VisionRT-based Deep Inspiration Breath-hold (DIBH) Respiratory Motion Management Strategy, A Pilot Study for Thoracic and Abdominal Tumors Stereotactic Body Radiotherapy
Phase: NA
Conditions: Thoracic Cancer, Abdominal Cancer
Sponsor: University of Texas Southwestern Medical Center

 
STU022017-075, Parsons, FormA-ResearchProtocol, Mod_17, 06-15-21 (2) 
 
 
 
 
CONFIDENTIAL 
This material is the property of the UTSW Simmons Comprehensive Cancer Center.  
Do not disclose or use except as authorized in writing by the study sponsor. 
 
Template Updated: 12/2012; 9/2013; 8/2014; 4/2015; 10/2015; 11/2016; 12/2018; 07/2020 
 
STU 022017-075 
VisionRT-based Deep Inspiration Breath-hold (DIBH) Respiratory Motion 
Management Strategy, A Pilot Study for Thoracic and Abdominal Tumors 
Stereotactic Body Radiotherapy 
 
Principal Investigator: 
 
David Parsons, Ph.D. 
UT Southwestern Medical Center 
2280 Inwood Rd, Dallas, TX, 75390 
Phone: (214)648-9941 
Fax: (214)-648-8051 
David.Parsons@UTSouthwestern.edu 
                                               
                                                Robert Timmerman, M.D. 
UT Southwestern Medical Center 
2280 Inwood Rd, Dallas, TX, 75390 
Phone: (214)645-7637  
Fax: (214)-645-8526 
Robert.Timmerman@utsouthwestern.edu 
 
 
     
Biostatistician:  
 
Department of Clinical Sciences 
 
 
 
 
Chul Ahn, Ph.D. 
UT Southwestern Medical Center 
2280 Inwood Rd, Dallas, TX, 75390 
(214)648-9418 
Chul.Ahn@UTSouthwestern.edu 
 
 
 
 
 
 
Funding Source:  
Supported by Vision RT Limited (London, United Kingdom) 
 
 
 
Initial version: 
 
Version 
Date 
Initial 
3/20/2017 
Version 2 
07/16/2019 
Version 3 
10/26/2020 
Version 4 
04/19/2021 
 
 
 
 
UT Southwestern Medical Center (UTSW) 
Harold C. Simmons Comprehensive Cancer Center 
Attn: Clinical Research Office 
5323 Harry Hines Blvd. MC 9179 

 
STU022017-075, Parsons, FormA-ResearchProtocol, Mod_17, 06-15-21 (2) 
 
 
 
 
CONFIDENTIAL 
This material is the property of the UTSW Simmons Comprehensive Cancer Center.  
Do not disclose or use except as authorized in writing by the study sponsor. 
 
Template Updated: 12/2012; 9/2013; 8/2014; 4/2015; 10/2015; 11/2016; 12/2018; 07/2020 
 
Dallas, Texas 75390-9179 
 

 
STU022017-075, Parsons, FormA-ResearchProtocol, Mod_17, 06-15-21 (2) 
 
 
 
 
CONFIDENTIAL 
This material is the property of the UTSW Simmons Comprehensive Cancer Center.  
Do not disclose or use except as authorized in writing by the study sponsor. 
 
Template Updated: 12/2012; 9/2013; 8/2014; 4/2015; 10/2015; 11/2016; 12/2018; 07/2020 
 
 
Signature Page 
 
 
The signature below constitutes the approval of this protocol and the attachments, and provides the necessary 
assurances that this trial will be conducted according to all stipulations of the protocol, including all statements 
regarding confidentiality, and according to local legal and regulatory requirements and applicable U.S. federal 
regulations and ICH guidelines. 
 
Version #4 
STU 022017-075 
VisionRT-based Deep Inspiration Breath-hold (DIBH) Respiratory Motion Management 
Strategy, A Pilot Study for Thoracic and Abdominal Tumors Stereotactic Body 
Radiotherapy 
 
 
Principal Investigator (PI) Name:_____________________________ 
 
 
 
PI Signature: _____________________________ 
 
 
 
Date:____________________ 
 

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i 
TABLE OF CONTENTS 
LIST OF ABBREVIATIONS (EXAMPLES) .................................................................1 
STUDY SCHEMA .............................................................................................................2 
..............................................................................................................................................2 
..............................................................................................................................................3 
..............................................................................................................................................3 
..............................................................................................................................................3 
STUDY SUMMARY ..........................................................................................................4 
1.0 
BACKGROUND AND RATIONALE ..................................................................5 
1.1 
Background ...................................................................................................................... 5 
1.2 
DIBH and Active Breathing Coordinator (ABC) ............................................................... 5 
1.3 
VRT and VRT-DIBH......................................................................................................... 6 
2.0 
STUDY OBJECTIVES ...........................................................................................6 
2.1 
Primary Objectives ........................................................................................................... 7 
2.2 
Secondary Objectives ...................................................................................................... 7 
2.3 
Exploratory Objectives ..................................................................................................... 7 
2.4 
Endpoints ......................................................................................................................... 7 
3.0 
PATIENT ELIGIBILITY ......................................................................................7 
3.1 
Inclusion Criteria .............................................................................................................. 7 
3.2 
Exclusion Criteria ............................................................................................................. 8 
4.0 
TREATMENT PLAN .............................................................................................8 
4.1 
Treatment Dosage and Administration ............................................................................ 8 
4.2 
Concomitant Medications/Treatments ............................................................................. 9 

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4.3 
Duration of Therapy ......................................................................................................... 9 
4.4 
Duration of Follow Up ...................................................................................................... 9 
4.5 
Removal of Subjects from Protocol Therapy ................................................................. 10 
4.6 
Subject Replacement..................................................................................................... 10 
5.0 
STUDY PROCEDURES ......................................................................................10 
5.1 
Screening/Baseline Procedures .................................................................................... 10 
5.2 
Procedures during Treatment ........................................................................................ 11 
5.3 
Follow-up procedures .................................................................................................... 12 
5.4 
Time and Events Table .................................................................................................. 13 
5.5 
Removal of Subjects from Study ................................................................................... 13 
6.0 
STATISTICAL CONSIDERATIONS ................................................................13 
6.1 
Study Design/Study Endpoints ...................................................................................... 14 
6.2 
Sample Size and Accrual .............................................................................................. 14 
6.3 
Data Analyses Plans...................................................................................................... 14 
7.0 
ADVERSE EVENTS ............................................................................................14 
7.1 
Adverse Event Monitoring ............................................................................................. 14 
7.2 
Steps to Determine If a Serious Adverse Event Requires Expedited Reporting to the SCCC 
DSMC 16 
7.3 
Unblinding Procedures .................................................................................................. 18 
7.4 
Stopping Rules .............................................................................................................. 19 
8.0 
STUDY MANAGEMENT ....................................................................................19 
8.1 
Conflict of Interest .......................................................................................................... 19 
8.2 
Institutional Review Board (IRB) Approval and Consent ............................................... 19 
8.3 
Registration Procedures ................................................................................................ 19 
8.4 
Data Management and Monitoring/Auditing .................................................................. 20 
8.5 
Adherence to the Protocol ............................................................................................. 20 
8.6 
Amendments to the Protocol ......................................................................................... 21 

