Progress in Nuclear Energy

Dose Analysis in Oral Cavity Cancer Therapy Using Boron Neutron Capture Therapy
Method Using PHITS 3.26
--Manuscript Draft--

Manuscript Number:

Article Type: Research Paper

Keywords: BNCT, Radiotherapy, Oral Cavity Cancer, PHITS

Corresponding Author: zuhdi ismail

INDONESIA

First Author: Ahsani Mufidah

Order of Authors: Ahsani Mufidah

Bambang Jati

Yohannes Sardjono

Isman Triatmoko

Gede Wijaya

zuhdi ismail

Suggested Reviewers: Tatsuhiko Sato

sato.tatsuhiko@jaea.go.jp

Yaser Kasesaz
ykasesaz@aeoi.org.ir

Hossein Khalafi
Hossein_khalafi@yahoo.com

Opposed Reviewers:

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Cover Letter

Zuhdi Ismail
National Research and Innovation
Agency of Indonesia
Jakarta

April 26, 2023

Dear Editor-in-Chief of the Journal of Progress in Nuclear Energy,

We wish to submit an original research article entitled “Dose Analysis in Oral Cavity Cancer Therapy
Using Boron Neutron Capture Therapy Method Using PHITS 3.26” for consideration by the Journal of
Progress in Nuclear Energy
We confirm that

 this work is original and has not been published elsewhere, nor is it currently under
consideration for publication elsewhere.

 All the authors equally contributed as the main contributors to this paper. All authors read and
approved the final version of the paper.

 All authors have been personally and actively involved in substantial work leading to the paper
and will take public responsibility for its content.

 This study did not receive any specific grant from public, commercial, or not-for-profit funding
agencies.

 All sources used are properly disclosed (correct citation). Copying of text must be indicated as
such by using quotation marks and giving proper references.

 We have no conflicts of interest to disclose.

Please address all correspondence concerning this manuscript to me at zuhdi.ismail@brin.go.id.

I appreciate your consideration of this manuscript.

Sincerely,

Zuhdi Ismail
Title page Click here to view linked References

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12 Dose Analysis in Oral Cavity Cancer Therapy Using Boron Neutron
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14 Capture Therapy Method Using PHITS 3.26
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23 Ahsani Mufidaha, Bambang Murdaka Eka Jatia, Yohannes Sardjonob, Gede Sutresna Wijayab, Isman
24 Mulyadi Triatmokob, Zuhdi Ismailb*
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* Corresponding author. Tel.: +62-857-2558-0001.
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E-mail address: zuhdi.ismail@brin.go.id
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Title page

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14 a
15 Department of Physics, Faculty of Mathematics and Natural Sciences, Gadjah Mada University,
16 Yogyakarta, Indonesia
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20 b
Research Center for Safety, Metrology and Nuclear Quality Technology – National Research
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and Innovation Agency of Indonesia, Tangerang Selatan, Indonesia
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* Corresponding author. Tel.: +62-857-2558-0001.
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E-mail address: zuhdi.ismail@brin.go.id
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Abstract

Abstract
Dose analysis research on oral cavity cancer therapy with Boron Neutron Capture Therapy (BNCT) was carried out to determine
the amount of equivalent absorption dose in healthy tissue around the oral cavity, as well as to find out how long the irradiation
time is when variations in boron concentrations are carried out in the tissues of the head and neck. This study was conducted by
simulation using particle and heavy ion transport code system (PHITS) 3.26 by providing input files in the form of geometry,
material, and Tally data to calculate the dose rate. Phantom geometry was depicted with phantom reference from Oak Ridge
National Laboratory (ORNL) for Adult Asian Men. Material data were obtained from the International Commission on Radiation
Units (ICRU) analysis and the International Commission on Radiological Protection (ICRP). The dose rate calculation in Tally
was carried out by providing variations in boron concentrations from 20, 40, 60, 80, 100, 120, and 140 μg/g of cancerous tissue.
The results of this study show that the greater the concentration of boron injected into the body, the value of the dose rate will
increase, and the irradiation time will be shorter. The shorter irradiation time will result in a smaller dose of equivalent absorption
of healthy tissue.

Keywords: BNCT, Radiotherapy, Oral Cavity Cancer, PHITS

* Corresponding author. Tel.: +62-857-2558-0001.

