Abstract
Recently introduced technologies in radiotherapy have significantly improved the clinical outcome for patients. Ion beam radiotherapy, involving proton and carbon ion beams, provides excellent dose distributions in targeted tumours, with reduced doses to the surrounding normal tissues. However, careful treatment planning is required in order to maximise the treatment efficiency and minimise the dose to normal tissues. Radiation exposure from secondary neutrons and photons, particle fragments, and photons from activated materials should also be considered for radiological protection of the patient and medical staff. Appropriate maintenance is needed for the equipment and air in the treatment room, which may be activated by the particle beam and its secondary radiation. This new treatment requires complex procedures and careful adjustment of parameters for each patient. Therefore, education and training for the personnel involved in the procedure are essential for both effective treatment and patient protection. The International Commission on Radiological Protection (ICRP) has provided recommendations for radiological protection in ion beam radiotherapy in
1. INTRODUCTION
Remarkable progress has been made in the application of radiotherapy over the last half-century. Recently introduced radiotherapy techniques can improve the dose conformation to the target tumour with better sparing of normal tissues. However, complicated treatment systems require careful handling of the equipment and basic knowledge of radiological protection. Thus, education and training specific to new treatment methods are essential for safe and efficient use of the clinical application. The International Commission on Radiological Protection (ICRP) has published recommendations for radiological protection in radiotherapy, including
Ion beam radiotherapy can theoretically provide excellent dose distribution due to the advantage of enhanced energy deposition at a certain depth in the body (Tobias et al., 1956). New treatment systems of ion beam radiotherapy permit further improvements in dose distribution with the advancement of treatment planning systems.
2. ION BEAM RADIOTHERAPY
Ion beams provide superior dose distributions due to their finite range in tissue, resulting in a significant reduction in radiation exposure to surrounding normal tissues. Ion beam radiotherapy is characterised by production of the maximum ionisation density at a certain depth in tissue, depending on the energy of the ion beams delivered, referred to as a ‘Bragg peak’. This provides improved dose conformation to the treatment volume, with better sparing of the surrounding normal tissue structures.
2.1. Patient selection
Ion beams are considered to have the optimum properties for dose localisation. The selection of patients suitable for ion beam radiotherapy is the first step in the treatment. Benefits of ion beam therapy can be achieved in patients with solid cancers with defined borders. Further, this treatment can be considered to be ideal for inoperable tumours.
Proton beam radiotherapy may offer clinical advantages compared with conventional photon radiotherapy for many cancers, mainly as a result of a more favourable distribution of radiation dose (Lundkvist et al., 2005). Carbon ion therapy has the advantage of high-linear-energy-transfer (LET) radiation for the treatment of various tumours which are resistant to conventional photon radiotherapy or chemotherapy (Chauvel, 1995). The benefits of carbon ion radiotherapy have been shown for non-squamous cell tumour types, including sarcoma, malignant melanoma, adenocarcinoma, adenoid cystic carcinoma, and chordoma (Tsujii and Kamada, 2012).
However, the advantage is more difficult to utilise in patients with cancer of the digestive tract, such as stomach and colon cancer, due to unexpected motions of the organ wall during the treatment process, and possible perforation of the wall by any severe damage caused by the treatment. Although ion beam radiotherapy has not yet demonstrated a substantial improvement in long-term survival for most patients (Soarers et al., 2005), it can provide similar outcomes as surgical resection with better quality of life.
2.2. Delivery of ion beams
An ion beam delivery system consists of an accelerator, a beam transport system, and an irradiation system. A high-energy ion beam is delivered through a beam transport system to an irradiation system. The original narrow beam extracted from the accelerator is not ready for use in treatment, except when using a beam scanning method. The irradiation system broadens the narrow beam for the specific target volume. This method is called the ‘broad beam method’ and is classified as the ‘passive method’. Alternatively, ‘beam scanning’ is a method to achieve a highly conformal field by three-dimensional scanning of the original beam, extracted from the accelerator, within the target tumour volume. The broad beam method has the advantage of providing uniform beam distribution in the target volume, while the beam scanning method requires precise control of beam delivery, but can theoretically achieve more conformal dose distributions, particularly for complex-shaped targets. Furthermore, scanning allows the delivery of intensity-modulated particle fields.
