HADRON THERAPY FOR CANCER USING HEAVY IONS

8/13/2019 HADRON THERAPY FOR CANCER USING HEAVY IONS

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HADRON THERAPY FOR CANCER USING

HEAVY IONS!"

Khalid Mohammed S Yamani

A dissertation submitted to the Department of Physics,

University of Surrey, in partial fulfilment of the degree of

Master of Radiation & Environment Protection

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H/'&)%( @Z PHHYSICAL AND RADIOBIOLOGICAL PROPERTIES OF

HADRONS QI

2.1 Physical characteristic of the beamQO

2.1.1 Depth-dose distribution and Bragg-peakQO

2.1.2 Defined range:QP

2.1.3 Lateral scattering:QP

2.1.4 Non-elastic nuclear reaction:QU

2.1.5 Positron emission tomography technique (PET)QU

2.2 Biological effectQW

2.2.1 The Relative Biological Effectiveness (REB) and Linear Energy

Transfer (LET):QB

2.2.2 Oxygen Enhancement Ratio (OER)@A

H/'&)%( SZHadrons Therapy equipments @@


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3.1 Conventional Accelerator Radiotherapy@@

3.2 Accelerator for heavy ions and proton @S

3.2.1 Fixed Field Alternation Gradient accelerator (FFAG)@O

3.2.2. The dielectric-wall accelerator (DWA)@O

3.4 Beam delivery systems and techniques @O

3.4.1 Passive beam shaping@P

3.4.2 Active beam shaping:@U

3.5 Gantry design for proton and carbon hadrontherapy facilities @W

3.6 Cost-effectiveness of hadron therapy in cancerS@

H/'&)%( IZTREATMENT PLANNING SS

4.1 Imaging protocolSI

4.2Organs contouringSI

4.3Dose calculation algorithmsSI

4.4Choice of the portsSI

4.5Positioning and treatmentsSI

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Appendix A SB

Appendix B IA

Appendix C I@

Appendix D IO


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The application of hadron accelerators (proton and light ions) in cancer treatment is

relatively new. They are far from standardized, but the use of hadron therapy as an alternative

to conventional radiation has led to important developments and refinements in conventional

treatment technique. Hadron beams allow highly conformal treatment of deep-seated tumours

with great accuracy, while delivering minimal doses to normal surrounding tissue.

This overview of hadron therapy covers the following topics: an introduction of

radiotherapy represents the relationship between cancer and radiotherapy, and the historical

development of radiation therapy, physical and radiobiological properties of hadrons, hadrons

therapy equipments with the cost of hadron facilities.


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#1234567897:73.

I would like to thank Pro. Paddy Regan for his supervision, and guidance throughout this

project, I did appreciate his help and advice.

I would like to thank my wife for support I was provided with during the completion of

dissertation masters.


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(=9B/7 LC Homogeneity region in a plan orthogonal to the beam direction

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It is necessary to define the homogeneity along the beam direction in correspondence

to the SOBP region for example with proton beams. The region of homogeneityis defined

as the region between two distal fall-off widths (below) inside the 50% dose point distally

and one distal fall-off width inside 90% dose point proximately. It is assumed that 100%

corresponds to the point of maximum dose in the SOBP as shown in Fig. 2 .

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Cancer can be defined as the uncontrolled growth and proliferation of groups of cells.

It is reported that is affecting the industrial countries in Europe, 26% of deaths are in relation

with cancer. The average survival of a 5 years-cancer is 40%. Many factors are involved in

cancer development: food, medicines, genetics, infections, and professional. The

radiotherapy, chemotherapy and surgery are the main therapist against cancer.

Figure 1.1:Present situations of the different treatments against solid tumors by EC (Haberer,

2002)

Figure1.1 present situation in cancer treatment, as we can see that of 45% of all patient

are cured, among various cancer treatments; surgical removal of the tumor tissue,

radiotherapy, and chemotherapy. Surgery and radiotherapy are today of crucial important and

successful in 22% and 12% of cases respectively. Moreover, radiotherapy is involved in

almost half of the curative treatment of the localized cancer when combined the 12% for

another 6% of the cases. For 18% of all cancer patients the local control of the primary

tumour without metastasis fails. And these patients could be cured successfully if improved

treatment modalities as the application of proton and ion beams in radiation therapy (haberer,

2002)

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ions, alpha particles, mesons, etc) to target cancerous tissue by; external beam therapy, sealed

source therapy (Brachytherapy) and unsealed source therapy. External beam therapy is the

most common form of radiation therapy. It is performed with electron or photon beams; these

are produced by a linear accelerator

Charged particles beams have been used for radiotherapy such as protons and heavier

ions. E. Rutherford who is discovered the protons atthe end of the second decade of the 19th

Century. In 1955, the Lawrence Berkeley Laboratory (LBL) was the first organisation in the

world that is performed the first clinical application for a proton beams in California. During

this period 1919-1955, there are two significant on proton therapy occurred; in 1930, E. O.

