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1.  A possible biomedical facility at the European Organization for Nuclear Research (CERN) 
The British Journal of Radiology  2013;86(1025):20120660.
A well-attended meeting, called “Brainstorming discussion for a possible biomedical facility at CERN”, was held by the European Organization for Nuclear Research (CERN) at the European Laboratory for Particle Physics on 25 June 2012. This was concerned with adapting an existing, but little used, 78-m circumference CERN synchrotron to deliver a wide range of ion species, preferably from protons to at least neon ions, with beam specifications that match existing clinical facilities. The potential extensive research portfolio discussed included beam ballistics in humanoid phantoms, advanced dosimetry, remote imaging techniques and technical developments in beam delivery, including gantry design. In addition, a modern laboratory for biomedical characterisation of these beams would allow important radiobiological studies, such as relative biological effectiveness, in a dedicated facility with standardisation of experimental conditions and biological end points. A control photon and electron beam would be required nearby for relative biological effectiveness comparisons. Research beam time availability would far exceed that at other facilities throughout the world. This would allow more rapid progress in several biomedical areas, such as in charged hadron therapy of cancer, radioisotope production and radioprotection. The ethos of CERN, in terms of open access, peer-reviewed projects and governance has been so successful for High Energy Physics that application of the same to biomedicine would attract high-quality research, with possible contributions from Europe and beyond, along with potential new funding streams.
PMCID: PMC3635800  PMID: 23549990
2.  Patterns of relapse in glioblastoma multiforme following concomitant chemoradiotherapy with temozolomide 
The British Journal of Radiology  2013;86(1022):20120414.
Different methods for contouring target volumes are currently in use in the UK when irradiating glioblastomas post operatively. Both one- and two-phase techniques are offered at different centres. 90% of relapses are recognised to occur locally when using radiotherapy alone. The objective of this evaluation was to determine the pattern of relapse following concomitant radiotherapy with temozolomide (RT-TMZ).
A retrospective analysis of patients receiving RT-TMZ between 2006 and 2010 was performed. Outcome data including survival were calculated from the start of radiotherapy. Analysis of available serial cross-sectional imaging was performed from diagnosis to first relapse. The site of first relapse was defined by the relationship to primary disease. Central relapse was defined as progression of the primary enhancing mass or the appearance of a new enhancing nodule within 2 cm.
105 patients were identified as receiving RT-TMZ. 34 patients were not eligible for relapse analysis owing to either lack of progression or unsuitable imaging. Patterns of first relapse were as follows: 55 (77%) patients relapsed centrally within 2 cm of the original gadolinium-enhanced mass on MRI, 13 (18%) patients relapsed >4 cm from the original enhancement and 3 (4%) relapsed within the contralateral hemisphere.
Central relapse remains the predominant pattern of failure following RT-TMZ. Single-phase conformal radiotherapy using a 2-cm margin from the original contrast-enhanced mass is appropriate for the majority of these patients.
Advances in knowledge:
Central relapse remains the predominant pattern of failure following chemoradiotherapy for glioblastomas.
PMCID: PMC3608050  PMID: 23385995
3.  Revisiting the ultra-high dose rate effect: implications for charged particle radiotherapy using protons and light ions 
The British Journal of Radiology  2012;85(1018):e933-e939.
To reinvestigate ultra-high dose rate radiation (UHDRR) radiobiology and consider potential implications for hadrontherapy.
A literature search of cellular UHDRR exposures was performed. Standard oxygen diffusion equations were used to estimate the time taken to replace UHDRR-related oxygen depletion. Dose rates from conventional and novel methods of hadrontherapy accelerators were considered, including spot scanning beam delivery, which intensifies dose rate.
The literature findings were that, for X-ray and electron dose rates of around 109 Gy s–1, 5–10 Gy depletes cellular oxygen, significantly changing the radiosensitivity of cells already in low oxygen tension (around 3 mmHg or 0.4 kPa). The time taken to reverse the oxygen depletion of such cells is estimated to be over 20–30 s at distances of over 100 μm from a tumour blood vessel. In this time window, tumours have a higher hypoxic fraction (capable of reducing tumour control), so the next application of radiation within the same fraction should be at a time that exceeds these estimates in the case of scanned beams or with ultra-fast laser-generated particles.
This study has potential implications for particle therapy, including laser-generated particles, where dose rate is greatly increased. Conventional accelerators probably do not achieve the critical UHDRR conditions. However, specific UHDRR oxygen depletion experiments using proton and ion beams are indicated.
PMCID: PMC3474025  PMID: 22496068
4.  Dilemmas concerning dose distribution and the influence of relative biological effect in proton beam therapy of medulloblastoma 
The British Journal of Radiology  2012;85(1018):e912-e918.
