First published online September 3, 2007
British Journal of Radiology (2007) 80, 855-858
© 2007 British Institute of Radiology
doi: 10.1259/bjr/29504942
Laser-driven proton oncology — a unique new cancer therapy?
K W D Ledingham, DSC
1,3
W Galster, PhD
1 and
R Sauerbrey, PhD
2
1 SUPA, Department of Physics, University of Strathclyde, Glasgow G4 0NG, Scotland, 2 Forschungszentrum, Dresden Rossendorf, Germany, 3 AWE plc, Aldermaston, Reading RG7 4PR, UK
Correspondence: Dr Wilfried Galster, Department of Physics, University of Strathclyde, 107 Rottenrow East, Glasgow G4 0NG, Scotland. E-mail: wilfred.galster{at}strath.ac.uk
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Abstract
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In 2000, the University of Strathclyde, collaborating with the Rutherford Appleton Laboratory, organized the first workshop dealing with the potential of high-power laser technology in medicine. Two areas of potential were identified: firstly the production of positron emission tomography (PET) isotopes; and secondly, the potential for laser-accelerated proton and heavy ion beams for therapy. The attendees, mainly clinicians and radiation physicists, emphasised that the laser community should concentrate on developing laser and target technology for therapy rather than isotope production because of the potential advantages over conventional accelerator technology for that purpose. On the 30 March 2007, the universities of Strathclyde and Paisley organized a follow-up meeting to identify the progress made in laser-driven proton and ion beam technology with applications leading to proton and ion beam therapy for deep-seated tumours. The meeting was supported by the Scottish Universities Physics Alliance (SUPA) — an organization set up in Scotland to bring together all of the physics departments collaborating with life scientists to work on ground-breaking new science which no single university could attempt. This is a summary of the meeting.
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Introduction
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In recent articles [1, 2], Bleddyn Jones and Neil Burnet argue the case for charged particle therapy (CPT), stating that proton and ion therapy holds much promise for the future. An increase in the number of CPT centres in the UK would benefit both children and young adults, with a reduction in radiation-induced malignancy, as well as older patients in more routine situations such as lung and liver disease. Compared with X-ray therapy, charged particles heavier than electrons produce excellent dose distributions to tumours while minimizing doses to normal tissue. In particular, proton and carbon beams produced by cyclotrons or synchrotrons were an important development in radiotherapy. CPT with heavy particles has proved a very effective therapy for deep-seated tumours in many countries around the world. However, the recent introduction of new facilities, especially in Switzerland and Germany, has posed the question — what is the UK doing in this exciting new field? Although the Clatterbridge Centre for Oncology (CCO) has been carrying out important work with a 60 MeV cyclotron, the limited maximum range permits only the treatment of eye tumours. Unfortunately, the UK has no facilities for carrying out CPT on deep-seated tumours, which requires protons in excess of 200 MeV. The reason for this, as is often the case in the NHS, is one of cost — a 200 MeV accelerator with shielding and state-of-the-art gantries costs about £100 million. However, UK clinicians now argue that a national centre is essential because patients in the UK will demand treatment abroad in these new European facilities.
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Laser-driven proton and ion beams
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Firstly, let us emphasise that we are not in competition with our colleagues developing new and improved conventional accelerator technology for CPT and who are attempting to establish a UK national centre through the British Accelerator Science and Radiation Oncology Consortium (BASROC) [3]. There is no question that the present radiofrequency (RF) accelerator technology could provide CPT for the next few years, but the potential for laser accelerator technology in the longer term is so compelling that, in our view, a pilot study should be set up without delay. The 1-day meeting in Strathclyde [4] was held to identify where we are in laser accelerator technology and to identify what we have to do to deliver the vision of laser-driven proton and ion beams for oncology. To this end, we invited a number of outstanding world-leaders in laser proton beam technology, as well as some of the most prominent UK practitioners using RF accelerator technology.
Before summarizing the contributions from the speakers, we feel it is necessary to describe briefly laser accelerator technology for those who are not aware of this relatively new development in physics. A review of the applications for nuclear phenomena generated by ultra-intense lasers can be found in [5].
In Figure 1
, high-intensity laser (>1019 W cm–2) is incident on a thin metal target. Although the figure shows the beam incident at 45°, all angles of incidence are permitted. Thin metal foils, or even non-conducting materials like mylar, have been used as a target. The laser beam is focused by an off axis parabola within an irradiation vessel at an ambient pressure of typically 10–6 mbar. At this pressure, layers of impurities of water vapour or pump oil lie on the surfaces at a thickness of about 10 nm. It is these layers of impurities that are the source of the protons and heavy ions. The laser impinges on the surface of the target and ionises the hydrogen-bearing molecules. Essentially, photon pressure causes the electrons to be accelerated into the target, which then ionize the molecules on the back surface. A cloud of electrons are emitted from the back surface, causing a very strong electrostatic field that accelerates protons. These proton beams are very intense (1012 protons per pulse) and well collimated. Protons of up to 58 MeV have been accelerated in distances of a few microns when lasers with intensities of about 1020 W cm–2 were applied; this high acceleration field gradient (
1013 V m–1) is one of the greatest attractions of laser accelerators, owing to its ability to considerably reduce the size and cost of accelerators for medical applications. We can now envisage a proof-of-concept facility costing less than £10 million which, if funded, could lead to clinically viable beams in the next 10 years.
