Carbon Ion Beam Radiotherapy (In Comparison to Photon and Proton RT)

After the discovery of X-rays in the year 1895 by Roentgen, X-rays, electron beams and gamma rays, also known as photons, have been mainly used in the external beam radiotherapy in the treatment of malignant cancerous tumors as conventional radiotherapy. In the year 1946 Dr. Robert R. Wilson was the first person who discovered the medical usage of protons for cancer treatment (Wilson 1946). However, just within the next 10 years of its discovery protons were used in radiotherapy to treat different types of cancerous patients and first patient was treated with the proton beam in the year 1954 at Lawrence Berkeley National Laboratory (LBNL) in USA (Ertner et al. 2006). In the years between 1977 and 1992 the first clinical trial with Helium and Neon ions with promising results also took place at LBNL (Castro et al. 1994). The first clinical experience in the treatment of malignant tissues with the help of carbon ion beam was launched at the National Institute of Radiological Science (NIRS) in the year 1994 using Heavy Ion Medical Accelerator in Chiba (HIMAC) (Torikoshi et al. 1995). Currently there are five carbon ion beam radiotherapy centers established all over the world, three in Japan, one in China and other one in Germany. In addition, right now seven new carbon ion RT centers are under construction, Italy - one, Germany - two, Austria - one, China - one and Japan - two (Bhatt 2013).

Radiotherapy works by damaging the gene (DNA) of the cancerous cell to prevent its growth and division. However irreparable damage of DNA of the cell can occur with the help of double strand DNA break instead of single strand DNA break. Radiation treatment with conventional photons leads only to a single strand DNA break and repeating the treatment with this photon radiation leads to cellular death. However, treating the lesion with ionizing radiation several times can harm the normal tissues around the lesion and also damage the other parts of the body which may lead to complications with normal tissues. This type of normal tissue complication problem can be overcome with the help of high ionizing radiation having high Linear Energy Transfer (LET) values. Carbon ion beam provides high ionizing radiation having greater energy than photons leading to double strand DNA break during its single hit to targeted lesion due to its maximum dose deposition at the Bragg peak region (Kanematsu et al. 2019; Ishikawa et al. 2019). Since, the relative biological effectiveness of carbon ion beam, due to its high LET value, is greater than that of proton and photon, it is extensively used nowadays in external beam radiotherapy.

Carbon Ion Beam or Heavy Charged Particle Beam

Particle Nature

Carbon ion beam is a type of heavy ion beam or heavy charged particle beam having masses several times more than that of an electron. Here heavy ion stands for the ion larger than the proton. Heavy charged particles like alpha particles, carbon, oxygen, argon, neon etc. can be generated with the help of a particle accelerator (either electrostatic or oscillating field accelerator). These heavy charged particles have energies higher than that of electrons and photons such that it can ionize the medium deeper than electrons and photons.

Beam Features

The depth dose distribution of HCP beams, when the HCP beam incident on any medium is very low in the entrance region, shows a straight trajectory, and prominent dose (as a peak) in the stopping region, also called Bragg peak, which results in the irradiation of very small confined tumors or other malignant cells within the patient's body. HCP passing through any medium loses its maximum energy due to interaction with atomic electrons of the medium (Tobias et al. 1952). It also undergoes elastic or inelastic collisions with the nucleus. The main difference of the electron beam and heavy charged particle beam is due to the rest mass of the electron which is less than the HCP mass. Thus, the electron beam loses its maximum energy during its first interaction with the matter but the scattering angle of HCP is very low, resulting in a sharper lateral dose distribution and traversing a long distance through the medium along with producing secondary electron and higher order electron.

