Particle Accelerators and Gamma-therapeutic Devices - an Effective
Tool for Cancer Treatment
VLADIMIR KRASILNIKOV
Department of Nanomaterials
Belgorod State University
St. Pobeda 85, Belgorod, 308015
RUSSIA
EDUARD KUPLENNIKOV
Department of Nuclear Physics
National Scientific Center "KIPT"
St. Akademicheskaya 1, Kharkov, 61108
UKRAINE
Abstract: - The review is based on the analysis of the state and the concept of modernization of world radiation
oncology. The material contains brief information about the reasons for the use of radiation therapy for the
treatment of cancer foci; active sources of particles; achieved results of therapy, etc. The role of accelerator
technology, innovative related equipment and nuclear physics methods for the treatment of oncological diseases
is described. The main characteristics of linear electron accelerators with the energy Ee = 6 MeV, the
parameters of multifunctional installations with Ee = (4 - 25) MeV generating several photon and electron
beams and accelerators of protons and carbon ions are given. It is shown that to date, the treatment of malignant
foci with beams of protons and carbon ions has surpassed all existing methods in terms of efficiency.
Key-Words: - particle accelerators, ionizing radiation, malignant neoplasms, (e,)-treatment, hadron
therapy.)
Received: April 12, 2022. Revised: November 9, 2022. Accepted: December7, 2022. Published: December 31, 2022.
1 Introduction
Over the past hundred years, cancer incidence and
mortality in the world has moved from 10th to 2nd
place, second only to diseases of the cardiovascular
system. Specialists of the International Agency for
the Study of Malignant Tumors have reviewed the
situation with the disease in 185 countries of the
world in recent years [1]. Data were analyzed only
in those regions where medical care is at a
sufficiently high level and it is possible to make at
least rough estimates. The forecast of scientists is
disappointing. According to oncologists, by 2040
the number of annual cases of malignant
localizations will increase by 47% and reach 28.4
million. The research results show that the number
of diseases is increasing from year to year and so
far, no changes in this trend are visible in the near
future. Therefore, the search for the causes of the
appearance of malignant tumors, promising
technologies for diagnosis and treatment continues.
The emergence and development of oncological
localizations in initially healthy tissues have not
been sufficiently studied. It is only known that the
growth of cancerous foci in peacetime is observed
primarily in industrial centers and regions with
unfavorable environmental conditions; when people
are employed at enterprises with the impact of
harmful production factors, with works related to
the creation and operation of nuclear materials, etc.
The situation becomes especially critical in places
of local and large-scale radiation accidents. The
most important condition for the successful
treatment of cancerous tumors is their early
detection. Tumors of the 1st and 2nd stages of
growth are most often painless, there are no
pronounced symptoms.
Therefore, the primary task of physicians, aimed
at reducing the mortality and disability of potential
cancer carriers, is to regularly conduct mass
preventive examinations of the population as is done
in some countries. So, in the United States, on
average, 40 people per thousand of the population
undergo diagnostic radioisotope examinations per
year, in Japan - 25, in Austria - 19, in Russia - 7. In
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Russia, almost 60% of diseases are first registered in
the third or fourth stages of the disease [2].
Currently, in practical medicine, the main
methods of treating various forms of tumors and
metastases are: surgery ~ 49%, radiation therapy
(RT) with ionizing radiation ~ 40% and
chemotherapy ~ 11% [3]. RT of cancer foci is
carried out by exposing the tumor to various types
of radiation (-particles, -particles, electrons,
protons, neutrons, pi-mesons, heavy ions, X-rays
and -radiation). This direction of treatment, the so-
called radiotherapy (RT), has become widespread in
all developed countries. Modern technologies using
RT have proven to be one of the most advanced
ways to combat the disease.
Paying tribute to the past, we note that active
research work on the use of radiation in science,
industry, and especially in medicine [4] began
almost immediately after the discovery of
electromagnetic (X-ray) radiation with an energy of
~ (30 – 250) keV by V. Roentgen in 1895, and
phenomena of radioactivity (spontaneous emission
of uranium salts) by A. Becquerel in 1896. Later,
both types of radiation were called ionizing
radiation (IR). During the first experiments on the
use of RT for the treatment of various diseases,
including malignant tumors, it was noticed that
severe burns and ulcers occurred on the skin of the
testers with sufficiently long work and the healing
process lasted in several months. Moreover, it
turned out that radiation not only affects the skin,
but can also cause radiation damage to internal
organs and tissues, or even lead to the death of
living organisms.
