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CLINICAL IMPLEMENTATION OF LUNG STEREOTACTIC 
BODY RADIATION THERAPY (SBRT) 
 
 
 
 
This thesis/dissertation is submitted to the University of Ghana, Legon, in partial fulfilment of 
the requirement for the award of MPHIL in MEDICAL PHYSICS Degree.  
 
 
BY 
 
ABIGAIL NAA MOMOEDE QUAYE 
(10804981) 
 
 
DECEMBER, 2021
 
University of Ghana http://ugspace.ug.edu.gh 
DECLARATION 
 
This thesis results from the research work undertaken by Abigail Naa Momoede Quaye in the 
Department of Medical Physics, University of Ghana, supervised by Mr Eric C. D. K. Addison, 
Dr Mark Pokoo-Aikins and Prof. Ernest Osei. 
To the best of my knowledge, it contains no material previously published by any person or 
material accepted for the award of any degree of the university, except due acknowledgement has 
been made in the text. 
 
 
 
 
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DEDICATION  
This research work is dedicated to my parents, Mr Napoleon Darko Quaye and Mad. Patience 
Yaaley Adjei and my sisters, Francisca Korkor Quaye and Roberta Naa Karley Quaye. 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
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ACKNOWLEDGEMENTS 
First, uttermost gratitude to Almighty Father for the grace and resources He gave to go through 
the programme and successfully undertake this research study. Secondly, I sincerely appreciate 
the supervisors for their immense support and instructions throughout the study to ensure 
successful work. Again, special thanks to the Komfo Anokye Teaching Hospital for allowing this 
study to be performed at their institution, specifically the Oncology Directorate. Sincere gratitude 
to the Medical Physics staff for the access to their systems and equipment, massive support, and 
guidance in carrying out this study. 
Again, special thanks to Samuel Ona-Adu of the Kwame Nkrumah University of Science and 
Technology for his expertise and assistance in the fabrication of the lung phantom; Mr Saheed 
Ganiyu for his support in developing the motion platform.   
Profound gratitude to my parents and siblings; Mr Napoleon Darko Quaye, Mad. Patience Yaaley 
Adjei, Francisca Korkor Quaye and Roberta Naa Karley Quaye for their love and support in diverse 
ways.  
Finally, a special thanks to Mrs Valerie Fumey Nassah and her family, the Addison family, Mr 
Kingsley Akosah, Ms Juliana Adu-Gyamfi, and Ms Wilhemina Aniagyei for their enormous 
encouragement and support in diverse ways.  
 
 
 
 
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TABLE OF CONTENT 
DECLARATION ............................................................................................................................. i 
DEDICATION ................................................................................................................................ ii 
ACKNOWLEDGEMENTS ........................................................................................................... iii 
List of Figures ................................................................................................................................ ix 
List of Tables ............................................................................................................................... xiii 
ABBREVIATIONS ...................................................................................................................... xv 
ABSTRACT ............................................................................................................................... xviii 
CHAPTER ONE ............................................................................................................................. 1 
INTRODUCTION .......................................................................................................................... 1 
1....................................................................................................................................................... 1 
1.1 BACKGROUND .............................................................................................................. 1 
1.1.1 CANCER EPIDEMIOLOGY ................................................................................... 3 
1.1.2 AETIOLOGY FOR CANCERS ............................................................................... 4 
1.1.3 SIGNS AND SYMPTOMS OF CANCER ............................................................... 8 
1.1.4 DIAGNOSIS OF CANCER ...................................................................................... 9 
1.1.5 CANCER STAGING .............................................................................................. 11 
1.1.6 TREATMENT OVERVIEW AND MODALITIES ............................................... 13 
1.2 PROBLEM STATEMENT ............................................................................................ 17 
1.3 OBJECTIVES ................................................................................................................ 18 
1.4 RELEVANCE AND JUSTIFICATION ........................................................................ 19 
1.5 SCOPE OF THE STUDY .............................................................................................. 20 
1.6 ORGANIZATION OF THESIS ..................................................................................... 20 
CHAPTER TWO .......................................................................................................................... 22 
LITERATURE REVIEW ............................................................................................................. 22 
2..................................................................................................................................................... 22 
2.1 LUNG – ANATOMY AND FUNCTION ..................................................................... 22 
2.2 LUNG CANCER............................................................................................................ 23 
2.3 LUNG CANCER EPIDEMIOLOGY ............................................................................ 25 
2.4 LUNG CANCER AETIOLOGY ................................................................................... 28 
2.4.1 SMOKING .............................................................................................................. 28 
2.4.2 RADON EXPOSURE ............................................................................................. 30 
2.4.3 EXPOSURE TO HAZARDOUS CHEMICALS .................................................... 31 
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2.4.4 CANCER TREATMENTS ..................................................................................... 31 
2.4.5 DIETARY FACTORS ............................................................................................ 32 
2.4.6 GENETIC PREDISPOSITION AND FAMILY HISTORY OF LUNG CANCER32 
2.4.7 OTHER DISEASES................................................................................................ 32 
2.5 LUNG CANCER PATHOPHYSIOLOGY (SYMPTOMS) .......................................... 33 
2.6 LUNG CANCER DIAGNOSIS ..................................................................................... 33 
2.7 CLASSIFICATION OF LUNG CANCER .................................................................... 38 
2.7.1 SMALL CELL LUNG CANCER (SCLC) ............................................................. 39 
2.7.2 NON-SMALL CELL LUNG CANCER (NSCLC) ................................................ 39 
2.8 LUNG CANCER STAGING ......................................................................................... 40 
2.9 LUNG CANCER TREATMENT AND MANAGEMENT ........................................... 46 
2.9.1 SURGERY .............................................................................................................. 46 
2.9.2 CHEMOTHERAPY ................................................................................................ 47 
2.9.3 RADIOTHERAPY ................................................................................................. 48 
2.10 STEREOTACTIC BODY RADIATION THERAPY (SBRT) .................................. 49 
2.10.1 OVERVIEW ........................................................................................................... 49 
2.10.2 LUNG SBRT .......................................................................................................... 53 
2.11 LUNG SBRT IMPLEMENTATION PROCESS ....................................................... 54 
2.12 TREATMENT AND SIMULATION ........................................................................ 54 
2.12.1 TARGET MOVEMENT ......................................................................................... 55 
2.12.2 IMMOBILISATION AND POSITIONING ........................................................... 56 
2.12.3 RESPIRATORY MOTION ASSESSMENT AND CONTROL ............................ 57 
2.12.4 TREATMENT PLANNING ................................................................................... 60 
2.12.5 SBRT QUALITY ASSURANCE PROGRAMME ................................................ 61 
2.12.6 TREATMENT DELIVERY AND VERIFICATION ............................................. 62 
2.12.7 IMAGE-GUIDANCE RADIOTHERAPY (IGRT) ................................................ 62 
2.12.8 FOLLOW-UP AND OUTCOMES ASSESSMENT .............................................. 63 
CHAPTER THREE ...................................................................................................................... 64 
MATERIALS AND METHODS .................................................................................................. 64 
3..................................................................................................................................................... 64 
3.1 ETHICAL STATEMENT .............................................................................................. 64 
3.2 STUDY SITE ................................................................................................................. 64 
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3.3 EQUIPMENT ................................................................................................................. 65 
3.3.1 LINEAR ACCELERATOR ....................................................................................... 65 
3.3.2 COMPUTED TOMOGRAPHY (CT) SCANNER MACHINE ................................. 66 
3.3.3 DOSIMETRY EQUIPMENT ..................................................................................... 67 
3.3.4 RADIOTHERAPY TREATMENT PLANNING SYSTEM (RTPS) ........................ 69 
3.4 LUNG PHANTOM FABRICATION ............................................................................ 70 
3.4.1 TISSUE EQUIVALENCE OF WOOD AND TUMOUR SAMPLES ................... 70 
3.4.2 WATER TANK-TYPE LUNG PHANTOM DESIGN AND DEVELOPMENT .. 73 
3.5 MOTION PLATFORM.................................................................................................. 76 
3.6 SCANNING OF FABRICATED LUNG PHANTOM .................................................. 77 
3.7 CT SCANNER ELECTRON DENSITY CALIBRATION ........................................... 80 
3.8 PHANTOM STUDY ...................................................................................................... 80 
3.8.1 CONTOURING OF VOLUMES ............................................................................... 80 
3.8.2 TREATMENT PLANNING ....................................................................................... 81 
3.8.3 CLINICAL CASE STUDY .................................................................................... 88 
3.9 TREATMENT PLAN EVALUATION ......................................................................... 90 
CHAPTER FOUR ......................................................................................................................... 92 
RESULTS AND DISCUSSION ................................................................................................... 92 
4..................................................................................................................................................... 92 
4.1 LUNG AND TUMOUR SIMULATION SAMPLE ...................................................... 92 
4.2 CT ELECTRON DENSITY CALIBRATION ............................................................... 93 
4.2.1 RESULTS OF FEASIBILITY TEST ......................................................................... 95 
4.2.2 RESULTS OF PHANTOM STUDY .......................................................................... 99 
4.2.3 RESULTS OF CLINICAL CASE STUDY.............................................................. 107 
CHAPTER FIVE ........................................................................................................................ 119 
CONCLUSIONS AND RECOMMENDATIONS ..................................................................... 119 
5.1 CONCLUSIONS .......................................................................................................... 119 
5.2 RECOMMENDATIONS ............................................................................................. 120 
REFERENCES ........................................................................................................................... 122 
APPENDICES ............................................................................................................................ 152 
APPENDIX A ............................................................................................................................. 152 
APPENDIX B ............................................................................................................................. 153 
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LIST OF FIGURES 
Figure 2.1: Lymphatic system showing the network of lymph nodes (photo credit: Edwards, 2019).
 ...................................................................................................................................... 2 
Figure 2.1: Structure of the Lung (American Cancer Society, 2019). .......................................... 23 
Figure 2.2: Lung with cancerous mass (MedicineNet, 2010). ...................................................... 24 
Figure 2.3: Lung cancer metastasis to other organs in the body (LUNGEVITY, 2021). ............. 25 
Figure 2.4: Lung cancer metstasised to lymphatic systems causing cervical lymphadenopathy 
(Anath, 2021) ............................................................................................................. 35 
Figure 2.5: Chest X-ray of normal lungs against cancer affected lungs (Mayo Clinic, 2020) ..... 35 
Figure 2.6: Lung CT image showing (a) normal lung and (b) lung cancer with an arrow pointing 
at the tumour (Anifah et al., 2018) ............................................................................. 36 
Figure 2.7:PET/CT images showing the difference between normal surrounding tissue and tumour 
with active cancer cells coloured. (a) CT image (b) PET/CT image (Hochhegger et al., 
2015) .......................................................................................................................... 37 
Figure 2.8: CT-guided biopsy (NCCN, 2021). ............................................................................. 38 
Figure 2.9: Lung cancer primary tumour T1 illustration (Kay et al., 2017). ................................ 42 
Figure 2.10: Lung cancer primary tumour T2 illustration (Kay et al., 2017). .............................. 42 
Figure 2.11: Lung cancer primary tumour T3 illustration (Kay et al., 2017). .............................. 43 
Figure 2.12: Lung cancer primary tumour T4 illustration (Kay et al., 2017). .............................. 43 
Figure 2.13: Lung cancer regional lymph node illustration (Kay et al., 2017). ............................ 44 
Figure 2.14: Lung metastasis illustration (Kay et al., 2017). ........................................................ 44 
Figure 2.15: Lung cancer stages (St. Stamford Modern Cancer Hospital Guangzhou, 2019). .... 45 
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Figure 2.16: Lung cancer surgical treatment options and resected specimen in dark red  (Hu, 2016).
 .................................................................................................................................... 47 
Figure 3.1: Varian Clinac iX. ........................................................................................................ 66 
Figure 3.2: Siemens Somatom Perspective CT scanner ............................................................... 67 
Figure 3.3: (a) Handheld Traceable barometer, (b) Siemens CT phantom, (c) Max 4000 Plus 
electrometer and (d) Exradin A19 ionisation chamber. ............................................. 68 
Figure 3.4: Varian EclipseTM treatment planning system user interface showing isodose 
distribution. ................................................................................................................ 69 
Figure 3.5: Siemens Somatom Perspective CT scanner used in this study (Komfo Anokye 
Teaching Hospital, Kumasi). ..................................................................................... 70 
Figure 3.6: Setup for the determination of air and water CT numbers. ........................................ 71 
Figure 3.7: Lung and tumour simulating samples. ....................................................................... 72 
Figure 3.8: CT scan images (a) wood sample; (b) perspex, chalk, and sawdust samples. ........... 73 
Figure 3.9: Schematic diagram of lung phantom. (a): phantom design; (b): schematic diagram of 
simulated lung field inserts; (c): diagram of the wood slab with indentation to 
accommodate simulated tumour and ionisation chamber cable. ................................ 74 
Figure 3.10: Prototype lung phantom (a) top view; (b) frontal view ............................................ 74 
Figure 3.11: Lung phantom; (a) frontal view (b) side view (c) top elevation. ............................. 75 
Figure 3.12: (a) Simulated tumour buried in wood slabs with groove (b) ionisation chamber 
inserted into the simulated tumour in the lung field. ................................................. 76 
Figure 3.13: Motion platform with wiper motor connected to trolley. ......................................... 77 
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Figure 3.14: (a) and (b) set up for scanning fabricated lung phantom; (c), (d) and (e) are CT scan 
images of the fabricated lung phantom to assess the Hounsfield units of phantom 
components. ............................................................................................................... 78 
Figure 3.15:  CT scan set-up of fabricated lung phantom on the motion platform. ...................... 79 
Figure 3.16: CT scan user interface showing elevation and frontal view of the phantom. .......... 79 
Figure 3.17: (a) CIRS Electron Density Phantom 062M (b) CT scan image of CIRS Electron 
Density Phantom. ....................................................................................................... 80 
Figure 3.18: Contouring interface displaying transverse, sagittal and frontal views of the phantom 
CT image. ................................................................................................................... 81 
Figure 3.19: Eclipse TPS displaying external beam treatment plan of the fabricated lung phantom
 .................................................................................................................................... 83 
Figure 3.20: Static treatment plan with 50 Gy/5 prescription dose; (a) Transverse view, (b) 3D 
view, (c) Coronal view and (d) Sagittal view. ........................................................... 84 
Figure 3.21: Treatment plan with 50 Gy/5 prescription dose for phantom in 0.5 cm motion ...... 85 
Figure 3.22: Treatment plan with 50 Gy/5 prescription dose for phantom in 1 cm motion ......... 85 
Figure 3.23: Varian Clinac iX linear accelerator at Oncology Directorate, KATH (without On-
Board Imager) ............................................................................................................ 86 
Figure 3.24: Lung phantom treatment set-up, (b) researcher setting up electrometer and (c) 
electrometer displaying radiation measurement. ....................................................... 87 
Figure 3.25: Image verification set up (a) anterior; (b) lateral. .................................................... 88 
Figure 3.26: Treatment plan with 50 Gy/5 for a 3cm tumour ....................................................... 90 
Figure 3.27: Treatment plan with 50 Gy/5 for 1cm tumour ......................................................... 90 
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Figure 4.1: The relative electron density (RED) curve of the Siemens Somatom Perspective CT 
scanner incorporated in the Eclipse TPS. ................................................................... 94 
Figure 4.2: Cumulative DVH for a four-field treatment plan with 10 Gy/5 prescription dose. ... 97 
Figure 4.3: Dose-volume histogram (DVH) of the treatment plan with dose prescription of 50 
Gy/5. ......................................................................................................................... 101 
Figure 4.4: Dose-volume histogram (DVH) of the treatment plan with dose prescription of 50 Gy/5 
for phantom in 0.5 cm motion. ................................................................................. 102 
Figure 4.5: Dose-volume histogram (DVH) of the treatment plan with dose prescription of 50 Gy/5 
for phantom in 1 cm motion. .................................................................................... 102 
Figure 4.6: DVH of the treatment plan with 48 Gy in 4 fractions for tumour size of 3 cm. ...... 108 
Figure 4.7: DVH of the treatment plan with 50 Gy in 5 fractions for tumour size of 3 cm. ...... 109 
Figure 4.8: DVH of the treatment plan with 50 Gy in 5 fractions for tumour size of 1 cm. ...... 110 
 
 
 
 
 
  
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LIST OF TABLES 
Table 1.1: Primary Tumour classification. ............................................................................... 12 
Table 1.2: Regional Lymph nodes classification. ..................................................................... 12 
Table 1.3: Distant Metastasis ..................................................................................................... 13 
Table 2.1: Lung cancer staging using TNM system 8th edition (Kay et al., 2017). ................ 41 
Table 2.2: Tumour staging ......................................................................................................... 45 
Table 3.1: RTOG planning dose-volume constraints (Bezjak et al., 2011; Videtic et al., 2014).
 ................................................................................................................................. 82 
Table 4.1: CT data of samples assessed for the fabrication of lung phantom. ...................... 93 
Table 4.2: Planned and reported absorbed dose metrics for lung phantom feasibility 
treatment planning assessment. ............................................................................ 98 
Table 4.3: Results of fabricated lung phantom dosimetry - planned versus delivered dose. 99 
Table 4.4: Dose statistics of treatment plan with dose prescription of phantom in motion.
 ............................................................................................................................... 104 
Table 4.5: Comparison of average measure dose to TPS calculated dose for 50 Gy/5 dose 
fraction in static mode. ........................................................................................ 105 
Table 4.6: Comparison of average measure dose to TPS calculated dose for 50 Gy/5 
prescription dose delivered to phantom with 0.5 cm motion. .......................... 106 
Table 4.7: Comparison of average measure dose to TPS calculated dose for 50 Gy/5 
prescription dose delivered to phantom with 1 cm motion. ............................. 106 
Table 4.8: Dose evaluation indices for prescription doses of 48 Gy/4 and 50 Gy/5 PTV. .. 112 
Table 4.9: Dosimetric analysis of the bilateral lung for treatment plans with 48 Gy in four 
fractions and 50 Gy in 5 fractions. ..................................................................... 113 
Table 4.10: Dosimetric analysis of the left and right lung for treatment plans with 48 Gy in 
four fractions and 50 Gy in 5 fractions. ............................................................. 114 
Table 4.11: Dosimetric analysis of the heart for treatment plans with 48 Gy in four fractions 
and 50 Gy in 5 fractions. ..................................................................................... 115 
Table 4.12: Dosimetric analysis of the bronchial tree for treatment plans with 48 Gy in four 
fractions and 50 Gy in 5 fractions. ..................................................................... 116 
Table 4.13: Dosimetric analysis of the oesophagus volume with 48 Gy in four fractions and 
50 Gy in 5 fractions. ............................................................................................. 116 
Table 4.14: Dosimetric analysis for trachea for treatment plans with 48 Gy in four fractions 
and 50 Gy in 5 fractions. ..................................................................................... 117 
Table 4.15: Dosimetric analysis of the spinal cord for treatment plans with 48 Gy in four 
fractions and 50 Gy in 5 fractions. ..................................................................... 117 
Table 4.16: Dosimetric analysis of the ribs for treatment plans with 48 Gy in four fractions 
and 50 Gy in 5 fractions. ..................................................................................... 118 
 
 
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ABBREVIATIONS  
2DCRT  Two Dimensional Conformal Radiation Therapy 
3-D CT  Three-Dimensional Computed Tomography 
4-D CT  Four-Dimensional Computed Tomography 
AAA   Analytical Anisotropic Algorithm 
AAPM   American Association of Physicists in Medicine 
ABC   Active Breathing Control 
AC   Abdominal Compression 
AIDS   Acquired Immune Deficiency Syndrome 
AJCC   American Joint Committee on Cancer 
AP   Anterior-Posterior 
BED   Biological Effective Dose 
CBCT   Cone-beam Computed Tomography 
CI   Conformality Index 
CIRS   Computerized Inspection Reporting System 
CO2   Carbon Dioxide 
COPD   Chronic Obstructive Pulmonary Disease 
CT   Computed Tomography 
CTV   Clinical Target Volume 
DIBH   Deep-Inspiration Breathe Hold 
Dmax   Maximum Dose 
Dmin   Minimum Dose 
DNA   Deoxyribonucleic Acid  
Dp   Prescription Dose 
DVH   Dose Volume Histogram 
EBUS   Endobronchial Ultrasound 
ECBAS  Ethics Committee for Basic and Applied Sciences 
EPA   Environmental Protection Agency 
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EPIDs   Electronic Portal Imaging Devices 
GLOBOCAN  Global Cancer Observatory 
GI   Gradient Index 
GTV   Gross Tumour Volume 
HCAs   Heterocyclic amines 
HI   Homogeneity Index 
HIV   Human Immune Virus 
HU   Hounsfield Unit 
ICRP   International Commission on Radiological Protection 
ICRU    International Commission on Radiation Units and Measurements 
IGRT   Image-guided Radiation Therapy 
ITV   Internal Target Volume 
KATH IRB  Komfo Anokye Teaching Hospital Institutional Review Board 
LINAC  Linear Accelerator 
MIBH   Mid-inspiration breath-hold 
MU   Monitor Unit 
MV   Megavolt 
NSCLC  Non-Small Cell Lung Cancer 
OAR   Organs at Risk 
OBI   On-Board Imager 
OS   Overall Survival 
PMMA  Polymethyl methacrylate 
PTV   Planning Target Volume 
QA   Quality Assurance 
RED   Relative Electron Density 
RFA   Radiofrequency Ablation 
ROI   Region of Interest 
RPM   Real-time Position Management System 
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RT   Radiation Therapy 
RTOG   Radiation Therapy Oncology Group 
RTOG   Radiation Therapy Oncology Group 
SALT   Saint-Anne, Lariboisiere and Tenon 
SBRT   Stereotactic Body Radiation Therapy 
SCLC   Small Cell Lung Cancer 
SI   Superior Inferior 
TMP   Thermoplastic masks 
TPS   Treatment Planning System 
TV   Target Volume 
TVPIV  Target Volume covered by the prescribed dose 
UICC   Union for International Cancer Control 
VCS   Vacuum cushions 
VPIV   Volume covered by the prescribed dose 
WHO   World Health Organisation 
 
 
 
 
 
 
  
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ABSTRACT 
The stereotactic Body Radiation Therapy (SBRT) technique was developed to treat lung cancers 
at the Komfo Anokye Teaching Hospital without a four-dimensional computed tomography (4-D 
CT) scanner to account for motion in treatment planning and delivery. A tank-type water lung 
phantom was designed and developed from locally available materials, including wood, perspex 
and acrylic filled roll-on ball implanted in the wood to simulate the lung field, body, and tumour. 
A motion platform was developed to mimic breathing. The lung phantom underwent a standard 
and a slow CT scan to account for motion (0.5 cm and 1 cm). Radiation treatment plans were 
generated according to the Radiation Therapy Oncology Group (RTOG) 0915 protocol for lung 
SBRT and delivered with a Varian Clinac iX linear accelerator to the phantom for dosimetric 
verification with a dose prescription of 50 Gy in five fractions. Clinical tumour sizes of 1 cm and 
3 cm were used as case studies to demonstrate the dose to organs at risk (OARs). Average 
measured doses were compared to treatment planning calculated doses for the phantom with and 
without motion. Dose deviation for treating static mimicked tumour was 8.43%, -4.31% for 
phantom in 0.5 cm motion, and -25.96% for phantom in 1 cm motion. Phantom dosimetric analysis 
for PTV V100%, V99%, V90% at 50 Gy/5 without motion were 86.77%, 91.19% and 99.96%; with 
0.5 cm motion were 98.60%, 99.61% and 100%; and with 1 cm motion were 72.72%, 90.47% and 
99.65%, respectively. Clinical analysis for  PTV V100%, V99%, V90% at 48 Gy/5 were 101.10%, 
102.62% and 100.49%, respectively. For a tumour size of 3 cm at 50 Gy/5 were 98.10%, 99.68% 
and 100%, respectively; and for 1 cm tumour size were 97.36%, 99.19% and 100 %, respectively. 
SBRT treatment planning and delivery were feasible without 4-D CT from phantom studies at the 
study site. The statistics propose that the target was sufficiently covered with the dose for all 
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scenarios, thereby achieving the primary radiotherapy goal without excessively dosing OARs to 
minimise toxicity.  
 