Lawrence was built the first cyclotron with high energy for application of cancer treatment,

and in 1946, Robert Wilson was used the proton beams for deep-seated tumour treatment.Moreover, Wilson referred to the physical aspects of the dose distribution of the proton

beams, such as an advantage for proton compared to X-ray therapies. (Subramania,

1996;Aferd.2009)

There is an on going level of interest in using charge particles as beams of hadrons in

radiation therapy such as protons, neutrons and heavy ions. Particles therapy act to damage

the DNA of cancerous tissues that they cannot multiply and grow, and minimizing damage to

the surrounding healthy cells. At the present, there are now about 25 developed facilities

around the world using protons and light ions (carbon) for cancer treatment; they have been

treated more than 55,000 patients with proton therapy and 5000 patients with carbon ions

(Aferd.2009).

According to Dale et al.project that the Royal College of Radiologists (2003) in the

European study was found 11% tumours that are treated by chemotherapy, 40% by

radiotherapy and 49% are cured by surgery. As a result, the 40% is very respectable and

provides a strong indication of why the research is continuing and investment in this modality

is justified (Dale et al, 2009).

In general proton therapy and light ions therapy is more expensive than photon therapy.

The ratio of the cost was found about 2.4 relating to Goitein et al. project in 2002, and they

expected that the cost will be reduced to 1.7 or less in the next few years. Also Alfred pointed

out on his project that the refund rate is currently somehow sufficient to develop hadrons

facilities with the progress of technologies and a reasonable incoming margin. In the future,

the cost of these modalities will decrease more and will be spread more than before among


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more patient.

.Fig 1.2:Development of radiation therapy linear accelerator (a)-4MeV AEI linac with an in line

treatment head, mfd. in 1955;(b)- the SL75 Philips linac with a horizontal accelerating structure

and 90 bending magnet, suitable for full rotation therapy, mfd. in 1964;(c)- the Dynaray 4 linac

with 270 achromatic magnet, mfd. in 1971; (d)- a present-day system with an in- line treatment

head, without beam binding, e.g. 4MeV LMR-4 Toshiba Linac with 35 cm along accelerating

structure.


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)H0I.7/ ?C Physical and Radiobiological Properties of Hadrons

Hadrons are compound subatomic particles made of quark and antiquarks, bound

either in doublets or in triplets by strong force. The hadrons that are employed for

radiotherapeutic purpose are protons, neutrons and light ions (such as carbon, helium, neon

and oxygen). Among the use hadrons, protons show approximately the same LET as

conventional photons and electron beams when they going into treated body, but have an

increasing LET at the end of their track in tissues. However, neutrons and light ions are high-

LET particles (table 2.1)

Table 2.1: LET (L ) of ionizing particles and radiations of radiations of interest inradiotherapy and radiobiology, after (Wioletta & Waldemer, 2001)

The ability to change the radiative properties is due to the fact that the biological

affects are correlated with the distribution of energy deposited. This distribution is influenced

by the atomic number Z (for carbon=8, for proton=1) and the energy of the impinging

hadrons. The basic physical and radiobiological properties of photons and ions are compared

in table 2.2

Hadron therapy is using of charge particle beams of protons or carbon ions for

treatment of cancer. Ion beam therapies have a major of important advantages over

conventional radiation therapy for deep-seated cancerous cells, also for tumors closed to a

critical tissue of organ. The development of the physical characteristic of particles beamsfrom proton to carbon and of ion accelerator, they hold promise due to its capability to deliver


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high dose to target volume. The heavy charge particles have rather reduced depth-dose

outline, but enhanced responses biological effectiveness (Wioletta & Waldemer, 2001)

Table 2.2: Differences between photons and ions, after (Wioletta & Waldemer, 2001)

2.1 Physical characteristic of the beam

The physical properties of charge particles interaction with critical organs introduce an

eminent benefit of hadron therapy compared to conventional radiation therapy, it allows a

delivery adequate high dose to stop a tumors growth, destroy it, and prevent damage to the

normal cell that is surrounding tumors as much as possible. According to Weyrather and

Debus project that they have reviewed the physical properties of particle beams interaction

with tissue, and summarized it as the following (2003):

2.1.1 Depth-dose distribution and Bragg-peak


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The dose decreases exponentially for penetrating depths beyond the build-up depth for

photon conventional radiation therapy. At the same time as a charge particle beam loses just a

small quantity of its energy at the access until the maximum penetration depth where the

remaining energy lost over a short distance consequences in a high dose presented as Bragg-

peak (Fig.1.3)

Figure 2.1: Comparison of Depth-dose curves for photons, proton, and carbon beams

(Weyyrather&Debus, 2003|)

As we know that the target volume of tumours is much larger than the unmodified

Bragg peak width. In clinical applications a relatively consistent dose distribution be able to

deliver to tumours by spreading out the Bragg peak (SOBP) through a Range Modulated

Wheel (RMW) or through modulating the energy from pulse to pulse as can achieved with a

synchrotron.

2.1.2 Defined range

The particles beam prevents damage to healthy tissue beyond the tumour by the

defined range, and after the Bragg peak drops almost to zero. It is determined the density of

the target tissue and the energy of particles. A rang straggling in Bragg peak due to multiple

scattering of the particles which depend on the atomic number of the particles, and this

straggling for protons is highest and it decreases quadratically with atomic number of the

projectile ion.