Further medical and biological experiments
showed that the ability of photons and elementary
particles or atomic nuclei to ionize a substance can
result to the observed consequences, i.e., strip an
electron (electrons) from neutral atoms or
molecules, as well as capture electrons, creating
negative ions in the process of interaction. It has
been proven that the cause of damage of organs and
tissues due to ionization is the cessation of cell
division mainly due to: a) single or double strand
breaks of DNA helices; b) ionization damage to
intracellular membranes and other important cell
structures; c) radiolysis of water [5,6] which in
biological objects is ~ (60 - 70) %. The latter
process leads to the formation of chemically highly
active free radicals and peroxides interacting with
protein molecules, enzymes and other structural
elements of living tissue that results in disruption of
the normal functioning of cells.
As shown by the experiments that were started
by the French physicians E. Besnier and A. Danlos
in 1901, the most sensitive to radium radiation, as
well as to X-rays, are young, rapidly growing,
multiplying cells. Irradiation causes them serious
damage up to complete destruction and death. Thus,
it became possible in principle to use ionizing
radiation to destroy malignant tumors consisting of
just such cells.
The purpose of the work is to acquaint the reader
with the development of charged particle accelerator
technology for RT of neoplasms. Also, to show that
modern accelerators, high-tech auxiliary equipment
and nuclear physics treatment technologies have the
qualities and technical capabilities of successful
treatment of a wide range of cancerous localizations.
2 Progress of accelerating technology
Researchers at the turn of the 19th - 20th centuries
worked, relying mainly on knowledge related to
chemical elements, and therefore much of the IR
phenomenon remained incomprehensible. Only in
the 1930s, scientists began actively to study the
phenomenon of IR and realize the prospects that
promise its application in science, technology, and
medicine. It became clear that for the further
scientific and practical development of this
direction, sources are needed that are capable of
generating streams of charged particles of different
energies and intensities in particular. The number of
accelerators of various modifications and directions
began to grow rapidly [7]. In the late twenties -
early thirties of the last century, the following were
developed and launched: the Wideröe linear
accelerator (1928), the cascade accelerator (1929),
the Van de Graaff electrostatic accelerator (1931),
the proton cyclotron (1931). In 1937, a linear
electron accelerator (LEA) with an energy of ≤ 1
MeV was put into operation in London which was
first used to treat oncological localizations of
various nature. In the fifties, e-accelerators
competed with - therapeutic devices using
radioactive nuclides 226Ra, 137Cs and 60Co as a
radiation source. In the early seventies, more than
300 accelerators of various types: 157 betatrons, 118
LEAs, 22 Van de Graaff accelerators and 9 resonant
transformers were already operating in medicine. In
general, out of ~ 40 thousand accelerators operating
in the world in 2015, about 25 thousand worked in
industry, about 1200 units in fundamental science,
and about 35% did in medicine. The world
leadership in the number of medical accelerators
was held by the USA 36.1%, EU countries 26.8%,
Japan 7.9%, China 9.4%, Russia 1.3%, and other
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states 18.5%. Manufacturers planned to increase the
number of medical units to 21,000 units [7] in 2020.
As an example, Fig. 1 shows a typical view of a
modern radiotherapy LEA for RT [8].
In the eighties,
mass production
of LEA for RT
was begun taking
into account the
requirements of
practical
medicine. They
began to crowd
out other types of
sources. Only the
companies Varian,
Elekta, IBA,
Siemens, Philips
increased the
annual production of installations from 700 to 1000.
All accelerators have the qualities and technical
capabilities to carry out treatment with the least
negative impact on surrounding tissues, maximum
comfort for the patient and effective treatment of a
wide range of cancerous locations. The company's
products are successfully operating in 117 countries.