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Summary of the 1-day meeting
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The meeting consisted of presentations from seven invited leading international speakers. A critical summation was made of their contributions, and the meeting finished with a round table discussion emphasising where the field was heading. In this summary, each of the contributions of the main speakers is presented.
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Laser-accelerated protons for radiation therapy
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Professor Chang Ming Ma (Director of Radiation Physics, Medical Science Division, Fox Chase Cancer Centre, PA)
At the Fox Chase Cancer Centre, rapid advances in laser acceleration technology have been made with laser-induced plasmas, demonstrating that it was the first medical laser facility for particle acceleration studies. Professor Ma described the rapid progress he has achieved with his system that has been funded. Theoretically, his team has compared isodose distributions for laser proton beams with known intensity modulated radiotherapy (IMRT) and intensity modulated proton therapy (IMPT) and found them to be similarly effective, as can be expected for any proton beam, although the radiation dose to healthy tissue for IMRT was considerably greater. In its final form, his laser-driven proton facility will be compact, cost-effective and capable of delivering energy- and intensity-modulated proton therapy. His research is now focused on the target design for proton acceleration, the conception and implementation of systems for energy selection and beam collimation, and on dosimetric studies of laser-accelerated protons for cancer therapy. The cost of the basic laser-driven cancer facility was $10 million, and with sufficient ongoing support the Fox Chase facility could be completed in the near future, with the potential to treat patients relatively quickly.
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Proton and carbon ion cancer therapy at GSI Darmstadt
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Professor Markus Roth (Technical University of Darmstadt and GSI)
GSI has established a three-dimensional Rasterscan carbon ion cancer therapy and has successfully treated patients over the past 2 years using conventional RF technology. A second centre will be established in Heidelberg in a joint collaboration with GSI and Siemens. Although most of the present therapy is being carried out on brain tumours, GSI is exploring the application of heavy ion treatment to other tumours and is also investigating future acceleration schemes for compact medical accelerators. The German Helmholtz Foundation has established a Virtual Institute to explore the acceleration of ions by ultra-intense laser beams. The main thrust of this research is to couple short pulse laser ion sources to compact accelerator structures with the motivator to shrink the size and cost of ion accelerators for medical applications. Lasers produce 1011 protons per shot, whereas 108 are sufficient for therapy. For carbon therapy, 5 GeV carbon ion energy is needed.
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Proton and ion beam radiotherapy from laser light
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Professor Roger Dale (Director Radiation Physics and Radiobiology, Hammersmith Hospitals NHS Trust, and Professor of Cancer Radiobiology, Imperial College, London)
Professor Dale indicated that the contributions to cancer cure from surgery, radiation therapy and chemotherapy are 49%, 40% and 11%, respectively. The role of radiotherapy as a major modality in the successful treatment of cancer is thus assured for many years. Although there are other developments that have the scope to improve radiotherapy, it is expected that at least 1%, and possibly as many as 12%, of patients currently treated with X-rays would be better treated with protons or ions. Using ion therapy, the radiation-induced cancer risk for children, in particular, is reduced, as much less energy is deposited in the body when compared with conventional X-ray based radiotherapy. He identified also other advantages of laser-produced CPT:
- (a) a drastic reduction in the size of the beam-generation plant and guidance system, allowing more centres to accommodate a proton facility within an existing department
- (b) a reduction in imaging costs on account of in-beam and in vivo imaging using the activation of short-lived low-Z isotopes
- (c) an opportunity to perform mixed-beam radiobiological studies
- (d) on account of the cheaper technology, there is reduced pressure to quickly ramp-up to a high patient throughput merely to recover capital costs
- (e) the scope for industrial manufacture of the lasers and target systems, including potential intellectual property rights
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Medical applications with laser plasma accelerators
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Professor Victor Malka (Research Director at CNRS, Ensta, Ecole Polytechnique, Paris)
Professor Malka described how intense laser beams can produce protons, electrons and X-rays, and that plasmas can support electric fields at least four orders of magnitude greater than conventional accelerators, which results in compact laser accelerators, a point made by many speakers. Although the principal reason for the meeting was to investigate laser-induced ion therapy, Professor Malka stressed that a laser-induced high-energy electron beam was also useful for therapy; quasi mono-energetic electron beams in excess of 100 MeV were generated by lasers and their properties have been simulated by Monte-Carlo methods, with the dose deposition in water indicating sharp lateral penumbra and deep longitudinal penetration similar to high-energy photon beams. The interaction of laser and electron beams can produce monochromatic X-ray beams of interest for imaging cancer tumours and for K-edge therapy techniques.
