Changes in biological effectiveness of the neutron beam at Clatterbridge (62 MeV p on Be) measured with cells in vitro

Chinese hamster V79 cells have been used to assess changes in RBE of the p(62)Be neutron beam at the Clatterbridge Hospital with depth in a phantom and with use of a hydrogenous filter. The cells were exposed at depths of 2 and 12 cm and at a depth of 2 cm with a hydrogenous filter. Two groups of experimenters each conducted two experiments. The ratios of relative biological effectiveness (RBE) at a depth of 12 cm to that at 2 cm were found by the two groups to be 0.99 +/- 0.04 and 0.96 +/- 0.02 (standard errors). The effect of a polythene filter 4.5 cm thick was measured at a depth of 2 cm and the ratio of RBE with and without the filter was found by both groups to be 0.99 +/- 0.02. All the experiments suggest that there may be small effects of beam hardening by depth and filtration but these results are in marked contrast with those obtained using an in vivo system.     

The Clatterbridge high-energy neutron therapy facility: measurements of beam parameters for clinical use

Measurements have been performed on the 62 MeV proton cyclotron at the Douglas Cyclotron Centre, Clatterbridge Hospital, to determine the variation in beam parameters necessary for clinical use of the neutron therapy facility. These measurements are of total (neutron and gamma) doses, and include: depth doses for wedged and unwedged fields at various treatment distances; profile measurements and the production of associated isodose charts; calibration of the dosimetry system of the cyclotron; and determination of variations in calibration associated with changes in field size, wedge and focus-skin distance. Measurements have also been performed to estimate the degree of long-term stability of both calibration and field uniformity.     

基于微剂量学的钆中子俘获治疗释放低能电子相对生物效应计算

目的基于微剂量学方法计算钆中子俘获治疗(157GdNCT)中释放低能电子的相对生物效应(RBE)值。方法使用蒙特卡罗(MC)程序Geant4-DNA包模拟钆中子俘获治疗中释放的低能电子在不同敏感靶标体积和物理模型中径迹结构的能量沉积分布情况及微剂量学参数,并基于微剂量动力学模型(MKM)获取其RBE值。结果低能电子RBE值在不同的敏感靶标体积下差异性较大,且随着敏感靶标体积增大而减小。以敏感靶标直径6 nm的RBE值1.77为参考,敏感靶标直径10 nm的RBE值1.53,相比于6 nm的差异百分比为13%,而直径15 nm的RBE值1.40,相比于6 nm的差异百分比高达21%。不同Geant4-DNA物理模型对低能电子RBE影响较小。以物理模型option2的RBE值1.53作为参考,option6和option7的RBE值分别为1.49和1.52,相比于option2的差异百分比分别为2.6%和0.6%。结论利用MKM计算157GdNCT释放低能电子在不同敏感靶标体积及物理模型下的RBE值为1.40~1.77。     

The Clatterbridge high-energy neutron therapy facility: specification and performance

A new high-energy neutron therapy facility has been installed at the Douglas Cyclotron Centre, Clatterbridge Hospital, Merseyside, in order to extend the clinical trials of fast neutrons initiated by the Medical Research Council. The neutron beam is produced by bombarding a beryllium target with 62 MeV protons. The target is isocentrically mounted with the potential for 360 degrees rotation and has a fully variable collimator. This gives a range of rectilinear field sizes from 5 cm x 5 cm to 30 cm x 30 cm. Basic neutron beam data including output, field flatness, penumbra and depth-dose data have been measured. For a 10 cm x 10 cm field, the 50% depth dose occurs at 16.2 cm in water and the output is 1.63 cGy microA-1 min-1 at the depth of dose maximum. The effectiveness of the target shielding and the neutron-induced radioactivity in the treatment head have also been measured. It is concluded that the equipment meets both the design specifications and also fully satisfies criticisms of earlier neutron therapy equipment. A full radiation survey of the centre was also carried out and it was found that radiation levels are low and present no significant hazard to staff.     