In recent decades, public and private specialized
medical institutions in different countries have been
actively purchasing therapeutic accelerators and
auxiliary equipment from well-known
companies. The range of accelerating devices
offered on the market is distinguished by the
maximum electron beam energy, intensity, radiation
dose rate, main directions of therapy, etc. An
additional attraction for potential customers is that
the accelerators are supplied with ready-made
diagnostic, therapeutic, radiological equipment;
medico-physical technologies for radiation
treatment planning; clinical dosimetry; guarantee of
quality and radiation safety, etc.As for -therapeutic
devices using radioactive sources, their number in
the leading countries, according to the IAEA,
decreased to 2046 (the sum of -devices of the first
15 countries with the largest number of them) in
2019. In the last century, the number of such
devices reached tens of thousands [6] in the world,
not counting the X-ray machines numbered by
several million [7]. To a large extent, this was
facilitated by the mass production of LEA which
could successfully replace obsolete -devices in
many cases. However, LEA cannot yet completely
replace these -installations since modern devices
have changed a lot structurally and outwardly. They
are automated, computerized and able to effectively
treat a certain class of malignant tumors. Due to the
relatively high photon energy and specific activity,
the distance from the source to the patient's body
can vary from 80 cm or more. The head of the
device rotates in a plane around the axis making it
possible to irradiate the tumor at different angles
thereby increasing the sparing effect for nearby
organs. While revolving around the patient, the
source remains “pointed” at the pathological
formation. The therapy table on which the patient is
located has three degrees of freedom allowing the
patient to be positioned in the beam field of -
installation using radioactive cobalt 60Co. All of this
allows us to solve
Fig. 2. Radiation with Gamma Knife [6]
extraordinary medical problems. As an example, let
us cite the Gamma Knife (Cyber-knife) stereotaxic
surgical system [6] which literally burst into
practical medicine quite recently.
The concept of the method was proposed in 1951
and finally implemented in 1968. The essence of
surgery lies in the fact that radiation from about
two hundred of tiny 60Co - sources of high specific
activity is focused on the tumor from the outside
with collimators (see Fig. 2) [6]. Pointing accuracy
is 0.3 mm. A high concentration of energy at the
intersection of the beams (dose up to 10 Gy)
destroys cancer cells and adjacent healthy tissues
receive minimal radiation exposure. "Gamma
Knife" allows you to treat vascular neoplasms, brain
tumors including metastases without surgery and
weeks of brain irradiation. In many cases, one
treatment session is sufficient. So far, the
application of the method is limited by the size of
Fig. 1. Ellus-6М [8]
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the cancerous tumor measured by a size 3 cm. In
2019, there were ~ 314 such systems in the world.
Initially a significant role was played by
therapeutic LEAs with an energy of Ee ≤ 6 MeV in
the successful treatment of oncological
localizations. The use of low-energy installations
was beneficial not only in terms of physical and
technical characteristics, but also from an economic
point of view which is extremely important in
conditions of clinics that did not have sufficient
funding. Thus, LEA with Ee ≤ 6 MeV is a kind of
compromise between the energy, the efficiency of
treating a certain class of tumors, the cost of the
accelerator and related equipment. And nowadays,
many specialized firms are engaged in the
development and production of more advanced
LEAs with a maximum energy of 6 MeV. There are
developments of similar installations in the Russian
Federation. So, the ELLUS-6M automated
radiotherapy complex was developed and put into
operation at NIIEFA, St. Petersburg [8]. Since the
1980s, NIIEFA has been producing LEA SL-75-5-
MT under license from PHILIPS [9]. To date, ~ 60
copies have been released. The main operational
characteristics of two foreign accelerators of the
latest generation with a maximum energy of 6 MeV
are described below. These are the Clinac 600C
radiotherapy LEA and the Cyber-Knife
radiosurgical complex.
Clinac 600C. Maximum energy is 6 MeV,
manufactured by Varian (USA). Dimensions ~
272x127x269 cm, weight ~ 6.7 t, dose rate 250
IU/min (1 IU = 10-2 Gy) for energy 4 MV and 400
IU/min for 6 MeV. Possible therapeutic procedures:
photon radiotherapy, including "Photon-arc
Therapy", "3D-CRT", "IMRT", full body
irradiation. The accelerator is equipped with Portal
Vision, Portal Dosimetry, Portal Imagine systems.
There is a 120-leaf collimator for the formation of
static and dynamic fields of complex shape. The
deviation of the beam center from the isocenter
during rotation is less than ± 1 mm. The system is
mounted on a turntable rotating around a horizontal
axis in the range of ± 180.