 
 
 
 
 
 
 
 
 
 
 
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CHAPTER ONE 
 INTRODUCTION  
1  
1.1 BACKGROUND 
Abnormal cell growth is an oncogene. Cancer cells proliferate fast as they have no volume 
constraints, no resources shared by extra cells, and no signals from the body to stop them from 
reproducing. (Hanahan & Weinberg, 2000; Hanselmann & Welter, 2022). Cancer cells are often 
structured differently from healthy cells, do not function correctly, and may spread to many places 
of the body. Tumours, or irregular tissue development, are collections of cells capable of 
uncontrollably expanding and distributing; their growth is unregulated (Baba & Câtoi, 2007; 
Hanahan & Weinberg, 2000). Tumours may be noncancerous (benign) or cancerous (malignant). 
Benign tumours propagate gradually without spread, but malignant tumours mature fast, may 
infiltrate into neighbouring normal tissues, and spread to other parts of the body (Baba & Câtoi, 
2007; Hanahan & Weinberg, 2000; Lambert et al., 2017). Locally invasive cancer occurs when 
malignant tumours extend into nearby normal tissues, and metastatic cancer occurs when the 
tumour spreads to distant tissue (Cady, 2007; I. J. Fidler, 1989). The original tumour is the primary 
tumour, and metastatic tumours are those malignant cells that advance to other parts of the body. 
Cancerous cells utilise the circulatory (Dong et al., 2013; Plaks et al., 2013) and lymphatic systems 
(Alitalo & Detmar, 2011; Leong et al., 2011; Padera et al., 2016; H. Zhou et al., 2021) to migrate 
to other body areas and form secondary tumours (Figure 1.1). The lymphatic system oversees 
flushing waste, poisons, and other undesired material from cells and tissues so that they may be 
evacuated out of the body. The lymphatic system comprises lymphatic veins, lymph nodules, 
lymph liquid, and lymphocytes, all of which work together to protect the body against infection 
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and illness (Alitalo & Detmar, 2011). Cancer cells may detach from the tumour and enter the 
lymphatic vessel and subsequently travel from the local site to a distant part of the body 
(metastasis) (Cady, 2007; Hanahan & Weinberg, 2000; Lambert et al., 2017; Leong et al., 2011; 
Padera et al., 2016; H. Zhou et al., 2021). In cancer patients, lymph nodes are the primary route 
for metastasis (Hoshida et al., 2006). Cancer is considered to have metastasised when it has spread 
from its initial location to other sections of the body. Cancer may spread to practically any body 
region, while some forms of cancer are more likely than others to migrate to specific sites, such as 
the bone, liver, and lung. 
 
Figure 1.1: Lymphatic system showing the network of lymph nodes (photo credit: Edwards, 2019). 
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1.1.1 CANCER EPIDEMIOLOGY 
Cancer is the world's second-largest cause of death. According to the World Health Organization, 
approximately 70% of cancer fatalities occur in poor and middle-income nations, where late-stage 
presentation and diagnosis are frequent and a lack of access to treatment. (GLOBOCAN, 2020b) 
estimated about 19.3 million new cancer cases worldwide and around 10 million cancer-related 
deaths in 2020. Breast cancer incidence has exceeded lung cancer incidence worldwide, 
accounting for 11.7 per cent of all cancer cases, while the latter accounts for 11.4 per cent. 
Conversely, lung cancer is the leading cause of mortality, accounting for 18% of all fatalities in 
2020 for both sexes and all ages. Cancer incidence and death rates vary across areas and nations 
(Fidler et al., 2016). Cancer incidence and mortality are rising globally for intricate reasons. 
However, they may be attributed to ageing, a growing population, late-stage presentation, and 
inaccessibility to early diagnosis and treatment. Along with an increase in cancer incidence and 
mortality, one of the causes of the rise in cancer incidence and mortality in economically 
developing countries is an increase in the adoption of cancer-causing behaviours such as obesity, 
physical inactivity, reproductive activities, and smoking (Becher & Winkler, 2011). 
A cancer diagnosis is usually low in Africa, with most cases presenting in late stages. Developing 
nations, including Ghana, accounted for 63 per cent of the anticipated 12.7 million new cancer 
cases globally in 2020. Access to cancer data is restricted due to the absence of accurate cancer 
registries in most cancer centres in Africa. Cancer data problems in most developing countries 
have been documented by (Becher & Winkler, 2011; Bray et al., 2018; Laryea et al., 2014). The 
availability of population-based cancer statistics differs by country. In 2012, Ghana launched the 
Kumasi Cancer Registry, the country's first population-based cancer registry, to make data on 
cancer cases registered in Kumasi public. Laryea et al. (2014) examined the 2012 data from the 
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Kumasi Cancer Registry and determined that women accounted for most cancer diagnoses, 
accounting for 69.6 per cent of all registered cases. In 2015, the total cancer incidence in Kumasi 
was 46.1 per 100,000 people. A 54.1 per 100,000 occurrence rate was predicted for women, 
whereas men had a 37.1 per 100,000 incidence rate (Laryea et al., 2014). Breast and cervical 
cancers were common among Ghanaian women, with incidence rates of 16.1 and 13.7 per 100,000, 
respectively. In Ghanaian males, prostate cancer had the highest incidence rate of 10.5 per 100,000 
(Amoako et al., 2019). Most malignancies are now preventable via evidence-based preventative 
techniques and early detection programmes. According to Mensah & Mensah (2020), 30–50% of 
all cancer cases are avoidable by avoiding identified risk factors. Again, early identification 
reduces the death rate of the remaining 50% of all cancer patients.  
1.1.2 AETIOLOGY FOR CANCERS 
Cancer has no one origin, but experts think the interaction of various elements, some of which are 
environmental, hereditary, or constitutional. Mutations in the cell's deoxyribonucleic acid (DNA) 
cause cancer. DNA is a genetic substance containing biological instructions for growth, survival, 
and reproduction that makes every individual unique. DNA informs the cell of its function and 
how to grow and spread. Various interactions with the DNA can lead to either single or double 
DNA strand breaks, which could lead to either DNA repair, death or miss-repair, and it is the miss-
repair of the DNA that can lead to cancer induction. Mutations may instruct a healthy cell to enable 
fast growth, fail to halt uncontrolled cell growth, or produce errors while fixing DNA errors, 
resulting in malignant cells. Childhood malignancies often develop from cell changes or mutations 
in stem cells (Lupo et al., 2019; Lupo & Spector, 2020). Leukaemia, Hodgkin lymphoma, 
medulloblastoma, retinoblastoma, and Wilms tumour are only a few examples of pediatric cancers. 
However, there is a crowning in the incidence of bone and soft-tissue sarcomas in mid-adolescence 
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and an increased incidence of lymphoma and other solid tumours that continues well into 
adulthood (Fidler et al., 2018; Lupo & Spector, 2020; Schonfeld et al., 2019).   Epithelial cells are 
the sort of cells that become malignant in adulthood. These cells would have been exposed to 
various environmental factors throughout time. Most adults who have survived childhood cancers 
have an increased risk of experiencing late cancer or therapy effects (Fidler et al., 2018; Schonfeld 
et al., 2019).  
Adult malignancies have been associated with risk factors that raise an individual's chances of 
developing a disease. Risk factors also describe cancer recurrence. Risk variables might not always 
imply causation. Therefore, some individuals with several risk factors never get cancer, while 
others with no known risk factors do. Common risk factors for cancer include age, lifestyle 
(tobacco use, obesity, and alcohol consumption), family history, genetic disorder, environmental 
exposures, exposure to certain viruses such as the human papillomavirus (HPV), and prior 
radiation therapy, and exposure to specific chemicals. Some risk factors, such as smoking, being 
overweight, and drinking alcohol, can be avoided by abandoning the harmful behaviours involved, 
while others, such as becoming older, cannot be avoided. 
1.1.2.1 ENVIRONMENTAL EXPOSURE 
The environment in which a person lives may raise his or her chance of acquiring cancer. 
Carcinogens are any chemical or exposure that can cause cancer development, and such may be 
present in our surroundings, including our homes, workplaces, and outdoor spaces. Cancer 
incidence also increases by exposure to substances such as asbestos and high levels of benzene 
(Hang et al., 2020; Jemal et al., 2010; UNSCEAR, 2006). 
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1.1.2.2 RADIATION EXPOSURE 
Radon gas is a carcinogen which may be found in the air or accumulates in rooms from the earth 
(Conrath, 2012; Hunter et al., 2015). Radiation exposure for therapeutic or diagnostic reasons 
increases one's risk of developing cancer (Ali et al., 2020; Andersson et al., 2017; DeLaney et al., 
2020; Dracham et al., 2018; Journy et al., 2017; Linet et al., 2012). Other radiation exposures that 
are cancer risk factors include radioactive fallout from nuclear weapons testing, Chornobyl and 
Fukushima accidents that are risk factors (Cardis et al., 2006; Land et al., 2010; Walsh et al., 2014). 
 
1.1.2.3 INFECTIONS  
Among cancer risk factors is infections, though its association is controversial. Infections boost 
cancer risk in a variety of ways. Some viral infections cause malignant alterations in the DNA 
directly. Hepatitis B (HBV) and C viruses (HCV), Epstein-Barr virus (EBV), human 
papillomavirus (HPV), human immunodeficiency virus type 1 (HIV-1), Helicobacter pylori (H. 
pylori), and Streptococcus bovis (S. bovis) are involved in the development of around 5% of all 
malignancies. (De Flora & La Maestra, 2015; Ohshima & Bartsch, 1994). Other infections may 
cause lasting irritation, increasing one’s risk. Other diseases, such as HIV, impair the immune 
system, making it incapable of protecting against cancer progression (Kirk et al., 2007; Sigel et 
al., 2012). The human papillomavirus (HPV) raises the chances of cervical, anal, vulvar, or vaginal 
cancer development. According to research, HPV may play a role in various head and neck 
malignancies (Barta et al., 2019; M. Fidler et al., 2016; Jonathan M. Samet et al., 2009).  
 
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1.1.2.4 AGE 
Cancer may strike at any age, and the typical age for a cancer diagnosis, depending on the kind, is 
between 65 and 74 years (NCI, 2021). After being exposed to carcinogens and inflammatory 
processes, the human body becomes less effective in detecting and destroying malignant and 
precancerous cells. Cancer is considered an age-related disease because most cancers increase with 
age, and some investigations showed that age is related to cancer (SMETANA et al., 2016; White 
et al., 2014). Nevertheless, old age does not necessarily lead to cancer. 
1.1.2.5 LIFESTYLE  
Individual lifestyle and personal choices contribute to many cancer developing risk factors (Ferlay 
et al., 2015; Khan et al., 2010). That is to say; people have control over their exposure to such risk 
factors as smoking, alcoholism, obesity and diet (Freisling et al., 2020; Katzke et al., 2015; 
McKenzie et al., 2016). Smoking harms the lungs and raises the risk of numerous cancers (Hecht, 
1999, 2012; L. Jacob et al., 2018; Kispert & McHowat, 2017; McKenzie et al., 2016; O’Keeffe et 
al., 2018). Quitting smoking lowers the risk of cancer development (Dryden, 2016; Rogotti, 2022; 
US Department of Health and Human Services, 2020). Alcohol is an irritation that may harm cells 
and encourage the formation of carcinogenic substances in the colon. Limiting the quantity of 
alcohol consumed daily lowers cancer risk (Deng et al., 2021). Obesity is one of the primary causes 
of cancer and increases the risk of breast cancer, colorectal cancer, endometrial cancer, 
oesophageal cancer, pancreatic cancer, and kidney cancer. Excess fat cells create more oestrogen 
and insulin, which encourage cancer development. Maintaining or achieving a healthy body weight 
may lower cancer risks. Several foods and nutrients may be associated with cancer risk factors 
(Agudo et al., 2018; Bertuccio et al., 2019). However, refrigerator usage was associated with a 
reduced risk of gastric cancer (Yan et al., 2018). Unsafe sex practices may increase the chance of 
HPV, HIV, and hepatitis B and increase cancer risk.  
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1.1.2.6 GENETICS 
Certain gene types have contributed to cancer, and these genetic changes are present in most 
malignancies (Knudson, 2002; Mendiratta et al., 2021; Van Cott, 2020). Oncogenes, tumour 
suppressor genes, and mismatch-repair genes are three categories of genes that may regulate cell 
proliferation and change (mutated) in some malignancies (Tomasetti et al., 2015; Yarbro, 1992; 
Zingde, 1993). Some genetic changes are inherited, while others occur sporadically acquired 
(Kuchenbaecker et al., 2017; Priedigkeit et al., 2021). Sporadic cancers are those that occur 
sporadically due to environmental exposures. Hereditary breast and ovarian cancer (HBOC) is an 
example of cancer caused by an inherited mutation in either the BRCA1 or BRCA2 gene (Feuvret 
et al., 2006a; Kuchenbaecker et al., 2017; Pallonen et al., 2022). 
1.1.3 SIGNS AND SYMPTOMS OF CANCER 
Cancer can manifest itself in various ways, each symptom cancer-specific and dependent on the 
affected body part (Holtedahl et al., 2021). Benign tumours or other disorders cause the majority 
of such symptoms. Early cancer and some types of cancer may not exhibit any symptoms. On the 
other hand, some symptoms may result from cancer or a less severe condition. Cancer patients 
experience a variety of symptoms, including pain, dyspnea, fatigue, depression, cough, cognitive 
impairment, neurological problems, abnormal lumps, weight loss, bleeding, and changes in the 
skin, breast, bladder, and bowel (Holtedahl et al., 2018, 2021; Laird et al., 2011). These symptoms 
negatively impact patients' daily functioning and quality of life (Dodd et al., 2001; S. Y. Wang et 
al., 2008). A persistent symptom or screening test result indicating the presence of cancer 
necessitates additional research to confirm that the ailment is cancer-related. If a condition persists 
for more than a few weeks, it is critical to consult a doctor. 
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1.1.4 DIAGNOSIS OF CANCER 
Despite the vital role of prevention in reducing the enormous burden of cancer on the world's 
population, screening and early diagnosis are integral in setting up timely therapeutic management 
to save many lives. A comprehensive assessment of a person's history, physical examination, and 
diagnostic tests is required to diagnose cancer correctly. Effective diagnostic testing confirms or 
rules out the presence of sickness, monitors the disease process and is sometimes a basis to prepare 
for and assess treatment success. The doctor may obtain a patient's personal and family medical 
history to begin the diagnosing procedure. A cancer diagnosis may entail imaging, laboratory tests, 
tumour biopsy, endoscopic examination, surgery, or genetic testing. These investigations are 
required based on the severity of the symptoms. 
Because cancer symptoms include high or low quantities of chemicals in the body, laboratory 
testing for these compounds may assist physicians in making a diagnosis. These compounds are 
measured in laboratory tests of blood, urine, tissue samples, or other bodily fluids for tumour 
markers or other body fluids. However, abnormal laboratory findings are not a reliable indicator 
of cancer. Most tumour markers are generated by both normal and cancer cells, but cancer cells 
produce them in considerably more significant quantities (M. J. Duffy et al., 2007; Michael J. 
Duffy, 2013; Kabel, 2017). 
Imaging techniques represent internal body components that help clinicians determine if a tumour 
is present. In recent years, diagnostic radiography has evolved significantly, owing to the 
introduction of new strategies and techniques that may identify cancer earlier and help patients 
avoid surgery (Beyer et al., 2020; Kourou et al., 2015; Lloyd & McHugh, 2010; Martinelli et al., 
2019; Pucci et al., 2019). X-rays, ultrasound scans, computed tomography (CT) scans, magnetic 
resonance imaging (MRI), positron emission tomography (PET) scans, and nuclear medicine scans 
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are the imaging modalities used for diagnosis, staging and monitoring of cancer (Auweter et al., 
2014; Bandyopadhyay et al., 2019; Burglin et al., 2017; Campos & Diaz, 2018; Capalbo et al., 
2015; Eary, 1999; Frega et al., 2020; Guo et al., 2018; Hernando et al., 2010; Hochhegger et al., 
2015; Husband, 1985; Kapoor & Kasi, 2021; Khiewvan et al., 2016, 2017; Kiratli et al., 2016; 
Luining et al., 2022; McCarten et al., 2019; Mendhiratta et al., 2016; Otoni et al., 2017; Paydary 
et al., 2019; Prado et al., 2009; Rao & Grigsby, 2018; Rix et al., 2018; Salmanoglu, 2021; Serrano 
et al., 2010; Sureshkumar et al., 2020; Tedesco et al., 2019; Wu et al., 2021; Zaucha et al., 2019; 
Y. Zhang & Yu, 2020).  
X-rays use low doses of radiation to photograph the intended body part. Ultrasound examination 
produces a sonogram (picture) of the bodily part by using high-intensity soundwaves (not in the 
hearing range). A CT scan generates a sequence of pictures that provide a three-dimensional (3-
D) representation of the area of interest exposed to X-rays from various angles. Before scanning, 
patients may be given a contrast substance to emphasise certain body regions in the picture. An 
MRI employs a strong magnet and radio waves to generate comprehensive images of the body's 
interior, which may highlight the difference between healthy and sick tissue. A contrast agent is 
sometimes used during an MRI scan to make tumours seem brighter in the pictures. A nuclear 
medicine scan uses radioactive material to create images of the body's interior. Before the scan, a 
small amount of radioactive material is injected into the bloodstream, accumulating in bones and 
other organs. A scanner creates images of bone or other organs using radioactivity detected and 
quantified in the body. The radioactive material in the body degrades over time and may pass 
through urine or stools. This type of nuclear medicine scan examines the bones for damage or 
abnormalities. It may be used to detect metastatic bone tumours. The intravenous injection of 
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radioactive material causes hot spots in the bone. The PET scan is another nuclear medicine scan 
that produces complete 3-D pictures of inside body areas where glucose is taken up. 
PET scanning is an imaging modality used primarily in oncology. It uses radiotracers to assess the 
body's metabolic processes. Commonly used tracers include 18F fluoro-deoxyglucose (FDG), or 
[18F] FDG PET. The cells use 18F-FDG instead of glucose for metabolism. Oncogenic sites have 
high metabolic activity and thus high glucose uptake. These areas are very well taken up by 18F-
FDG, which is a bright spot on the PET scan (Kapoor & Kasi, 2021). This aids in metastasis 
detection. If any of these tests reveal that a person has cancer, another testing may be necessary to 
help the doctor plan therapy. This test is done to define the cancer stage since understanding the 
grade of the tumour is critical for deciding on the appropriate therapy. 
1.1.5 CANCER STAGING  
Staging determines the location, growth rate, and spread of cancer to other organs. Cancer staging 
helps determine prognosis and treatment options. Physical exams, blood tests, and imaging tests 
like MRI, CT, and ultrasound are used to stage patients. Biopsies are sometimes conducted to 
analyze microscopic tissue samples from the suspected tumour site. If surgery is performed, 
pathologists can determine the operative stage by examining the excised tissue. Different 
malignancies, including the brain, spinal cord, and blood cancers, have distinct staging procedures. 
Most staging systems, such as the Tumour Node Metastasis staging system, consider the tumour's 
location, cell type, size, lymph node metastasis, and grade. (Brierley et al., 2017). 
Following testing, practitioners use TNM staging to determine a patient's stage and treatment 
options. After that, the TNM method is used to classify cancer into stages (0-IV), with 0 being the 
least advanced. The TNM technique is used to stage most cancers and considers tumour size, 
number, vascular invasion, lymph node involvement, and metastasis. The primary tumour is 
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denoted by the letter 'T'. This grouping can be a letter or a number in Table 1.1 (Brierley et al., 
2017; UICC, 2016).  
Table 1.1: Primary Tumour classification. 
Classification Description 
TX Primary tumours cannot be measured 
T0 No indication of the primary tumour 
Tis Cancer cells only grow in a layer of cells without advancing into deeper layers. This 
may be termed in situ or pre-cancer. 
T1, T2, T3 or Describes the tumour's size and/or spread to nearby organs. The T number indicates 
T4 the tumour's size and/or metastasis into neighbouring tissues. 
‘N' is the lymph node involvement based on number and location. Classifications in N can be 
assigned to a letter or number Table 1.2. (Brierley et al., 2017; UICC, 2016)  
Table 1.2: Regional Lymph nodes classification. 
Classification Description 
NX No information about nearby lymph nodes 
N0 Neighbouring lymph nodes do not have cancer 
N (N1, N2, or The size, location, and/or the number of neighbouring lymph nodes affected by 
N3) cancer. The higher the N number, the more significant cancer spreads to nearby lymph 
nodes. 
‘M’ stands for any spread to other organs from the primary tumour and is termed metastasis. 
Description of distant metastasis grouping in Table 1.3 (Brierley et al., 2017; UICC, 2016). 
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Table 1.3: Distant Metastasis 
Classification Description 
M0 No distant spread found 
M1 The cancer advance to distant organs 
 