2.1.3 Lateral scattering:

Heavy ions such as carbon have the advantage of the small scattering angle as they

penetrate the target. The expansion of carbon beam is less than 1mm at 10 cm depth, while for


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proton it goes more than 2mm. this advantage give more accuracy for irradiating of deep-

seated tumour close to a critical tissue (Fig.3.2)

Figure 2.2: Comparison of the lateral scattering of photon,proton and carbon beams asfunction of the penetration depth(Weyyrather&Debus, 2003|)

2.1.4 Non-elastic nuclear reaction:

The interactions depend on the type of the charge particles and the cross-sectional of

the target volumes, as we know the particle beams undergoes nuclear interaction with target

materials. In the proton case, the non-elastic nuclear interaction results in attenuation of the

primary beam and emission of secondary proton and other particle with relatively lower

energy. However, for carbon, a small amount of the primary beam transferred to lighter

nuclear fragments causing a long dose tail beyond the Bragg peak, but it continues within the

acceptable limits.

2.1.5 Positron emission tomography technique (PET)

The PET technique allows 3D retrospective analysis for the dose distribution inside

the body of patients. There is a small percentage of the passage particle beam that going to

body tissue can be transferred to nuclear fragments with the same atomic number of the

projectile due to the only one or two neutrons are lost. As unstable carbon isotopes (10C, 11C,

and15

O) are produced. The decay of these isotopes with 19 second, 20 minutes, and 2 minutes

respectively of its half-life are under emission of a positron and neutrino. In carbon therapy, a

10C and 11C ranges differ only slightly from the range of stable 12C and the stopping point

can be screened by measuring the coincident emission of tow annihilation quanta of the

positron decay, by using PET-camera outside the body without extra dose to the patient.


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However, the range of positron emitters is few mm in proton therapy shorter than the range of

primary proton due to the threshold of energy of nuclear reaction and fragmentation. On the

other hand, the positron emitter stopping point is somehow correlated with the Bragg peak.

This is an advantage for proton therapy to using PET; also the activity of positron emitters is

higher then for carbon approximately three times at the same depth. This is help to increase

the sensitivity of PET imaging in proton therapy over carbon therapy.

2.2 Biological effect:

The biological effects of ionizing radiation result generally from ionization and

excitation of atoms and molecules in the matter via radiation. These primary processes initiate

a complex chain of events in a living cell, which lead to chemical changes in some

biomolecules (DNA that is the most important target) and to bio functional changes such as

cell death, transformation and mutation (.'C'+%))1 3( &E),??,0.

Figure 2.3: Comparison of tracks of sparsely and densely ionizing radiation with the relevant

biological targets (Amaldi & Siliari,1996)2.2.1 The Relative Biological Effectiveness (REB) and Linear Energy Transfer (LET):

The different biological effect depending on the energy atomic number of the ion and

can occur from the same dose in high-LET as a hadron beams, while the low-LET radiation


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such as "-rays, X-ray and electrons that is used in conventional therapy, exhibit the same

biological effect when applied the same dose.

The Relative Biological Effectiveness (REB) can be calculated from measured data as

we can show that in Fig 3.3. For example, the ratio between the dose of X-ray and the ion

particle dose necessary to produce the same biological effect.(Weyrather&Debus, 2003|)

Figure 2.4: Definition of the relative biological electiveness, RBE, illustrated for cell

survival curves with carbon ions of differentenergy(Weyrather&Debus, 2003|)

As we can see at Fig.2.4, the shoulder in heavy ions (carbon ions) dose-effect curve is

much smaller, while in the proton represents repair capacity of the cell at low doses. This

represents a high ionization density is reduced the repair capacity of cell at the same dose.

And the most interesting conclusion is that protons in plateau are as the lethal as "-rays, while

protons in the Bragg peak show a higher effectiveness.


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Table 2.3: RBE for inactivation of cultured mammalian cells irradiated with proton

beams of high initial energies (Amaldi & Siliari, 1996)

The RBE in hadron therapy is dependent on several biological and physical factors.

As the Weyratherand Kraftmentioned to Experiments revealed a dramatic dependence of

RBE on the dose level, atomic number and the repair capacity of the biological system. It also

showed that carbon ion are the optimal choice for high-LET therapy; later scattering and its

range are small producing an optimum precision in dose delivery system(2004). The

efficiency of ions to induce biological damage changes along their path. Local ionisation

density increases at the end of the range, and causing difficulty repairing for high DNA

damage and RBE increases up to maximum, while the high energies and light ions at the

entrance channel are easily repaired for the induced damage, and RBE is close to those

induced by low-LET radiation (Weyrather&Debus, 2003). At Fig. 3.3 that clears the RBE is

inversely dependent on the dose, its large for low doses and small for high dose. And high

RBE is related with lower dependence on Oxygen to have an effect on the cancerous tissues.

Therefore, heavier ions and carbon can effective to slow or stop growth of radio-resistance

and poorly oxygenated tumours (Dale et al, 2009).

2.2.2 Oxygen Enhancement Ratio (OER)


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The Oxygen enhancement ratio is an additional indicator for realising the therapeutic

effects giving by a certain type of radiation. The OER is the ratio of doses with or without

oxygen to produce the same biological effect. Therefore, the OER has a strong dependence on

the LET; it decreases as LET exceeds approximately 10 and approaches unity at very high

LET, as a result, the better oxygen enhancement ratio when its lower value.