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8.7 
Record Retention ........................................................................................................... 22 
8.8 
Obligations of Investigators ........................................................................................... 22 
9.0 
REFERENCES ......................................................................................................22 

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1 
LIST OF ABBREVIATIONS (EXAMPLES) 
AE 
Adverse Event 
ABC                Active Breathing Coordinator 
ALC 
ASCO 
Absolute Lymphocyte Count 
American Society of Clinical Oncology 
BH 
Breath Hold 
CR 
Complete Response 
CT 
Computed Tomography 
CTCAE 
Common Terminology Criteria for Adverse Events 
DLT 
Dose Limiting Toxicity 
DOT 
Disease Oriented Team 
DSMB 
Data and Safety Monitoring Board 
FDA 
Food and Drug Administration 
GCP 
Good Clinical Practice 
H&P 
History & Physical Exam 
HRPP 
Human Research Protections Program 
IHC 
Immunohistochemistry 
IND 
Investigational New Drug 
IV (or iv) 
Intravenously 
MRI 
Magnetic Resonance Imaging 
MTD 
Maximum Tolerated Dose 
MV 
Mega Voltage 
NCI 
National Cancer Institute 
ORR 
Overall Response Rate 
OS 
Overall Survival 
pCR 
Pathologic Complete Response 
PD 
Progressive Disease 
PET 
Positron Emission Tomography 
PFS 
Progression Free Survival 
p.o. 
peros/by mouth/orally 
PR 
Partial Response 
RCB 
Residual Cancer Burden 
RECIST 
Response Evaluation Criteria in Solid Tumors 
SAE 
Serious Adverse Event 
SCCC 
Simmons Comprehensive Cancer Center 
SD 
Stable Disease 
SOC 
Standard of Care 
VRT 
Vision RT 
VRT-DIBH 
VRT-assisted DIBH 
 
 

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STUDY SCHEMA 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Thoracic and abdominal cancer patients eligible for SBRT treatment 
Pre-oxygenation VRT-DIBH patient training and find a patient-specific optimal 
deep inspiration breath hold (DIBH) level assisted with a Spirometer 
Free breathing tumor motion > 5mm 
(SOC evaluated with imaging) 
Yes 
No
A single DIBH duration >= 30 
seconds 
Yes
No 
VRT Real-time coaching coupled with DIBH (VRT-DIBH) training 
Inter- & Intra-VRT-DIBH surface 
variation <= 5mm 
No
 Intra-VRT-DIBH tumor motion 
<=5mm(evaluated with imaging) 
Yes 
Yes 
No
Consent 
Yes 
Not eligible for the study, 
Not eligible for the study. 
Use other SOC for 
motion control 
Inter- VRT-DIBH patient tumor position & surface stability/repeatability study with CT images: 
• SOC high-resolution CT images acquisition within DIBH 
• Repeat a low-resolution/low-dose CT image acquisition in another DIBH within 10mins 
interval 
• Acquire two low-resolution CT at ±10% DIBH levels 
 Inter-VRT-DIBH tumor motion 
<=5mm(evaluated with imaging) 
No
Yes 
Off study. Data 
collection only, use other 
SOC for  motion control 
Off study. Data 
collection only, use other 
SOC for  motion control 
Off study/ Data 
collection only, use other 
SOC for  motion control 

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Treatment planning with the acquired SOC CTs 
VRT-SBRT treatment setup 
• 
Spirometer – setup with tidal volume 
• 
VRT – surface alignment 
• 
CBCT – target alignment 
VRT-SBRT treatment delivery monitoring/recording per SOC (unless otherwise noted) 
• 
Spirometer  –  Tidal volume stability/reproducibility 
• 
VRT  – Surface stability/reproducibility -Research 
• 
kV fluoro  – in any two VRT-DIBH durations to evaluate tumor position accuracy   
• 
Intra-fraction CBCT  – one CBCT before the first beam delivery and one CBCT before 
the last beam delivery (not during arc delivery) 
Data analysis 
• 
Treatment time 
• 
Inter/intra VRT-DIBH patient surface stability/reproducibility 
• 
Inter/intra VRT-DIBH  tumor position accuracy/stability/reproducibility  
• 
Inter VRT-DIBH surface/tumor position correlation 
• 
VRT-DIBH  SBRT planned/delivered dose variation 

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STUDY SUMMARY 
Title 
VisionRT-based Deep Inspiration Breath-hold (DIBH) Respiratory 
Motion Management Strategy, A Pilot Study for Thoracic and 
Abdominal Tumors Stereotactic Body Radiotherapy 
Short Title 
VRT-DIBH for Thoracic and Abdominal Cancer SBRT 
Protocol Number 
STU 022017-075 
Phase 
Pilot 
Methodology 
Prospective study with retrospective data analysis 
Study Duration 
2 year 
Study Center(s) 
Single-center  
Objectives 
To prove the feasibility of using VRT-DIBH for thoracic and 
abdominal tumors SBRT 
Number of Subjects 
10 
Diagnosis and Main 
Inclusion Criteria 
• Patients with tumors in thorax and abdomen  
• Patients are eligible for SBRT  
Study Product(s), Dose, 
Route, Regimen 
No therapeutic intervention – per SOC 
Duration of 
administration 
Per SOC 
Statistical Methodology 
Descriptive statistics will be computed to investigate the feasibility 
of the trial. 
 
 
 
 
 
 
 

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1.0 
BACKGROUND AND RATIONALE 
1.1 
Background 
Respiratory motion affects all tumor sites in the thorax and abdomen. The disease of most 
prevalence and relevance for motion-management needed radiotherapy are lung and liver 
cancer.  Lung cancer is the leading cause of cancer-related mortality in the United States. 
During 2016, an estimated 224,390 new cases of lung cancer are diagnosed, representing 
13% of all cancer patients1, and an estimated 158,080 deaths of lung cancer were expected1. 
The five-year survival rate for all stages combined is 17.7%, lower than many other leading 
cancer sites, such as the colon (64.4%), breast (89.7%) and prostate (98.9%)2. Liver cancer 
is the 10th most common cancer. In 2016, an estimated 39,230 adults (28,410 men and 
10,820 women) in the United States will be diagnosed with primary liver cancer1. The 5-
year survival rate of liver cancer is 17%2. 
 
Stereotactic body radiotherapy (SBRT) is a therapeutic paradigm developed in the mid 
1990’s. It administers very high, biological potent doses in few fractions (1 - 5 fractions) 
using unique beam arrangements and special immobilization equipment. It has 
demonstrated excellent local control in patients with inoperable non-small cell lung cancer 
(NSCLC)3 and liver cancer4 . 
 
