Pediatric Radiation Oncology With Movie Induced Sedation Effect (PROMISE): A Phase II Clinical Trial to Safely Reduce Anesthesia Use
Phase: PHASE2
Conditions: Pediatric Cancer
Sponsor: University of Texas Southwestern Medical Center

 
STU2021-1005, Kumar, FormA-Protocol-V2.2-12.21.23, Mod_6, 01-22-24 
 
 
 
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 
 
STU-2021-1005 
 
Pediatric Radiation Oncology with Movie Induced Sedation Effect (PROMISE):  
A Phase II Clinical Trial to Safely Reduce Anesthesia Use  
 
Principal Investigator:  
Kiran A. Kumar, MD MBA 
UT Southwestern Medical Center 
2280 Inwood Rd, Dallas, TX, 75390 
Telephone: (214) 645-8525 
Fax: 214-645-8526 
E-mail: Kiran.Kumar@UTSouthwestern.edu 
 
Lead Sub-Investigator(s): 
Department of Radiation Oncology 
 
 
 
 
Tu Dan, MD  
 
 
 
 
Malgorzata Kozak, MD 
 
 
 
 
 
 
 
 
 
Department of Anesthesia, Pediatrics 
 
 
 
 
Christopher Setiawan, MD 
 
 
 
 
Edgar Kiss, MD  
 
 
 
 
 
 
Department of Pediatrics, Hematology-Oncology 
 
 
 
 
Matthew Campbell, MD 
 
 
 
 
Avanthi Shah, MD 
 
Department of Radiation Physics 
Tsuiecheng Chiu, Ph.D. 
Steve Jiang, Ph.D. 
 
Biostatistician: 
 
Department of Clinical Sciences 
 
 
 
Chul Ahn, PhD 
                                       UT Southwestern Medical Center 
 
 
 
5801 Forest Park Rd, Dallas, TX, 75390 
 
 
 
(214)648-9418 
                                       Chul.Ahn@UTSouthwestern.edu 
 
Study Drug/Treatment: 
PROMISE 
 
Funding Source:  
Wipe Out Kids’ Cancer 
 
NCT Number: 
NCT05148078 
 
Initial version: 
1.0 (7/1/2021) 
 
Amended: 
 
Version 2 – 8/15/2023 
 
 
Version 2.1 – 8/28/2023 
 
 
Version 2.2 – 12/21/2023 
 
 
UT Southwestern Medical Center (UTSW) 
Harold C. Simmons Comprehensive Cancer Center 
Attn: Clinical Research Office 
5323 Harry Hines Blvd. MC 9179 
Dallas, Texas 75390-9179 
 

 
STU2021-1005, Kumar, FormA-Protocol-V2.2-12.21.23, Mod_6, 01-22-24 
 
 
 
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 
 
 
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. 
 
Amendment/Version # 2.2  
 
STU-2021-1005 
 
Pediatric Radiation Oncology with Movie Induced Sedation Effect (PROMISE): A Phase II Clinical 
Trial to Safely Reduce Anesthesia Use  
 
 
Principal Investigator (PI) Name: ___Kiran A. Kumar, MD MBA__ 
 
 
 
PI Signature: _____________________________ 
 
 
 
Date: ____________________ 
 

STU-2021-1005 and protocol version #2.2 
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TABLE OF CONTENTS 
LIST OF ABBREVIATIONS ............................................................................................................. 1 
STUDY SCHEMA ............................................................................................................................ 2 
 
STUDY SUMMARY .......................................................................................................................... 3 
1.0 ............................................................................................. BACKGROUND AND RATIONALE
 .......................................................................................................................................................... 4 
1.1 
Disease Background........................................................................................................ 4 
1.2 
Study Agent(s)/Therapy(ies) Background and Associated Known Toxicities ................. 4 
1.3 
Rationale .......................................................................................................................... 6 
2.0 .................................................................................................................. STUDY OBJECTIVES
 .......................................................................................................................................................... 7 
2.1 
Primary Objectives ........................................................................................................... 7 
2.2 
Secondary Objectives ...................................................................................................... 7 
2.3 
Endpoints ......................................................................................................................... 8 
3.0 ................................................................................................................ SUBJECT ELIGIBILITY
 .......................................................................................................................................................... 8 
3.1 
Inclusion Criteria .............................................................................................................. 8 
3.2 
Exclusion Criteria ............................................................................................................. 9 
4.0 ..................................................................................................................... TREATMENT PLAN
 .......................................................................................................................................................... 9 
4.1 
Treatment Dosage and Administration ............................................................................ 9 
4.2 
Toxicities and Dosing Delays/Dose Modifications ......................................................... 10 
4.3 
Concomitant Medications/Treatments ........................................................................... 10 
4.4 
Duration of Therapy ....................................................................................................... 10 
4.5 
Duration of Follow Up .................................................................................................... 10 
4.6 
Removal of Patients from Protocol Therapy .................................................................. 10 

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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 .................................................................................................. 12 
5.5 
Removal of Subjects from Study ................................................................................... 13 
6.0 ..................................................................................................... MEASUREMENT OF EFFECT
 ........................................................................................................................................................ 13 
7.0 ...................................................................................................................... ADVERSE EVENTS
 ........................................................................................................................................................ 13 
7.1 
Experimental Therapy.................................................................................................... 13 
7.2 
Adverse Event Monitoring ............................................................................................. 13 
7.3 
Steps to Determine If an Adverse Event Requires Expedited Reporting ...................... 15 
8.0 .......................................................................................... DRUG/TREATMENT INFORMATION
 ........................................................................................................................................................ 18 
9.0 ............................................................................................. STATISTICAL CONSIDERATIONS
 ........................................................................................................................................................ 18 
9.1 
Study Design/Study Endpoints ...................................................................................... 18 
9.2 
Sample Size and Accrual .............................................................................................. 18 
9.3 
Data Analyses Plans...................................................................................................... 19 
10.0 ............................................................................................................. STUDY MANAGEMENT
 ........................................................................................................................................................ 19 
10.1 
Conflict of Interest .......................................................................................................... 19 
10.2 
Institutional Review Board (IRB) Approval and Consent ............................................... 19 
10.3 
Registration Procedures ................................................................................................ 19 
10.4 
Data Management and Monitoring/Auditing .................................................................. 20 
10.5 
Adherence to the Protocol ............................................................................................. 20 
10.6 
Amendments to the Protocol ......................................................................................... 21 

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10.7 
Record Retention ........................................................................................................... 21 
10.8 
Obligations of Investigators ........................................................................................... 22 
11.0 ............................................................................................................................ REFERENCES
 ........................................................................................................................................................ 23 
12.0 ............................................................................................................................. APPENDICES
 ........................................................................................................................................................ 26 