Figure 3.1 is shown the comparison of the relative biological effectiveness (RBE) and

oxygen enhancement ratio (OER) values for different radiation particles and ions. It is clear

that to obtain the optimum curative effect; the RBE value should be high while the OER

should be low.

(=9B/7 D


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)H0I.7/ DCHadrons Therapy equipments

Nowadays, the main source of radiation therapy carried with types of accelerators for

electron, and X-ray radiotherapy such as Linear accelerator, betatrons and microtrons. All

these accelerate electrons to high velocities that have varying energy, also as we mention

before the electrons are accelerated, the tissue penetration depth, the tissue at that greatest

dose of radiation is absorbed. (Bertil J, Alan M, 2006).

Hadron therapy is the one of the therapeutic technique that used to treatment cancer, and

its varied application of treatment that uses the widespread range of particle accelerators from

the use of small electron linear accelerators for radiotherapy, to the use of proton cyclotron for

radionuclide production is 10-20 MeV, and to the application of 50-60 MeV proton

accelerator for proton therapy or neutron treatment of eye melanomas to the hadron

accelerators that it is installed in radiation treatment centres for cancer therapy with ion beam

or proton (Amaldi U, et all, 1996).

3.1 Conventional Accelerator Radiotherapy

(=9B/7 D


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Hadron accelerators have two types (cyclotron and synchrotron) to produce a charge

particle beam with sufficient energy that passing trough the beam transport system to reach

the target volume with enough intensity, due to achieve a typical medical treatment.

The cyclotrons are made up of the particle beam and a large magnet to moves starting

from machine center with a long spiral path, and it is working at fixed field and fixed

frequency of energy due to continuous beam, also operating reliability and simplicity. In

synchrotrons the radio frequency and magnetic fields are varying that provide a sufficiently

high dose rate for treatment compared to cyclotrons. However, cyclotrons have a capacity to

produce sufficient beam with high intensity (flux). (Chu et al, 1993).

In recent years, the building accelerators have increased throughout the world for

medical treatment, and the development and improvement is providing a new generation of

accelerators, which are more compact, efficient and inexpensive.

3.2 Accelerator for heavy ions and proton

Theoretically, the hadron beams that used in cancer (protons, light ions such as carbon)

has developed considerably since the middle of the last century and the hadron therapy

presents the potential of both physical (protons and ions) and biological (neutrons and ions)

advantages in the therapy of localised tumour (Lodge M, et all, 2007). The use of protons in

the treatment cancer depend on the superior dose distribution which can be achieved with

respect to electrons and photons, as a result, it is due to the low lateral scattering undergone

by protons, their will-defined range and the increasing dose deposition (ionization) with

increasing penetration in cell tissue, that produces theBragg peak (Fig. 2.1)

The depth at which the Bragg peak occurs depends on the initial energy of the protons

and its width on the energy spread of the beam. Fig. 4.1 shows that, an even enhanced dose

distribution and the additional advantages of an increasing the relative biological

effectiveness (RBE) at the end of range in tissues for protons. The therapy beam which used

in treatment cancer must have enough range to reach the deepest point of volume of the body,

in order to irradiate tumors that the minimum energy required for carbon ions are 400 MeV/u

and for protons are 200 MeV. All the clinical procedures can be requests satisfied among light


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ions range energies between 120-400 MeV/u and 109-1010 ions/s of beam intensities, which

depends on the ion type. For protons corresponding figure are 60-250 MeV and 5 #1010-1011

(Fig. 4.3). (Amaldi, et al.1996).

These requirements stand for hadron accelerator considered for cancer treatment that the

basic specification must be met by ion radiation or proton therapy facility to represent an

Fig. 3.2: Depth-dose curves for photons, electrons, neutrons and 200MeV

protons.

Fig. 3.3: Range-energy curves in tissues for light ions and photons


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effective and reliable instrument against cancer. The performance standards of the accelerator

and of delivery systems and beam transport must satisfy a number of clinical requirements.

These performance standards are expressed in terms of beam intensity, energy variability and

range, distal dose fall-off, time structure of extracted beam, lateral penumbra, beam abort time

and raster scanning specifications (Goitein M, 2007).

According to Alfred project that is summarized the new accelerator technologies for

proton therapy designed such as:

3.2.1Fixed Field Alternation Gradient accelerator (FFAG):

In Japan, the Energy Accelerator Research Organization (KEK) was built the first

proton FFAG accelerator in 1999. The energy range of several FFAG accelerators which is

manufactured tell this point are 150-250 MeV, and it is join the fixed magnetic field of

cyclotrons and the energy variability of the synchrotrons. In addition, the easy operation and

compact size of the FFAG accelerators make them more attractive for hadron therapy. In the

UK, the British Accelerator Science and Radiation Oncology Consortium (BASROC) aim to

build non-scaling FFAG accelerators to be used for hadron therapy.

3.2.2

The dielectric-wall accelerator (DWA)

In USA, the Lawrence Livermore National laboratory (LLNL) has developed the

dielectric-wall accelerator. This technology uses to accelerate the proton approximately

100MV/m of high electric gradients. It will be employed the development of a high

accelerator gradient LINAC for proton therapy.