Respiratory motion causes significant geometric and dosimetric uncertainties in lung and 
upper abdomen cancer radiotherapy treatment simulation, planning, and delivery5. These 
uncertainties are particularly large in SBRT, potentially leading to significant collateral 
toxicity6-8 when using large beam apertures or, conversely, potential marginal miss with 
very small apertures. Researchers and clinicians have been investigating respiratory 
motion-management techniques for over a decade.9, 10 A variety of motion management 
strategies have been explored and implemented for clinical use, including motion-
encompassing methods [e.g. 4D CT and ITV (internal target volume) approach], abdominal 
compression techniques to decrease motion amplitude, breath-holding methods, 
respiratory-gating techniques, and real-time tumor-tracking methods. All of these 
techniques aim to mitigate dosimetric uncertainties induced by respiratory motion by either 
restricting or compensating for motion.  
1.2 
DIBH and Active Breathing Coordinator (ABC) 
Among various respiratory motion management techniques, deep-inspiration breath-hold 
(DIBH) technique has been developed and applied in lung and liver SBRT.11, 12 DIBH has 
shown advantages for treating thoracic and abdominal tumors because it can significantly 
reduce respiratory tumor motion and changes internal anatomy in way that often protects 
critical normal tissues.  
  
There are several ways to assist DIBH during radiation treatments. One common way is by 
using a commercially available system Active Breathing Coordinator (ABC; Elekta, 
Crawley, UK) device. The ABC system has a digital spirometer that records real time 
breathing. When the patient inspires to a preset DIBH level, a balloon valve is inflated so 
as to prevent the patient from breathing out and thereby maintain a consistent chest wall 
expansion with each DIBH. A nose clip prevents air leakage. The therapist monitors the 

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respiratory cycle and DIBH signals on the screen during the radiation delivery. When the 
patient depresses a handheld thumb switch, treatment is stopped and valve opens so 
breathing can resume normally again. Dosimetric advantages of cardiac sparing using 
DIBH ABC technique have been shown.13, 14 Currently, UTSW lung and liver SBRT and 
left breast conventional irradiation are used ABC assisted DIBH (ABC-DIBH) for 
respiratory motion management. 
 
Several studies have pointed out potential drawbacks of the ABC system. For example, 
even though the patient’s tidal volume remains consistent with ABC, different breathing 
maneuvers (abdominal versus thoracic breathing) can cause for variations in breath-hold.15 
They reported that for the same vital capacity, abdominal and thoracic breathing led to an 
average difference of chest wall expansion of 1.9 cm. Remouchamps et al. also showed 
that that overshoot can occur with ABC device where the patient can inhale a larger air 
volume than the pre-determined set limit.13, 16 More recently, Mittauer et al. showed 
through using an optical surface-tracking system to monitor ABC-assisted DIBH, that large 
positional variations can occur in some patients due to their different breath hold 
techniques17 and concluded that optical tracking system is a valuable tool for ABC-assisted 
DIBH.  
1.3 
VRT and VRT-DIBH  
A more recent competing technology for implementing the DIBH technique is real-time 
surface photogrammetry using the AlignRT system (Vision RT Ltd., London, UK). 
AlignRT system use non-ionization near infrared light to track patient surface motion. The 
system has one projector projecting near infrared optical pattern on patient surface. The 
optical pattern is imaged by optical cameras (two per pod) at ~25 Hz. The user selects a 
region-of-interest (ROI) on the surface and the software calculates and displays the real-
time position in six degrees (3 translations and 3 rotations) in real-time. Once the patient 
has matched the pre-determined DIBH position (within threshold accuracy), the radiation 
beam is enabled to be turned on for treatment. 
 
Currently, VRT-DIBH has already applied to left breast radiotherapy to spare lung and 
heart. Compared to ABC-DIBH, VRT-DIBH has several potential advantages: 
1. VRT monitors patient (surface) position in addition to DIBH signal,  while ABC only 
check the tidal volume, which can remain the same even if the patient shifts slightly on 
the couch; 
2. VRT is more cost effective, as patient tubing needs to be replaced daily for ABC; 
3. VRT potentially has advantage on patient compliance, as with ABC breath is forced 
impeded while with VRT breath-hold is voluntary.   
 
In this study, we renovate the established DIBH motion management strategy by adopting 
AlignRT system. The purpose of this study is to develop, validate, and prove the feasibility 
of VRT-DIBH technique for lung and liver SBRT. 
 
2.0 
STUDY OBJECTIVES 

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2.1 
Primary Objectives 
2.1.1 To investigate the feasibility of applying VRT-DIBH to lung/liver cancer 
SBRT  
2.2 
Secondary Objectives 
2.2.1 To determine planning target volume margin by investigating tumor 
residual motion in VRT-DIBH 
2.2.2  To determine VRT surface monitoring threshold by investigating inter/intra 
VRT-DIBH patient surface stability/reproducibility/sensitivity  
2.3 
Exploratory Objectives 
2.3.1 To quantify SBRT dose variation between planned and delivered with VRT-
DIBH technique. 
2.3.2 Treatment time 
2.4 
Endpoints 
2.4.1 VRT-DIBH feasibility 
2.4.2 To determine target margin in VRT-DIBH lung/liver SBRT  
2.4.3   To determine threshold used for surface monitoring in VRT-DIBH assisted 
lung/liver SBRT  
   
3.0 
PATIENT ELIGIBILITY 
Eligibility waivers are not permitted. Subjects must meet all of the inclusion and exclusion 
criteria to be registered to the study. Study treatment may not begin until a subject is 
registered. 
3.1 
Inclusion Criteria 
3.1.1 Patients must be willing and capable to provide informed consent to 
participate in the protocol. 
3.1.2 Patient with presumed pulmonary function capable of holding breath for at 
least 30 seconds – later to be confirmed. 
3.1.3 
All men, as well as women of child-bearing potential must agree to use adequate 
contraception (hormonal or barrier method of birth control; abstinence) prior to study 
entry, and until study imaging is complete. Should a woman become pregnant or 
suspect she is pregnant while participating in this study, she should inform her 
treating physician immediately. 
 
3.1.6.1 A female of child-bearing potential is any woman (regardless of sexual 
orientation, marital status, having undergone a tubal ligation, or 
remaining celibate by choice) who meets the following criteria: 
 
 
Has not undergone a hysterectomy or bilateral oophorectomy; or 
 
Has not been naturally postmenopausal for at least 12 consecutive 
months (i.e., has had menses at any time in the preceding 12 
consecutive months). 
 

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3.1.4 Patients must be compliant to all required pretreatment evaluations (section 
5.1) 
3.2 
Exclusion Criteria 
3.2.1 Pregnant or lactating women, as treatment involves unforeseeable risks to 
the embryo or fetus 
3.2.2 Patients are not compliant to all required pretreatment evaluations (section 
5.1). 
 