Each form of cancer has its TNM classification, with distinct descriptions of letters or numbers 
allocated to TNM groups. 
The grade of a tumour is often considered in staging. The grade influences the growth and spread 
of cancer. Well-differentiated cancer cells appear normal and grow slowly, while poorly 
differentiated cells appear abnormal and develop rapidly. However, grading impacts cancer 
therapy (Rakha et al., 2010; van Dooijeweert et al., 2021). 
Cell type (such as oesophageal cancer), tumour location, tumour marker levels in the blood (such 
as prostate cancer), test results on cancer cells (such as breast cancer), and patient age (for example, 
thyroid cancer) are additional variables that affect cancer staging (American Cancer Society, 2020; 
Buranaruangrote et al., 2014; Canadian Cancer Society, 2021; National Cancer Institute, 2015). 
1.1.6 TREATMENT OVERVIEW AND MODALITIES 
Cancer therapy is situation-dependent and may be administered alone or with other therapeutic 
modalities. The most often used cancer treatment treatments include radiotherapy, chemotherapy, 
and surgery, all of which aim to cure, reduce, or prevent cancer progression. Primary, adjuvant, 
and palliative care are possible treatment alternatives. The primary goal of treatment is the cure; 
adjuvant therapy is used to remove remaining cancer cells following primary treatment to prevent 
a recurrence, and palliative therapy is used to reduce treatment-related side effects or disease-
related signs and symptoms. There are many ways to treat cancer, such as surgery, chemotherapy, 
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radiotherapy, hormone therapy, and immunotherapy. The best one is chosen based on the type and 
stage of cancer, the patient's overall health, and preferences. After the patient and doctor weigh the 
pros and cons of each option, a treatment modality is chosen (Abbas & Rehman, 2018; Diwanji et 
al., 2017; Ezer et al., 2015; Kumar et al., 2017; Z. Wang et al., 2018; S. Yang et al., 2019; Zappa 
& Mousa, 2016). 
Childhood cancer is distinct from adult cancers in diagnosis, treatment, and prognosis, especially 
survival rate and illness origin. Children have a five-year survival rate of more than 80%, while 
adults have a rate of 68%. The disparity could be explained by the increased sensitivity of 
paediatric cancer to treatment and children's tolerance for more aggressive therapy 
(Akinkuotu et al., 2021; Jensen et al., 2021; Siegel et al., 2021; Ward et al., 2014). 
1.1.6.1 SURGERY  
Surgery assists in treating cancer by physically removing the tumour from the body. Subject to the 
tumour site and other considerations, this treatment is performed openly or via minimally invasive 
incisions. Surgery may be curative (removal of all cancer), debulking (removal of a portion of the 
tumour when removal of the entire tumour would cause harm to adjacent organs), or palliative 
(done to alleviate pain and impairment) (Abbas & Rehman, 2018). When medication fails to 
manage pain, palliative surgery may be utilised. Reconstructive surgery is used to enhance a 
patient's outlook after surgery. 
In contrast, preventive surgery involves the removal of tissues that are likely to become malignant 
even if no evidence of cancer is present. Surgery is a mechanical method of temporarily removing 
a large tumour resistant to chemotherapy and radiation treatment. Nonetheless, several aspects of 
surgery are challenging and ineffective for subclinical metastases. Surgery has certain limitations, 
including the inability to eradicate cancer cells.  
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1.1.6.2 CHEMOTHERAPY  
Chemotherapy is a cancer treatment that uses chemicals to destroy rapidly developing cancer cells. 
Chemotherapy may help slow cancer progression, halt its spread, or prevent recurrence. 
Chemotherapy may be used alone or in conjunction with other therapeutic options (Curran et al., 
2011; MacHtay et al., 2012; Seike et al., 2021; van Dooijeweert et al., 2021). Hair loss, weariness, 
mouth sores, and stomach issues may occur due to the treatment and must be controlled (Abbas & 
Rehman, 2018). Chemotherapy is the delivery of anticancer medications that rapidly travel 
throughout the body, destroying cancer cells on the spot. It inhibits primary tumour development 
and dissemination and metastasis, and subclinical metastases. Chemotherapy destroys not just 
malignant cells but also normal cells, shortening patients' lives over time.  
1.1.6.3 RADIOTHERAPY  
Radiotherapy uses high-energy radiation such as photons or X-rays to destroy cancer cells. 
Radiotherapy damages DNA and other essential biological molecules directly and indirectly 
through the creation of free radicals. Radiotherapy may be delivered based on the type of cancer, 
the size, and location of the tumour, its proximity to healthy and radiosensitive tissues, the overall 
health of the patient, the patient's age, and past cancer treatments. Radiotherapy is either curative 
or palliative. Radiotherapy is a painless procedure that does not require anaesthesia. Radiotherapy 
is effective and is used to treat many cancers; however, it has risks and side effects. Radiation 
therapy can affect nearby tissues depending on their proximity to the tumour. Radiotherapy can 
cause diarrhoea, tiredness, nausea, and anorexia, although such effects are transitory (Dilalla et al., 
2020). Long-term treatments have more negative effects than short-term ones (Brook, 2020; 
Majeed & Gupta, 2021). Radiation has long-term side effects like shortness of breath and 
narrowing the gullet. Lung diseases like radiation pneumonitis can be caused by radiation. 
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Radiation pneumonitis occurs in 5–15% of lung cancer patients getting radiotherapy(Arroyo-
Hernández et al., 2021; Hanania et al., 2019; Rahi et al., 2021).  
Before treating a patient in Radiation Oncology, a CT simulation of the treatment site is conducted. 
Computed tomography creates images of the patient to target radiation therapy precisely. It also 
helps avoid overdosing normal tissues around the tumour, lowering unwanted effects. The 
photographs are placed into a treatment planning system. The radiation therapy delivery technique, 
beam energy, number of treatment fields, and treatment angles are chosen at this step. Medical 
physicists ensure treatment plans meet radiation oncologists' specifications. The presence of 
normal tissue in the beam path during therapy determines radiation side effects. After examining 
the treatment plans, the radiotherapist delivers them to the patient. X-rays are frequently taken 
before therapy to ensure appropriate posture. External beam radiotherapy (EBRT) and interstitial 
radiotherapy (brachytherapy) are two types of radiation therapy that can be used to treat cancer. 
Brachytherapy is a type of radiotherapy used to treat small oral and oropharyngeal tumours. 
External beam radiation is the most common type of radiotherapy, targeting the tumour and 
surrounding tissues with X-rays or electrons. The treatment course is usually once or twice a day 
for 4 – 7 weeks. 
Radiation therapy has evolved to better treat cancer by targeting the tumour while sparing normal 
tissues. External beam radiotherapy can use a range of methods and radiation types. Stereotactic 
radiosurgery (SRS), stereotactic radiation therapy (SRT), stereotactic body radiation therapy 
(SBRT), and proton therapy are examples of EBRT.  
One of the problems with radiotherapy for small tumours that move a lot when people breathe is 
that there is much uncertainty related to substantial tumour motion (Atkins et al., 2015; Langen & 
Jones, 2001; Liu et al., 2007; Mageras et al., 2004; Shirato et al., 2004; Torshabi & Dastyar, 2017; 
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S. Yoganathan et al., 2017; Yu et al., 2012). Several studies applied diverse motion management 
techniques such as abdominal compression, active breathing control and respiratory gating adept 
at limiting or decreasing target motion or tracing the target motion during treatment (Giraud & 
Houle, 2013; Keall, Mageras, et al., 2006; Langen & Jones, 2001; Van Gelder et al., 2018; S. 
Yoganathan et al., 2017). Due to target coverage ambiguity, the impact of respiratory motion on 
lung tumour treatment has been questioned. Mageras et al. (2004) used four-dimensional CT 
(4DCT) to quantify lung tumour motion and found that in seven of twelve patients, tumour motion 
exceeded 1 cm. According to Yu et al. (2012), early-stage non-small cell lung cancer patients 
showed more than 50% greater tumour mobility than locally advanced patients. They found a 
relationship between diaphragm motion and tumour movement.  
1.2 PROBLEM STATEMENT 
Radiation therapy for lung cancers is administered using several modalities such as 3DCRT, 
IMRT, VMAT, and, more recently, SBRT (Abbas & Rehman, 2018; Lemjabbar-Alaoui et al., 
2015). SBRT is an advanced unique technique that accurately administers highly focused escalated 
radiation doses (five fractions or less) to treat malignant target volumes. SBRT has been employed 
to treat some cancers, including lung, spine, liver, pancreas, kidney and adrenals (Atkins et al., 
2015; Benedict et al., 2010; Diwanji et al., 2017; Kumar et al., 2017; Stumpf et al., 2016). SBRT 
has been delivered using either 3DCRT, VMAT or IMRT. One of the challenges associated with 
the radiotherapy of minor tumour sizes sited inside organs in motion due to respiration (i.e. lung) 
is the significant target coverage uncertainty related to substantial tumour motion (Atkins et al., 
2015; Langen & Jones, 2001; Liu et al., 2007; Mageras et al., 2004; Shirato et al., 2004; Torshabi 
& Dastyar, 2017; S. Yoganathan et al., 2017; Yu et al., 2012). Several studies applied diverse 
motion management techniques such as abdominal compression, active breathing control and 
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respiratory gating adept at limiting or decreasing target motion or tracing the target motion during 
treatment (Giraud & Houle, 2013; Keall, Mageras, et al., 2006; Langen & Jones, 2001; Van Gelder 
et al., 2018; S. Yoganathan et al., 2017).  
The Oncology Directorate of the Komfo Anokye Teaching Hospital (KATH) currently treats lung 
malignancies as static tumours without motion management strategies. Thus, comparatively more 
significant margins are used to account for tumour motion during treatment planning, resulting in 
the irradiation of relatively larger healthy tissue sizes around the tumour and leading to relatively 
high toxicity in the lungs and radiation injuries such as radiation pneumonitis. Consequently, this 
study aims to develop an approach for lung cancer radiotherapy at KATH that considers tumour 
motion. This technique can significantly conform the dose to the target volume for tumour 
management. It could result in improved biochemical degeneration-free survival, cancer 
progression-free survival, and cancer-specific survival. Consequently, it will significantly affect 
the care offered to lung cancer patients at KATH. In addition, irradiating less healthy lung tissue 
will reduce treatment toxicities and potentially improve patients' quality of life. 
1.3 OBJECTIVES 
The main objective is to develop a treatment technique for lung cancers using the Stereotactic 
Body Radiation Therapy method at the Oncology Directorate of the Komfo Anokye Teaching 
Hospital (KATH) that considers the target motion and minimises treatment toxicity. The specific 
objectives include: 
1. To design and develop lung phantom for SBRT dosimetric verification 
2. To develop SBRT treatment planning and treatment delivery protocols. 
3. To maximise target coverage while minimising dose to normal tissue.  
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1.4 RELEVANCE AND JUSTIFICATION 
The influence of respiratory motion on treating thoracic tumours has been challenged with target 
coverage uncertainty connected with significant tumour motion. Mageras et al. (2004) used four-
dimensional CT (4DCT) to look at lung tumour movement. In seven out of twelve patients, they 
found that tumour movement could be more than 1 cm, especially in the craniocaudal direction. 
(Yu et al., 2012) investigated lung tumour motion characteristics in non-small cell lung cancer 
patients and reported that early-stage lung cancer patients had more than 50% higher tumour 
motion than the locally progressed patients cohort. They also observed a link between tumour 
movements and location, volume, and diaphragm motion. 
The success of radiotherapy is dependent on the total radiation dosage to the target, but the dose 
prescribed for lung cancer treatment is limited by the radiation tolerances of surrounding normal 
tissues and organs. In recent years, various treatment methods have been developed to help escalate 
the dose to targets leading to tumour control while at the same time reducing the dose to normal 
tissue surrounding the target leading to fewer toxicities. In the absence of motion management 
techniques for lung cancer radiotherapy, there is the potential for geometrical misses due to 
respiratory-induced tumour movements and anatomical changes during radiation administration, 
potentially leading to local control failures. Further, relatively large volumes of normal lung tissue 
are usually included in the treatment field to ensure adequate target coverage, leading to high 
incidence and severity of normal tissue damage and potentially life-threatening to patients.  
Consequently, this study aims to develop an approach for lung cancer radiotherapy at KATH that 
takes into consideration the tumour motion. This approach has the potential to extremely 
conforming doses close to the target volume related to tumour control, leading to enhanced 
biochemical degeneration-free survival, cancer progression-free survival, and cancer-precise 
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survival. Thus it will have a very high impact on the care provided to lung cancer patients at 
KATH. Furthermore, irradiating less healthy lung tissue will lessen treatment toxicities and 
potentially increase patients' quality of life.  
SBRT also allows for shorter treatment times, greater comfort, and convenience. SBRT is 
especially beneficial to Ghana, as most patients now commute from remote areas to Accra or 
Kumasi, the country's only metropolis with radiation facilities. Komfo Anokye Teaching Hospital 
(KATH) welcomes patients from 12 of Ghana's 16 regions and Burkina Faso and Ivory Coast. 
Most patients, particularly those coming from remote locations outside the region for radiation 
therapy, must find lodging in Kumasi for many weeks. These fees are in addition to therapy, which 
most patients cannot afford. Finally, some patients stop therapy to go back to work to pay the 
remaining bills. Radiotherapy gaps affect treatment outcomes, although only marginally. As a 
result, the use of SBRT at KATH and throughout Ghana would reduce patient and staff costs 
without compromising treatment outcomes. 
This technology could be expanded to additional cancer sites to improve the therapeutic ratio for 
patient benefit.  
1.5 SCOPE OF THE STUDY 
The scope of the study is limited to the lung phantom studies and a clinical case study of a patient 
CT data set at the Oncology Directorate, Komfo Anokye Teaching Hospital (KATH). 
1.6 ORGANIZATION OF THESIS 
The first chapter of this thesis introduces cancer, the research issue, and the problem studied. 
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Chapter 2 discusses lung cancer. The chapter first explains the forms of lung cancer, symptoms, 
diagnosis, risk factors, and treatment techniques. Further, stereotactic body radiation treatment 
(SBRT) is discussed in the chapter. This chapter's final portion discusses radiation. 
Chapter 3 discusses the study's methodologies and equipment. A lung phantom and motion 
platform were fabricated to test SBRT treatment plans. A motionless phantom received several 
treatment plans. An experimental investigation was done to compare the planned and delivered 
doses. 
Chapter 4 discusses the findings from the study. 
Chapter 5 summarises the findings and addresses recommendations and future research objectives. 
Finally, the appendices provide the study's ethical clearances.  
 
 
 
 
 
 
 
 
 
 
 
 
 
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CHAPTER TWO 
LITERATURE REVIEW 
2  
2.1 LUNG – ANATOMY AND FUNCTION 
Every cell in the body requires oxygen to survive and expel carbon dioxide produced by cell 
processes. The lungs are thoracic organs that allow people to breathe by inhaling oxygen and 
exhaling carbon dioxide. This gas exchange occurs in alveoli within the lungs. Besides this 
fundamental role, the lungs also regulate the blood pH by increasing or decreasing CO2 levels. 
The lungs filter microscopic gas bubbles from the blood and convert angiotensin I to angiotensin 
II, which helps regulate blood pressure. The right and left lungs each have three lobes. The trachea, 
the tube that transports air into and out of the lungs, ends here. The bronchus connects the lungs 
to the trachea. The bronchi divide into bronchioles, which are even smaller tubes. Every lung has 
30,000 bronchioles, some as thin as hair. Each bronchiole tube ends in a cluster of alveoli, which 
resemble small grape clusters. The lungs contain around 600 million typical alveoli, each with a 
surface area comparable to a tennis court. The interstitium is a thin layer of cells that supports the 
alveoli and contains blood vessels. The pleura surrounds the lungs. Each breath lubricates the 
lungs, allowing them to expand and contract freely. The lungs are shown in Figure 2.1. Any organ 
in the body might be harmed by diseases that produce abnormal lung function. 
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Figure 2.1: Structure of the Lung (American Cancer Society, 2019).  
2.2 LUNG CANCER 
Lung cancer is a lung disease in which normal lung cells transform into harmful abnormal cells 
known as cancer cells. Lung cancer begins in the lungs, most commonly in the cells that line the 
bronchi and other lung structures such as the bronchioles or alveoli. Cancer cells multiply to form 
clusters known as tumours, which grow and destroy lung tissue. Figure 2.2 depicts a cancerous 
mass in the lung.  
 
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Figure 2.2: Lung with cancerous mass (MedicineNet, 2010). 
Lung cancer may progress to other body areas through the blood or lymph fluid (a natural liquid 
that aids in the collection of undesired waste material from the body), resulting in a condition 
known as lung cancer metastasis. Lung cancer metastases can progress to lymph nodes near the 
lungs and other organs via the bloodstream via the bloodstream, such as bones, the adrenal glands, 
and the brain (Figure 2.3). Cancer can begin in other organs before spreading to the lungs and is 
referred to as metastasis of the initial form of cancer, not lung cancer. Lung cancer is the only 
cancer that starts in the lungs (NCCN, 2021). 
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 Figure 2.3: Lung cancer metastasis to other organs in the body (LUNGEVITY, 2021). 
2.3 LUNG CANCER EPIDEMIOLOGY 
Lung cancer is the most typical disease in males and the third commonest cancer in women, with 
2 million new cases documented in 2020 (GLOBOCAN, 2020b). Lung cancer is the leading cause 
of cancer mortality in both genders (Barta et al., 2019; Bray et al., 2018; GLOBOCAN, 2020c; 
Malhotra et al., 2016). According to WHO (2020), lung cancer is one of the most typical cancers, 
accounting for 2.26 million cases, and it is the leading cause of cancer death, accounting for 1.8 
million deaths in 2020. According to GLOBOCAN (2020c), lung cancer is placed eighth, with 478 
deaths out of 535 new cases, or almost 50% of new cases.  
Globally, lung cancer is most frequent in older people. People mostly diagnosed with lung cancer 
are 65 years or older, with only a small number of people diagnosed younger than 45 years. (NCI, 
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2021). The typical age at diagnosis is approximately 70 years. Overall, the lifetime chance of lung 
cancer is approximately 1 in 15 for men and 1 in 17 for women. These numbers include both 
smokers and nonsmokers. The risk is significantly higher for smokers and much lower for 
nonsmokers (Barta et al., 2019; Malhotra et al., 2016).  
Increased understanding of the dangers of smoking and other risk factors has led to significant 
declines in lung cancer mortality rates in high-income countries (Gaafar & Aly Eldin, 2005). In 
contrast, incidence and mortality rates for lung cancer have increased in some low- and middle-
income nations (Huerta & Grey, 2007). In industrialised countries, women had a higher lung 
cancer mortality rate than men. In contrast, lung cancer death rates are low in developing countries. 
In industrialised nations, lung cancer mortality has reduced considerably due to a greater 
understanding of lung cancer risk factors, particularly the harmful effects of smoking. 
Additionally, early detection contributes to this decline (Jemal et al., 2010).  
According to GLOBOCAN (2020b),  females have a lower incidence rate. However, lung cancer 
is currently the third most prevalent disease among women (8.4 per cent of all cancers) and the 
leading cause of cancer mortality globally (18 per cent of the total). In Western Africa, the 
incidence rates among males and women were 11.1 per cent and 5.7 per cent, respectively. Cancer 
kills more than half of all people in low- and middle-income countries (Barta et al., 2019; Bray et 
al., 2018; GLOBOCAN, 2020c; Hamdi et al., 2021; Malhotra et al., 2016; L. A. Torre et al., 2016).  
In 2011, at the 18th Union Conference of the African Region on Lung Cancer and Tuberculosis 
Awareness, it was reported that 67% of lung cancer cases worldwide occur in men aged 50 to 69. 
Africa had 4,525 lung cancer deaths in 2006 (AFRO UNION Conference, 2011; Bello et al., 2011).  
GLOBOCAN (2020c) estimated the incidence rate of lung cancer in various African regions and 
reported that men had a higher incidence rate than women. Furthermore, the incidence of lung 
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cancer was lower in the East, Middle, and West African regions than in the Southern and Northern 
parts of Africa. Urman et al. (2016) attributed the low incidence in Africa to a lack of research 
studies on the aetiology of lung cancer and a lack of cases or detection biases. GLOBOCAN 
(2020c) has the lowest lung cancer mortality rate in Sub-Saharan Africa, excluding South Africa. 
The population-based data on lung cancer incidence and mortality are unavailable, and the 
GLOBOCAN relies on local registries to estimate these figures (Becher & Winkler, 2011).  
Lung cancer is increasing in Northern and Southern Africa in both men and women, according to 
Hamdi et al. (2021), with a 3 to 5 fold increase in males compared to females. Southern Africa has 
twice the IR of North Africa. Southern Africa's heavy cigarette, cannabis, and alcohol consumption 
may explain this. In 2018, less than 3 cases per 100,000 people in the Eastern, Central, and Western 
regions.  
In 2018, the WHO (2020b) reported 250 lung cancer cases in Ghana. Lung cancer incidence and 
mortality are ranked eighth in Ghana, with 2.2 and 3.1 per cent of the total, respectively. Males 
had an age-standardised world incidence rate of 3.8, while females had an incidence rate of 2.8 
(GLOBOCAN, 2020a). Lung cancer accounts for 1.6% of all cancers in Ghana, according to 
Laryea et al. (2014). In 2014, lung cancer was the third most common malignancy in males (5.3%) 
but not among the top five in women. Based on Ghana's cancer profile, the WHO (2020b) predicted 
348, 250, and 511 lung cancer cases in 2012, 2018, and 2040. (Kitson-Mills et al., 2019) studied 
cancer prevalence in an Accra neighbourhood and found uranium deposits in particular areas 
increase the risk of lung cancer.   
 
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2.4 LUNG CANCER AETIOLOGY  
Lung cancer rarely affects those under 40 but primarily affects the elderly. Lung cancer can strike 
anyone at any age, and age is a risk factor (Dela Cruz et al., 2011). Many risk factors for lung 
cancer can be addressed, such as smoking cessation and family history. Some people with many 
risk factors never get lung cancer, whereas others do. This phenomenon is still being studied.  
In Africa, smoking is responsible for 90% of lung cancers; nevertheless, HIV/AIDS is also a cause 
of lung cancer (Kirk et al., 2007; Malhotra et al., 2016; Sigel et al., 2012; Urman et al., 2016; 
Winstone et al., 2013). Africa is the most affected region by HIVAIDS (Kharsany & Karim, 2016). 
The incidence of lung cancer in the HIV-infected population is more comparable to that of the 
general population (Sigel et al., 2012, 2017).  
Geographic location and occupational setting are significant risk factors for lung cancer in Ghana 
(Laryea et al., 2014). Even though smoking is not part of the Ghanaian culture, it has been 
established as a risk factor for cancer. 
A person's age, specific illnesses and treatments (previous radiotherapy), family history of lung 
cancer, and exposure to cancer-causing substances (radon, asbestos, arsenic, beryllium, cadmium, 
chromium, nickel) are all risk factors for lung cancer (Barta et al., 2019; Clark & Alsubait, 2020; 
NCCN, 2021; NCI, 2021; Zappa & Mousa, 2016). 
2.4.1 SMOKING 
Smoking is the leading cause of lung cancer, and around 85 per cent of lung cancer patients have 
smoked at some time in their life (L. A. Torre et al., 2016). The risk increases with the number of 
cigarettes smoked daily and decreases with the duration of smoking. Additionally, the risk grows 
with smoking duration and initiation age. There are approximately 70 recognised carcinogens in 
cigarette smoke (Dela Cruz et al., 2011; Malhotra et al., 2016). Smoke also contains hazardous, 
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radioactive chemicals, such as radon and decay products (Malhotra et al., 2016; L. Torre et al., 
2015; L. A. Torre et al., 2016; Urman et al., 2016).  
Secondhand smoking involves breathing smoke from other people's cigarettes, which is akin to 
cigar smoking and causes lung cancer. (Fukumoto et al., 2015; Hang et al., 2020; A. S. Kim et al., 
2018; Li et al., 2016; Naeem, 2015; Sheng et al., 2018; Sun et al., 2017).  
Thirdhand smoke (THS) is a newly identified tobacco smoke danger that has been a public issue 
recently due to its widespread indoor presence and considerable unfavourable biological and 
physiological impacts (Hang et al., 2019; Thomas et al., 2014). There is evidence that third-hand 
smoking (THS) can cause cancer (Hang et al., 2018, 2020; P. Jacob et al., 2017). Infants and 
children living in a smoking household are susceptible to THS and secondhand smoke, and 
exposure has been associated with an increased risk of lung cancer later in life (Sarker et al., 2020; 
Thomas et al., 2014). 
Never smokers are individuals who have never smoked and have never smoked more than 100 
cigarettes in their lives. Globally, the fraction of lung cancers unrelated to cigarette smoking is 
around 15% in males and 53% in women (A. S. Kim et al., 2018; Jonathan M. Samet et al., 2009; 
Toh & Tan, 2017; Wakelee et al., 2016). Never smokers account for 25% of lung cancer cases, 
and adenocarcinoma is the most often diagnosed cell type of lung cancer among them (Dubin & 
Griffin, 2020; Malhotra et al., 2016; Parker, 2019; Jonathan M. Samet et al., 2009; Toh & Tan, 
2017; Wakelee et al., 2016).   
 