2.3. Physical and biological characteristics
Ion beams are characterised by conformal dose concentration in tissue and enhanced biological effects. The clinical advantage results from a steeply rising absorbed dose, or Bragg peak at a certain depth, depending on the energy of the ion beams. Therefore, a superior dose concentration can be achieved by targeting the tumour within the Bragg peak. This advantage is similar for both proton and carbon ion beams.
The absorbed dose in Gy is the primary quantity to determine the biological and clinical effectiveness of any radiation beam, but radiation quality of an ion beam also affects the outcome. The most commonly used quantity for specifying radiation quality is the LET (ICRU, 1970). Values of relative biological effectiveness (RBE) are defined as the ratio of a dose of a low-LET reference radiation to a dose of the radiation considered that gives an identical biological effect. Proton beams in current clinical use have been conventionally considered as low-LET radiation, and thus the RBE values used are close to that of high-energy x rays. However, this simplistic view has recently been questioned as protons in the region of the distal Bragg peak can have RBE values as high as fast neutrons, and late-reacting normal tissues may be more sensitive to subtle increases in LET and thus RBE (Dasu and Toma-Dasu, 2013; Paganetti, 2014; Jones, 2015; Tommasino and Durante, 2015). Carbon ions, on the other hand, have higher RBE values than protons, and these increase with depth and have their maximum values near the depth where the Bragg peak occurs. RBE-weighted absorbed physical doses, Gy(RBE), can be used for clinical purposes when considering the biological effect of ion beams (ICRU, 2007; Wambersie et al., 2011; Bentzen et al., 2012).
2.4. Procedures of treatment
2.4.1. Diagnostic imaging
The accurate delineation of the tumour boundary is the first step of this treatment. Diagnostic imaging, such as x-ray computed tomography (CT), magnetic resonance imaging (MRI), and positron emission tomography (PET), is indispensable for reliable treatment planning. Combined imaging devices, such as PET-CT or PET-MRI, have also become available to provide valuable diagnostic information for treatment planning. The excellent outcomes of ion beam radiotherapy, which have been proven in recent papers, are partly due to advances in diagnostic imaging.
2.4.2. Treatment planning
Treatment planning is based on calculation of the ion beam doses delivered to the tumour and surrounding tissues, considering the physical and biological characteristics of ion beams. Careful treatment planning is expected for optimising the dose to the tumour, with minimum dose and thus effects in surrounding healthy tissues.
Treatment planning for ion beam radiotherapy usually starts from CT scans, which should be taken under the same conditions as the real treatment. The patient is immobilised on the treatment couch under the same breathing condition as for treatment.
The clinical target volume and organs at risk (OARs) are first defined on the planning CT images, followed by determination of the planning target volume, which allows for physiological changes between the planning CT and treatment, including organ motion and daily variations in set-up positions (ICRU, 1993, 1999). Unlike in conventional therapy, ion beam radiotherapy also requires the consideration of range uncertainties (Rietzel et al., 2007; Paganetti, 2012).
2.4.3. Immobilisation and irradiation
After treatment planning, the procedures of ion beam radiotherapy include patient immobilisation, patient positioning, and beam delivery for irradiation. It is essential to manage the entire process with extreme care in order to achieve the planned dose to the tumour, and also to avoid accidental overexposure and unnecessary damage in the surrounding tissues.
During the treatment process, the patient is immobilised and positioned for treatment, and the ion beams are delivered for a period of seconds or minutes depending on the intensity of the beams. The conditions of beam delivery, the patient, and devices are monitored constantly, and the beam is stopped when the prescribed dose has been administered.
In spite of careful handling and monitoring, the movement of organs in the body cannot be avoided, which may cause inaccuracy in the dose calculation and unexpected doses to tissues, particularly due to changes in the beam range and thus the position of the Bragg peak. Therefore, these factors should always be considered in treatment planning.
2.4.4. Respiratory motion
The motion of organs always degrades the precision in dose delivery. Respiratory breathing is the most common cause of organ motion, with significant movement in both the thoracic and abdominal regions. However, this problem can be solved in two ways: by breath holding during irradiation; or by gating of the irradiation delivery over the respiratory cycle.
