Advancements Of Proton Therapy

Running Head: ADVANCEMENTS OF PROTON THERAPY 1

ADVANCEMENTS OF PROTON THERAPY

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Student’s Name

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ADVANCEMENTS OF PROTON THERAPY 2

Abstract

The study explores the advancement of proton therapy. It goes further to explains how

patients with cancer are treated using this technique and also neutron and heavy ion carbon.

Proton therapy advances from conventional treatment that involves X-rays, gamma rays, and

electron therapy. The proton beam therapy physics, mechanism, biological and physical concepts

are detailed. The effectiveness of the PBT in treating different cancers such as head and neck,

prostate, gastrointestinal, thoracic, pediatric and other cancers reveals its competitiveness as

opposed to the conventional type. This efficiency of proton therapy makes it a better option in

the treatment of tumors in children and adults as it results in cancer medication with reduced

adverse effects. Again, neutron and heavy ion carbon have shown their efficiency in treating

different complications brought about by these ailments. There is also a discussion of merits and

demerits of proton therapy in the study. Further research is ongoing to provide promising

advancement that destroys cancer hence hope for a healthy community in the forthcoming days.

ADVANCEMENTS OF PROTON THERAPY 3

Table of Contents

Abstract ........................................................................................................................................... 2

List of Figures ................................................................................................................................. 4

1.0 INTRODUCTION.............................................................................................................. 6

2.0 PARTICLE THERAPY .................................................................................................... 7

2.1 Proton therapy ................................................................................................................ 7

2.1.1 Physics of Proton Therapy ........................................................................................... 9

2.1.2 PBT Physical Aspect ................................................................................................... 12

2.1.3 PBT Biological Features ............................................................................................. 13

2.2 Proton Therapy Advancements ....................................................................................... 14

2.2.1 Pencil beam scanning (PBS) ...................................................................................... 14

2.2.2 Paralleling PBS ........................................................................................................... 15

2.2.3 Intensity modulated proton therapy (IMPT) ........................................................... 15

2.2.4 Proteus One ................................................................................................................. 16

2.2.5 Pro-Beam System ........................................................................................................ 16

2.2.6 PT-specific version ...................................................................................................... 16

2.3 Neutron therapy ................................................................................................................ 16

2.4 Heavy ion carbon therapy ................................................................................................ 20

3.0 DISCUSSION ........................................................................................................................ 23

3.1 Proton Therapy for different Cancers ............................................................................ 24

3.1.1 Head and neck cancers ............................................................................................... 24

3.1.2 Thoracic tumors .......................................................................................................... 25

3.1.3 Abdominal and pelvic cancers ................................................................................... 26

3.1.4 Pediatric cancers ......................................................................................................... 27

3.1.5 Other tumors ............................................................................................................... 27

3.2 Controversies of PBT ........................................................................................................ 28

3.3 Drawbacks of PBT ............................................................................................................ 28

4.0 CONCLUSION ..................................................................................................................... 30

5.0 RECOMMENDATION ........................................................................................................ 31

REFERENCES ............................................................................................................................ 32

APPENDIX .................................................................................................................................. 34

ADVANCEMENTS OF PROTON THERAPY 4

List of Figures

Figure 1: Proton interaction mechanism {(e) electron, (p) proton, (n) neutron} .......................... 10

Figure 2: an Inelastic nuclear reaction against the energy of proton across nuclear barrier ......... 11

Figure 3: Percentage depth-dose distribution curve of proton beam vs. photon beam ................. 12

Figure 4: Comparison of high LET and low LET electrons ......................................................... 17

Figure 5: Photon therapy ............................................................................................................... 18

Figure 6: Neutron therapy ............................................................................................................. 18

Figure 7: Survival of cancer cell ................................................................................................... 20

Figure 8: Minimized irradiation of C-ions to the adjacent areas .................................................. 21

Figure 9: Target cancer irradiated with heavy ion beams ............................................................. 23

ADVANCEMENTS OF PROTON THERAPY 5

ADVANCEMENTS OF PROTON THERAPY 6

ADVANCEMENTS OF PROTON THERAPY

1.0 INTRODUCTION

Cancer is a global cause of life destruction with millions of deaths occurring worldwide.

It is a multicellular and multi-genic disease that can happen in all types of cells and organs. If not

treated the cellular growth can spread and lead to life loss of an individual. As a result, there

exists continuous progress in the advancement of cancer treatment that can help cure the ailment.

At the same time, the improvement minimizes radiation to the uninfected areas making it safer

and more effective.

X-ray discovery in the earlier days was the first cancer treatment that was clinically

useful. From then, radiation therapy emerged which was applicable in the medical specialty

where a group of science and health professionals gathered (Schippers & Lomax, 2011). The

radiotherapy is of great importance in cancer medication with a high application of cost

efficiency. Furthermore, there is a rapid advancement in this field which continues to grow due

to the radiation therapy machines, computerized planning devices, and imaging techniques.

Tumors, especially the brain ones are highly distinct in their prognoses and treatment.