3.3 Beam transport system

The extracted beam is transported from the accelerator to treatment radiation therapy

room by beam transport system. A beam lines consist of quadruple and dipole magnets,

vacuum chamber and diagnostic instrumentation. An efficient and stable transport of the

beam from the accelerator to the treatment room is needed to achieve a reliable therapy and

reproducible dosimetry. The stability of the centroid of the beam position is adjusted by

focusing magnets to control the beam position and profile, which is called tuning beam line. It

means adjusting the beam optics to transport the given beam to the required location with the

desired physical parameters (Chu et al, 1993).


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3.4 Beam delivery systems and techniques

This system is located at the treatment room; it lies between the beam end line at the

vacuum window and the patient. The beam delivery system has a technical components and a

number of devices to adapt the beam such as; modulating devices and range changing, also

laterally spreading and shaping devices. It also has a number of monitors to manage the

prescribed 3D dose distribution inside the target volume (Wioletta & Waldemer, 2001). In

practice, the role of the beam delivery system technique are divided into two principle

according to the method of the beam spreading as following:

3.4.1Passive beam shaping

Passive beam shaping is the most commonly used in proton and heavy ion therapy. It

has three steps; a modulator designed modifies the monoenergetic beam from the accelerator

to provide a predefined depth dose modulation. Numerous modulators are available to cover

different depth modulation in tissue. In order additional range shifts are needed to adjust the

modulated Brag peak to the desired radiological depth. Finally, a clinically useful field widthis produced using a double scattering system or a magnetic beam wobbler. It has three major

disadvantages (IAEA, 2007):

The depth dose can only tailored to the distal end of the target due to the factwhich the compensator shifts the SOBP towards the entrance region. A

considerable amount of the high dose region (and high LET region) is located

in the normal tissue in front of the target volume, especially at the lateral field

borders

The amount of material in the beam line is considerable, leading to an increasein nuclear fragments produced by nuclear interactions with the material of the

beam modifiers. These nuclear fragments have lower energies and lead to a

higher LET and thus an increased biological effective dose of the beam already

in the entrance region

The large number of patient specific beam modifiers, which have to bemanufactured (a compensator and a collimator for each treatment field) and the

necessity to produce a number of modulators that may have to be exchanged


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for different patients.

At HIMAC using the passive depth dose system, the depth dose is fixed by the

modulator hardware, which is designed to achieve a prescribed homogenous biological dose

effective dose for single field. The design of the modulators reflects the fixed dependence of

the RBE with depth for dose level.

3.4.2Active beam shaping:

This system takes advantage of the electric charge of ions to produce a firmly focused

pencil beam that is deflected laterally by a magnetic field instated the foils in the passive

scattering technique to allow a scanning of the beam over the treatment field. In clinical

applications the target volume is dissected into layers of equal ion energy, each layer is

covered by a grid pixels and the beam is scanned in a row pattern over these pixels (Alferd,

2009). Moreover, the energy from a synchrotron can be switched from pulse to pulse to adapt

the range of the particles in tissue. This technique is able to scan the target volume in three-

dimensional and the dose distribution can be tailored to any irregular shape without any

patient specific devices (such as collimators or compensators) or passive absorbers. Thus, the

high dose region can be conformed to the proximal end of the target volume and the integral

dose as well as the volume receiving high LET radiation is summarized (IAEA, 2007).

Fig. 3.4: Principal of passive beam shaping


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3.5 Gantry design for proton and carbon hadrontherapy facilities

The tumor is treated several times with beams coming from different direction, so the

device that is used to allow directing beam from several directions onto the patient who is

lying on the treatment table and to reduce the dose to the surrounding health tissues is called

gantry. However, the necessity of choosing a gantry or not is influenced by many factors,

mainly by the design of each treatment facility and the kind of tumor to be treated. Building a

gantry for heavy charged particles is a technological challenge. It is lies in the production of

large and heavy gantries still achieving the same position stability of the ion beam. The first

hospital-based gantries had a diameter of 12 meters. The innovation PSI project compact

spot- scanning gantry (Pedroniet al, 1995) is a very good optimization of the size (diameter of

4m) predominantly because of the alternative chosen to move patient during the treatment (Fig

4.5).

The hydrotherapy aims for gantries-despite the higher magnetic rigidity. Th!rigidity i"

d!fin!d #" th!$r%duct %f th! b!nding r#diu" #nd th! r!quir!d m#gn!tic fi!ld "tr!ngthR In

proton therapy several facilities are already running gantries in routine process with a

magnetic rigidity of about 2.5 Tm. However, this situation is not yet reached in carbon

therapy due to higher magnetic rigidity of about 6.5 Tm.

Fig. 3.5: The exocentric PSI Gantry (PSI Web pages)


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The area of the treatment for proton gantry (Fig. 4.6), the gantry typically directs the beam from on

In radiotherapy and are called isocentric gantries. Therefore, at PSI used the exocentric

gantry for proton Gantry 1, which the patient table has a different position for each gantry

angle. A set of the used gantry angles is exemplified in Figure 3.7

Fig. 3.6: Layout of proton gantry delivered by Mitsubishi; after (Weinrich, 2006)

Fig. 3.7: Calcification of the different types of gantries; after (Kraft, 2000).


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Then the advantage is that it can be built in a more compact manner; and it is shown in figure

3.8

In tables 4.1 and 4.2 an overview the important parameters of some proton and carbon

gantries in Europe and Japan.