E-mail address: zuhdi.ismail@brin.go.id
Manuscript File Click here to view linked References

1
2
3
4
5
6
7
8
9
10
11
12 Dose Analysis in Oral Cavity Cancer Therapy Using Boron Neutron
13
14 Capture Therapy Method Using PHITS 3.26
15
16
17 Ahsani Mufidaha, Bambang Murdaka Eka Jatia, Yohannes Sardjonob, Gede Sutresna Wijayab, Isman
18 Mulyadi Triatmokob, Zuhdi Ismailb*
19 a
20 Department of Physics, Faculty of Mathematics and Natural Sciences, Gadjah Mada University, Yogyakarta, Indonesia
b
Research Center for Safety, Metrology and Nuclear Quality Technology – National Research and Innovation Agency of Indonesia, Tangerang Selatan,
21 Indonesia
22
23
24
25
26
27 Abstract
28 Dose analysis research on oral cavity cancer therapy with Boron Neutron Capture Therapy (BNCT) was carried out to determine
29 the amount of equivalent absorption dose in healthy tissue around the oral cavity, as well as to find out how long the irradiation
30 time is when variations in boron concentrations are carried out in the tissues of the head and neck. This study was conducted by
31 simulation using particle and heavy ion transport code system (PHITS) 3.26 by providing input files in the form of geometry,
32 material, and Tally data to calculate the dose rate. Phantom geometry was depicted with phantom reference from Oak Ridge
33
National Laboratory (ORNL) for Adult Asian Men. Material data were obtained from the International Commission on Radiation
34
35 Units (ICRU) analysis and the International Commission on Radiological Protection (ICRP). The dose rate calculation in Tally
36 was carried out by providing variations in boron concentrations from 20, 40, 60, 80, 100, 120, and 140 μg/g of cancerous tissue.
37 The results of this study show that the greater the concentration of boron injected into the body, the value of the dose rate will
38 increase, and the irradiation time will be shorter. The shorter irradiation time will result in a smaller dose of equivalent absorption
39 of healthy tissue.
40
41 Keywords: BNCT, Radiotherapy, Oral Cavity Cancer, PHITS
42
43
44 1. Introduction
45
Cancer of the oral cavity is a group of diseases characteristic of uncontrolled cell growth accompanied by an abnormal spread
46
47 in the oral cavity area. Oral cavity cancer is the most common cause of head and neck cancer. In Indonesia in 2020, oral cavity
48 cancer was ranked 17th in cancer cases with a total of 5,780 patients, with death cases ranked 11th with a total of 3,087 deaths
49 [1].
50 Several methods are chosen to treat oral cavity cancer, such as surgery, chemotherapy, and radiotherapy. Surgical methods
51 constitute a significant modality in cancer therapy[2]. However, from the existing methods, it is considered that it still has some
52
shortcomings. In the surgical method, this therapy cannot be used in cancer cases with a deep enough location from the skin's
53
54 surface. Furthermore, the radiotherapy method also still has dangerous side effects for oral cancer therapy patients, namely,
55 radiation exposure caused by radiation therapy can potentially damage healthy tissue around the cancer tissue[3], [4].
56 Chemotherapy methods it is also considered that it still has some shortcomings and side effects, namely the frequent occurrence
57 of malabsorption and hair loss in post-therapy patients[5], [6].
58 Research and subjugation of cancer therapy must be carried out to increase cancer patients' life expectancy and reduce the
59
risk of recurrence for post-therapy patients. Analysis for oral cavity cancer is also carried out as an effort to develop existing
60
61
* Corresponding author. Tel.: +62-857-2558-0001.
62
E-mail address: zuhdi.ismail@brin.go.id
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 therapeutic methods considering that patient safety is the main thing. Boron Neutron Capture Therapy (BNCT) is offered as one
of the therapeutic methods for curing oral cavity cancer, in this BNCT is a form of upgrading from radiotherapy methods but
will only focus radiation exposure on cancerous tissues[5]–[8]. BNCT is carried out by exposing neutron beam radiation to
1 cancer tissues that have been given boron compounds before. Neutron beams used in BNCT therapy are sourced from cyclotron-
2 type accelerators with an output of 30 MeV protons. The output of this cyclotron will be moderation and collimation at the Beam