There is curing of some patients conservatively, although others require a profound combination

of chemotherapy, radiation, and surgery. These therapies aim to destroy the cells that have

tumors and to hinder regrowth while protecting the healthy cells from destruction. More so, the

treatment is essential for children. This therapy is possible since their growing brains and bodies

are highly sensitive to the prolong radiation effect.

Radiation therapy destroys cancer cells. Likewise, it inhibits the growth of such tissues

by relaying energy particles to the infected area or the surrounding healthy tissues where the

ADVANCEMENTS OF PROTON THERAPY 7

tumor occurs. The extended treatment region facilitates the possibility that cancer may also

happen in healthy parts. Frequently, this area has some healthy cells which if damaged may

cause prolonged side effects. This research focuses on exploring proton therapy advancement

that aid in the effective treatment of cancer for long-term benefits of patients and also studies

neutrons and heavy-ion carbon particles.

2.0 PARTICLE THERAPY

Particle therapy is a type of radiotherapy that operates externally using energetic beams

of neutrons, protons or heavy ion for cancer treatment. This therapy is sometimes called hadron

therapy. Particle therapy works by targeting energetic particles at the tumor cells. As a result,

they damage the DNA tissues destroying the cancerous cells. The inability of the abnormal cells

to repair themselves after damage, make them vulnerable to the reaction.

2.1 Proton therapy

Proton beam therapy (PBT) was applicable in the early days although its use is still

present in the treatment of a variety of cancers today. Its usage is due to its outstanding physical

characteristics and superior dosimetry factors. PBT is radiation therapy (RT) type that improves

the survival rate of people living with cancer by enhancing treatment local tumor rate (Schippers

& Lomax, 2011). At the same time, PBT reduces the injury that could occur in healthy body

parts. Utilization of PBT results in fewer harmful effects and higher healing efficiency as

opposed to conventional RT that uses beams of X-ray. Thus, despite the high cost of PBT

equipment, there is a construction of its facilities worldwide.

A proposition of PBT took place in 1946 by William (Schippers & Lomax, 2011). After a

dozen years, it was published at the laboratory of Lawrence-Berkeley by researchers (Schippers

& Lomax, 2011). Later decades, other centers that used proton treatment emerged globally

ADVANCEMENTS OF PROTON THERAPY 8

making PBT approximately 60 years usage in the clinical setting. Its practicability by the end of

2015 was for about ten thousands victims who had varieties of cancers. Over the last decades, the

number of the upcoming programs of this treatment is developing. The reason behind the

development is that the distribution of proton dose is better than that of conventional photon one.

PBT is likely to improve patient survival rate by increasing the rate of treatment in the

affected area while at the same time decreasing the adverse effect induced. In contrary to the

conventional medication, its denser sub-atomic particles are capable of delivering their energy

more accurately to the affected cells without spreading to the subsequent tissues. According to

Schippers & Lomax (2011), photon therapy involves higher side effects which make PBT a

better option.

Conversely, PBT functions remain controversial as a result of the high cost of treatment

that comes with high maintenance and the price of the proton facility. The raised value, however,

may fail to be an issue due to its effectiveness as opposed to photon therapy. It offers improved

life quality and reduces costs that relate to advanced disease treatment. However, its adoption is

not widespread due to some challenges related to cost and technicalities as compared to photon

therapy.

These obstacles, however, do not limit the progress made in this medical system.

Recently, there are about ten centers of proton therapy in the United States and other 38 global

centers (Sakurai et al., 2016). The primary aim of PBT is its superiority in the distribution of

spatial dose in infected individuals. This proton advantage over photons increases its usability

over photon therapy such as volumetric arc therapy and modulated photon therapy (Sheets et al.,

2012).

ADVANCEMENTS OF PROTON THERAPY 9

In the US, about 80% children and 65% adults still survive after cancer diagnosis (De

Moor et al., 2013). Long-term survivors of photon treated patients are likely to exhibit fertility

complications, cardiovascular diseases, and other cancers. Today, approximately 3% of the

United States citizen is survivors of cancer that amount to 11 million individuals as stated by De

Moor et al. (2013). By 2022 the figure is likely to rise to about 18 million as suggested by De

Moor et al. (2013). Due to these projections, there is growing curiosity in the exploitation of

tissue-sparing potential of proton therapy. There is a high expectation that this therapy will

decrease the complication associated with the treatment of patients.

2.1.1 Physics of Proton Therapy

There exist advances in physics regarding proton therapy that relates to time. Similarly,

there are several mechanisms in the interaction of protons with the nucleus. Many protons move

in a straight path due to a higher mass of about 1832 times than electrons (Paganetti, 2012). In

contrast, those shifting near the nucleus have a repulsive interaction as a result of the more

significant mass of the nucleus that reflects these positive particles from their original path. The

inelastic reactions between the atom and protons are not frequent but have a profound impact.

In such reactions, the positive particles enter the nucleus, although these nuclei may emit

tritons, deuterons, protons, heavier ions or even single or multiple neutrons (Stathakis, 2010).