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LIST OF ABBREVIATIONS 
AE 
Adverse Event 
ALT 
Alanine Aminotransferase 
AST 
Aspartate Aminotransferase 
BUN 
Blood Urea Nitrogen 
BT 
Brachytherapy 
CBC 
Complete Blood Count 
CBCT 
Cone Beam Computed Tomography 
CMP 
Comprehensive Metabolic Panel 
CT 
Computed Tomography 
CTCAE 
Common Terminology Criteria for Adverse Events 
DOT 
Disease Oriented Team 
DSMB 
Data and Safety Monitoring Board 
ECOG 
Eastern Cooperative Oncology Group 
FDA 
Food and Drug Administration 
GCP 
Good Clinical Practice 
H&P 
History & Physical Exam 
HDR 
High Dose Rate 
HRPP 
Human Research Protections Program 
IHC 
Immunohistochemistry 
IV (or iv) 
Intravenously 
LDR 
Low dose rate 
mpMRI 
Multi-parametric Magnetic Resonance Imaging 
NCCN 
National Comprehensive Cancer Network 
OS 
Overall Survival 
pCR 
Pathologic Complete Response 
PET 
Positron Emission Tomography 
PFS 
Progression Free Survival 
p.o. 
peros/by mouth/orally 
PROMISE 
Pediatric Radiation Oncology with Movie Induced Sedation Effect 
RECIST 
Response Evaluation Criteria in Solid Tumors 
SAE 
Serious Adverse Event 
SAbR 
Stereotactic ablative body radiotherapy 
SBRT 
Stereotactic body radiotherapy 
SCCC 
Simmons Comprehensive Cancer Center 
scRNAseq 
Single cell RNA sequencing 
SGOT 
Serum Glutamic Oxaloacetic Transaminase 
SPGT 
Serum Glutamic Pyruvic Transaminase 
TRUS 
Transrectal ultrasound 
WBC 
White Blood Cells 
 
 
 

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STUDY SCHEMA 
 
 
 
 
 
 
 
      
 
 
 
          
 
         Success  
 
 
 
Fail 
 
 
 
 
 
 
 
        Fail any treatment 
 
 
                                                                                                              Fail 
 
 
 
 
                           Success 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
              
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Primary Endpoint & Hypothesis 
• 
Percentage of Children Ages 3-7 Requiring General Anesthesia: We hypothesize that PROMISE will 
lead to a reduction in the percentage of patients ages 3-7 who require general anesthesia during 
radiation treatment from 70% (institutional historical control) to 30%. 
 
Secondary Endpoints 
Secondary endpoints will be analyzed for those on trial treated with PROMISE vs. anesthesia. 
• 
Patient/family-reported health quality of life (PedsQL 3.0 Cancer Module) and anxiety (mYPAS-SF). 
• 
Workflow data: treatment time, average patient movement, and number of beam turn offs due to 
movement beyond threshold. 
• 
Overall cost of treatment. 
 
PROMISE 
(anesthesia on 
standby)  
Anesthesia 
Per standard of care for 
remaining treatments. May 
reattempt PROMISE at 
physicians discretion (Day 8). 
Reattempt PROMISE 
At physicians discretion   
(anesthesia on standby) 
Eligibility: 
• 
Child age 3-11 who is 
planned to undergo 
radiation treatment 
• 
ECOG PS <=2 
• 
No psychiatric, behavioral, 
or other medical condition 
that would necessitate 
anesthesia use 
Consult 
PROMISE clinical trial discussed, 
screening/enrollment 
CT Simulation Session 
PROMISE evaluation/trial 
(anesthesia on standby) 
PROMISE 
For all radiation 
treatments  

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STUDY SUMMARY 
Title 
Pediatric Radiation Oncology with Movie Induced Sedation Effect 
(PROMISE): A Phase II Clinical Trial to Safely Reduce Anesthesia Use  
 
Short Title 
PROMISE Clinical Trial to Reduce Anesthesia Use 
 
Protocol Number 
STU-2021-1005 
 
Phase 
Phase II 
 
Methodology 
Single-arm, open label 
 
Study Duration 
2 years 
 
Study Center(s) 
Single-center  
 
Objectives 
Primary: To decrease the total number of pediatric patients who require 
general anesthesia through the use of PROMISE. 
 
Secondary:  
- 
To assess the impact that PROMISE has on patient/family anxiety 
and quality of life, treatment time and clinical efficiency, and overall 
cost. 
- 
To determine the average patient movement and beam stoppages 
with the use of PROMISE. 
 
Number of Subjects 
30 
 
Diagnosis and Main 
Inclusion Criteria 
Age 3-11 and planned to undergo radiation therapy. 
 
Study Product(s), Dose, 
Route, Regimen 
PROMISE: an audio/visual technology for children to focus on during 
each radiation treatment to prevent movement. 
 
Duration of administration 
PROMISE will be used for each fraction of radiation treatment; number of 
fractions will vary by patient depending on individual diagnosis and 
treatment plan. 
 
Reference therapy 
Institutional historical control of percentage of patients age 3-7 who 
required general anesthesia during radiation therapy. 
 
Statistical Methodology 
We hypothesize that PROMISE will lead to a reduction in the percentage 
of patients ages 3-7 who require general anesthesia use from 70% 
(historical control) to 30%. Using a two-sided exact binomial test with a 
significance level of 0.05 and power=80%, a sample size of 13 patients 
(ages 3-7) will be needed to detect this difference.  
 
In our past experience, ~42% of children ages 3-11 (eligibility criteria) are 
between 3-7 years old, so 30 children total will be needed to enroll 13 
who are between 3-7 years old.  
 
 
 
 

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1.0 
BACKGROUND AND RATIONALE 
1.1 
Disease Background 
Pediatric Radiation Oncology: 
Childhood cancers are the leading cause of death in children in the United States. Over 
10,000 children are diagnosed annually1,2 and, each year, the disease claims more lives 
than asthma, cystic fibrosis, diabetes, and pediatric AIDS combined. Very little is known 
about childhood cancer prevention3, and the most common types include leukemias, 
lymphomas, and central nervous system tumors1,2. Both pediatric cancer incidence and 
cure rates increased from 1975 to 2004, with cure rates increasing in part because of the 
advancements in radiation therapy1,4. Some of the innovations that have improved both 
local tumor control and systemic spread include conformal radiotherapy, brachytherapy, 
proton beam therapy, and stereotactic radiosurgery5. For children with a diagnosis of 
cancer, radiotherapy is a main curative and palliative treatment modality often 
administered in combination with surgical resection and/or chemotherapy6. While 
radiation treatments are effective, they are also very intensive. The entire course of 
radiotherapy for a pediatric patient often consists of 25 to 30 fractions, lasting for 5 to 6 
weeks. 
 
General Anesthesia Use in Pediatric Radiation Oncology: 
Due to the precise nature of radiation therapy, immobilization is crucial for treatment 
effectiveness and patient safety3,4,7. For this reason, according to current standard 
radiotherapy practice most pediatric cancer patients under 7 years of age receive general 
anesthesia at each fraction to ensure that the patient remains still during the treatment. 
Almost all children under the age of three, the majority of children under 7, and even 
some children up to age 12 require general anesthesia7. Based on a study by Ntoukas, 
we estimate 70% of patients age 3-7 can avoid general anesthesia with the 
implementation of Pediatric Radiation Oncology with Movie Induced Sedation Effect 
(PROMISE)8, which is further described below.  
 
