒张功能的影响,并采用NBT 还原法测定血管环生成超氧阴离子(O2􀀀) 水平,加入外源性超氧化物歧化酶(SOD) 干预探讨了O2􀀀在内皮功能损伤中的作用。研究结果表明,2.0,4.0 和6.0 Gy 的12C6+离子束辐照大鼠胸主动脉环后,可致血管内皮依赖性舒张功能的剂量依赖性明显受损(P <0.01 vs control group),并可致血管环NBT 还原能力剂量依赖性增加(4.0 Gy 时,P <0.05;6.0 Gy 时,P <0.01 vs control group)。辐照前加入外源性SOD 对6.0 Gy 12C6+离子束辐照所致血管环NBT 还原能力升高有明显抑制作用(P <0.01),对血管环内皮依赖性舒张功能也有明显的保护作用(P<0.01),但辐照后10 min 加入外源性SOD,其保护作用明显不及前者。结论显示,12C6+ 离子束辐照大鼠胸主动脉环可致血管内皮功能受损,O2 清除剂SOD 对内皮功能受损有保护作用,说明O2􀀀介导了辐照所致内皮功能损伤。Heavy ion beam has many characteristics,and it is expected to be the most suitable radiation therapy technique for malignant tumor. It is lack of depth-understanding on the potential adverse reactions caused by using this technique, because heavy ion radiotherapy is applied to clinical for a short time. Studies have shown that the vascular injury plays a pivotal role in normal tissue damage induced in the conventional radiation therapy, but there was no research report on heavy ion beam irradiation-induced vascular injury. In the present study, the isolated aortic rings of rats were irradiated by 12C6+ ion beam (300 MeV/u, 0.5 Gy/min) delivered by HIRFL(Heavy Ion Research Facility in Lanzhou), the effects of 12C6+ ion beam irradiation on aortic rings with endothelium dependent diastolic function have been investigated.NBT reduction method was used for assaying the vascular ring formation of superoxide anion (O2􀀀) level, and the involvement of superoxide anion in endothelial function injury in rats was investigated through the intervention test of exogenous superoxide dismutase (SOD) on O2. The results showed that, the vascular endothelial dependent vasodilation was impaired significantly (P < 0:01 vs control group) by irradiation with 2.0, 4.0 and 6.0 Gy 12C6+ ion beam in a dosedependent manner, and the NBT reduction of vascular rings increased dose-dependently (P <0.05 at 4.0 Gy, P <0.01 at 6.0 Gy vs control group). Adding exogenous SOD before irradiation could significantly inhibit the increasing of NBT reduction (P<0.01), and also had protective effect on vascular endothelium dependent diastolic function (P<0.01), but 10 min after irradiation with exogenous SOD, its protective function was significantly less than before. Conclusion indicated that 12C6+ ion beam irradiation could cause endothelial function impaired, O2􀀀 scavenger SOD has a protective effect on endothelial dysfunction, suggesting that O2􀀀 mediates endothelial injury induced by heavy ion irradiation.     

重离子束治癌中深度剂量分布优化

针对兰州重离子研究装置所加速的120MeV/u ¹²C离子束,利用模拟退火优化算法进行了Bragg峰展宽的剂量优化.取相同的展宽区域(30mm),4种不同的步长(2,1,0.5,0.25mm)进行Bragg峰展宽模拟.对所得到的剂量平均值,均方差,入射口剂量,峰坪比等优化结果的参数做了比较.讨论了重离子束治癌临床上最优的Bragg峰展宽模型的选取.