4.0 
TREATMENT PLAN 
4.1 
Treatment Dosage and Administration 
Patient recruit on this treatment protocol will go through training-screening 
sessions: 
1. Patient will go through a tumor motion evaluation session. Since we would like 
to test the effectiveness of our proposed motion management strategy, we 
would like to recruit patient with tumor motion in one direction is larger than 5 
mm.  Tumor motion in free-breathing mode will be evaluated under imaging 
study.. 
2. Patient will go through a pre-oxygenation training-screening session. Research 
studies18, 19 already shown that pre-oxygenation can effectively prolong breath-
holds in patients with cancer. In this study we will combine patient training, 
screening, and pre-oxygenation to prolong patient breath-hold duration in 
radiotherapy procedure. Patient will be asked to breathing oxygen-enhanced air 
through a facial mask and take deep inspiration breath hold. We will use 
spirometer to find the maximum deep inspiration breath level and set a 
comfortable/optimal breath hold level ~75% of the maximum deep inspiration.  
Only patient can have single DIBH duration >= 30 seconds will be eligible for 
the study. 
3. Patient will go through a real-time coaching training session assisted by DIBH 
technique. After being trained, patient will go through motion assessment 
section. Patient will be set on treatment couch with chest exposed which allows  
cameras catch patient body surface information. Spirometer will be used to 
assist DIBH setup. Optical camera system will be used to acquire patient 
chest/abdomen surface. During the surface image acquisition, imaging will be 
used to acquire tumor position or diaphragm position. The surface images and 
tumor positions acquired in single DIBH durations will be used to quantify 
intra-DIBH patient surface and tumor position stability. The surface images and 
tumor positions acquired across several DIBH durations will be used to quantify 
inter-DIBH patient surface and tumor position repeatability. The intermittent 
time between DIBH durations can be varied between 1-10 minutes. 
4. Only patient with inter/intra-DIBH tumor position variation <=5 mm and 
inter/intra-DIBH surface level variation <= 5 mm will be move on for this VRT-
DIBH protocol study. Otherwise, patients will be off study and treated per 
standard of care. 

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DIBH qualified patient will experience one high-resolution CT scan as SOC and 
additional lower dose CT scans to further investigate inter-DIBH patient surface 
and tumor position stability and repeatability.  
1. Spirometer will be used to select DIBH level and monitor DIBH status 
during CT simulation. One SOC high-resolution CT will be acquired in 
single DIBH duration. Within 10 minute, a low-resolution/low-dose CT 
image in single DIBH duration will be acquired. This study is to quantify 
inter-DIBH tumor position and patient surface repeatability.  
2. Patient will then be scanned using a lower dose CT protocol with DIBH 
level set at ±10% deviated from the selected DIBH level. This study is to 
find the correlation between DIBH level and tumor position /chest-abdomen 
surface level.  
 
The SOC DIBH CT scan will be transferred to Eclipse treatment planning system 
for treatment planning. Tidal volume measured by spirometer and DIBH surface 
from CT image will be used as a reference surface for patient treatment initial setup. 
CBCT will be acquired before each fractional treatment for the patient alignment 
before beam delivery.  
 
During the treatment delivery, patient will perform DIBH while AlignRT system 
monitors patient surface. As a pilot study, we will also use spirometer to monitor 
patient breath-hold tidal volume, and imaging acquired in any two DIBH periods 
to quantify inter- and intra- DIBH tumor position variation. Following our SBRT 
treatment protocol, patient will get CBCT scan before the last beam delivery. We 
will follow the same protocol to acquire CBCT images. These CBCT images will 
be used to evaluate treatment dose variation to quantify treatment delivery 
accuracy.  
 
 
4.2 
Concomitant Medications/Treatments 
Concomitant medications allowable as deemed appropriate by treating physicians. 
4.3 
Duration of Therapy 
End of protocol therapy will be the last day of radiation. Other exceptions may 
apply: 
 Disease progression 
 Inter-current illness that prevents further administration of treatment 
 Unacceptable adverse event(s) 
 Subject  decides to withdraw from the study, OR 
 General or specific changes in the patient’s condition render the subject 
unacceptable for further treatment in the judgment of the investigator”. 
4.4 
Duration of Follow Up 
No follow-up required for this study after radiation completed.  

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4.5 
Removal of Subjects from Protocol Therapy 
Subjects will be removed from therapy when any of the criteria listed in Section 5.5 
apply. Notify the Principal Investigators, and document the reason for study 
removal and the date the subject was removed in the Case Report Form. The subject 
should be followed-up per protocol.  
4.6 
Subject Replacement 
If a subject is withdrawn from the study prior to completing radiation therapy due 
to standard concerns for treatment side effects, an additional subject may be added. 
Notify the Principal Investigators, and document the reason for study replacement 
and the date the subject was removed in the Case Report Form. 
5.0 
STUDY PROCEDURES 
5.1 
Screening/Baseline Procedures 
Assessments performed exclusively to determine eligibility for this study will be 
done only after obtaining informed consent. Assessments performed for clinical 
indications (not exclusively to determine study eligibility) may be used for baseline 
values even if the studies were done before informed consent was obtained. 
 
All screening procedures must be performed within 60 days prior to registration 
unless otherwise stated. The screening procedures include: 
5.1.1 Informed Consent 
5.1.2 Medical Diagnosis 
5.1.3 Demographics 
Age 
5.1.4 Review subject eligibility criteria 
5.1.5 Physical exam including vital signs, height and weight 
Vital signs (temperature, pulse, respirations, blood pressure) for each 
protocol related visit. 
5.1.6 Adverse event assessment 
 
 
None 
5.1.7 Pregnancy test (for females of child bearing potential) 
See section 3.1.3 for definition. This is done prior to enrollment. Patients 
may refuse testing if they attest they are not pregnant. 

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5.1.8 Breathing evaluation 
Treatment target motion, surface motion and breathing duration will be 
evaluated before SBRT (does not have to be done prior to registration). The 
following screening procedures will be pursued sequentially: 
1. Free-breathing tumor motion evaluation: imaging will be acquired and 
physician will determine whether tumor motion > 5 mm. 
2. For those patients with tumor motion > 5 mm, breath-holding duration 
will be evaluated. At this stage, patient will be positioned supine in a 
stable position. Patient will be asked to breathe oxygen-enhanced air and 
then take deep inspiration breath hold. Ask patient to repeat breath-
holding 3 times and record breath-holding time. If patients can hold 
breath >= 30 seconds in all three times, patients will be eligible for the 
study. 
3. Patient will be monitored by optical cameras to assess surface motion. 
Air tube will be setup to assist oxygen-enhanced air breathing. Care must 
be taken to ensure tubing is not over patient chest, as optical cameras 
will acquire surface images for motion evaluation. Patient will be 
instructed to conduct DIBH and optical cameras will monitor patient 
surface during breath hold. If surface motion > 5 mm during the breath 
hold, patient will not be qualitied for this trial. Another test is that we 
will instruct patient to repeat breath hold three times. If patient is able to 
repeat breath hold to the level of the first setting within 5 mm tolerance, 
patient will move on for the further study step. 
4. DIBH tumor motion evaluation: after surface motion evaluation, DIBH 
tumor motion evaluation will be conducted under imaging one more 
time. Imaging will be acquired and physician will determine whether 
tumor motion <= 5 mm in one direction. 
5.2 
Procedures during Treatment 
5.2.1 
CT simulation  
 CT Simulation scans at DIBH will be assisted by spirometer ---must 
ensure tubing from spirometer not over chest wall so skin rendering is 
able to be reproduced. 
 CT simulation scan (full-length) will be acquired with at a single DIBH 
duration, starting at least 10 cm above the superior extent of tumor and 
continuing on every CT slice to at least 10 cm below the inferior extent 
of the tumor. DIBH signal will be monitored by spirometer. If there is no 
contraindication to contrast administration, patient will receive DIBH CT 
scans with contrast administration. 
 CT acquisition should be done with gantry 0 degree with spacing ≤ 2 
mm.  
 Additional DIBH CT scans will be conducted using lower dose CT scan 
protocol. One at the same DIBH level and the other two will be ±10% 
deviated from DIBH breath level 

