Free Breathing Versus Deep Inspiration Breath Hold Technique in Adjuvant Radiotherapy for Left Sided Breast Cancer: A Dosimetric Comparison of Target Volumes, Heart and Left Lung
Phase: NA
Conditions: Carcinoma Breast, Radiation Therapy for Primary Breast Cancer, Radiation Tolerance, Radiation Induced Cardiac Damage, Radiation Induced Lung Injury (RILI), Radiotherapy; Adverse Effect, Radiotherapy, Adjuvant
Sponsor: Nishat Tasnim

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Free Breathing versus Deep Inspiration Breath Hold 
Technique in Adjuvant Radiotherapy for Left Sided 
Breast Cancer: A Dosimetric Comparison of Target 
Volumes, Heart and Left Lung 
 
 
 
 
 
 
 
 
 
 
 
 
Dr. Nishat Tasnim 
MD(Oncology) – Phase B 
 
 
Bangabandhu Sheikh Mujib Medical University 
Shahbagh, Dhaka. 
 
 
 
 
 

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Abbreviations 
3DCRT 
 Three-dimensional conformal radiotherapy 
AJCC  
 American Joint Committee on Cancer 
BCS 
 Breast Conservation Surgery 
BMI 
 Body Mass Index 
BSMMU 
 Bangabandhu Sheikh Mujib Medical University 
CMH 
 Combined Military Hospital 
DIBH 
 Deep Inspiration Breath Hold 
DVH 
 Dose Volume Histogram 
ECOG 
 Eastern Co-operative Oncology Group 
ERR 
 Estimated Risk Ratio 
GLOBOCAN 
 Global Cancer Incidence, Mortality and Prevalence 
HDI 
 Human Development Index 
ICRU 
 International Commission on Radiation Units 
IMRT 
 Intensity Modulated Radio Therapy 
LAD 
 Left Anterior Descending Artery 
LINAC 
 Linear Accelerator 
MCE 
 Major Coronary Events 
MHD 
 Mean Heart Dose 
MRM 
 Modified Radical Mastectomy 
NCCN 
 National comprehensive cancer network, USA 
OAR 
 Organs At Risk 
OSI 
 Optical Surface Imaging 
PMRT 
 Post Mastectomy Radiation Therapy 

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PTV 
 Planning Target Volume 
RILD 
 Radiation Induced Ling Disease 
RP 
 Radiation Pneumonitis 
RPM 
 Real time Position Management 
RT 
 Radiotherapy 
RTOG 
 Radiation Therapy Oncology Group 
SGRT 
 Surface Guided Radiotherapy System 
SPSS 
 Statistical Packages for Social Sciences (SPSS Inc. Chicago IL 
USA) 
VMAT 
 Volumetric Modulated Arc Therapy 
WHO 
 World Health Organization 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 

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Abstract for the Institutional Review Board 
Background 
Breast cancer is the most common cancer among Bangladeshi females. Radiotherapy 
(RT) is an essential treatment option for most of the patients. However, it can cause 
significant late cardiac and pulmonary toxicity specially in left-sided breast cancer 
patients which is directly correlated with dose. Newer technique like deep inspiration 
breath hold (DIBH) RT can reduce doses to the heart and left lung than RT with free 
breathing (FB) without compromising doses to the planning target volumes (PTV). 
 
Aim and Objective: 
To compare between radiation doses to the target volumes, heart and left lung with free 
breathing and deep inspiration breath hold technique in adjuvant radiotherapy for left 
sided breast cancer. 
 
Materials and Methods: 
This quasi-experimental study will be conducted in 4 different centers of Bangladesh 
over a period of one year. A total of 50 left sided breast cancer patients meeting the 
inclusion and exclusion criteria will be enrolled in this study and then divided equally 
into 2 arms (Arm A and Arm B). Arm A participants will undergo computed tomography 
(CT) simulation and RT with FB. For Arm B, CT simulation and RT will be done in 
DIBH technique. All participants will receive 40.05 Gray (Gy) radiation, at 2.67 Gy 
daily single fraction, 5 days a week, for 3 weeks by IMRT. The dose volume histograms 
(DVH) will then be calculated to measure the dose to PTV, heart and left lung. 
 
Ethical Considerations and Maintenance of Confidentiality: 
After conclusive recruitment of subjects, the nature, purpose, potential risks, and 
benefits of the study will be explained in detail to them and informed written consent 
will be taken. To assess current condition, detailed history will be noted as well as 
clinical examination will be done. Participant’s confidentiality will be maintained 
strictly throughout the time by giving them a unique code. No papers will contain name 
of any participant. The selected participants will be given Bangla version of consent to 
read by them. If they voluntarily agree to participate and give their full informed 
consent, only then they will be recruited as study participants. 

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Statistical Method: 
All the relevant data will be compiled on a master chart first and then statistical analysis 
of the results will be obtained by using Windows based computer software facilities 
with Statistical Packages for Social Sciences (SPSS-24) (SPSS Inc, Chicago IL USA). 
The data will be analysed using Chi-square test and ‘t’ test. The results will be presented 
in tables, figures, diagrams. All reported P values are two sided and P <0.05 will be 
considered statistically significant. 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 

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Title of the Protocol 
 
Free Breathing versus Deep Inspiration Breath Hold Technique in Adjuvant 
Radiotherapy for Left Sided Breast Cancer: A Dosimetric Comparison of Target 
Volumes, Heart and Left Lung 
 
Name of the student : Dr. Nishat Tasnim 
 
Place of study  
: Department of Clinical Oncology, BSMMU 
: Department of Radiation Oncology, Combined Military 
  Hospital 
: Department of Oncology, Delta Hospital Limited 
: Lab Aid Cancer Hospital 
 
Type of the study 
: Quasi-Experimental study 
 
Name of the guide 
: Dr. Most. Rokaya Sultana 
 
 
 
  Associate Professor 
  Department of Clinical Oncology 
 
 
 
  Bangabandhu Sheikh Mujib Medical University (BSMMU) 
 

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Table of Contents 
 
Serial 
No.
Topic 
Page No. 
1
Title
-
2
Introduction
1
3
Rationale of the study
6
4
Research question
7
5
Objectives
8
6
Materials & Methods
9
 
a) Study design
9
b) Duration of study
9
c) Centre of study
9
d) Study Population
9
e) Sampling technique 
9
f)
Sample size
10
g) Selection criteria of patients
11
h) Research Instrument 
11
i) Grouping
12
j) Study procedure
12
k) Case collection
14
l) Pre-treatment evaluation
14
m) Intervention
15
n) Variables
15
o) Data collection
16
p) Consort flow chart
17
q) Operational definition
18
r) Analysis of Data
20
s) Data presentation
20
t)
Quality assurance
20
u) Timetable of the study
21
7
Ethical Considerations
22
8
Dummy tables
23
9
Limitations of the study
24
10
Reference
25
11
Budget
32
12
Appendices
Xiv

1 
 
 
Introduction 
 
‘‘Cancer is a large group of diseases that can start in almost any organ or tissue of the 
body when abnormal cells grow uncontrollably, go beyond their usual boundaries to 
invade adjoining parts of the body and/or spread to other organs’’ (World Health 
Organization [WHO]). The incidence, prevalence and fatality of cancer is rising 
worldwide with the increase in life expectancy and change in lifestyle. It represents a 
significant global health, social and economic burden. 
 
According to WHO in 2022, estimated new cases were approximately 20 million, about 
1 in 5 people suffer from cancer in their lifetime. It has become the second leading 
cause of death worldwide accounting for an estimated 9.7 million deaths that is 1 in six 
deaths (16.8%) and 1 in 4 deaths (22.8%) from noncommunicable diseases. 1 in 9 men 
and 1 in 12 women die of this approximately. At the same time in Bangladesh, expected 
number of new cases was around 167256 with 116598 deaths and 5-year prevalence of 
about 346337 (Global Cancer Observatory [GLOBOCAN]- Bangladesh, 2022). Among 
men, the most common causes are lung, prostate, colorectal, stomach and liver cancer 
and for women, breast, lung, colorectal, cervical and thyroid cancer ranked as the 
commonest ones. 
 
Breast cancer is the most commonly diagnosed cancer in female globally. According to 
WHO in 2022, there were 2.3 million women diagnosed with breast cancer. Statistics 
show disparity in breast cancer burden according to human development index (HDI). 
In a very high HDI country, 1 in 12 women will be diagnosed in their lifetime whereas 
in countries with low HDI, this data is about 1 in 27 women though they are at increased 
mortality risk from late diagnosis and inadequate access to treatment. 
 