Cyber-knife - radiosurgical complex. The first
operation was carried out with its use in 1999. The
setup consists of a compact LEA with a photon
energy of 4 or 6 MeV and a mobile robotic
manipulator with 6 degrees of freedom for RT at an
energy of 6 MeV. The unit allows one session to
irradiate the tumor and many metastases from 1200
possible directions. The accelerator generates a
photon beam on a target, including one of an
asymmetric shape, regardless of its position in the
body, with an accuracy of 0.5 mm. In this case, the
edge of the tumor practically coincides with the
irradiated area. Treatment is carried out during one
session. The installation allows irradiating a large
number of malignant foci in different parts of the
human body. Currently, ~ 326 robotic systems are
operating in the world [6] (153 of them in the USA,
9 in Russia).
Science and practice in this segment of medicine
has shown that bremsstrahlung energies of more
than 6 MeV are required for the treatment of many
forms of cancer. The list of diseases that can be
treated by high-energy beams is noticeably wider
than one does by low-energy beams. There is a
higher quality of therapy. It turns out, for example,
that the likelihood of recurrence of prostate cancer
decreases with increasing radiation energy. In the
range (8 - 20) MeV, the probability of recurrence is
constant and equal to ~ 10% (at an energy of 6
MeV, the probability is ~ 18%). The survival factor
of patients treated with high-energy beams is (2–4)
times higher than when exposed to kilovoltage X-
rays [10]. These and other similar results encourage
the use of high-energy photons for therapy. At the
same time, such installations have a more complex
design, large dimensions and weight, require
increased radiation protection, are much more
expensive and require appropriately qualified
personnel. Despite the "shortcomings" described
above, specialized companies develop and create
multi-profile facilities with Ee = (4 - 25) MeV
which have several photon and electron beams.
They are capable of operating both with a current of
up to 100 μA for the formation of bremsstrahlung
photons and with a low intensity current of up to
500 nA for direct electron irradiation (about 10% of
patients) [11]. To date, in medical practice, the main
tool for RT of cancerous tumors is the beams of
bremsstrahlung photons of the LEA. At the same
time, more than 97% of LEAs have an energy of (4
– 25) MeV.
Due to the large number and variety of
multifunctional models with several beams only a
small part of the installations is presented below for
review. As an example, innovative models of
Mobetron and Novak7 accelerators [6, 7], as well as
multi-profile LUEs with several electron and photon
beams, were chosen. The latest systems such as SL-
20, Primus and Clinac-2100C [9] are used in the
clinical oncology of the Russian Federation, as well
as Elekta Synergy is used in Ukraine. The presented
samples are the developments of the latest
generation of well-known companies.
Mobetron. The main task of the accelerator is to
destroy the tumor cells remaining in the tissue after
a surgical operation, and its bed is irradiated with an
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electron beam once. That’s what this complex is
used to generate electrons in modern clinics. It can
work directly in the operating room without special
protection and does not provide for special
requirements for the equipment of the room. This
procedure is due to the fact that there is a possibility
of infection of the wound during the transportation
of the patient from the operating room to the
experimental room of the traditional accelerator and
back. The installation consists of an accelerator, a
power supply modulator and a control panel. The
maximum dimensions are 250 cm high and 290 cm
long. Weight is 1140 kg. The possibility of
installation is electron beams with energies of 4, 6, 9
and 12 MeV with a therapeutic range of up to 4 cm.
The system provides a dose of (10 - 25) Gy per
fraction with a dose rate of 10 Gy / min and allows
you to deliver a high dose of radiation to the patient
once.
Novak7 is a miniature LEA mounted on a robotic
arm with four rotating "joints". The facility
generates electrons with energies of 3, 5, 7 and 9
MeV with a pulsed dose of (2 - 9) cGy/pulse. The
repetition rate is 5 Hz, the pulse duration is 4 μs.
The irradiation time for the prescribed dose of 20
Gy is (1 - 2) min. Application, dimensions, weight,
placement in the operating room is about the same
as the Mobetron system. Mobetron and Novak7
installations are shown in Fig. 3. [6].
Fig. 3. Installations: а) Mobetron, b) Novak7 [6]
By the way, there is a project of a more advanced
device based on a split microtron with a beam
energy of 4 to 12 MeV [7]. The unique accelerator
is placed in a container measuring 24×13×48 cm.
The weight of the microtron is ≤ 120 kg. Power
consumption is about 1 kW.
SL-20. The radiotherapy complex manufactured
by Philips (England). It has two photon energies and
eight electron ones. It is operated in "RONTS
RAMS". St. Petersburg. RF.
Primus. The radiotherapy complex manufactured
by Siemens (Germany). It has two photon energies
and six electron ones. It works in “RONTS RAMS”.
St. Petersburg. RF.