General anesthesia reduction is important because, if a child requires general 
anesthesia, he or she may receive up to 30 episodes of general anesthesia in 
succession6,9,10. This also means that, for the 6-week duration of radiotherapy, a child 
may never fully return to his/her baseline activity. More importantly, the excessive use of 
sedatives introduces many risks and side effects that, combined with chemotherapy, and 
cancer itself, can greatly affect the overall treatment experience for the children and their 
families10–12. Multiple other factors associated with frequent anesthesia administration 
worsen the treatment experience, and would be immediately eliminated if general 
anesthesia was no longer needed. For example, fasting on a daily basis, a necessary 
part of the anesthesia process, is often difficult in the pediatric population and strains 
both the child and parents13. Currently, pediatric radiation visits last multiple hours 
because of the need for lengthy pre- and post- anesthesia care. These visits could easily 
be shortened to minutes if anesthesia were avoided. Lastly, the anxiety, stress, and fears 
both patients and families experience largely due to anesthesia administration would 
dissipate with its disuse14. 
 
1.2 
Study Agent(s)/Therapy(ies) Background and Associated Known Toxicities 
PROMISE 
Pediatric Radiation Oncology with Movie Induced Sedation Effect (PROMISE) is an 
interactive, incentive-based movie system that integrates with a video surveillance gating 
module (VisionRT) to help keep a children’s attention and prevent him or her from moving 
during radiation treatment. This technology is being studied as an alternative sedation 

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solution for pediatric patients needing radiation treatment. There are no known or 
expected toxicities associated with PROMISE. 
 
As part of the trial, patients will be attempted to have CT simulation scan and first 
radiation treatment(s) using PROMISE, with general anesthesia on standby should 
PROMISE be unsuccessful. The only toxicity that could be indirectly associated with 
PROMISE is if the child moves during radiation treatment and this results in radiation 
temporarily being delivered to the wrong target. However, PROMISE is integrated with 
the video surveillance gating module VisionRT, so that if the patient moves beyond 
predefined safety threshold, the beam will automatically stop, so this is not an event that 
would ever be expected to happen. This auto-beam off ability is a unique feature of 
PROMISE that is not seen in competing technologies. 
 
If PROMISE is unsuccessful for a given patient, then standard of care general anesthesia 
will be used for that patient’s radiation treatments. 
 
Side Effects of General Anesthesia: 
Studies have discovered a plethora of adverse effects of anesthesia that manifest in 
pediatric patients even after they are discharged from the hospital. These effects range 
from motor imbalance and restlessness to excessive sedation, which requires admittance 
to the emergency room11. In a recent study, after a single episode of general anesthesia, 
31% of patients exhibited motor imbalance, 23% experienced gastrointestinal effects, and 
4% required medical advice after dismissal11. Furthermore, 5% of the children did not 
return to baseline activity until the second day after the procedure11. All effects were 
experienced after the patients had already been discharged from the hospital, meaning 
that they were able to meet the nationally recommended discharge criteria, but still were 
not functioning at a baseline level. Many pediatric cancer patients receive general 
anesthesia before every single fraction (essentially every 24 hours); for patients with six-
week treatments, this translates to a minimum of 30 episodes of anesthesia over the 
course of 40 days. For small children, 24 hours may not be enough time to fully recover 
from the effects of anesthesia; thus, for the 6-week duration of radiotherapy, a child may 
never fully return to his/her baseline activity given the potential duration of the effects 
sustained from each administration. 
 
Short-Term and Long-Term Risks of General Anesthesia: 
Upon receiving general anesthesia, some patients may experience a paradoxical 
reaction15,16, rendering them irritable and violent. This outcome is unpredictable and 
cannot be foreseen by anesthesiologists. If a patient exhibits this response, the sedation 
regimen must be recalculated using alternative sedatives. Other potential risks of 
anesthesia include primary failure, where the prescribed dose of the drug is not enough 
to elicit the desired state of consciousness for the patient, and secondary failure, where 
the effects wear off more quickly than expected and the patient unexpectedly awakes 
during treatment. Primary or secondary failure result in an undesired, heighted level of 
patient consciousness, referred to as anesthesia awareness17,18. Not only have 
anesthesia awareness patients reported excruciating surgical pain upon premature 
arousal, but anxiety, PTSD, and sleep disturbances are frequently reported in the wake of 
such incidents17,18. Even when anesthesia is successfully administered, the use of 
intubation for airway assistance is needed, possibly leading to a laryngospasm that can 
be fatal within a minute for children7,15,19. Respiratory, cardiovascular, and gastric 
complications as well can be life threatening even when anesthesia is administered 
properly7. Propofol sedation, a commonly used pediatric radiation therapy anesthesia 
method, can produce a wide spectrum of side effects ranging from increased secretions 
to seizures15. The short-term risks associated with anesthesia grow exponentially with 
increased administration, possibly leading to anesthesia failure and/or a laryngospasm. 
Additionally, following several episodes of general anesthesia, there is a chance that the 
child may incur long-term permanent neurological damage20–22. Neurological adverse 

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effects are currently being investigated. Although the long-term risks of repeated general 
anesthesia have not been thoroughly studied, there is consensus within the clinical 
community that repeated general anesthesia should not be used to children if possible. 
 
Lowered Efficacy and Added Costs with General Anesthesia: 
Daily rounds of general anesthesia can easily double the amount of time patient, parents, 
and medical staff (including anesthesiologists) spend in the hospital for administration 
and recuperation, making the process less efficient and increasingly expensive. For 
example, anesthesia costs average $50,000 per child over a typical six week treatment, 
therefore a reliable alternative to general anesthesia would drastically and immediately 
decrease costs23. Logistically, involvement of anesthesia is difficult. Radiation oncology 
suites are often stand-alone structures not located near or in major hospitals or academic 
centers, where anesthesia is more easily provided6. Because anesthesiologists are not 
normally on site in a radiation oncology suite, it creates obstacles in scheduling, 
transportation, and compensation. This problem is likely to worsen moving forward 
because radiation oncology suites are more frequently being built further from, not closer 
to, major hospitals or academic centers24. Anesthesia care provided in pediatric radiation 
therapy oncology suite is also often less efficient and safe. Anesthesiologist may be 
accustomed to working in operating room suites, which compared to radiation oncology 
suites, are relatively more efficient and have safer facilities, equipment, and personnel24. 
One such example is an anesthesiologist is not allowed in the radiation suite during 
treatment, which is not the case in a typical operating room3,6. 
 
Current Attempts to Minimize Anesthesia in Pediatric Oncology 
Multiple options are being explored to minimize the use of anesthesia in pediatric 
radiation oncology with varying levels of success:  music therapy plays music pre-
selected by the patient during treatment3,25; interactive intervention and 
psychoeducational therapy entails preparatory play therapy, interactive support, and 
behavioral modeling3,26–28; psychological preparation prepares patients emotionally and 
mentally for the upcoming treatments3,29. Electronic monitors working in concert with 
behavioral training display movies or cartoons to distract patients during treatment used 
to increase patient cooperation and avoid anesthesia3,28. AVATAR, a similar device to 
PROMISE created by Stanford, has shown promising results. Stanford’s study, published 
online January 11, 2020 reviewed 224 pediatric patients three years before and three 
years after AVATAR implementation.  They found that more patients avoided general 
anesthesia for all ages; 73.2% before AVATAR implementation versus 63.4% after 
implementation.  AVATAR use also demonstrated a reduction in treatment time per 
session by 38% and 326 fewer anesthesia sessions over a three year period, a total cost 
savings of roughly $500,00030. 
1.3 
Rationale 
In pediatric neuroimaging studies, it is critical to keep children motionless during the long 
periods of scanning31–34. Programmed feedback loops between movement and continued 
access to audio/video systems and mock MRI scanners have been used to train children 
to remain still during the scanning, using operant conditioning20,35–37. Great success has 
been achieved. Patients under study were reported35 meeting a movement criterion of 2 
mm per second or less, during a 20-min simulated scan. Subsequently, these patients 
cooperated with actual MRI scans without sedation. One hundred percent task 
compliance38 during fMRI scan was observed among pediatric patients who were trained 
with  multiple-reward compliance tactics. 
 