Table 4.1: Proton Gantries in Europe & Japan;after (Weinrich, 2006)

Town No. Status Type Energy Length Radius Dipoles Quads

Germany

Munich 4 Validation Isocentric 250 MeV 10.1 m 5 m 2 7

Switzerland

Villingen Gantry 1 Operation Excentric 230 MeV 10.2 m 1.4 m 3 7

Switzerland

Villingen Gantry 2 Assembly Isocentric 230 MeV 11.6 m 3.2 m 3 7

Japan

Fig. 3.8: the exocentric Gantry 1 at PSI; after (Weinrich, 2006)


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Hyogo 2 Operation Isocentric 230 MeV 9.5 m 4.8 m 2 7

Chiba 2 Operation Isocentric 235 MeV 10.7 m 5 m 2 9

Tsukuba 2 Operation Isocentric 250 MeV 9 m 5 m 3 6

Shizuoka 2 Operation Isocentric 235 MeV 9 m 4.8 m 3 4

In addition, the treatments with carbon ions are currently delivered in three facilities;

HIMAC, HIBM in Japan and GSI Germany, table 4.2 shown the properties of some carbon

gantries.

Table 4.2: Carbon Gantries in Germany & Japan;after (Weinrich, 2006)

Town No. Status Type Energy Length Radius Dipoles Quads

Germany

Heidelberg 1 Assembly Isocentric430

MeV/u19 m 5.6 m 3 8

Japan

Chiba 1 Design Isocentric400

MeV/u16.9 m 7.1 m 3 7

T%#chi!v!#r!#"%n#bl!b!nding r#diu", much high!r fi!ld "tr!ngth"#nd thu"l#rg!r #nd

h!#vi!r m#gn!t"#r!n!c!""#ry f%r i%n". Whil!th!w!ight %f #$r%t%n g#ntry i"#lr!#dy #r%und

100 t%n"(#t length %f 10m), #n i"%c!ntric g#ntry f%r c#rb%n i%n"i"!x$!ct!d t%h#v!w!ight %f

#b%ut 600 t%n"#t length about %f 18 m.

Th!!n%rm%u""iz!#nd w!ight %f "uch #g#ntry t%g!th!r with th!high "$#ti#l #ccur#cy

r!quir!d f%r th!b!#m $%"iti%n #t th!i"%c!nt!r i"$r%b#bly th!r!#"%n why n%"uch g#ntry h#"

b!!n built u$ t% n%w. In"t!#d %f fl!xibl! b!#m d!liv!ry "y"t!m", fix!d inclin!d b!#m lin!"

h#v!b!!n r!#liz!d #t th! tw%%$!r#ting clinic#l i%n f#ciliti!" in J#$#n, wh!r!v!rtic#l b!#m"

#nd b!#m" with 45inclin#ti%n #r! #v#il#bl! t%g!th!r with h%riz%nt#l b!#m". &n%th!r

$%""ibility i" t%m%v! th!$#ti!nt r#th!r th#n th!b!#m. &t "%m!$r%t%n #"w!ll #"h!#vy i%n

f#ciliti!", tr!#tm!nt ch#ir"#r!#v#il#bl!%r m%uld"th#t c#n b!r%t#t!d ("!!$#ti!nt $%"iti%ning

f%r d!t#il"). It "h%uld b!m!nti%n!d th#t "iz!#nd w!ight %f #g#ntry c%uld b!r!duc!d by th!

u"! %f "u$!rc%nducting m#gn!t". Th! cry%g!nic" inv%lv!d, h%w!v!r, r!quir!" c%n"id!r#bl!

"$#c!#nd i"m%r!d!lic#t!t%h#ndl!in t!rm"%f "t#bility #nd $#ti!nt "#f!ty.

Hadrontherapy is developing to provide the same geometrical flexibility, as photon

therapy gantries have to be used for also these facilities. At the same time as the proton


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gantries are in routine operation now this is not achieved for carbon treatment. However,

advanced design efforts have reached the implantation step at GSI, but are under

consideration Riesenrad gantry. Because of the high costs of a gantry, alternatives to gantry

system have been experienced and considered at Chiba, Hyogo and NIRS.

3.6 Cost-effectiveness of hadron therapy in cancer

In the study by Mark Lodge et al (2007), they identified a total of 7209 articles, after

they de-duplication it, they reduced to 5089 articles, then they found the following number of

articles to be relevant to his review: neutron therapy (563), proton therapy (137), ion therapy

(49); economic viability and cost-effectiveness (10). Table 4.3 is shown the results literature

review in comparison with conventional therapy classified by tumour site.

Table 4.2: Results literature review in comparison with conventional therapy classified

by tumour site;after (Lodge et al, 2007)

The current literature shows that the existing data do not suggest the rapid expansion of

hadron therapy, as a major treatment modality would be appropriate. The formation of a

European hadron therapy would offer a simple way of accelerating the rate at which they

obtain high-quality evidence that should be used in assessing the role of hadron therapy in the

management of cancer.

The heavy charge particle therapy will be more expensive than the conventional

radiotherapy (magnetic fields required, concrete thickness, training and level of the

staff)(Goitein, 1997). Oliv


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)H0I.7/ LCTreatment planning

In this section we well describe the procedure that used for intracranial treatments for

proton therapy (at CPO: Centre de Protonthrapie d'Orsay, French)(8'*4%5^ @AAQd.