Also in our country, breast cancer is one of the major health concerns in female. Though 
there is lack of nationwide exact data but it is estimated as the most common cancer 
among women. It constitutes 18% of new cancer cases estimated to be 12989 new 
diagnoses made in 2022 with 6162 deaths (GLOBOCAN- Bangladesh, 2022,). It is also 
consistent with cancer registry report of National Institute of Cancer Research & 
Hospital over a period of 2018 to 2020 (Cancer Registry Report 2018-2020, 2022). 

2 
 
 
Breast cancer is a heterogeneous and potentially curable disease. It can occur at any age 
but increasing age is one of the most important risk factors. Additional predisposing 
factors include family history (nearly 25% of breast cancer cases are related to family 
history), genetic mutations (specially in high penetrance genes like BRCA1 or 
BRCA2), early menarche (before 12 years), late age of first pregnancy (three times 
higher in women who have their firstborn after 30 years), late menopause (after 55 
years), use of oral contraceptives or hormone replacement therapy, exposure to 
radiation at early age, obesity etc (Symonds et al., 2019, p. 401). 
 
The commonest site of breast cancer is the upper outer quadrant (⁓ 40%) followed by 
the central area (29%), the upper inner quadrant (14.2%), the lower outer quadrant 
(8.8%), and the lower inner quadrant (5%) (Halperin et al., 2019). In developed 
countries at the time of diagnosis, maximum patients usually have localized disease. 
But in many other parts of the world including in our country, about 60% of patients 
will present with locally advanced or metastatic disease (Abraham & Gulley, 2022). 
 
Treatment modalities include different types of surgery, chemotherapy, RT depending 
on histology, stage, age of the patient, performance status, co morbidities etc. As many 
of our patients present with advanced stage due to lack of mass screening programmes 
and awareness, MRM is done mostly than breast conservative surgery (BCS) (Rastogi 
et al., 2017). As significant risk of local recurrence can still remain (Clarke et al., 2005), 
post mastectomy radiotherapy (PMRT) is essential for most of them to reduce the 
locoregional recurrence and improve overall survival (OS) (McGale et al., 2014) by 
eradicating the microscopic reservoirs (DeVita et al., 2022, p. 993). 
  
PMRT is recommended in patients with 4 or more positive axillary lymph nodes (ALN) 
and should be strongly considered in patients with 1–3 positive ALN. In patients with 
negative ALN, PMRT can be considered for tumors more than 5 cm or negative 
pathological margin less than 1mm. It may also be considered for patients with multiple 
high-risk recurrence factors, including central/medial tumors or tumors ≥2 cm and at 
least one of the following: grade 3, ER-negative, or lymphovascular invasion LVI 
(National Comprehensive Cancer Network [NCCN], version 2.2024, p. BINV-3). 
 

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RT techniques include two-dimensional (2D) therapy, three-dimensional conformal 
radiotherapy (3DCRT), intensity modulated radiotherapy (IMRT), volumetric 
modulated arc therapy (VMAT) etc. Though there have been tremendous improvements 
in technology, still proper dose of radiation cannot be given precisely to the area of 
interest only. According to the International Commission on Radiation Units (ICRU), 
“The normal tissues which lie adjacent to tumor & may therefore be included within 
the treated volume with a risk that the radiation may impair their normal functioning 
are known as organ at risk (OARs)” (Morris et al., 2024, p. 40). These side effects may 
be early or late resulting in treatment delay, increased morbidity, poor quality of life 
(QoL), financial burden to the patient and nation and in many cases- undue mortality. 
 
During Left-breast RT, two of the important OARs are the heart and left lung as they 
receive incidental doses. Radiation to heart causes circulatory changes by damaging 
cardiac micro and macro vasculatures resulting in fibrosis (Correa et al., 2007). It 
ultimately increases the risk of major coronary events (MCE) like myocardial infarction 
(MI), coronary revascularization or death from ischemic heart disease (Darby et al., 
2013). These effects are usually not evident immediately. Latent period ranges from 
months for subclinical disorders like pericarditis, to decades for clinical diseases like 
MCE (Sardaro et al., 2012). Preexisting risk factors (hypertension, diabetes mellitus, 
total cholesterol, family history of early MI, previous cardiotoxic chemotherapy, 
smoking) increase the absolute risk (Shapiro et al., 1998; Wilson et al., 1998). 
 
A linear relationship has been found between the rate of MCE and Mean Heart Dose 
(MHD) without any threshold which means no minimum dose with the absence of risk 
(Hayden et al., 2012). Study reveals 7.4% relative increase in MCE risk for per Gy 
increase in MHD received (Darby et al., 2013). Cardiac mortality has been estimated 
as 0.041 Excess Rate Ratio (ERR) per Gy whole heart dose (Taylor et al., 2017). 
 
Pulmonary toxicities also occur from RT which may be clinical or sub clinical. 
Documented ones are- reduced lung function, radiation pneumonitis (RP), lung fibrosis, 
lung cancer (Lawler et al., 2017). Pre-existing patient-related risk factors for radiation 
induced lung disease (RILD) are- older age, history of chronic lung disease, smoking, 
concurrent chemotherapy with RT etc (Marks et al., 2010). No specific threshold is 
there for RILD, with risks increasing as dose increases (Halperin et al., 2019). 

4 
 
 
Course of RP is divided into several phases ranging from immediate phase occurring in 
hours to days to final fibrosis phase occurring in 6–12 months after RT (Gokula et al., 
2013) and related with surfactant producing type II pneumocytes. RP risk increases with 
mean dose to the lung or irradiated lung volume (Oechsner et al., 2019). Incidence of 
lung cancer ≥ 10 years after RT 0.11 ERR per Gy whole lung dose (Taylor et al., 2017). 
 
As patients are becoming long survivors, more patients are at risk of late effects (Duarte 
et al., 2022). Advanced irradiation techniques are being developed to avoid or reduce 
these. RT with optimisation of beam angles, DIBH technique, using heart lung shielding 
Multileaf collimators (MLCs), prone positioning, partial breast irradiation (PBI), 
IMRT, tomotherapy, proton therapy etc are notable (Taylor et al., 2015). Among these, 
heart lung shielding MLCs are preferable for upper pole breast cancers and may results 
in underdose to target volume specially when the PTV is located at lower part; prone 
positioning is more suitable for sparing lungs but heart dose may vary (Varga et al., 
2014) due to variable patients’ anatomy and the options for PBI are very selective. Very 
advanced techniques are also not suitable for resource poor setting due to unavailability. 
 
DIBH is a specialized respiratory gating system. Patients are instructed to hold their 
breath after a deep inspiration for an extended time. This produces a large enough 
window to treat the tumor with limited motion (Kepka, 2021). An inflated lung pushes 
the chest wall up and the heart inferiorly and posteriorly away from the treatment field. 
This results in substantial exclusion of irradiated heart and lung volumes from the high-
dose area without compromising PTV coverage (Stranzl et al., 2008). Ultimately, the 
heart and left lung receive reduced radiation doses as compared to conventional 
technique (Yeung et al., 2015). 
 
Precise reduction of cardiac and pulmonary doses is critical due to anatomic proximity 
(Rochet et al., 2014).  Surface image-guided RT (SGRT) system along with optical 
surface imaging (OSI) is a very useful tool for this (Wolf et al., 2023) by which 
reproducible patient setups as well as reasonably consistent distances between the heart 
and the chest wall during each breath holds can be achieved (Cerviño et al., 2009). 
Radiation beam is on only during inspiration and when the patient’s current surface is 
within a preset tolerance of the DIBH reference surface (Macrie et al., 2013). It ensures 
reliability of the procedure without compromising doses to the target volumes. 

5 
 
 
Breast Cancer Expert Panel of the German Society for Radiation Oncology (DEGRO) 
has recommended that MHD should be as low as <2.5 Gy (Piroth et al., 2019). Whereas 
in conventional tangential left-breast RT, the MHD ranges from 1.7–9.0 Gy (Latty et 
al., 2014). This is clearly higher than expected safe range.  Studies reveal that, it can be 
reduced upto ~0.7–5.0 Gy by DIBH technique. CT-based studies showed the magnitude 
of benefit- approximately half of the patients had complete removal of heart from 
radiation field and 80% had overall reduction in cardiac volumes (Lu et al., 2000). 
 