Clinac-2100C. The radiotherapy complex
manufactured by Varian (USA). It has two photon
energies and five electron ones. It operates in the
oncological center "Innovation". Kyiv. Ukraine.
Elekta Synergy. The radiotherapy complex
manufactured by Elekta (Sweden). It has three
photon energies and six electron ones. It is operated
in the Spizhenko Clinic, Kyiv. Ukraine.
3 (е,)-Therapy of cancer foci
The successful practical application of remote (e,)-
therapy of malignant localizations, relapses and
metastases has advanced this technique to a leading
position in the treatment of the disease. Suffice it to
say that therapeutic LEAs have amounted to more
than 13 thousand out of 14,000 operating
accelerators in 2015 [7]. Moreover, -radiation
received a clear priority. A wide range of energies
of existing -emitters provides high penetrating
power and is used to treat deep-lying localizations.
In addition, bremsstrahlung is fairly well collimated
and has low radiotoxicity. The latter circumstance
allows the use of large doses of radiation which
guarantees the reliability of the results obtained and
reduces the treatment time. All of the above
explains the fact that the bulk of radiation therapy
procedures used in the world is implemented by
photon irradiation. About 70% of the total number
of patients need traditional types of RT (electrons,
gamma, X-rays). -therapy is the decisive factor
providing a positive outcome of the procedure in
approximately 40% of all cases [6].
A radical dose of radiation (55 - 70) Gy (1Gy =
100 rad) is required for the complete destruction of
a malignant neoplasm. Such a dose is detrimental
for healthy tissue. An effective means of protecting
the patient's healthy cells is to irradiate the focus
from different directions and use the fractionation
technique (the course of therapy is carried out daily
in small doses until the required total value is
reached). Standard fractionation involves 5
exposures per week once a day for 2 Gy. The
positive effect is due to the fact that healthy cells,
when receiving a relatively small dose, will recover
much faster than cancer cells [12]. Apparently, the
fact that increasing the energy of -quanta leads to a
shift of the position of the maximum dose deep into
the biological object can be considered as a certain
disadvantage of the technique. Deeper penetration
of radiation leads to a high dose at the outlet of the
tumor volume. This means that healthy tissues,
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including "critical organs", receive practically
comparable dose loads behind the irradiated area.
As for electrons, therapy is carried out in ~ 20%
of patients from the number of people with
recommended RT. A free particle travels a certain
distance in tissues spending energy on ionization
acts and excitation of atoms. Electrons with energies
up to tens of MeV pass several centimeters deep
into the tissue and have a maximum ionization
density close to the surface of the tissue/air
interface. Therefore, they are used to treat tumors
located close to the skin surface or at the level of the
patient's body [13,14]. Since the mass of electrons is
small, they scatter strongly increasing the volume of
the irradiated tissue. The absorbed dose falls off
rapidly after reaching its maximum, preventing
damage to underlying important biological organs.
The maximum absorbed dose is at different depths
depending on the energy of the electrons. The
maximum absorbed dose is at a tissue depth of ~ 10
mm at Ee = 6 MeV. Then the dose gradually
decreases.
In connection with the appearance of compact
LEA, the quality of treatment of neoplasms with
intraoperative RT (IORT with electrons) has
noticeably increased [6,7]. This is discussed in more
detail above.
4 Formation of hadron therapy (HT)
Despite the successes achieved in the treatment of
cancers with electromagnetic radiation, it turned out
that a fairly large number of patients have tumors
that are resistant to photon therapy. Therefore, it is
advisable to use densely ionizing particles, mainly
protons, neutrons, pimesons, heavy ions for ~ 20%
of patients with heavy radioresistant forms [15,16].
This is due to a more pronounced damaging effect
of cancer cells compared to electrons, X-rays and
radiation.
With regard to light and heavy ions, their use for
medical purposes has begun much later than the use
of electrons and -quanta. Only in 1946, the medical
journal “Radiology” published an article by R.
Wilson where the author noted that proton and
heavy ion beams would be ideal for the treatment of
malignant tumors, since their inertial characteristics
predict releasing of most of an energy in immediate
vicinity of the end of a particle path. It is possible to
set with a high accuracy of ~ 1 mm the place where
the particles must stop and give up their energy by
smoothly changing the energy. It should be noted
that increasing the maximum energy of the
particles is needed with increasing a ion mass
which is associated with technical difficulties,
increasing energy consumption and the cost of the
accelerator complex.