Beam Superiority

The biological effect of any beam completely depends upon the beam quality i.e. upon LET which measures the energy loss distribution of a particular beam along its tracks. It is observed that heavy ion passing through any medium slows down and makes the interaction with nuclei resulting in the disintegration of the incident ion. The above destruction of the incident ion depends on the ion type, ion energy and also on the surroundings of the medium. According to Bichsel the variation in energy loss directly depends on the square of the nuclear charge, which results in a large discrepancy in the energy loss and their ranges in a medium for different type of particles (Bichsel 1972). In-elastic collision with the absorber nucleus leads to fragmentation of the absorber nucleus. The energy of target nucleus fragments has less energy than the projectile fragments and therefore the dose due to target nucleus fragments is locally deposited.

Thermoluminescence Dosimetry

TL dosimetry is used as a dosimetry of ionizing radiation since the last several decades and can be used in the measurement of ionizing radiation in radiation affected areas where the absorbed dose is in the range of micro grays and also in radiotherapy where doses are in the range of several grays. TL material also found its application in measurement of nuclear radiation doses from the early 1950s, where the patient swallowed the crystal when he/she was injected with radioactive isotopes and after his recovery in few days, the accrued dose was measured with the help of the intensity of TL signal emitted by the crystal in a particular unit (Su et al,1985).Thus for this purpose several types of TL materials are developed nowadays. Some of the materials that have been investigated earlier are CaS04: Dy, CaF2: Dy, LiF: Mg, Ti and A1203: C. Instead of several electronics and other dosimeters, TLDs are useful in point dose measurement in vivo dosimetry due to their small size and need no requirement of high voltage supplies.

TL is the phenomenon of emitting light during heating of some special type of crystalline materials, after irradiation with different types of electromagnetic or other ionizing radiation which may be gamma rays, alpha rays, electron beam or may be different types of heavy charged particle beams. This phenomenon was first observed by Robert R. Boyle in 1663 after observing a glimmering light from diamond on heating in a dark room (Boyle 1664). The use of TL as a radiation detector has a long history from early 1895, when this process was used as a measurement of radiation due to electrical discharge with the help of artificially prepared CaS04: Mn phosphor by Wiedmann and the same method was used again by Lyman in the year 1935 for far-ultraviolet range (Wiedman and Schmidt 1895; Lyman 1935). However the word, TL was first coined in literature by E. Weidman and Schmidt in the year 1895 (Wiedman and Schmidt 1895). Randall and Wilkins along with Garlick and Gibson in the year 1945 and 1949 were able to provide some understanding of certain features of the TL process. Whereas, this phenomenon became a subject of inclusive interest from the year 1953 when its effectiveness in radiation dosimetry was established by Daniels et al. (Daniels et al. 1953), on the other hand Cameron et al. were successful in utilizing the property of thermoluminescence of LiF as a radiation dosimeter for the measurement of X-rays, gamma rays, electron and beta rays and thermal neutrons (Cameron et al. 1964). Since, the use of TLDs as a dosimetry of ionizing radiation has many advantages over the other dosimeteric systems viz. small size, roughness, range, effortlessness in reading and sensitivity and also due to its low cost it has attracted a lot of attention from investigators. During the 60s and 70s a lot of work was done in this field and the technique is still a part of recent investigations.

Heavy Charged Particle (HCP) Interaction with TL Materials

Carbon ion beam is a type of heavy charged particle beam and, as we know, when the heavy charged particle beam interacts with matter the ion beam loses its energy by a number of mechanisms, such as (i) Ionization and excitation, (ii) Nuclear collisions, (iii) Photon generation and (iv) Nuclear reactions. When TL materials are irradiated with HCP, total HCP stopping power is due to the contribution of the first two mechanisms electronic and nuclear stopping powers. Total electronic energy loss can further be subdivided into three main energy regions. They are (i) high energy region, (ii) intermediate energy region and (iii) low energy region. In the high energy region the velocity of a heavy charged particle is too high given by the formula v > vaZ^3 (where v0 indicates c/137, here c is the velocity of the light) i.e. incident ion velocity is faster than the atomic electrons of the medium. According to the corrected Bethe formula electronic energy loss related to the medium through which HCPs travels and also on the velocity of the projectiles (Bethe 1930). This Bethe formula is not appropriate in the case of low ion velocities. In the low energy region the ion's velocity is very low given by the formula v « v^Z^3 and also the low energy region practically shows the neutrality to both target and projectile. In this region total stopping power is given with the help of the theory of Lindhard-Scharff (Lindhard and Scharff 1961). But in the intermediate energy region the total electronic energy loss can be predicted by the semi-empirical formula of Biersack and Haggmark (Biersack and Haggmark 1980) which is actually the combination of both Bethe and Lindhard-Schraff formulation.