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2.4.2 RADON EXPOSURE 
Radon-222 is a byproduct of the decay of radium-226, whereas radium is a byproduct of the decay 
of uranium-238. Uranium and radium are present in varying amounts in the earth's crust, including 
soil, rock, and stone. Radon is a naturally occurring radioactive gas that is colourless, odourless, 
and tasteless and has a half-life of 3.82 days. Radon is a well-known carcinogen and a source of 
ionising radiation exposure in the environment (Bissett & McLaughlin, 2010; O’Keeffe et al., 
2018). Radon is harmless, but its breakdown products, termed radon daughters, are solid 
radioactive particles that can attach to surfaces like dust or lung epithelium, causing DNA damage 
and perhaps lung cancer (Eidy & Tishkowski, 2021; Garcia-Rodriguez, 2018; Laughlin, 2012).  
Radon is the world's second-largest cause of lung cancer after smoking (Lorenzo-González et al., 
2019). Radon causes roughly 20,000 lung cancer cases every year, according to the EPA in the 
US. They suggest testing indoor radon levels in households and applying mitigation measures to 
mitigate excessive radon concentration levels (Conrath, 2012).  
Although Ghana does not have a geologic radon potential reference level, some study has been 
done on radon levels in Ghana. (Badoe, 2007) measured radon gas levels in the Ashanti Region 
for six years to create a vulnerability map for Ghana. The radon concentrations were within the 
United States Environmental Agency's tolerance range. In addition, Akortia (2010) and Kitson-
Mills et al. (2019) have evaluated the indoor radon levels in some Ghanaian communities. Akortia 
(2010) observed that the effective dosage equal to the population was two to three times lower 
than the 1 mSv indicated by the ICRP, while Kitson-Mills et al. (2019) discovered that the average 
indoor concentration was below the WHO's globally recommended level. These researches' low 
levels and outcomes do not rule out the need for radon gas evaluations in Ghana, notwithstanding 
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the low amounts measured. Radon gas is widely recognised as a critical lung cancer risk factor; 
thus, a national geologic radon potential evaluation is recommended.  
2.4.3 EXPOSURE TO HAZARDOUS CHEMICALS  
Occupational exposures cause 3 – 15% of lung cancer cases. Some proven and suspected 
compounds that cause lung cancer are arsenic, asbestos, chromium, mustard gas, nickel, silicon, 
iron ore, wood dust and acrylonitrile. The danger of asbestos exposure varies depending on the 
exposure type. Occupational exposure is far riskier than environmental exposure.  
Cooking and other fumes are significant danger concerns, especially in developing nations like 
Ghana (Barta et al., 2019; Dela Cruz et al., 2011; Malhotra et al., 2016; Urman et al., 2016). The 
type of coal utilised affects the results. Smoky coal enhances the risk of lung cancer. Diesel exhaust 
causes lung cancer (Attfield et al., 2012; Silverman et al., 2012).  
2.4.4 CANCER TREATMENTS 
Some cancer treatments increase the risk of lung cancer. The risk rises after receiving radiotherapy 
to the chest, particularly in smokers. Amadori & Ronconi (2005), Seike et al. (2021) and  Wang et 
al. (2021) from their studies, observed radiation-induced solid tumours, including lung cancer, in 
individuals treated with radiotherapy for thoracic malignancies. Radiotherapy uses high-energy 
radiation that can damage DNA and cause cancer. Regardless of radiotherapy delivery modality, 
critical chest structures get considerable radiation resulting in radiation-induced damage. These 
injuries may be treatable or irreparable. According to research on Hodgkin's disease and breast 
cancer, irradiating the lungs triples the chance of lung cancer later in life (Kaufman et al., 2008; 
Wennstig et al., 2021).  
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2.4.5 DIETARY FACTORS 
Some chemicals found in food, such as Heterocyclic amines (HCAs) in high-protein foods, have 
been carcinogenic (Rizwan Khan et al., 2017). Arsenic is a carcinogen, and its presence in drinking 
water may increase the risk of lung cancer(Roy et al., 2018; Q. Zhou & Xi, 2018).  
2.4.6 GENETIC PREDISPOSITION AND FAMILY HISTORY OF LUNG CANCER 
Lung cancer in nonsmokers appears to have a distinct genetic profile, tumour microenvironment, 
and epidemiology (de Alencar et al., 2020). It has been linked to several risk factors, including 
hereditary propensity (Benusiglio et al., 2021; de Alencar et al., 2020). Researchers have 
discovered a genetic predisposition within the bronchial epithelium of the lung that has yet to be 
resolved (Kanwal et al., 2017; I. A. Yang et al., 2013). Some researchers have linked specific 
genetic mutations to lung cancer, and having these genes may be the reason for never smokers 
developing lung cancer (Ankathil, 2010; Koeller et al., 2018). If a person's parent, sibling, or child 
has had lung cancer, developing lung cancer increases (Benusiglio et al., 2021; Osann, 1991; J. M. 
Samet et al., 1986). Suppose lung cancer occurs at a younger age or in multiple relatives, the risk 
increases. 
2.4.7 OTHER DISEASES 
Two lung diseases linked to lung cancer are chronic obstructive pulmonary disease (COPD) and 
pulmonary fibrosis. COPD makes it difficult to breathe because the lung tissue is damaged or too 
much mucus. Pulmonary fibrosis is severe scarring of lung tissue that makes breathing difficult. 
COPD history increases the risk of lung cancer and pulmonary fibrosis (Yoo et al., 2019). 
HIV infected persons have a greater risk of developing lung cancer than the universal populace 
(Chaturvedi et al., 2007; Shiels et al., 2010; Sigel et al., 2017). The HIV patient's weakened 
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immune system increases inflammation, and chronic lung problems may contribute to increased 
cancer risk. Nonetheless, HIV treatment does not result in lung cancer. 
2.5 LUNG CANCER PATHOPHYSIOLOGY (SYMPTOMS) 
Lung cancer does not typically exhibit symptoms in its early stages, but advanced malignancies 
do. The most common symptoms include chronic cough, coughing with blood, chest discomfort, 
persistent breathlessness, aching when breathing or coughing, unexplained weariness and weight 
loss, hoarseness, lack of appetite, and face or neck swelling. Cough occurs in 50–70% of 
individuals with primary lung lesions due to a mass that irritates the cough receptors in the airway 
(Latimer, 2018; NCCN, 2021; Ruano-Raviña et al., 2020; Siddiqui et al., 2021). Squamous cell 
carcinoma and small cell lung cancer have this symptom. Weight loss affects 46% of people, while 
pleuritic chest discomfort affects roughly 20% (NCCN, 2021; Siddiqui et al., 2021). Patients often 
arrive with advanced illness due to the lack of symptoms in the early stages of cancer. Lung cancer 
is often revealed due to symptoms and is less frequently seen in X-rays before symptoms appear. 
Lung cancers may be discovered as part of a cancer screening programme or in an X ray by 
coincidence. 
2.6 LUNG CANCER DIAGNOSIS 
Some lung cancers may be discovered through screening; however, most lung cancers are 
discovered because they are causing issues. As a result, people with an increased risk of lung 
cancer in the United States and other developed countries may consider annual lung cancer 
screenings with low-dose CT scans. Lung cancer screening is typically provided to older adults 
who have smoked heavily for many years or quit smoking within the last 15 years. On World 
Cancer Day 2015, Ghana's Ministry of Health unveiled its National Cancer Control Strategy with 
the theme "Not Beyond Us." The goal was to reduce the rising number of cancer cases through 
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primary prevention, effective screening, and early detection. (Mensah & Mensah, 2020) noted in 
their narrative review that despite establishing a national cancer control plan, there is still an 
increasing incidence of cancers due to a lack of cancer control preparedness.  
If a doctor believes a patient has lung cancer, numerous tests must be performed to ensure that the 
signs and symptoms are caused by cancer and not by another condition. X-rays, MRI, CT, and 
PET scans provide better information and detect tiny lesions in suspected lung cancer patients. 
Sputum cytology can also detect cancerous cells in the patient's phlegm. Bronchoscopy, 
mediastinoscopy, or needle biopsy may detect whether tumour cells are malignant. The accurate 
diagnosis of lung cancer is made in the laboratory by examining a sample of lung cells. Body tissue 
and fluid testing are required for diagnosis. A patient's malignant cells are sampled to establish the 
kind of lung cancer cell. Samples are taken from the fluid surrounding the lungs, a lung tissue 
sample known as a biopsy, or a sputum sample. The samples are taken to the lab, magnified, and 
a diagnosis is made based on the cells' characteristics.  
Lung cancer may spread to lymph nodes and cause them to enlarge (Figure 2.4), and a physical 
examination can be performed. Lung cancer often spreads to lymph nodes in the chest and neck. 
Body temperature, breathing rate, weight, blood pressure, lung, heart, and gut sound, pulse, look 
of the eyes, skin, nose, ears, mouth, organ size and amount of discomfort when touched are 
assessed during this examination. 
 
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Figure 2.4: Lung cancer metstasised to lymphatic systems causing cervical lymphadenopathy 
(Anath, 2021) 
The initial test performed to identify lung cancer is generally a chest X-ray. Most lung tumours 
look like a white-grey mass in X ray images (Figure 2.5). On the other hand, chest X-rays cannot 
provide a conclusive diagnosis since they often fail to discriminate between cancer and other 
illnesses, such as lung abscesses. If a chest x-ray indicates that a person has lung cancer, more tests 
are performed to determine the existence of lung cancer and, if present, what kind it is and how 
far it has progressed. 
 
Figure 2.5: Chest X-ray of normal lungs against cancer affected lungs (Mayo Clinic, 2020) 
Following a chest X-ray, the next test is generally a CT scan. CT scans are more diagnostic than 
ordinary chest X-rays, particularly in detecting lungs (Figure 2.6). A CT scan s an X-ray does not 
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combine a computer and X-rays to produce three-dimensional pictures of the interior of the 
patient's body. A contrast medium is provided before a CT scan to increase picture quality.  
 
Figure 2.6: Lung CT image showing (a) normal lung and (b) lung cancer with an arrow pointing 
at the tumour (Anifah et al., 2018) 
If a CT scan reveals that a patient has cancer at an early stage, a PET-CT scan may be performed. 
PET-CT can show where active cells are in the body (as shown in Figure 2.7), aiding diagnosis 
and treatment selection. A radiopharmaceutical is injected into the person before the scan. PET/CT 
enables the fusion of functional and anatomical information about the lung, allowing for more 
accurate disease staging (Hochhegger et al., 2015). 
 
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Figure 2.7:PET/CT images showing the difference between normal surrounding tissue and 
tumour with active cancer cells coloured. (a) CT image (b) PET/CT image (Hochhegger et al., 
2015) 
A biopsy is a procedure that removes tissue or fluid from the body for examination. Biopsies for 
lung tumours come in a variety of forms. When a CT scan reveals the risk of cancer in the central 
area of the chest, a bronchoscopy is recommended. A bronchoscopy is a technique that enables a 
doctor to examine a person's airways and extract a tiny sample of cells. A narrow tube with a 
camera at the end, known as a bronchoscope, is pushed through the mouth, nose, throat, and 
airways. Endobronchial ultrasound scan (EBUS) is a novel method that combines bronchoscopy 
with an ultrasound scan. EBUS enables lymph nodes in the centre of the chest for biopsy and the 
capacity to view within the airways. A lymph node biopsy may reveal whether or not malignant 
cells form in the node and what sort they are. 
Other biopsy modalities include thoracoscopy, mediastinoscopy, and cutaneous biopsy using a 
needle (Figure 2.8). The CT image aids the clinician in seeing where the abnormal tissue is in the 
lung. A needle is inserted through the chest wall and into the abnormal lung tissue to remove a 
small piece of the tissue (NCCN, 2021). Tissue obtained during a biopsy is submitted to a 
pathologist to analyse and classify the illness. The pathology report indicates whether cancer began 
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in the lung or elsewhere. If the disease began in the lungs, the report would specify the kind of 
lung cancer.  
 
Figure 2.8: CT-guided biopsy (NCCN, 2021). 
 
2.7 CLASSIFICATION OF LUNG CANCER 
There are several forms of lung cancer, and the only way to establish which type a patient has is 
by sampling. It is critical to determine the kind of cancer since it influences treatment choices and 
prognosis. 
Lung cancer is categorised into small cell lung cancer (SCLC) and non-small cell lung cancer 
(NSCLC). These categories are so-called for the sort of cancer cells and how they look under a 
microscope.  
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2.7.1 SMALL CELL LUNG CANCER (SCLC) 
As the name implies, small cell lung cancer (SCLC) is composed of microscopic cells that have 
not grown entirely. SCLC is predominant among women who have a lengthy history of smoking. 
It is the top cause of cancer death in men and the second-highest cause of cancer death in women 
worldwide. Small cell lung cancer, which often begins in the bronchi and rapidly spreads to other 
body regions and lymph nodes, is divided into limited and extensive stages. It is the most 
aggressive lung cancer, growing and spreading faster. Usually, it would have spread to other body 
regions when it is identified. SCLC accounts for around 15% of all lung malignancies (Yang et 
al., 2019; Zhao et al., 2018). 
2.7.2 NON-SMALL CELL LUNG CANCER (NSCLC) 
Non-small cell lung cancer is the most recurrent type of lung cancer, accounting for 85 per cent of 
all cases (Z. Chen et al., 2014). NSCLC consists of large mature cells, and the respiratory tract has 
many mature cells. So, depending on whether the mature cell has turned malignant, this category 
of lung cancer includes subcategories (Clark & Alsubait, 2020; Society, 2019; Zappa & Mousa, 
2016). less common types of NSLC include as carcinoid tumour, salivary gland carcinoma, 
pleomorphic carcinoma, and unclassified carcinoma. Carcinoids are found in about 5% of all 
NSCLCs. Both men and women are equally at risk of getting carcinoid cancers, although smoking 
is no apparent relation. 
2.7.2.1 ADENOCARCINOMA  
Mucin is vital for maintaining the lungs wet and is generated in the lung by particular lung gland 
cells. When these cells become cancerous, they are referred to as adenocarcinoma, where “adeno” 
means "from a gland," and glands generate mucin. Adenocarcinoma accounts for 40% of all 
NSCLCs, mainly affecting women, although it may afflict smokers and non-smokers (Zappa & 
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Mousa, 2016). Adenocarcinoma develops slowly and has a better chance of being detected early 
before spreading to other organs. 
2.7.2.2 SQUAMOUS CELL CARCINOMA 
Matured cells are also seen in the normal lung, but they are flatter than adenocarcinoma cells and 
are held together by proteins that form a desmosome. Desmosomes assist cells in forming an 
obstruction between the airways and the rest of the body. When these cells become malignant, they 
are referred to as squamous cell carcinoma, which happens around 30% of the time and is prevalent 
in men who have a history of smoking. Squamous cell carcinoma has the most substantial relation 
to smoking (Zappa & Mousa, 2016).  
2.7.2.3 LARGE CELL CARCINOMA 
Large cell carcinoma does not have many distinguishing features other than that, thus its name. It 
occurs in 10% of all NSCLCs and is more common among male smokers (Zappa & Mousa, 2016). 
This kind of lung cancer is closely linked to smoking and often begins in the core area of the lungs 
before spreading to surrounding lymph nodes, the chest wall, and distant organs.  
2.8 LUNG CANCER STAGING 
Staging is done to define the location of the lung cancer cells, the size of the lung tumour, and the 
degree to which the lung cancer has spread. Lung cancer procedures for medical practice are 
subject to staging models, which are essential for predicting prognosis and determining therapy 
options. However, it does not specify the number of years of survival. The findings of tests and 
tissue samples aid in determining the stage of lung cancer. 
The Tumour, Node, Metastasis (TNM) staging approach, which is used to grade distinct regions 
of cancer development, has been approved by the Union for Worldwide Cancer Control (UICC), 
the American Joint Committee on Cancer (AJCC), and many other international cancer centres 
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(UICC, 2016). The letter T in TNM stands for the size and extent of the primary tumour. The letter 
N denotes whether or not the tumour has spread to the lymph nodes. The letter M in the TNM 
acronym stands for metastasis, which indicates the degree to which cancer has spread throughout 
the body. Each letter has a number in the system that indicates the amount of tumour development: 
the greater the number, the more dangerous the increase. The TNM staging method for lung cancer 
from the 8th edition of the TNM staging handbook for staging and directing lung cancer therapy 
in multidisciplinary centres is shown in Table 2.1. 
Table 2.1: Lung cancer staging using TNM system 8th edition (Kay et al., 2017).  
Primary Tumour 
Tx Cannot be assessed; Tumour in sputum/bronchial washings not in imaging/bronchoscopy 
T0 No evidence 
Tis Carcinoma in situ 
T1 ≤ 3 cm surrounded by lung/visceral pleura, not involving the main bronchus 
T1a (mi) Minimally invasive adenocarcinoma  
T1a ≤ 1 cm 
T1b > 1 to ≤ 2 cm 
T1c > 2 to ≤ 3 cm 
> 3 to ≤ 5 cm or Involves the main bronchus without carina involvement or Visceral 
T2 
pleural invasion or atelectasis/post obstructive pneumonitis extending to the hilum 
T2a > 3 to ≤ 4 cm 
T2b > 4 to ≤ 5 cm 
> 5 to ≤ 7 cm or Separate tumour in the same lobe or Direct invasion of the chest wall 
T3 
(includes parietal pleura and superior sulcus)/parietal pericardium/phrenic nerve 
T4  > 7 cm or 
Separate tumour in different lobe of ipsilateral lung or Invasion of heart/ great 
 vessels/diaphragm/mediastinum/trachea/carina/oesophagus/ recurrent laryngeal 
nerve/vertebral body 
 Regional lymph node 
Nx Cannot be assessed 
N0 No involvement 
N1 Ipsilateral peribronchial and/or hilar nodes and intrapulmonary nodes 
N2 Ipsilateral mediastinal and/or subcarinal nodes 
N3 Contralateral mediastinal or hilar; ipsilateral/contralateral scalene/supraclavicular 
 Distant metastasis 
M0 No distant metastasis 
M1 Distant metastasis is present 
M1a Tumour (s) in contralateral lung; pleural/pericardial nodule/malignant effusion 
M1b Single extrathoracic metastasis 
M1c Multiple extrathoracic metastases in one/ more organs 
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Figures 2.9 to 2.14 are the illustrations for the various TNM categories. 
 
Figure 2.9: Lung cancer primary tumour T1 illustration (Kay et al., 2017). 
 
Figure 2.10: Lung cancer primary tumour T2 illustration (Kay et al., 2017). 
 
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Figure 2.11: Lung cancer primary tumour T3 illustration (Kay et al., 2017). 
 
 
Figure 2.12: Lung cancer primary tumour T4 illustration (Kay et al., 2017). 
 
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 Figure 2.13: Lung cancer regional lymph node illustration (Kay et al., 2017). 
 
 
Figure 2.14: Lung metastasis illustration (Kay et al., 2017). 
 
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Cancer stages are determined by a combination of TNM classifications and prognosis. Although 
occult carcinoma and stage 0 are uncommon diagnoses, there are four (4) significant stages of 
cancer, as detailed in Table 2.2 and represented in Figure 2.15. 
Table 2.2: Tumour staging 
Stage Meaning 
Stage 0 cancer cells are found in the lining of the airways 
Stage I a small tumour is found inside the lung 
Stage II Cancer grows and spreads to nearby lymph nodes or non-lung tissues. 
The tumour grows into any size and is found in lymph nodes on the same side 
Stage III A 
of the chest or nearby organs. 
This is similar to stage III-A, but in this case, cancer cells are found in lymph 
Stage III B nodes on the opposite side of the chest. Cancer may also be found in lymph 
nodes above the collarbone. 
Tumours might be found in both lungs. Additionally, cancer may have spread 
Stage IV 
to distant organs such as the brain, liver, skin, and other distant tissues. 
 
 
Figure 2.15: Lung cancer stages (St. Stamford Modern Cancer Hospital Guangzhou, 2019).  
SCLC has fewer components than NSCLC, and most doctors use a two-stage technique, restricted 
and expanded. On one side of the chest, cancer can be treated with a single radiation field. 
Cancercancer may have spread to the other side of the chest or distant organs. 
Cancer staging is performed twice for some individuals: before treatment (clinical stage) and after 
surgery (pathologic stage).  
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2.9 LUNG CANCER TREATMENT AND MANAGEMENT 
Early identification of lung cancer is essential for achieving a cure; regrettably, many patients seek 
medical assistance after the illness has progressed. Lung cancer therapy is determined by the kind 
of cancer mutation, the level of dissemination, and the patient's overall health. A team of Radiation 
Oncologists, Radiation Therapists, and Medical Physicists collaborate to provide the best therapy 
for each patient. The doctor also talks with the patient about the treatment choices available for 
their cancer kind and stage, including the advantages, dangers, and side effects of each modality. 
Surgery, radiation, chemotherapy, targeted therapy, or a combination of these therapies may be 
used to treat non-small cell lung cancer. Radiotherapy and chemotherapy are the most often used 
treatments for small cell lung cancer. Radiofrequency ablation (RFA), targeted medication 
therapy, immunotherapy, and palliative operations are some of the additional therapeutic 
possibilities. 
2.9.1 SURGERY 
Surgery is a typical therapy for lung cancer; however, the technique varies from person to person. 
Lung cancer surgery entails removing a piece or the complete lung. A surgeon performs the 
operation, which includes one of the following procedures: wedge resection, segmental resection, 
lobectomy, and pneumonectomy, as illustrated in Figure 2.16. Lobectomy and pneumonectomy 
are the most prevalent. The excision of a piece of the lung containing the tumour and a margin of 
healthy tissue is known as a wedge resection. Segmental resection removes a more considerable 
volume of the lung but not the whole lobe. A lobectomy removes one whole lung lobe, while a 
pneumonectomy is the removal of the entire lung. Surgical resection for resectable and operable 
early-stage cancer might be used as a treatment for NSCLC, depending on the feasibility of the 
cure (Lemjabbar-Alaoui et al., 2015). 
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However, patients may refuse surgery or be inoperable, in which case the malignancy may be 
treated with radiation. 
 
Wedge Resection Segmentectomy Lobectomy Pneumonectomy 
Figure 2.16: Lung cancer surgical treatment options and resected specimen in dark red  (Hu, 
2016).  
2.9.2 CHEMOTHERAPY 
Chemotherapy employs the use of medications to destroy cancer cells. One or more medicines 
may be delivered intravenously or consumed orally in cycles. Lung cancer chemotherapy 
chemicals are injected into the veins and circulate throughout the body, treating cancer. Adjuvant 
chemotherapy or concomitant chemo-radiation are often used to destroy remaining malignant cells 
in patients. Chemotherapy may help individuals with metastatic cancer relieve pain and other 
symptoms (Nakamura & Maeda, 2022; S. Yang et al., 2019). The rationale for treating lung cancer 
with concurrent chemo-radiation is to enhance regional and systemic cancer control, which has 
resulted in increased overall survival for NSCLC (Curran et al., 2011; Postmus et al., 2017).  
Cancer cell death is caused by targeted medication treatment, which focuses on particular defects 
inside cancer cells. Immunotherapy uses the immune system of patients to combat cancer. 
Palliative care is a kind of supportive care offered to patients to help them cope with the signs, 
symptoms, and side effects of cancer therapy. The care provides patients comfort before and after 
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cancer treatment and has been shown to enhance patient mood and quality of life(Melin-Johansson 
et al., 2010; Nottelmann et al., 2021).   
2.9.3 RADIOTHERAPY 
Radiotherapy employs high-energy X-rays or particles to treat lung cancer. Radiotherapy is often 
used as the primary treatment before surgery to decrease the tumour volume and then as the 
secondary treatment after surgery to kill any cancer cells that may remain in the treated region or 
treat lung cancer that has spread to other areas of the body. In other circumstances, radiation is the 
primary treatment, either alone or in conjunction with chemotherapy. Radiotherapy is used in 
conjunction with surgery for NSCLC and chemotherapy for SCLC. Radiotherapy is also utilised 
when a patient is inoperable or refuses surgery. In advanced cancer patients, radiotherapy may be 
used to ease discomfort. 
External beam radiation treatment is the most often utilised approach for conforming radiation 
beams from an external source to the tumour contour. The goal is to send the highest amount of 
radiation to the tumour while giving the least amount of radiation to the surrounding normal 
tissues. Three-dimensional conformal radiation treatment (3D-CRT), intensity-modulated 
radiation therapy (IMRT), stereotactic body radiation therapy (SBRT), and proton therapy are 
some of the procedures used to treat lung cancer. 
Three-dimensional conformal radiation treatment (3D-CRT) produces an x-ray beam that fits the 
geometry of the target; however, it is not as focused as IMRT. 
Intensity-modulated radiation treatment (IMRT) uses x-ray beams tailored to the target's form 
while sparing normal tissue. It takes roughly six weeks to complete treatment. 
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Stereotactic body radiation treatment (SBRT) uses high-dose X-ray beams to treat cancer. High 
radiation dosage is provided for each treatment, but only for a fraction of the time. Treatment 
typically takes approximately a week and a half. 
Proton therapy uses proton beams to treat cancer. Proton beams administer radiation primarily 
inside the tumour, and therapy takes around six weeks. 
A multidisciplinary team of radiation oncology experts creates the treatment plan and administers 
it to lung cancer patients. A radiation oncologist, a medical physicist, a thoracic surgeon, a 
radiologist, a histopathologist, an oncology nurse, and a palliative care representative are all part 
of the team. 
Currently, most patients with small inoperable lung cancer are treated with stereotactic body 
radiation treatment (SBRT). Inoperable patients include the elderly, those with chronic heart 
failure, and those who are in danger of postoperative haemorrhage because they are using blood-
thinning medications (Keall, Balter, et al., 2006; Keall, Mageras, et al., 2006; Robert Timmerman 
et al., 2010; Zappa & Mousa, 2016). 
 