DIBH is specifically important in PMRT because reducing cardiac dose is more 
challenging here due to the need of treating much larger surgical bed including scars. 
Left lung dose reduction has also been reported with DIBH (Vikström et al., 2011). 
Moreover, by eliminating the breathing motion, treatment uncertainties can be reduced 
resulting in improved and accurate dose distribution (Rice et al., 2017). 
 
As a whole, DIBH during PMRT is more beneficial for whom cardiac shielding may 
also shield the PTV resulting in underdosing, cardiac doses likely to exceed safety 
guidelines, maximum heart depth 1 cm on digital reconstructed radiograph (DRR), 
patient with established cardiac risk factor (Symonds et al., 2019, p. 417). 
 
The most important issues with DIBH technique are individual patient’s anatomical 
differences (high body mass index- BMI, structural abnormalities, adherence of heart 
to chest wall) as well as patient’s cooperation and reproducibility which often limit the 
feasibility (Bruzzaniti et al., 2013). Another important aspect is patient-individualized 
variables like type of surgery, disease stage (especially nodal involvement affecting 
field size and shape), RT dose regimen (standard or hypofractionated) etc. 
 
From patient’s, DIBH method demands proper understanding of the procedure as well 
as some degree of effort and cooperation to maintain the breathing pattern during 
simulation and each treatment session (Borst, et al., 2009). For a complete successful 
RT session with DIBH, determination of patient benefit and capability, as well as 
optimal positioning, reproducibility and verification methods, are also required. 
 
The main objective of this study is to evaluate dosimetric benefits of the DIBH RT over 
FB RT during left sided post mastectomy chest wall irradiation. 

6 
 
 
Rationale of the Study 
 
Due to high prevalence of breast cancer and various awareness programmes, more 
patients are being diagnosed and treated now with curative intention. 
 
PMRT plays a vital role in treatment plan and is associated with improved overall 
survival. As a result, these patients are at long-term risk of cardiac and pulmonary 
sequels which causes undue morbidity and mortality specially in case of left sided 
breast cancer. The 2005 Early Breast Cancer Trialists’ Collaborative Group (EBCTCG) 
shows, beneficial effects of PMRT are counterbalanced by a 30% increase in cardiac 
deaths. So, issue of survivorship is a big concern now. 
 
Various treatment modalities are being developed with these concerns ranging from 
optimisation of beam angles to utilisation of very advanced methods like tomotherapy 
or proton therapy. Unique irradiation techniques are also being tailored by simple 
changes in treatment position or set up. Among all these, DIBH technique utilises the 
patient’s own anatomy by reproducible shift of heart from targeted radiation area due 
to increased volume of left lung in between. 
 
Maximum western studies recommend to adopt this technique for eligible left sided 
breast cancer patients by proving the efficacy of DIBH RT to reduce heart and left lung 
doses with better dose delivery to the PTVs. In countries with limited resources, it is 
important to distribute the available resources accordingly for best treatment outcome. 
DIBH RT seems to be more effective, practicable and economically feasible compared 
to other modalities for cardio pulmonary sparing. Thereby, it may help to decrease 
future disease load and the associated economic burden both for the patients and the 
nation. 
 
To the best of my knowledge, there is no study comparing target volumes, heart and 
left lung doses in FB RT and DIBH RT in our population. So, this study will be carried 
out to compare the dosimetric benefits of the DIBH technique during left sided PMRT 
over FB RT. This study may help to optimize PMRT approaches. 
 

7 
 
 
Research Question 
 
Does deep inspiration breath hold technique in adjuvant radiotherapy for left sided 
breast cancer reduces doses to the heart and left lung without compromising target 
volume doses? 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 

8 
 
 
Objectives 
 
General Objective: 
To compare radiation doses of target volumes, heart and left lung by free breathing 
technique and deep inspiration breath hold technique in adjuvant radiotherapy for left 
sided breast cancer. 
 
Specific Objectives: 
1. To evaluate target volume doses during adjuvant radiotherapy for left sided 
breast cancer with free breathing and deep inspiration breath hold technique. 
2. To assess cardiac doses during adjuvant radiotherapy for left sided breast 
cancer with free breathing and deep inspiration breath hold technique. 
3. To analyse left lung doses during adjuvant radiotherapy for left sided breast 
cancer with free breathing and deep inspiration breath hold technique. 
4. To demonstrate other organ at risks (right lung, right breast, esophagus, spinal 
cord) doses during adjuvant radiotherapy for left sided breast cancer with free 
breathing and deep inspiration breath hold technique. 
5. To observe different demographic variables. 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 

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Materials & Methods 
 
Study Design 
Quasi-Experimental study 
 
Duration of Study 
One year after approval from Institutional Review Board (IRB) of BSMMU. 
 
Centres of Study 
This study will be conducted in- 
1. Department of Clinical Oncology 
Bangabandhu Sheikh Mujib Medical University (BSMMU) 
Shahbagh, Dhaka. 
 
2. Department of Radiation Oncology 
Combined Military Hospital 
CMH road, Dhaka cantonment, Dhaka. 
 
3. Department of Oncology  
Delta Hospital Limited 
26/2, Principal Abul Kashem Road, Mirpur 1, Dhaka - 1216. 
 
4. Lab Aid Cancer Hospital 
26 Green Road, Dhaka. 
 
 
Study Population 
Carcinoma left breast patients attending the outpatient departments (OPD) of study 
centres for post mastectomy radiotherapy. 
 
Sampling Technique 
After meeting inclusion and exclusion criteria, participants will be enrolled in this study 
and then divided equally into 2 arms by purposive sampling. 

10 
 
 
Sample Size 
For determination of sample size following formula has been applied: 
 
n = 2 × 𝜎ଶ× ൫𝑍ఈ+ 𝑍ఉ൯2
(𝜇ଵ−𝜇ଶ)2
 
 
n = Sample size 
µ1 = Mean of control group (From previous study) 
µ2 = Mean of experimental group (From previous study) 
ơ = Standard deviation (SD) of control group 
Zα= Z- value (two tail) at a given level of significance e.g. 1.96 at 5% level of 
significance 
Zβ= Z- value (two tail) at a given power e.g. 1.28 at 90% power 
 
PMRT in free breathing technique is expected to give radiation doses to V25% of heart 
in 2.5 (SD 2.4) Gy (Rochet, et al., 2014). 
PMRT in DIBH technique is expected to give radiation doses to V25% of heart in 0.1 
(SD 0.2) Gy (Rochet, et al., 2014). 
 
Here, 
 
µ1 = 2.5 
 
 
 
 
Zα = 1.96 
 
µ2 = 0.1 
 
 
 
 
Zβ = 1.28 
 
ơ = 2.4 
 
 
n= 
ଶ×ଶ.ସమ×(ଵ.ଽ଺ାଵ.ଶ଼)మ
(ଶ.ହି଴.ଵ)మ
 = 23 
 
With a 10% allowance for lost to follow up final sample size is 23 + 2.3 = 25  
 
 
 
 
 
 

11 
 
 
Selection of Patients 
Participants will be selected after fulfilment of inclusion and exclusion criteria. 
 
Inclusion Criteria 
1. Histopathologically proven left sided invasive breast cancer patients who 
underwent modified radical mastectomy. 
2. Post mastectomy patients for whom radiotherapy including supraclavicular 
irradiation is indicated. 
3. Patients having ECOG performance status up to 1. 
 
Exclusion Criteria 
1. Left sided breast cancer patient underwent BCS. 
2. Patient received any chemotherapy other than Doxorubicin, Cyclophosphamide 
and taxane (Paclitaxel/ Docetaxel) in any settings (neoadjuvant or adjuvant). 
3. Patients who have comorbidities that would hinder DIBH (extreme obesity, 
mental disorder, hypoacusis etc.). 
4. Known case of patients with respiratory diseases. 
5. Known case of patients with ischemic heart diseases. 
6. Patients with previous history of radiotherapy to chest. 
7. Male breast cancer patients. 
8. Bilateral breast cancer patients. 
9. Pregnant or lactating women. 
10. Age ˂ 18 years. 
 
Criteria of Discontinuation of Treatment 
1. Patient’s refusal to continue study participation. 
2. Justifiable withdrawal at the investigator’s discretion. 
3. Occurrence of unacceptable issues requiring major modification of treatment. 
4. Clear lack of clinical benefit. 
 
Research Instrument 
A semi-structured data collection form consisting of sociodemographic information, 
relevant history, clinical examination and investigations made by the researcher will be 
used as research instrument (appendix IV). 

