Science & Applications: Hadron therapy for cancer treatment
Relevance of hadron therapy
In 1946, when Robert Wilson published  the physical advantages of ion beams for therapy, there was no significant reaction from the medical community. However, the idea of proton- and carbon- tumour therapy is presently exploding within this community (fig.1). Up to now, 300 patients have been treated at GSI, Germany, with carbon ions and 2,000 at Chiba, Japan and 10, 000 at Loma Linda University Medical Center, US. Proton therapy is an effective treatment against cancers located in areas which are inaccessible to the surgeon's instruments or which are hard to treat by radiotherapy. This is the case for brain tumours, in areas close to the spinal cord, or inside the eye.
Fig. 1: In red, the number of proton therapy centres already in use (left values) and under construction (right values) and ion facilities, in black.
The main difference between X-rays and particles is their different biological action and different depth-dose distribution. For X-rays the dose decreases exponentially for larger penetration depths (fig. 2). Therefore deep-seated tumours have to be irradiated from many parts in order to distribute the non-wanted dose in front of the tumour over a large volume when delivering a lethal dose to the tumour. In the very modern technique of Intensity Modulated radio-therapy, IMRT, up to 10 fields from different directions are individually shaped. IMRT leads to excellent tumour control although a large volume of healthy tissues can be exposed to radiation. The major problem of this therapy is the induction of secondary tumours.
General solutions regarding the dose issue and as well as greater precision are possible with particle therapy . Hadron beams have an inverse dose profile that produces a greater dose to the tumour than to the healthy tissue in the entrance, even though only one treatment field is used (fig.2). With the most advanced technique, Intensity Modulated Particle Therapy (IMPT), where the pencil of hadron beams is guided according to the shape of the zone to be treated, the tumour can be delineated in all its contours with a precision of 2-3 mm.
Fig. 2: Comparison of depth dose distribution in water as tissue equivalent. Ions have a peaked profile which allows greater tumour dose at lower dose to the normal tissue around. Changing the ion energy shifts in depth the position of energy deposition.
Proton and heavy ion therapy
Because of higher atomic numbers, the lateral and range scattering is much smaller for carbon or neon ions than for protons. One of the major advantages of heavy ion tumour therapy is the increase in relative biological effectiveness (RBE) of particle beams in particular at the end of their penetration depth, i.e. in the tumour volume (Fig. 3). This increased effectiveness has to be taken into account for treatment planning. The RBE cannot be represented by a single number, but depends in a complex way on different factors like e.g. ion type and energy, depth in tissue, dose level and the tissue type. For applications of ion beams in tumour therapy, the increased RBE requires a corresponding general reduction in dose. In particular, due to the variation of RBE with depth, the shape of the depth dose profile has to be adapted accordingly. In general ions are better for radio-resistant tumours while protons minimize the risk of appearance of secondary tumours.
Fig. 3: Compared relative biological effectiveness (RBE) for proton, carbon and neon beams versus linear energy transfer (LET).
Contribution of laser-accelerated hadron beams
Improvement of heavy ion therapy can be achieved with less expensive accelerator technologies. Recently, it has been demonstrated that short pulse lasers can accelerate protons [4-7] or carbon ions up to a few MeV . For a potential use in therapy, these energies have to be increased to 150 MeV for protons and to 350 MeV/ for carbon ions. The latest experiments performed with more and more intense lasers (fig. 4) demonstrates that the route is not far from achieving protons with the right energy for medical treatment .
Fig. 4: Measured maximum proton energy versus the laser intensity as achieved over different facilities worldwide. From the blue curve (λl 2)1/2 scaling law λ that is the laser wavelength and I its intensity-, it appears that lasers able to produce intensity near 10 21 Wcm-2 at the focal spot will enter the medical region.
Moreover, the energy spectrum should have a narrow maximum at energies between 100 MeV/u to the full energy that could be changed from pulse to pulse, at least by a few percent. Work achieved by H. Schwoerer  demonstrated that micro-structured targets may drive peaked energy proton beams. They also confirm by 2D PIC modelling that a PW-class laser may produce 170 MeV proton beams with energy spread, ΔE/E, around 1% fitting the medical requirements. 
Figure 5: Proton spectra from the Thomson spectrometer simulation and scalability of the technique. The blue squares show a spectrum obtained from the irradiation of the micro-structured targets and exhibits a peak at energy of 1.2 MeV, as opposed to exponential spectra (red squares) in the case of irradiating unstructured foil. The experimental data (blue squares) is in excellent agreement with the results obtained from a 2D-PIC simulation (black line). The inset shows a simulation for a petawatt laser system and smaller dot size, demonstrating the scalability of presented technique. The spectrum then exhibits a narrow peak at 173 MeV with ΔE/E ≈ 1%.
Proton beam handling and focusing is still expensive and difficult. Eccentric or isocentric machines are used to transport proton beams from the last section of the accelerator to the tumours. These structures are made up of heavy magnet for beam deflexion weight from 100 to 200 tonnes and have a diameter from 4 to 10 meters (fig. 6), fitting hardly within a hospital. Specialized centres with an average cost of 150 M€ are required. Petawatt-class lasers are not necessarily much smaller than the accelerators used for conventional hadron acceleration. However, since the targets used for proton acceleration are a few centimetres in size, people consider with interest the possibility to place the target as close as possible to the patient, which means that only small mirrors are required for laser beam transport instead of heavy and costly magnets. Although particle selection and focusing systems  will be necessary after the target, the whole equipment should be much lighter, smaller and affordable than the current machines. Also one may imagine several distributed operation rooms, far from a central laser with only mirrors for beam distribution.
Fig. 6: Picture of an isocentric arm used for proton therapy.
Lasers are also relevant to reduce the overall very expensive shielding of the building since most often the accelerator is tens of meters away from the patient, meaning that the hadron path has to be highly radio-protected with thick concrete walls. In comparison, laser safety is much simpler since it only requires simple systems (goggles, plastic screens, fast shutters etc) to prevent from damaging medical staff or patients’ eyes.
Another important development will be to increase the driving laser repetition frequency close to the kHz. The front-end of ELI will be designed so as to produce petawatt laser beams with repetition rates above 100 Hz . We will consider both the diode-pump techniques currently under development in Germany  or the fibre lasers.
REFERENCES AND CREDITS
This web page has been partially constructed based on the R. Ferrand’s presentation (Institut Curie- France) on June 14th, 2007 and from the article G. Kraft, Nucl. Phys. News, Heavy ion tumor therapy: from the scientific principles to the clinical routine, 17, 1 p29 (2007).
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