The figure below illustrates the interaction mechanism of protons where (a) represents energy

loss through interaction, (b) is the proton trajectory deflection as a result of repulsion that scatters

the nucleus. Finally, (c) is the primary proton removal and the making of secondary particles

through inelastic nuclear interaction.

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Figure 1: Proton interaction mechanism {(e) electron, (p) proton, (n) neutron}

Source: http://iopscience.iop.org/article/10.1088/0031-9155/60/8/R155/meta

As related to the figure above, there also exists nuclear interaction where proton interacts

through non-elastic atomic reaction with atomic resulting to transform nucleus irreversibly. For

instance, in action where core absorbs a proton, an electron gets ejected. In a therapeutic region,

the main nuclear reaction effect of a proton is usually a little absorption of the dose (Paganetti,

2012). The absorption occurs due to the elimination of primary proton. This reaction gets

compensated by production of secondary protons and other charged particles. As the proton get

depleted gradually, other protons become liberated due to the activity.

The reduced protons number at the range end, occur due to ions that come out and their

absorption occurs within the medium. For a proton to enter a nucleus, it must have enough

energy to overcome the nucleus barrier that becomes determined by the atomic number as shown

below.

ADVANCEMENTS OF PROTON THERAPY 11

Figure 2: An inelastic nuclear reaction against the energy of proton across the atomic barrier

Source: www.nds.iaea.org/endf

The different atomic action is essential to clinical PBT where the result can produce

energetic triton, proton, deuteron,

He,

He and other ions. 10% of the proton include the

secondary ones that have little and non-negligible effects in the patient scattered dose

distribution (Paganetti, 2012). Heavy carbon ions and deuterons occur in a small amount

accounting for 1% or less of the total dose absorbed during therapy. These particles energy is

little, and they produce their kinetic energy near the creation point.

Approximately high beams of protons occur in the equipment delivered to the patients,

and they produce neutrons that bring about safety hazards. The personnel ensures that they limit

the exposure of neutron to the patients. Care must be taken to harden and shield the electronic

system so that the neutrons do not damage them. Attention is also necessary when activating the

neutrons in water, air, and other materials. The strength of neutrons is highly dependent on the

direction and the energy of the proton beam (Schippers & Lomax, 2011).

ADVANCEMENTS OF PROTON THERAPY 12

2.1.2 PBT Physical Aspect

There exist heavily charged particles called protons that have a relatively higher mass

than electrons. This mass and induced acceleration provide every proton a particular momentum

that becomes produced after moving to a specified direction where it slows down after meeting

with the targeted section. This interaction increases the energy deposited at the end of the proton

path. Here, there is no further delivery of the dose hence called Bragg peak (Stathakis, 2010).

This property offers a significant advantage over electrons or photons. Thus, instead of

traversing the target, there is movement hindrance of these protons at the depth where energy is

necessary. There is no exit dose which entirely spares destruction of healthy tissues.

Generation of beams of these positively charged particles is by synchrotron or cyclotron

which accelerate them to the required target. The figure below shows the percentage distribution

of depth-dose proton beam curve versus photon beam. The curve implies that at a certain depth,

the proton beam does not offer extra dose, unlike the photon beam.

Figure 3: Percentage depth-dose distribution curve of proton beam vs. photon beam

Source: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5772792/

ADVANCEMENTS OF PROTON THERAPY 13

In the curve above the conventional radiation depicts a reducing deposition of energy

with raising depth of the tissue. On the other hand, protons demonstrate an increased build-up of

energy with penetrating intensity that leads to a Bragg peak. Protons that penetrate through the

tissue decelerate when losing power in the nuclear or atomic interaction events. This movement

decreases the proton energy and as a result increases the interaction with the electrons in orbit

(Paganetti, 2012).

Optimum interaction with these harmful particles occurs at the range end leading to the

release of maximum energy within the required area. This characteristic is more advantageous

than that of photon radiation because there is deposition of maximum intensity in the targeted

region which is generally created by the Bragg peak spread-out. As a result, there is a high

possibility of tumor volume coverage with increased accuracy. Also, the technique offers lower

doses to the uninfected tissues than the electron technique. Similarly, there is a slight difference

between the two methods at the lateral penumbra (Paganetti, 2012). The level of penumbra for

proton beams is broader than that of a photon.

2.1.3 PBT Biological Features

In radiotherapy, the determination of proton dose is by multiplication of the relative

biological efficiency (RBE) and physical treatment. Therefore, the natural and clinical impact

may vary when the dose is constant, and the radiation quality deviates. Paganetti (2012)

explained that RBE helps to link the effect to a radiation of

Co. RBT exterior uses electrons

and photons where the RBE usually is 1. The distribution properties of proton dose differ unlike

those of photons. This variation enables them to avoid targeting surrounding areas.

ADVANCEMENTS OF PROTON THERAPY 14

The momentum usually slows down after interactions that become associated with the

charge and their mass. They are then stopped abruptly at a particular depth where the proton

interact with the surrounding electrons releasing energy that causes molecule ionization

destruction of radiation of the target cell’s DNA (Westerly et al.,2013). These protons have

reduced linear strength, and the damage they cause on the tissue is generally by the break of a

single strand of DNA. It results in loss of sub-lethal radiation and its subsequent repair.