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Grouping 
Fifty post mastectomy left sided breast cancer patients who meet the inclusion and 
exclusion criteria will be enrolled in this study. Then they will be divided equally into 
2 arms (Arm A and Arm B) by purposive sampling. 
 
Study Procedure 
For Arm A participants, CT simulation scans will be performed on a supine breast board 
by Brilliance, CT Big Bore (Philips, Cleveland, USA) in BSMMU, Biograph mCT Sim 
edition (Siemens Healthineers AG, Germany) in CMH and Somatom 16 CT (Siemens 
Healthineers AG, Germany) in other institutes with arms raised above head in supports 
with free breathing. The board will be angled around 5°-25°, to level participant’s chest 
as horizontal as possible. The head will be extended comfortably with face turned to 
the right side. Radio-opaque wires will be placed over surgical scars. Skin markers, 
room laser alignment, and breast-board scale will be used for standard patient 
positioning. Scans will be acquired with a 4 mm slice width from above the shoulder to 
include the neck to 5.0 cm below inframammary fold (using right inframammary fold 
as reference). 
 
For Arm B participants, procedure will be same except the following- 
 
Breath Holding Technique 
Participants will be trained for 2-3 days for obtaining the desired breathing cycle by 
trained technologists. No extra equipment will be needed. At first, they will be assured 
and asked to relax. Then instructed to breath in and out twice followed by a slow, deep 
breath in to a comfortable higher level than normal and to hold it for at least 20 seconds 
then again breath normally. Once they are ready with expected breath holding, 
simulation will be done. 
 
During this procedure in BSMMU, SGRT system (C-RAD, Uppsala, Sweden) will be 
used. At the time of simulation with this system, no marker is usually needed on or 
around the participant; ceiling mounted laser tracking system in the room automatically 
monitor for consistency by matching with anterior and lateral tattoos.  
 

13 
 
 
In CMH, Varian RGSC (Respiratory Gating for Scanners) and in other institutes, Varian 
RPMTM system (Varian Medical System, Palo Alto, CA) will be used. A 4-dotted 
reflective marker box will be placed outside the treatment field between xiphoid level 
and umbilicus. It will act as an external surrogate to simulate the breathing pattern and 
tracked by the infrared camera at the foot end of CT couch. 
 
For all patients, audio-visual communication through in-room speakers will assist the 
participant to follow the optimal breathing pattern. Each participant will have 2 CT 
simulation scans in this arm. One just like participants in Arm A with FB, used as the 
reference for treatment setups; and another in DIBH position used for the actual 
treatment plan. 
 
A 30-35 minute in-room time (which included participant’s dressing and undressing, 
set-up, daily imaging, DIBH practice, and subsequent gated RT delivery) was given to 
each participant for first RT day. For subsequent days, 15–20-minute time was enough, 
which is double than the allocated time for radiation delivery with FB. 
 
Contouring 
For all participants, contouring will be done as per the Radiation Therapy Oncology 
Group (RTOG) protocol. For left chest wall, superiorly caudal border of the clavicle 
head, inferiorly loss of CT apparent right breast tissue, laterally mid axillary line 
excluding latissimus dorsi muscle, medially sternal–rib junction, posteriorly rib–pleural 
interface, anteriorly skin will be drawn. Nodal area will be contoured including 
supraclavicular field. For heart, the superior point is where pulmonary trunk and right 
pulmonary artery seen separately. The major blood vessels will be excluded but the left 
anterior descending (LAD) artery will be included in the heart contour as a whole. 
Lungs and other OARs will be contoured accordingly using the planning system. 
 
Treatment Planning and Evaluation 
In BSMMU, data acquired by CT scanner and sentinel will be transferred to central 
database for automatic tracking of same surface points and breathing pattern with a 
Catalyst™ system in the treatment room during every fraction, without any manual 
intervention. IMRT planning will be done by Monaco® Treatment Planning Software 
(TPS) 5.11 (Elekta AB, Stockholm, Sweden) consist of 6 MV tangential beams. 

14 
 
 
In other institutes, data will be imported to console automatically from RGSC and 
RPM™ and a treatment gate window will be established. IMRT planning will be done 
using TPS Eclipse v15.1(Varian Medical Systems, Palo Alto, CA, USA) in CMH and 
v16.1 in Lab aid. 
 
Plans will be evaluated using dose constraint as MSKCC dosimetric planning 
guidelines for breast IMRT: for heart- V25Gy <25%, mean dose, Dmean<20Gy, maximum 
dose, Dmax ≤53 Gy; for lungs- V20Gy ≤ 30%, mean dose, Dmean ≤ 22 Gy. 
 
Case Collection 
From the OPD of study centres, a total of 50 participants will be recruited after 
justifying inclusion and exclusion criteria. Before participating in the study, written 
informed consent will be taken from each selected participant. Interviews will be taken 
focusing their medical and relevant history by the researcher and will be documented 
in the preformed data-sheet in respected department with proper privacy. Also, 
necessary clinical examinations and investigations will be done. Many left sided post 
mastectomy patients come to these centres regularly for PMRT from all over 
Bangladesh. Therefore, it will be easy to enrol an adequate number of participants. 
 
Pre-treatment Evaluation 
Following procedures will be done to evaluate the participant’s condition before 
treatment: 
 
General examination: 
 Complete history, performance status and general physical examination 
including supraclavicular lymph nodes. 
Local examination: 
 Right breast examination including draining lymph node areas. 
 For left side, chest wall, scar and axilla. 
Systemic examination: 
 Respiratory system examination. 
 Cardiovascular system examination. 
 

15 
 
 
Investigations: 
 Plain chest radiograph PA view 
 ECG 
 Echocardiography 
 Lung function test 
Along with these, all pre surgical imaging and reports will be thoroughly checked. 
 
Intervention 
All participants will receive RT with Elekta Versa HD (Elekta AB, Stockholm, Sweden) 
machine in BSMMU and Varian TrueBeam (Varian Medical Systems, Palo Alto, CA, 
USA) in other institutes.  
 
Arm A: FB RT arm  
Participants will be treated with 40.05 Gy radiation, at 2.67 Gy daily single fraction, 5 
days a week, for 3 weeks by IMRT in free breathing technique. 
 
Arm B: DIBH RT arm  
Participants will be treated with 40.05 Gy radiation, at 2.67 Gy daily single fraction, 5 
days a week, for 3 weeks by IMRT in DIBH technique. As the sentinel (C-RAD, 
Uppsala, Sweden) and Varian RGSC and RPMTM system (Varian Medical System, Palo 
Alto, CA) is linked to the corresponding linear accelerator (LINAC), beam-hold will 
be automatically triggered when participant’s breathing falls outside the acceptable 
range. It will ensure radiation delivery only at deep inspiration. 
 
Variables 
 
Demographic variables: 
o Age 
o Risk factors 
 Age of menarche 
 Age at first child birth 
 Lactation history 
 Use of oral contraceptive pill 

16 
 
 
 Age of menopause 
 Use of hormone replacement therapy 
 Pre-existing hypertension / diabetes mellitus 
 Family history breast cancer or ovarian cancer 
o Educational status 
o Body mass index (BMI) 
 
Clinical variables: 
o Involved quadrant of the breast 
o Histological variety 
o Tumor grade 
o Hormone receptor and HER-2 receptor status 
o Stage of the disease 
o Performance status 
 
Study variables: 
o Planning target volume 
 Total volume 
 Maximum dose, Dmax 
 Mean dose, Dmean 
 V95 of PTV 
o Heart 
 Mean heart dose, Dmean 
 Maximum heart dose, Dmax 
 V25 of heart 
o Left lung 
 Mean dose to left lung, Dmean 
 V20 of left lung 
 
Data Collection 
Findings will be recorded in data collection form (Appendix-IV). 
 
 
 

17 
 
 
Consort Flow Chart 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Assessed for Eligibility 
Excluded 
 Not meeting inclusion criteria 
 Refused to participate 
Randomization 
Allocated to RT with Free 
Breathing Technique 
Allocated to RT with Deep 
Inspiration Breath Hold 
Technique 
Analysed 
Analysed 
 
 Lost to 
follow up 
 Discontinued 
treatment 
 Lost to 
follow up 
 Discontinued 
treatment 

18 
 
 
Operational Definition 
 
Deep Inspiration Breath Hold Radiotherapy 
The approach of delivering prescribed radiation doses only during breath holding at 
deep inspiration is considered as deep inspiration breath hold radiotherapy. 
 