Fig. 4 [17] shows the actual ratio of the dose to
the depth of tissue penetration by protons, -mesons
and carbon ions. The same figure shows the
dependence of the dose on the tissue penetration
depth for photons with the energy of 18 MV.
Narrow maxima, the so-called Bragg peaks,
correspond to the release of the greatest energy in
the region of the finite path of particles. It can be
seen that the dose increases with increasing the ion
mass; the destructive effect of radiation is growing.
The relative biological efficiency is ~ 3 at the peak
for carbon ions and it is for protons ~ 1.1 for
protons, i. e. the damaging effect of carbon ions in
tumor cells is several times higher than that of
protons. In practice, to irradiate the tumor
throughout its depth, the sharp Bragg peak is
modified into a distribution that is uniform over a
certain area. The dose ratio at the peak to the dose at
the tissue entry is the best for carbon nuclei among
ions from He to Fe [6]. A “fragmentation tail” is
visible behind the peak. When an ion interacts with
a substance the nucleus breaks up into fragments
which leads to the appearance of a dose after a peak
where, in principle, a “critical biological organ” can
be located and subjected to unwanted irradiation.
The contribution of the "tail" increases with
increasing mass of the ion, for comparison, it is ~ 1 -
2% for protons, ~ 15% for carbon, ~ 30% for neon
[15]. For a number of objective reasons, practical
medicine prefers carbon therapy as the best
treatment option.
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Fig. 4. Dose dependence on tissue penetration depth [17]
Biomedical research on beams of protons,
deuterons and alpha particles of the
synchrocyclotron at Berkeley (USA) was first
performed by Tobiash and Lawrence in 1952. The
first patient using proton therapy was cured in 1954
[18]. Clinical experiments on the use of high-energy
protons in RT were started by Kilberg in 1959 at the
synchrocyclotron with an energy of 160 MeV.
Later, it turned out that at proton energies > 10 MeV
the deviation of the particle trajectory from a
straight line is statistically insignificant. Ionization
processes are dominant and the absorbed energy is
concentrated along the track for the proton energies
which are used in RT. As a result of ionization, a
"coat" of secondary electrons most of which have an
energy of less than 100 eV is formed. The
mechanism of heavy particle interaction with atoms
and molecules of living tissue is fundamentally the
same as for protons [6]. The optimal parameters for
therapy were determined by the analysis of
radiobiological experiments: proton energy (70 -
250) MeV which corresponds to the path of particles
in the tissue (5 - 30) cm; size of the extracted beam
on the target (3 – 5) mm; particle intensity on the
tumor ~5∙109 s-1; position stability on the object 1
mm; exposure time (1 - 3) min.
“Gantry” units including superconducting are
one of the key elements of the equipment of modern
centers for both proton and ion therapy. This
mechanical design is intended to rotate the transport
device and form the beam around the patient in the
range of angles (0-180). The independent rotation
of the "gantry" in combination with the rotation of
the patient at an angle of (0-180) allows irradiation
from any direction. The systems are very complex,
expensive and cumbersome (for proton RT, the
length of the "gantry" is ~ 10 m, the height is ~ (10 -
15) m, the weight is ~ 100 t; for the carbon beam,
the length is ~ 20 m, the diameter is ~ 12 m, the
weight is from ~ 200 to ~ 600 t) [6]. However, their
use allows: a) to ensure the conformity of
irradiation, when the maximum of the generated
dose distribution with an accuracy of 1 mm
corresponds to the shape of the target when
irradiated from several sides; b) increase the number
of locations recommended for irradiation from 7 to
30%.
To date, there are 71 proton therapy centers in
the world, 44 ones are under construction, and it is
planned to build 21 more centers in the near future
[18]. Linear accelerators, cyclotrons, synchrotrons,
synchrocyclotron, as well as superconducting
synchrocyclotron, synchrotrons, and cyclotrons can
be used to obtain beams of protons and ions (see, for
example, [19]). However, linear accelerators have
not found wide practical application due to their
large length.
Studies have begun on the clinical application of
beams of various ions after the launch of the
Phasotron at the Lawrence Laboratory (LBL, USA),
and the BEVALAC synchrotron [15, 20] later in
1975. The construction of the world's first heavy ion
accelerator laboratory HIMAC (Heavy Ion Medical
Accelerator in Chiba) began in Japan in 1984. Two
heavy ion synchrotrons were launched at HIMAC to
carry out radiotherapy of neoplasms with ions from
helium to argon at the end of 1993. The first session
with a beam of carbon ions was carried out in 1993.