3 Shaping Assembly (BSA) to produce neutron rays that are safe for the body but can still damage cancerous tissue[9]–[11].
4 The design and simulation of oral cavity cancer therapy using the BNCT method was carried out using one of the Monte
5 Carlo programs, the Particle and Heavy Ion Transport Code System (PHITS). PHITS is used in designing simulations of oral
6
7 cavity cancer therapy and calculating dosimetry due to reactions between neutrons and the material contained in BNCT therapy.
8
9 2. Computational Methods of BNCT Dosimetry in Oral Cavity Cancer Therapy
10 2.1. Oral Cavity Cancer
11 Cancer is a group of diseases with characteristics of uncontrolled cell growth accompanied by abnormal spread, which
12
external or internal factors can cause. Cancer occurs at several locations/points in the oral cavity with distribution: 32 % occurs
13
14 in the buccal mucosa, 22% occurs in the tongue, 11% in the lower lip, 11% in the palate, 8% in the vestibulum, 5% in the
15 alveolus, 5% in the floor of the mouth, and 3% in the gingival [12]. The most common type of oral cavity cancer is Oral
16 Squamous Cell Carcinoma (OSCC) or Oral Squamous Cell Carcinoma of the oral cavity. SCC, or Squamous Cell Carcinoma, is
17 the most common cause of cancer in head and neck cancer, with 90% of head and neck cancers being SCCs[13]. Squamous cell
18 carcinoma of the oral cavity appears due to various risk factors. Some of the common risk factors associated with oral cancer
19
include tobacco and alcohol intake, as well as several other supporting elements[14].
20
21
2.2. Neutron Interaction with Matter
22
23 The interaction of neutrons with matter occurs when neutrons move closer to the atomic nucleus of a case and enter the field
24 of influence of the atomic nucleus of an issue. Then several possibilities will occur, namely:[15].
25 1. Elastic Scattering Reaction (n, n)
26 Elastic scattering reactions occur due to collisions between neutrons and the nucleus of a matter, and neutrons will scatter
27 after pounding the atomic nucleus. Elastic scatter reactions condition that momentum and kinetic energy are or are not changed
28
before and after the collision.
29
30 2. Inelastic scattering reaction (n, n')
31 In an inelastic scattering reaction, in the collision process, the neutron will hand over part of its kinetic energy to the atomic
32 nucleus of matter so that the atomic nucleus will be excited. The excited atomic nucleus becomes unstable and will return to
33 stability by emitting gamma radiation.
34 3. Neutron Capture Reaction (n, γ)
35
In the catch reaction, neutrons can be absorbed or captured by an atomic nucleus of matter. This reaction excites the atomic
36
37 nucleus and emits gamma radiation to reach its ground state.
38 4. Nuclear Transmutation Reactions (n, x)
39 A nuclear transmutation reaction is when a neutron interacts with the atomic nucleus of one matter and causes that atomic
40 nucleus to mutate into another atomic nucleus. This transmutation reaction is used in BNCT therapy. That is, neutrons interacting
41
with boron will produce alpha particles, and lithium nuclei can be written into 10𝐵 (𝑛, 𝛼)𝐿𝑖
42
43 The interaction of neutrons with the material is expressed in the physical Cross Section. Cross sections describe the
44 interaction of neutrons with core particles in matter. The unit of a cross-section is the barn, with 1 barn equal to 10 -24 cm2. The
45 number of reactions that occur at each second in the material can be formulated in equation (1)
46
47 𝑅 = 𝐼[𝑛/(𝑚2 𝑠)][𝑁(𝑖𝑛𝑡𝑖/𝑚3 )][𝐴(𝑚2 )][∆𝑥[(𝑚)][𝜎(𝑚2 )]] (1)
48
49 With R being the number of reactions that occur in each second, I is the neutron intensity that pounds the target at each
50
51 second. N is the target's core, A is the area of the target ground by neutrons, ∆𝑥 is the thickness of the target, and 𝜎 is the cross-
52 section.
53
54 2.3 Boron Neutron Capture Therapy
55 BNCT is a binary radiotherapy modality based on nuclear capture and fission reactions that occur when stable isotopes of
56 boron-10 are irradiated with neutrons to produce high-energy alpha particles. The nuclear reactions that occur in BNCT therapy
57 are as follows:
58
[ 4𝐻𝑒 ] + [ 73𝐿𝑖 ] + 2.79 𝑀𝑒𝑉 (6.1 %)
59 [ 105𝐵 ] + [ 10𝑛] → [ 115𝐵 ]∗ → { 42
60 [ 2𝐻𝑒 ] + [ 73𝐿𝑖 ]∗ + 2.31 𝑀𝑒𝑉 (93.9%)
61 ↓
62 [ 73𝐿𝑖 ] + 𝛾 (0.48 𝑀𝑒𝑉)
63
64
65