Dose Volume Histogram 
It is a graphical representation of the dose of radiation received by the critical structures 
or organs at risk per 2cc volume. 
 
Intensity-modulated radiation therapy 
It refers to a radiation therapy technique in which a nonuniform fluence is delivered to 
the patient from any given position of the treatment beam to optimize the composite 
dose distribution. 
 
Mean dose 
Statistical mean dose to the critical structure specified measured using predictive dose 
calculation algorithm integrated in the treatment planning system. 
 
Maximum dose 
Statistical maximum dose to the critical structure specified measured using predictive 
dose calculation algorithm integrated in the treatment planning system. 
 
Organ At Risk 
Normal tissues which lie adjacent to tumours and may therefore be included within 
treated volumes, with a risk that the radiation may impair their normal functioning. 
 
Performance Status  
Performance status refers to the level of activity to which a patient is capable of. 
 
Respiratory Gating 
Respiratory gating refers to the process of limiting the radiation beam to selected 
portions of the respiratory cycle, thus treating the tumor at a specific position. 
 

19 
 
 
Surface Guided Radiotherapy System 
Surface imaging systems can help facilitate patient setup and allow for intrafraction 
monitoring without the use of additional ionizing radiation, this is known as Surface-
Guided Radiation Therapy. 
 
V5 
Volume of the structure receiving at least 5 Gy dose expressed as percentage of the total 
volume of that structure. 
 
V20  
Volume of the structure receiving at least 20 Gy dose expressed as percentage of the 
total volume of that structure. 
 
V25 
Volume of the structure receiving at least 25 Gy dose expressed as percentage of the 
total volume of that structure. 
 
V95% 
95% volume of the structure receiving the prescribed dose expressed as percentage of 
the total volume of that structure. 
 
 
 
 
 
 
 
 
 
 
 
 
 
 

20 
 
 
Analysis of Data 
The data will be tabulated in separate tables for both Arm-A and Arm-B. It will be 
checked, edited, coded manually and finally saved in computer. Data analysis will be 
done according to the objectives of the study by using the SPSS (Statistical Package for 
Social Science) software program for Windows, version 21. 
 
Data Presentation 
Data will be presented using tables, graphs or charts as appropriate. 
 
Quality Assurance 
Quality will be ensured during data collection and analysis. 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 

21 
 
 
Timetable of the Study 
 
  
Month 
Activities 
1  
2  
3  
4  
5  
6  
7  
8  
9  
10  
11  
12  
Approach to 
problem and 
designing 
and protocol 
submission 
  
  
  
  
  
  
  
  
  
  
  
  
Preparation 
of 
data 
collection 
sheet, 
pretesting 
and 
finalizing 
  
  
  
  
  
  
  
  
  
  
  
  
Data 
collection 
  
  
  
  
  
  
  
  
  
  
  
  
Data 
entry 
and analysis   
  
  
  
  
  
  
  
  
  
  
  
Report 
writing and 
submission 
  
  
  
  
  
  
  
  
  
  
  
  
Correction 
and 
final 
submission 
  
  
  
  
  
  
  
  
  
  
  
  
 
 
 
 
 
 
 

22 
 
 
Ethical Consideration 
Ethical issues related to this study will be maintained carefully. In this study, following 
criteria will be ensured to maintain the ethical standard- 
 All participants will be given an explanation of the study including the risks and 
benefits. 
 All participants will be included in the study after taking their informed consent. 
 Informed consent form will be supplied in Bengali & English versions. 
 It will also be explained to them that they have the right to refuse or accept to 
participate in the study. 
 All data obtained during the study period from the participant will remain 
confidential. 
 Permission will be taken by the institutional review board of BSMMU. 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 

23 
 
 
Dummy Tables 
 
Table 1: Distribution of participants by age in Arm A and Arm B  
 
Age of the patients 
(years)  
Arm A (n=25) 
Arm B (n=25) 
p value**  
n  
%  
n  
%  
18-29  
 
 
 
 
 
 
 
 
30-39  
 
 
 
 
40-49  
 
 
 
 
50-59  
 
 
 
 
 
Table 2: Cardiac dose in Arm A and Arm B  
Doses (in Gy) 
Arm A (n=25) 
Arm B (n=25) 
p value**  
Dmean  
 
 
 
Dmax 
 
 
 
V25  
 
 
 
 
** p value from Chi square test  
S = Significant 
 
 
 
 

24 
 
 
Limitations of the Study 
 Different study centres use different radiotherapy machine and treatment 
protocol. 
 Existing risk factors are not adjusted for participants. 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 

25 
 
 
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32 
 
 

xiv 
 
 
APPENDIX - I 
অবিহতοেম সљিতপϏ 
 
এই সљিতপেϏর উেгশҝ হল আপনােক ϕেয়াজনীয় তথҝ ϕদান করা έয তথҝვেলা আপনােক 
িসдাо িনেত সাহাযҝ করেব, আপিন এই গেবষণায় অংশςহণ করেবন িকনা। 
 
গেবষণার নামঃ Free Breathing versus Deep Inspiration Breath Hold Technique in 
Adjuvant Radiotherapy for Left Sided Breast Cancer: A Dosimetric Comparison 
of Target Volumes, Heart and Left Lung. 
 
ϕধান গেবষকঃ ডাঃ িনশাত তাসনীম 
 
উেгশҝ ও ϕᄿিতঃ 
বাংলােদেশ ѷন কҝাхার একΜট উেѣখেযাগҝ কҝাхার। ѷন কҝাхােরর িবিভт িচিকৎসা পдিত 
রেয়েছ, যা έরােগর িবিভт ধাপ অনুযায়ী িবিভт রকম হয়। এ έরােগর িচিকৎসার একΜট অনҝতম 
উপায় হেИ έরিডওেথরািপ। έরিডওেথরািপ চলাকালীন সময় এবং িচিকৎসা পরবতλ সমেয়ও 
িবিভт পাѩ κϕিতΝοয়া έদখা যায়। িচিকৎসা পরবতλ এসব পাѩ κϕিতΝοয়ার মােঝ হাটκ এবং 
ফুস্ফুেসর সমসҝা অনҝতম িবেশষত বাম ѷেনর έরিডওেথরািপ পাওয়ার পর। যার জনҝ 
কҝাхার আοাо έরাগীরা কҝাхার έথেক মুЅ হেলও পরবতλেত হাটκ এটাক এবং ফুস্ফুেসর 
সমসҝার বাড়িত ঝুঁিকেত পেড় যায়। িবѩবҝপী িবিভт গেবষণােত έদখা িগেয়েছ, যিদ লїা কের 
দম িনেয় পযκাч সময় দম বс রাখা অবѸায় έরিডওেথরািপ έনয়া হয় , তাহেল έযখােন 
έরিডেথরািপ পাওয়ার কথা έসখােনও পযκাч έডাজ পেড় আবার ჊ৎিপн এবং ফুস্ফুস ও 
έরিডেয়শন কম পায় যার ফেল পরবতλেত হাটκ এটাক এবং ফুস্ফুেসর সমসҝার বাড়িত ঝুঁিক 
এড়ােনা অেনকাংেশই  সјব হয়। এই গেবষণায় আপনার έরিডওেথরািপ চলাকালীন সমেয় লїা 
কের দম িনেয় পযκাч সময় দম বс έরেখ বুেকর , ჊ৎিপн এবং ফুস্ফুেসর έরিডেয়শন έডাজ 
έমেপ এই িবেশষ পдিতΜটর উপেযািগতা ও কাযκকািরতা έদখা হেব, যা এই গেবষণার মূল 
উেгশҝ। 
 
গেবষণার ঝুিকঃ 
এই গেবষণায় অংশςহেণ আপিন খুবই সামানҝ ঝুঁিকর সљুখীন হেত পােরন। সমসҝা έদখা িদেল 
তা ϕিশϠণϕাч িচিকৎসেকর মাধҝেম িনয়ϴণ এবং সমাধান করা হেব। 
 
গেবষণায় অংশςহেণর সুিবধািদঃ 
এই গেবষণায় অংশςহণ করেল আপিন বҝΝЅগতভােব έতমন লাভবান না হেলও , উЅ গেবষণা 
কҝাхােরর িচিকৎসা পдিত সѕেকκ আরও জানেত এবং অনҝানҝ έরাগীেদরেকও উтত  
িচিকৎসা িদেত সাহাযҝ করেব। 
 