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Ion beams in biology and medicine
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Dr Karen Kirkby (Surrey Ion Beam Centre, University of Surrey) and Professor Melvyn Folkard (Gray Cancer Institute, Northwood)
These speakers highlighted that, although therapy was the main object of the meeting, ion beams created by RF accelerators or lasers could be used quantitatively to map the spatial and depth distribution of a wide range of elements at "parts per million" concentrations in biological and medical samples. The response of cells to precisely controlled doses of radiation at specific parts of their structure, and at specific temporal points in the cell cycle, can provide important insights into the mechanisms by which ion beams interact with living cells and tissue. Indeed, the use of micro- and nano-irradiation techniques is the most robust and versatile method of obtaining this information. This research is important as it is a route to the development of improved strategies for cancer treatment and better estimates of the risks associated with occupational and environmental exposures to ionizing radiation, including the thorny problem of whether harmful radiation effects exist at low doses.
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Progress towards delivering laser accelerated proton beams for biological studies and radiation therapy
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Professor Ken Ledingham (Sir William Penney Professor of Laser Nuclear Physics, University of Strathclyde, Glasgow)
Since 2000, the Strathclyde team has researched the fundamental physics involved in laser-driven proton and ion beams and, while working recently with the University of Jena, has identified how to produce quasi mono-energetic proton beams using titanium targets with microdots of hydrogen-containing molecules. Attaining quasi mono-energetic beams is essential for medical applications. In addition, this group has also shown that high-intensity laser beams can produce positron emission tomography (PET) isotopes with activities >107 Bq. Thus, by using lasers, the proton beams can be used for therapy and simultaneously for PET isotope production for diagnostics. The laser approach to producing ion beams may offer considerable cost savings in facility construction, as well as during operation and finally in the decommissioning phase after tens of years of service. These laser-driven proton beams also have the unique property of ultra-short ion pulses, which could hold the promise of a completely new approach to ion therapy. Professor Ledingham identified two lasers: Gemini at the Rutherford Appleton Laboratory and Polaris at the University of Jena, both petawatt lasers capable of generating laser intensities of between 1021 W cm–2 and 1022 W cm–2. Current theoretical calculations for micro-structured targets irradiated at these high intensities predict that the electrostatic fields produced can accelerate protons to energies of about 200 MeV.
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Summation
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Professor Roland Sauerbrey (Director of Forschungszentrum Dresden (FZD) Rossendorf and visiting Professor, University of Strathclyde)
Summing up the details of the talks that were presented, Professor Sauerbrey also described the Laser Oncology Programme at the FZD working in collaboration with the Universities of Jena and Strathclyde and onCOOPtics, a cooperative radiation oncology centre researching in the improvement of cancer treatment. onCOOPtics is the only established laser oncology centre in Europe focused on laser-driven proton oncology. He stressed that the initial work at Rossendorf will include fundamental work dealing with proton and ion irradiation of biological material and, eventually, irradiation of tumours in mice, which is a prerequisite before human treatment is to be contemplated. Such animal experiments could not be carried out at any of the UK laser centres.
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Round table discussion
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In addition to the main speakers, two further experts were introduced to lead the discussions: Dr Andrzej Kacperek, Director of the CCO, and Professor Wilfried Pilloy, Centre Hospitalier du Luxembourg. Generally, it was expressed that physicists, clinicians and life scientists should come together to develop laser-driven proton and ion beams and their medical applications, and that the laser community must work closely with the established CPT cyclotron community to deliver the national UK CPT centre. Only then would ion therapy as a whole be accepted by the NHS. This acceptance would lead to many smaller and less expensive laser-driven ion facilities in the long-term. It was also felt that SUPA could not work alone in this field but should be encouraged to work with the large UK and European Laboratories such as the Rutherford Appleton Laboratory and Rossendorf before laser-driven proton therapy could be delivered.
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Acknowledgments
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The authors are indebted for discussions and encouragement to Professors Bleddyn Jones, Roger Dale, Wilfried Pilloy, Michael Baumann and Wolfgang Enghardt, and Dr Andrzej Kacperek.
Received for publication April 27, 2007.
Revision received July 13, 2007.
Accepted for publication July 24, 2007.
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References
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- Jones B. The case for particle therapy. Br J Radiol 2005;78:1–8.[Free Full Text]
- Jones B, Burnet N. Radiotherapy for the future. Br Med J 2005;330:979–980.[Free Full Text]
- British accelerator science and radiation oncology consortium (BASROC). Available from: http://basroc.rl.ac.uk
- Laser Driven Proton Oncology – A Unique New Cancer Therapy in Scotland? Meeting; 2007 March 30; University of Strathclyde, Glasgow
- Ledingham KWD, McKenna P and Singhal RP. Applications for Nuclear Phenomena Generated by Ultra-Intense Lasers. Science 2003;300:1107[Abstract/Free Full Text]
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Abstract
Introduction