High energy neutron therapy programme at the Douglas Cyclotron Centre, Clatterbridge Hospital

Preliminary results are reviewed on the outcome of patients treated within two randomized studies with either p(60) + Be-neutrons or photons. Since April 1987 67 patients have been treated of which twelve have been included in a randomized study on head and neck cancer and 40 on pelvic cancer. The clinical treatment planning is presented in detail and discussed. The results presented are considered to be very preliminary, so that no attempt has been made to analyse and discuss them in detail.     

Experimental study of the relative biological effectiveness (R.B.E.) of a fast neutron beam (author's transl)

A preliminary experimentation has been done with the synchrocyclotron (28 MeV deuton) in Lyon. The different characteristics of the beam have been determined through various dosimetric measurements. C57Bl mice have been irradiated with single doses and fractionated schedules (5 sessions). 7 day survival has been analysed. Comparison of neutron and cobalt gamma ray shows a R.B.E. of 1.95 for single dose and 2.5 for five fractions. This work is a confirmation of the effect of fractionation on the R.B.E. of the neutrons.     

Toxicity and relative biological effectiveness of alpha emitting radioimmunoconjugates

Radioimmunotherapy based on α-particle emitters has excellent properties as a treatment against micrometastatic and disseminated cancers because of the short path length (50 - 80 μm) and high linear energy transfer (～ 100 keV/ μm). Alpha-particles produce clustered DNA double-strand breaks and highly reactive hydroxyl radicals when hitting biological tissue. Hence, targeted α-particle therapy offers the potential of selective tumor cell killing with low damage to surrounding normal tissue. The ideal applications for targeted α-therapy are in treating neoplastic cells in circulation or when cancer cells are present as free-floating cells or spread along compartment walls. This review will provide a brief overview of the most promising radionuclides for targeted α-therapy and compare their relative biological effectiveness (RBE) and normal tissue toxicity.     

Calculation of the relative biological efficiency (RBE) of neutron radiation

The Relative Biological Effectiveness (RBE) of radiation with different LET has to be recognized in the planning of radiation therapy especially if one type of radiation should be replaced by another type or if both should be used within the same irradiation course. In radiation therapy it is suitable to consider the RBE in connection with dose dependent cell survival rates. These rates can be described by means of corresponding mathematical models. A simple way to calculate the RBE on the basis of the modern LQ-model is demonstrated. In that procedure the alpha/beta-ratios which are known at least approximatively for many organs and tissues can be used. The proposed method is demonstrated for the human skin and lung. For these organs we obtained RBE ranges from 3.4 to 1.2 and from 3.8 to 0.8, respectively, considering increasing doses. Thereby, for the lung it can be observed that the dose dependency of the RBE for small doses is especially strong. The obtained results are in good coincidence with experiences in clinical practice.     

用于硼中子俘获治疗的超热中子束理论设计

目的 设计用于硼中子俘获治疗(BNCT)的超热中子束理论方案。方法 基于清华大学试验核反应堆,以其1号孔道为材料布放孔道,设计了由慢化材料、热中子吸收材料、γ屏蔽材料组成,但材料布放位置具有差异的5种理论方案;利用蒙特卡罗(MC)模拟方法,分别计算5种方案束出口处的中子注量率、剂量率及γ剂量率值,通过与BNCT技术指标对比,从5种方案中选择一种合适的方案。结果 得到了一个符合BNCT各项技术指标的超热中子束理论方案,其慢化材料厚度为53.5 cm、热中子吸收材料厚度为2 mm、γ屏蔽材料厚度为9 cm。结论 本研究给出的超热中子束理论方案为基于反应堆实现BNCT提供一定的理论参考。     