 The above reaction shows how 10B interacts with neutrons resulting in 11B as an unstable nucleus and eventually decaying
into lithium and alpha with a half time of 10-12 sec, which has the energy of 2.79 MeV (6.1%) and 2.31 MeV (93.9%). The energy
of the alpha particles released was 1.78 MeV and 1.47 MeV. Lithium energy was 1.01 MeV and 0.84 MeV. Most interactions
1 result in unstable lithium nuclei, emitting gamma rays with an energy of 0.48 MeV to be stable. Lithium becomes stable after
2 releasing gamma rays, with a half-time of 7×10-14 sec. Alpha and lithium resulting from this reaction are particles with high LET
3 values, i.e., alpha particles close to 150 keV/μm and lithium close to 175 keV/μm. Meanwhile, the size of one cell in the tissue
4 only ranges from 4.5-10 μm, which results in the radiance of alpha and lithium rays being deposited only in one cell diameter[16]
5 BNCT works through two stages; namely, the patient is injected with a boron-carrying agent (BPA or BSH compound) at the
6
7 tumor site, and the tumor target volume is irradiated with thermal or epithermal neutrons [17].
8
9 2.3.1 Boron Carrier Agent
10 Boron carrier agents currently used in the BNCT process are BSH (Sodium Borocaptate) and BPA
11 (Boronophenylalanine)[18]. BPA and BSH were chosen as boron carrier agents because BPA and BSH compounds are
12 compounds that can meet the requirements of boron carrier agents, namely:
13 1. Has low toxicity
14
2. Uptake in tumor tissue is high, and uptake in normal tissue is low.
15
16 3. The tumor/brain and blood pressure concentration ratio is high (>3-4:1)
17 4. The concentration of boron is 20-35 𝜇g/g tumor.
18 5. Relatively fast cleansing of normal tissues and blood
19
20 2.3.2 Neutron Source
21 The neutron radiation system in BNCT performs neutron radiation on the target tissue with a qualified neutron
22 flux. In irradiation systems in BNCT, neutrons are divided into three types based on their energy: thermal neutrons,
23 epithermal neutrons, and fast neutrons. Thermal neutrons have an energy of less than 0.5 eV; epithermal neutrons have
24
energy between 0.5 eV to 10 keV, and fast neutrons have an energy of more than 10 keV. In the BNCT irradiation system,
25
26 a neutron source can deliver thermal neutrons to arrive precisely in the cancer tissue. Reactors, accelerators, and generators
27 are sources of neutrons capable of producing neutrons with a wide range of energy. In accelerant BNCT therapy, it is
28 considered more concise and effective when compared to reactors.
29 Cyclotron is a particle-accelerating technology invented by Ernest Lawrence in 1929-1930. Cyclotrons accelerate
30 particles with a spiral trajectory, producing particles with high kinetic energy. The particles produced by cyclotrons can be
31
either protons or deuterons. Protons output from cyclotrons needs to be collated to convert them into neutrons, and the
32
33 resulting flux is suitable for BNCT therapy. BSA (Beam Shaping Assembly) collimator is one tool system that can generate
34 neutron flux from cyclotrons according to neutron flux for BNCT therapy. The formation of neutron beams by BSA
35 collimators occurs when protons from the 30 MeV cyclotron enter the BSA and accumulate beryllium plates. The reactions
36 that occur are as follows:
37
9 1 9 ∗ 1
4𝐵𝑒 + 1𝑝 (30 𝑀𝑒𝑉) → 5𝐵 + 0𝑛 (28 𝑀𝑒𝑉)
38
39
40 ↓
41 9 ∗ 9 0
42 5 𝐵 → 5 𝐵 + 0 𝛾 (0.48 𝑀𝑒𝑉)
43
44 Next, the neutrons will be moderated in the moderation chamber to lower the rapid neutron energy to the thermal neutron
45 energy.
46
47 2.4. Dosimetry
48 According to Wolfgang Sauerwein, the total dose components received by cancer tissue and healthy tissue in the BNCT
49 therapy method are boron dose, gamma dose, proton dose, and neutron scattering dose, as described below:
50 1. Boron Dose
51
The boron dose is the reaction between thermal neutrons and 10B, which produces alpha particles and lithium nuclei with
52
53 an energy of 2.33 Mev. to destroy cancerous tissues. The reaction equations that make boron doses are:
54
[ 4𝐻𝑒 ] + [ 73𝐿𝑖 ] + 2.79 𝑀𝑒𝑉 (6.1 %)
55 [ 105𝐵] + [ 10𝑛] → [ 115𝐵 ] → { 42
56 [ 2𝐻𝑒 ] + [ 73𝐿𝑖 ]∗ + 2.31 𝑀𝑒𝑉 (93.9%)
57
58 ↓
59 [ 73𝐿𝑖 ] + 𝛾 (0.48 𝑀𝑒𝑉)
60
61
62 2. Gamma Dose
63 The gamma dose is the dose that is produced when gamma radiation ionizes body tissues.
64
65
 [ 11𝐻 ] + [ 10𝑛] → [ 21𝐻 ] → [ 21𝐻 ] + 𝛾 (2.33 𝑀𝑒𝑉)