The determination of biological impacts is by every dose per treatment which is usually

higher than

Co and X-ray energy. In such an instance, the proton RBE is generally 1.1. Near

the edge of the proton range, the power raises hence increasing the RBE. Given that RBE used in

proton planning is 1.1, then the changing RBE at the range end is usually ignored (Schippers &

Lomax, 2011). The PBT with angles is not applicable in treating critical organs with tumors.

Instead, multiple beams are suitable in such an area to spread out the uncertainty range end. Use

of pencil beam scanning requires an evaluation of the dynamic delivery interaction with the

shifting target and then minimized (Westerly et al., 2013).

2.2 Proton Therapy Advancements

Proton therapy is ever growing and involves a combination of various innovation that

shows an enlarging role for proton therapy. These advancements are as a result of new

technologies that increase the precision even better. The improvements are:

2.2.1 Pencil beam scanning (PBS)

The PBS is a type of proton therapy that further raises the dose conformity. It deposits

more radiation than the previous PBT directly in the infected cells, while still preserving the

healthy tissues from harm. The advantages of this therapy are many enabling more patients to get

assistance from it. It reduces or nearly gets rid of the neutron scattering, more so when treating

ADVANCEMENTS OF PROTON THERAPY 15

pediatric cancer. This therapy increases the chance to dose paint hence sparing healthy tissues in

the surrounding from the high dose tumor capacities (Westerly et al., 2013). Moreover, it is

faster implying that patients with multiple complications can get treatment in only 30 minutes.

This speed allows for more patients to become treated as per the schedules.

This type offers a narrower and single proton beam which becomes magnetically moved

across cancer. It does not need a beam-shaping gadget. This kind of technology provides a more

accurate 3-D beam that corresponds to the depth and shape of the tumor (Gill et al., 2014).

Further, the PBS reduces the impacts that surround healthy brain tissues, critical organs and the

cells adjacent to the infected region hence decreasing the side effect. Such therapy is more

appropriate for cancers with complex shapes that are near vital organs.

2.2.2 Paralleling PBS

This technology help in hardware downscaling. Gill et al. (2014) claimed that the

advances in imaging are essential in enhancing treatment planning and facilitating adaptive

treatment by enabling optimization of the medication as cancer reduces over time. Such

advancement minimizes the proton therapy cost as they shorten the planning and treatment

duration. They also aid in making the facilities and equipment smaller which in turn benefit the

payer, patients, and the hospital system as well as the overall society.

2.2.3 Intensity modulated proton therapy (IMPT)

It is a faster technology developed by Mevion, and it is made from Hyper-scan PBS

hence quicker and precise. It is made for a single room and has features such as adaptive aperture

and reduced profile minute multi-leaf collimator which acquires 2-3mm correct sizes necessary

for all energy (Sheets et al., 2012). The Mevion also had a plan of partnering with the photon

makers to combine the CBCT mechanism to enhance the volumetric images. The IBA treated

ADVANCEMENTS OF PROTON THERAPY 16

50,000 patients in 2016 September with their system after introducing a small proton therapy

system called Proteus One.

2.2.4 Proteus One

This innovation operates in a single room whereby it offers different methods of delivery

such as IMPT and other proton therapy mechanisms that are image-guided. The centers made

globally by the IBA occur in countries like UK, France, Belgium and Japan (Sakurai et al.,

2016).

2.2.5 Pro-Beam System

The technology is an even smaller version made by Varian that provides similar benefits

as the other proton therapy techniques including extensive peak scanning that facilitates

application of rays simultaneously from a various angle for IMPT (Schippers & Lomax, 2011).

Moreover, the space for its cyclotron is more effective than the linear accelerators.

2.2.6 PT-specific version

This model uses software called eclipse planning that conjoins with both systems of Pro-

Beam treatment. This software uses many protocols such as standardization and automation to

ensure the workflow is smoothly carried out especially the Smart Segmentation (Sakurai et al.,

2016). There include other characteristics such ass field specific target (FST) that aid in

compensation of range uncertainty, target motion difficulties as well as setup error that surrounds

the target volume in the facility.

2.3 Neutron therapy

This therapy type is highly efficient in treating cancer, unlike the conventional radiation

that does not destroy the radio-resistant anomalies. While traditional therapy involves electrons

and X-ray radiation, hadron therapy uses the protons and neutrons generated by the use of

ADVANCEMENTS OF PROTON THERAPY 17

deuteron or proton accelerators. The main impact of ionizing radiation is to kill the ability of

tissues to divide by breaking down their DNA strands (Barth et al., 2012).

Figure 4: Comparison of high LET and low LET electrons

Source: (Barth et al., 2012)

Electron, proton, photon radiations use activated radical of low linear energy

transmission (LET). On the other hand, neutrons use high LET radiation to damage the DNA by

use of nuclear interaction as demonstrated in the figure above. Given that the use of low LET

radiation destroys a tumor cell, chances of repairing itself and continuing to grow high unlike

when using high LET radiation that damages the tissues thoroughly preventing them from

regenerating (Barth et al., 2012).