4.1Imaging protocol

Physician counter the tumour and all surrounding critical organ by using the Computed

Tomography (CT scan) data with transverse slices of 1 mm to simulate the dose deposition

inside the patient. They also use Magnetic Resonance Image (MRI). Technical progress in the

software contributed the achievement of the fusion between CT and MRI images. Because CT

scans are based upon the photons interactions in the middle, then a calibration curve helps to

convert from X-rays absorption to protons stopping power (Fig. 4.1)

Fig. 4.1: Calibration curves for intracranial treatment (CPO); after (8'*4%5^ @AAQd


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4.2Organs contouring

ICRU is fixed standardised volumes of contouring:

I. Gross Tumour Volume (GTV); tumour visible on the images.II. Clinical Target volumes (CTV); tumour with possible microscopic

extension.

III. Planning Target Volumes (PTV); positive margins of treatment includingthe treatment uncertainties.

4.3Dose calculation algorithms

Numerous models are used for the dose calculating as the following:

I. The ray-tracing model is a one-dimension model. The SOBP parameters arematched to the different densities and thickness for one direction of the

tissue. It is incorrect and limited for example to bone and air cavities,

because of scattering effect.

II. The classical Monte-Carlo model is very efficient.III. The pencil beam models are good compromise between accuracy and

calculation time.

4.4Choice of the ports

To deliver the prescribed dose to the tumour and do not exceed the maximal dose for

surrounding healthy critical organs; the dosimetrist must find the good compromise. For

example the maxima(empiric data known by physician) dose for the optic chiasma is 55

Gy.

4.5Positioning and treatments

The ballistic properties that are used for hadron therapy have a specific positioning

system. At CPO, 1mm and 1 used for basic requirement for intracranial proton therapy.

Therefore, a specific system (frames, mask, foams, byte blocks,.) is used with patient

immobilizer to adjust the real position to the reference position prescribed by the planning

system of treatment 4 or 5 of fiduciary markers are fixed in the patient skull (Fig. 4.2). The

DRR (Digital Reconstructed radiography) extracted from CT data are compared with the axial

and the perpendicular X-rays radiography of the patient seated. The robot moves to position

the patient in several iterations by specific software, while there are other techniques such as

anatomic references or CCD camera (NAC) avoids the implantation of marks (Fig. 4.2). Thenthe dose during the treatment is monitored with transmission ionisation chamber. And in


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passive scattering technique, the classical irradiation last is about 1 minute (2 Gy EQ CO per

session, 2 Gy/min). Besides, there is no specific perception or pain of the patient during the

treatment.

On other hand, the comparison of treatment plans using photon and proton is shown in

Figure 4.3 with different number of fields for cancer of Glandular parotid that locates nearest

to the ear, as we can see that on the left image, 100% dose is delivered by overlapping two

beams of photon from two entry points. The attenuation after beams hits the tumour; the

remaining doses are received by other part of the head up to 30%. Moreover, the use of

photon beam of 5 fields in middle image; the doses receive by other parts beyond the tumour

is lessen since lower energy beams can be used to overlapping at the tumour location but

remain delivering 100% dose to tumour. As a result, a large amount of healthy tissues are

irradiated. However, the proton beams in 3 fields on the right image; as described with the

depth-dose profile of proton treatment that the doses received by other body parts after the

Bragg peak is very small as shown in this treatment due to doses are very conformed to thetumour site.

Fig. 4.2: Patient in position treatment at CPO, after (8'*4%5^@AAQd

Fig. 4.3: Treatment plan comparison of using photon and proton


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.'C% SP

)H0I.7/ NCConclusion

There is a worldwide interest in the development of heavy charged particles therapy as

a conformal tool in radiotherapy. Due to hadron that has its unique depth-dose track with low

entry dose and an ionising intensity peak near the of its range, i.e Bragg Peak.

Wh!r!#" th! fir"t f#ciliti!" w!r! b#"!d %n r!"!#rch c!nt!r" in nucl!#r $hy"ic", th!

curr!nt t!nd!ncy g%!" t%w#rd" #$r%gr!""iv! int!gr#ti%n in"id! th! h%"$it#l, with m%d!rn

!qui$m!nt d!v!l%$!d "$!cific#lly f%r thi" #$$lic#ti%n. Du! t% it" "!v!r#l inn%v#ting

t!chniqu!"#nd %rg#niz#ti%n", %n!%f th!m#in ch#ll!ng!%f thi" th!r#$y i" t%r!#ch #r%utin!

r#t!%f tr!#tm!nt.

F%r it"inh!r!nt b#lli"tic qu#liti!", h!#vy ch#rg!d $#rticl!"b!#m"c#n incr!#"!th!d%"!

t%th!t#rg!t v%lum!, l%w!ring th!int!gr#l d%"!d!liv!r!d t%th!$#ti!nt #nd $r%t!cting critic#l

%rg#n" . F%r # c!rt#in numb!r %f clinic#l indic#ti%n", th!$r%t%n"c%n"titut!#lr!#dy th!b!"t

ch%ic!$r%v!n by clinic#l tri#l". F%r %th!r indic#ti%n", th!$%t!nti#l b!n!fit %f $r%t%n" "till

r!quir!"#clinic#l v#lid#ti%n, #"w!ll #"c%"t-!ff!ctiv!n!"""tudi!"c%m$#ring with #lt!rn#tiv!

t!chniqu!""uch #"c%nf%rm#l #$$r%#ch!"with $h%t%n b!#m". H!#vy i%n"b!#m"will h#v!t%

c%nfirm in th!n!xt y!#r"th!ir #ttr#ctiv!bi%l%gic#l $r%$!rti!".