িবকџঃ 
এই গেবষণায় অংশςহণ করা িকংবা না করার িবষেয় আপনার িসдাоই চূড়াо। অংশςহণ 
করার পর έয έকান সমেয় আপিন িনেজেক এই গেবষণা έথেক সিরেয় িনেত পােরন। 
 

xv 
 
 
έগাপনীয়তাঃ 
গেবষণা চলাকালীন ও পরবতλেত সকল তথҝ কেঠার ভােব έগাপন রাখা হেব। আপনার আই িড 
নїর সїিলত সব ধরেনর কাগজপেϏ আপনার নাম ও Μঠকানা বিসেয় έগাপনীয়তার সােথ রাখা 
হেব এবং আপনার বҝΝЅগত িবষয়ািদ তথҝ িবেѫষণ, ϕিতেবদন ίতিরেত বা έকান ϕকাশনার 
কােজ বҝব჊ত হেব না এবং গেবষণার পরীϠক বҝতীত কােরা কােছ ϕকাশ করা হেব না। 
 
খরচঃ 
এই গেবষণায় অংশςহেণর জনҝ আপনার গতানুগিতক িচিকৎসার বাইের έকান অিতিরЅ খরচ 
করেত হেব না বা আপনােক έকান অথκ ϕদান করা হেব না। 
 
গেবষণাকারীর দািয়Яঃ 
এই গেবষণায় অংশςহেণর ফেল আপিন অসুѸ হেল গেবষণাকারী আপনার উপযুЅ 
িচিকৎসার বҝবѸা করেব। 
 
έѾИামূলক অংশςহণঃ 
এই গেবষণায় আপনার অংশςহণ έѾИামূলক। আপিন গেবষণায় অংশςহেণ অѾীকৃিত 
জানােত পােরন অথবা গেবষণা চলাকালীন έয έকান সমেয় গেবষণা έথেক িনেজেক ϕতҝাহার 
কের িনেত পােরন। এর ফেল এই হাসপাতােল আপনার িচিকৎসায় έকান ϕভাব পরেব না। এই 
ফেমκ ѾাϠর করেল আপনার έকান আইনগত অিধকার খবκ হেব না। 
 
ϕѨাবলীঃ 
যিদ আপনার έকান ϕѨ থােক তেব দয়া কের Νজϡাসা ক჈ন। আমরা তার উЫর ϕদান করার 
যথাসাধҝ έচѭা করব। যিদ ভিবষҝেত আপনার অিতিরЅ έকান ϕѨ থােক, তেব গেবষণারত 
ডাЅােরর সােথ έযাগােযাগ করেত পারেবন। 
 
সљিতর ѾীকােরাΝЅঃ 
আিম গেবষণায় িনেয়াΝজত িচিকৎসেকর সােথ এই গেবষণা িনেয় আেলাচনায় সᅀΜѭ ϕকাশ 
করিছ। আিম এটা বুেঝিছ έয গেবষণায় অংশςহণ έѾИামূলক এবং আিম έয έকান সময় έকান 
বাধҝবাধকতা ছাড়াই গেবষণা έথেক িনেজেক িবরত রাখেত পাির। আিম উেপােরাЅ শতκვেলা 
পেড়িছ / আমার সљুেখ পΜঠত হেয়েছ এবং έѾИায় গেবষণায় অংশςহণ করেত সљিত ϡাপন 
করিছ। 
 
……………………………… 
ডা: িনশাত তাসনীম 
ϕধান গেবষক 
έমাবাইল নং- 
.......................................... 
ѾাϠর / বৃдাДুলীর ছাপ 
 
ѾাϠীর নাম : 
.......................................... 
ѾাϠর / বৃдাДুলীর ছাপ 
 
ѾাϠীর নাম : 
.......................................... 
ѾাϠর / বৃдাДুলীর ছাপ 
 
অংশςহণকারী নাম : 
 
έমাবাইল নং : 
 
έকাড নং : 
 

xvi 
 
 
APPENDIX - II 
Informed Written Consent 
The purpose of this consent form is to provide you with the necessary information, 
which will help you decide to participate in the following research. 
 
Name of the Study: Free Breathing versus Deep Inspiration Breath Hold 
Technique in Adjuvant Radiotherapy for Left Sided Breast Cancer: A Dosimetric 
Comparison of Target Volumes, Heart and Left Lung. 
 
Name of the Investigator: Dr. Nishat Tasnim 
 
Purpose of the Study: 
Breast cancer is a leading cancer among Bangladeshi female. For breast cancer, there 
are different available treatment options according to the stage of disease. One of the 
important ones is radiotherapy (RT). Various side effects can occur during and after 
RT. Among the late side effects, numerous cardiac and pulmonary problems are 
significant specially in case of left sided breast cancer. In such cases, patients are being 
cured from cancer but the treatment itself endangering patients’ general health and well-
being by increasing risk of future life threatening cardiac and pulmonary diseases. 
Studies from around the world have shown that, during RT of left sided breast cancer, 
holding the breath for certain time after deep inspiration can reduce the radiation doses 
to heart and left lung without compromising doses to the chest wall. As a result, they 
can avoid the extra risk of treatment related late toxicities. This study will look at the 
utility and efficacy of DIBH RT over free breathing RT in reducing the heart and left 
lung doses without compromising the dose to the target volumes in left sided post 
mastectomy breast cancer patient, which is the main objective of this study. 
 
Participating in the Study: 
Your participation in the proposed study is voluntary. Your decision to participate as 
well as to withdraw from the study at any time without any reason after participating in 
the study is final. Signing this form does not waive any of your legal rights. 
 
Obligation to Participate: 
Non-participation or subsequent withdrawal from the proposed research program will 
not affect your treatment at this hospital. 

xvii 
 
 
Risk and Benefit: 
By participating in the study, you may not be benefitted personally but it will help to 
know more precisely about better delivery of radiotherapy to other patients. Like other 
treatments, it has some side effects. Necessary measures will be taken to avoid or 
minimize complications. Even if there is any, it will be treated by trained physician. 
 
Protection of the Confidentiality of Information: 
All information will be kept strictly confidential during and after the research. Your 
name and address will be omitted on all documents rather an ID number will be used. 
All necessary information will be verified, analysed and if necessary, can be used for 
report preparation and publication, but your personal information, name, identity, 
address will not be mentioned anywhere. 
 
Cost and Responsibilities of the Investigator: 
Participation in this research program will not cost you anything or provide you with 
any financial or other benefits. But if you become ill while participating in this research 
program, the researcher will provide you with appropriate treatment. 
 
Questions and Answers: 
If you have any questions, please ask. We will try our best to answer it. If you have 
additional questions in the future, you can contact the researcher. 
 
Declaration of Consent: 
I have discussed this study in detail with the doctor and express my satisfaction. I 
understand that participation in the study is voluntary and that I may withdraw from the 
study at any time without obligation. I have read the above conditions / have been read 
in front of me and agree to participate in the study voluntarily. 
 
…………………… 
Dr. Nishat Tasnim 
Chief Investigator 
Mobile no: 
.......................................... 
Sign / Finger print 
 
Witness: 
.......................................... 
Sign / Finger print 
 
Witness: 
.......................................... 
Sign / Finger print 
 
Name of Participant 
Mobile no: 
 
 

xviii 
 
 
APPENDIX - III 
Face-sheet 
 
ID no -            
 
Reg. No 
 
 
 
: 
Participant’s name  
 
: 
Father’s/Husband’s name  
: 
Mother’s name 
 
 
: 
Mobile No. 
 