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 All images will be transferred to the treatment planning computers for 
tumor motion evaluation and planning. 
5.2.2 
Tumor motion evaluation and target volume delineation 
On the acquired four different DIBH CTs, gross tumor volume (GTV) will 
be contoured by an appropriately trained physician. Tumor center point 
(center of mass) will be the identified and used for motion evaluation. Both 
inter- and intra- motion amplitude will be analyzed and margins will be 
estimated. The acquired high-resolution DIBH CT will be used as a primary 
image for planning. Physician will expand the GTV to PTV by adding 
proper size margins. 
5.2.3 
Critical organs delineation 
SOC 
5.2.4 
Treatment planning 
SOC 
5.2.5 
Daily treatment 
- Patient will be positioned with vac lock bag in stereotactic body frame and 
setup with stereotactic coordinates recorded during simulation; 
- Setup DIBH tidal volume use spirometer to reproduce simulated tidal 
volume; 
-  Initial setup patient position with AlignRT system using CT surface; 
-  Patient will receive a CBCT scan and align to simulated CT images; 
- Right after CBCT alignment, AlignRT system will acquire a new surface 
image for treatment monitoring; 
-  Treatment delivery follows routine SBRT treatment, with one CBCT 
check before and one CBCT before last beam (not during treatment beam 
delivery). 
 
 
5.2.8   Post-Radiation analysis                                                                                                         
-  Analyze recorded daily AlignRT treatment setup delta values 
-  Analyze recorded daily position shift using CBCT alignment 
- Analyze recorded daily AlignRT treatment delta values, investigate 
surface stability and reproducibility 
- Delineate tumor on  recorded CBCT images and investigate the position 
error 
-  Project treatment beams on CBCT images and recalculate dose with 
CBCT images. Evaluate dose difference between the planned and the 
delivered. 
-  Treatment time analysis 
5.3 
Follow-up procedures 
- 
No follow-up required for this study after radiation completed. Follow-up per 
standard of care for SBRT treatment per treating radiation oncologist. 

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5.4 
Time and Events Table  
 
 
 
Pre-study 
Treatment 
Assessment 
 
 
Informed Consent 
X 
 
History and PEA 
X 
XC 
Pregnancy TestB 
X 
 
CBCT scans 
 
X 
 
 A include vital signs 
              B Recommended but patient may refuse if they attest they are not pregnant 
 
C Only vital signs, once per week 
5.5 
Removal of Subjects from Study 
Subjects can be taken off the study treatment and/or study at any time at their own 
request, or they may be withdrawn at the discretion of the investigator for safety, 
behavioral or administrative reasons. The reason(s) for discontinuation will be 
documented and may include: 
5.5.1 Subject voluntarily withdraws from treatment (follow-up permitted); 
5.5.2 Subject withdraws consent (termination of treatment and follow-up); 
5.5.3 Subject is unable to comply with protocol requirements; 
5.5.4 Subject demonstrates disease progression (unless continued treatment with 
study drug is deemed appropriate at the discretion of the investigator); 
5.5.5 Subject experiences toxicity from standard of care radiation treatment that 
the treating physician wants to stop the subject’s continuation on the 
protocol 
5.5.6 Treating physician judge’s continuation on the study would not be in the 
subject’s best interest; 
5.5.7 Subject becomes pregnant 
5.5.8    Development of second malignancy (except for basal cell carcinoma or 
squamous cell carcinoma of the skin) that requires treatment, which would 
interfere with this study; 
5.5.9 Lost to follow-up. 
 
6.0 
STATISTICAL CONSIDERATIONS  
In this pilot study that aims to investigate the feasibility of applying VRT-DIBH to assist 
lung/liver cancer SBRT, we will recruit 10 patients. A sample size justification was not 
made since this is a pilot study to explore the feasibility of using VisionRT guided DIBH. 
Descriptive statistics will be computed to estimate the sample size needed for a future 
larger trial if the study results look promising. The trial is considered feasible and 
promising if 50% of enrolled patients can finish breath-holding SBRT. 

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6.1 
Study Design/Study Endpoints 
A single-center prospective pilot study will be conducted according to the schema 
outlined at the beginning of this document. Informed consent will be obtained from 
10 thoracic or abdominal cancer patients, each to be treated with SBRT technique. 
In order to quantify tumor motion/surface stability and repeatability during VRT-
DIBH, several CT images will be acquired during treatment simulation, as well as 
CBCT and VRT surface images during treatment delivery. The designed study aims 
to explore the geometry and dosimetry accuracy of VRT-DIBH in thoracic or 
abdominal cancer SBRT. 
6.2 
Sample Size and Accrual 
As this is a pilot study, we will recruit 10 patients and use descriptive statistics to 
characterize tumor motion/surface stability & repeatability during VRT-DIBH and 
its dosimetric impact in terms of dose deviation to tumor and critical organs. 
 A sample size justification was not made since this is a pilot study. Descriptive 
statistics will be computed to estimate the sample size needed for a future larger 
trial if the study results look promising. We anticipate that the proposed trial will 
be completed in 2 years since at least 5 patients are expected to be recruited a year. 
6.3 
Data Analyses Plans 
All recorded CBCT images will be used for tumor and critical organs geometry 
accuracy study by exporting to Velocity software. PTV and critical organs will be 
delineated. Tumor position accuracy will be evaluated. Further delivered 
dosimetric accuracy will be evaluated with through dose calculation on acquired 
CBCT images. 
7.0 
ADVERSE EVENTS 
7.1 
Adverse Event Monitoring 
Adverse event data collection and reporting, which are required as part of every clinical 
trial, are done to ensure the safety of subjects enrolled in the studies as well as those 
who will enroll in future studies. Adverse events are assessed in a routine manner at 
scheduled times during a trial. Additionally, certain adverse events must be reported in an 
expedited manner to allow for optimal monitoring of subject safety and care.  
 
All subjects experiencing an adverse event, regardless of its relationship to study 
therapy, will be monitored until:  
 the adverse event resolves or the symptoms or signs that constitute the adverse 
event return to baseline or is stable in the opinion of the investigator;  
 there is a satisfactory explanation other than the study therapy for the changes 
observed; or 
 death. 
 