2.10 STEREOTACTIC BODY RADIATION THERAPY (SBRT) 
2.10.1 OVERVIEW  
Stereotactic Body Radiation Therapy (SBRT) is a cutting-edge procedure used to treat primary 
and metastatic tumours in various anatomical areas. SBRT uses cutting-edge technology to target 
deep-seated tumours inside the body with high doses of radiation. It is a non-invasive technique 
since it is utilised when surgery is either impossible or complicated. In contrast to conventional 
fractionated therapy, which is provided in relatively moderate doses over 5 - 6 weeks, SBRT 
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includes administering high-dose radiation treatment, often up to five sessions. Each therapy 
session lasts between 30 and 60 minutes. SBRT has the potential to be utilised to treat malignancies 
of the liver, lung, abdomen, lymph nodes, and spine.  
SBRT treats extracranial malignancies with highly conformal radiation in 5 fractions. The 
administration of a very high dosage in a short period results in a high biologically effective dose 
(BED). SBRT is also more convenient for patients and more cost-efficient due to the short total 
treatment period. As scientifically proven, patients treated at the centre with SBRT will have 
superior cosmetic treatment results than those treated with surgery (Ezer et al., 2015; Grills et al., 
2010; Shaverdian et al., 2015; X. Wang et al., 2018; Yamamoto et al., 2014). Nonetheless, centrally 
placed tumours need extra caution in radiotherapy delivery since their placement implies a high 
potential of typical tissue damage, which might have adverse clinical effects (Bahig et al., 2016; 
Haseltine et al., 2016; Kang et al., 2015; Modh et al., 2014; Thompson & Rosenzweig, 2019; 
Yamashita et al., 2014). As a result, SBRT necessitates a high degree of precision and accuracy 
throughout the treatment delivery procedure. The American Association of Physicists in Medicine 
(AAPM), as well as the ACR-ASTRO, have made recommendations on the use of SBRT, 
including safety, treatment planning, setup, and therapy delivery, among other things, to ensure 
safe and quality SBRT (Benedict et al., 2010; Halvorsen et al., 2017). These therapies have been 
administered effectively utilising the respiratory gating approach (Diwanji et al., 2017; Giraud et 
al., 2011; Nagata & Kimura, 2018; Saito et al., 2014; Videtic et al., 2017). KATH presently 
features a Varian CLINAC iX with SBRT and gating capabilities. Respiratory gating approaches 
were chosen for this investigation because they have a high potential for improving irradiation of 
tumour areas influenced by respiratory motion, namely the lung. The adoption of this approach 
minimises pulmonary toxicity at large dosages. Gated Stereotactic Body Radiation Therapy 
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(SBRT) will be investigated in this case study of lung malignancies to counteract the respiratory 
generated motion effect since there is more clinically verified evidence of greater local 
control(Aparicio et al., 2019; Lagerwaard et al., 2008; Mahadevan et al., 2018; Nagata & Kimura, 
2018; Singh et al., 2014; Robert Timmerman et al., 2010; Yeung et al., 2017). Timmerman et al. 
(2010) assessed the effectiveness and toxicity of SBRT in 55 medically inoperable patients with 
early-stage lung cancer. After three years, the research found a patient survival rate of 55.8 per 
cent, excellent rates of local control, and modest treatment-related morbidity. 
SBRT also offers patients the logistical benefit of a substantially shorter radiation schedule without 
sacrificing results. The benefits of geometric accuracy and dosimetric improvements are predicted; 
however, this work focuses on employing respiratory gating. 
Bromgren, Lax, and co-workers at Karolinska University Hospital pioneered stereotactic radiation 
to treat lung and liver tumours in 1991 (Blomgren et al., 2004; Lax et al., 1998). SBRT was 
developed and successfully deployed in Japan for lung tumours in 1994 (Uematsu et al., 1997). 
Following this novel invention, several centres in Japan, Europe, and America utilised SBRT, with 
remarkable outcomes recorded (Blomgren et al., 2009; Robert Timmerman et al., 2003; Uematsu 
et al., 1997). In instances where treatment choices were previously restricted, stereotactic body 
radiation therapy is now employed. It is primarily employed when there are a limited number of 
recurring locations to give an ablative dosage of radiation, such as lymph nodes, lungs, spine, and 
liver. It has been the therapy of choice for many persons with low-volume tumours for whom 
surgery may not be the best option. SBRT is distinguished by patient immobilisation, the limitation 
of average tissue exposure to high-dose radiation, the prevention or accounting for organ 
movements such as respiratory motion, the use of stereotaxy, and the delivery of doses with 
subcentimeter precision. Target delineation, treatment planning, and radiation administration are 
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the three main components of an SBRT therapy. A radiation oncologist, medical physicist, 
radiation therapist, and, depending on the body location and indication, a diagnostic radiologist, 
nurse, anesthesiologist, and dosimetrist are all part of the therapy team. Surgeons and other medical 
experts may also be part of the treatment team. 
SBRT differs from other forms of external beam radiation therapy (EBRT) in that it uses high-
dose radiation, delivers one to five fractions within a few days, is non-invasive, reduces overall 
treatment time, has high effectiveness, accuracy, and improved treatment response, and is available 
as an outpatient service. SBRT employs image-guided technology with millimetre-scale precision 
and the capacity to protect healthy tissue while increasing the radiation dosage. SBRT has a 
sizeable local control rate ranging from 60% to 90%, which is a significant advantage over other 
modalities (Aparicio et al., 2019; Janssen et al., 2016; Lee et al., 2021; Singh et al., 2015; von 
Reibnitz et al., 2018). Some multicentre studies have been conducted to support the use of SBRT. 
Local immune function is often intact, particularly when compared to conventional radiation. 
SBRT obtained a 98 per cent local control rate in the phase II RTOG 0236 experiment (Nyman et 
al., 2016a; R Timmerman et al., 2014). SBRT gave a total dosage of 60 Gy to the tumour in three 
fractions for one week. In NSCLC patients with proven comorbidities such as emphysema, heart 
disease, and stroke, three-year overall survival (OS) was 56% (R Timmerman et al., 2014). SBRT 
does not require hospitalisation due to the short duration of the treatment course, giving patients 
more freedom in their busy lives, even if they are travelling from a distance, resulting in little or 
no interruption of their treatment schedule. Standard fractionated radiotherapy (2D-CRT, 3D-
CRT, and intensity-modulated radiation treatment (IMRT)) is commonly administered in 25–50 
fractions over five days per week for 5 to 10 weeks. SBRT has a significant drawback in that it 
requires reasonable motion control and an image guiding system, which may not be accessible in 
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all departments or health care institutions. Again, SBRT is not appropriate for many situations; it 
is only appropriate for tiny, well-defined tumours that can be observed on imaging such as CT or 
MR scans. 
Furthermore, if the cancer is adjacent to a fine, typical structure, such as the spinal cord or intestine, 
the quantity of radiation that may be safely supplied may be restricted. SBRT may sometimes 
induce side effects ranging from minor tiredness and temporary oesophagitis to catastrophic 
occurrences like pneumonitis or bleeding. SBRT is less hazardous than standard radiation since it 
does not need surgical incisions. Some general side effects and complications of radiation may 
occur, including weariness, nausea, and oedema. 
2.10.2 LUNG SBRT 
Lung SBRT/SABR is a well-established therapeutic option for individuals with early-stage non-
small cell lung cancer and those with one or more lung metastases (secondary). For the treatment 
of non-small cell lung cancer, it is considered that exceptionally high radiation doses are required 
(Kumar et al., 2017; Newman et al., 2019; Robert Timmerman et al., 2010). Lung SBRT was 
initially utilised for peripheral lung tumours (tumours on the lung's margins). However, it is now 
being employed for more central tumours (tumours towards the middle of the lungs and deeper in 
the lungs). The movement of the patient's breathing may be controlled, allowing for extremely 
high and targeted radiation doses to be delivered. In several clinical studies, patients with a minor 
amount of metastatic lung disease (secondary tumours from other cancers that have spread to the 
lung) may also benefit from lung SBRT (Chinniah et al., 2017; Lindberg et al., 2015; Miyakawa 
et al., 2017; Navarro-Martin et al., 2016; Nyman et al., 2016a, 2016b; Ricardi et al., 2010; 
Shibamoto et al., 2015; R Timmerman et al., 2014). 
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SBRT delivery has been made feasible by various technical developments, including the ability to 
comfortably immobilise patients during treatment, tumour movement monitoring, improved 
tumour identification, and more precise and accurate radiation therapy administration. IMRT, 
image-guided radiotherapy (IGRT), and volumetric-modulated arc treatment (VMAT) are 
advanced approaches used. The SBRT process comprises patient positioning for comfort, CT 
image capture (potentially with respiratory information to reconstruct tumour movement), 
verification imaging before treatment, and radiation administration using a linear accelerator.  
2.11 LUNG SBRT IMPLEMENTATION PROCESS 
The patient is immobilised, the lung and target are defined, and advanced techniques like IMRT, 
IGRT, and VMAT are used to tailor the dosage to the target. Using lung SBRT in an oncology 
centre requires several technical and clinical issues. Dahele et al. (2008) addressed patient 
evaluation, simulation and treatment planning, tumour and organ at risk characterisation, trial setup 
before treatment, online image guiding, and patient follow-up. 
In most cases, SBRT begins with simulation. Using immobilising devices during CT simulation 
guarantees that the patient's posture is reproducible during therapy delivery. Due to mobility, 
particularly in lung tumours, a four-dimensional (4-D) scan is conducted to incorporate time in the 
CT scan. Treatment planning takes about a week after the 4-D scan. The treatment plan includes 
identifying the target organs and orienting the radiation beam to provide the recommended dose. 
The patient is then immobilised and scanned to determine the tumour's position and account for 
any changes that day. Daily personalised therapy for a patient is generated. 
2.12 TREATMENT AND SIMULATION 
SBRT requires determining each organ's radiation tolerance. This simulation procedure includes 
marking up for set up and target motion systematic and random errors. Image-guided radiotherapy 
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uses numerous imaging modalities before or during radiation treatments to align and evaluate the 
structural agreement between the simulation anatomy, radiotherapy treatment plan, and patient 
(IGRT). 
2.12.1 TARGET MOVEMENT 
The role of respiratory-generated motion has hampered the accuracy and precision of dose 
distribution to cancers while sparing normal tissues. According to Mageras et al. (2004), 7 out of 
12 patients had tumour motion of more than 1 cm craniocaudally. Yu et al. (2012) discovered that 
early-stage non-small cell lung cancer patients had more than 50% greater tumour mobility than 
locally advanced individuals. Tumour movement is linked to location, volume, and diaphragm 
motion. 
Respiration is semi-periodic and predictable for each patient. Since respiratory motion patterns 
vary between fractions and even within a fraction, no common respiratory motion patterns can be 
anticipated for a single patient. Lung tumour motion was linked to diaphragm motion, superior-
inferior lung tumour implantation, GTV, and illness T stage (Liu et al., 2007). It has been reported 
that the range of respiratory motion is up to 50 mm, with the lower lung demonstrating the most 
significant tumour movement (Harada et al., 2016; Jan et al., 2015; Keall, Balter, et al., 2006; Liu 
et al., 2007; Seppenwoolde et al., 2002; Shimizu et al., 2001; Shirato et al., 2004). Similarly, 
Langen & Jones (2001) and Liu et al. (2007) found that tumour motions are highest superior-
inferior, with critical parts anterior-posterior and left-right.  However, when studying lung tumours 
in general, the tumour mobility is generally less than 5 mm (Liu et al., 2007). According to (Liu et 
al., 2007), only 40% of lung tumours migrate 5 mm or more, and only 12% migrate 10 mm or 
more. 
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Torshabi & Dastyar (2017) studied the effects of tumour motion on treatment quality and 
irradiation of thoracic tumours and compensating strategies. Using a correlation model to observe 
the amount of tumour mobility revealed ways that may increase precise targeting of dynamic 
tumours for high tumour control and minimal normal tissue problems, Yoganathan et al. (2017) 
investigated the prevalence, effect, and management of respiratory-induced target motion in 
radiation treatment using a correlation model to assess the amount of tumour movement. Their 
findings suggest that respiration-induced motion affects radiotherapy. Respiratory motion, for 
example, adds dosimetric error. Tracking, motion encompassing, and gating are three strategies 
for managing respiratory motion. 
Respiratory-induced lung tumour mobility has affected imaging and radiation treatment (Mageras 
et al., 2004; Shimizu et al., 2001; Yu et al., 2012). Respiratory motion affects picture capture for 
radiation, generating artefacts when ignored. They distort the target volume and produce 
inaccurate positional and volumetric data. Artefacts are frequent in thoracic CT images. 
There are imaging and treatment planning methods to address the issue of tumours moving due to 
respiratory activity. Since tumour mobility occurs during imaging and medication administration, 
it is essential to account for tumour movement in imaging and planning. 
2.12.2 IMMOBILISATION AND POSITIONING 
SBRT for lung cancer patients requires a precise, repeatable, and comfortable immobilisation 
device. Lung cancer immobilisation devices mimic the patient's posture during simulation and 
radiation. Ideal immobilisation methods and technologies reduce intrafraction motion, restrict 
beam attenuation, and do not interfere with patient localization systems (Molitoris et al., 2019). 
Thermoplastic masks (TMPs) and vacuum cushions (VCs) are two standard SBRT immobilisation 
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devices (Chen et al., 2019). Furthermore, abdominal compression strategies have been utilised to 
restrict respiratory tumour mobility during the simulation and subsequent radiation treatments. 
2.12.3 RESPIRATORY MOTION ASSESSMENT AND CONTROL  
In SBRT, mobility is a significant issue, especially in lung cancer, as the tumour moves a lot while 
the patient breathes. If there is little mobility, it is integrated into the desired volume. If the motion 
is significant, a large quantity of normal lung tissue may be treated to account for it. This condition 
demands motion management. Several malignancies, most often lung, liver, and abdominal 
tumours, require accurate computed tomography (CT) studies in the presence of respiratory 
activity. 
2.12.3.1 EVALUATION OF MOTION 
Managing tumour mobility during simulation and therapy is accomplished after placement and 
immobilisation. The phases of this exercise are evaluation and control. Motion assessment 
measures the time-dependent 3-D displacements of a tumour target or a reliable surrogate. Most 
motion evaluations use 4-D CT but can be done with real-time fluoroscopy or slow CT. 
2.12.3.1.1 COMPUTED TOMOGRAPHY IN FOUR DIMENSIONS (4-D CT) 
The 4-D scan is used during simulation to help locate tumour movements, which is employed in 
treatment planning and therapy. Incorporating time and motion into a three-dimensional computed 
tomography scan creates a unique volumetric data set of the human body. That depends on the CT 
scan series. For better diagnosis and therapy, a 4D CT scan delivers exact information about 
moving interior organs (Ford et al., 2003; Hugo & Rosu, 2012; Hutchinson & Bridge, 2015; Pakela 
et al., 2022; Vedam et al., 2003; W. J. Wang et al., 2018). Unlike a 3D CT scan, a 4D CT scan 
requires the body part to be stationary. 4D visuals show breathing, tumour movement, and how 
surrounding organ movement affects tumour position. Using 4D CT, radiation can be delivered at 
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a specific time in the respiratory cycle, reducing treatment-side effects (Atkins et al., 2015; Harada 
et al., 2016; Hof et al., 2009; Wang et al., 2009). Despite the benefits of 4D CT, variability in 
breathing patterns limits collecting. Artefacts can be visible even with breathing instruction. As 
well as higher patient radiation exposure and increased clinician work in delineating the target, 
4DCT has its drawbacks.  
2.12.3.1.2 SLOW CT SCAN 
Currently, 4D-CT is used to remove the effects of respiratory motion to reduce tissue toxicity and 
ensure implementation accuracy. No four-dimensional computed tomography (4D-CT) machine 
is currently available in Ghana's three radiation oncology centres. Before 4-D CT, most European 
cancer centres employed slow CT, which proved beneficial (Chinneck et al., 2010; Lagerwaard et 
al., 2001; Van Sörnsen De Koste et al., 2001, 2003; S. A. Yoganathan et al., 2017). As a result, 
this study will utilise a slow CT scan. Slow CT scanning is performing many CT scans throughout 
numerous breathing cycles. A slow CT scan is performed with a slow gantry rotation speed to 
capture the entire spectrum of tumour movement within each slice. A slow CT scan produces a 
volume that encapsulates the tumour. 
2.12.3.2 MOTION CONTROL TECHNIQUES 
2.12.3.2.1 ABDOMINAL COMPRESSION 
Abdominal compression (AC) is a systematic method for controlling respiratory motion in lung 
cancer patients receiving SBRT. Several studies have demonstrated its usefulness in reducing the 
amplitude of respiratory-induced tumour movements (Heinzerling et al., 2008; Negoro et al., 2001; 
Qi et al., 2021). However, it is difficult to replicate the compressive effects of AC throughout an 
SBRT treatment due to changes in the patient's anatomy, girth, and breathing patterns. Due to these 
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modifications, the likelihood of underdosing and overdose of neighbouring normal tissues may 
increase. 
2.12.3.2.2 INHALATION AND EXHALATION BREATH-HOLD CT 
Breath-hold CT scans are done twice during the breathing cycle, at the end of the inspiration and 
the expiration. Breath-hold is linked to a duty cycle in which the beam is turned on and off based 
on how well the tumour's location is known at all times.  
2.12.3.2.3 GATING  
The therapy beam may be 'gated' or administered only during specified respiratory phases or 
amplitudes set during treatment planning. During treatment, an external surrogate is employed to 
assess the breathing cycle. The association between surrogate gesture and tumour motion must be 
evaluated regularly to verify that there is no geographical miss. Gating may be done in two ways: 
by phase or amplitude, although phase-based gating is more prevalent. Respiratory gating has been 
explored, and many motion approaches have been used as surrogates for tumour placement 
(Giraud et al., 2011; Giraud & Houle, 2013; Kraus et al., 2021; Saito et al., 2014). 
2.12.3.2.4 TRACKING  
Tumour tracking techniques are enhanced motion management that enables real-time tumour 
position tracking while continually irradiating the tumour (Giraud & Houle, 2013; Seppenwoolde 
et al., 2002; Shimizu et al., 2001).  
2.12.3.3 TUMOUR AND OAR DELINEATION 
For effective and safe lung stereotactic body radiation therapy planning, accurate identification of 
the tumour and surrounding organs at risk is crucial (SBRT). SBRT utilises the target criteria 
established by the International Commission on Radiation Units and Measurements in its Reports 
50 and 62 (ICRU 50, 1993; ICRU 62, 1999). The clinical target volume (CTV) and the position 
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may change due to respiratory movements or organ dynamics in specific locations. Respiratory 
motion is often compensated for by increasing the CTV by an internal motion margin, resulting in 
an internal target volume (ITV) volume. Because the demarcation of an ITV implicitly includes 
the CTV under the premise that microscopic disease expansion is integrated within the zone of 
internal motion, the CTV is often left undefined in these instances. Stable locations may not need 
the use of an ITV.   
 
2.12.4 TREATMENT PLANNING 
The planning CT is imported into the Treatment Planning System (TPS). A treatment plan 
employing the optimal combination of radiation beams to the target while sparing normal tissues 
is developed. Treatment Planning System (TPS) is specialised software used to produce patient-
specific treatment plans. Before treating patients, these systems primarily enable clinicians to 
anticipate the dose delivered to each voxel in the patient for a particular orientation of the radiation 
beams and other factors. The ideal treatment plan with the highest therapeutic ratio is selected. 
Simple non-overlapping beams or arcs covering a sizeable angular range are used to achieve rapid 
dose fall-off in SBRT. Assuring that the PTV dose coverage is adequate, the radiation oncologist 
checks dose/volume statistics. The volume of nearby normal tissues exposed to high and medium 
doses is reduced. An optimised 3-D design eliminates excessive prescription dosage levels within 
normal tissues. Dose/volume statistics for surrounding tissues and organs ensure that volume-
based restrictions are not exceeded. 
PTV margins can be estimated utilising enhanced treatment planning methods that account for 
image guidance's improved positional precision and thoracic tissue density fluctuations. Treatment 
planning options include 3-D CRT, IMRT, VMAT, and ARC.   
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Before treatment plan approval, evaluation occurs. There are numerous evaluation techniques 
available for radiation plans. In general, the evaluation of a treatment plan is conducted on two 
levels: the treatment portals and the isodose distribution. On five different levels, the isodose 
distribution can be examined: isodose curves, orthogonal planes and isodose surfaces, dose 
distribution statistics, differential dose-volume histogram, and cumulative dose-volume histogram. 
In radiotherapy treatment planning, dose-volume histograms (DVHs) connect radiation dose to 
tissue volume and are commonly utilised. Differential and cumulative DVHs are two often 
employed forms. Differential DVH represents the proportion or absolute volume (depending on 
the mode of the display) receiving dosage in the corresponding dose bin. 
In contrast, cumulative DVH reflects the percentage or absolute volume getting a value greater 
than or equal to the corresponding dose bin's value. These DVHs are also utilised to construct 
additional radiobiological plan parameters, including tumour control probability (TCP) and normal 
tissue complication probability (NTCP) (NTCP). Cumulative DVH is employed at the research 
centre to evaluate treatment plans. It is the conversion that determines which volume receives 
which dose. It offers dose distribution statistics over a three-dimensional matrix of points 
representing the patient's anatomy as a quantitative evaluation tool.  
2.12.5 SBRT QUALITY ASSURANCE PROGRAMME 
SBRT needs higher precision and accuracy criteria than traditionally fractionated radiation therapy 
or intensity-modulated delivery because of the high radiation doses used per fraction. Several task 
groups and studies exist to aid in the commissioning and quality assurance of SBRT delivery 
devices (Lambrecht et al., 2019; Moustakis et al., 2020; Solberg et al., 2012; Xia et al., 2020). 
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2.12.6 TREATMENT DELIVERY AND VERIFICATION 
Each therapy requires accurate patient positioning, radiation beam placement, and stereotactic 
localisation of the target, which is achieved by imaging and implanting a fiducial marker (s). The 
projected effects are identical whether delivery systems use room-mounted or on-board x-ray or 
CT-based localisation for image guidance. Visible tumours, fiducial markers, or pertinent 
anatomic landmarks are utilised for any localisation strategy. Imaging can also confirm the 
localization or preceding filling/emptying (i.e. full bladder treatments) of critical normal 
structures. Image-guided stereotactic surgery aims to confirm or modify the patient's position 
relative to the anticipated image data collection. 
The inability of motion assessment methodologies to effectively account for changes in breathing 
patterns between the time of image capture and therapy is a disadvantage. Researchers have 
considered respiratory gating to mitigate this drawback, which includes using a trigger to activate 
and deactivate therapy. Some tumour mobility management techniques may be required for SBRT 
to reduce lung tumour migration. This will reduce the extent of the radiation field, hence 
decreasing the amount of healthy tissue exposed to a high radiation dose. Four-dimensional 
imaging (4-D MRI and 4-D CBCT), gating, monitoring, and breath-hold techniques are some of 
the tumour motion control measures performed in the room before therapy administration. 
2.12.7 IMAGE-GUIDANCE RADIOTHERAPY (IGRT) 
Image-guided therapy administration is a crucial aspect of stereotactic treatment administration. 
The primary objective of IGRT is to improve treatment precision by accurately matching the 
patient and his or her tumour before radiation administration. Improved image guidance may result 
in shorter PTV margins and lower doses to OARs while preserving optimal target coverage. 
Multiple studies have demonstrated that image-based verification of the target location has the 
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most significant impact on improving the precision of lung SBRT. Therefore, daily pre-treatment 
imaging is performed with online correction of set-up errors and baseline shifts; imaging must 
reveal the lung tumour directly or implanted markers as proxies for cancer location. During or after 
SBRT, imaging serves as a quality control measure. Kilovolt (kV)/megavolt (MV) orthogonal X-
rays or cone-beam (CB) kV/MV CT scans may give precise alignment. 
Electronic portal imaging systems were used after using planar film for image guiding (EPIDs). 
Verifying the treatment field via MV imaging is still common. While MV imaging is suitable for 
soft tissue contouring, it is inferior for bone. The addition of kV imaging arms to linear accelerators 
and EPID data collection have been widely used due to lower patient dosage and improved image 
quality. The EPID has limitations in imaging dosage, fiducial requirements, volumetric spatial 
resolution, and directional beam entrance. CBCT enables patient placement modification based on 
3D soft tissue architecture, unlike the planning scan. 
2.12.8 FOLLOW-UP AND OUTCOMES ASSESSMENT 
All treated patients should be monitored for local control, survival, and normal tissue damage. In 
addition to participating in medical follow-up, radiation oncologists should review post-SBRT 
diagnostic imaging for possible post-treatment sequelae. Subacute or late toxicities can arise 
months or even years after radiation therapy. A legislative or regulatory peer-review method 
should be used to acquire confidential peer-review data. 
  