It turned out that approximately 30% of patients
require protons for treatment, and only carbon ions
can help for 10-15% of patients in the course of
clinical studies. To date, about 20,000 patients have
been treated with carbon ion beams in the world (5
centers in Japan), Germany (2 centers), Italy (1
center), China (2 centers) [20].
It should be noted that so far radiotherapeutic
complexes for HT (treatment with protons and
carbon ions) are less than 1% of the total number of
medical accelerators [6]. However, the positive
aspects of this technology prevail over all other
radiation techniques. In particular, a) fluxes of
protons and heavy ions satisfy the requirement of
irradiating only the zone of the pathological site to a
greater extent than other types of ionizing particles
(electrons, -radiation, neutrons), and living tissues
located nearby are practically not affected; b) the
particles can be easily formed into well-directed
narrow beams that penetrate the tissue almost
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without scattering to a depth determined by the
choice of energy; c) HT significantly reduces the
radiation load on the surrounding organs, the
duration of exposure, the risk of adverse reactions,
is better tolerated by patients and does not require
mandatory hospitalization which allows ambulatory
treatment; d) the number of sessions of irradiation
with protons and carbon ions can be reduced up to
10 or more times instead of (30 - 40) procedures
used in traditional radiotherapy today; e) HT has
surpassed all existing methods of treatment in terms
of efficiency. In practice, up to 90% of cancer
patients are cured. As for the side irradiation of
living tissue, protons allow you to halve the
radiation load on healthy tissues surrounding the
tumor compared to -rays. Carbon ions, on average,
activate normal tissues 4 times less than X-rays at
the same dose in the tumor and half as much as
protons. Protons are the most effective for tumors
located near critical organs; when a sharp drop in
radiation dose is needed.
The number of HT centers in the world is
continuously growing. And this is despite the fact
that the construction of a modern clinical complex
for proton therapy takes (3 - 4) years; it takes (3 - 5)
years to master the equipment, and its cost reaches
$200 million. The creation of an ion therapy center
requires more time for construction and
commissioning and costs twice as much. To date,
there are about 70 HT complexes in the world. Only
eight of them use beams heavier than proton ones
[6]. It is predicted that there will be ~ 300 centers in
the world by 2032. Two of the AT complexes under
construction and those being prepared for operation
will use a superconducting cyclotron with a proton
energy of 250 MeV and six will use a
superconducting synchrocyclotron with the same
energy [16].
There is development of promising HT projects
all over the world including Russia. Compact, high-
field, medical accelerators are becoming more
widespread in modern conditions. This also applies
to the creation of superconducting cyclotrons and
synchrocyclotron and "gantry" systems. This does
not require the creation of a specialized cryogenic
infrastructure. Such technologies can be
implemented within oncological hospital centers
[16]. Since the 1990s, only multi-cabin clinical
centers have been built; there is one proton or ion
accelerator which allows splitting the beam into
several treatment cabins with "gantry". A project
was proposed in [20] to create an irradiation center
with carbon beams at the National Research Center
"Kurchatov Institute" (RF) based on elements of the
IHEP U-70 accelerator complex and existing
infrastructure facilities. Projects of a
superconducting carbon synchrotron [21] and a
cyclotron [22] have been created at JINR (RF)
which also include the gantry system. In INP named
after G.I. Budker, the project was developed for a
proton-ion therapeutic complex based on a fast-
cycling booster and an ion synchrotron with electron
cooling [23], etc.
It should be noted that a necessary condition for
the successful implementation of all stages of RT is
the provision of specialized clinics with qualified
personnel, and not only with modern radiotherapy
accelerator complexes, high-tech devices and
mechanisms. It takes about 10 years to educate
high-class specialists according to leading Western
scientists. For example, medical physicists undergo
at least (5-7) years of postgraduate medical-physical
and clinical training, internships at research and
educational centers, and only then are they certified
in the United States. Table 1 shows the main
staffing of accelerators and radiotherapy centers in
Europe, the USA and Russia per 1 million
population [24].