[Inserted from Adverse Event Definitions and Reporting Section – Appendix II of 
the SCCC DSMC Plan] 

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7.1.1 
Definitions  
An adverse event is defined as any untoward or unfavorable medical occurrence in a 
human research study participant, including any abnormal sign (for example, abnormal 
physical exam, imaging finding or clinically significant laboratory finding), symptom, 
clinical event, or disease, temporally associated with the subject’s participation in the 
research, whether or not it is considered related to the subject’s participation in the 
research. 
Adverse events encompass clinical, physical and psychological harms. Adverse events 
occur most commonly in the context of biomedical research, although on occasion, they 
can occur in the context of social and behavioral research. Adverse events may be 
expected or unexpected. 
Acute Adverse Events  
Adverse events occurring in the time period from the signing of the informed consent, 
through the last day of treatment will be considered acute adverse events. 
Severity  
Adverse events will be graded by a numerical score according to the defined NCI 
Common Terminology Criteria for Adverse Events (NCI CTCAE) Version 5.0. Adverse 
events not specifically defined in the NCI CTCAE will be scored on the Adverse Event log 
according to the general guidelines provided by the NCI CTCAE and as outlined below.   
 
Grade 1: Mild  
 
Grade 2: Moderate 
 
Grade 3: Severe or medically significant but not immediately life threatening 
 
Grade 4: Life threatening consequences 
 
Grade 5: Death related to the adverse event 
 
Serious Adverse Events  
OHRP and UTSW HRPP define serious adverse events as those events, occurring at 
any dose, which meets any of the following criteria:  
 
results in death; 
 
is life-threatening (places the subject at immediate risk of death from the event as 
it occurred); 
 
results in inpatient hospitalization1,2 or prolongation of existing hospitalization; 
 
results in a persistent or significant disability/incapacity; 
 
results in a congenital anomaly/birth defect; or 
 
based upon appropriate medical judgment, may jeopardize the subject’s health 
and may require medical or surgical intervention to prevent one of the other 
outcomes listed in this definition. 
 
 
Note: A “Serious adverse event” is by definition an event that meets any of the above 
criteria. Serious adverse events may or may not be related to the research project. A 
serious adverse event determination does not require the event to be related to the 
research. That is, both events completely unrelated to the condition under study and 
events that are expected in the context of the condition under study may be serious 
adverse events, independent of relatedness to the study itself. As examples, a car 
accident requiring >24 hour inpatient admission to the hospital would be a serious 
adverse event for any research participant; likewise, in a study investigating end-stage 

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cancer care, any hospitalization or death which occurs during the protocol-specified 
period of monitoring for adverse and serious adverse events would be a serious adverse 
event, even if the event observed is a primary clinical endpoint of the study. 
1Pre-planned hospitalizations or elective surgeries are not considered SAEs. Note: If 
events occur during a pre-planned hospitalization or surgery, that prolong the existing 
hospitalization, those events should be evaluated and/or reported as SAEs.   
2 NCI defines hospitalization for expedited AE reporting purposes as an inpatient hospital 
stay equal to or greater than 24 hours. Hospitalization is used as an indicator of the 
seriousness of the adverse event and should only be used for situations where the AE 
truly fits this definition and NOT for hospitalizations associated with less serious events. 
For example: a hospital visit where a patient is admitted for observation or minor 
treatment (e.g. hydration) and released in less than 24 hours. Furthermore, 
hospitalization for pharmacokinetic sampling is not an AE and therefore is not to be 
reported either as a routine AE or in an expedited report. 
7.1.2 
Unanticipated Problems Involving Risks to Subjects or Others (UPIRSOs): 
The phrase “unanticipated problems involving risks to subjects or others” is found, but not 
defined in the HHS regulations at 45 CFR 46, and the FDA regulations at 21 CFR 
56.108(b)(1) and 21 CFR 312.66. For device studies, part 812 uses the term 
unanticipated adverse device effect, which is defined in 21 CFR 812.3(s). Guidance from 
the regulatory agencies considers unanticipated problems to include any incident, 
experience, or outcome that meets ALL three (3) of the following criteria: 
• 
Unexpected in terms of nature, severity or frequency given (a) the research procedures 
that are described in the protocol-related documents, such as the IRB-approved research 
protocol and informed consent document; and (b) the characteristics of the subject 
population being studied;  
 
 
 
 
AND 
• 
Related or possibly related to participation in the research (possibly related means there 
is a reasonable possibility that the incident, experience, or outcome may have been 
caused by the procedures involved in the research); 
 
AND  
• 
Suggests that the research places subjects or others at greater risk of harm (including 
physical, psychological, economic, or social harm) than was previously known or 
recognized. Note: According to OHRP, if the adverse event is serious, it would always 
suggest a greater risk of harm. 
 
Follow-up  
All adverse events will be followed up according to good medical practices.  
  
7.2 
Steps to Determine If a Serious Adverse Event Requires Expedited Reporting to the 
SCCC DSMC 
Step 1: Identify the type of adverse event using the NCI Common Terminology Criteria 
for Adverse Events (CTCAE v5).  
 
Step 2: Grade the adverse event using the NCI CTCAE v5. 
 
Step 3: Determine whether the adverse event is related to the protocol therapy.  
Attribution categories are as follows: 
- 
Definite – The AE is clearly related to the study treatment. 

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- 
Probable – The AE is likely related to the study treatment. 
- 
Possible – The AE may be related to the study treatment. 
- 
Unlikely – The AE may NOT be related to the study treatment. 
- 
Unrelated – The AE is clearly NOT related to the study treatment. 
Note: This includes all events that occur to the end of the acute adverse events reporting 
period as defined in section 7.1.1.  
 
Step 4: Determine the prior experience of the adverse event. Expected events are those 
that have been previously identified as resulting from administration of the treatment. An 
adverse event is considered unexpected, for expedited reporting purposes only, when 
either the type of event or the severity of the event is not listed in: 
 
the current known adverse events listed in the Agent Information Section of this 
protocol (if applicable); 
 
the drug package insert (if applicable); 
 
the current Investigator’s Brochure (if applicable) 
 
the Study Agent(s)/Therapy(ies) Background and Associated Known Toxicities 
section of this protocol 
 
7.2.1 
Reporting SAEs and UPIRSOs to the Simmons Comprehensive Cancer Center 
(SCCC) Data Safety Monitoring Committee (DSMC) 
 
SAEs and UPIRSOs at all sites, which occur in research subjects on protocols for which 
the SCCC is the DSMC of record require reporting to the DSMC regardless of whether 
IRB reporting is required. All SAEs occurring during the protocol-specified monitoring 
period and all UPIRSOs should be submitted to the SCCC DSMC within 5 business days 
of the study team members awareness of the event(s). In addition, for participating 
centers other than UTSW, local IRB guidance should be followed for local reporting of 
serious adverse events or unanticipated problems. 
 