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CHAPTER THREE 
MATERIALS AND METHODS 
3  
3.1 ETHICAL STATEMENT 
The research protocol was reviewed and approved by the Ethics Committee for Basic and Applied 
Sciences (ECBAS) of the University of Ghana (ECBAS 05/20-21) and Komfo Anokye Teaching 
Hospital Institutional Review Board (KATH IRB) (KATH IRB/AP/095/21) in Appendix A. 
3.2 STUDY SITE 
The study was carried out at the Oncology Directorate of Komfo Anokye Teaching Hospital 
(KATH). There are only three radiotherapy centres in Ghana, two public (Komfo Anokye 
Teaching Hospital and Korle Bu Teaching Hospital) and the other private (Sweden Ghana Medical 
Centre). Komfo Anokye Teaching Hospital is a 1200-bed facility located in Kumasi, the Regional 
Capital of the Ashanti Region, with a total projected population of 4,780,380 (2010 Ghana 
population census). KATH’s geographical location, the country's road network, and the 
commercial nature of Kumasi make the hospital accessible to all the areas that share boundaries 
with the Ashanti Region and Ghana. The Hospital serves patients from twelve out of the sixteen 
administrative regions in Ghana. It also receives patients from neighbouring countries, including 
Ivory Coast and Eastern Faso. The Hospital is made up of thirteen clinical Directorates and two 
non-clinical Directorates. The oncology Directorate is part of the clinical Directorates.  
KATH Oncology Directorate provides outpatient services: radiation oncology, medical oncology, 
and haematology. The oncology Directorate is resourced with a medical linear accelerator, cobalt 
60 teletherapy unit, X ray simulator, LDR brachytherapy, and 3D and 2D treatment planning 
systems to provide cancer care to patients in areas ranging from primary, secondary and tertiary 
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care. The centre treats all cancers, with over 1200 patients treated yearly. Lung malignancies 
referred to as KATH are treated as static tumours without the use of any motion management 
strategies. Thus, comparatively more significant margins are used to account for tumour motion 
during treatment planning, resulting in the irradiation of relatively larger healthy tissue sizes 
around the tumour and leading to relatively high toxicity in the lungs and radiation injuries such 
as radiation pneumonitis. Therefore, it is imperative to develop and implement an approach for 
lung cancer radiotherapy at KATH that considers the tumour motion. The medical linear 
accelerator used in KATH for external beam radiotherapy is equipped to deliver SBRT treatment. 
However, such has not been done. This approach can significantly conform dose tightly to the 
target volume related to tumour control and could lead to enhanced biochemical degeneration free 
survival and cancer advancement free survival. Thus, it will have a very high impact on the care 
provided to lung cancer patients at KATH. Furthermore, irradiating less healthy lung tissue will 
mean fewer treatment toxicities and a potential increase in patients' quality of life. 
 
3.3 EQUIPMENT 
3.3.1 LINEAR ACCELERATOR  
A medical linear accelerator (LINAC) is a device used for external beam radiotherapy for patients 
with cancer. Varian Clinac iX is the linear accelerator used at the Oncology Directorate of KATH 
for cancer treatment. The Clinac iXTM linear accelerator (Figure 3.1) by Varian Medical Systems, 
Incorporation. is a customised external beam radiotherapy equipment for treating cancer with 
image guidance. The Clinac offers 3D CRT, IMRT, IGRT, VMAT, RapidArc™ and stereotactic 
radiosurgery treatments. Clinacs are usually equipped with On-Board Imager (OBI), high-intensity 
mode, RapidArc, RPM gating and motion management tools to deliver fast and effective patient 
treatments with accuracy. The Clinac iX installed at KATH for the treatment of cancer patients 
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has two-photon energies (6 MV and 16 MV) and four-electron energies (6 MeV, 9 MeV, 12 MeV 
and 16 MeV). The Clinac iX offers two photon beams (6 and 16 MV) and four-electron energies 
(6, 9, 12 and 15 MeV). The Clinac customizes high energy x-rays or electrons to conform to a 
tumour's shape and destroy cancer cells while sparing surrounding normal tissue. Clinac iX is used 
to treat all body sites using conventional techniques.  
 
Figure 3.1: Varian Clinac iX. 
 
3.3.2 COMPUTED TOMOGRAPHY (CT) SCANNER MACHINE 
A CT scanner machine is medical diagnostic equipment that uses x rays to generate 3D images of 
the interior of patients for diagnostic purposes. The Siemens SOMATOM Perspective shown in 
Figure 3.2 is a computed tomography with a 128-slice configuration, 70 cm gantry aperture and a 
50 cm scan field. The patient couch can hold patients' weights up to 200 kg and offers a 
reconstruction of 64 images.  
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Figure 3.2: Siemens Somatom Perspective CT scanner 
 
3.3.3 DOSIMETRY EQUIPMENT 
Dosimetry is a method for measuring, estimating, and evaluating absorbed doses of radiation. 
Medical physicists utilise dosimetry to ensure that radiotherapy equipment is calibrated 
appropriately and provides accurate radiation to patients. Figure 3.2 depicts the dosimetric 
equipment used for dose verification in this study. 
 
(a)       (b) 
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(c)       (d)     
Figure 3.3: (a) Handheld Traceable barometer, (b) Siemens CT phantom, (c) Max 4000 Plus 
electrometer and (d) Exradin A19 ionisation chamber. 
For dosimetry measurements, detectors are typically paired with a phantom. Dosimetry detectors 
include radiographic film, radio-chromic film, ionisation chambers, thermoluminescent detectors 
(TLDs) and optically-stimulated luminescent detectors (OSLDs), metal oxide semiconductor field-
effect transistors (MOSFETs), diamond detectors, Alanine – Electron paramagnetic resonance and 
Gel dosimetry detectors. In this investigation, the ionisation chamber was chosen for dosimetry 
measurements. The Exradin® ion chamber is designed for clinical dosimetry measurements. 
Exradin® A19 ionisation chamber (Standard Imaging, Inc.) is a waterproof classic farmer type ion 
chamber characterised for absolute dosimetry. 
A traceable digital barometer shows the barometric pressure trend and contains a stopwatch/timer 
and compass. A thermometer and altimeter are included. International dosimetry protocols require 
a temperature-pressure correction factor for vented ionisation chamber measurements. When 
measuring conditions comparable to reference conditions under which the ionisation chamber was 
calibrated, measurements are valid without adjustment considerations. 
Max 4000 Plus electrometer is a display device for the radiation measurements done by the 
ionisation chamber. MAX 4000 Plus electrometer is designed for output measurements and data. 
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CT phantom is a highly specialised artefact used in medical imaging for quality control, equipment 
calibration, dosimetry, and education. CT phantom is a calibration phantom with known densities. 
3.3.4 RADIOTHERAPY TREATMENT PLANNING SYSTEM (RTPS) 
Eclipse Treatment Planning System (Varian Medical Systems, Palo Alto, CA; version 15.6) is a 
three-dimensional (3D) radiotherapy treatment planning system (Figure 3.4). The KATH Eclipse 
TPS features network connectivity for the automated transmission of image datasets and digital 
data interchange between workstations and other systems. Eclipse generates optimised treatment 
plans for patients undergoing external beam radiotherapy in the Directorate. Analytical 
Anisotropic Algorithm (AAA) is the dose algorithm for dose distribution computations now 
utilised at the study site. The AAA models the contributions of primary photons, extra-focal 
photons, and contaminated electrons individually and better accounts for the lateral flux. 
Additionally, AAA improves precision, particularly for dose estimations in heterogeneous media 
such as the lung. 
 
Figure 3.4: Varian EclipseTM treatment planning system user interface showing isodose 
distribution. 
 
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3.4 LUNG PHANTOM FABRICATION 
3.4.1 TISSUE EQUIVALENCE OF WOOD AND TUMOUR SAMPLES 
The tissue equivalence of locally accessible materials, such as wood and tumour-simulating 
samples, was evaluated. Some selected wood samples from a wood workshop were assessed to 
determine their lung tissue equivalence. To replicate the tumour, samples of chalk and perspex 
were created. 
Computed tomography scans were performed on the Siemens Somatom Perspective CT at KATH's 
Accident and Emergency Unit shown in Figure 3.5.  
 
Figure 3.5: Siemens Somatom Perspective CT scanner used in this study (Komfo Anokye 
Teaching Hospital, Kumasi). 
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First, the CT scanner was calibrated by scanning a Computed Tomography phantom with a known 
radiodensity to determine whether the scanner data provided the appropriate quantity of 
Hounsfield Units (HU) (Figure 3.6). 
 
 
Figure 3.6: Setup for the determination of air and water CT numbers. 
The prepared wood, chalk, sawdust plugs, and perspex samples were positioned on the couch 
(Figure 3.7) for CT scanning to assess their CT numbers and determine lung and tumour tissue 
equivalence. There were six wood samples, three sawdust plugs, two perspex plugs, and three 
chalk tumour samples. 
 
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Sawdust plugs 
Wood samples 
Spherical chalk sample 
Perspex plug 
Acrylic filled roll-on ball 
 Flat chalk samples 
 Figure 3.7: Lung and tumour simulating samples. 
The adult CT procedure was employed for the scan, and the lung window was applied to see the 
wood samples. As shown in Figure 3.8, regions of interest were created to display the CT numbers 
on the pictures. Based on the CT scans, a suitable wood sample was chosen to create the lung field 
for the phantom. 
 
 
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(a)        (b) 
Figure 3.8: CT scan images (a) wood sample; (b) perspex, chalk, and sawdust samples. 
3.4.2 WATER TANK-TYPE LUNG PHANTOM DESIGN AND DEVELOPMENT 
Phantoms are used in clinical and preclinical radiation dosimetry to study the effects of radiation 
on an organ or tissue. They can be made of water or more complicated materials and have definite 
shapes and sizes (Biglin et al., 2019). Following the design of Nishio et al. (2014), a lung SBRT 
phantom was built using locally accessible materials. These materials include PMMA, wood, and 
acrylic filled roll-on balls. Using the schematic diagram in Figure 3.9, an initial prototype, as 
shown in Figure 3.10, was built using locally accessible materials. 
25 cm 
23 cm 10 cm 
 
 20 cm 10 cm 
20cm 
15 cm 
 cm 
6.5 cm 
 
      (a)   6.5 cm 
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20 cm 
 
20 cm 
 2 cm 
     (b) 
 
20 cm 
 
10 cm 
20 cm 
 1.5 cm 
2 cm 
     (c) 
Figure 3.9: Schematic diagram of lung phantom. (a): phantom design; (b): schematic diagram of 
simulated lung field inserts; (c): diagram of the wood slab with indentation to accommodate 
simulated tumour and ionisation chamber cable. 
 
   
  (a)         (b) 
Figure 3.10: Prototype lung phantom (a) top view; (b) frontal view 
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 As PMMA is extensively used in radiation dosimetry and was approved by the IAEA as a 
substitute for water, it was selected as the phantom material. Figure 3.11 depicts a generated 
heterogeneous lung phantom comprised of a 3 mm thick polymethyl methacrylate (PMMA), a 
lung field comprised of eight 2 cm wood slabs, and a simulated 2.9 cm spherical tumour buried in 
the lung field. The form and size of the phantom offer the possibility of simulating a human torso, 
and the PMMA tank can be filled with water, a tissue-equivalent material, via an opening on the 
front view.  
       
  (a)     (b)      (c)   
Figure 3.11: Lung phantom; (a) frontal view (b) side view (c) top elevation. 
As illustrated in Figure 3.12, the simulated tumour consisted of a roll-on ball filled with acrylic 
powder and a 1 cm hole in the centre to accommodate the effective length of the sensitive part of 
the ionisation chamber to detect the radiation. The tumour size was determined because most 
treated tumours are between 1.5 and 7.2 cm in diameter (Wolthaus et al., 2008). The two main 
wood slabs that sandwich the simulated tumour are a 0.5 cm semi-circular groove on each to house 
the ionisation chamber. 
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   (a)       (b) 
Figure 3.12: (a) Simulated tumour buried in wood slabs with groove (b) ionisation chamber 
inserted into the simulated tumour in the lung field. 
3.5 MOTION PLATFORM 
A motion platform was created to imitate the breathing effect.  Sarudis et al. (2017) found that 95 
per cent of the tumours in 126 individuals travelled 20 mm (2 cm) in the inferior-superior direction. 
The purpose of the motion platform was to enable the measurement of the real dosage distribution 
when the target is in motion. The movements were intended to be in the superior-inferior (SI) 
direction (z-axis), the long axis from the centre for distances between 0.5 cm and 1 cm. The SI 
direction was chosen because Liu et al. (2007) found that most of their individuals' tumours 
progressed more than 0.5 cm along the SI axes compared to the lateral and anterior-posterior (AP) 
axes. A motion platform with a car wiper motor installed as a variable displacement motor and a 
base trolley for the phantom, as depicted in Figure 3.13. 
 
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Power supply 
Trolley seat 
for phantom 
Car wiper 
motor 
 
Figure 3.13: Motion platform with wiper motor connected to trolley. 
3.6 SCANNING OF FABRICATED LUNG PHANTOM 
The 4D CT scan is a novel image acquisition method that captures the tumour's position and 
mobility during distinct breathing phases. This allows investigation of the influence of intrafraction 
mobility on the tumour and adjacent tissue. However, in the absence of a 4D CT scanner at the 
study site, slow CT scanning was used to image moving targets in this study. 
As shown in Figure 3.14, the phantom was scanned to determine the Hounsfield units of its 
constituent components. In this study, the adult chest protocol was used for all the CT scans 
 
 
 
(a)       (b) 
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(c)       (d)    (e) 
Figure 3.14: (a) and (b) set up for scanning fabricated lung phantom; (c), (d) and (e) are CT scan 
images of the fabricated lung phantom to assess the Hounsfield units of phantom components. 
The lung phantom was set up as depicted in Figure 3.15 to obtain the standard and slow CT scans 
using the adult protocol with the following parameters: 110 kVp, 1 s gantry rotation time, 64 x 0.6 
mm slice thickness, with a pitch of 0.4. A slow CT scan was performed, which portrays the 
spectrum of tumour movements more appropriately. Standard CT images were acquired at around 
4s per slice, which is comparable to a typical breathing cycle. Slow CT scans of the moving 
phantom were taken using the same imaging approach as done for the standard CT, but with the 
longest available gantry rotation time of 0.6 s and the pitch reduced to 0.35 for 0.5 cm and 1 cm 
motions. Using a slice thickness of 1 mm, approximately 15 cm of the phantom containing the 
simulated tumour was scanned.   
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Figure 3.15:  CT scan set-up of fabricated lung phantom on the motion platform. 
 
A sample of  CT images is presented in Figure 3.16. 
 
 Figure 3.16: CT scan user interface showing elevation and frontal view of the phantom. 
 
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3.7 CT SCANNER ELECTRON DENSITY CALIBRATION 
The link between CT Hounsfield units and electron densities is critical for radiation treatment 
planning. To calibrate the treatment planning system's CT scanner, a CIRS electron density 
phantom was scanned to get Hounsfield units of tissue-equivalent materials (Figure 3.17). The 
phantom was aligned with lasers in the centre of a CT gantry and scanned using an adult abdominal 
imaging technique utilising kVp tube voltage. To calibrate the TPS, we used the CT numbers from 
the scan and the electron densities of the substitute tissues. 
 
 
 
 
 
   (a)        (b) 
Figure 3.17: (a) CIRS Electron Density Phantom 062M (b) CT scan image of CIRS Electron 
Density Phantom. 
 
3.8 PHANTOM STUDY 
3.8.1 CONTOURING OF VOLUMES 
The lung phantom's standard and slow CT datasets were sent to the Eclipse TPS for treatment 
planning. Planning tumour volumes (PTVs) and organs at risk (OARs) were defined as 
recommended by ICRU 50 (1993), ICRU 62 (1999), and ICRU 83 (2010) reports. 
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As shown in Figure 3.18, only the PTV, lung, normal tissue, body of the phantom, and ionisation 
chamber cavity were outlined for the phantom experiments. 
 
 
 
 
 
  A simulated tumour (target)  Simulated lung  
Figure 3.18: Contouring interface displaying transverse, sagittal and frontal views of the 
phantom CT image. 
 
3.8.2 TREATMENT PLANNING  
The Radiation Therapy Oncology Group (RTOG) lung protocol 0915 specifies the requirements 
for SBRT plans used in this study. Some clinical trials have shown improved local control rates 
and long term survival with these RTOG protocols (Chinniah et al., 2017; Hoffman et al., 2019; 
Osei et al., 2020; Videtic et al., 2015, 2019). RTOG prescription dose constraints for treatment 
planning and dose constraints employed in the treatment planning are in Table 3.1. 
 
 
 
 
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Table 3.1: RTOG planning dose-volume constraints (Bezjak et al., 2011; Videtic et al., 2014).  
Dose-volume constraints 
Volume/ OAR 
48 Gy in 4 fractions 50 Gy in 5 fractions 
V100%PD  ≥ 95%  V100%PD  ≥ 95%  
PTV 
  V90%PD ≥ 99% maximum dose inside ITV V90%PD ≥ 99% maximum dose inside ITV 
V11.6 Gy  < 1500cc V12.5 Gy  < 1500cc 
Bilateral lungs 
V12.4 Gy  < 1000cc V13.5 Gy  < 1000cc 
V20.8 Gy  < 0.35cc, V13.6 Gy  < 1.2cc V22.5 Gy  < 0.25cc, V13.5 Gy  < 0.5cc 
Spinal Cord 
Maximum point dose < 26 Gy Maximum point dose < 30 Gy 
Skin V33.2 Gy  < 10cc maximum point dose < 36 Gy V30 Gy  < 10cc maximum point dose < 32 Gy 
Oesophagus V18.8 Gy  < 5cc maximum point dose < 30 Gy V27.5 Gy  < 5cc maximum point dose < 105% PD 
 Heart V28 Gy  < 15cc maximum point dose < 34 Gy V32 Gy  < 15cc maximum point dose < 105% PD 
 Great Vessels V43 Gy  < 10cc maximum point dose < 49 Gy V47 Gy  < 10cc maximum point dose < 105% PD 
 Trachea + 
V15.6 Gy  < 4cc maximum point dose < 34.8 Gy V18 Gy  < 4cc maximum point dose < 105% PD 
bronchus  
Ribs V32 Gy < 1cc maximum point dose < 40 Gy  
 
 FEASIBILITY TEST TREATMENT PLANNING 
Before the SBRT treatment planning for the phantom, a feasibility test was conducted by 
producing a 3-D treatment plan utilising a four-field box approach consisting of two para-opposed 
fields and two lateral fields with 6 MV photon beams and a dosage prescription of 10 Gy in 5 parts 
(10 Gy/5). In Figure 3.19, the Eclipse TPS interface depicts the treatment plan for a 90 per cent 
isodose prescription. 
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Target 
Isodose 
Water  
 
Lung 
 
Figure 3.19: Eclipse TPS displaying external beam treatment plan of the fabricated lung phantom 
Dose analysis of the dose-volume histogram (DVH) was performed for the plan quality before 
treatment was delivered.  
 LUNG SBRT TREATMENT PLANNING 
3D CRT designs were generated for the phantom to meet target coverage and normal tissue sparing 
requirements. The treatment dose plans comprised eight (8) non-opposing and coplanar static 
beams with 6 MV. Several clinical trials have utilised dose prescriptions of 34 Gy in 1 fraction (34 
Gy/1), 50 Gy in 5 fractions (50 Gy/5), and 48 Gy in 4 fractions (48 Gy/4) for lung SBRT. In this 
investigation, a prescribed dose of 50 Gy in 5 portions (50 Gy/5) was employed. Based on the 
RTOG 0915 (Videtic et al., 2014) and (Osei et al., 2020) studies, dose-volume limits served as a 
guideline for the three fractionated treatment plans.  
The treatment plans were divided into two categories: with and without mobility. These were 
divided into three subcategories: 
 Initially, a static plan based on conventional CT images was supplied to the phantom. 
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 Secondly, plans were created using slow CT scans that accounted for ITV and were 
executed on phantoms without motion. 
 Thirdly, plans were developed on slow CT images and provided with the phantom in 
motion. 
Figures 3.20, 3.21 and 3.22 show the static beam plan as it appears in the Eclipse TPS. The plan 
entails 3-D plan beam alignments and dose distribution. 
 