ADVANCEMENTS OF PROTON THERAPY 18

Figure 5: Photon therapy

Sources: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4691008/

The figure above is a photon therapy photo. The photon hits the atomic particles in the

cancerous cells hence displacing its outer negative ions (e

). Given the atom get hold of the lost

electrons, the DNA of the tumor can reconstruct itself and continue harming the patient (Barth et

al., 2012).

Figure 6: Neutron therapy

Source: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4691008/

ADVANCEMENTS OF PROTON THERAPY 19

The figure above is a neutron therapy picture. It illustrates that an incoming neutron can

destroy the cancerous cells via nuclear activities which splits these affected cells into a pair of

distinct atoms that cannot recombine hence preventing further tumor growth.

Generally, fast neutrons can get rid of the massive tumor since they do not require

oxygen to kill these cells. Additionally, the biological effects of neutrons are not dependent on

the stage or time of cancer cells lifecycle as opposed to low LET rays. Neutron destruction of the

tumor cell is via nuclear interaction whereby atoms splitting into the affected cells are effectively

preventing them from recombining (Barth et al., 2012).

In such a case, use of neutrons is efficient and controlling the primary tumors after which

chemotherapy becomes utilized in limiting the spread of this cancer to the other parts. Due to the

neutrons effectiveness biologically, the needed tumor dose necessary for killing the cancer cell is

approximately one-third of those used by proton, electron or photons. Neutron therapy full

course requires about 10-12 treatments, unlike low LET radiation that needs 30-40 medication.

This medication is offered in the Fermilab and the Northern Illinois University (Barth et al.,

2012).

Neutrons deposit increased energy along the cancer path unlike gamma or X-rays

resulting to more damage of such cells. The use of cyclotron accelerator that releases a proton

and a strong magnet bend series with the aim of targeting the beryllium area that produces

neutrons after an interaction. The uniqueness of this neutron makes it only available in the US at

three locations. Its utility has made it possible to treat more than 3100 people. The figure below

is an illustration of the relative efficiency of neutrons and photon therapy. For one to reduce the

tumor cells number to 0.001 fractions of the previous number, a photon dose of 28 grays as

opposed to the 7 gray of the neutron is necessary as stated by Barth et al. (2012). The reduced

ADVANCEMENTS OF PROTON THERAPY 20

grays indicate that the neutrons are more efficient four times than photons in eradicating the

cancer cell.

Figure 7: Survival of cancer cell

Source: https://www.sciencedirect.com/topics/medicine-and-dentistry/cell-survival-curve

The neutron has high effectiveness on ACC type of cells, unlike other cancer types. It has

successfully destroyed the cancer of the salivary gland, the inoperable sarcomas, adenoid-cystic

carcinoma and prostate cancer. It also can ruin tumors of the neck and the head and with it,

comes with other advancements in this research that provide other alternative measures to cancer

eradication.

2.4 Heavy ion carbon therapy

Application of this treatment is based on an essential principle of acquiring the exact dose

localization in the targeted area. At the same time, it aims at decreasing damage to the tissues

surrounding the tumor. Therapy of charged particles containing carbon ions and protons

facilitates high deposition of localized energy utilized for raising the radiation doses to the target

area while reducing irradiation to the adjacent healthy cells as shown below. Moreover, the

beams of the carbon ions have some biological merits concerning reduced oxygen facilitation

ADVANCEMENTS OF PROTON THERAPY 21

ratio and high linear energy transmission (Schardt et al., 2010). There is also decreased volume

for sub-lethal and increased damage repairs.

Figure 8: Minimized irradiation of C-ions to the adjacent areas

Sources: http://www.mdpi.com/2072-6694/10/3/75/pdf

Consequently, there is decreased tissue cycle radiosensitive dependence as opposed to

those using X-rays and proton beams. Despite this effectiveness, the C-ion RT, there exist a few

centers that are operative that use the carbon ions. Recently, there are constructions of more

facilities globally. Unfortunately, the operation and construction cost of these facilities is a

challenge facing C-ion RT application.

The facility uses electron-cyclotron resonance (ECR) that produces the ions. There is

assembling of permanent magnets used to generate magnetic field and sextuple. In comparison

with conventional type, the kind of ECR in the C-ion RT has a magnet that is small in size but

useful and straightforward to maintain and operate (Schardt et al., 2010). The construction of

ECR is such that the design starts working without having to warm the carbon therapy.

ADVANCEMENTS OF PROTON THERAPY 22

Compared with the protons, these carbon ions are heavier and hence accumulate more energy to

the tumor resulting in more destruction of these cells.

Again, the C-ions require only a few sessions of treatment. For instance, treatment of

liver cancer only requires thirty days of treatment with proton therapy, but when using carbon, it

just takes four days. Patients treated with carbon especially those with tumors of the brain have a

survival rate of about 90%. When using C-ion, risky organs are typically spared especially the

brain stem. Schardt et al. (2010) argued that survival rate of those treated against pancreatic

cancer is about 48% unlike where radiation and chemotherapy are used resulting to

approximately 10-20% (Schardt et al., 2010). However, there are delivery challenges of these

beams. The ions can efficiently treat liver, rectal, prostate, lung cancers and soft tissues and

bones sarcomas which are known to have radiation resistance.