The UTSW study PI is responsible for ensuring SAEs/UPIRSOs are submitted to the SCCC 
DSMC Coordinator. This may be facilitated by the IIT project manager, study team, sub-
site or other designee. Hardcopies or electronic versions of the eIRB Reportable Event 
report; FDA Form #3500A forms, or other sponsor forms, if applicable; and/or any other 
supporting documentation available should be submitted to the DSMC Coordinator.  The 
DSMC Coordinator forwards the information onto the DSMC Chairman who determines if 
immediate action is required.  Follow-up eIRB reports, and all subsequent SAE or UPIRSO 
documentation that is available are also submitted to the DSMC Chair who determines if 
further action is required. (See Appendix III of the SCCC DSMC Plan for a template Serious 
Adverse Event Form which may be utilized). 
  
 
If the event occurs on a multi-institutional clinical trial coordinated by the UTSW Simmons 
Comprehensive Cancer Center, the IIT Project Manager or designee ensures that all 
participating sites are notified of the event and resulting action, according to FDA 
guidance for expedited reporting. DSMC Chairperson reviews all SAEs and UPIRSOs 
upon receipt from the DSMC Coordinator.  The DSMC Chairperson determines whether 
action is required and either takes action immediately, convenes a special DSMC session 
(physical or electronic), or defers the action until a regularly scheduled DSMC meeting.  
 
 
Written reports to: 
(Investigator/study team: Insert names, fax numbers, an addresses for required 
notifications)  
 
 

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UTSW SCCC Data Safety Monitoring Committee Coordinator 
Email: SCCDSMC@utsouthwestern.edu 
Fax: 214-648-5949 or deliver to BLB.306 
 
UTSW Institutional Review Board (IRB) 
Submit a Reportable Event via eIRB with a copy of the final sponsor 
report as attached supporting documentation 
 
 
Reporting Unanticipated Problems Involving Risks to Subjects or Others 
(UPIRSOs) to the UTSW HRPP 
 
UTSW reportable event guidance applies to all research conducted by or on behalf of UT 
Southwestern, its affiliates, and investigators, sites, or institutions relying on the UT 
Southwestern IRB. Additional reporting requirements apply for research relying on a non-
UT Southwestern IRB. 
 
According to UTSW HRPP policy, UPIRSOs are incidents, experiences, outcomes, etc. 
that meet ALL three (3) of the following criteria: 
1. Unexpected in nature, frequency, or severity (i.e., generally not expected in a 
subject’s underlying condition or not expected as a risk of the study; therefore, not 
included in the investigator’s brochure, protocol, or informed consent document),AND 
2. Probably or definitely related to participation in the research, AND 
3. Suggests that the research places subjects or others at a greater risk of harm 
(including physical, psychological, economic, or social harm) than was previously 
known or recognized.  Note: According to OHRP, if the adverse event is serious, it 
would always suggest a greater risk of harm. 
 
For purposes of this policy, UPIRSOs include unanticipated adverse device effects 
(UADEs) and death or serious injury related to a humanitarian use device (HUD).  
 
UPIRSOs must be promptly reported to the UTSW HRPP within 5 working days of 
study team awareness. 
 
For research relying on a non-UT Southwestern IRB (external, central, or single IRB): 
 
Investigators relying on an external IRB who are conducting research on behalf of UT 
Southwestern or its affiliates are responsible for submitting LOCAL UPIRSOs to the UT 
Southwestern IRB within 5 working days of study team awareness. Investigators must 
report to their relying IRB according to the relying IRB’s policy. In addition, the external 
IRB’s responses or determinations on these local events must be submitted to the UT 
Southwestern IRB within 10 working days of receipt. 
 
Events NOT meeting UPIRSO criteria: 
 
Events that do NOT meet UPIRSO criteria should be tracked, evaluated, summarized, 
and submitted to the UTSW HRPP/IRB at continuing review. 
 
For more information on UTSW HRPP/IRB reportable event policy, see 
https://www.utsouthwestern.edu/research/hrpp/quality-assurance/ 
7.3 
Unblinding Procedures 
Not applicable 

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7.4 
Stopping Rules 
Not applicable 
8.0 
STUDY MANAGEMENT 
8.1 
Conflict of Interest 
Any investigator who has a conflict of interest with this study (patent ownership, 
royalties, or financial gain greater than the minimum allowable by their institution, 
etc.) must have the conflict reviewed by the UTSW COI Committee and IRB 
according to UTSW Policy on Conflicts of Interest.  All investigators will follow 
the University conflict of interest policy. 
8.2 
Institutional Review Board (IRB) Approval and Consent 
It is expected that the IRB will have the proper representation and function in 
accordance with federally mandated regulations. The IRB must approve the consent 
form and protocol. 
 
In obtaining and documenting informed consent, the investigator should comply 
with the applicable regulatory requirement(s), and should adhere to Good Clinical 
Practice (GCP) and to ethical principles that have their origin in the Declaration of 
Helsinki. 
 
 
Before recruitment and enrollment onto this study, the subject will be given a full 
explanation of the study and will be given the opportunity to review the consent 
form. Each consent form must include all the relevant elements currently required 
by the FDA Regulations and local or state regulations. Once this essential 
information has been provided to the subject and the investigator is assured that the 
subject understands the implications of participating in the study, the subject will 
be asked to give consent to participate in the study by signing an IRB-approved 
consent form. 
 
Prior to a patient’s participation in the trial, the written informed consent form 
should be signed and personally dated by the subject  and by the person who 
conducted the informed consent discussion. 
8.3 
Registration Procedures 
All subjects must be registered with the Clinical Research Office, Department of 
Radiation Oncology, UTSW, before enrollment to study. Prior to registration, 
eligibility criteria must be confirmed with the Clinical research office Study 
Coordinator. To register a subject, call 214-633-1753 Monday through Friday, 
9:00AM-5:00PM.  
 
Each newly consented subject should be numbered using the schema provided 
above. 
Upon 
registration, 
the 
registrar 
will 
assign 
the 
additional 
registration/randomization code according to the numbering schema outlined 

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above, which should then be entered as the patient study id in Velos upon updating 
the status to enrolled. 
 
The numbering schema should clearly identify the site number; the sequential 
number of the subject enrolled as well as the status of the subjects enrolled so that 
the number of subjects consented versus the number of subjects actually enrolled 
may be easily identified.   
8.4 
Data Management and Monitoring/Auditing 
REDCap is the UTSW SCCC institutional choice for the electronic data capture of case 
report forms for SCCC Investigator Initiated Trials. REDCap will be used for electronic case 
report forms in accordance with Simmons Comprehensive Cancer Center requirements, 
as appropriate for the project 
 
Trial monitoring will be conducted according to the study specific monitoring plan. For 
guidance on creating a monitoring plan, refer to the UTSW SCCC IIT Management 
Manual.   
   
 
 
The UTSW Simmons Comprehensive Cancer Center (SCCC) Data Safety Monitoring 
Committee (DSMC) is responsible for monitoring data quality and patient safety for all 
UTSW SCCC clinical trials.  As part of that responsibility, the DSMC reviews all serious 
adverse events and UPIRSOs in real time as they are reported and reviews adverse 
events on a quarterly basis.  The quality assurance activity for the Clinical Research 
Office provides for periodic auditing of clinical research documents to ensure data 
integrity and regulatory compliance.  A copy of the DSMC plan is available upon request. 
 