   
    (a)        (b) 
   
   (c)        (d) 
Figure 3.20: Static treatment plan with 50 Gy/5 prescription dose; (a) Transverse view, (b) 3D 
view, (c) Coronal view and (d) Sagittal view. 
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Figure 3.21: Treatment plan with 50 Gy/5 prescription dose for phantom in 0.5 cm motion 
 
 
Figure 3.22: Treatment plan with 50 Gy/5 prescription dose for phantom in 1 cm motion 
 LUNG SBRT TREATMENT DELIVERY 
The treatment plan was delivered using the Varian Clinac iX treatment machine (Figure 3.23).  
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Figure 3.23: Varian Clinac iX linear accelerator at Oncology Directorate, KATH (without On-
Board Imager) 
This same setup for CT image acquisition was used at the time of dose delivery for target 
localization, as depicted in Figure 3.24, with an Exradin A19 ionisation chamber placed in the 
centre of the simulated lung region for radiation detection during treatment and coupled to a MAX 
400 Plus electrometer that displayed the radiation in charges. Using the formula in the equation, 
the measured electrometer reading was converted to dose.    
𝑀 = 𝑅(𝐶) 𝑥 𝑁𝐷𝑊 𝑥 𝑃  ( 3.1) 
𝑅 = 𝑒𝑙𝑒𝑐𝑡𝑟𝑜𝑚𝑒𝑡𝑒𝑟 𝑟𝑒𝑎𝑑𝑖𝑛𝑔 (𝑪)   
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𝑁𝐷𝑊 = 𝑖𝑜𝑛𝑖𝑠𝑎𝑡𝑖𝑜𝑛 𝑐ℎ𝑎𝑚𝑏𝑒𝑟 𝑐𝑜𝑒𝑓𝑓𝑖𝑐𝑖𝑒𝑡 = 4.771 𝐸7 𝐺𝑦/𝐶 
𝑃 = 𝑝𝑒𝑟𝑡𝑢𝑟𝑏𝑎𝑡𝑖𝑜𝑛 𝑓𝑎𝑐𝑡𝑜𝑟 =  𝐾𝑄 𝑥 𝐾𝑇,𝑃 𝑥 𝐾𝑝𝑜𝑙 𝑥 𝐾𝑠  
𝐾𝑄 =  𝑏𝑒𝑎𝑚 𝑞𝑢𝑎𝑙𝑖𝑡𝑦 𝑢𝑠𝑒𝑑 𝑓𝑜𝑟 𝑐𝑎𝑙𝑖𝑏𝑟𝑎𝑡𝑖𝑜𝑛 𝐶𝑜 − 60 
𝐾𝑇,𝑃 =  𝑡𝑒𝑚𝑝𝑒𝑟𝑎𝑡𝑢𝑟𝑒 𝑎𝑛𝑑 𝑝𝑟𝑒𝑠𝑠𝑢𝑟𝑒 𝑐𝑜𝑟𝑟𝑒𝑐𝑡𝑖𝑜𝑛 𝑓𝑎𝑐𝑡𝑜𝑟 
𝐾𝑝𝑜𝑙 =  𝑝𝑜𝑙𝑎𝑟𝑖𝑡𝑦 𝑐𝑜𝑟𝑟𝑒𝑐𝑡𝑖𝑜𝑛 𝑓𝑎𝑐𝑡𝑜𝑟 
𝐾𝑠 =  ion recombination factor 
 
 
 
 
 
(a)     (b)     (c) 
Figure 3.24: Lung phantom treatment set-up, (b) researcher setting up electrometer and (c) 
electrometer displaying radiation measurement. 
Electronic portal imaging device (EPID) images were obtained for orthogonal fields (Figure 3.25) 
using the Clinic's gantry to verify the phantom setup. Target localization and phantom 
repositioning were performed for all treatment sessions, and EPID pictures were matched with 
planned CT images. During treatment, imaging permits the visualisation of the actual tumour. The 
availability of respiratory information within the obtained images enables creative anatomical 
collation. Each tumour position was recorded relative to the initial intended position, allowing the 
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daily average position to be calculated. To achieve symmetrical dosage distribution, baseline shifts 
were then rectified by aligning the average position photographs with the target position recorded 
during planning. Exradin® A19 ionisation chamber and MAX 4000 Plus electrometer were used 
for the dosimetric measurements and verification of the prescribed and planned doses.  
 
 
 
 
 
 
             
  (a)        (b) 
 Figure 3.25: Image verification set up (a) anterior; (b) lateral. 
3.8.3 CLINICAL CASE STUDY 
The lung phantom only provided information on the dose to the target volume. Hence, a clinical 
case was simulated to demonstrate exposure to organs at risk (OARs). One patient's CT dataset of 
a thoracic CT scan demonstrating full lung coverage was located and utilised in a clinical case 
study for dosimetric analysis of OARs not included in the phantom investigation. At the Oncology 
Directorate of the Komfo Anokye Teaching Hospital, CT scans were accessed through the Eclipse 
Treatment planning system. This patient was not diagnosed with lung cancer but with other cancers 
that required thoracic CT scans. 
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 Target and OARs Delineation 
SBRT planning incorporates features that are not typically contoured in conventional fractionated 
plans, which frequently depend on the tumour's location to be treated. Normal OAR structures and 
targets were defined and contoured per the atlas for OARs in thoracic radiation therapy based on 
RTOG 0813 and 0915 standards. The OARs consist of the lungs, heart, spinal cord, ribs, bronchial 
tree, oesophagus, and trachea. For the clinical example, the identified targets and OARs include 
bilateral lung (right and left), heart, spinal cord, oesophagus, tracheaproximal bronchial tree (left) 
and ribs. To simulate the phantom scenario and a clinical lung case, respectively, 3 cm and 1 cm 
tumours were contoured. 
 Lung SBRT Treatment Planning 
Using the Eclipse TPS, eight-field 3D treatment plans were developed with 6-MV photon beams 
and a target prescription dose of 48 Gy in four fractions (48 Gy/4) and 50 Gy in five fractions 
(Varian Medical Systems, Palo Alto, USA, version 15.6). Analyses were conducted using 
dosimetric data concerning vital structures. Figures 3.26 and 3.27 depict the beam static plans in 
the Eclipse TPS used in this investigation for the dose prescription of 50 Gy/5 for 3 cm and 1 cm 
tumours, respectively. The Figures depict 3-D plan beam alignments and dosage distribution. 
 
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Figure 3.26: Treatment plan with 50 Gy/5 for a 3cm tumour 
 
 
Figure 3.27: Treatment plan with 50 Gy/5 for 1cm tumour 
 
3.9 TREATMENT PLAN EVALUATION 
Targets and normal tissue doses of produced treatment regimens were thoroughly examined. Plan 
quality assessment utilised recommended practical criteria for dosimetry measurements from 
RTOG 0831 and 0915. Each treatment plan's DVH for the goal and OAR was analysed for the two 
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prescribed doses. Plans for normal structures were evaluated based on dose statistics comprising 
minimum, maximum, and mean dose/volume parameters from dose-volume histograms (DVH). 
Target coverage, heterogeneity indices, conformance indices, dosage spillage, and gradient index 
were utilised to evaluate dose distribution objectively. Conformity index (CI) and gradient index 
were calculated using dose information from the treatment planning system. Homogeneity index 
(HI) was computed using a ratio of the dose received by 5 per cent of the target volume (D5) to 
the dose received by 95 per cent of the target volume (D95), as described in equation 3.2. 
𝐷
𝐻𝐼5⁄95 =
5    ( 3.2) 
𝐷95
Plan acceptability for target coverage is considered when the maximum dose is within the PTV, at 
least 99% of the PTV volume is covered by 90% of the prescription dose (V90%PD > 99%), and the 
prescription dose covers at least 95% of the PTV volume (V100% PD > 95%). Plan acceptability for 
OARs is governed by organ dose-volume constraints (Table 3.1). 
 
 
  
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CHAPTER FOUR 
RESULTS AND DISCUSSION 
4  
4.1 LUNG AND TUMOUR SIMULATION SAMPLE 
CT data of locally available materials sampled to simulate lung tissue and tumour located within 
the lung were obtained using a Siemens Somatom Perspective CT scanner. Kalef-Ezra et al. (1999) 
studied the lungs of healthy subjects from entire lung scans and reported mean CT numbers (HU) 
of -722 and -746 for women and men, respectively. Ohkubo et al. (2016) also studied the lung 
volume and defined the CT number to be between -950 and -701. Mayer et al. (1998) noted a lung 
tumour CT number threshold of 13 HU in their study on CT number distribution and its association 
with local control and as a marker of lung tumour response to radiation. Paul et al. (2017) 
investigated lung cancer response during radiotherapy and observed substantial changes in the 
gross tumour volume mean HU between 11 to 48 HU (median 30). From these studies, the HU 
range of 11 to 48 was used to select suitable materials to simulate tumours. 
Table 4.1 presents the CT data of the various samples assessed. Wood samples 2 and 4 were found 
most suitable with CT numbers comparable to a normal lung and therefore used to develop the 
lung of the phantom. Comparing the measured HU of the various samples scanned to the reference 
HU given by literature the following were found suitable: wood samples 1 and 3 for lung tissue 
equivalent, and acrylic filled roll-on ball. Wood sample one was used for simulating the lung as 
that was more solid and feasible to work with.  
 
 
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Table 4.1: CT data of samples assessed for the fabrication of lung phantom. 
Hounsfield units Measurements 
 
Materials Reference Measured 
 Number of ROIs Mean SD Minimum Maximum 
Wood sample 1 2 -653.9 51.55 -747.5 -571 
Wood sample 2 3 -401.2 94.4 -618 -307 
Lung 
Wood sample 3 3 -657.2 33.1 -701.3 -562 
- 950 to - 701 HU 
Wood sample 4 3 -403.7 120.6 -653 -16.6 
(Kalef-Ezra et al., 
Wood sample 5 3 -431.7 93.9 -635 -296.3 
1999; Ohkubo et 
Sawdust plug 1 2 -613.0 37.2 -675 -463 
al., 2016) 
Sawdust plug 2 1 -565.7 38.8 -639 478 
Sawdust plug 3 1 -667.7 39.8 -759 -587 
Perspex plug 1 3 111.8 11.4 88 133 
Perspex plug 2 3 114.1 11 65 134 
Spherical chalk 
3 856.7 122.4 507 112.1 
sample 11 - 48 HU  
Flat chalk sample (Mayer et al., 1998; 
1 574.1 223.5 -108 865 
1 Paul et al., 2017) 
Flat chalk sample  
2 760.7 163.4 154.5 996.5 
2 
Acrylic filled roll-
1 61 8.4 43 79 
on ball 
 
A lung phantom was fabricated using the selected suitable maerials containing a simulated tumour 
and lung 
 
4.2 CT ELECTRON DENSITY CALIBRATION 
In radiotherapy planning, tissue inhomogeneities are corrected for in the TPS using CT scans of 
patients. It is therefore essential to achieve the right association between CT number electron 
densities. The Model 062M Electron density phantom was scanned and regions of interest were 
drawn to obtain the CT data of the seventeen (17) tissue-equivalent substitutes. The HU for the 
electron density phantom substitutes and their corresponding relative electron densities specified 
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on the sample by the manufacturer were entered into the Eclipse TPS (Varian Medical Systems, 
Palo Alto, CA, USA) and were used to generate the CT scanner calibration curve in Figure 4.1. 
 
Figure 4.1: The relative electron density (RED) curve of the Siemens Somatom Perspective CT 
scanner incorporated in the Eclipse TPS. 
The dose delivered to a patient treated by a treatment planning system is typically determined 
using computed tomography data. Multiple tissue categories, including lung, fat, muscle, general 
organ, cartilage, bone, and tooth, contribute to the complexity and heterogeneity of the natural 
body. CT number to electron density (CT-ED) calibration is typically accomplished with a 
calibration phantom containing many tissue substitutes to determine the proper radiation dose for 
the human body. In an inhomogeneous medium, dosage calculations rely heavily on the precision 
of CT number to electron density calibration. The CT number, expressed in Hounsfield units (HU), 
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is a normalised measurement of the linear attenuation coefficient of each voxel (volume pixel) in 
a CT picture, where the CT number of air is -1000 and that of water is 0. The relationship between 
HU and ED is often determined using a calibration curve empirically derived from CT scans of a 
tissue characterization phantom containing inserts of tissue-equivalent materials with a wide range 
of densities. However, the scanner-dependent calibration curve permits the conversion of CT 
numbers to densities for use in dosage computation (IAEA, 2008; Mutic et al., 2003).  
4.2.1 RESULTS OF FEASIBILITY TEST  
One of the key steps in the radiotherapy workflow is plan evaluation. The quality of a treatment 
plan depends on certain parameters. Plan quality is commonly assessed by evaluating the dose 
distribution calculated by the treatment planning system. Treatment plan evaluation is generally 
considered on two levels; the treatment portals and dose distributions. The dose distribution can 
be analysed using isodose curves in the orthogonal planes, isodose surfaces, dose distribution 
statistics, and Dose Volume Histograms (DVH). The evaluation of the calculated dose distribution 
is often based on dose-volume histograms (DVHs). Dose Volume Histograms summarize the dose 
information in a 3D-dose distribution by excluding detailed positional information about the 
location of dose levels within a region of interest and are very useful in the initial stages of 
comparing and evaluating alternative plans in an external beam. There are two types of DVHs. 
1.                  Differential Dose Volume Histogram 
2.                  Cumulative Dose Volume Histogram 
Differential Dose Volume Histogram: For a given anatomical structure, the differential DVH 
describes the fraction of total volume irradiated to the stated dose. It shows volume V(D) plotted 
against dose, where V(D) is the volume of tissue in which dose ranges between D and (D + dD), 
where dD is the ‘bin width’ of the histogram. Bin width is defined using the maximum dose defined 
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for the plan. Bin width (dD) = Maximum Dose for plan/Number of Bins. You can manually adjust 
the number of bins to change the histogram resolution. That means if a total of 5000 cGy are 
prescribed and 50 bins are selected for DVH representation, then DVH will show volume 
distribution for the doses in the steps (or bin width) of approximately 100 cGy (i.e. 5000/50). The 
Cumulative Dose Volume Histogram, on the other hand, is an integration of the differential DVH. 
It describes the fraction of the total volume irradiated to the stated dose or more. In cumulative 
DVH, the volume (V(D) is plotted against dose (D), where V(D) is the volume of tissue receiving 
a dose greater than or equal to D. In this thesis all DVHs are presented as cumulative DVH. The 
cumulative DVHs are used to analyse a patient plan by taking points on the DVH to tell how much 
volume is covered by a stated dose.  
A conventional treatment plan for a feasibility test with a dose prescription of 10 Gy in five parts 
(10 Gy/5) was administered and measured. The dosimetric characteristics of the treatment plan for 
the feasibility test were assessed. The conformity index (CI) and gradient index for treatment with 
a dose prescription of 50 Gy/5 using 3-D CRT technology was derived from the dose statistics on 
the TPS. Dose coverage of the planned target volume (PTV) and organs at risk (OAR) (lung) was 
evaluated by analysing dose-volume histograms (DVHs). From the DVH curve of the prescribed 
dosage of 10 Gy/5 shown in Figure 4.2, the lung phantom target volume, mean, maximum, and 
minimum doses, as well as the dose received by 95% and 99% of the PTV, were determined.  
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Figure 4.2: Cumulative DVH for a four-field treatment plan with 10 Gy/5 prescription dose. 
Then PTV dose coverage D5 and D95 from the DVH were respectively. Heterogeneity and 
conformity index (HI5/95) were 1.12 and 1.06 respectively. Homogeneity characterises the 
uniformity of the absorbed-dose distribution within the PTV and the “squareness” of the DVH is 
a measure of the absorbed dose uniformity. An HI value of zero indicates that the absorbed-dose 
distribution is almost homogeneous. 
The conformity index characterises the degree to which the high-dose region conforms to the PTV. 
The overlap between the isodose surface defining a significantly large absorbed dose and the 
surface of the PTV give a measure of the conformity. 
 Dosimetric parameters analysed (PTV volume, maximum, minimum and mean doses, the PTV 
V100% and V95%) from the DVH suggest adequate conformal target coverage was achieved for the 
feasibility test treatment plan with minimal toxicity to the lung (Table 4.2). The data show that for 
a prescription dose of 10 Gy in 5 fractions to treat the 3cm tumour, the PTV V100%, and V95% were 
85% and 95% respectively. The maximum, minimum and mean PTV doses (%) were 109.5%, 97.6 
and 103.2 respectively. 
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Table 4.2: Planned and reported absorbed dose metrics for lung phantom feasibility 
treatment planning assessment. 
Dose parametre 10 Gy / 5 
Maximum PTV Dose (%) 109.5 
Minimum PTV dose (%) 97.6 
Mean PTV dose (%) 103.2 
V100% 85% 
V95% 95% 
50% PD 1 Gy 
CI 1.06 
HI5/95 1.12 
GI 2.15 
 
Outcomes in Table 4.2 show that the PTV volume conformally covered by the prescribed dose 
was 95% and is acceptable for target coverage, thus the plan was accepted and approved for test 
delivery. The planned treatment was delivered to the phantom and measured by using the 
ionisation chamber/electrometer combination. The electrometer was inserted in the middle of the 
tumour. These measured values were converted to doses to indicate the delivered dose using 
equation (1).  The verification of the dose delivered requires comparisons of measured and 
calculated dose distributions. The delivered doses were comparable to the clinical treatment 
planned doses for the target and are presented in Table 4.3. The deviation in Table 4.3 is calculated 
using equation (4.1). 
𝑇𝑃𝑆 𝐷𝑜𝑠𝑒−𝑀𝑒𝑎𝑠𝑢𝑟𝑒𝑑 𝐷𝑜𝑠𝑒
𝑅𝑒𝑙𝑎𝑡𝑖𝑣𝑒 𝑑𝑒𝑣𝑖𝑎𝑡𝑖𝑜𝑛 =  × 100  (4.1) 
𝑇𝑃𝑆 𝐷𝑜𝑠𝑒
 
 
 
 
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Table 4.3: Results of fabricated lung phantom dosimetry - planned versus delivered dose. 
Measured Dose (Gy) TPS Relative 
MU Average STD Calculated Deviation 
1 2 3 4 5 Dose (Gy) (%) 
93 0.52 0.54 0.50 0.48 0.48 0.50 0.02 0.50 0 
107 0.46 0.48 0.45 0.44 0.44 0.45 0.02 0.50 10 
106 0.47 0.49 0.47 0.46 0.46 0.47 0.01 0.50 6 
90 0.53 0.55 0.53 0.51 0.51 0.53 0.02 0.50 - 6 
Total 1.99 2.07 1.95 1.88 1.89 1.95 0.07 2.00 10 
 
The ideal and acceptable variation between planned and delivered doses is ± 5% according to 
ICRU which was achieved for the composite dosimetry. Some reasons for discrepancies between 
delivered and planned doses for individual fields have been attributed to anatomical changes, 
geometrical changes, irregular irradiated volume dimensions, variations in beam output (the 
further drift in beam output during a patient’s treatment, and the random day-to-day fluctuations 
in beam output) and intra- and inter-fractional movements (Bolt et al., 2021; Heukelom et al., 
2020). The discrepancies between delivered and planned doses in Table 4.3 could be mainly 
attributed to the uneven mass distribution within the tumour and set-up uncertainties. However, 
using a standardised phantom, the variation will be less than 5%. 
 
4.2.2 RESULTS OF PHANTOM STUDY 
After designing and assessing the feasibility of dose delivery, the phantom was treated with 50 
Gy/5 3D CRT and DVH plots were obtained for dose analysis. The quality of each treatment plan 
developed for the phantom in static mode and motion was evaluated by analysing the degree to 
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which each plan satisfied the dosimetric objectives according to the RTOG 0915 standards (Table). 
The DHVs for the target and lung were analysed. Data are shown as mean SD, median, and range 
(minimum-maximum) doses to target volumes and OARs for the two treatment approaches and 
prescription doses.  
Riet et al. (1997) based on the study by Saint-Anne, Lariboisiere, and Tenon (SALT) group and 
Lomax and Scheib defined conformality number as expressed in equation 1, taking into account 
the volume of healthy tissue irradiated by the prescribed dose. It can better represent dose 
conformity than other definitions (Cao et al., 2019; Shaw et al., 1993). Dose distribution uniformity 
was evaluated in the target volume (TV) using the homogeneity index (HI). Feuvret et al. (2006) 
defined HI as the ratio of the maximum dose (Dmax) to minimum dose (Dmin) or prescription 
dose (Dp) in PTV. The ideal HI value is 1 indicating that each voxel in the TV receives the same 
dose (Feuvret et al., 2006b; Shaw et al., 1993). Gradient index (GI) is the volume of 50% 
prescribed dose to that of the prescribed dose which describes the dose fall-off steepness outside 
the TV as expressed in equation 3 (Cao et al., 2019; G. G. Zhang et al., 2011). The value of GI is 
positive, and a lower value means a steeper dose fall-off outside the target and better sparing of 
normal tissue. For the target coverage, a plan is considered acceptable when at least 95% of the 
target (PTV) volume is covered by the prescription dose (V100% ≥ 95%), at least 99% of the PTV 
volume is covered by 90% of the prescription dose (V90%PD > 99%) and the maximum dose is 
inside the PTV. The plan was acceptable for the organs a risk based on the organ dose-volume 
constraints (Table 3.1).   
 
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Figures 4.3, 4.4 and 4.5 present the DVH plots for the three plans generated for the various 
scenarios described in chapter 3 and used to assess the quality of each treatment plan by examining 
the extent to which the target dose coverage and lung dosimetric constraint were achieved.   
 
Figure 4.3: Dose-volume histogram (DVH) of the treatment plan with dose prescription of 50 
Gy/5. 
 
 
 
 
 
 
 
 
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Figure 4.4: Dose-volume histogram (DVH) of the treatment plan with dose prescription of 50 
Gy/5 for phantom in 0.5 cm motion. 
 
 
Figure 4.5: Dose-volume histogram (DVH) of the treatment plan with dose prescription of 50 
Gy/5 for phantom in 1 cm motion. 
 
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Data of the PTV volumes, mean, maximum and minimum doses, the PTV V90%, V95%, andV100% 
for all treatment plans for the prescription dose of 50 Gy/5 stratified by phantom in different modes 
are shown in Tables 4.4. The homogeneity and conformity index extracted from the DVH were 
1.07 and 1.04 respectively. Kim et al., (2015) reported a CI of 1·05 ± 0·07 and Weyh et al., (2013) 
reported a mean CI of 1·36 ± 2·9. Herbert et al., (2013) reported a CI of 1·21 for the 3DCRT plan 
at a prescription dose of 48 Gy/4. Dose statistics presented in Table 4.5 suggest that sufficient dose 
conformity to the target was achieved without delivering extreme doses to OARs to reduce toxicity 
which is the main objective of radiation therapy. Adequate target coverage is associated with 
tumour control which leads to improved biochemical relapse-free survival, cancer progression-
free survival and cancer-specific survival. In analysing the DVH, points are taken on the DVH to 
know how much volume is covered by a stated dose. The dose gotten from these points is compared 
to the dose-volume constraints to ensure the dose constraint for the stated target is achieved organ 
is not exceeded.  For instance, in table 4.5, a dose V99% Gy means 99% of the PTV volume should 
receive more than 90% of the prescription dose and for a prescription dose of 50 Gy/5, 99% of the 
target volume (PTV) received 91 Gy which is more than 90% of the 50 Gy.  Per the requirements 
of RTOG 0915, the plan is acceptable from the DVH evaluation with maximum target coverage 
achieved.  
 