In the high and intermediate energy region the contribution of nuclear stopping power is very little but is predominant in the low energy region. The total nuclear stopping power can be calculated in three different steps: in first step we can calculate the abundant projectile target scattering potential (Berger and Seltzer 1964); in second step we can determine the elastic scattering cross section with the help of classical mechanics and finally the last step consists of the total transferred energy calculation of the target atom through elastic scattering. In passing through a medium, HCPs cover a distance before coming to rest which is also called range of the HCPs. The stopping power of charged particle can be defined as the loss of particle energy when these HCPs pass through any medium; its inverse provides the distance covered per unit energy loss. For comparison purposes the track of both HCP and low charge particle is shown in effect and defect creation by HCP.

The defect structures present in the TL materials are responsible for the TL signal, and also represent the dosimetric properties of TL materials. Irradiation of TL sample with high energy particle introduces defects in TL materials through the creation of electrons, holes and exciton (Horowitz et al. 2001). These electrons and holes may recombine or may diffuse through the materials and can be trapped in the forbidden energy gap of the materials while these trapped charges can again be excited by the low energy radiation of HCP and results in the trapping of these charge carriers at the deep traps. This may lead to permanent damage of the crystal, also known as ionization damage. Instead of focusing attention on the defect creation mechanism inside the TL materials after irradiation it is important to know the type of defects present inside the TL materials at the thermodynamic equilibrium. The vacancy defect (simplest point defect) also called Schottky defect and

a. Diagram of highly localized HCP track follow almost straight trajectory inside the matter

Fig. 11.1a. Diagram of highly localized HCP track follow almost straight trajectory inside the matter. (Reprinted with permission from Y.S. Horowitz, "Theory of heavy charged particle response (efficiency and supralinearity) in TL materials", Nuclear Instruments and Methods in Physics Research B, 184 (2001): 85-112)

b. Diagram of low energy particle track which shows twisted path inside the matter

Fig. 11.1b. Diagram of low energy particle track which shows twisted path inside the matter. (Reprinted with permission from Y.S. Horowitz, "Theory of heavy charged particle response (efficiency and supralinearity) in TL materials", Nuclear Instruments and Methods in Physics Research B, 184 (2001): 85-112) interstitial defect or the pair of vacancy and interstitial known as Frenkel defects is found to be present in the most of TL materials, whereas Frenkel defects are mainly found at a higher temperature. Moreover, a number of point defects can be created inside the crystal after its irradiation with high energy particles in which the incident particle displaces the atom from its lattice points and results in the creation of new point defects (Doan and Martin 2003; Yu et al. 2019). This type of radiation damage inside the materials is known as displacement damage. Flere point defect creation is the complete function of the incident particle and the nature of the TL materials or crystals and independent of temperature (Yanwen et al. 2014). Since the TL materials are mainly insulators or semiconductors having very less number of free charge carriers on irradiation to very low doses can lead to the modification in electrical and optical properties of any material. Flowever, on the basis of some experimental results it has been observed that the nanocrystalline materials show a prominent resistance against the irradiation, while few experiments show structural disorder in the nanomaterials as compared to bulk materials after irradiation (Zhou et al. 2018). Ixr spite of thermal growth mechanism of nanomaterials, the irradiation induced growth mechanism of various nanomaterials has also been reported by many Investigators while nanocrystalliire materials become amorphous in nature at low doses of ionizing radiation. The irradiation of nanomaterials, however, can be used to modify the grain size, phase structure, optical properties and physical properties of various materials (Andrievski 2011; Krasheniimikov and Nordlund 2010).

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