 
: 
Address 
 
 
 
: 
 
 
 
 

xix 
 
 
APPENDIX – IV 
Data Collection Sheet 
Title of the Study: 
Free Breathing versus Deep Inspiration Breath Hold Technique in Adjuvant 
Radiotherapy for Left Sided Breast Cancer: A Dosimetric Comparison of Target 
Volumes, Heart and Left Lung 
Principal investigator: Dr. Nishat Tasnim 
Section A: Participants Personal Information 
 
 
ID No:       
S.N. 
Questions 
Options 
Code 
Skip 
01. 
What is your age? 
years 
 
 
02. 
What is your religion? 
Islam -1 
Hinduism-2 
Christianism-3 
Buddhism-4 
Others-0 
 
 
03. 
What is your educational 
status? 
Illiterate-1 
Below primary-2 
Above primary up to 
SSC-3 
HSC-4 
Graduate-5 
Post graduate-6 
Others-0 
 
 
04. 
What is your Occupation? 
Student-1 
Housewife-2 
Service holder-3 
Business-4 
Others-0 
 
 
 
05. 
Age at menarche 
 
Years 
 
 

xx 
 
 
06. 
What is your marital 
status? 
Unmarried-1 
Married-2 
Widowed-3 
Separated-4 
 
 
For code 
1 skip 
question 
No.6 
07. 
Age at marriage? 
 
years 
 
 
 
08. 
Age at 1st pregnancy? 
                     
years 
 
 
 
09. 
Did you breastfeed your 
children? 
Yes-1 
No-2 
 
 
10. 
Are you menopausal? 
Yes-1 
No-2 
 
For code 
2 skip 
question 
No.09 
11. 
Age at menopause? 
years 
 
 
12. 
Do you have any history 
of using OCP? 
Yes-1 
No-2 
 
For code 
2 skip 
question 
No.11 
13. 
Duration of using OCP 
 
years 
 
 
14. 
Do you have any history 
of using HRT? 
Yes-1 
No-2 
 
For code 
2 skip 
question 
No.13 
15. 
Duration of using HRT 
 
years 
 
 
16. 
Do you have any family 
history of cancer? 
(mention if any) 
 
 
 
17. 
Comorbidity (if any) 
 
 
 
 
 
 

xxi 
 
 
έসকশন-এ : অংশςহনকারীর বҝাΝЅগত তথҝসমূহ  
আইিড :       
 
নং 
ϕѨ 
উЫর 
έকাড 
বাদ 
১. 
আপনার বয়স কত? 
 
বৎসর 
 
 
২. 
আপিন έকান ধেমκর অনুসারী? 
ইসলাম-১ 
িহрু-২ 
িρѭান-৩ 
έবৗд-৪ 
অনҝানҝ-0 
 
 
৩. 
আপনার িশϠাগত έযাগҝতা িক? 
অিশিϠত-১ 
ϕাথিমক পযκо-২ 
ϕাথিমক έথেক এসএসিস 
পযκо -৩ 
এইচএস িস -৪ 
ςҝাজুেয়ট -৫ 
έপাѶ ςҝাজুেয়ট-৬ 
অনҝানҝ -0 
 
 
 
 
 
 
৪. 
আপনার έপশা িক? 
ছাϏ/ছাϏী-১ 
গৃিহনী-২ 
চাকুিরজীিব-৩ 
বҝবসায়ী-৪ 
অনҝানҝ -0 
 
 
 
 
 
৫. 
কত বছর বয়স έথেক আপনার 
রজ:Νοয়া ზ჈ হেয়িছল? 
                
বৎসর 
 
 
৬. 
আপনার ίববািহক অবѸা িক? 
অিববািহত-১ 
িববািহত-২ 
িবধবা -৩ 
িববাহিবেИদ-৪ 
 
 
έকাড ১ 
এর 
জনҝ  ৭ 
নং ϕѨ 
বাদ 
৭. 
িববাহ কােল আপনার বয়স কত 
িছল? 
            
বৎসর 
 
 
 

xxii 
 
 
৮. 
ϕথম সоান জেфর সময় 
আপনার বয়স কত িছল? 
 
বৎসর 
 
 
 
৯. 
আপিন িক আপনার বাЗােক 
বুেকর দুধ খাইেয়িছেলন? 
হҝা ১ 
না ২ 
 
 
১০. 
আপনার িক মািসক এেকবাের 
বс হেয় έগেছ? 
হҝা ১ 
না ২ 
 
έকাড ২ 
এর জনҝ  
১১ নং ϕѨ
বাদ 
১১. 
কত বছর έথেক মািসক বс 
আেছ? 
                 
বৎসর 
 
 
 
১২. 
আপিন িক জф িবরিতকরণ িপল 
έখেয়েছন কখেনা? 
হҝা ১ 
না ২ 
 
έকাড ২ 
এর জনҝ  
১৩ নং 
ϕѨ বাদ
১৩. 
আপিন কতিদন জф িবরিতকরণ 
িপল έখেয়েছন 
                 
বৎসর 
 
 
১৪. 
মািসক বс হওয়ার পের έকােনা 
হরেমােনর টҝাবেলট έখেয়েছন? 
হҝা ১ 
না ২ 
 
έকাড ২ 
এর জনҝ  
১৫ নং 
ϕѨ বাদ
১৫. 
আপিন কতিদন হরেমােনর 
টҝাবেলট έখেয়েছন 
                 
বৎসর 
 
 
১৬. 
জানামেত পিরবােরর কােরা 
έকান কҝাхার έরাগ িছল িক না? 
(থাকেল িববরণ) 
 
 
 
১৭. 
 আপনার ডায়ােবΜটস, 
উЗরЅচাপ, িকডনী বা অনҝানҝ 
দীঘκেময়াদী সমসҝা আেছ িকনা? 
থাকেল έকানΜট? 
 
 
 

xxiii 
 
 
Section B: Clinical Examination Findings 
 
ID No: 
i. General and Local Examination: 
Serial No 
General examination 
Option 
Code 
01. 
Performance status 
 
 
02. 
Body-weight (in kg) 
 
 
03. 
Height (in cm) 
 
 
04. 
Body mass index 
(in kg/m2) 
kg/m2
 
05. 
Anemia 
Yes-1 
No-2 
 
06. 
Jaundice 
Yes-1 
No-2 
 
07. 
Edema 
Yes-1 
 No-2 
 
08. 
Dehydration 
Yes-1 
No-2 
 
09. 
Palpable lymph node (if 
yes, mention site) 
Yes-1 
No-2 
 
10. 
Body temperature 
 
 
11. 
Breast examination 
 
 
12. 
Others 
 
 
ii. Systemic Examination: 
01. Respiratory system examination 
 
 
 
02. Cardiovascular system examination 
 
 
 

xxiv 
 
 
Section C: Findings of Investigations                                      ID No. 
i. 
Imaging Test 
 Chest xray PA view 
 ECG 
 Echocardiography 
 Lung function test 
ii. 
Histopathological Examination: 
 Tumor size 
 Nodal involvement 
 Histopathological variety 
 Grade 
iii. 
Immunohistochemistry: 
 Estrogen receptor, ER 
 Progesterone receptor, PR 
 HER-2 receptor 
Section D: Previous Treatment 
 
 
 
 
ID No: 
o Chemotherapy:  
□ Neoadjuvant 
□ Adjuvant 
o Regimen of chemotherapy with doses: 
 
 
 
o Number of cycles: 
o Date of completion: 
o Date of surgery: 
o Duration from surgery or chemotherapy: (whichever is shorter) 
Section E: Treatment Delivery 
 
 
 
 
ID No: 
Technique of Irradiation 
Arm 
Code 
IMRT with FB technique 
Arm A =1 
 
IMRT With DIBH technique 
Arm B = 2 

xxv 
 
 
Section F: Radiation Doses 
 
 
 
 
 
ID No: 
o Planning target volume 
 Total volume 
 Maximum dose, Dmax 
 Mean dose, Dmean 
 V95 of PTV 
o Heart 
 Mean heart dose, Dmean 
 Maximum heart dose, Dmax 
 V25 of heart 
 
o Left lung 
 Mean dose to left lung, Dmean 
 V20 of left lung 
 
 
 
 
 
 
 
 
 
 
 
 
 
 

xxvi 
 
 
APPENDIX-V 
EASTERN COOPERATIVE ONCOLOGY GROUP (ECOG) PERFORMANCE 
SCALE 
0  
 
: Normal activity; asymptomatic 
1  
 
: Symptomatic; fully ambulatory 
2  
 
: Symptomatic; in bed < 50% of time 
3  
 
: Symptomatic; in bed > 50% of time; bedridden 
4  
 
: 100% bedridden 
5  
 
: Dead

xxvii 
 
 
APPENDIX- VI 
UICC/AJCC TNM Staging for Breast Cancer- 8th edition, 2017 
Primary Tumor (T) 
TX 
Primary tumor cannot be assessed 
T0 
No evidence of primary tumor 
Tis (DCIS) 
Ductal carcinoma in situ 
Tis (Paget) 
Paget disease of the nipple NOT associated with invasive carcinoma 
and/or carcinoma in situ (DCIS) in the underlying breast parenchyma 
T1 
Tumor ≤20 mm in greatest dimension 
T1mi Tumor ≤1 mm in greatest dimension 
T1a 
Tumor >1 mm but ≤5 mm in greatest dimension (round any 
measurement >1.0–1.9 mm to 2 mm) 
T1b 
Tumor >5 mm but ≤10 mm in greatest dimension 
T1c 
Tumor >10 mm but ≤20 mm in greatest dimension 
T2 
Tumor >20 mm but ≤50 mm in greatest dimension 
T3 
Tumor >50 mm in greatest dimension 
T4 
Tumor of any size with direct extension to the chest wall and/or to the skin 
(ulceration or macroscopic nodules) * 
T4a 
Extension to the chest wall ** 
T4b 
Ulceration and/or ipsilateral macroscopic satellite nodules and/or edema 
(including peau d’orange) of the skin that does not meet the 
criteria for inflammatory carcinoma 
T4c 
Both T4a and T4b are present 
T4d 
Inflammatory carcinoma 
 
* Invasion of the dermis alone does not qualify as T4. 
** Invasion or adherence to pectoralis muscle in the absence of invasion of chest wall 
structures does not qualify as T4. 
 
