Proton radiotherapy is a specific branch of the radiation therapy that uses a beam of accelerated protons to deposit energy in the target volume area. Like other modalities, it uses the physical properties of the given type of radiation for the best possible dose distribution.
All heavy charged particles, protons in this case, feature specific behavior when interacting with the matter. Inside the material (i.e. tissues in the case of radiotherapy) the beam of protons is gradually decelerated (unlike e.g. photon radiation, which retains its energy, but is attenuated in terms of intensity). During the deceleration, the intensity of energy transmission to the surrounding gradually increases, while passing of the proton through the material gets slower. Just before the proton completely stops in the material, the amount of energy transmitted abruptly increases. The described mechanism is reflected in the course of in-depth energy deposition, and can be described by the Bragg’s curve having its peak of transmitted energy in the area of final deceleration of particles in the material.
In the treatment of deep target volumes with irradiation, protons offer the chance to choose the depth of maximum energy deposition, while limiting the burden to the healthy surrounding tissue to a minimum dose. If the irradiation is performed e.g. from a single radiation field only, the dose before the target volume is always lower (two to three times) than the dose in the target volume, and the burden to healthy tissues behind the target volume is zero. Because of this property, it is often possible to choose simple irradiation techniques with a small number of radiation fields, which leads to a much lower integral dose to the patient. It is also possible to follow the threshold dose to critical organs, even with dose escalation to the target volume.
Technological developments in the field of proton therapy have recently been quite tumultuous. For many decades, the proton therapy has been underestimated in terms of clinical use, and the developed technologies included primarily beam forming, generation of a high-quality and consistent beam with a sufficient dose rate and parameters suitable for the treatment of patients. Although patients were treated with proton beams since the early 1950’s, such treatment was virtually always only about a research beam application to a selected group of patients in clinical trials. The first proton therapy center with a purely clinical focus was built in Loma Linda, USA, in 1990. Along with technological advances and increasing computing performance, the possibility of building medically oriented centers of proton therapy has increased, and at the beginning of 2015, about 50 centers were operational worldwide primarily with clinical focus. Moreover, a trend towards the growth of these centers has been clearly noticeable in recent years.
Initially, simple mechanical systems were predominant, wherein a beam of accelerated protons was directed to target structures using purely passive techniques, similarly to 3D conformal photon radiotherapy. For the initial deployment and with very strong selection of diagnoses, this approach was sufficient, but naturally it lacks a broad base of treated patients. At first glance, this is problematic from the perspective of the evidence-based medicine approach. However, it is important to realize that this is not a new medical procedure or a new drug, requiring randomized clinical trials to demonstrate safety and efficacy. In terms of therapy, it is a technological advance that is in principle equivalent to the introduction of multi-leaf collimators in photon radiotherapy. A sufficient justification for the use of this treatment modality is a dosimetric advantage of using proton therapy. In radiotherapy, the principle of minimizing the dose to healthy organs and maximizing the dose in the target volume is a fundamental principle that is often much better by proton radiotherapy than other available treatment options. This does not mean, however, that proton therapy has no room for further evolution, as has been finally demonstrated by the history of recent years. The passive scattering technique, which is suboptimal from many different perspectives, has been followed by active techniques, particularly the technique of pencil beam scanning, which makes the superiority of proton radiotherapy more visible.
In addition to the proton source, the first treatment configurations contained a beam guidance system meeting only the basic conditions for maintaining the flow of protons on route to the radiation room without major requirements for its parameters. In principle, proton accelerators as a source of particles are not located directly in the irradiation room (unlike the common practice in photon radiotherapy), but protons are accelerated in the designated areas and then transported to the treatment room(s). Beam shaping occurs in the treatment room.