The successful results obtained in non-sedated pediatric neuroimaging techniques have 
inspired us to develop similar technologies to facilitate pediatric radiotherapy without 
repeated general anesthesia. We have developed and validated technologies to facilitate 
pediatric radiotherapy without general anesthesia, which we have called Pediatric 
Radiation Oncology with Movie Induced Sedation Effect (PROMISE). While other 

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audiovisual distraction techniques have previously been described, as outlined above, 
PROMISE is the first system that allows for real time monitoring of patient motion and 
automatic shutting off of the beam if the patient moves outside of defined parameters, 
activating a built-in safety mechanism. When video integration becomes available, the 
video will also shut off if the patient moves allowing for real time behavioral training that 
incentivizes patients not to move. 
 
We propose implementing PROMISE for all children between ages 3-11 undergoing 
radiation treatment through a phase II clinical trial with the following workflow: 1) During 
the CT simulation scan, a training session will be conducted, where the child will learn to 
lie still with positive and negative feedbacks provided by our system for behavioral 
training. This session will also be used as a screening test to choose children suitable for 
PROMISE. Only children meeting the movement-requirements during the training session 
will be selected as candidates for the following non-sedated radiation treatment. 2) 
During the treatment, a child will watch an age-appropriate movie or video of his/her 
choice. A 3D surface imaging system will be used to monitor the motion of the child. If the 
motion exceeds any pre-defined positioning thresholds (e.g., conventional radiotherapy 
(CRT): 0.5 cm in translation movements and 2° in three rotational angles; stereotactic 
radiotherapy (SBRT): 0.15 cm and 0.5 degree), the treatment beam will be shut off and 
the movie will be paused. 3) Beyond threshold movements the child will be instructed 
with the effectiveness of movement control strategy. 4) If the child reverts to treatment 
position within a pre-defined temporal threshold (e.g. 1 minute), the treatment will be 
resumed with a continuing movie. 5) If the child cannot revert to the treatment position 
within a pre-defined time threshold/or the movement is beyond any pre-defined re-
alignment threshold value (e.g., 1 cm / 5° in three rotational angles), the radiation beam 
and the movie will be turned off, the patient will be readjusted and the treatment will 
resume. 6) In any treatment fraction, PROMISE treatment will be ceased if according to 
the physician, excessive movement is compromising the childs safety.. If the child is 
consecutively noncompliant with PROMISE treatments for two fractions, he/she will 
receive radiotherapy treatment with general anesthesia for all subsequent fractions, 
unless instructed by physician to re-attempt PROMISE. 
 
This proposed PROMISE project offers several innovation features: 1) safer cancer 
radiotherapy modality for pediatric patients; 2) replacing repeated general anesthesia 
with behavioral training and motion monitoring to enable pediatric radiotherapy without 
sedation; 3) using a video/audio system and movies/cartoons for behavioral training; 4) 
using a 3D surface imaging system to monitor the patient motion and to provide negative 
feedback for operant conditioning. Our work success will lead to a novel radiotherapy 
modality for pediatric cancer patients with reduced risks and side effects, and also 
lowered cost and increased efficiency. Most children who currently need general 
anesthesia for radiotherapy will benefit from this new technology. 
 
2.0 
STUDY OBJECTIVES 
 
Hypothesis: We hypothesize that PROMISE will lead to a reduction in the percentage of pediatric 
patients ages 3-7 who require general anesthesia use for daily radiation treatment from 70% 
(historical control) to 30%. 
2.1 
Primary Objectives 
2.1.1 
To decrease the total number of pediatric patients who require general 
anesthesia through the use of PROMISE. 

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2.2 
Secondary Objectives 
2.2.1 
To assess the impact that PROMISE has on patient/family anxiety and quality of 
life, treatment time and clinical efficiency, and overall cost. 
 
2.2.2 
To determine the average patient movement and beam stoppages with 
PROMISE. 
2.3 
Endpoints 
2.3.1 
Primary: The percentage of pediatric patients age 3-7 who require daily general 
anesthesia for all treatments, compared to historical control. (Correlates with 
Primary Objective 2.1.1) 
 
2.3.2 
Secondary: Secondary outcomes will be measured comparing those who 
successfully are treated using PROMISE for any fraction vs. those who require 
general anesthesia for all fractions. (Correlates with Secondary Objective 2.2.1) 
- Patient/family-reported health quality of life, assessed using PedsQL 3.0 
Cancer Module. 
- Patient anxiety, measured by the modified Yale Preoperative Anxiety Survey 
Short Form (mYPAS-SF). 
 
2.3.3 
Exploratory: Exploratory outcomes will also be measured comparing those who 
successfully are treated using PROMISE for any fraction vs. those who require 
general anesthesia for all fractions. (Correlates with Secondary Objectives 2.2.1 
and 2.2.2). 
- Treatment time per fraction. 
- Workflow data: treatment time, average patient movement (magnitude, vertical, 
longitudinal, lateral, yaw, roll, and pitch), the number beam turn offs due to 
movement beyond threshold and total time out of tolerance.  
- Cost savings. 
 
3.0 
Subject 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 
Planned to undergo radiation treatment 
 
3.1.2 
Age 3-11 years 
 
3.1.3 
Eastern Cooperative Oncology Group (ECOG) performance status ≤ 2 at 
screening (See Section 12.1, Appendix A). 
 
 
3.1.4 
Parents or guardians with the ability to understand and the willingness to sign a 
written informed consent. 
3.2 
Exclusion Criteria 
3.2.1 
Subjects with documented medical behavior conditions or other conditions 
necessitating anesthesia use 
 
3.2.2 
Uncontrolled intercurrent illness including, but not limited to, ongoing or active 
infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac 
arrhythmia, or psychiatric illness/social situations that, in the opinion of the 
investigator, would limit compliance with study requirements. 

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3.2.3 
Subjects whose parents opt to not include them (the subject) in the clinical trial. 
 
4.0 
TREATMENT PLAN 
4.1 
Treatment Dosage and Administration 
Pediatric Radiation Oncology with Movie Induced Sedation Effect (PROMISE) is an 
interactive, incentive-based movie system that integrates with a video surveillance gating 
module (VisionRT) to help keep a children’s attention and prevent him or her from moving 
during radiation treatment. This technology is being studied as an alternative sedation 
solution for pediatric patients needing radiation treatment. 
 
All patients on study will receive radiation treatment per standard of care for patient’s 
diagnosis. The dose, fractionation, and possible concurrent treatments will all vary from 
patient to patient.  Because we plan to enroll such a wide variety of patients, treatment 
will be unique for every patient.  PROMISE will be consistent throughout the study, 
though, and attempted in every patient that can tolerate it. 
 
