Proton and Heavy Ion Therapy: An overview: January 2017
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To produce protons, negatively charged electrons are split from hydrogen atoms leaving the
positively
charged protons, which are accelerated in a cyclotron or synchrotron to 40 to 70 per
cent of the speed of light, then directed through a magnetic beam steering system to the
treatment room.
1
Photons (used in conventional radiotherapy) and protons both have a low
density of ionisation events or linear energy transfer (LET)
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, however protons are believed to have
an increased 10 per cent relative biological effectiveness (i.e. RBE of 1.1) on both healthy and
cancerous tissue.
Carbon ions are of particular interest due a high rate of energy loss towards the end of the particle
range, resulting in a larger increase of the LET at the Bragg Peak.
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For carbon ion production,
newer facilities utilise carbon dioxide gas as an ion source. Heavier than protons, carbon ions
undergo a two-stage acceleration process: initial acceleration in a linear accelerator up to 10 per
cent of light speed; followed by further acceleration in a synchrotron up to 75 per cent of light
speed.
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Carbon ions are considered to have as good or better distribution of absorbed dose as
protons, are superior to photons
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, and with a higher RBE (between 1.5 and 3.4) may prove to be a
more effective treatment option.
24
High-LET ions such as carbon have a reported range of
radiobiological advantages compared with photons or protons for treating tumours resistant to
low-LET irradiation, such as adenocarcinomas, adenoid cystic carcinomas, malignant melanomas
and sarcomas.
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Additionally, due to the physical and biological properties of carbon ions, there is
potential for increased use of treatment hypo-fractionation (delivery of radiation by larger doses
over a shorter timeframe)
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, which can reduce patient treatment times and improve cost-
effectiveness. However, as there are only a limited number of carbon ion facilities in operation
internationally, further investigations are needed, especially in the area of dose-distribution of
carbon ions during treatment,
20
and translation into radiobiological and clinical effects.
A summary of the advantages and disadvantages of protons and carbon ions,
compared to
traditional photons, are presented below in Table 2.
Proton and Heavy Ion Therapy: An overview: January 2017
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Table 2
Biological advantages and disadvantages of conventional radiotherapy and particle therapy
Treatment
Advantages
Disadvantages
Photon (X-rays) Radiotherapy
Established treatment modality and
protocols
High integral radiation dose
High risk for tumours located near vital
organs or tissues
Low LET reduces effectiveness for
tumours resistant to low LET irradiation
Proton Beam Therapy
Lower integral radiation dose compared to
conventional radiotherapy
Believed increased relative biological
effectiveness compared to x-rays
Use in tumours located near vital organs
or tissues
Low LET reduces effectiveness for
tumours resistant to low LET irradiation
Some uncertainties in relation to
radiobiological effectiveness, treatment
protocols, and effectiveness in range of
tumour types
Higher establishment and running costs
compared to conventional radiotherapy
Limited cost-effectiveness evidence
Carbon Ion Beam Therapy
Lowest integral radiation dose
High relative biological effectiveness
Use in tumours located near vital organs
or tissues
High LET for use in tumours resistant to
low LET irradiation
Potential for hypo-fractionation (reduced
number of treatments in a course of
treatment)
Emerging treatment
Limited effectiveness evidence
Uncertainties in relation to radiobiological
effectiveness, treatment protocols, and
effectiveness in range of tumour types
Unknown cost-effectiveness
Higher establishment and running costs
compared to conventional radiotherapy
and proton therapy
Particle Therapy Facilities
In relation to particle beam generation, cyclotrons and synchrotrons are used to generate proton
and carbon/heavy ion particles. Proton beams are generated either in a cyclotron which uses a
single-stage acceleration process (i.e. the cyclotron alone can accelerate the protons to the
required energies), or a synchrotron, with subsequent delivery through high vacuum ‘beamline’
structures to treatment rooms.
Proton and Heavy Ion Therapy: An overview: January 2017
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Synchrotrons are necessary for the generation of heavy ion beams due to the increased energies
required in accelerating heavy particles to clinical therapy velocities. However, as synchrotrons are
unable to accelerate particles from zero kinetic energy, they require a two-stage acceleration
processes (i.e. a pre-accelerator structure that injects the particle beam into the synchrotron for
further acceleration). Therefore, facilities that utilise a synchrotron accelerator typically require a
larger footprint than a cyclotron installation.
A cyclotron is only able to accelerate to a set maximum energy, which then requires an energy
degrader to reduce the energy at the expense of some beam current and “sharpness” of the Bragg
peak. A synchrotron can accelerate the particle to a given energy before extraction which can then
be delivered to the patient, allowing beam current and the sharpness of the Bragg peak to be
optimally maintained.
Figures 2 and 3 demonstrate a typical layout of a conventional large-scale proton or combination
proton/carbon ion-beam facility utilising a synchrotron. The beams are produced at position 1,
with hydrogen gas used to obtain protons and carbon dioxide used for carbon ions. The two-stage
linear accelerator is situated at position 2, where protons or carbon ions are accelerated in high-
frequency structures to up to 10 per cent of the speed of light. The protons or carbon ions are
then sent into the synchrotron (position 3), where six 60° magnets bend the beams into a circular
path. The protons or carbon ions are accelerated to up to 75 per cent of the speed of light orbit by
orbiting the synchrotron approximately a million times.
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Figure 2
Diagram demonstrating the ion sources, the 2-stage linear accelerator and the synchrotron
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