3. Proton Dose
1 The proton dose is the dose resulting from the interaction of thermal neutrons with nitrogen in the body, which this reaction
2 produces protons.
3 [ 147𝑁] + [ 10𝑛] → [ 157𝑁] → [ 146𝐶 ] + [ 11𝑝] (0.66 𝑀𝑒𝑉)
4
5
4. Neutron Dose
6
7 Neutron dose is the dose resulting from the reaction of rapid neutron scattering with hydrogen on body tissues.
1 1 1 ′ 1
8 1𝐻 + 0𝑛 → 0𝑛 + 1𝑝
9
10 In irradiation therapy, the components of the dose used consist of absorbed, equivalent, and effective doses [17]. Absorption
11 dose (D) is the amount of energy deposited per unit mass in a material, for example, body tissue. The unit of absorption dose
12
is gray (Gy). Gray is equivalent to the energy value of 1 joule per unit of mass (J.kg-1), or mathematically it can be written down
13
14 by the equation:
15 𝑑𝐸 (3)
𝐷=
16 𝑑𝑚
17
18 The absorbent dose also has a rad unit, which stands for radiation absorbed dose with a value of 0.01 Gy, or it can also be
19 expressed by 1 𝐺𝑦 = 100 𝑟𝑎𝑑
20
We can determine the average amount of energy absorbed by an organ or tissue, that is, it is indicated by the magnitude of
21
22 the dose rate, which the following equation can search:
23 𝑑𝐷
𝐷̇ =
24 𝑑𝑡
25 𝑑 𝑑𝐸 (4)
𝐷̇ = ( )
26 𝑑𝑡 𝑑𝑚
27 The dose rate unit is joule/kg hour or Gray/second.
28 The equivalent dose is the dose used in radiation protection. This radiation protection is needed because exposure to
29
30 radiation that hits the body's organs will cause different effects, even though the radiation given has the same dose. The equivalent
31 dose is expressed in symbol H with the equation:
32 𝐻=𝐷𝑄𝑁 (5)
33
34 With D as the value of the absorbent dose (Gy), Q is the weight factor, and N is the modification factor. On radiation
35 protection, the magnitude of N is always 1. The weight factor is a value that is applied to distinguish the influence of different
36 types of radiation on a human organ.
37
38 The value of the radiation weight factor used in the calculation of BNCT dosimetry can be seen in Table 3.1.
39
40
Table 3.1. Radiation Weight Factor on BNCT Dosimetry
41
42
Radiation Sources Radiation weight factor
43
44 Alfa (CBE) 3,8 (tumor)
45 1 (healthy tissue)
46 Proton (RBE) 3,2
47 Neutron scattering 3,2
48
(RBE)
49
50 Gamma (DRF) 1
51 The equivalent dose (H) has a sievert unit (Sv).
52 1 𝑆𝑣 = 1 𝐺𝑦 = 1 𝐺𝑦𝐸𝑞𝑢𝑖𝑣𝑎𝑙𝑒𝑛𝑡
53 Furthermore, the equivalent dose weighted with the radiation organ's weight factor is the effective dose (E). The equation
54 for effective dose is as follows:
55
56 𝐸 = ∑ 𝑊𝑇 𝐻
57 𝑇

