Bleddyn Jones

Do the various radiations present in BNCT act synergistically? Cell survival experiments in mixed alpha-particle and gamma-ray fields

In many radiotherapy situations patients are exposed to mixed field radiation. In particular in BNCT, as with all neutron beam exposures, a significant fraction of the dose is contributed by low LET gamma ray photons. The components of such a mixed field may show a synergistic interaction and produce a greater cell kill effect than would be anticipated from the independent action of the different radiation types. Such a synergy would have important implications for treatment planning and in the interpretation of clinical results. An irradiation setup has been created at the Medical Research Council in Harwell to allow simultaneous irradiation of cells by cobalt-60 gamma rays and plutonium-238 alpha-particles. The setup allows for variation of dose and dose rates for both sources along with variation of the alpha particle energy. A series of cell survival assays for this mixed field have been carried out using V79-4 cells and compared to exposures to the individual components of the field under identical conditions. In the experimental setup described no significant synergistic effect was observed.

Revisiting the ultra-high dose rate effect: implications for charged particle radiotherapy using protons and light ions

OBJECTIVE To reinvestigate ultra-high dose rate radiation (UHDRR) radiobiology and consider potential implications for hadrontherapy. METHODS 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. RESULTS The literature findings were that, for X-ray and electron dose rates of around 10(9) 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. CONCLUSION 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.

Charged particle therapy for cancer : The inheritance of the Cavendish scientists?

The history of developments in atomic physics and its applications follows the decisive input provided by Maxwell and subsequent discoveries by his successors at the Cavendish Laboratory. In medicine the potential applications of particle physics (with the notable exception of the electron) were unfortunately delayed by the disappointing experiences with neutron therapy, which produced long-term scepticism. Neutrons are not appropriate for cancer therapy because not only their physical dose distributions offer no advantages over X-rays, but also their biological dose distributions are worse. The much improved dose distributions achieved with charged particles offer real prospects for better treatment outcomes because of the large reduction in the volume of unnecessarily irradiated tissue in many situations. Charged particle therapy is relatively new and can be applied with increasing confidence due to advances in radiology and computing, but at present there are insufficient numbers of treatment facilities to produce statistically powerful studies to compare treatment outcomes with those of X-rays. Considerable progress has been achieved in Japan and Germany with pilot studies of carbon ions but their efficacy compared with protons needs to be tested: in theory carbon should be better for intrinsically radio-resistant and for the most hypoxic tumours. The optimisation of proton and ion beam therapy in clinical practice remains to be achieved, but there are good scientific reasons why these modalities will be preferred by patients and their physicians in the future. Regrettably, despite hosting many of the momentous discoveries that enabled the development of charged particle therapy, the UK is slow to adopt and implement this very important form of cancer treatment.

PAMELA - a model for an FFAG based hadron therapy machine

Approximately one third of the worlds 15000 accelerators are used for tumour therapy and other medical applications [1]. The characteristics of FFAGs make them ideally suited to such applications, as the much smaller magnet size and greater compactness offers considerable cost and operational benefits. In the first stage the work on PAMELA will focus on the optimization of the FFAG design to deliver the specific machine parameters demanded by therapy applications. In this phase of the PAMELA project the effort will concentrate on the design of a semi-scaling type FFAGs to deliver a 450 MeV/u carbon ion beam, including detailed lattice and tracking studies. The second stage will use the existing expertise in the BASROC consortium [2] to undertake a design of the magnets and RF system for PAMELA. An outline of the overall concept of PAMELA will be discussed and the actual status of the work will be presented.