Respiratory gating of radiation exposures has been proposed and used in conventional external beam radiotherapy. Breathing motion can be detected and monitored with an infra-red light spot and a position-sensitive charge-coupled device camera, which provides a respiration waveform signal as used for gating delivery of ion beams in certain phases of the respiratory cycle. Fluoroscopic imaging can also be used for this purpose. As the movement of organs is usually more stable at the end of expiration, gating for beam extraction is usually set to this phase of respiration.
3. RADIOLOGICAL PROTECTION
3.1. Medical exposure
3.1.1. Therapeutic dose
Treatment planning in ion beam radiotherapy can theoretically provide a curative radiation dose to be delivered to the target volume. Obviously, the therapeutic dose delivered to the target tumour could cause serious damage if normal tissues are included; however, the definitive determination of the tumour boundary is not always easy in a clinical setting, and irradiation to the marginal zones should always be considered. Treatment planning should optimise that situation, providing sufficient dose to the tumour while avoiding potential serious tissue damage in critical organs, similar to other general radiotherapy methods. The treatment planning method for proton radiotherapy, as described in ICRU Report 78 (ICRU, 2007), is essentially the same for carbon ion radiotherapy, except for the consideration of RBE variations in carbon ion therapy.
3.1.2. Dose in out-of-field volumes
Doses in out-of-field volumes can be estimated in the treatment planning of ion beams, but additional dose also arises from secondary neutrons and photons, particle fragments, and photons from activated materials. These undesired but unavoidable doses should be considered for the purpose of radiological protection. Secondary neutrons are the main factor to contribute to dose in the areas distant from the treatment volume. The use of the pencil beam scanning method can reduce this type of radiation exposure significantly.
Studies comparing conventional photon radiotherapy, intensity-modulated radiotherapy (IMRT), and proton radiotherapy showed that both IMRT and proton radiotherapy have a similar ability to improve the dose distribution in the target volume, but proton radiotherapy provides a more favourable dose distribution in the out-of-field volumes (Palm and Johansson, 2007). Carbon ion radiotherapy can reduce the maximum dose to OARs due to its lower scattering power.
3.1.3. Medical exposure from imaging
Imaging procedures involved in ion beam radiotherapy include x-ray CT for treatment planning, radiographic and fluoroscopic procedures for treatment rehearsal, and patient set-up verification at the beginning of each dose fraction. Although these imaging procedures provide significant information for ion beam radiotherapy, they also result in additional radiation doses to the patient. Typical doses delivered from various imaging procedures during ion beam radiotherapy and after treatment could sometimes reach 100 mGy. This will vary according to the treatment fractionation schedule and frequency of x-ray imaging.
3.1.4. Risk of second cancer after radiotherapy
The expanding use of radiotherapy and significant improvement in long-term patient survival have resulted in the need to monitor and evaluate patients for possible risks of second cancers (NCRP, 2011). The risk of second cancer for a patient depends on the volume of the high-dose region in the irradiation field and the low-dose region outside that field. Proton and carbon ion radiotherapy achieves the best dose distribution for the target volume, as mentioned above, and obviously results in not only reducing side effects in OARs but also minimising the risk of second cancer within or near the irradiation field. The risk of second cancer in the low-dose region remains a controversial issue, as the exposure is considerably lower than that close to the treatment target volume, but it may not be negligible for risk assessment, especially in younger patients. Previous studies have suggested that proton radiotherapy, particularly using the scanning method, can reduce the incidence of second cancer compared with IMRT or conventional photon radiotherapy (Newhauser and Durante, 2011; Moteabbed et al., 2014).
3.1.5. Protection of family members
High-energy ion beams, such as protons or carbon ions, induce nuclear reactions in a patient’s body, resulting in the activation of nuclei. The major radionuclides induced are short-lived positron-emitting radionuclides, such as C-11, N-13 and O-15. This requires the assessment of radiation exposure to people who stay close to the patient after ion beam radiotherapy, such as working staff, comforters and carers, and family members. However, radiation exposure of family members and caretakers due to this activation is quite small, and no specific protection procedures are required (Tsujii et al., 2009).