58 𝐸 = ∑ 𝑊𝑇 𝐷 𝑄 𝑁 (6)
59 𝑇
60 E is the effective dose and is the weight factor of the organ. The unit of the effective dose is the sievert
61
62 1 𝑆𝑣 = 1 𝐺𝑦 = 1 𝐺𝑦𝐸𝑓𝑓𝑒𝑐𝑡𝑖𝑣𝑒
63
64
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 2.5. Monte Carlo PHITS
The Monte Carlo method is a simulation method that combines a collection of computational techniques to find solutions in
the form of estimated values or approaches to mathematical problems based on the use of random samples[19]. PHITS (Particle
1 and Heavy Ion Transport Code System) is a software that uses the Monte Carlo method, which has a microdosimetry function
2 that can calculate linear energy distribution and determine relative biological effectiveness through combination with the
3 parameters of the stochastic microdosimetry kinetic model. PHITS helps simulate the neutron flux shot at the phantom with the
4 geometry of the cancer cells present in it [20].
5 The sections in the program writing structure on PHITS can be seen in Table 3.2.
6
7
Table 3.2 Section Sections on PHITS
8
9
Section Name Description
10
11 [title] Heading
12 [parameters] Types of parameters
13 [source] Source definition
14 [material] Material definition
15
16 [surface] Surface definition
17 [cell] Cell definition
18 [transform] Definition of coordinate transformations
19 [volume] Volume definition
20
[multiplier] Definition of multiplication factor
21
22 [mat name color] Definition of names and colors for graphic plots
23 [end] End of input
24
25
26 3. Results and Discussion
27
28 3.1. Irradiation Geometry
29 The oral cavity cancer therapy simulation with the BNCT method was simulated using head and neck phantoms and a
30 neutron source in the form of a 30 MeV cyclotron. The cancer case used in this simulation is a case of oral cavity cancer, which
31 was uploaded on the research of Misleidy Nápoles Morales. The geometric depiction of head and neck tissues uses references
32 from the ORNL (Oak Ridge National Library) for adult Asian men. The cancer case used as a reference for research and
33
geometric depiction of cancer is a case of OSCC with stage IIIA in a 71-year-old man. Cancer tissue is modeled in the form of
34
35 a sphere, where the cancer tissue itself is divided into three parts, namely Gross Tumor Volume (GTV), Clinical Target Volume
36 (CTV), and Planning Target Volume (PTV). GTV has a radius of 1.39 cm and is located at a depth of 4.9-7.6 cm from the skin
37 surface, CTV is located at a depth of 4.4-8.1 cm from the skin surface, and PTV is located at a depth of 3.9-8.6 cm from the skin
38 surface. Furthermore, the composition of the geometric design of organ tissues is also equipped with the addition of material to
39 each organ.
40
41
42
43
44
45
46
47
48
49
50
51
52
53
54
55
56
57 Figure 1. Irradiation Geometry of Head and Neck Tissues
58
59 The irradiation of neutron rays to the phantom is carried out from the right or Right-Lateral (RLAT) direction because this
60
irradiation direction is closest to the cancerous tissue. The irradiation geometry shown in Figure 1 shows the irradiation process
61
62 is carried out, with the quality of the color that can be seen indicating the magnitude of the flux distribution at each depth. The
63 red indicates a higher flux, and the blue indicates a smaller flux.
64
65
 3.2. Neutron Flux Distribution in Phantom
The neutron flux is the number of neutrons that pass through the unit area of the medium per unit of time. The magnitude
of the neutron flux distributed to the phantom is used as a material to react with boron compounds to destroy cancer cells. In
1 BNCT therapy, thermal neutron rays reach cancer tissue located inside the surface, while epithermal neutron rays reach cancer
2 tissues located on the surface.
3 According to the IAEA, when the epithermal neutron enters the body's tissues, it will be moderated into thermal neutrons
4 so that the thermal neutrons will experience their peak increase at a depth of 2-3 cm. Epithermal neutrons will subsequently
5 decrease exponentially when they enter the body's tissues. The results of the distribution of neutron fluxes in phantom head and
6
7 neck tissues can be seen in Figure 2
8
9
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
25
26
27 Figure 2. Neutron Flux Distribution in Phantom
28
29
The results of neutron flux distribution in the head and neck phantom follow the IAEA recommendation reference.
30
31 The flux of epithermal neutrons entering the body's tissues decreases exponentially, caused by epithermal neutrons being
32 moderated by the body's tissues into thermal neutrons. The epithermal neutron flux begins to run out at a depth of 10 cm.
33 The thermal neutron flux enters the body's tissues, increasing and reaching its peak at a depth of 2 cm. These thermal
34 neutrons will be used in BNCT therapy, later becoming reaction materials with boron compounds to destroy cancer tissue.
35 Thermal neutrons are used as reaction materials for treatment due to their numbers that are still high at the depth at which
36
the cancer tissue is located, shown in number 6, Figure 2.
37
38
3.3. Dose Rate
39
40 The dosing rate is calculated by varying the concentration of boron injected into the phantom. From the simulation results
41 that have been presented, it is known that there is a relationship between boron concentration and the total dose rate in each
42 organ. The higher the boron concentration, the higher the dose rate value in each organ. The higher the boron concentration
43 injected, the more boron will react with thermal neutrons. The results of the simulation of oral cavity cancer BNCT therapy
44 produced dose rate data for each organ with variations in boron concentrations found in Figure 3
45
46 Total Dose Rate
47
48 2.00E-02
49
Dose Rate (Gy/s)