To improve medulloblastoma proton therapy. Although considered ideal for proton therapy, there are potential disadvantages. Expected benefits include reduced radiation-induced cancer and circulatory complications, while avoiding small brain volumes of dose in-homogeneity when compared with conventional X-rays. Several aspects of proton therapy might contribute to reduced tumour control due to (a) the use of more homogenous dose levels which can result in under-dosage, (b) differences in relative biological effectiveness (RBE) between that prescription RBE of 1.1 and the RBE of brain and spinal cord (likely to exceed 1.1) and in medulloblastoma cells (where RBE is likely to be below 1.1). Such changes, although speculative for RBE, might result in potential underdosage of tumour cells and a higher bio-effect in brain tissue.
Dose distributions for X-ray and proton treatment are compared, with allocation of likely RBE values for fast growing medullolastoma cells and stable central nervous system tissue.
These physical and radiobiological factors are shown to combine to give a higher risk of tumour recurrence with further risks on tumour control when dose reduction schedules used for X-ray therapy are replicated for proton therapy for “low-risk” patients.
The dose distributions and prescribed doses of proton therapy, taking into account RBE, in children and adults with medulloblastoma, need to be reconsidered.
PMCID: PMC3474038  PMID: 22553304
5.  An update on radioactive release and exposures after the Fukushima Dai-ichi nuclear disaster 
The British Journal of Radiology  2012;85(1017):1222-1225.
On 11 March 2011, the Richter scale 0.9-magnitude Tokohu earthquake and tsunami struck the northeast coast of Japan, resulting in widespread injury and loss of life. Compounding this tragic loss of life, a series of equipment and structural failures at the Fukushima Dai-ichi nuclear power plant (FDNP) resulted in the release of many volatile radioisotopes into the atmosphere. In this update, we detail currently available evidence about the nature of immediate radioactive exposure to FDNP workers and the general population. We contrast the nature of the radioactive exposure at FDNP with that which occurred at the Chernobyl power plant 25 years previously. Prediction of the exact health effects related to the FDNP release is difficult at present and this disaster provides the scientific community with a challenge to help those involved and to continue research that will improve our understanding of the potential complications of radionuclide fallout.
PMCID: PMC3487052  PMID: 22919005
6.  Fast neutron relative biological effects and implications for charged particle therapy 
The British Journal of Radiology  2011;84(Spec Iss 1):S011-S018.
In two fast neutron data sets, comprising in vitro and in vivo experiments, an inverse relationship is found between the low-linear energy transfer (LET) α/β ratio and the maximum value of relative biological effect (RBEmax), while the minimum relative biological effect (RBEmin) is linearly related to the square root of the low-LET α/β ratio. RBEmax is the RBE at near zero dose and can be represented by the ratio of the α parameters at high- and low-LET radiation exposures. RBEmin is the RBE at very high dose and can be represented by the ratio of the square roots of the β parameters at high- and low-LET radiation exposures. In principle, it may be possible to use the low-LET α/β ratio to predict RBEmax and RBEmin, providing that other LET-related parameters, which reflect intercept and slopes of these relationships, are used. These two limits of RBE determine the intermediate values of RBE at any dose per fraction; therefore, it is possible to find the RBE at any dose per fraction. Although these results are obtained from fast neutron experiments, there are implications for charged particle therapy using protons (when RBE is scaled downwards) and for heavier ion beams (where the magnitude of RBE is similar to that for fast neutrons). In the case of fast neutrons, late reacting normal tissue systems and very slow growing tumours, which have the smallest values of the low-LET α/β ratio, are predicted to have the highest RBE values at low fractional doses, but the lowest values of RBE at higher doses when they are compared with early reacting tissues and fast growing tumour systems that have the largest low-LET α/β ratios.
PMCID: PMC3473886  PMID: 22374547
7.  Malignant induction probability maps for radiotherapy using X-ray and proton beams 
The British Journal of Radiology  2011;84(Spec Iss 1):S070-S078.
The aim of this study was to display malignant induction probability (MIP) maps alongside dose distribution maps for radiotherapy using X-ray and charged particles such as protons. Dose distributions for X-rays and protons are used in an interactive MATLAB® program (MathWorks, Natick, MA). The MIP is calculated using a published linear quadratic model, which incorporates fractionation effects, cell killing and cancer induction as a function of dose, as well as relative biological effect. Two virtual situations are modelled: (a) a tumour placed centrally in a cubic volume of normal tissue and (b) the same tumour placed closer to the skin surface. The MIP is calculated for a variety of treatment field options. The results show that, for protons, the MIP increases with field numbers. In such cases, proton MIP can be higher than that for X-rays. Protons produce the lowest MIPs for superficial targets because of the lack of exit dose. The addition of a dose bath to all normal tissues increases the MIP by up to an order of magnitude. This exploratory study shows that it is possible to achieve three-dimensional displays of carcinogenesis risk. The importance of treatment geometry, including the length and volume of tissue traversed by each beam, can all influence MIP. Reducing the volume of tissue irradiated is advantageous, as reducing the number of cells at risk reduces the total MIP. This finding lends further support to the use of treatment gantries as well as the use of simpler field arrangements for particle therapy provided normal tissue tolerances are respected.
PMCID: PMC3473888  PMID: 22374550
8.  The potential impact of relative biological effectiveness uncertainty on charged particle treatment prescriptions 
The British Journal of Radiology  2011;84(Spec Iss 1):S061-S069.