Mutu#l t!chn%l%gic#l tr#n"f!r b!tw!!n c%nf%rm#l t!chniqu!" m#k!" it $%""ibl! t%

incr!#"! th! qu#lity #nd th! $r!ci"i%n %f tr!#tm!nt" #nd c%n"%lid#t! th! $l#c! %f h!#vy

ch#rg!d $#rticl!"th!r#$y within th!th!r#$!utic #r"!n#l %f tr!#tm!nt #g#in"t th!c#nc!r.


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@7G7/7317-

QR Goitein M, Radiation Oncology; A Physicists-Eye view, (Biological and MedicalPhysics, Biomedical engineering),Springer-Verlag New York, LLC, 2007

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SR Amaldi U., Silari M. Biomedical Applications of Hadron Accelerators, Nuclearinstruments & methods in physics research. Section B, Beam interactions with

materials and atoms, Elsevier Science, Amsterdam, 1996, vol. 113, pp. 513-521

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of the European Society for Therapeutic Radiology and Oncology, Elsevier,

Ireland,2007, vol. 83, pp. 110-122.

A/ Jones, D.T.L., Schreuder, A.N. and Symons, J.E. Particle therapy at NAC: physicalaspects. In Proc.14th Int. Conf. on Cyclotrons and their Applications, ed. Comell,

J.C., World Scientific, Singapore, 491-498, 1996.

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Paul Scherrer Institute: conceptual design and practical realization. Med.Phys.1995;

22:37-53

QARWeinrich, Udo(GSI, Darmstadt), Gantry Design for Proton and CarbonHadrontherapy Facilities, 10th European Particle Accelerator Conference,Edinburgh, UK, 26 - 30 Jun 2006, pp.964-968

QQRG. Kraft, Tumor Therapy with Heavy Charged Particles, Prog. Part. Nucl. Phys. 45:S473-S544, 2000.

Q@RTakashi Nakamura & Lawrence Heilbronn, Handbook on Secondary ParticleProduction & Transport by High-Energy Heavy Ions, World Scientific Publishing

Company (2006)

QSR8'*4%5 >^ 3( &E) !"#$" &'($) *+, ")(-. $"(,/)0 &(,1#$')2 #3 ,(0#+1"),(&.4.(,2%%=1+C0 -,( )/% 2,4(0%e F/%('&"^ )&@* #11767/0.4/ +1H446 ZXE0/.=167

#11767/0.4/- G4/ :78=1=37 038 W38B-./=7-Y QA)/ `QU)/ >'" @AAQ ` .(4/,+12%

cHfd

QIRS. Lacombe, C. Le Sech, Advances in radiation biology: Radiosensitization inDNA and living cells, Surface Science, Volume 603, Issues 10-12, 1 June 2009,

Pages 1953-1960

QORg'+ gR L15T%+0^ 9]% K%5-T%^ 5#,)$1 6+7&(,#2+3 +* 8#+'+/#$(''. 9&1#7#:)0;&,)(0)(?2 *+, >,+1+32 (30 6(,@+3 A+32) *9(389&(>G9&E HG789&E GI

;>&(>G9 J96GEGKLMN>GEGKLM6O^ PGE753 Q?) *OO73 .^ . H&97&8L ,??F^ G9&E HG789&E GI ;>&(>G9 J96GEGKLMN>GEGKLM6O^ PGE753 A1)

*OO73 ,^ . H793 ,??,^


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.'C% SW

.F/Dale R G, et al, A 2009 why more needs to be known about RBE effect in modernradiotherapy, Applied Radiation & Isotopes; including data, instrumentation, and

method for use in agriculture, industry and medicine, vol 67, p.p 387-92

.S/. IAEA-TECDOC-1560, Dose Reporting in Ion Beam Therapy, Proceedings of ameeting organized jointly by the International Atomic Energy Agency and the

International Commission on Radiation Units and Measurements, Inc. and held inOhio, United States of America, 1820 March 2006

,?/T. Haberer,Advances n Charged Particles Therapy, Nuclear Physics in 21st Century:Int. Nucl. Phys. Conf. INPC 2001. AIP Conf. Proc., Vol. 610, pp. 157-166, 2002


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Appendix A: Proton Beam Facilities at the world & Particle Therapy Facilities in

operation


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.'C% IA

Appendix B: Hadron therapy patient statistics (data received per end of Feb 2009);

( from PTCOG website:

http://ptcog.web.psi.ch/Archive/Patientstatisticsupdate02Mar2009.pdf) log on 2/9/2009.


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Appendix C: Hadron therapy facilities in planning stages or under construction and in

operation


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.'C% II


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.'C% IO

Appendix D: Hadron therapy design and layout of;

1. HIMAC FACILITIES

2. HIT FACILITIES


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3. PIMMS FACILITES

4. CANO FACILITIES

Documents

HADRON THERAPY FOR CANCER USING HEAVY IONS