 
 
 

xxviii 
 
 
Regional Lymph Nodes- Clinical (cN) 
cNX* Regional lymph nodes cannot be assessed (e.g., previously removed) 
cN0 
No regional lymph node metastases (by imaging or clinical examination) 
cN1 
Metastases to movable ipsilateral Level I, II axillary lymph node(s) 
cN1mi** 
Micro metastases (approximately 200 cells, larger than 0.2 mm, 
but none larger than 2.0 mm) 
cN2 
Metastases in ipsilateral Level I, II axillary lymph nodes that are clinically fixed 
or matted; or in ipsilateral internal mammary nodes in the absence of axillary 
lymph node metastases 
cN2a Metastases in ipsilateral Level I, II axillary lymph nodes fixed to one 
another (matted) or to other structures 
cN2b Metastases only in ipsilateral internal mammary nodes in the absence of 
axillary lymph node metastases 
cN3 
Metastases in ipsilateral infraclavicular (Level III axillary) lymph node(s) with 
or without Level I, II axillary lymph node involvement; or in ipsilateral internal 
mammary lymph node(s) with Level I, II axillary lymph node metastases; or 
metastases in ipsilateral supraclavicular lymph node(s) with or without axillary 
or internal mammary lymph node involvement 
cN3a Metastases in ipsilateral infraclavicular lymph node(s) 
cN3b Metastases in ipsilateral internal mammary lymph node(s) and axillary 
lymph node(s) 
cN3c Metastases in ipsilateral supraclavicular lymph node(s) 
* The cNX category is used sparingly in cases where regional lymph nodes have 
previously been surgically removed or where there is no documentation of physical 
examination of the axilla. 
** cN1mi is rarely used but may be appropriate in cases where sentinel node biopsy is 
performed before tumor resection, most likely to occur in cases treated with 
neoadjuvant therapy. 
Regional Lymph Nodes- Pathological (pN)  
pNX 
Regional lymph nodes cannot be assessed (e.g., not removed for pathological 
study or previously removed) 
pN0 
No regional lymph node metastasis identified or ITCs only 

xxix 
 
 
pN0(i+) 
ITCs only (malignant cell clusters no larger than 0.2 mm) in 
regional lymph node(s) 
pN0(mol+) 
Positive molecular findings by reverse transcriptase polymerase 
chain reaction (RT-PCR); no ITCs detected 
pN1 
Micro metastases; or metastases in 1–3 axillary lymph nodes; and/or clinically 
negative internal mammary nodes with micro metastases or macro metastases 
by sentinel lymph node biopsy 
pN1mi  
Micro metastases (approximately 200 cells, larger than 0.2 mm 
but none larger than 2.0 mm) 
pN1a   
Metastases in 1–3 axillary lymph nodes, at least one metastasis                       
larger than 2.0 mm 
pN1b  
Metastases in ipsilateral internal mammary sentinel nodes, 
excluding ITCs 
pN1c  
pN1a and pN1b combined 
pN2 
Metastases in 4-9 axillary lymph nodes; or positive ipsilateral internal 
mammary lymph nodes by imaging in the absence of axillary lymph node 
metastases 
pN2a  
Metastases in 4-9 axillary lymph nodes (at least one tumor 
deposit larger than 2.0 mm) 
pN2b  
Metastases in clinically detected internal mammary lymph nodes 
with or without microscopic confirmation; with pathologically negative 
axillary nodes 
pN3 
Metastases in –  
pN3a  
Metastases in 10 or more axillary lymph nodes (at least one 
tumor deposit larger than 2.0 mm); or metastases to the infraclavicular 
(Level III axillary lymph) nodes 
pN3b  
pN1a or pN2a (positive Level I, II axillary lymph nodes) in the 
presence of cN2b (positive internal mammary nodes by imaging); or 
pN2a in the presence of pN1b (more than three axillary lymph nodes 
and micro/macro-metastases by sentinel lymph node biopsy in clinically 
negative ipsilateral internal mammary lymph nodes) 
pN3c  
Metastases in ipsilateral supraclavicular lymph nodes 
 
 

xxx 
 
 
Distant Metastasis (M) 
M0 
No clinical or radiographic evidence of distant metastases* 
cM0(i+) 
No clinical or radiographic evidence of distant metastases in the 
presence of tumor cells or deposits no larger than 0.2 mm detected 
microscopically or by molecular techniques in circulating blood, bone 
marrow, or other nonregional nodal tissue in a patient without symptoms 
or signs of metastases 
cM1 Distant metastases detected by clinical and radiographic means 
pM1 Any histologically proven metastases in distant organs; or if in non-regional 
nodes, metastases greater than 0.2 mm 
* Note that imaging studies are not required to assign the cM0 category 
Stage/Prognostic Grouping 
Stage 0 
Tis N0 M0 
Stage IA 
T1 N0 M0 
Stage IB 
T0-1 N1mi M0 
Stage IIA 
T0-1 N1 M0; T2 N0 M0 
Stage IIB 
T2 N1 M0; T3 N0 M0 
Stage IIIA 
T0-3 N2 M0 
Stage IIIB 
T4 N0-2 M0 
Stage IIIC 
Any T N3 M0 
Stage IV 
Any T Any N M1 
 
 
 
 
 
 

xxxi 
 
 
APPENDIX- VII 
Percentage points or critical values of standard normal distribution (Z-
distribution or Z table or Zα table) 
P-Value or level of 
significance(α) 
Confidence level 
Percentage point 
One tail 
Two tail 
0.5(50%) 
 
0.00 
0.67 
0.4(40%) 
 
0.25 
0.84 
0.3(30%) 
 
0.52 
1.04 
0.2(20%) 
80% C. Level 
0.84 
1.28 
0.1(10%) 
90% C. Level 
1.28 
1.64 
0.05(5%) 
95% C. Level 
1.64 
1.96 
0.02(2%) 
98% C Level 
2.05 
2.33 
0.01(1%) 
99% C Level 
2.33 
2.58 
0.005(0.5%) 
99.5% C Level 
2.58 
2.81 
0.002(0.2%) 
99.7% C Level 
2.88 
3.09 
0.001(0.1%) 
99.9% C Level 
3.09 
3.29 
0.0001(0.01%) 
99.99% C Level 
3.72 
3.89 
 
 
 
 
 
 
 
 
 
 
 
 
 
 

xxxii 
 
 
APPENDIX- VIII 
Critical Values (Zβ) of Standard Normal Distribution (Z-Distribution) at Different 
Power 
Power 
Β (Type-II error) 
Zβ 
0.70 
0.30 
0.52 
0.80 
0.20 
0.84(0.85) 
0.90 
0.10 
1.28 
0.95 
0.05 
1.64 
0.99 
0.01 
2.33 

xxxiii 
 
 
APPENDIX – XI 
 
HELSINKI DECLARATION: 
Clinical trial involving human subjects-to indicate whether the procedures followed 
were in accordance with the ethical standard of responsible committee or with the 
Helsinki declaration of 1975, as revised in 2013. 
1. Direct student should not be included in the clinical trial / research. 
2. Children should not be included (unless benefit will be obtained by the children). 
3. Prisoners, pregnant women and acutely ill patients should not be included. 
4. Patients should not be deprived of their basic human right. 
5. Patient's name, initials or hospital numbers should not be used. 
6. Informed written consent of the patient should be taken after explaining the 
objective, risk and benefit of the experiment. 
7. No incentive cash or kind for healthy volunteer should be allowed.