There continues to be uncertainty regarding the relative biological effectiveness (RBE) values that should be used in charged particle radiotherapy (CPT) prescriptions using protons and heavier ions. This uncertainty could potentially offset the physical dose advantage gained by exploiting the Bragg peak effect and it needs to be clearly understood by clinicians and physicists. This paper introduces a combined radiobiological and physical sparing factor (S). This factor includes the ratio of the most relevant physical doses in tumour and normal tissues in combination with their respective RBE values and can be extended to contain the uncertainties in RBE. S factors can be used to study, in a simplified way for tentative modelling, those clinical situations in which high-linear energy transfer (LET) irradiations are likely to prove preferable over their low-LET counterparts for a matched tumour iso-effect. In cases where CPT achieves an excellent degree of normal tissue sparing, the radiobiological factors become less important and any uncertainties in the tumour and healthy tissue RBE values are correspondingly less problematic. When less normal tissue sparing can be achieved, however, the RBE uncertainties assume greater relevance and will affect the reliability of the dose-prescription methodology. More research is required to provide accurate RBE estimation, focusing attention on the associated statistical uncertainties and potential differences in RBE between different tissue types.
PMCID: PMC3473889  PMID: 22374549
9.  Accelerator science in medical physics 
The British Journal of Radiology  2011;84(Spec Iss 1):S004-S010.
The use of cyclotrons and synchrotrons to accelerate charged particles in hospital settings for the purpose of cancer therapy is increasing. Consequently, there is a growing demand from medical physicists, radiographers, physicians and oncologists for articles that explain the basic physical concepts of these technologies. There are unique advantages and disadvantages to all methods of acceleration. Several promising alternative methods of accelerating particles also have to be considered since they will become increasingly available with time; however, there are still many technical problems with these that require solving. This article serves as an introduction to this complex area of physics, and will be of benefit to those engaged in cancer therapy, or who intend to acquire such technologies in the future.
PMCID: PMC3473892  PMID: 22374548
10.  Investing in science: securing future prosperity 
The British Journal of Radiology  2011;84(1001):389-392.
A meeting concerned with UK science and technology investment was held at Chatham House, London, in November 2010. The UK science and technology research budget has been preserved at a fixed cash level whereas other areas of government face significant reductions in their financial support. This is in marked contrast to some East Asian countries, such as China, where investment in science and technology is increasing. The UK needs to change many aspects of education at school level and beyond to preserve its status as a first rate scientific country. It also has to solve the long-term problem, with some notable exceptions, of being unable to translate basic research discoveries into manufactured products. This article discusses the impact of these issues along with some tentative suggestions on how to improve these, with particular reference to the radiological sciences.
PMCID: PMC3473654  PMID: 21511747
11.  ENLIGHT and other EU-funded projects in hadron therapy 
The British Journal of Radiology  2010;83(994):811-813.
Following impressive results from early phase trials in Japan and Germany, there is a current expansion in European hadron therapy. This article summarises present European Union-funded projects for research and co-ordination of hadron therapy across Europe. Our primary focus will be on the research questions associated with carbon ion treatment of cancer, but these considerations are also applicable to treatments using proton beams and other light ions. The challenges inherent in this new form of radiotherapy require maximum interdisciplinary co-ordination. On the basis of its successful track record in particle and accelerator physics, the internationally funded CERN laboratories (otherwise known as the European Organisation for Nuclear Research) have been instrumental in promoting collaborations for research purposes in this area of radiation oncology. There will soon be increased opportunities for referral of patients across Europe for hadron therapy. Oncologists should be aware of these developments, which confer enhanced prospects for better cancer cure rates as well as improved quality of life in many cancer patients.
PMCID: PMC3473750  PMID: 20846982
12.  The apparent increase in the β-parameter of the linear quadratic model with increased linear energy transfer during fast neutron irradiation 
The British Journal of Radiology  2010;83(989):433-436.
The issue of whether the β-parameter of the linear quadratic model changes with linear energy transfer (LET) remains controversial. Retrospective analysis of UK fast neutron experimental data using human cell lines at Clatterbridge shows that the β-parameter of the linear quadratic model probably does increase with LET during neutron irradiation. For cells without a deficiency in DNA damage repair and for experiments in which β-parameter estimates were considered to be unreliably low, a provisional relationship of βH = 1.82 βL was found (where the suffixes refer to high and low LET exposures, respectively). This implies that √β increases by around 1.35 in the specific case of 62.5 MeV neutrons relative to 4 MeV X-rays. Increments in the β-parameter with LET influence the relative biological effect (RBE), especially at high doses per fraction. Large fractions are being used in experimental carbon ion therapy, in which broadly similar RBE values to fast neutrons are found. These interesting findings after fast neutron exposure need to be studied further for applications in charged particle beam therapy using light ions, which is presently undergoing a worldwide expansion.
PMCID: PMC3473575  PMID: 20019177

Results 1-13 (13)