The SCCC DSMC meets quarterly and conducts annual comprehensive reviews of 
ongoing clinical trials, for which it serves as the DSMC of record. The Quality Assurance 
Coordinator (QAC) works as part of the DSMC to conduct regular audits based on the level 
of risk. Audit findings are reviewed at the next available DSMC meeting.  In this way, 
frequency of DSMC monitoring is dependent upon the level of risk.  Risk level is determined 
by the DSMC Chairman and a number of factors such as the phase of the study; the type 
of investigational agent, device or intervention being studied; and monitoring required to 
ensure the safety of study subjects based on the associated risks of the study. Protocol-
specific DSMC plans must be consistent with these principles.   
 
8.5 
Adherence to the Protocol 
Except for an emergency situation, in which proper care for the protection, safety, and 
well-being of the study subject requires alternative treatment, the study shall be 
conducted exactly as described in the approved protocol.  
8.5.1 
Exceptions (also called single-subject exceptions or single-subject waivers): 
include any departure from IRB-approved research that is not due to an 
emergency and is: 
 intentional on part of the investigator; or 
 in the investigator’s control; or 
 not intended as a systemic change (e.g., single-subject exceptions to eligibility 
[inclusion/exclusion] criteria) 

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 Reporting requirement*: Exceptions are non-emergency deviations that require prospective 
IRB approval before being implemented. Call the IRB if your request is 
urgent. If IRB approval is not obtained beforehand, this constitutes a major 
deviation. For eligibility waivers, studies which utilize the SCCC-DSMC as the 
DSMC of record must also obtain approval from the DSMC prior to submitting 
to IRB for approval. 
8.5.2 
Emergency Deviations: include any departure from IRB-approved research that 
is necessary to:  
 avoid immediate apparent harm, or 
 protect the life or physical well-being of subjects or others 
 Reporting requirement*: Emergency deviations must be promptly 
reported 
to the IRB within 5 working days of occurrence. 
 
8.5.3 
Serious Noncompliance (formerly called major deviations or violations): 
include any departure from IRB-approved research that: 
 
Increase risk of harm to subjects; and/or 
 
 
adversely affects the rights, safety, or welfare of subjects (any of which may 
also be an unanticipated problem); and/or  
 
adversely affects the integrity of the data and research (i.e., substantially 
compromises the integrity, reliability, or validity of the research) 
 Reporting requirement*: Serious Noncompliance must be promptly 
reported tothe IRB within 5 working days of discovery.. 
 
8.5.4 
Continuing Noncompliance: includes a pattern of repeated    
noncompliance (in  or more protocols simultaneously, or over a period of time) 
which continues after initial discovery, including inadequate efforts to take or 
implement corrective or preventive action within a reasonable time frame. 
 Reporting requirement*: Continuing Noncompliance must be promptly 
reported to the IRB within 5 working days of discovery. 
 
8.5.5 
Noncompliance (that is neither serious nor continuing; formerly called 
minor deviations) any departure from IRB-approved research that: 
 
Does not meet the definition of serious noncompliance or continuing 
noncompliance 
 Reporting requirement*: Noncompliance that is neither serious nor continuing  
should be tracked and summarized the next IRB continuing review, or the notice 
of study closure- whichever comes first.. 
 
*Reporting Requirements reflect UTSW HRPP/IRB guidelines; participating sites should follow 
the reporting guidelines for their IRB of record 
 
8.6 
Amendments to the Protocol 
Should amendments to the protocol be required, the amendments will be originated 
and documented by the Principal Investigator.  A summary of changes document 
outlining proposed changes as well as rationale for changes, when appropriate, is 
highly recommended.  When an amendment to the protocol substantially alters the 

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study design or the potential risk to the patient, a revised consent form might be 
required.  
 
The written amendment, and if required the amended consent form, must be sent to 
the IRB for approval prior to implementation.  
8.7 
Record Retention 
Study documentation includes all Case Report Forms, data correction forms or 
queries, source documents, Sponsor-Investigator correspondence, monitoring 
logs/letters, and regulatory documents (e.g., protocol and amendments, IRB 
correspondence and approval, signed patient consent forms). 
 
Source documents include all recordings of observations or notations of clinical 
activities and all reports and records necessary for the evaluation and reconstruction 
of the clinical research study. 
 
Government agency regulations and directives require that the study investigator 
retain all study documentation pertaining to the conduct of a clinical trial. In the 
case of a study with a drug seeking regulatory approval and marketing, these 
documents shall be retained for at least two years after the last approval of 
marketing application in an International Conference on Harmonization (ICH) 
region. In all other cases, study documents should be kept on file until three years 
after the completion and final study report of this investigational study. 
8.8 
Obligations of Investigators 
The Principal Investigator is responsible for the conduct of the clinical trial at the 
site in accordance with Title 21 of the Code of Federal Regulations and/or the 
Declaration of Helsinki. The Principal Investigator is responsible for personally 
overseeing the treatment of all study patients. The Principal Investigator must 
assure that all study site personnel, including sub-investigators and other study staff 
members, adhere to the study protocol and all FDA/GCP/NCI regulations and 
guidelines regarding clinical trials both during and after study completion. 
 
The Principal Investigator at each institution or site will be responsible for assuring 
that all the required data will be collected and entered onto the Case Report Forms. 
Periodically, monitoring visits may be conducted and the Principal Investigator will 
provide access to his/her original records to permit verification of proper entry of 
data. At the completion of the study, all case report forms will be reviewed by the 
Principal Investigator and will require his/her final signature to verify the accuracy 
of the data. 
9.0 
REFERENCES 
 
1. 
Siegel, R.L., K.D. Miller, and A. Jemal, Cancer statistics, 2016. CA Cancer J Clin, 2016. 
66(1): p. 7-30. 

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2. 
Wu, J., et al., Early-Stage Non-Small Cell Lung Cancer: Quantitative Imaging 
Characteristics of 18F Fluorodeoxyglucose PET/CT Allow Prediction of Distant 
Metastasis. Radiology, 2016: p. 151829. 
3. 
Timmerman, R., et al., Stereotactic Body Radiation Therapy for Inoperable Early Stage 
Lung Cancer. Jama-Journal of the American Medical Association, 2010. 303(11): p. 
1070-1076. 
4. 
Chang, E.L., et al., Phase I/II study of stereotactic body radiotherapy for spinal 
metastasis and its pattern of failure. Journal of Neurosurgery: Spine, 2007. 7(2): p. 151-
160. 
5. 
Huang, M., et al., Brain tumor segmentation based on local independent projection-based 
classification. IEEE Trans Biomed Eng, 2014. 61(10): p. 2633-45. 
6. 
Chi, A., et al., Systemic review of the patterns of failure following stereotactic body 
radiation therapy in early-stage non-small-cell lung cancer: clinical implications. 
Radiother Oncol, 2010. 94(1): p. 1-11. 
7. 
Matsuo, Y., et al., Dose--volume metrics associated with radiation pneumonitis after 
stereotactic body radiation therapy for lung cancer. Int J Radiat Oncol Biol Phys 2012. 
83: p. e545-549  
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