The following protocol will be used to implement PROMISE for each patient: 
▪ 
1) Consultation:  
• 
During initial consultation with eligible patients, the clinical trial will be 
discussed and should they agree to participate, patients/families will be 
consented. 
▪ 
2) CT simulation session:  
• 
Initial screening for PROMISE will occur in CT simulation suite.  
• 
Patient will be instructed to be NPO for 6 hours, and anesthesia will be 
available as stand-by.  
• 
CT scan of region of interest, per standard clinical practice, will be 
attempted with modified version of PROMISE for audiovisual distraction, 
with patient under direct observation.  
• 
If the patient cannot comply with instructions of laying still for a few minutes 
for the CT scan, the attending radiation oncologist will be asked to re-
evaluate the appropriateness of evaluating the child with PROMISE.  
• 
If PROMISE ultimately is unsuccessful, the patient will undergo general 
anesthesia for the CT simulation and subsequent treatments. 
▪ 
3) Treatment sessions: 
• 
For the first treatment, a 60-minute slot will be scheduled. Patient will be 
instructed to be kept NPO for 6 hours and anesthesia will be available on 
stand-by. Patient will be immobilized with PROMISE, and treatment will be 
attempted. 
• 
If patient successfully completes treatment with PROMISE, future 
treatments will be scheduled in 30-minute slots without anesthesia available 
on standby 
• 
If patient cannot successfully complete PROMISE, second treatment will be 
scheduled and planned similar to the first treatment, in a 60-minute slot with 
patient NPO and anesthesia on standby.  
• 
If second treatment is also not successful, no more attempts will be made 
with PROMISE and remaining treatments will be done under general 
anesthesia. 
• 
If the second treatment is successful, third treatment will be performed 
similarly.  
• 
If third treatment is successful, remaining treatments will be with PROMISE 
only, in 30-minute slots without anesthesia on standby.  

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• 
If third treatment is not successful, no more attempts will be made with 
PROMISE and remaining treatments will be done under general anesthesia. 
• 
For each treatment session, the following workflow data will be measured: 
1) total treatment time, 2) average patient movement (VisionRT), 3) number 
of beam turn offs due to movement beyond threshold (VisionRT). 
4.2 
Toxicities and Dosing Delays/Dose Modifications 
There are no known or expected toxicities associated with PROMISE. The only toxicity 
that could be indirectly associated with PROMISE is if the child moves during radiation 
treatment and this results in radiation temporarily being delivered to the wrong target. 
However, PROMISE is integrated with the video surveillance gating module VisionRT, so 
that if the patient moves beyond predefined safety threshold, the beam will automatically 
stop, so this is not an event that would ever be expected to happen. This auto-beam off 
ability is a unique feature of PROMISE that is not seen in competing technologies. 
4.3 
Concomitant Medications/Treatments 
N/A. Radiation and any other concomitant medications/treatments will be done as per 
standard of care. If patient cannot do PROMISE, general anesthesia will be used for each 
radiation treatment as per standard of care. 
4.4 
Duration of Therapy 
In the absence of treatment delays due to adverse events, treatment (PROMISE) may 
continue for duration of radiation treatment course or until any of the following that 
may necessitate stopping radiation treatment: 
• 
Disease progression 
• 
Inter-current illness that prevents further administration of treatment 
• 
Unacceptable adverse event(s) 
• 
Subject’s parent or guardian decides to withdraw subject 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. 
4.5 
Duration of Follow Up 
Follow up will occur 30 days (+/- 14 days) after treatment termination.  
4.6 
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 Investigator, and document the reason for treatment discontinuation 
and the date of discontinuation. The subject should be followed-up per protocol.  
 
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 30 days prior to registration unless 
otherwise stated. The screening procedures include: 

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5.1.1 Informed Consent 
5.1.2 Medical history 
  
 Complete medical and surgical history 
5.1.3 Demographics 
  
 Age, gender, race, ethnicity 
5.1.4 Review subject eligibility criteria 
5.1.5 Review previous and concomitant medications 
5.1.6 Physical exam including vital signs, height and weight 
 
 Vital signs (temperature, pulse, respirations, blood pressure), height, weight 
5.1.7 Performance status 
Performance status evaluated prior to study entry according to Appendix A 
(Section 12.1) 
5.1.8 Quality of life (QOL) questionnaires 
Baseline patient/family-reported health quality of life (QOL), assessed using 
PedsQL 3.0 Cancer Module, and patient/family-reported anxiety, measured by 
the modified Yale Preoperative Anxiety Survey Short Form (mYPAS-SF), will be 
assessed. The PedsQL for the patient will be optional. 
 
5.2 
Procedures During Treatment 
5.2.1 
Prior to Initiation of Treatment 
• 
History, physical exam, vital signs 
• 
PROMISE Screening  
o 
Initial screening for PROMISE will occur in CT simulation suite.  
o 
Patient will be instructed to be NPO for 6 hours, and anesthesia will 
be available as stand-by.  
o 
CT scan of region of interest, per standard clinical practice, will be 
attempted with modified version of PROMISE for audiovisual 
distraction, with patient under direct observation.  
o 
If the patient cannot comply with instructions of laying still for a few 
minutes for the CT scan, the attending radiation oncologist will be 
asked to re-evaluate the appropriateness of evaluating the child with 
PROMISE.  
o 
If PROMISE ultimately is unsuccessful for the CT simulation, the 
patient will undergo general anesthesia for the CT simulation and (at 
treating physician’s discretion) subsequent treatments. 
5.2.2 
Radiation Treatment 
• 
For the first treatment, a 60-minute slot will be scheduled. Patient will be 
instructed to be kept NPO for 6 hours and anesthesia will be available on 
stand-by. Patient will be immobilized with PROMISE, and treatment will be 
attempted. 
o 
If patient successfully completes treatment with PROMISE, future 
treatments will be scheduled in 30-minute slots without anesthesia 
available on standby 

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If patient cannot successfully complete PROMISE, the second treatment 
may be scheduled and planned similar to the first treatment at treating 
physician’s discretion, in a 60-minute slot with patient NPO and 
anesthesia on standby, or patient can proceed with anesthesia for 
subsequent treatments.The patient may continue subsequent treatments 
with anesthesia at the physician’s discretion.. 
• 
At the treating physicians discretion, the same procedures undertaken on 
Day 1 may be attempted a week later (+/- 7 days) if PROMISE was 
previously unsuccessful.  By this time, many patients will potentially be 
calmer and more accustomed to treatment, a new environment, etc. and 
more likely to tolerate PROMISE. 
5.2.3 
At Each Treatment 
• 
For each radiation treatment session, the following workflow data (as 
applicable) will be measured for all patients: 1) total treatment time, 2) 
average patient movement (VisionRT), and 3) number of beam turn offs due 
to movement beyond threshold (VisionRT).  
5.2.4 
Weekly (starting Day 1 +/- 5 days) 
• 
Patient/family-reported health quality of life (QOL), assessed using PedsQL 
3.0 Cancer Module, and patient/family-reported anxiety, measured by the 
modified Yale Preoperative Anxiety Survey Short Form (mYPAS-SF), will be 
assessed once a week during standard of care weekly on treat visit. The 
PedsQL for the patient will be optional. 
5.3 
Follow-up Procedures 
Subject will be followed up  30 days (+/- 14 days) after treatment termination for:  
• History & physical exam, vital signs 
• 
Patient/family-reported health quality of life (QOL), assessed using PedsQL 
3.0 Cancer Module, and patient/family-reported anxiety, measured by the 
modified Yale Preoperative Anxiety Survey Short Form (mYPAS-SF). The 
PedsQL for the patient will be optional. 
5.4 
Time and Events Table  
 
PROMISE 
 
Pre-
study 
Daily For Each 
Radiation 
Treatment Session 
Weekly During 
Radiation 
Treatment3 
Follow-up 
(30 days +/-  
14 days) 
Procedures 
 
 
 
 
Informed Consent 
X 
 
 
 
History and PE 
X 
 
 
X 
Performance Status 
X 
 
 
X 
QOL Questionnaires1 
X 
 
X 
X 
Workflow data2 
 
X 
 
 
 
1: Patient/family-reported health quality of life (QOL), assessed using PedsQL 3.0 Cancer Module, and patient/family-
reported anxiety, measured by the modified Yale Preoperative Anxiety Survey Short Form (mYPAS-SF). The PedsQL for 
the patient will be optional. 
 