5 Conclusion
This review is based on the methodology of
nuclear medicine, which is based on radiation
therapy (RT). In particular, RT of cancer foci
implies exposure of the tumor to various particle
flows, such as -particles, -particles, electrons,
protons, neutrons, π-mesons, heavy ions, X-rays and
gamma
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radiation. Malignant tumors are destroyed by such
an exposure. At the same time, it is important to
prevent damage and even destruction of cells of
nearby healthy tissues which imposes certain
requirements on the methods of influencing particle
flows on the neoplasm area. It has become clear
since the time of Becquerel and Roentgen that
radiation not only affects the skin but can also cause
radiation damage to internal organs and tissues or
even lead to the death of living organisms. The
formulated direction has become widespread in
developed countries around the world.
Here we come to an important element of the
methodology of nuclear medicine, namely to
accelerator technology which provides the
generation of beams of various particles for the
treatment of oncological diseases. Modern
accelerators with associated innovative equipment
have proven to be one of the most advanced means
of combating the disease. The review consistently
acquaints the reader with the development of
accelerator technology for RT of neoplasms from
the days of the discovery of ionizing radiation by
Roentgen and Becquerel to the present, passing
through such important milestones as the creation of
a linear accelerator, Van de Graaff electrostatic
accelerator, gamma-therapeutic apparatus,
cyclotron, phazotron, and so on. The methodology
of nuclear medicine required each time an increase
in the energy of the generated particle beams used
by RT in the creation of a new accelerator facility
starting from kilovolt values to tens of megavolts at
the modern level. Modern accelerators, high-tech
ancillary equipment and nuclear physics treatment
technologies have the qualities and technical
capabilities to successfully treat a wide range of
cancer sites as shown in the review.
RT can be used not only as an independent
method but also in combination with chemotherapy
or with surgical methods. Moreover, a significant
contribution to the methodology of nuclear medicine
was made by a -installation using radioactive
cobalt 60Co, called the “Gamma Knife” (Cyber-
knife), for performing radiosurgery in the brain
described in section 2 the Progress of accelerating
technology of this review.
The success of radiation therapy is also
associated with the emergence of new designs of
devices such as "gantry" mounted in modern centers
for both proton and ion therapy (see section 4
Formation of hadron therapy (HT) of this
review). It has been demonstrated that the treatment
of malignant foci with beams of protons and carbon
ions is currently the most effective since the dose
for pathological tissues increases and the dose for
normal tissues decreases in this case. Irradiation with
protons and heavy ions is called by hadron therapy (HT).
It should be noted that so far there are quite a few
radiotherapeutic complexes for HT in the total number of
medical accelerators. But the number of HT centers is
constantly growing in the world due to the clear
predominance of the positive aspects of this technology
over all other radiation techniques. There is development
of promising HT projects all over the world
including in Russia. There is a rapid growth and
complication of radiotherapy and radiosurgical
equipment and technologies in order to improve the
quality of radiation therapy.
Compact, high-field, medical accelerators have
been widely used recently. However, for the future
development of this work, it is required to carry out
the development of large (expensive) projects for
the creation of superconducting cyclotrons,
synchrocyclotron, and "gantry" systems in the field
of radiation medical physics including new methods
of clinical radiotherapy, a network of educational
and service structures. The latter circumstance is
due to the fact that a necessary condition for the
implementation of RT is the provision of specialized
clinics not only with modern radiotherapy
accelerator complexes, high-tech devices and
mechanisms but also with qualified personnel since
the maintenance of medical accelerator complexes
Table 1. Staffing of radiotherapy centers and
accelerators in Europe, USA, RF [24]
USA
RF
Radiotherapy centers
8
1
Medical physicists and
dosimetrists
33
2
Radiation oncologists
and therapists
49
8
Medical technologists
17
7
Accelerators
14
0.7
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requires special training. Only in this case it is
possible to bring closer the solution of the priority
task of physicians to reduce the mortality and
disability of potential cancer carriers.
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Contribution of Individual Authors to the
Creation of a Scientific Article (Ghostwriting
Policy)
Vladimir Krasilnikov carried out the editing, formal
analysis, and data curation.
Eduard Kuplennikov has implemented the selection
of references, formal analysis, and written the
original draft.
Sources of Funding for Research Presented in a
Scientific Article or Scientific Article Itself
The article was written with self-funding.
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(Attribution 4.0 International, CC BY 4.0)
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International Journal on Applied Physics and Engineering
DOI: 10.37394/232030.2022.1.9
Vladimir Krasilnikov, Eduard Kuplennikov
E-ISSN: 2945-0489
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Volume 1, 2022