About 60 carbon ion centers can be appropriately used to treat global demand of those

with cancers. Although there are heavier elements than this ion, they tend to damage healthy

tissues while at the same time targeting tumor. However, for the tumors that are highly

insensitive to radiotherapy, high-density oxygen ions are desirable to use. As opposed to protons,

the carbon ions are harder in locating targeted cancer. The countries that use the carbon therapy

include Italy, Japan, China, and Germany. Use of this therapy globally will be more versatile and

cheaper than that of Heidelberg facility (Yeung & Palta, 2013).

Among other ions, carbon has the potential to treat cancer due to its ideal properties and

the capabilities of killing the effects brought about by the disease. In the C-ion RT, the ions

accelerate to the speed of light of about 70% to attack the tumors located inside the body as

shown in the figure below. As opposed to these ions, the conventional X-ray radiations reduce as

they penetrate in the body. The carbon ions radiation penetrates faster with the aim is producing

ADVANCEMENTS OF PROTON THERAPY 23

Bragg peak. As such, it can select, through irradiation, the abnormally accelerated cells (Yeung

& Palta, 2013).

Figure 9: Target cancer irradiated with heavy-ion beams

Source: http://www.mdpi.com/2072-6694/10/3/75/pdf

With this radiotherapy, a significant dose gets concentrated in the target region whereby a

peak conforms to the position and shape of that lesion. To deliver these beams precisely to the

irregularly shaped abnormalities, individually designed devices called collimator and filter are

applicable in this sector. The irradiated ions of carbon are singularly emitted easing the

minimization of unrequired doses to critical tissues and organs such as the intestines, spinal cord

and brain stem (Yeung & Palta, 2013).

3.0 DISCUSSION

ADVANCEMENTS OF PROTON THERAPY 24

3.1 Proton Therapy for different Cancers

3.1.1 Head and neck cancers

Patients with this challenge can benefit from this therapy. This type of treatment can

reduce the risk from recurring by raising the dose to cancer. As a result of a small dose of the

maxilla, mandible and salivary glands, there are high chances of decreasing the threat of dental

caries, xerostomia, osteoradionecrosis and dental extraction. An increased dose of PBT can aid in

the improvement of the rate of local control of respiratory cancer (Yeung & Palta, 2013).

Patients with this condition have a higher survival chance than those if they continuously control

the primary lesions.

Focusing on intraocular melanoma, the use of surgical approach is essential since there is

a chance of sensitivity while using both plague brachytherapy and proton therapy. While using

PBT, there are high merits which include no surgery requirement, hospitality stay and the

medical workers are not at risk of the exposure. The treatment can occur in five days only as

argued by Barth et al. (2012). As a result, patients prefer this therapy, unlike the radioactive

method. Ocular tumor such as benign, melanoma, and malignant that uses the PBT become

associated with the primary development and achievement with time.

In uveal melanoma, there are fewer risks of recurrence of the tumor while using PBT as opposed

to other forms of treatment. PBT can be applied as the primary salvage or combined with

modality treatment. The physical qualities of PBT are that it allowed for the minimum spread,

uniform distribution and increased the dose on the ocular tumors where critical structures exist.

PBT can prevent the spread of cancer from the collateral destruction of the adjacent cells while

increasing radiation doses hence useful for ocular tumor control. The therapy of uveal melanoma

ADVANCEMENTS OF PROTON THERAPY 25

and other ocular cancers evaluation has been extensive, and PBT stands out compared to other

(Yeung & Palta, 2013).

When focusing on the chordoma of the skull base, results show that there are higher

chances of control of tumors in the long run while using PBT instead of X-ray without increasing

further risk. Further studies can help improve the treatment plan of PBT to help overcome the

disease in delicate organs (Barth et al., 2012). Similarly, PBT can treat paranasal and nasal

lesions, and skull base lesions. PBT can also reduce optic nerve, CNS, and eyes problems.

3.1.2 Thoracic tumors

Lung cancer is a widespread tumor type that requires radiotherapy intervention. PBT has

the potential to minimize the RT toxicity through its Bragg peak characteristic. In contrast, with

a photon, proton therapy plans may produce reduced doses to the nearby tissues at risk including

bone marrow, esophagus and lungs hence the improvement of the therapeutic ration. Early

treatment using PBT demonstrated that the patients with lung cancers could use medication that

has both PBT and chemotherapy to minimize the toxicity rate and achieve higher survival

chances. This treatment is insignificant with 3DCRT and photon therapy (Yeung & Palta, 2013).