2: Workflow data to be measured: 1) treatment time, 2) average patient movement (magnitude, vertical, longitudinal, 
lateral, yaw, roll, and pitch), and 3) the number beam turn offs due to movement beyond threshold and total time out of 
tolerance.  
 
3: During standard of care weekly on treat visits QOL questionnaires were be administered. This will not result in 
additional visits for the patient or family. 

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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’s parent or guardian voluntarily withdraws subject from treatment (follow-
up permitted); 
5.5.2 
Subject’s parent or guardian 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/treatment is deemed appropriate at the discretion of the investigator); 
5.5.5 
Subject experiences toxicity that makes continuation in the protocol unsafe; 
5.5.6 
Treating physician judges continuation on the study would not be in the subject’s 
best interest; 
5.5.7 
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; 
5.5.8 
Lost to follow-up:  If a research subject cannot be located to document survival 
after a period of 30 days, the subject may be considered “lost to follow-up.” All 
attempts to contact the subject during the 30 days must be documented. 
6.0 
MEASUREMENT OF EFFECT 
 
Because PROMISE is not a treatment, it will have no direct impact on cancer progression or 
remission, but its effects on other aspects of treatment and patient quality of life will be measured 
as discussed in section 2.3. 
7.0 
ADVERSE EVENTS 
7.1 
Experimental Therapy 
 
No experimental therapy (standard of care radiation treatment is used) 
7.2 
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 reported 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. 

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7.2.1 
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, temporarily 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 end of radiation treatment will be considered acute adverse 
events. These events will not be captured. 
Late Adverse Events 
Adverse events occurring up to 30 days (+/- 14 days) after the acute adverse 
event period will be considered late adverse events. These events will not be 
captured. 
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  
ICH Guideline E2A and the UTSW IRB define serious adverse events as those 
events, occurring at any dose, which meets any of the following criteria:  
• 
Results in death   
• 
Immediately life-threatening  
• 
Results in inpatient hospitalization1,2 or prolongation of existing 
hospitalization  
• 
Results in persistent or significant disability/incapacity  
• 
Results in a congenital anomaly/birth defect  
• 
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. 

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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 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. 
7.2.2 
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.  

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7.3 
Steps to Determine If a Serious Adverse Event Requires Expedited Reporting to 
the SCCC DSMC and/or HRPP 
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. 
- 
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 during the acute adverse event period, as 
defined in section 7.2.1, and is attributed (possibly, probably, or definitely) to the use of 
PROMISE. Any event that occurs during the late adverse event period and is attributed 
(possibly, probably, or definitely) to the use of PROMISE must also be reported as 
indicated in the sections below. 
 
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 
 
7.3.1 
Reporting SAES and UPIRSOs to the Simmons Comprehensive Cancer 
 
 
Center (SCCC) Data Safety Monitoring Committee (DSMC) 
 
All SAE/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/UPIRSOs occurring 
during the protocol-specified monitoring period should be submitted to the SCCC 
DSMC within 5 business days of the PI or delegated 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. 
 
The UTSW study team is responsible for submitting SAEs/UPIRSOs to the SCCC 
DSMC Coordinator.  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/UPIRSO documentation that is available are also 
submitted to the DSMC Chair who determines if further action is required. (See 

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Appendix III of the SCCC DSMC Plan for a template Serious Adverse Event Form 
which may be utilized when a sponsor form is unavailable and SAE submission to 
the eIRB is not required). 
  
 
If the event occurs on a multi-institutional clinical trial coordinated by the UTSW 
Simmons Comprehensive Cancer Center, the DOT Manager or lead coordinator 
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/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.  
 
Telephone reports to: 
Sarah Neufeld, Clinical Research Manager 
(214) 648-1836 
Written reports to: 
Department of Radiation Oncology 
Clinical Research Office 
The University of Texas Southwestern Medical Center 
Attention: Sarah Neufeld, Clinical Research Manager 
2280 Inwood Rd. 
Dallas, Texas 75390-9303 
Fax: (214) 645-8913 
Email: Sarah.Neufeld@utsouthwestern.edu 
 
UTSW SCCC Data Safety Monitoring Committee Coordinator 
Email: SCCDSMC@utsouthwestern.edu 
Fax: (214) 648-5949  
 
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/IRB 
 
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/IRB 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 
 

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effects (UADEs) and death or serious injury related to a humanitarian use device 
(HUD).  
 
UPIRSOs must be promptly reported to the UTSW IRB within 5 working days of 
PI 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 PI 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/research-
administration/irb/assets/policies-combined.pdf. 
8.0 
DRUG/TREATMENT INFORMATION 
N/A (This trial does not use any non-standard or unapproved drug therapy). 
9.0 
STATISTICAL CONSIDERATIONS 
9.1 
Study Design/Study Endpoints 
9.1.1 
To decrease the total number of pediatric patients who require general 
anesthesia compared to historical controls through the use of PROMISE (Primary 
Outcome). 
 
9.1.2 
To assess the impact that PROMISE has on patient anxiety and quality of life, 
treatment time and clinical efficiency, and overall cost. 
 
9.1.3 
To determine the average patient movement and beam stoppages with 
PROMISE. 
9.2 
Sample Size and Accrual 
In order to detect a reduction in the rate of general anesthesia use in pediatric patients 
age 3-7 from the historical control of 70% to the hypothesized 30%, the total number of 
patients needed to achieve 84% power is 13, using a two-sided exact binomial test with a 
significance level of 0.05. Over the last two years (2018-2019) at the University of Texas 
Southwestern we treated 52 pediatric patients aged 3-11 who would be eligible for this 
study, so on average 26 patients/year. We estimate the ability to enroll the large majority 
(>80%) of patients who are eligible for this trial, and so we estimate enrolling 20 patients 
per year. Of these patients, ~42% are ages 3-7, so we estimate that 8-9 patients in our 3-
7 age target range per year will be enrolled. Thus, we expect to enroll a total of 30 
patients, of whom 13 will be ages 3-7, in ~1.5 years, with the total trial completed in ~2 
years. 