低剂量氚相对生物效能的实验研究与建议

笔者从辐射防护的角度概述了核聚变燃料氚低剂量照射下的相对生物效能 (RBE）的研究。选择指数递减剂量率和恒定剂量率2种氚照射方式,观察研究以下生物学指标：卵母细胞和精母细胞的显性致死突变率,显性骨骼突变率,初级卵母细胞和精原细胞的存活率,以及外周血淋巴细胞和胎肝嗜多染红细胞微核细胞率。计算2种氚照射方式下的RBE值,并分析RBE的影响因素。结果显示,在累积剂量为0.2、0.3、0.4、0.5、0.6 Gy/10 d的条件下,指数递减剂量率和恒定剂量率2种氚照射方式下的RBE值为2.9~4.2。为了辐射防护的目的,建议将低传能线密度（LET）辐射对生物群的RBE值设定为3.0~3.5。如果估计暴露于氚β粒子或其他低LET辐射或接近导出考虑参考水平下,则可能需要采用较高的RBE值进行评估,以更为准确地估计辐射的危险度。     

Effect of air space and depth dose in electron beam therapy

In electron beam therapy, alterations in dosimetry occur as a result of air space between the end-of-treatment cone and the skin surface. A large air gap may be introduced in order to obtain a field size larger than that available at the cone end. Needed dosimetry corrections related to these air space problems are discussed, along with a proposed method of measuring effective source-to-cone end distance. Data presented show the modifications of a dosimetric field which occur with an increase in the air space below the treatment cone.     

Theoretical implications of incorporating relative biological effectiveness into radiobiological equivalence relationships

Objective:

Earlier radiobiological equivalence relationships as derived for low-linear energy transfer (LET) radiations are revisited in the light of newer radiobiological models that incorporate an allowance for relative biological effectiveness (RBE).

Methods:

Linear-quadratic (LQ) radiobiological equations for calculating biologically effective dose at both low- and high-LET radiations are used to derive new conditions of equivalence between a variety of radiation delivery techniques. The theoretical implications are discussed.

Results:

The original (pre-LQ) concept of equivalence between fractionated and continuous radiotherapy schedules, in which the same physical dose is delivered in each schedule, inherently assumed that low-LET radiation would be used in both schedules. LQ-based equivalence relationships that allow for RBE and are derived assuming equal total physical dose between schedules are shown to be valid only in limited circumstances. Removing the constraint of equality of total physical dose allows the identification of more general (and more practical) relationships.

Conclusion:

If the respective schedules under consideration for equivalence both involve radiations of identical LET, then the original equivalence relationships remain valid. However, if the compared schedules involve radiations of differing LET, then new (and more restrictive) equivalence relationships are found to apply.

Advances in knowledge:

Theoretically derived equivalence relationships based on the LQ model provide a framework for the design and intercomparison of a wide range of clinical techniques including those involving high- and/or low-LET radiations. They also provide a means of testing for the validity of variously assumed tissue repair kinetics.Radiobiological equivalence relationships continue to play an important role in radiation oncology, providing a means of intercomparing alternative radiotherapy treatment schedules in terms of their biological effectiveness and, in principle, allowing the fine-tuning and optimisation of treatments. Such relationships allow any treatment schedule to be converted into a therapeutically equivalent (or improved) alternative through manipulation of various schedule parameters (fraction size, dose rate etc.) or through the consideration of different physical methods of dose delivery (brachytherapy, targeted therapy, permanent implants etc.).In this paper, the original concept of radiobiological equivalence (the so-called Liversage equivalence, applicable only to intercomparisons between fractionated and continuous schedules) is revisited and re-assessed in the light of more recent advances in radiobiological modelling. In doing so, we demonstrate that Liversage-type equivalence is a special and restricted case of a much wider range of possible equivalence relationships, including, for example, those involving radiations with increased linear energy transfer (LET). High-LET therapies such as those using protons or light ions have been the subject of much interest in recent years because of the therapeutically advantageous dose distributions afforded by the Bragg-peak phenomenon and (especially in the case of light ions) on account of their improved radiobiological effectiveness [1]. Updating equivalence relationships to include allowance for relative biological effectiveness (RBE) is therefore timely. In the same way that the concept of equivalence currently assists in assessing low-LET therapies, it is expected that this will become increasingly relevant in the high-LET domain as these therapies emerge and mature, especially in relation to clinical trials where comparisons will inevitably need to be made with low-LET treatment outcomes. This article does not attempt to provide a clinical evaluation of these equivalence relationships but rather seeks to update the theoretical model by incorporating what is now known about RBE and to discuss some important implications.