50 1.50E-02
51
52 1.00E-02
53
54 5.00E-03
55
56 0.00E+00
GTV CTV PTV Skin Soft Tissue Facial Spine-Upper Skull Brain
57 Skeleton Cranium
58
Organ
59
60
61 20 μg/g 40 μg/g 60 μg/g 80 μg/g 100 μg/g 120 μg/g 140 μg/g
62
63
64
65
 Figure 3. Dose Rate in Each Organ with Variations in Boron Concentration

From the simulation results that have been presented, it is known that there is a relationship between boron concentration
and the total dose rate in each organ. The higher the boron concentration, the higher each organ's total dose rate value. This is
1
2 because the higher the boron concentration injected, the greater the amount of boron that will react with thermal neutrons.
3
4 Furthermore, for each organ, the ratio of the dose rate of each dose component can be seen in Figure 4.
5
6
7 Comparison of Component Dose in Cancer Tissue and
8 Healthy Tissue
9
8.00E-03
10
Dose Rate (Gy/s)

11 6.00E-03
12 4.00E-03
13
2.00E-03
14
15 0.00E+00
16 GTV CTV PTV Kulit Jaringan Tulang Spine Tulang Otak
17 Lunak Wajah Upper Tengkorak
18 Organ
19
20 Laju Dosis Proton Laju Dosis Gamma Laju Dosis Neutron Laju Dosis Boron
21
22
23 Figure 4. Comparison of Component Dose in Cancer Tissue and Healthy Tissue
24
25 A comparison of dosage components in cancerous and healthy tissue can be seen in Figure 4. The boron dose rate has the
26
highest value when compared to other parts of the dose rate. This is because, with every increase in boron concentration, the
27
28 value of the boron dose rate will increase.
29
30 3.4. Irradiation Time
31 The total dose rate value is then used to calculate how long it takes for irradiation to destroy cancerous tissue. Cancerous
32 tissue will be destroyed at an irradiation exposure of 50 Gy. The time required to produce an irradiation of 50 Gy in cancerous
33 tissue can be sought by multiplying the dose rate value in GTV by 50 Gy. From the results of the multiplication between the
34 minimum dose of cancer tissue destroyer and the total dose rate, the results of irradiation time for each variation in boron
35
36 concentration were obtained. The irradiation time for each of the boron concentration variations is presented in Figure 5.
37
38 Irradiation Time of Each Concentration
39 140.00 121.51
40
Irradiation time (minute)