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9.3 
Data Analyses 
Interim Reports: Interim reports will be prepared annually until the results of the study is 
closed to enrollment. In general, the interim reports will contain information about patient 
accrual rate with projected completion dates of the trial, as well as other preliminary data 
as available including PROMISE success rate (i.e. percentage of children enrolled who 
do not need general anesthesia).  
10.0 
STUDY MANAGEMENT 
10.1 
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. 
10.2 
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. 
10.3 
Registration Procedures 
All subjects must be registered with the Research Office before enrollment to study. Prior 
to registration, eligibility criteria must be confirmed with the Research Office Study 
Coordinator.  
 
New subjects will receive a number beginning with 001 upon study consent such that the 
first subject consented is numbered 001, the second subject consented receives the 
number 002, etc.  
 
Upon confirmation of eligibility and enrollment as per the aforementioned instructions, the 
subject will be assigned a secondary number in the order of enrollment. For example, 
subject 001 will become 001-01 upon enrollment. If subject 002 screen fails, and subject 
003 is the next subject enrolled, subject 003 will become 003-02 and so-on.  
 
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 above, which should then be entered as the 
patient study id in Velos upon updating the status to enrolled. 

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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.   
 
Subjects that previously enrolled and are receiving subsequent treatments will be eligible 
at any time, while study is open to enrollment, to continue the study under the same 
subject number.   
10.4 
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 
 
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 local 
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. 
 
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 SCCC DSMC meets quarterly and conducts annual comprehensive reviews of 
ongoing clinical trials, for which it serves as the DSMC of record. The 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.  
10.5 
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.  
10.5.1 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) 
➢ 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 

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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. 
10.5.2 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. 
10.5.3 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. 
 
10.5.4 
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. 
10.5.5  
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 
10.6 
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 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.  
10.7 
Record Retention 
Study documentation includes all Case Report Forms, data correction forms or queries, 
source documents, Sponsor-Investigator correspondence, monitoring logs/letters, and 

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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. 
10.8 
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. 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 

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11.0 
REFERENCES 
 
1. Jairam, V., Roberts, K. B. & Yu, J. B. Historical Trends in the Use of Radiation Therapy for Pediatric 
Cancers: 1973-2008. Int. J. Radiat. Oncol. 85, e151–e155 (2013). 
2. Herzog, C. E., Andrassy, R. J. & Eftekhari, F. Childhood cancers: hepatoblastoma. The Oncologist 5, 
445–453 (2000). 
3. Pediatric Radiation Oncology. (Lippincott, Williams & Wilkins, 2016). 
4. Khurmi, N., Patel, P., Koushik, S., Daniels, T. & Kraus, M. Anesthesia Practice in Pediatric Radiation 
Oncology: Mayo Clinic Arizona’s Experience 2014-2016. Paediatr. Drugs 20, 89–95 (2018). 
5. Habrand, J.-L., Abdulkarim, B. & Roberti, H. Radiotherapeutical innovations in pediatric solid tumors. 
Pediatr. Blood Cancer 43, 622–628 (2004). 
6. McFadyen, J. G., Pelly, N. & Orr, R. J. Sedation and anesthesia for the pediatric patient undergoing 
radiation therapy. Curr. Opin. Anaesthesiol. 24, 433–438 (2011). 
7. Verma, V. et al. Anesthesia complications of pediatric radiation therapy. Pract. Radiat. Oncol. 6, 143–
154 (2016). 
8. Ntoukas, S. M. et al. Minimizing General Anesthetic Use in Pediatric Radiation Therapy. Pract. 
Radiat. Oncol. 10, e159–e165 (2020). 
9. Harris, E. A. Sedation and anesthesia options for pediatric patients in the radiation oncology suite. 
Int. J. Pediatr. 2010, 870921 (2010). 
10. Frush, D. P., Bisset, G. S. & Hall, S. C. Pediatric sedation in radiology: the practice of safe sleep. 
AJR Am. J. Roentgenol. 167, 1381–1387 (1996). 
11. Malviya, S., Voepel-Lewis, T., Prochaska, G. & Tait, A. R. Prolonged recovery and delayed side 
effects of sedation for diagnostic imaging studies in children. Pediatrics 105, E42 (2000). 
12. Karian, V. E. et al. The development of a pediatric radiology sedation program. Pediatr. Radiol. 32, 
348–353 (2002). 
13. Cook-Sather, S. D. & Litman, R. S. Modern fasting guidelines in children. Best Pract. Res. Clin. 
Anaesthesiol. 20, 471–481 (2006). 

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14. Mavridou, P., Dimitriou, V., Manataki, A., Arnaoutoglou, E. & Papadopoulos, G. Patient’s anxiety and 
fear of anesthesia: effect of gender, age, education, and previous experience of anesthesia. A survey 
of 400 patients. J. Anesth. 27, 104–108 (2013). 
15. Golparvar, M., Saghaei, M., Sajedi, P. & Razavi, S. S. Paradoxical reaction following intravenous 
midazolam premedication in pediatric patients - a randomized placebo controlled trial of ketamine for 
rapid tranquilization. Paediatr. Anaesth. 14, 924–930 (2004). 
16. Fillmore, M. T., Rush, C. R., Kelly, T. H. & Hays, L. Triazolam impairs inhibitory control of behavior in 
humans. Exp. Clin. Psychopharmacol. 9, 363–371 (2001). 
17. Ghoneim, M. M. Awareness during anesthesia. Anesthesiology 92, 597–602 (2000). 
18. Spitellie, P. H., Holmes, M. A. & Domino, K. B. Awareness during anesthesia. Anesthesiol. Clin. N. 
Am. 20, 555–570 (2002). 
19. Cravero, J. P. et al. The incidence and nature of adverse events during pediatric sedation/anesthesia 
with propofol for procedures outside the operating room: a report from the Pediatric Sedation 
Research Consortium. Anesth. Analg. 108, 795–804 (2009). 
20. Bakri, M. H. et al. Behavioral and emotional effects of repeated general anesthesia in young children. 
Saudi J. Anaesth. 9, 161–166 (2015). 
21. Ing, C. et al. Long-term differences in language and cognitive function after childhood exposure to 
anesthesia. Pediatrics 130, e476-485 (2012). 
22. Flick, R. P. et al. Cognitive and behavioral outcomes after early exposure to anesthesia and surgery. 
Pediatrics 128, e1053-1061 (2011). 
23. Scott, M. T. et al. Reducing Anesthesia and Health Care Cost Through Utilization of Child Life 
Specialists in Pediatric Radiation Oncology. Int. J. Radiat. Oncol. Biol. Phys. 96, 401–405 (2016). 
24. Buchsbaum, J. C. et al. Repetitive pediatric anesthesia in a non-hospital setting. Int. J. Radiat. Oncol. 
Biol. Phys. 85, 1296–1300 (2013). 
25. Barry, P., O’Callaghan, C., Wheeler, G. & Grocke, D. Music therapy CD creation for initial pediatric 
radiation therapy: a mixed methods analysis. J. Music Ther. 47, 233–263 (2010). 
26. Klosky, J. L. et al. Brief report: Evaluation of an interactive intervention designed to reduce pediatric 
distress during radiation therapy procedures. J. Pediatr. Psychol. 29, 621–626 (2004). 