Past results show that PBT is more advantageous in term of dose escalation which

enables the sick to survive for long with lowered risks of severe toxicity and recurrence and

increased chemotherapy. PBT is efficient and a safer option for treatment of stage three NSCLC

(Yeung & Palta, 2013). Unfortunately, the delayed toxicities are vague, and the patients must

continuously follow up for detection of such risks. For gastro-esophageal and gullet cancers, the

food pipe is centrally located in the thoracic cavity. Therefore, there is a need to balance the dose

to the targeted cells while at the same time decreasing the dose to the adjacent tissues. The

reason behind this is that the toxicities may result in myocardial and pneumonitis infection.

ADVANCEMENTS OF PROTON THERAPY 26

Technological advancement such as IMRT, a photon therapy reduces such harmfulness,

although a lot of evidence shows that PBT is capable of minimizing this risk further (Fuji et al.,

2014). The fact that PBT has an exit dose equivalent to zero; there is a high chance of reduction

of exposure of radiation to the normal tissues hence increasing the benefit in the treatment of

gullet cancer. Furthermore, complications related to the heart and high rate of death can be

minimized by this therapy while treating cancer of the gullet. Without chemotherapy, high dose

of proton therapy can be safe and more efficacious for treating clients with esophagus ailment.

Generally, there is emerging evidence that suggests that proton therapy may reduce toxicities,

unlike conventional radiotherapies. This suggestion provides future hope for esophageal cancer

medication.

Breast cancer treatment, on the other hand, is cost efficient when using PBT as

demonstrated by different researchers unlike X-rays and electron beams (Fuji et al., 2014). At the

same time, it is technically feasible and safer. Furthermore, it improves the normal tissues'

healthy life by sparing them. As compared with interstitial and intracavitary brachytherapy, this

therapy is cheaper.

3.1.3 Abdominal and pelvic cancers

Despite the use of PBT in treating prostate cancer for various years, the treatment is still

controversial. The purpose of this therapy in the medication of prostate tumor has no advantage

over IMRT. Also, current treatment varieties including IMRT, prostatectomy, and brachytherapy

are better options due to their cost-effectiveness unlike the PBT (Fuji et al., 2014). Therefore,

further research is necessary to assess the clinical advancement required for medication of

prostate cancer using PBT. This advancement should be in term of minimizing acute and the

long-run toxicity of the radiation as well as improvement of cancer control. There is little

ADVANCEMENTS OF PROTON THERAPY 27

intervention regarding the significance of PBT use for healing this cancer. However, PBT is safer

in reducing localized cancer although it requires optimization. Further studies are fundamental to

address the social, economic issues, safety, adverse impacts and quality life.

3.1.4 Pediatric Cancers

Radiotherapy technology is essential in treating cancer-related to organs and tissues

although they have adverse effects that require renovation. This challenge occurs more in the

pediatric patients as a result of tissues and organs and longevity. The RT affects the growth and

development of the endocrine parts hence affecting their functions (Fuji et al., 2014). Therefore,

the impacts on the healthy tissues should get reduced when using this conventional therapy. On

the other hand, PBT has the merit of minimizing the exposure of these tissues to a therapeutic

dose that may lead to lower adverse effects hence preferable in the medication.

Studies show that treating pediatric tumors such as bone sarcoma, orbital

rhabdomyosarcoma, medulloblastoma, pelvic soft tissue sarcoma and retinoblastoma using PBT

has an advantage over the X-ray therapy. In children, reports were suggesting that use of RT

resulted to secondary cancer unlike when using intensive proton therapy. The raised threats of

valvular dysfunction and coronary artery problems were due to their association with cardiac

irradiation as the medication of Hodgkin's lymphoma using X-ray (Fuji et al., 2014). Thus, the

minimization of pain, mortality, morbidity and raised hospital bills of these remnants, proton

therapy is a better option. Irradiating the dose to the healthy organs should, therefore, be

minimized considerably by employing PBT advancement in treating the pediatric tumor.

3.1.5 Other tumors

Proton beam therapy is vital in treating anal and rectal tumors, especially when using the

lower dose in hip joints, bowel, and bladder. Again, it can be applicable in treating pancreatic,

ADVANCEMENTS OF PROTON THERAPY 28

hepatobiliary and gastric tumors since PBT has the capability of delivering minimized dose to

the lung, liver, heart, small bowel, kidney and spinal cord. Similarly, it is applicable in the

treatment of soft tissues and bone sarcomas.

3.2 Controversies of PBT

The central debate in PBT is cost-oriented. There is an argument about who should

receive therapy and pay the bill since the new centers are expensive (Efstathiou et al., 2013). The

high prices of proton therapy hinder patients' accessibility to PBT centers. There exist resources

that make disease treatment adequately handled with old type cause debate if the treatment with

proton therapy even if it has an additional incremental benefit on health. So far, the most

argument to date for this therapy comes from the prostate cancer treatment. It occurred where the

paradigm shift context for cancer and its treatment require the most significant amount of money

for either the proton or proton-based radiation center.

The most current research, publicized by Yale, show that IMRT for cancer may be

similar to that of expensive proton therapy in males aged 66 and above (Efstathiou et al., 2013).