 
 
 
 
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Table 4.4: Dose statistics of treatment plan with dose prescription of phantom in motion. 
Volume/ 50 Gy/5 50 Gy/5 
Metric description 50 Gy/5 
OAR (0.5 cm motion) (1 cm motion) 
PTV V100% ≥ 95%  86.77 98.60 72.71 
  V99% > 90% 91.19 99.61 90.47 
V90% ≥ 99% maximum dose inside 
  99.96 100.00 99.65 
ITV 
  D5 52.62 54.10 57.37 
  D95 48.98 50.66 48.14 
  Maximum dose (Gy) 53.44 (106.9%) 54.36 (108.7%) 58.29 (116.6%) 
  Minimum dose (Gy) 43.54 (81.1%) 48.41 (96.8%) 36.09 (72.2%) 
  Mean dose (Gy) 51.29 (102.6%) 52.62 (105.2%) 53.91 (107.8%) 
  Heterogeneity index (HI5/95) 1.07 1.07 1.19 
  Conformity Index (CI) 1.04 1.39 1.38 
  Gradient Index (GI) 0.93 1.41 1.84 
     
Lung V5 Gy   13.00 83.69 52.77 
  V10 Gy   9.46 66.47 32.23 
  V20 Gy   2.07 22.44 16.94 
  V30 Gy   0.79 9.22 10.27 
 
The planned treatments were delivered, and the electrometer readings were converted to doses 
using equation 1. The planned and delivered dose prescription of 50 Gy/5 in different modes were 
compared yielding the results in Tables 4.5, 4.6 and 4.7. The deviation in the tables is calculated 
using equation 4.1.  
 
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Table 4.5: Comparison of average measure dose to TPS calculated dose for 50 Gy/5 dose 
fraction in static mode. 
TPS Relative 
Measured Dose (Gy) 
MU Average STD Calculated Deviation 
Dose (Gy) (%) 
1 2 3 4 5 
210 1.06 1.04 1.16 1.18 1.29 1.15 0.09 1.33 13.55 
239 1.14 1.10 1.34 1.39 1.48 1.29 0.15 1.33 2.67 
243 1.21 1.15 1.37 1.46 1.56 1.35 0.15 1.33 -1.83 
204 0.95 0.93 1.05 1.08 1.18 1.04 0.09 1.06 2.23 
191 0.95 0.94 1.17 1.16 1.20 1.09 0.11 1.06 -2.22 
205 1.05 1.04 1.23 1.23 1.23 1.16 0.09 1.06 -9.00 
147 0.69 0.68 0.82 0.81 0.80 0.76 0.06 0.89 13.96 
158 0.78 0.77 0.92 0.91 0.99 0.88 0.09 0.89 0.94 
54 0.07 0.07 0.06 0.08 0.15 0.08 0.03 0.27 68.10 
57 0.19 0.20 0.23 0.19 0.15 0.19 0.03 0.27 28.20 
52 0.08 0.08 0.06 0.07 0.07 0.07 0.01 0.27 72.54 
69 0.10 0.09 0.08 0.11 0.12 0.10 0.01 0.27 62.25 
Total 8.27 8.10 9.50 9.68 10.23 9.16 0.83 10.00 8.43 
 
 
 
 
 
 
 
 
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Table 4.6: Comparison of average measure dose to TPS calculated dose for 50 Gy/5 
prescription dose delivered to phantom with 0.5 cm motion. 
TPS Relative 
Measured Dose (Gy) 
MU Average STD Calculated Deviation 
Dose (Gy) (%) 
1 2 3 4 5 
185 1.23 1.12 1.26 1.26 1.25 1.22 0.05 1.32 7.16 
271 1.79 1.74 1.76 1.79 1.79 1.77 0.02 1.60 -10.76 
130 0.88 0.86 0.89 0.90 0.90 0.89 0.02 0.94 5.68 
242 1.58 1.55 1.55 1.58 1.58 1.57 0.01 1.41 -11.07 
202 1.31 1.29 1.32 1.34 1.34 1.32 0.02 1.22 -7.67 
155 1.02 1.00 1.03 1.03 1.03 1.02 0.01 0.94 -8.50 
214 1.57 1.49 1.56 1.58 1.58 1.56 0.03 1.43 -8.72 
152 1.09 0.97 1.12 1.12 1.11 1.08 0.05 1.13 4.28 
Total 10.48 10.02 10.49 10.59 10.57 10.43 0.21 10.00 -4.31 
 
Table 4.7: Comparison of average measure dose to TPS calculated dose for 50 Gy/5 
prescription dose delivered to phantom with 1 cm motion. 
Measured Dose (Gy) TPS Relative 
MU Average STD Calculated Deviation 
1 2 3 4 5 Dose (Gy) (%) 
2 0.02 0.02 0.02 0.02 0.02 0.02 0.00 0.01 -94.19 
11 0.07 0.07 0.07 0.07 0.07 0.07 0.00 0.05 -34.95 
210 1.31 1.32 1.39 1.27 1.32 1.32 0.04 1.25 -5.90 
196 1.16 1.17 1.17 1.16 1.16 1.17 0.00 0.98 -18.90 
230 1.37 1.39 1.39 1.38 1.39 1.38 0.01 1.16 -19.23 
170 1.04 1.04 1.04 1.04 1.04 1.04 0.00 0.89 -16.61 
829 5.61 8.33 7.02 5.62 5.62 6.44 1.09 4.58 -40.61 
171 1.15 1.18 1.16 1.15 1.15 1.16 0.01 1.07 -8.36 
Total 11.74 14.51 13.25 11.72 11.77 12.60 1.12 10.00 -25.96 
 
The difference observed between planned and delivered doses can be explained by the design of 
the detector hole precision to fit the specific detector thereby reducing the geometric uncertainty 
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and the risk of surrounding air gap. The dosimetric variations observed between the planned and 
the measured dose would be attributed to the uneven mass distribution of acrylic powder within 
the simulated tumour, set-up uncertainties and style of measurement. However these discrepancies 
could be reduced by establishing international and/or national guidelines on dose prescription and 
reporting, volume definitions (e.g. intersection and union of targets and organs at risk), margin 
status, and volume extension in build-up region and overlapping structures as suggested elsewhere 
(Das et al., 2008). The dose variation also shows the need to employ motion management 
techniques as well as image-guided techniques in the planning and treatment delivery of SBRT.  
 
4.2.3 RESULTS OF CLINICAL CASE STUDY 
The clinical case study was done to demonstrate dose to critical organs since the phantom only 
gave dose statistics on the target. Treatment plans were considered acceptable when at least 95% 
of the PTV volume is covered by the prescription dose (V100%PD > 95%), at least 99% of the 
PTV volume is covered by 90% of the prescription dose (V90%PD > 99%) for target coverage. 
Based on the organ dose-volume constraints the plan's acceptability was determined for the OARs 
(Table 3.1). The DVHs for the various treatment plans on the patient planning CT is displayed in 
Figures 4.6, 4.7 and 4.8. The DVH plots were used to quantitatively assess the acceptability of 
each treatment plan by examining the extent to which each plan achieved the target dose coverage 
and OAR dosimetric constraints. 
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Figure 4.6: DVH of the treatment plan with 48 Gy in 4 fractions for tumour size of 3 cm. 
 
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Figure 4.7: DVH of the treatment plan with 50 Gy in 5 fractions for tumour size of 3 cm. 
 
 
 Zoomed part 
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Figure 4.8: DVH of the treatment plan with 50 Gy in 5 fractions for tumour size of 1 cm. 
  
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4.2.3.1 DOSE STATISTICS AND DVH EVALUATION OF THE PTV 
The quality of treatment plans generated was evaluated by calculating the heterogeneity index 
(HI5/95), but the conformity index (CI) and gradient index were calculated by the treatment 
planning system. Improved dose conformity to the target is indicated by a conformity index value 
close to 1.0. HI5/95 < 1·2 is considered ideal or minor deviation for HI5/95 < 1·5 which indicates 
greater heterogeneity within the target volume. Kim et al., (2015) reported a CI of 1·05 ± 0·07 and 
Weyh et al., (2013) reported a mean CI of 1·36 ± 2·9. Herbert et al., (2013) reported a CI of 1·21 
for the 3DCRT plan at a prescription dose of 48 Gy/4. Data of the PTV volumes, mean, maximum 
and minimum doses, the PTV V90%, V95%, andV100% for all treatment plans for the prescription 
dose of 50 Gy/5 and 48 Gy/4 shown in Tables 4.8. 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
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Table 4.8: Dose evaluation indices for prescription doses of 48 Gy/4 and 50 Gy/5 PTV. 
50 Gy/5 50 Gy/5 
Metric description 48 Gy/4 
(3 cm tumour) (1 cm tumour) 
Volume (cm3) 131.4 
V100%PD ≥ 95% 101.10 98.10 97.36 
V99% > 90% 102.62 99.68 99.19 
V90%PD ≥ 99% maximum dose inside 
100.49 100 100 
ITV 
Maximum dose (Gy) 51.71 53.47 54.78  
(% PD) (107.7%) (107%) (109.6%) 
Minimum dose (Gy) 45.72  48.36  48.59  
(% PD) (95.3%) (96.7%) (97.2%) 
Mean dose (Gy) 49.88 51.76  52.51  
(% PD) (103.9%) (103.5%) (105%) 
0.49  0.68  1.24  
STD (Gy) 
(3.4%) (1.4%) (2.5%) 
D5 50.53 52.61 54.33 
D95 48.96 50.41 50.34 
Heterogeneity index (HI5/95) 1.03 1.04 1.08 
Conformity Index (CI) 1.24 1.17 1.48 
Gradient Index (GI) 2.88 3.06 1.69 
 
Dose fractionation schemes of 48–60 Gy in 4–5 fractions are commonly used for treating stage I 
primary NSCLC and result in high local control rates and low OARs toxicities (Goldsmith & Gaya, 
2012; X. Wang et al., 2018; Y. Zhao et al., 2020). Concerning tumour control, MacHtay et al. 
(2012) reported that higher radiotherapy doses are associated with improved local-regional control 
and survival in patients with locally advanced NSCLC that received chemoradiation. Korzets 
Ceder et al. (2018), Rowe et al. (2012), Verstegen et al. (2015) also treated patient with SBRT and 
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had about 80% tumour control. Though,   pneumonitis and bronchial stenosis were the most 
frequent side effects. 
4.2.3.2 DOSE STATISTICS AND DVH EVALUATION OF THE OARS  
Dose to OARs is usually a dose restricting factor for the target dose. Doses to OARs were evaluated 
from the DVHs of the treatment plans with a prescription dose of 48 Gy in four fractions and 50 
Gy in five fractions for tumour sizes of 3 cm and 1 cm. The doses to organs at risk were indexed 
by the percentage volume of the specified organ receiving 5 Gy (V5 Gy), 10 Gy (V10 Gy), 20 Gy (V20 
Gy) and 30 Gy (V30 Gy), minimum, maximum and mean doses. Doses to critical structures are 
presented in Tables 4.9 to 4.16.  
Table 4.9: Dosimetric analysis of the bilateral lung for treatment plans with 48 Gy in four 
fractions and 50 Gy in 5 fractions. 
Dosimetric parameter 48 Gy/4 50 Gy/5 (3 cm) 50 Gy/5 (1 cm) 
Volume 2639.1 
Maximum dose (Gy) 51.71 Gy  53.48  54.78  
(% PD) (107.7%) (107%) (109.6%) 
Minimum dose (Gy) 0.06  0.04  
0 
(% PD) (0.1%) (0.1%) 
Mean dose (Gy) 11.94  12.32  1.39  
(% PD) (24.9%) (24.6%) (2.8%) 
16.07  17.03  4.23  
STD (Gy) 
(33.5%) (34.1%) (8.5%) 
V5 Gy (%) 40.20 51.44 10.60 
V10 Gy (%) 32.33 36.98 7.26 
V20 Gy (%) 25.65 32.64 4.47 
V30 Gy (%) 18.28 29.34 2.76 
 
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Table 4.10: Dosimetric analysis of the left and right lung for treatment plans with 48 Gy in 
four fractions and 50 Gy in 5 fractions. 
OAR Dosimetric parameter 48 Gy/4 50 Gy/5 (3 cm) 50 Gy/5 (1 cm) 
Volume (cm3) 1170.4 
V5 Gy (%) 8.03 20.18 0.58 
V10 Gy (%) 0 0.37 0.35 
V20 Gy (%) 0 0 0.10 
Left Lung V30 Gy (%) 0 0 0 
Maximum dose (Gy) (% PD) 8.90 (18.5%) 7.14 (14.3%) 27.70 (55.4%) 
Minimum dose (Gy) (% PD) 0.06 (0.1%) 0.043 (0.1%) 0 
Mean dose (Gy) (% PD) 1.57 (3.3%) 1.15 (2.3%) 0.16 (0.3%) 
STD (Gy) 1.83 (3.8%) 1.33 (2.6%) 1.12 (2.2%) 
Volume (cm3) 1463.3 
V5 Gy (%) 65.80 76.25 12.63 
V10 Gy (%) 58.02 66.07 7.79 
V20 Gy (%) 46.06 58.57 2.19 
Right 
V30 Gy (%) 32.82 52.68 0.58 
Lung  
Maximum dose (Gy) (% PD) 51.70 (107.7%) 53.48 (107%) 54.78 (109.6%) 
Minimum dose (Gy) (% PD) 0.32 (0.7%) 0.31 (0.6%) 0.04 (0.1%) 
20.2  2.38  
Mean dose (Gy) (% PD) 21.21 (42.4%) 
(42%) (4.8%) 
STD (Gy) 17.54 (36.5%) 18.48 (37%) 5.39 (10.8%) 
 
 
 
 
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Table 4.11: Dosimetric analysis of the heart for treatment plans with 48 Gy in four fractions 
and 50 Gy in 5 fractions. 
50 Gy/5  50 Gy/5 
Dosimetric parameter 48 Gy/4 
(3 cm tumour)  (1 cm tumour) 
Volume 750.9 
Maximum dose (Gy) 51.2 52.71 1.87 
(% PD) (106.7%) (105.4%) (3.7%) 
Minimum dose (Gy) 
0.22 (0.5%) 0.18 (0.4%) 0 
(% PD) 
5.24 0.80 0.06 
Mean dose (Gy) 
(10.9%) (9.6%) (0.1%) 
4.71 5.38 0.07 
STD (Gy) 
(9.8%) (10.8%) (0.1%) 
V5 Gy (%) 51.54 38.43 0 
V10 Gy (%) 10.83 7.68 0 
V20 Gy (%) 1.46 3.27 0 
V30 Gy (%) 0.17 0.61 0 
 
 
 
 
 
 
 
 
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Table 4.12: Dosimetric analysis of the bronchial tree for treatment plans with 48 Gy in four 
fractions and 50 Gy in 5 fractions. 
Dosimetric 50 Gy/5  50 Gy/5  
OAR 48 Gy/4 
parameter (3 cm target) (1 cm target) 
Volume 1.5 
Maximum dose (Gy) 10.91 (22.7%) 8.04 (16.1%) 0.13 (0.3%) 
Bronchial Tree Minimum dose (Gy) 7.00 (14.6%) 5.26 (10.5%) 0.05 (0.1%) 
(Left) Mean dose (Gy) 9.74 (20.3%) 7.12 (14.2%) 0.10 (0.2%) 
  STD (Gy) 0.70 (1.5%) 0.43 (0.9%) 0.01 (0%) 
   
V5 Gy (%) 100 100 0 
V10 Gy (%) 43.90 100 0 
V20 Gy (%) 0 0 0 
V30 Gy (%) 0 0 0 
Volume 3.8 
Maximum dose (Gy) 46.72 (97.3%) 49.56 (99.1%) 8.49 (17%) 
Minimum dose (Gy) 10.44 (21.8%) 7.10 (14.2%) 0.10 (0.2%) 
Bronchial Tree 
Mean dose (Gy) 14.70 (30.6%) 12.82 (25.6%) 0.53 (1.1%) 
(Right)  
  STD (Gy) 5.70 (11.9%) 6.43 (12.9%) 0.92 (1.8%) 
V5 Gy (%) 100 100 3.85 
V10 Gy (%) 100 57.70 1.24 
V20 Gy (%) 11.57 11.65 0 
V30 Gy (%) 4.44 4.10 0 
 
Table 4.13: Dosimetric analysis of the oesophagus volume with 48 Gy in four fractions and 
50 Gy in 5 fractions. 
Dosimetric parameter 48 Gy/4 50 Gy/5 (3 cm) 50 Gy/5 (1 cm) 
Volume 26.6 
Maximum dose (Gy) 11.56 (24.1%) 8.72 (17.4%) 2.39 (4.8%) 
Minimum dose (Gy) 0.27 (0.6%) 0.23 (0.5%) 0.02 (0%) 
Mean dose (Gy) 3.33 (6.9%) 2.48 (5.0%) 0.14 (0.3%) 
STD (Gy) 3.64 (7.6%) 2.68 (5.4%) 0.16 (0.3%) 
V5 Gy (%) 30.77 32.31 0 
V10 Gy (%) 3.26 25.00 0 
V20 Gy (%) 0 0 0 
V30 Gy (%) 0 0 0 
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Table 4.14: Dosimetric analysis for trachea for treatment plans with 48 Gy in four fractions 
and 50 Gy in 5 fractions. 
Dosimetric parameter 48 Gy/4 50 Gy/5 (3 cm) 50 Gy/5 (1 cm) 
Volume 15.5 
Maximum dose (Gy) 11.25 (23.4%) 8.05 (16.1 %) 0.11 (0.2%) 
Minimum dose (Gy) 0.06 (0.1%) 0.06 (0.1%) 0 
Mean dose (Gy) 1.32 (2.7%) 0.96 (1.9%) 0.04 (0.1%) 
STD (Gy) 2.22 (4.6%) 1.37 (2.7%) 0.03 (0.1%) 
V5 Gy (%) 7.67 4.36 0 
V10 Gy (%) 1.24 0 0 
V20 Gy (%) 0 0 0 
V30 Gy (%) 0 0 0 
 
Table 4.15: Dosimetric analysis of the spinal cord for treatment plans with 48 Gy in four 
fractions and 50 Gy in 5 fractions. 
Dosimetric parameter 48 Gy/4 50 Gy/5 (3 cm) 50 Gy/5 (1 cm) 
Volume 24.7 
Maximum dose (Gy) 1.12 (2.3%) 1.10 (2.2%) 5.14 (10.3%) 
Minimum dose (Gy) 0 0 0 
Mean dose (Gy) 0.37 (0.8%) 0.34 (0.7%) 0.12 (0.2%) 
STD (Gy) 0.32 (0.7%) 0.30 (0.6%) 0.26 (0.5%) 
V5 Gy (%) 0 0 0 
V10 Gy (%) 0 0 0 
V20 Gy (%) 0 0 0 
V30 Gy (%) 0 0 0 
 
 
 
 
 
 
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Table 4.16: Dosimetric analysis of the ribs for treatment plans with 48 Gy in four fractions 
and 50 Gy in 5 fractions. 
Dosimetric parameter 48 Gy/4 50 Gy/5 (3 cm) 50 Gy/5 (1 cm) 
Volume 541.2 
Maximum dose (Gy) 42.84 (89.2%) 46.98 (93.9%) 32.45 (64.9%) 
Minimum dose (Gy) 0 0 0 
Mean dose (Gy) 3.21 (6.7%) 3.42 (6.8%) 0.35 (0.7%) 
STD (Gy) 7.12(15%) 7.99 (16%) 2.19 (4.4%) 
V5 Gy (%) 21.02 20.40 1.60 
V10 Gy (%) 14.92 13.71 1.05 
V20 Gy (%) 10.12 10.94 0.52 
V30 Gy (%) 8.34 7.89 0.03 
 
Critical organ constraints were met for all structures in all three scenarios except the heart in the 
plan with a 3 cm tumour size, which had a volume dose higher than 34 Gy. This was due to the 
tumour being close to the heart. Suitable conformal target coverage was achieved for all dose 
prescriptions which is the primary aim of radiotherapy devoid of extreme doses of OARs to 
minimise toxicity. Sufficient target coverage is associated with tumour control which leads to 
improved biochemical relapse-free survival, cancer progression-free survival and cancer-specific 
survival (Zheng et al., 2014).  
 
  
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CHAPTER FIVE 
CONCLUSIONS AND RECOMMENDATIONS  
5.1 CONCLUSIONS  
In this study, a lung phantom has been fabricated and has been used to investigate  the treatment 
of lung tumours with the SBRT technique without a 4D CT scanner. The study investigated SBRT 
prescription doses for treating lung tumours according to RTOG 0915. The fabricated lung 
phantom contained a centrally placed simulated tumour embedded in a tissue-equivalent lung. In 
this study, the use slow CT scanning for acquiring image dataset for moving targets have been 
demonstrated to be feasible for achieving greater target dose conformity, rapid dose fall-off from 
PTV and minimising doses to the organs at risk as done in other.   
The study has shown that predefined dose-volume constraints and objectives for SBRT technique 
can be achieved, resulting in improved dose optimisation and coverage of target volume, reduction 
in OARs volume receiving high doses and therefore with the potential to reduce the rate of toxicity, 
decrease pain and improve the quality of life for lung cancer patients in a low resourced setting. 
Doses were measured with the phantom in both the static and moving cases using an ionisaiton 
chamber. Average measured doses were compared to treatment planning calculated doses for the 
phantom in both the static and moving cases. Dose deviation for treating static mimicked tumour 
was 8.43%, -4.31% for phantom in 0.5 cm motion, and -25.96% for phantom in 1 cm motion. 
Phantom dosimetric analysis for PTV V100%, V99%, V90% at 50 Gy/5 without motion were 86.77%, 
91.19% and 99.96%; with 0.5 cm motion were 98.60%, 99.61% and 100%; and with 1 cm motion 
were 72.72%, 90.47% and 99.65%, respectively. Clinical analysis for  PTV V100%, V99%, V90% at 
48 Gy/5 were 101.10%, 102.62% and 100.49%, respectively. For a tumour size of 3 cm at 50 Gy/5 
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were 98.10%, 99.68% and 100%, respectively; and for 1 cm tumour size were 97.36%, 99.19% 
and 100 %, respectively.  
SBRT treatment planning and treatment delivery protocols have been developed  in this study and 
used to demonstrate that SBRT treatment planning and delivery are feasible at the study site 
without 4-D CT scanner. The statistics propose that the target was sufficiently covered with the 
dose for all scenarios, thereby achieving the primary radiotherapy goal without excessively dosing 
OARs to minimise toxicity. It was demonstrated that sufficient dose conformity to the target in the 
lung was achieved for all scenarios, thereby fulfilling the radiotherapy goal of maximum tumour 
control and minimum tissue complication. SBRT treatment planning and delivery are possible to 
achieve at KATH in the absence of 4D CT based on the results of this study. Thus patients could 
benefit from highly conformal target coverage for increased tumour control while at the same time 
minimising dose to surrounding critical structures for minimal treatment-associated toxicities. 
Recent advances in radiotherapy have enabled safe delivery of SBRT which delivers a high dose 
per fraction. Although surgery remains the standard of care for operable patients, SBRT offers 
superior local control and overall survival rates with acceptable toxicity. 
5.2 RECOMMENDATIONS 
Using 3DCRT for SBRT can be achieved in the study facility. Implementation of the SBRT 
technique in KATH will ensure adequate target coverage, minimised toxicity to other structures 
and as a result will prolong patient life. I will therefore recommend the implementation of SBRT 
at KATH. After the implementation, the technique could be extended to other sites such as the 
liver and spine. Slow CT scans can be used for acquiring planning CT images of small tumours 
for treatment planning and delivery. Also, the target range where the tumour can be viewed should 
be used as ITV during treatment planning. A margin of about 5 mm can be added to the ITV to get 
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CTV. Then a margin of about 5 mm can be added to the CTV to create the PTV. Planning should 
be generated on the PTV to ensure the criteria specified by RTOG are fulfilled. Also to further 
minimise the risk of radiation pneumonitis respiratory gating can be introduced to reduce lung 
dose. 
  
 
 
 
  
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APPENDICES 
APPENDIX A 
 
 
 
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APPENDIX B 
 
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