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27. Haeberli, S. et al. A psychoeducational intervention reduces the need for anesthesia during 
radiotherapy for young childhood cancer patients. Radiat. Oncol. Lond. Engl. 3, 17 (2008). 
28. Slifer, K. J. A video system to help children cooperate with motion control for radiation treatment 
without sedation. J. Pediatr. Oncol. Nurs. Off. J. Assoc. Pediatr. Oncol. Nurses 13, 91–97 (1996). 
29. Engvall, G. et al. Children’s experiences and responses towards an intervention for psychological 
preparation for radiotherapy. Radiat. Oncol. Lond. Engl. 13, 9 (2018). 
30. Balazy, K. E. et al. Impact of Audiovisual-Assisted Therapeutic Ambience in Radiation Therapy 
(AVATAR) on Anesthesia Use, Payer Charges, and Treatment Time in Pediatric Patients. Pract. 
Radiat. Oncol. (2020) doi:10.1016/j.prro.2019.12.009. 
31. Byars, A. W. et al. Practical aspects of conducting large-scale functional magnetic resonance imaging 
studies in children. J. Child Neurol. 17, 885–890 (2002). 
32. Akshoomoff, N. et al. Outcome classification of preschool children with autism spectrum disorders 
using MRI brain measures. J. Am. Acad. Child Adolesc. Psychiatry 43, 349–357 (2004). 
33. Raschle, N. M. et al. Making MR imaging child’s play - pediatric neuroimaging protocol, guidelines 
and procedure. J. Vis. Exp. JoVE (2009) doi:10.3791/1309. 
34. Schumann, C. M. et al. Longitudinal magnetic resonance imaging study of cortical development 
through early childhood in autism. J. Neurosci. Off. J. Soc. Neurosci. 30, 4419–4427 (2010). 
35. Slifer, K. J., Cataldo, M. F., Cataldo, M. D., Llorente, A. M. & Gerson, A. C. Behavior analysis of 
motion control for pediatric neuroimaging. J. Appl. Behav. Anal. 26, 469–470 (1993). 
36. Slifer, K. J., Koontz, K. L. & Cataldo, M. F. Operant-contingency-based preparation of children for 
functional magnetic resonance imaging. J. Appl. Behav. Anal. 35, 191–194 (2002). 
37. Epstein, J. N. et al. Assessment and prevention of head motion during imaging of patients with 
attention deficit hyperactivity disorder. Psychiatry Res. 155, 75–82 (2007). 
38. Schlund, M. W. et al. Pediatric functional magnetic resonance neuroimaging: tactics for encouraging 
task compliance. Behav. Brain Funct. BBF 7, 10 (2011). 
 
 
 
 
 

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12.0 
APPENDICES 
 
12.1  
Appendix A: ECOG Performance Status 
 
ECOG/ZUBROD PERFORMANCE STATUS 
 
0  
Fully active, able to carry on all pre-disease activities without restriction 
(Karnofsky 90-100). 
 
1  
Restricted in physically strenuous activity but ambulatory and able to carry work of a light 
or sedentary nature. For example, light housework, office work (Karnofsky 70-80). 
 
2  
Ambulatory and capable of all self-care but unable to carry out any work activities. Up 
and about more than 50% of waking hours (Karnofsky 50-60). 
 
3  
Capable of only limited self-care, confined to bed or chair 50% or more of waking hours 
(Karnofsky 30-40). 
 
4  
Completely disabled. Cannot carry on self-care. Totally confined to bed or (Karnofsky 10-
20). 
 
5  
Death (Karnofsky 0). 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 

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12.2  
Appendix B: PedsQL Cancer Module 3.0 
 
 
 
 
 
 
PedsQL 3.0 (8-12) Cancer Acute 
03/00 
Not to be reproduced without permission 
Copyright © 1998 JW Varni, Ph.D. 
All rights reserved 
 
PedsQL ™ 
Cancer Module 
Acute Version 
Version 3.0 
CHILD REPORT (ages 8-12) 
In the past 7 days, how much of a problem has this been for you … 
ID#   
 
Date:  
 
DIRECTIONS 
Children with cancer sometimes have special problems. Please tell us how 
much of a problem each one has been for you during the past 7 days by 
circling: 
0 if it is never a problem 
1 if it is almost never a problem 
2 if it is sometimes a problem 
3 if it is often a problem 
4 if it is almost always a problem 
There are no right or wrong answers. 
If you do not understand a question, please ask for help. 

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PedsQL 3.0 - Parent (8-12) Cancer Acute 
03/00 
Not to be reproduced without permission 
Copyright © 1998 JW Varni, Ph.D. 
All rights reserved 
 
PedsQL ™ 
Cancer Module 
Acute Version 
Version 3.0 
PARENT REPORT for CHILDREN (ages 8-12) 
In the past 7 days, how much of a problem has your child had with … 
ID#  
 
Date:  
 
DIRECTIONS 
Children with cancer sometimes have special problems. On the following page 
is a list of things that might be a problem for your child. Please tell us how 
much of a problem each one has been for your child during the past 7 days 
by circling: 
0 if it is never a problem 
1 if it is almost never a problem 
2 if it is sometimes a problem 
3 if it is often a problem 
4 if it is almost always a problem 
There are no right or wrong answers. 
If you do not understand a question, please ask for help. 

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12.3  
Appendix C: Modified Yale Preoperative Anxiety Survey Short Form (mYPAS-SF) 
• 
A. Activity 
o 
1 = Looking around, curious, playing with toys, reading (or other age-appropriate 
behavior); moves around holding area/treatment room to get toys or go to parent; may 
move toward OR equipment 
o 
2 = Not exploring or playing, may look down, may fidget with hands or suck thumb 
(blanket); may sit close to parent while waiting, or play has a definite manic quality 
o 
3 = Moving from toy to parent in unfocused manner, nonactivity-derived movements; 
frenetic/frenzied movement or play; squirming, moving on table, may push mask away or 
clinging to parent 
o 
4 = Actively trying to get away, pushes with feet and arms, may move whole body; in 
waiting room, running around unfocused, not looking at toys or will not separate from 
parent, desperate clinging 
• 
B. Vocalizations 
o 
1 = Reading (nonvocalizing appropriate to activity), asking questions, making comments, 
babbling, laughing, readily answers questions but may be generally quiet; child too young 
to talk in social situations or too engrossed in play to respond 
o 
2 = Responding to adults but whispers, “baby talk,” only head nodding 
o 
3 = Quiet, no sounds or responses to adults 
o 
4 = Whimpering, moaning, groaning, silently crying 
o 
5 = Crying or may be screaming “no” 
o 
6 = Crying, screaming loudly, sustained (audible through mask) 
• 
C. Emotional expressivity 
o 
1 = Manifestly happy, smiling, or concentrating on play 
o 
2 = Neutral, no visible expression on face 
o 
3 = Worried (sad) to frightened, sad, worried, or tearful eyes 
o 
4 = Distressed, crying, extreme upset, may have wide eyes 
• 
D. State of apparent arousal 
o 
1 = Alert, looks around occasionally, notices/watches what anesthesiologist does with 
him/her (could be relaxed) 
o 
2 = Withdrawn, child sitting still and quiet, may be sucking on thumb or face turned into 
adult 
o 
3 = Vigilant, looking quickly all around, may startle to sounds, eyes wide, body tense 
o 
4 = Panicked whimpering, may be crying or pushing others away, turns away 
Scoring: Divide each item rating by the highest possible rating (i.e., 6 for the “vocalizations” item and 4 for 
all other items), add all of the produced values, divide by 4, and multiply by 100.