Given that the two treatments have the same cost, there would be a lesser controversial issue

(Efstathiou et al., 2013). No further study reveals a long-term conclusion on the patient since the

recently reported research covered only a year follow up hence, unclear if the argument is valid.

Given that the cost will lower down, particle therapies especially proton therapy will be less

controversial.

3.3 Drawbacks of PBT

Recently, protons have huge limitations comparative to photons that healthcare providers

must comprehend to utilize the opportunities that enhance treatment. First, the PBT is not

globally available. As a result, patients hear it from their referral clinicians although superior to

ADVANCEMENTS OF PROTON THERAPY 29

X-ray therapy (Barth et al., 2012). The considerable cost of traveling and housing can prevent the

patients from utilizing this technology although physicians want to make use of proton. Second,

it is a long process to go through proton therapy than photon therapy. As a consequence, it is

only applicable for emergency cases.

Third, the PBT needs the treatment team to have the required expertise to control

different types of cancer; be it multiple tumors that are in the spine or brain in adult and children.

As the proton centers increase in number, the best methods of exploiting them will become

globally taught and comprehended. Fourth, the proton beam dosimetry, in the biological sense, is

not linear and the procedures present for mitigating the raised biologic dose at the Bragg peak

end are not so apparent to the individuals who do not carry proton therapy practice routinely.

There is a need for careful attention in beam selection, pausing location and the beams number

information is necessary to prevent unexpected results.

Fifth, protons are more complicated than photons hence tricky to routinely fix them. This

limitation implies that staffing is an essential factor to these centers unlike in photon facilities.

The curve of learning the protons is somehow challenging, and the opportunities of studying are

more limited resulting to difficulties in staffing the centers of PBT. Finally, due to the sensitivity

of proton therapy to distance, to the stopping point from where the patient is, it is possible to

miss out the location when using proton compared to the photon. By mitigating this scenario,

clients need to be carefully assessed routinely and most probably imaged with IMR scan or high-

quality CT to determine significant changes (Barth et al., 2012). The department that applies

protons in their work must, therefore, respond to these changes faster to avoid patients from

exhibiting risky issues.

ADVANCEMENTS OF PROTON THERAPY 30

4.0 CONCLUSION

This research focused on exploring proton therapy advancement necessary for effective

treatment of cancer for long-term benefits of patients. It further studied the neutrons and heavy-

ion carbon particles. As tackled, PBT is of high relevance. It is a radiation therapy type that

requires acceptance in the society. The upcoming technology in this field makes it benefiting

than photon therapy. The reason being that it only focuses on the targeted cancerous tissues and

no other parts hence limited adverse effects as opposed to conventional therapies. However, the

cost of this treatment is expensive making it unavailable and its application reduced.

Only time will tell if this technology will have a lower cost to encourage its utility

routinely. In the current days, this technology is a topline consideration in the medication of

thoracic, head and neck, pelvis, and pediatric and other tumors. Other treatment can occur

especially for patients who have prostate, breast and lung cancer. For sure, PBT is not as

effective, in many ways, as the conventional therapies due to the discussed controversies and

limitations.

As a result, it is difficult for patients to apply this method. By discussing the issue with

the centers, the referral clinicians should be able to encourage patients to take this option.

However, proton therapy aims at staying and treating different types of cancers and

complications. The advancement will occur because there exist varieties of clinical trials

targeting at making this process less costly and more effective. Moving ahead with technology

will facilitate the radiation oncologists to create a better future that offers hope for the cancer

patients due to fewer side effects.

ADVANCEMENTS OF PROTON THERAPY 31

5.0 RECOMMENDATION

In about 4-5 years to come, physicists such as Yeh and Lennox have proposed a new

version of cancer therapy capable of treating 3000 patients per year using limited time possible

per patient. This new invention would have new techniques, equipment, and accelerators for both

proton and neutron therapy and more advances in the hadron therapy field. The proposed

innovation would be comparable with neutron, photons, and protons of the current generation.

This comparison would be essential for evaluation purposes that would help in the development

of a better mechanism capable of destroying many cancer types.

Therefore, there is need to recognize, create, analyze, apply and manage information and

knowledge that relate to proton beam therapy. This knowledge is to help transform the delivery

procedure of cancer care and to enhance accountability. Again, it will aim at providing

affordable technology that has reduced harm and cost to the society at large, patients, oncologists

and nurses. The technology will require a better definition for clients to benefit the most from

PBT. Also, there will be the need for determining the side effects and other outcomes such as

overall survival, tumor control, cost efficiency and clients' feedback.

Further medical research is necessary to determine the kind of patients to benefit from

proton therapy. Again, referral cases should become well debated among the multi-disciplinary

team including the oncologist and clinicians. This discussion will help determine the required

funding for different ministries of health. After approval, the duty for the referral, the

communication teams with the facility of proton beam therapy and the post-therapy follow up

should proceed with the targeted oncologists as indicated in the appendix.

ADVANCEMENTS OF PROTON THERAPY 32

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Beam-Therapy-Exploiting

ADVANCEMENTS OF PROTON THERAPY 34

APPENDIX

Recommended healthcare pathway.

Source: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4189565/

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