3.2. Occupational exposure
In ion beam radiotherapy, interactions with atomic nuclei also result in activation of the air of the treatment room, the patient’s body, and the beam line devices. The sources for occupational exposures of radiation workers in the facilities are these activated materials, and the activity is highest just after irradiation of the patient as the physical half-lives of the induced radioactivity are relatively short, and the radioactivity decreases steadily according to the half-lives of these radionuclides.
Medical staff may have to enter the treatment room just after ion beam radiotherapy, where the activated air and equipment may cause radiation dose to the staff. The activation doses in proton radiotherapy are higher than those in carbon ion radiotherapy because the fluence of protons delivered to patients is generally higher than that for carbon ions. For both protons and carbon ions, the activation doses can be lower with the pencil beam scanning method than the broad beam method. Doses to workers, estimated in typical clinical settings, concluded that the current regulations for photon radiotherapy are also applicable to ion beam radiotherapy (Tsujii et al., 2009; ICRP, 2014).
3.3. Management of radiation safety
Appropriate handling and management are required for accelerators when radiation safety standards for high-energy particle accelerator facilities are applied. ICRP provided the scope of radiological protection control measures in
Appropriate management of therapy equipment is needed due to activation during the treatment process. It should also be considered that air in the treatment room is activated. Management should always conform with the criteria of the regulatory agency. The current regulations for occupational exposures in photon radiotherapy are also applicable to ion beam radiotherapy with protons or carbon ions.
4. PREVENTING ACCIDENTAL EXPOSURE
Recently introduced methods in radiotherapy provide highly conformal dose distribution, but even subtle errors during the treatment process would easily bring severe consequences. In order to avoid accidental exposures, prospective, structured, and systematic approaches to identify the system’s weaknesses are needed (ICRP, 2009). For this purpose, dissemination of the knowledge and lessons learned from accidental exposures is important in preventing re-occurrence of accidents. As ion beam radiotherapy has only been applied in a limited number of patients, the lessons learned from previous accidental exposures from conventional external beam radiotherapy are also helpful in preventing accidents in ion beam radiotherapy (ICRP, 2014).
The greatest advantage of ion beams for radiotherapy is dose localisation characterised by the Bragg peak, which enables excellent dose distribution to the target volume with adjacent OARs receiving the lowest dose possible. However, substantial concerns still exist due to uncertainties in the beam parameters, as target positioning is more critical in ion beam radiotherapy (ICRP, 2009). At present, because the lessons learned from published events are not yet available, prospective approaches to identify potential risks should be considered carefully for comprehensive quality assurance (QA). This can detect systematic errors, and decrease the frequency and severity of random errors (ICRP, 2000; Cantone et al., 2013).
5. RECOMMENDATIONS
Ion beam radiotherapy provides excellent dose distribution to the target tumour, and proper patient selection should be the first step for justification of the treatment to provide optimal benefit to the patient (ICRP, 2014). Careful treatment planning is required for optimisation to provide the maximum efficiency of treatment, and minimum dose to normal tissues. Proton and carbon ion therapies are more conformal than conventional therapy, which makes them more prone to the dosimetric effects of uncertainties.
An ion beam delivery system consists of an accelerator, a high-energy beam transporter, and an irradiation system. When ion beams pass through or hit these beam line structures, secondary neutrons and photons can be produced, as well as particle fragments and photons from the activated materials. Doses in out-of-field volumes arise from secondary neutrons and photons, particle fragments, and photons from activated materials.
Appropriate management is required for the equipment and air in the treatment room. The current regulations for occupational exposures in photon radiotherapy are also applicable to ion beam radiotherapy with protons or carbon ions. After treatment with ion beam radiotherapy, the patient is a radioactive source. However, radiation exposure of family members or the public is small, and no specific care is required.
Ion beam radiotherapy requires a much more complicated treatment system than conventional radiotherapy. As such, extensive training of staff and an adequate QA programme are recommended to avoid possible accidental exposure of the patient.
Incorporating lessons learned from past accidental exposures into current training is crucial to prevent re-occurrence. A number of lessons learned in photon radiotherapy may also be applicable to ion beam radiotherapy. This retrospective approach should be complemented with prospective methods for identification of system weaknesses and their prevention in ion beam radiotherapy.