41 120.00 103.33
42 100.00
43 77.81
80.00 64.88
44 57.47 52.79
45 60.00 43.48
46 40.00
47
48 20.00
49 0.00
50 20 μg/g 40 μg/g 60 μg/g 80 μg/g 100 μg/g 120 μg/g 140 μg/g
51
52 Boron Concentration
53
54
55 Figure 5. Irradiation Time of Each Concentration
56
57 Figure 5 shows that the greater the boron concentration injected, the less irradiation time is required to destroy cancerous
58 tissue. This is because the more boron is deposited in the tissue, the more reactions between boron and thermal neutrons will
59 be. The more reactions occur, the faster the cancer tissue will be destroyed due to irradiation.
60
61 The shortest irradiation time was indicated at a concentration of 140 μg/g of tissue, i.e., the irradiation time was 43.48
62
minutes. The shortest irradiation time is obtained at the maximum boron concentration. The length of irradiation time obtained
63
64
65
 in this therapy simulation is not the fastest when compared to other existing BNCT therapy studies or simulations. This is
because the cancer tissue used in this simulation is quite large, so it takes longer for the cancer tissue to absorb an irradiation
dose of 50 Gy, which is a minimum dose to destroy cancer tissue. In this study, boron concentration was only limited to 140
1 μg/g of tissue because the maximum limit of boron concentration in body tissues was 150 μg/g of tissue. The minimum
2 irradiation time obtained in this study and the most effective irradiation time can destroy cancer tissue while ensuring that the
3 concentration of boron injected into the body does not poison the body.
4
5 3.5. Equivalent Absorption Dose and Effective Absorption Dose
6 This equivalent dose value is the value of the dose rate multiplied by the radiation weight factor in each component of the
7
dose rate of each unit of time. The equivalent absorption dose is derived from the physical amount of the absorbed dose that
8
9 considers the biological effectiveness of radiation depending on the type of radiation and energy. The known irradiation time for
10 the irradiation process is used to calculate the magnitude of the equivalent absorption dose received by healthy tissue. A large
11 comparison of absorption doses for each organ at each concentration can be seen in Figure 6.
12
13 Equivalent Absorption Dose
14
15 60
Equivalent Absorption Dose (Gy)

16 50
17
18 40
19
30
20
21 20
22
23 10
24
0
25 GTV CTV PTV Kulit Jaringan Tulang Spine-Upper Tulang Otak
26 Lunak Wajah Tengkorak
27
28 Organ
29
30 20 μg/g 40 μg/g 60 μg/g 80 μg/g 100 μg/g 120 μg/g 140 μg/g
31
32
33 Figure 6. Equivalent Absorption Dose
34
35 A smaller equivalent absorption dose value indicates that the health of tissue indicates that tissue will receive fewer risk
36 factors from exposure to irradiation. The value of the absorbent dose in healthy organs needs special attention to ensure the
37 absence of excess tissue damage. Organs that need special attention to prevent damage include the skin and brain. The maximum
38
dose limit that the brain can accept is 12 Gy. In this study, the highest equivalent absorption dose received by the brain is 7.8
39
40 Gy, at a concentration of 20 g / g of tissue. The maximum acceptable dose limit for the skin is 12 Gy[21]. Referring to Bapeten's
41 regulations that for dose ranges above 12 Gy, the skin will begin to experience wet desquamation to necrosis[22].
42
43 After successfully calculating the value of the equivalent absorption dose, a significant result of the effective absorption
44 dose for healthy tissue was obtained. This effective dose shows the effects of biological factors caused by each organ. The
45 magnitude of the effective dose for each organ at each concentration is shown in Figure 7.
46
47
48
49
50
51
52
53
54
55
56
57
58
59
60
61
62
63
64
65
 Effective Dose
0.70
1 0.60

Effective Dose (Sv)

2
0.50
3
4 0.40
5 0.30
6
7 0.20
8 0.10
9
10 0.00
11 Kulit Jaringan Lunak Tulang Wajah Spine-Upper Tulang Otak
12 Tengkorak
13 Organ
14
15 20 μg/g 40 μg/g 60 μg/g 80 μg/g 100 μg/g 120 μg/g 140 μg/g
16
17
18 Figure 7. Effective Dose
19
20 The size of the effective dose for each healthy body tissue at each concentration indicates that the effective dose of tissue
21
will be smaller with each significant concentration increase. In radiation protection systems, the smaller the value of the
22
23 equivalent and effective absorption dose indicates, the smaller the risk of side effects of damage received by the organ.
24
25 4. Conclusion
26 The amount of absorption dose equivalent received by healthy tissue located around the cancer tissue can be determined by
27 a simulation method using PHITS 3.26. The absorption dose the organ receives will decrease with the increased concentration
28 of boron injected. The irradiation time required in the simulation of BNCT therapy depends on the magnitude of the concentration
29
of the injected boron; the greater the concentration of the injected boron results in a faster irradiation time.
30
31
32
33 Authors Contribution
34 All the authors equally contributed as the main contributors to this paper. All authors read and approved the final version of the
35
paper. The authors declare no conflict of interest.
36
37
38
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Declaration of interests

☒ The authors declare that they have no known competing financial interests or personal
relationships that could have appeared to influence the work reported in this paper.
☐ The authors declare the following financial interests/personal relationships which may be
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