The initial cohort of patients consisted of those with radio-resistant tumors of the skull base or target volumes in the eye. These very rare tumors were indicated for proton irradiation without evidence-based documents, only based on dosimetric advantages (a sufficient dose to the target volume with adequate protection of critical organs). At this point, however, the clinical desire was higher than the technical possibilities of that time and the centers started using the available technologies with only essential modifications to focus on other tumor localizations. In the meantime, however, rapid development of the photon irradiation technology continued. While the proton community focused on detailed and precise (perhaps too precise for routine clinical practice) determination of uncertainties within the range of the beam, the photon world has moved towards advanced imaging, adaptive radiation therapy and motion management. Thus, although the physical advantage was clearly on the side of proton radiotherapy, other components of the radiation therapy process remained far behind the photon competition. An unfortunate consequence of this is an inconclusive clinical comparison between the different modalities. Naturally, the overall treatment outcome depends not only on how to deliver the exact dose, but especially on with what accuracy it should be delivered. A sad monument in this direction is a comparative study of the outcomes in the treatment of prostate cancer with the photon technique and protons using the aforementioned scattering techniques, which failed to demonstrate any superiority of protons.
Like irradiation with cobalt irradiators or first linear accelerators that have been well forgotten (or perhaps are subject to nostalgic memories), it is also necessary to forget the outdated technologies of proton therapy. A quite obvious trend is the use of pencil beam scanning that goes hand in hand with the use of advanced approaches in treatment planning. Here it is advisable to make a minor note, since the irradiation technology alone is not decisive for the quality of the treatment. The crucial role is played by high-quality predictions of the dose distribution inside the patient’s body, allowing the determination of safe limits of the given radiation approach. Only the introduction of powerful computer technology opened the way to high-quality and in particular effective radiation therapy. The accuracy of algorithms for calculating the dose is an equally important parameter for the success of the respective radiation modality. While there has been a significant development in dosing algorithms for photon irradiation, no such development has taken place for protons. Advanced photon techniques, such as IMRT or VMAT, employ sophisticated optimization algorithms, fully using the potential of irradiators as well as of physical properties of photons. For protons, there has been only a marginal progress in this direction. The time has not come yet to have a scheduling system fully utilizing the advantages of proton irradiators, and the unique opportunities of pencil scanning. However, the current planning approaches allow the achievement of significantly better dose distributions than it has ever been or will be possible with photon radiotherapy. The possibility of individually modeled dose distributions not only in terms of the shape of the radiation field, but also the depth dose distribution in the patients ensures an opportunity to advance to a higher level of radiation treatment.
Glossary of Terms in Proton Therapy
Passive scattering technique – A method of forming a therapeutic proton beam so that materials are inserted in its path in order to disperse the materials to the sides or to depth. Although this is an obsolete approach in the proton treatment, it is still used in many centers.
Bragg curve – A curve describing the depth dose distribution of the proton beam. The characteristic shape can be basically divided into three areas. The first part is known as “plateau” and describes a continuous energy loss of the proton beam and braking of protons in the material. The second part of the curve rises relatively quickly as a result of an increase in the probability of interaction of protons with the material during the decline in their speed. This phase is followed by a steep decline. Protons in this area have already passed all of their energy to the environment, and no energy is transferred deeper. The region with the highest energy intensity of transmission is known as the Bragg peak.
Proton beam range – An area with a sharp decline in the depth dose curve after the Bragg peak. Uncertainty in the determination of this parameter is often an argument against the use of radiation techniques that are too conformal. Nevertheless, using an appropriate dosimetric approach and ensuring quality of the imaging and planning procedures, this uncertainty is well manageable.
IGRT (Image guided radiation therapy) – A general approach necessary for the implementation of high-quality and conformal radiotherapy. This is an entire complex of possible imaging procedures that ensures the delivery of the right dose to the right place in the body. The most common method is portal imaging (using linear photon accelerators) or the use of additional imaging methods using an x-ray beam (plain radiography imaging, orthogonal radiography imaging, computed tomography). Other methods include, e.g., ultrasound imaging, RFID technology, stereoscopic optical imaging, etc.
Pencil beam scanning – A dose delivery technique that uses a proton beam to ensure that the beam is not dispersed mechanically, but swept through the magnetic field in the space. This can be used to deliver a completely precise dose into target volumes with highly complicated shapes, and to select places with higher and lower dose (i.e. dose painting) inside the target volumes.
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